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10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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Do I Have Cancer

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Alternative Pathways to Colorectal Cancer

Figure 3.3 Genetic changes in HNPCC progression. Approximately 2-4 percent of colorectal cancers follow this pathway. Figure 3.3 Genetic changes in HNPCC progression. Approximately 2-4 percent of colorectal cancers follow this pathway. Most colorectal tumors have either MSI or CIN, but not both. Some form of accelerated mutation may be needed for progression to aggressive colorectal cancer (Jass et al. 2002a Kinzler and Vogelstein 2002). Individuals who inherit defects in MMR develop hereditary nonpoly-posis colorectal cancer (HNPCC) as well as other cancers that together make up Lynch's syndrome (Boland 2002). Some of the genetic steps in HNPCC progression and the rates of transition between stages differ from the classical pathway (Figure 3.3). In another study, Rajagopalan et al. (2002) found that 61 percent of 330 colorectal tumors had either a BRAF or K-RAS mutation, but a tumor never had mutations in both genes. Mutually exclusive mutation of these genes supports the suggestion...

Environmental Factors in the Etiology of Human Cancer Physical and Biological Agents

At our present state of knowledge, evidence argues that the majority of human neoplasms result from the chemical induction of neoplasia however, it is clear that radiation, both ionizing and ultraviolet, as well as infectious agents also contribute as primary factors in the development of a significant proportion of human neoplasia. Just as with chemical carcinogenesis, in the human the basis of our knowledge of the physical and infectious causation of human cancer derives from both epidemiological and experimental findings. However, unlike many chemical carcinogens whose carcinogenic activity in the human is based either entirely on experimental findings e.g., 2-acetylaminofluorene, dimethylnitrosamine, and ethyleneimine (Chapter 13) or solely on epidemiological findings e.g., organic arsenicals and ethanol (Chapter 11) , evidence for the ultraviolet and ionizing radiation-induced human neoplasia as well as a number of viruses as causative of human neoplasia is based solidly on both...

Of Dna Microarrays For Bladder Cancer Analysis

Several types of samples are available to study bladder cancer by expression profiling. Normal urothelia and tumor tissues can be obtained by transurethral resection, cystectomy, or cystoprostatectomy. Due to the close monitoring of bladder cancer patients, sequential biopsies obtained over time allow addressing critical issues related to tumor progression and response to treatment. Optimal results are achieved by handling tissue promptly and either extracting RNA immediately from fresh aliquots or deep freezing in liquid nitrogen in either tubes or using cryomolds and embedding medium. This latter format allows verification of histopathological characteristics, since it represents a frozen tissue block. It also provides adequate samples for tissue microdissection if required. Bladder cancer offers an additional source of material for tumor profiling studies based on direct access to exfoliated tumor cells through urine samples and bladder washes. This approach has not been reported...

Physical Carcinogenesis In Humans

It is likely that radiogenic neoplasms have occurred in humans sporadically since the dawn of civilization but only in the 20th century, with the advent of our greater knowledge of the components of the electromagnetic spectrum and the existence of ionizing and ultraviolet radiation, have the cancer-inducing properties of these latter two agents been recognized. Although experiments in animals have shown us a great deal about the basic aspects of radiogenic neoplasia, epidemiological studies in humans have advanced our knowledge of radiogenic neoplasms to an almost equal or greater extent. The most unfortunate and at the same time the greatest single incidence of radiation-induced cancers in humans resulted from the atomic bomb explosions at Hiroshima and Nagasaki.

Expression Profiling And The Study Of Bladder Cancer

Microarray-based gene expression profiling has found a number of important applications in the study of carcinogenesis and cancer biology. Broadly speaking, these applications can be described as gene and pathway discovery, functional classification of genes, and tumor classification. Tumor classification is one of the most exciting and potentially most powerful applications of expression profiling with DNA microarrays. Major goals for improving cancer treatment include the early and accurate diagnosis of tumor type and determining the extent of the disease. The traditional approach to tumor classification is based on clinicopathological criteria. It is expected that the integration of gene expression patterns, as determined by DNA microarrays, will provide a better means for classifying tumors into biologically meaningful and clinically useful categories. In addition, expression profiling of well-curated tumor specimens has the potential of identifying target genes for novel...

Application Of Dna Microarrays To The Study Of Bladder Cancer

The main advantage of DNA arrays is that they allow the study of the multiple tran-scriptional events that take place when normal urothelium is transformed into tumor tissue in single experiments. Expression profiling using cell lines has been used to gain an insight into the molecular events associated with the disease. An example of how the technology can be applied to the discovery of gene functions and pathways in bladder cancer is provided by the following study. Tumor cell growth inhibition mediated by genistein was induced in the susceptible bladder tumor line TCCSUP. Expression The following study provides an example of the functional classification of genes applied to bladder cancer, relating the expression patterns of p53-mediated apoptosis in resistant tumor cell lines vs sensitive tumor cell lines. The ECV-304 bladder carcinoma cell line was selected for resistance to p53 by repeated infections with a p53 recombinant adenovirus Ad5-cytomegalovirus (CMV)-p53. Its expression...

Cancer genetics services

A survey of cancer genetics services, particularly in relation to breast cancer, in 34 European countries was undertaken as part of a BIOMED II Demonstration Project - 'Familial Breast Cancer, an Audit of a New Development in Medical Practice in European Countries' - and the results have been published in detail (Hodgson et al., 1999, 2000). There was considerable variation between the current status of such services in the different countries. The UK, the Netherlands, Belgium and the Scandinavian countries were the first to develop these, profiting from relatively high levels of gross national product and healthcare funding. However, much of the initial funding was provided by research charities. Other countries with active service development are France, Austria, Italy and Germany, but in these countries genetic counsellors are not yet accepted as having a role in service development. Israel, Poland and Ireland are also actively developing these services, including the acceptance of...

Using Human Bladder Cancer Specimens

There have been few reports dealing with molecular classification of bladder cancer expression profiling using DNA microarrays. The most extensive one has monitored the expression patterns of superficial and invasive tumor cell suspensions prepared from 36 normal and 29 bladder tumor biopsies using oligonucleotide microarrays containing 6500 genes. This study also analyzed pools of cells made from normal urothelium as well as pools of tumors of different stages such as pTa grade I and II and pT2 grade III and IV bladder cancer specimens (34). The pooling approach may smooth out individual differences, but on the other hand, it can dilute strong intensities of relevant genes that may differentiate specific groups with different prognosis. Single cell suspensions were prepared from cooled biopsies immediately after surgery following a procedure previously used for the preparation of bladder tumors for flow cytometry (45). Single-cell suspensions can be inspected under the microscope to...

Biological Carcinogenesis In The Human

As noted earlier, in Chapter 4, biological factors as causes of cancer in lower animals have been known since the beginning of the twentieth century and were suspected even earlier. However, it was not until the latter half of the twentieth century that infectious agents began to be significantly appreciated as causative factors in human cancer. Perhaps the scientific embarrassment engendered by the irreproducibility of Febiger's experiment (Chapter 4) led to an aversion of scientists to try and relate infectious agents to the development of the neoplastic process. This was true despite the suggestion from ancient times of an association between infection with species of platyhelminth worms, especially Schistosoma haematobium, and bladder cancer this had been known or suspected for thousands of years beginning in ancient Egypt (cf. Elsebai, 1977 Hicks, 1983). That bacteria and viruses could cause human cancer was not substantially appreciated until the last four decades of the...

Nsabp Rectal Cancer Adjuvant Trials

This protocol was designed to explain the role of postoperative chemotherapy and radiotherapy in the treatment of patients with resected Stage II or III rectal cancer (20). Between November 1977 and October 1986, 555 eligible patients with follow-up entered. They were stratified by age, gender, and stage and randomized to receive entirely no further treatment, MOF (as in the treatment arm of C-01 and control arm of C-03), or radiation therapy. At 5 yr of follow-up, patients who received MOF demonstrated an overall improvement in DFS (p 0.006) and in survival (p 0.05) compared to the group treated by surgery alone. Gender was the primary stratification variable contributing to the DFS and survival benefit from chemotherapy however, to a lesser extent, age and stage also interacted. The benefit for chemotherapy, both in DFS (29 vs 47 , p< 0.001) and survival (37 vs 60 , p 0.001) was restricted to males, with the greatest benefit occurring in the younger age groups. This age benefit...

Other Applications Of Microarrays In Bladder Cancer Research

Oligonucleotide microarrays have also been used to analyze gene mutations in tumor samples for the presence of mutations in the TP53 tumor suppressor gene, which is a valuable predictor for bladder cancer outcome (34). The traditional manual dideoxy sequencing has been compared with the much faster microarray sequencing on a commercially available chip and the concordance between methods was 92 . DNA samples extracted from 140 human bladder tumors were subjected to a multiplex-PCR before loading onto the p53 GeneChip (Affymetrix, Santa Clara, CA, USA). Each of the 1464 gene chip positions corresponded to an analyzed nucleotide in the p53 gene sequence. If there is a heterozygous or homozygous mutation, the oligonucleotide probes will hybridize differently from the wild-type sequence and reveal a signal that detects this particular base change. It is possible to detect either a wild-type sequence or a mixture of wild-type and mutant alleles. The system is almost free from interference...

Weibull Analysis of Carcinogen Dose Response Curves

Peto et al. (1991) provided the most comprehensive experiment and analysis of carcinogen dose-response curves. In their analysis, they compared the observed age-specific incidence of cancer (the response) over varying dosage levels. They described the incidence curves by fitting the data to the Weibull distribution. They also related the Weibull incidence pattern to the classic Druckrey formula for carcinogen dose-response relations. The Druckrey formula summarizes the many carcinogen experiments that give linear dose-response curves when plotting the median time to tumor onset versus dosage of the carcinogen on log-log scales (Druckrey 1967). I discussed the Druckrey equation, the data from Peto et al.'s study, and some experimental results from other carcinogen experiments in Section 2.5. Here, I summarize the theory that ties the Weibull approximation for incidence curves to the Druckrey equation between carcinogens and tumor incidence. For carcinogen experiments, Druckrey and...

Identification Of Potential Carcinogenic Agents

A major factor in determining the carcinogenic potential of an agent is its identification as being carcinogenic. While this statement appears obvious and even redundant, identification of a carcinogen is necessary but not sufficient for determining carcinogenic potential. Still, identification is the starting point and for this reason has received the most attention. Generally speaking, the various tests that have been applied to identifying agents with carcinogenic potential may be classified into several general areas. These are seen in Table 13.2. As noted in the table, the time involved in the assay has been arbitrarily separated into short, medium, and long. Short-term assays usually involve days to a few weeks for development of an end point medium-term assays require weeks to some months but much less than a year. Long-term bioassays usually involve IV2 to 2 years of treatment of animals with a test agent. Each of these general categories consists of specific methods, and each...

Evaluation Of Carcinogenic Potential

The multiple in vivo and in vitro tests described thus far in this chapter present the experimentalist or the regulator with an extensive amount of data from which to draw conclusions about the carcinogenic potential of the test agent. In addition, epidemiological studies (Chapters 11 and 12) provide perhaps the most definitive means of estimating the carcinogenic potential to humans from exposure to a specific agent. While such studies, if definitively positive, are the best evidence for the carcinogenic potential of an agent to the human, the evidence is usually obtained after an exposure has occurred in a population. In general, epidemiological studies can detect differences between populations only when there is approximately a twofold increase above the background incidence of neoplasia in the control population. Since many more agents than those classified as group 1 by IARC exhibit carcinogenic potential, the in vitro and in vivo tests described earlier have been used as...

Riskbenefit Considerations In The Regulation Of Actual And Potential Carcinogenic Environmental Hazards

We have briefly reviewed the methods for determining the actual and potential carcinogenic agents in our environment, methods for the estimation of risk to the human population of such agents, and the governmental approach to the regulation of such agents in our environment. An equally important consideration includes somewhat undefined concepts such as benefit-risk analysis, cost-effectiveness, and risk-cost analysis in the regulation of hazardous agents in our environment. These concepts are concerned with such traditional regulatory terms as safe, lowest feasible, and best practicable technology.

Carcinogenesis In Organ Cultures

Attempts at the induction of neoplasia in organ cultures were made in a reasonably systematic way by Heidelberger (1973) after the earlier studies of Lasnitzki (1963). Heidelberger attempted to induce carcinomas in organ culture of rat prostate by the addition of carcinogenic polycyclic hydrocarbons to the cultures. Although significant morphological changes occurred, including squamous metaplasia and cytological anaplasia, no neoplasms were produced when the cultures exhibiting such changes were inoculated into suitable mouse hosts. Later studies by Lasnitzki (1976) in this system demonstrated that retinoids added to the cultures could reverse the morphological effects produced by 10 days of incubation with a polycyclic hydrocarbon. As an extension of these investigations, several investigators have developed an in vitro-in vivo format for carcinogenesis in organ cultures. Basically, the cultures are exposed to carcinogen for a specific time and then directly reimplanted into...

Pathogenesis of colon cancer

Colon carcinogenesis is a multistage process in which normal cells are initiated to form preneoplastic lesions which may then evolve into macroscopic adenomas and cancers (Chang, 1984, Morson, et al., 2003). The genetic alterations underlying the pathogenesis of colorectal carcinogenesis have been extensively studied (reviewed in Vogelstein and Kinzler, 2004) and it is now believed that neoplastic progression occurs as a stepwise process in which each step is caused by a genetic change (either in an oncogene or in a tumor suppressor gene) so that the development of the different histological stages is accompanied by an accumulation mutational burden (Morson et al., 2003). The study of hereditary bowel cancer syndromes such as familial adenomatous polyposis (FAP) or hereditary non polyposis colon cancer (HNPCC) have led to the discovery of important cancer genes which have also been found mutated in sporadic colorectal cancers. For instance, APC gene mutations are inherited in patients...

Current State Of Molecular Biology Of Pancreatic Cancer

A brief review of the current understanding of the genetic alterations associated with pancreatic cancer will help set the stage for a more detailed discussion of gene expression in pancreatic cancer. The last decade has seen a dramatic increase in our understanding of the molecular biology of pancreatic cancer, with pancreatic cancer now considered one of the better characterized neoplasms at the genetic level. Recent advances include the identification of the precursor lesions of invasive pancreatic carcinoma, known as pancreatic intraepithelial neoplasias (PanINs) (4-6). Just as there is a progression in the colorectum from normal epithelium, to adenoma, to infiltrating carcinoma, so too is there a genetic progression in the pancreas from normal duct epithelium, to PanINs, to invasive duct adenocarcinoma (7). This progression has been shown to be associated with the accumulation of multiple genetic alterations, including activating point mutations in the K-ras gene, telomere...

Evidence for Possible Anticancer Protection by Lycopene

Most of the indications with respect to cancer comes from human studies linking tomato intake, total estimated lycopene intake, and serum or plasma lycopene concentrations to the subsequent development of cancers (Table 5). There is a small amount of evidence from experimental animal studies, for instance, rat and mouse dimethylbenzanthracene-induced mammary tumor studies have supported Partly for historical reasons, there has been a particular interest in prostate cancer (Table 5). A large and early trial in the US (US Health Professionals Follow-up Study) reported an impressive difference between groups with high and low intakes of tomatoes and hence of lycopene for subsequent prostate cancer development, which was not shared with other carotenoids. Plausibility was enhanced by the fact that although human prostate lycopene concentrations are not especially high on an absolute basis (Table 3), they are higher than those of other carotenoids in this tissue. Subsequent studies have...

Invasive breast cancer

The commonly occurring invasive cancers and their relative frequencies are listed in Table 17.4 and are discussed in more detail below. The most commonly occurring type of breast cancer is the invasive ductal carcinoma of no special type (75-80 of all Table 17.4. Frequency of invasive breast cancers.

Cell Culture As A Tool In Our Understanding Of Carcinogenesis And Cancer

The transformation of cells in culture to the neoplastic state, both spontaneously and induced by chemical, physical, and biological agents, exhibits many similarities to carcinogenesis in vivo. In this chapter an effort has been made to emphasize the more important examples of close analogies between the carcinogenic process in vitro and in vivo. It is through a more careful study of the mechanisms of such analogies that a better understanding of the process of carcinogenesis may be forthcoming. On the other hand, an understanding of the mechanisms of the differences between the carcinogenic process in vivo and that in vitro may be equally rewarding.

Prostate Cancer Angiogenesis

Tumour hypoxia is thought to be the likely explanation for the induction of angiogenesis in prostate cancer (Izawa and Dinney 2001). Hypoxia induces vascular endothelial growth factor (VEGF) transcription via hypoxia-inducible factor-1 (Zhong et al. 1999). VEGF is a recognised stimulus of neoan-giogenesis in tumours, and is also a potent tissue permeability factor (Dvorak et al. 1995). Androgens seem to regulate VEGF expression in prostate cancer cells and prostatic fibroblasts (Joseph et al. 1997 Levine et al. 1998). It has been shown that VEGF is produced in abundance by the secretory epithe lium of normal, hyperplastic, and tumorous prostate glands (Jackson et al. 1997 Ferrer et al. 1998). The physiological role(s) of VEGF in the prostate is poorly understood and target cells may include cells other than the vascular endothelium. With respect to the vasculature, it is clear that VEGF is required for vascular homeostasis in the prostate gland and maintains the high fraction of...

Preneoplastic lesions in colon carcinogenesis

Preneoplastic lesions are considered an obligatory step in the development of cancer, and many efforts have been dedicated to the identification and characterization of preneoplastic lesions in experimental animals and humans. In fact, when preneoplastic lesions are easily identifiable, they can be used as biomarkers in experimental studies of cancer prevention. In 1987, Bird described foci of aberrant crypts (aberrant crypt foci ACF), identifiable in whole mount preparations of unsectioned colons in rodents treated with specific colon carcinogens as early as few weeks after carcinogen treatment (Bird, 1987). ACF are visible using a simple methylene blue staining of the colonic mucosa and can be observed under a light microscope at low magnification (Fig. 14.1). ACF appear as crypt aggregates, morphologically altered (larger, intensely stained and with a higher peri-cryptic area (Bird, 1987). ACF have also been identified in apparently normal colonic mucosa of patients with colorectal...

Telling the Truth about Cancer and Its Treatment

In the United States attitudes toward truth telling in cancer care have changed markedly in the last few decades. In 1946 Charles Lund wrote that a patient diagnosed with cancer should not be told the whole truth. He advised physicians to use a loosely descriptive word such as cyst or lesion in place of the word cancer and to give patients only some rough idea of the extent of treatment. That was sufficient information, Lund felt, on which to base a diagnostic discussion and consent to treatment. In the same vein, a 1961 survey reported that 90 percent of 219 Chicago doctors did not tell patients the truth about a diagnosis of cancer (Oken). Maintenance of hope, in contrast, was considered the single most important factor for physicians to take into account when discussing cancer with a patient. By contrast, 97 percent of physicians surveyed at the same Chicago institution in 1979 reported a preference for telling cancer patients the truth about their diagnoses, a dramatic reversal of...

For Cancer and Cardiovascular Diseases

Anticancer Drugs is More Efficacious Than Monotherapy Inhibition of Prenylation Radiosensitizes Human Tumors FTI-277 Induces Apoptosis by Blocking the PI-3 Kinase AKT-2 From Farnesyltransferase Inhibitors in Cancer Therapy Edited by S. M. Sebti and A. D. Hamilton Humana Press Inc., Totowa, NJ

Should the management of familial ovarian cancer differ from that of sporadic ovarian cancer

The management of familial ovarian cancer (FOC) is currently essentially the same as for sporadic ovarian cancer, but is FOC biologically different from sporadic ovarian cancer and should we be managing it differently There is some conflicting evidence. Greggi examined eight families with two or more first-degree relatives affected with epithelial ovarian cancer (EOC) among a series of 138 consecutive ovarian cancer patients. No significant difference was detected in clinical and pathological features between sporadic and familial cases. Papillary serous adenocarcinoma was the predominant histological type. However, in three high-risk families, EOC tended to develop at a younger age compared with other familial cases and with sporadic cancers, and nulliparity was less frequent in the familial group (Greggi et al., 1990). Similarly, Bewtra identified 37 FOC patients from FOC syndrome kindreds with documented cancers of the ovary, breast, colon or endometrium in two or more first-degree...

Probiotics and functional dairy products in experimental models of colorectal carcinogenesis

Probiotics alone or in combination with dairy products have been tested for their ability to decrease colon carcinogenesis induced by AOM or DMH. Rats initiated with AOM and fed with a semipurified diet supplemented with Bifidobacterium longum, had a significantly lower incidence and multiplicity of colonic tumors than control rats (Singh et al., 1997). Colonic proliferation and the expression of ras-p21 oncoprotein were also decreased in rats treated with probiotics, suggesting a mechanism for the observed inhibition of colon carcinogenesis (Singh et al., 1997). Although this report suggests a protective effect of probiotics, other studies have shown that this effect is not completely consistent and may depend on the experimental conditions (Goldin et al., 1996). Goldin and coworkers (1996) demonstrated that while Lactobacillus rhamnosum (strain GG) reduced colon cancer when given to rats 3 weeks before carcinogen administration, it was not active if given after the ninth week of DMH...

The Epigenetic Breakdown of Cancer Cells From DNA Methylation to Histone Modifications

Abstract The recognition of epigenetic defects in all types of cancer has represented a revolutionary achievement in cancer research in recent years. DNA methylation aberrant changes (global hypomethylation and CpG island hypermethylation) were among the first events to be recognized. The overall scenario comprises a network of factors in which deregulation of DNA methyltransferases leads to a cancer-type specific profile of tumor suppressor genes that become epigenetically silenced. Over recent years, a better understanding of the machinery that connects DNA methylation, chromatin and transcriptional activity, in which histone modifications stand in a key position, has been achieved. The identification of these connections has contributed not only to understanding how epigenetic deregulation occurs in cancer but also to developing novel therapies that can reverse epigenetic defects in cancer cells.

Combination Therapy Of Ftis Or Ggtis With Cytotoxic Anticancer Drugs Is More Efficacious Than Monotherapy

Evidence from our research and that of others (46-48) indicated that FTIs' antitumor effect is often cytostatic and reversible. This suggested that combination therapy may be beneficial. Furthermore, there are several reasons why combination therapy with FTIs or GGTIs and other clinically used anticancer drugs with different mechanisms ofaction may prove to be more beneficial than monotherapy. First, because a tumor is made up of a heterogeneous population of cells with different genetic alterations, treatment with more than one agent may avoid resistance of the tumor to a single drug. Second, Ras has been shown to induce resistance to radiation and some cytotoxic agents. Therefore, inhibition ofK-Ras prenylation may sensitize human tumors to cytotoxic agents or radiation (see Chapter 12). On the other hand, treatment with cytotoxic agents may also alter tumor cells such that they become even more sensitive to FTIs or GGTIs. To explore these possibilities we have implanted sc...

New Markers For Ovarian Cancer Diagnosis

Although we, and others, have identified many highly expressed genes encoding secreted proteins in ovarian carcinomas, we collectively lack the evidence at this time that these proteins are detectable in the serum of patients with ovarian cancer. Mok and coworkers have recently described one of the first examples of this type of translational diagnostic research, in which their observation of an overexpressed gene in ovarian carcinoma has led to the identification of the encoded protein in the serum of ovarian cancer patients (47). The authors previously described the overexpression of prostasin, a secreted protease originally identified in human seminal fluid, in ovarian carcinoma-derived cell-lines compared to those obtained from normal ovarian epithelium. IHC showed that the prostasin protein is expressed in ovarian tissues, albeit at significantly higher levels in the cytoplasm of ovarian carcinoma cells. Consistent with this observation, the authors demonstrated by ELISA that the...

Carcinogenicity testing the Ames test

The great majority of carcinogenic substances, that is, substances that cause cancer in humans and animals, are also mutagenic in bacteria. This fact has been used to develop an initial screening procedure for carcinogens instead of the expensive and time-consuming process of exposing laboratory animals (not to mention the moral issues involved), a substance can be tested on bacteria to see if it induces mutations. The Ames Test assesses the ability of a substance to cause reverse mutations in aux-otrophic strains of Salmonella that have lost the ability to synthesise the amino acid his-tidine (his-). Rates of back mutation (assessed by the ability to grow in a histidine-free medium) are compared in the presence and absence of the test substance (Figure 11.23). A reversion to his+ at a rate higher than that of the control indicates a mutagen. Many substances are procarcinogens, only becoming mutagenic carcinogenic after metabolic conversion by mammals in order to test for these, an...

Psychological distress associated with genetic counselling for breastovarian cancer

Relevant psychological issues have been raised and discussed regarding hereditary breast cancer (Lerman and Croyle, 1994). A point to note is that much of the current research work in this area is theoretical, and a variety of measures and inclusion criteria are used that make comparison between studies difficult. As studies have used different assessment tools for measuring psychological distress, apparent prevalence rates for distress vary (Hopwood et al., 1998), which has implications for clinicians who provide genetic counselling. A variety of measures are used. Some are specific to anxiety or depression (e.g. Hospital Anxiety and Depression Scale - Zigmond and Snaith, 1983 Beck Depression Inventory - Beck and Steer, 1987 State-Trait Anxiety Inventory - Spielberger et al., 1983), others assess more general psychiatric distress (e.g. General Health Questionnaire -Goldberg and Williams, 1988), and others are cancer specific, or can be adapted to be so (Cancer Worry Scale - Lerman et...

Nutrition and Cancer Cachexia Anorexia

The mechanisms of the development of cancer cachexia are complex and not completely understood. Costa (1977) likened the cachectic state to the diseases of protein-calorie malnutrition, kwashiorkor, and marasmus, which are more commonly seen in relatively undeveloped areas of the world. In fact, patients with advanced cancer may lose significant amounts of nitrogen and fat and exhibit protein-calorie malnutrition (Nixon et al., 1980). As with malnutrition, some of the characteristics of cachexia may be overcome by forced feeding programs involving either total parenteral nutrition, that is, intravenous feeding, or hyperalimentation by means of stomach intubation or similar methods. However, such methods do not appear to prolong survival or affect many of the complications of advanced neoplasia (Balducci and Hardy, 1985 Vigano et al., 1994). In view of this lack of effectiveness of such nutritional modalities, various pharmacological approaches to the treatment of cachexia in advanced...

Nitrosamine Exposure And Human Cancer

Experimental studies provide evidence that the biological activity of iV-nitroso compounds in humans is not substantially different from that in experimental animals (1). In contrast to animal experiments, in which exposure (normally at high concentrations) to single 2V-nitroso compounds may induce cancer (2), human exposure (3,6,7,17) results via several different sources (eg, diet, occupational exposure, and tobacco consumption) at a wide range of different concentrations. Dose-response studies using experimental animals show that NDEA, NMOR, and NPYR continuously administered in drinking water at exposure levels of 0.075 mg L (0.075 ppm), 0.07 mg L, and 0.01 mg kg body weight d, respectively, are sufficient to induce a significant incidence of tumors. In animal carcinogenicity experiments, the absence of a lower no-effect threshold and the syncarcinogenic activity of low concentration combinations of AT-nitroso compounds at concentrations at which individual iV-nitrosamine...

Peutz Jeghers Syndrome and Cancer Risk

Peutz-Jeghers syndrome is a hereditary cancer-susceptibility syndrome, as evidenced by the development of malignancies in the great majority of patients during their lifetimes, the early age of cancer diagnosis in these family members compared to the general population, and the occurrence of cancers in related individuals in these families. Although the polyps in PJS patients are restricted to the gastrointestinal tract, the malignancies that arise in these families can be found in a variety of organ sites, including the gastrointestinal tract. The gastrointestinal malignancies can occur anywhere in the mucin-secreting portion of the luminal GI tract as well as in the pancreas. Interestingly, although foci of dysplasia can be found in larger Peutz-Jeghers polyps, the hamartomatous polyp of Peutz-Jeghers syndrome is typically a benign neoplasm. Most gastrointestinal cancers are believed to arise from coexisting adenomatous polyps. Nongastrointestinal tumors occur in the skin, thyroid,...

Humoral Factors In Cancer Cachexia

As indicated earlier in this chapter, a variety of humoral or circulating factors influence the development of cancer cachexia and many nutritional aspects of the host-tumor relationship. Furthermore, the interactions and interrelations of many of these factors add to the complexity of the mechanisms of cachexia seen in the tumor-bearing host. No single amino acid, cytokine, steroid, or polypeptide hormone can account for the syndrome of cancer cachexia. A list of some of the major humoral factors and their interrelationships are seen in Table 17.6.

Tumor Necrosis Factora and Related Cytokines in Cancer Cachexia

The effects of TNF were first observed in the latter part of the nineteenth century by Coley (1893) based on the observation that patients with streptococcal infections might also exhibit a partial remission of some neoplasms. Subsequent investigations demonstrated that injection of bacterial products, specifically a lipopolysaccharide, could induce hemorrhagic necrosis of transplantable neoplasms in mice. Subsequently, a serum factor associated with administration of the bacterial product was isolated and named tumor necrosis factor (Carswell et al., 1975). Since that time, there has been a dramatic increase in our knowledge of TNF-a, its genetics, and its function. TNF-a is a member of a superfamily of genes of which more than 10 are presently known, along with their respective receptors (cf. Gruss, 1996). Neoplasms engineered to express high levels of TNF when grown in mice rapidly induce a syndrome of cancer cachexia (Oliff

The Complexity Of Cancer Cachexia

As indicated at the beginning of this chapter, the syndrome of cancer cachexia resembles several nutritional syndromes such as starvation or protein-calorie malnutrition. It is clear, however, that this aspect of the host-tumor relationship is extremely complex, involving not only nutritional factors but also a wide variety of humoral and hormonal components, many of which are known and a number of which are undoubtedly unknown. The idea that humoral factors or hormones may be critical in the causation of cachexia was actually first suggested more than four decades ago by Nakahara and Fukuoka (1958), who proposed that a hormone-like substance that they termed toxohormone was responsible for significant changes in the tumor-bearing host, particularly a depression of the level of the enzyme catalase in the liver. Although the concept of toxo-hormone is generally not considered as significant in the cachectic syndrome today, this original work pointed the way to the present-day...

Hereditary breastovarian cancer families

Prior to the detailed characterization of BRCA1 (and the discovery of BRCA2), a number of studies focused on individuals with a proven family history of breast and ovarian cancer, two reported rates of interest (definite or probable) in a genetic test being approximately 95 (Lerman et al., 1994 Struewing et al., 1995). A third study (Julian-Reynier et al., 1996) found a similar rate amongst unaffected women with at least one first-degree relative (FDR) affected, but a lower rate of interest (76 ) in affected women. Struewing et al. (1995) added a note regarding the fact that their sample was made up of people involved in linkage studies (some having given blood), and that this was possibly a factor in the high rate. Lerman et al. (1994) suggested that the request rate for tests among low-risk women would be high, based on a telephone poll of FDRs of women with ovarian cancer. Lerman et al. (1995), in a similar study that examined the FDRs of breast cancer Attitudes about genetic...

Modulation Of Pglycoprotein In Cancer Treatment

A major reason for the failure of chemotherapy treatment to cure human cancers is the ability of tumor cells to become resistant to several anticancer drugs simultaneously. Many mechanisms are known to contribute to MDR in tumor cells, of which the presence of multidrug efflux pumps is only one. Three ABC family members, Pgp, MRP1 (ABCC1), and BCRP (ABCG2), are likely to be the major drug efflux pumps expressed in human cancers.195 Tumor cells are notoriously heterogeneous, and correlations between drug resistance and the expression of efflux pumps have been difficult to establish. Some tumors express Pgp before chemotherapy treatment (e.g., colorectal and renal cancers), while in others, expression increases after exposure to MDR drugs (e.g., leukemias, lymphomas, myeloma, and breast and ovarian carcinomas). In general, patients with Pgp-positive tumors respond less well to chemotherapy and have a poorer outlook and long-term survival. There is strong evidence linking Pgp expression...

Is There a Relationship between Cancer Associated DNA Hypomethylation and DNA Hypermethylation

Hypomethylation of some DNA sequences and hypermethylation of other sequences has been found in rat hepatocarcinomas and human breast, colon, and prostate adenocarcinomas.45,76 72 Given the prevalence of both of these types of changes in cancers when they have been studied individually, they probably coexist in the vast majority of cancers but simply have not yet been documented to be simultaneously present. Hypermethylation of the GST P promoter and hypomethylation of LINE-1 repeats were found in some of the same prostate adenocarcinomas but no significant association was observed between these two types of epigenetic changes in this kind of cancer.41 Recently, in collaboration with Peter Laird and Emerich Fiala, we have shown that global DNA hypomethylation, satellite DNA hypomethylation, hypomethylation of a promoter, and hypermethylation of CpG island-promoters are present concurrently in many Wilms tumors.75 Global hypomethylation was significantly associated with Sat2...

Late Phase Ii Clinical Trials Of S1 In Advanced Gastric Cancer

According to the same schedule as that of the clinical pharmacological study, the late phase II clinical trial of S-1 was conducted subject to patients with advanced or recurrent gastric cancer at a dose of 40 mg m2, basically with four or more courses, each of which consisted of twice-a-day (once each after breakfast and dinner), 4-wk consecutive oral administration and of 2-wk withdrawal. The results of the late phase II clinical trials, which were reported by two groups, i.e., one of Sakata et al. (31) and another of Koizumi et al. (32), are summarized in Table 6 the overall response rate was 44.6 (45 101). As shown in Fig. 12, the survival curve was based to consider that MST was 244 d. Adverse reactions of a total of 362 patients in the late phase II clinical trials are shown in Table 7 the incidence of adverse reactions (> G3) was Response Rates in the Late Phase II Clinical Trial of S-1 (Gastric Cancer) Response Rates in the Late Phase II Clinical Trial of S-1 (Gastric Cancer)

Late Phase Ii Clinical Trial Of S1 In Colorectal Cancer

The response rate of S-1 for colorectal cancer in the early phase II clinical trial was as modes at 16.7 (Table 4). However, the response rate was 25 in patients without prior chemotherapy, thus warranting further research on this disorder. The late phase II clinical trial of S-1 was conducted to evaluate the efficacy and toxicities in patients with metastatic colorectal carcinoma. Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled in this clinical trial. None of the patients had received chemotherapy prior to this clinical trial, except the adjuvant setting. S-1 was administered orally at a standard dose of 80 mg m2d, twice daily for 28 consecutive days followed by 14-d withdrawal. This regimen was maintained until when the disease progressed, an intolerable toxicity developed, or the patient refused the drug. As shown in Table 8, the overall response rate was 35.5 . As shown in Fig. 13, the median survival time was 378 d. The main adverse reactions...

Phytochemicals And Cancer

Although there is abundant evidence implicating free radicals with cancer, the precise mechanism by which oxida- tive stress produces cancer is less clear. The free radicals (especially hydroxyl radicals), hydrogen peroxide, lipid peroxides, and singlet oxygen have been shown to cause DNA damage. The damage can occur through oxidative modification of the base and or sugar moiety, single- and double-strand breaks, and DNA cross-linking (10). All this damage can be repaired through DNA repair enzymes, but problems may arise. Mutations following the incorrect repair or replication of DNA may lead to carcinogenesis. The body employs a series of enzymatic and structural antioxidant defenses along with exogenous dietary antioxidants to combat oxidative damage. However, these defenses are not perfect, and if the rate at which DNA becomes oxidized exceeds the rate at which it can be repaired, problems will arise. Over time, DNA damage becomes cumulative and is believed to account for the...

Late Phase Ii Clinical Trial Of S1 In Head And Neck Cancer

This clinical trial was conducted to examine the antitumor activity and toxicities of S-1, in which 60 patients with head and neck cancer were enrolled. S-1 was administered at a dose of 40 mg m2d, with at least four courses, each of which consisted of twice-a-day (once each after breakfast and dinner), 28-d consecutive oral administration and of 14-d withdrawal two courses were repeated every 6 wk unless the disease progressed. As shown in Table 9, there were four complete response cases and 13 partial response cases (response rate 28.8 ) among 59 evaluable cases. The adverse events that were assessed to be Grade 3 or higher were as follows hemoglobinemia (6.8 ) neutropenia (5.1 ) leukopenia (1.7 ) decreased RBC (3.4 ) and anorexia, nausea vomiting, stomatitis, and fatigue (1.7 each) (34).

Ipsi and contralateral breast cancer recurrences

Lumpectomy followed by radiation therapy, i.e. the conservative management of breast cancer, has been accepted as a standard of care for the majority of women with early breast cancer. Long-term follow-up data have consistently shown a risk of ipsilateral breast tumour recurrence (IBTR) of 0.5-2 per year (Recht et al., 1988 Fourquet et al., 1989 Kurtz et al., 1989 Fisher et al., 1991 Veronesi et al., 1995), but breast cancer survival was not significantly affected by IBTR when compared with patients undergoing a radical mastectomy (Haffty et al., 1991a Fisher et al., 1995 Jacobson et al., 1995 Veronesi et al., 1995 Winchester et al., 1997). Early age of onset is associated with an increased risk of IBTR (Schnitt et al., 1984 Haffty et al., 1991b de la Rochefordiere et al., 1993), but an association was not consistently found when the patient reported a positive family history of breast cancer (Chabner et al., 1998 Harrold et al., 1998). Young age at primary breast cancer diagnosis, a...

Cancer and risk status

Up to 18 of the family members offered testing were affected with cancer (B), with two papers (W and M-H) concentrating only on pre-symptomatic testing, and one further work (S) not specifying what proportion of individuals contacted had a diagnosis of cancer. In most cases, the uptake amongst affecteds and unaffecteds is either directly reported or deducible from the data provided. Unsurprisingly perhaps, every paper that provided complete data on cancer status showed a higher rate of utilization of counselling (H) or testing in affecteds than in unaffecteds, except where data were only available for study participants (BB), where a rate of 79 was reported for both groups. J-R reports the lowest figures in each group, while L consistently reports the highest (23 vs 56 and 69 vs 74 unaffecteds and affecteds respectively). This may once more reflect differences in recruitment methodology. J-R, M-H and H provide the best descriptions of the chance of each unaffected individual...

Might There Be Deleterious Consequences of Introducing DNA Hypomethylation in the Genome As a Cancer Therapy

The DNA methylation inhibitors 5-azacytidine, 5-aza-2'-deoxycytidine (decitabine), and 5,6-dihydro-5- azacytidine have been used as cancer chemotherapeutic agents in clinical trials on various neoplasms, including refractory acute leukemia 89 myelodysplastic syndrome 90 advanced non-small cell lung cancer 91 malignant mesothelioma 92 accelerated or blast phase of chronic myeloid leukemia 93 advanced ovarian or cervical carcinoma 94,95 malignant melanomas and colorectal, head and neck, and renal carcinomas.96 For solid tumors, usually little or no clinical efficacy and often no disease stabilization was seen, but many toxic effects were observed.89,91,94-9 Combination therapy on malignant mesothelioma, which showed a low response to 5,6- dihydro-5-azacytidine alon,92 did not improve the response rate (17 ) and increased the toxicity.97 There has been considerable attention recently to testing the efficacy of treatment of high-risk myelodysplastic syndrome (MDS) with 5-azacytidine or...

Gastric Cancer and Stroke

There is a strong geographical correlation between stomach cancer and stroke mortality, both of which correlate with salt intake. There are four recognized major etiological factors for gastric adenocarci-noma infection with Helicobacter pylori, excessive salt consumption, and low intakes of ascorbic acid, carotenoids or more generically of vegetables and fruits. Sodium chloride induces atrophic gastritis and enhances the mutagenic effect of nitrosated foods. Salt may also play a role in the later steps involving the transformation of mucosal dysplasia to carcinoma. The salted pickles and salted fish of Japanese cultures appear to be strongly linked to the development of stomach cancers.

Childhood Cancer and Its Ethical Challenges

Cancer kills more children than does any other disease. Recent data show that after unintentional injury, childhood cancer continues to be the most common cause of death for children ages one to nineteen years in the United States (Hoyert et al., p. 257). Beyond the impact on mortality, the disease burden of childhood cancer is very significant. The quality of life of an afflicted child and his or her family are affected profoundly. The time of a new diagnosis is a particularly difficult period, with parents reporting tremendous stress and emotional turmoil (Dahlquist et al., p. 111 Levi et al., p. 244). Ethical issues in childhood cancer are complex and potentially difficult to resolve. Until recently children were compared to incompetent adults, for whom treatment-related decisions are made by a close family member. Ethicists now point out that this comparison fails to acknowledge a key distinction between children and incompetent adults The former are different because in most...

Familial ovarian cancer

Familial aggregation of ovarian cancer has been variably defined as occurring when (1) two first-degree relatives have ovarian cancer, or (2) the proband has ovarian cancer as well as one or more of her first- or second-degree relatives (Lynch and Lynch, 1992). Case-control studies designed to estimate the relative risk of developing ovarian cancer associated with a family history of the disease are summarized in Table 4.1. In a meta-analysis of case-control and cohort studies on family history and risk of ovarian cancer, the relative risk for all first-degree relatives was 3.1 (95 CI, 2.6-3.7), 1.1 (95 CI, 0.8-1.6) for mothers of cases, 3.8 (95 CI, 2.9-5.1) for sisters and 6.0 (95 CI, 3.0-11.9) for daughters, respectively (Stratton et al., 1998). In another study, the risk increased with the number of first-degree relatives affected (Kerber and Slattery, 1995). Initial work suggested that women who have one first-degree relative affected by, or who died of, ovarian cancer were at...

DNA Methylation in Urological Cancers

Urological cancers are a diverse group with different alterations of DNA methylation. In all urological cancers, DNA hypermethylation of specific genes has been described. In contrast, methylation of repetitive sequences is often diminished, resulting in decreased overall methylation levels (global hypomethylation). Altered imprinting is also found. Tes-ticular tumors are derived from more or less immature germ cells whose methylation patterns they often reflect. Subtypes can be distinguished by the extents of global hypomethylation and hypermethylation. Renal cell carcinomas typically display hypermethylation restricted to specific genes important for tumor development and progression. By comparison, methylation patterns are more severely disturbed in prostate and bladder cancers in which hypermethylation of multiple genes coexists with genome-wide hypomethylation. Causes of altered methylation may also differ. Hypermethylation could be incidental in renal cancers, but is more likely...

Stomach Cancer Gastric Adenocarcinoma

The most common (85 ) stomach cancers are adenocarcinomas the rest are non-Hodgkin's lymphomas and sarcomas. The incidence of gastric adenocarcinoma has declined with time. In the early part of the twentieth century it was the leading cause of cancer-related deaths in men in the US. Although the incidence remains relatively high in Japan, China, Chile, and Ireland, a decrease in incidence and mortality has been seen in these countries as well. The risk of gastric adenocarcinoma is greater in the lower socio-economic classes. Migrants from high-incidence countries to low-incidence countries maintain the same risk of gastric adenocarcinoma but their offspring tend to have similar risks to those who are originally from the host nation. This suggests that early environmental exposures have an effect on the development of gastric cancer. Gastric adenocarcinomas can affect different parts of the stomach. In the US, 37 of tumors arise from the proximal third, 20 arise from the mid-portion,...

Experimental models to study the effects of nutrients on colon carcinogenesis

14.4.1 Carcinogenesis induced by chemicals Among the various experimental models used to study colon carcinogenesis, those using azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH) to induce colonic cancer in rodents are very important, since these two carcinogens induce tumors through the sequential formation of histopathological lesions similar to those observed in spontaneous carcinogenesis in humans (Chang, 1984). Accordingly, these methods have been widely used to study the biology of the various phases of colon cancer but also to study the correlation between diet and cancer, by comparing cancer incidence in DMH AOM initiated rodents fed with different dietary regimens (Fig. 14.3). The DMH AOM model is also very popular for study of the effect on colon carcinogenesis of putative chemopreventive chemicals such as non steroidal anti-inflammatory drugs (Corpet and Tach , 2002). Other carcinogens more related to food, such as heterocyclic amines have also been used to induce...

Bioethics of Failure Antiheroic Cancer Narratives

In this chapter I problematize a particular mode of being ill and writing about being ill that attempts to reverse or revise the crisis of illness by describing a sort of heroism in the face of such a crisis. This heroic art of existence1 is, perhaps not surprisingly, quite common in illness narratives, as individuals who are ill attempt to exert a measure of control over their illness as well as the corresponding stories. In order to challenge and or supplement the heroic mode of being ill, I discuss two recent narratives about the experience of ovarian cancer Jackie Stacey's Teratologies A Cultural Study of Cancer (1997) and Gillian Rose's Love's Work A Reckoning with Life (1995). Both authors are British academics, and their accounts of illness represent journeys into uncharted narrative territories, although both writers also draw heavily from the theory and methods of their particular fields of study Stacey from feminist theory and British cultural studies, and Rose from...

An Overview of Urological Cancers

Urological cancers constitute a diverse group of tumors different in origin, biology, clinical course and treatment options (Fig. 1). Testicular cancers are usually diseases of younger men. Most share a common origin from germ cells that have become aberrant at different stages of development. Unlike many other carcinomas, they respond well to chemotherapy. The more common urological malignancies befall older people. This is most evident for prostate carcinoma which is now the most prevalent lethal cancer of older men in industrialized countries. This adenocarcinoma is derived from the secretory epithelium of the gland. Organ-confined cases can be cured by surgical removal of the prostate (prostatectomy) or by radiotherapy. Since testosterone is essential for the proliferation of normal and many transformed prostate cells, many locally advanced and metastatic tumors respond to androgen deprivation, although this treatment is not curative. Because of the difficulty to clinically...

Controlled clinical trials morphine cancer

The population from which the 10 patients in the study were drawn had progressive malignancy as the primary cause of their breathlessness. In one case, this was secondary to pleural effusion but in the other cases it was primary or metastatic lung cancer. To take this study a step further, Allard and his team conducted a multi-site randomized continuous sequential clinical trial exploring paired preferences for supplementary opioids in dyspnoea.7 Thirty-three patients with cancer, pain requiring stable doses of opioids and dyspnoea at rest despite oxygen were enrolled in the study. Details of comorbid lung conditions were not reported. A single additional dose of opioid at either a 25 or 50 per cent increment on their fourth hourly baseline dose by the route that they were already receiving was administered. Pairs at the two dose levels were assigned randomly using the same route of administration. Patients were followed for 4 hours with each subsequent measure of breathlessness...

Testing for Carcinogenicity and Teratogenicity

Carcinogenic potential can be detected by three types of tests long-term carcinogenicity studies, rapid screening tests, and biomarkers. Long-term tests are the most definitive. These generally use mice or rats and last the lifetime of the animals (18 and 24 months, respectively). Two or three dose levels are usually used, the highest being the maximum tolerated dose'' (MTD). The MTD is estimated from 90-day studies and is chosen so as not to produce severe noncarcinogenic toxicological effects or to reduce significantly the life of any organisms that do not develop tumors. The other doses are typically one-fourth to one-half of the MTD. The number of tumors is recorded by animal (location, whether benign or malignant, the presence of any unusual tumors), the number of animals with tumors, the number of tumors per animal, the number of tumor sites, and the time to onset. In the United States, a set of minimum test standards for carcinogenicity has been developed by the National...

Targeting Ras For Cancer Treatment

Despite their importance in cancer treatment, the clear therapeutic limitations of our current repertoire of cytotoxic anticancer drugs are well appreciated. Thus, it is widely embraced that novel drug development approaches will be required to accelerate our progress towards curing cancer. Much hope is placed in studying cancer genetics (the identification of specific genes whose aberrant function may promote the development of human cancers). There are high expectations that rational drug discovery efforts will be able to correct the biologic consequences of malfunctioning oncogenes and of non-functioning tumor suppressor genes. The 30 prevalence of ras mutations in human cancers has marked it as one of the most promising oncogene targets for such efforts. In particular, the high prevalence of ras gene mutations in carcinomas ofthe pancreas, lung, and colon lends anti-Ras drug strategies importance in the treatment of solid tumors for which current therapy is limited or ineffective....

Genetic Carcinogenesis The Key To Unlocking The Secrets Of Cancer

From this overview, the student will hopefully appreciate that the explosion in our knowledge of genetic mechanisms is reflected in a dramatic increase in our understanding of neoplasia and its genesis. In the remainder of this text, there are numerous other examples verifying this statement. However, as indicated earlier in this chapter, germline genetic alterations do not constitute the major cause of neoplasia in the human, although especially the multifactorial, polygenic area may be involved in the causation of a great percentage of all human cancer. The next chapter views the genetics of neoplasia not from the germline but from the inheritance of somatic cells. This process, as we have noted from our definition of neoplasia (Chapter 2), is ubiquitous, and much of our knowledge of somatic cell genetics has now evolved from the genetic revolution of the latter part of this century.

Controlled clinical trials nebulized morphine cancer

Although there are a relatively large number of reports in the literature16 about the use of nebulized opioids, most focus on the ability to work before stopping due to breathlessness. This functional improvement may not be the best primary end-point to measure in people with dyspnoea due to advancing life-limiting illnesses such as cancer or end-stage organ failure. One exception to this is the study by Davis and her group where 79 patients with lung pathology were enrolled in a double-blind, single dose, randomized placebo-controlled study exploring the effect on breathlessness at one hour after nebulized morphine.22 The patients needed to have demonstrated lung pathology from cancer on chest x-ray and relatively normal renal function. On consecutive days, patients were administered nebulized saline or nebulized morphine (dose 5-50mg).

Some Retroviruses Cause Cancer and AIDS

Retroviruses have featured prominently in recent advances in the molecular understanding of cancer. Most retroviruses do not kill their host cells but remain integrated in the cellular DNA, replicating when the cell divides. Some retroviruses, classified as RNA tumor viruses, contain an oncogene that can cause the cell to grow abnormally (see Fig. 12-47). The first retrovirus of this type to be studied was the Rous sarcoma virus (also called avian sarcoma virus Fig. 26-31), named for F. Peyton Rous, who studied chicken tumors now known to be caused by this virus. Since the initial discovery of oncogenes by Harold Varmus and Michael Bishop, many dozens of such genes have been found in retroviruses.

Cancer Tomorrow and the Future

In the 15 years since the publication of the third edition of this textbook, a veritable explosion of knowledge has occurred in the fields of cell and molecular biology, genetics, computer technology and bioinformatics, and many other basic and applied fields. Simultaneously, there has been an explosion in our knowledge of neoplasia. This knowledge has possibly led to some concrete results in that the overall death rate from cancer in the United States decreased by 3 during the period 1990-1995 (Cole and Rodu, 1996) and in the European Union by about 7 between 1988 and 1996 (Levi et al., 2000). However, as was the case 15 years ago, there is still no magic bullet to cure cancer, unlike the antibiotics that are able to cure the majority of bacterial infections in the human. Just as it was 15 years ago, despite the explosion in knowledge, medical science continues to be frustrated in its effort to establish a truly effective therapy for the most common forms of malignant neoplasms in...

Global View of DNA Methylation Alterations in Urological Cancers

The results presented in the previous section suggest that although hypermethylation of some genes (VHL, DBCCR1) occurs only in specific urological cancers, many genes are subject to DNA hypermethylation in several tumor types (Table 1). Such genes may interfere with universal properties of tumor cells, such as uncontrolled proliferation (CDKN2A) or decreased adhesion (CDH1). Nevertheless, some genes of general importance in human cancers seem to become hypermethylated never (PTEN) or rarely (RB1). The molecular basis for this difference has begun to be addressed by studies on Moreover, several genes, like CDKN2A, are inactivated by hypermethylation, point mutation, or homozygous deletion in different human cancers, but the contribution of each mechanism differs widely.73 The molecular basis for these differences is also unknown. Beyond the investigation of individual genes, several new methods developed recently aim at surveying methylation changes in cancers (see other contributions...

Hypermethylation During Breast Cancer Progression

Although the past decades of research have shed new light into the epigenetic mechanisms involved in breast carcinogenesis, it is still difficult to establish a precise timing for promoter hypermethylation of the cancer related genes involved in mammary carcinogenesis. This is due to two

Cancer Epidemiological Evidence

For the involvement of free radicals throughout the cancer process. Attempts to prevent cancer using vitamin E are based on the rationale that oncogen-esis results from free radicals attacking DNA. As an antioxidant, vitamin E may inhibit cancer formation by scavenging reactive oxygen or nitrogen species. Several studies of oral, pharyngeal, and cervical cancer found a relationship between vitamin E status and cancer risk. The evidence for stomach and pancreatic cancers has not been consistent, and no association with breast cancer has been found. The Linxian, China, intervention trial provided evidence that nutritional supplementation may lower the risk of certain cancers. A modest but significant reduction in cancer mortality was observed in a general population trial in those receiving daily (for 5.25 years) a combination of ft-carotene (15 mg), vitamin E (30 mg), and selenium (50 mg). The subjects who received this mixture had a 13 lower incidence of cancer and a 10 lower...

Plots of Cancer Incidence at Different Times and Places

The following plots show cancer incidence and acceleration patterns at different time periods and in different countries. In some cases, the acceleration plots fluctuate between countries because of the nature of the data, which may have small numbers of cases at early or late ages. Thus, it is best to focus only on the broad trends in the acceleration plots, particularly those patterns that recur in different years and in different locations. For example, prostate cancer shows a remarkably strong and linear decline in acceleration beginning in midlife (Figure A.2). Some cancers show midlife peaks in acceleration, for example, colon and bladder cancer (Figure A.4). Cervical cancer has an acceleration close to zero throughout life, with higher fluctuations outside the USA probably caused by smaller samples for those other countries (Figure A.12). However, cervical cancer in the USA follows different patterns of acceleration in different ethnic groups (not shown), emphasizing that...

DNA Methylation in Colorectal Cancer

In this chapter, it is pointed out that colorectal cancer is a heterogeneous disease. The case is early acquisition of DNA instability. DNA hypermethylation is likely to be of critical importance in driving this pathway. Inhibition of apoptosis is conceived as the first step. Thereafter, methylation of one of several DNA repair genes would result in a state of tolerated hyper-mutability. It remains to be shown whether this model applies to a small subset of colorectal cancers or in fact explains the great majority given the overall low risk of progression for an individual adenoma initiated by mutation of APC. Colorectal cancer is not only an important disease in terms of its frequency and contribution to human suffering but also because it provides an instructive model for neoplasia in general. There are two reasons why colorectal cancer has served as a successful model. First, the precancerous stages present as mucosal lesions (polyps) that can be identified and removed with...

Conclusion Of Ovarain Cancer

The rapidly evolving practice of clinical genetics is throwing up many questions to which we do not yet have clear answers. This is nowhere more apparent than in the genetics of common cancers, including breast cancer, which is the fastest growing area of genetic medicine. If this chapter has dwelt on problems rather than solutions, this is a reflection of the current 'state of the art' rather than of any underlying pessimism. We live in exciting and, above all, hopeful times. Given the pace of progress over the past decade, those involved in developing clinical and laboratory services for cancer families, in partnership with the families themselves, look forward with great confidence to a transformation scene within the next 20 years. Baildam AD (1999). The role of bilateral prophylactic mastectomy (BPMX) in women at high risk of breast cancer. Dis Markers 15 197-8. Barlow-Stewart KK, French JA, O'Donnell SM and Spigelman AD (2001). Genetic Discrimination Experienced by Australian...

Mouse Skin Multistage Carcinogenesis Model That Unmasks Epigenetic Lesions Responsible For Metastasis

Cancer Epigenetics Laboratory, Molecular Pathology Programme, Spanish National Cancer Centre (CNIO), Madrid, Spain Abstract Although there is a wide range of accepted models of tumorigenesis involving genetic lesions, the timing and hierarchy of epigenetic alterations associated with tumor progression and metastasis are still poorly understood. In this regard, the best characterized mouse carcinogenesis system, the multistage skin cancer progression model, has recently been used to identify epigenetic alterations during tumor progression and to provide decisive information about how epigenetic lesions precede metastasis. This model reveals a progressive global loss of genomic methylcytosine that is associated with the degree of tumor aggressiveness and that occurs in the context of increasing numbers of hypermethylated CpG islands of tumor-suppressor genes during the most malignant stages of carcinogenesis. DNA microarrays coupled with demethylating drug treatments confirm the...

Causes of Altered DNA Methylation in Urological Cancers

The causes of altered methylation may be distinct in different cancers (Fig. 2). In some cancers, apparently aberrant methylation may in fact largely reflect the methylation pattern of the affected stem cell. Thus, different germ cell tumors display methylation patterns at imprinted genes corresponding to distinct stages of germ cell development.8,10,14 Conversely, failure to set up proper methylation patterns of mature cells may underlie blocked differentiation. Clear-cell renal carcinomas may exemplify a group of cancers displaying a limited number of methylation changes. Some of these could be caused by incidental errors for which there is strong selection during tumor development because they lead to inactivation of crucial tumor suppressor genes such as VHL. Others such as CA9 hypomethylation62 may be secondary to alterations in transcriptional activators. In contrast, advanced prostate and bladder cancers are typically characterized by severely disturbed DNA methylation patterns...

Propionibacteria and cancer

Among the beneficial effects that have been attributed to probiotics, the prevention of cancer, with a main focus on colon cancer, constitutes the most promising and probably the most controversial potential. As stated by J. Rafter, there is no direct evidence for cancer suppression in humans as a result of probiotic consumption (Rafter, 2003). However, there is wealth of indirect evidence, based on experimental work, both in vivo and in vitro, of anticancer properties of some probiotics. Probiotics may interfere with the development of cancer via binding and degradation of carcinogens, production of anti-mutagenic compounds, modulation of the intestinal microbiota and or metabolic activities or by enhancing the host's immune response. Several dairy propionibacteria species were shown to induce apoptosis of two human colorectal cancer cell lines in vitro (Jan et al., 2002a). This effect was attributed to the secretion by propionibacteria of short chain fatty acids, acetate and...

Cpg Island Hypermethylation Changes During Prostate Cancer Initiation And Progression

In 1994, Lee et al. demonstrated that hypermethylation of CGI sequences within the regulatory region of GSTP1, which encodes the pi-class glutathione S-transferase (GST) enzyme, is an extremely frequent feature of human prostate cancer (49, 50). Since that initial study, numerous groups have independently corroborated these findings using a wide array of techniques applied to numerous prostate cancer DNA sources, including prostatectomy specimens, prostate autopsy specimens, prostate biopsy specimens, prostate secretions, and various bodily fluids from prostate cancer patients. Furthermore, GSTP1 CGI hypermethylation appears to be an extremely specific finding for prostate cancer as it is not characteristic of normal prostates or benign prostatic hyperplasia. The GST enzymes catalyze the detoxification of carcinogens and reactive chemical species via the conjugation of glutathione. It has been hypothesized that loss of this detoxification agent in prostate cells might make them...

Genetic Testing And Counseling In Hereditary Breast And Ovarian Cancer Syndrome

Genetic testing for HBOC has become generally accepted as part of standard clinical practice and should be offered to any patient that has personal or family history features suggestive of HBOC (Table 3) and when genetic testing results could influence the medical management of that patient or the patient's family members. Clinical laboratories employ a variety of molecular techniques to detect germline mutations in BRCA1 and BRCA2 in a peripheral blood sample (Table 4). The sensitivity of molecular testing for BRCA cancer-predisposing mutations is Table 1 Syndromes associated with hereditary breast and or ovarian cancer Hereditary cancer syndrome ovarian cancer BRCA2 Hereditary diffuse gastric cancer Hereditary nonpolyposis colorectal cancer Breast, ovarian, colon, and prostate cancer Breast, ovarian, prostate, pancreatic, bile duct and gall bladder, stomach cancer, and malignant melanoma Soft-tissue sarcomas, breast cancer, brain tumors, acute leukemia, and other epithelial and...

From the Normal Breast to Cancer the Concept of Breast Cancer Stem Cell

It is now well established that breast cancer originates from the TDLU, but it is not clear which are the cells targeted by tumorigenesis (6-10). A recent interesting hypothesis based on experimental evidence from tumor subpopulation transplantation and animal models suggests that mammary tumors may derive from adult breast stem cells (2, 11). The involvement of stem cells in carcinogenesis was suggested more than 30 years ago (10, 1214), but only recently the tools of stem cell biology were applied to the study of carcinogenesis (14). Adult stem cells are defined by their ability for self-renewal and differentiation into cell lineages present in the specific tissue. Self-renewal ensures propagation of the stem cell compartment, which sustains morphogenesis, tissue repair and maintenance, whereas differentiation generates the specialized cells that constitute each organ (7, 15-17) (Figure 1A). The adult mammary gland requires stem cells or stem cells like activity to fulfill the...

Neurotensin Receptor Implication in Cancer

Increasing evidence demonstrates that proNT and NTS1 are deregulated in several human cancers such as colon, pancreatic, prostate, and lung cancer, suggesting that NT may exert an autocrine activation of its own NTS1 receptor in cancer. Thus, the use of NT receptor antagonists to block the proliferative effect of NT on cancer cells is one of the promising prospects in cancer therapy. In this respect, it has been recently reported that SR 48692 could inhibit NT-stimulated growth of human colon, pancreatic, and lung cancer cell lines and, when administered alone to nude mice grafted with human NTS1-expressing colon cancer cells, could induce a reduction in tumor volume. It also seems that the proliferative effect of NT can be mediated not only by NTS1 but also by NTS3 since several of the cancer cells coexpressed both receptor subtypes. Selective NTS3 antagonists may thus be of particular interest in cancer therapy. Not only NT antagonists but also NT agonists may be useful in cancer....

The immunology of photocarcinogenesis

The first indication that UV radiation could produce systemic immunological alterations came from studies on UV-induced skin cancers in mice. These cancers are highly antigenic and are generally immunologically rejected upon transplantation into genetically identical mice. This unusual property of UV-induced tumors prompted studies to determine how such highly antigenic tumors could survive and grow progressively in the original host. Such studies demonstrated that the UV radiation-induced tumors were able to grow progressively when transplanted into mice that had been exposed to a short course of UV irradiation but had not yet developed primary skin cancers. Because the tumors would grow when transplanted into tissues not directly exposed to UV radiation, these studies demonstrated that UV exposure produced a systemic effect on the host that interfered with its ability to reject these highly antigenic skin cancers. The systemic effect was immunological becausc it could be transferred...

Pathology Pathogenesis and Carcinogenesis

Follicular carcinoma is characterized by a follicular appearance without the specific nuclear features seen in papillary cancers. These neoplasms are distinguished from follicular adenomas by the presence of neoplastic invasion of the tumor capsule and adjacent blood vessels. The cytologic appearance of these malignant follicular cells is often quite bland and fine needle aspiration biopsy cytology alone can not distinguish benign follicular adenomas from their malignant counterpart.3,5 Distinguishing the histologic features of a cellular follicular adenoma from a follicular carcinoma with minimal capsular invasion still remains a challenge for even the most experienced endocrine pathologist and intraoperative frozen section of these tumors has not been uniformly helpful. Likewise, DNA ploidy and cell cycle analysis have not proven reliable in identifying patients with follicular malignancy. Over the last five years, advances in the identification of oncogenes responsible for thyroid...

Definition and classification of breast cancer for staging

Breast cancer follow the system of the International Union Against Cancer. This system is based on the tumor, nodes, and metastases (TNM) nomenclature. Definitions for Breast Cancer Staging Classification of Breast Cancer Staging B. The HER-2 gene (c-erbB-2, HER-2 neu) has been identified, and the HER-2 receptor is correlated with aggressive biological behavior of the cancer and a poor clinical outcome. C. The staging of breast cancer dictates not only the prognosis but also directs treatment modality recommendations. The prognosis for women is based on their age, tumor type, initial tumor size, presence of nodes and staging, and hormone-receptor status. The overall 10-year survival rates for the more common breast cancer stages are greater than 90 for stage 0, greater than 75 for stage I, greater than 50 for stage IIA, and approximately 50 for stage IIB.

Cancer and the Oncologists Ethical Duties Some General Considerations

An oncologist's ethical responsibilities typically begin with a positive diagnosis of cancer, an event that triggers shock and anxiety in patients and their families. Cancer is associated by many people with disfigurement, dying, and death therefore, the first ethical duty of an oncologist and his or her team is to convey the diagnosis in a way that balances the reality of the disease and its implications with the overall need to maintain optimism and hope. Whereas the obligation to be honest about the reality of cancer derives from the ethics of truth telling in cancer care and in medicine generally (see below), the duty to foster hope taps several sources (Kodish et al., p. 2974) States. It articulates fundamental American notions about personhood, individual autonomy, and the power of thought (good and bad) to shape life course and bodily functioning (Good et al., p. 61). Several factors have to be assessed in promoting hope in a specific case, including the type and stage of...

Molecular Mechanisms In The Generation And Propagation Of Aberrant Dna Methylation Patterns In Prostate Cancer

In our discussions thus far, we have been continually alluding to a fundamental paradox concerning CGI hypermethylation in prostate cancer initiation and propagation DNA methylation processes appear to be dysregulated enough to cause hypermethylation of CGIs at multiple genes yet, the same DNA methylation processes have high enough fidelity that they can maintain the acquired changes in CGI hypermethylation through every step of prostate cancer initiation and progression. This observed paradox would suggest that the CGI hypermethylation changes in prostate cancer are not due to a total dysregulation of the DNA methylation machinery, with subsequent loss of discrimination and fidelity in which CGI sequences are stochastically hypermethylated. Rather, it appears that certain CGI sequences are targeted for hypermethylation resulting in silencing of the corresponding genes. One possibility is that targeting these genes for CGI hypermethylation provides a growth advantage for these cells...

Cancer Causing Chemicals

References to cancer have been found in the annals of human disease since ancient times, but the disease's association with carcinogen exposure is a relatively new concept. Sir Percival Potts, a British physician who lived in the eighteenth century, was the first to suggest that the induction of cancer might be linked to agents in the environment. Potts had observed high rates of scrotal and nasal cancer among England's chimney sweeps, men who were exposed to accumulated fireplace soot during their work. After some careful studies, Potts suggested correctly that exposure to soot caused the high cancer rates, providing the impetus for identifying other carcinogens present in the environment. In retrospect, it was fortuitous that soot was acknowledged as one of the first carcinogenic agents. Soot is a complex mixture of chemicals that arises from the combustion of organic material. As scientists and physicians separated soot's individual components, it became clear that chemicals called...

Possible Mechanisms Of Anticancer Effects

Because PA is ubiquitous to every mammalian cell, it is not surprising that it has a cancer protective effect on different tissues, in different experimental models and under various conditions. However, the mechanisms of PA action are not clear and are open to conjecture. The inhibition of enzymes within the digestive tract may lead to inhibition of digestion and absorption of dietary components 69,70 Figure 14.3(A) . PA may bind to enzymes necessary for starch digestion or, alternatively, it may also reduce the rate of digestion and absorption of starches Figure 14.3(B) either by hydrogen binding to starch 12,71 , binding to proteins that starch is bound to 12,70 or by binding amylase or enzyme cofactors such as Ca2+ 4 . Studies suggest that PA may slow starch digestion and absorption in vivo 72,73 . Such undigested and unabsorbed starch may reach the colon where it may either contribute to fecal bulk and increase the dilution of potential carcinogens, or it may be fermented to...

Models For The Development Of Prostate Cancer Metastases

The mechanisms underlying the dissemination of primary prostate cancer and establishment of metastatic deposits is a topic of great interest since these lesions are ultimately responsible for the vast majority of prostate cancer deaths. It is clear from clinical observations that prostate cancers have a predilection to metastasize to a distinct set of anatomical organ systems, such as lymph node, bone and liver. The first formal hypothesis suggesting an explanation for the non-random distribution of sites to which primary cancers metastasize was proposed by Stephen Paget in 1889 (111, 112). His seed and soil hypothesis suggested that factors in the target site environment promoted the growth of cancer cells there, much like fertile soil would promote the growth of seeds. A modern view of this hypothesis would suggest two possibilities i) that the target site microenvironment would either promote cancer cells to change and adapt when they reach the target site and then establish a...

Hormonal Response to Injury Infection and Cancer

Infection, cancer, or any injury to the body result in an increase in counterregulatory hormones as well as insulin concentration. As a result of cancer, sepsis, or injury, many patients develop the syndrome of insulin resistance even though they had no history of diabetes prior to cancer. In cancer patients, when the overall injury is smaller, many studies have failed to demonstrate an elevation in counterregula-tory hormones. Mild elevations in cortisol concentrations may contribute to the protein catabolism and increased gluconeogenesis. When serum insulin is measured with a sensitive assay, cancer patients demonstrate a small but significant elevation in serum insulin concentration. This is consistent with the observation that these patients have insulin resistance. Cancer patients, like diabetics, have a reduced glucose utilization and loss of the first-phase insulin response, and many have an increased fasting hepatic glucose production rate. As mentioned previously, underweight...

Studies of gene therapy for breast and ovarian cancer

Over the past 10 years there has been a large amount of research into gene therapy for ovarian and breast cancer. It is important to appreciate that many of these studies have only been involved in cell culture or animal models and have yet to be studied in human subjects. Others have proven initially successful in pre-clinical models but have failed to show a benefit in the treatment of humans. Unfortu Correction of genetic mutation in cancer cells The p53 tumour suppressor gene encodes a protein in response to DNA damage that leads to cell cycle arrest at the G1 M phase and may result in apoptosis or DNA repair. Mutation of this gene is found in about half of ovarian and breast cancers (Kohler et al., 1993 Vogelstein et al., 2000) and is associated with a decrease in sensitivity to chemotherapy along with aggressive tumour behaviour. Reintroduction of the wild type p53 gene is therefore a potential mechanism for treatment of chemoresistant tumours. Using this approach, Kigawa et al....

Experimental Biology Of Prostate Cancer

Several excellent reviews of the molecular biology of prostate cancer are available, and only a few of the more common molecular alterations and their potential significance are highlighted here (4,12). The analysis of chromosomal alterations in cancer has identified many changes reflecting loss or gain of function of particular genes. Consistent allelic loss is expected to reflect the location of putative tumor suppressor genes. Loss of heterozygosity at chromosome arms 8p, 10q, 13q, and 17p are frequent events in prostate cancer, and losses at 6q, 7q, 16q, and 18q also occur. Gains of genetic material are expected to reflect the location of oncogenes. In prostate cancer, gains at 8q and 7 are fairly common. Individual genes at these loci have not been definitely assigned a role in prostate cancer, but several reasonable candidate genes have been proposed based on their location and functional properties. One of the more common events in early prostate cancer development is loss of...

Cpg Island Hypermethylation And Lung Cancer Invasion And Metastasis

Abstract Invasion and metastasis are biological hallmarks of malignant tumors, and metastases are the major cause of cancer deaths. Invasion and destruction of BM is the earliest step in the multi-step process of metastases and it is the earliest morphological feature of invasive tumors. Disruption of organization or integrity of the basement membrane (BM) is a key histologic marker of the transition of a tumor from an in situ carcinoma to an invasive carcinoma. A fundamental and important question is what causes in situ cancers to become invasive even though cancer cells at the preinvasive and invasive stages are morphologically similar. One of the well-established mechanisms for invading and destroying BMs is by matrix metalloproteinases (MMPs), which are up regulated during invasion and metastasis. Developing molecular markers that mark the transition of in situ cancers to invasive cancer are very important because they may predict cancer for those who are at highest risk or those...

Naturally Occurring Carcinogens

It has been estimated that the total number of known chemicals exceeds 7 million, and that the great majority are naturally occurring. Although only a very small proportion (perhaps less than 0.01 ) of these chemicals have been tested for carcinogenic potential in laboratory studies, a high proportion (as high as 50 in some evaluations) have been found to be positive. Therefore, even allowing for the imperfect selection and testing process, it is likely that there are a very large number of naturally occurring carcinogenic chemicals in the universe of chemicals, and therefore in the food we eat. Naturally occurring substances identified as carcinogens in animals and humans by the range of approaches available for this purpose include inorganic compounds, organometallic compounds, and both simple and complex organic chemicals (see Table 1). These materials are present in the environment either as naturally occurring minerals or as a result of natural processes acting in the environment...

History Of Cancer Chemotherapy And Reflection Thereon

Originally, cancer chemotherapy started with nitrogen mustard, a derivative of poisonous gas yperite, a by-product in World War II. The pharmacological action of nitrogen mustard consists in cytotoxicities (e.g., leukopenia, diarrhea, and stomatitis) to the organism, and attempts were made to utilize these toxicities to obtain anticancer activity. Namely, the modality consisted in cancer therapy using toxicities to the organism that were inherent to nitrogen mustard. From the standpoint of establishing cancer chemotherapy that is ideally based on the premise that only the tumor should be attacked with the least damage to the organism, therefore, we cannot but consider that the approach was the tail wagging the dog (misoriented rescuing). A concept of high-dose chemotherapy, i.e., an anticancer agent fails to be effective unless provoking considerable adverse reactions, still remains at present when half a century has elapsed since the introduction of nitrogen mustard. The concept of...

Laparoscopic Surgery in Kidney Cancer

Renal cell carcinoma is the most common primary renal malignancy, accounting for approximately 25,000 cases annually in the United States and resulting in over 10,000 deaths. It is the tenth most common cancer, constituting 3 of all adult malignancies, and generally occurs in adults between the ages of 50 and 70. Males are affected twice as frequently as females.1 It occurs bilaterally in 2 to 4 of individuals either synchronously or metachronously. The incidence of renal carcinoma has steadily increased from 1935 to 1989. However, the mortality has decreased over the same interval,2 suggesting effective treatment or earlier diagnosis. 1. Boring CC, Squires TS, Tong T, Montgomery S. Cancer statistics, 1994. CA 1994 44 7-26. 2. Katz DL, Zheng T, Holford TR, Flannery J. Time trends in the incidence of renal carcinoma Analysis of Connecticut Tumor Registry data, 1935-1989. Int J Cancer 1994 58 57-64.

Carbohydrate Metabolism and Gluconeogenesis in the Cancer Bearing Organism

Resting Metabolic Rate Cancer

One of the earliest metabolic abnormalities described in cancer patients was that of glucose intolerance (Rohdenberg et al., 1919). Glucose intolerance is evidenced by increased concentrations and delayed clearance of blood glucose following oral or intravenous glucose administration (Holroyde and Reichard, 1981). Such an effect may be due, at least in part, to tissue insensitivity to insulin as well as a defective response of P cells of the pancreas to insulin secretion following hyperglycemia. Despite this fact, in experimental systems, insulin may actually modify or even reverse the cachexia of neoplasia (Moley et al., 1985 Beck and Tisdale, 1989a). Another abnormality commonly seen in cancer patients with advanced disease is an increase in glucose turnover as measured by isotopic techniques (cf. Chlebowski and Heber, 1986). Although few difference in the rates of glucose production and oxidation have been observed in patients with cancer, there is substantial evidence for...

Chronic Irritation And Trauma As Factors In Carcinogenesis

Although the general concept that chronic irritation is a carcinogenic stimulus is no longer accepted, in certain conditions chronic inflammation in humans may predispose to neoplasia. One of the best examples is the chronic draining sinus, usually resulting from chronic infections such as osteomyelitis. Such chronic infections are relatively rare today however, in the past, when bone infections were rather common, epidermoid carcinomas occasionally arose in the skin near chronic draining sinuses. The histology of these lesions before the production of the neoplasm demonstrated a peculiar type of hyperplasia of the squamous epithelium known as pseudo-epitheliomatous hyperplasia (Sommerville, 1953). Other sites of chronic inflammation considered to be associated with higher incidences of neoplasia are the lower lips of pipe smokers and nevi or moles in locations on the body subject to chronic irritation, such as the belt region or the back of the neck. As has already been suggested and...

Exogenous Modifiers And Cancer Prevention

Although the effective therapy of cancer is an ultimate goal of medical science, the prevention of cancer is, at our present state of knowledge, the most effective and, relatively, the most inexpensive mode of controlling this disease. The prevention of cancer has been discussed by a number of authors (Schottenfeld, 1981 Hirayama, 1992 Doll, 1996). Optimistically, our knowledge of the incidence of neoplasia in the human suggests that age-specific incidence rates might be reduced by as much as 80 , half of this reduction coming through the application of existing knowledge (Doll, 1996). In fact, such knowledge has already been applied to specific populations with significant results (Hirayama, 1992). As has been noted (Pitot, 1993), cancer prevention may occur passively or actively. Passive prevention of cancer involves a cessation or restriction of exposure to potentially carcinogenic influences, such as the cessation of smoking, dietary modification, and avoidance of excessive...

Conclusion On Ovarian Cancer

Patients who come from FOC families who have established ovarian cancer should be managed in the same way as those from sporadic ovarian cancer families. It may be that, with time, subtle biological differences will emerge. For the asymptomatic patient there are some very difficult decisions to make, particularly as regards genetic testing and prophylactic oophorectomy. The results of screening trials will hopefully go some way to help in making these decisions informed decisions. Advanced Ovarian Cancer Trialists' Group (2000). Chemotherapy for advanced ovarian cancer. for the diagnosis of ovarian cancer. Obstet Gynecol 96(1) 75-80. Berchuck A, Schildkraut JM, Marks JR, et al. (1999a). Managing hereditary ovarian cancer risk. Cancer 86 (11 Suppl.) 2517-24. Berchuck A, Carney ME and Futreal PA (1999b). Genetic susceptibility testing and prophylactic oophorectomy. Eur J Obstet Gynecol Reprod Biol 82(2) 159-64. Bewtra C, Watson P, Conway T, et al. (1992). Hereditary ovarian cancer a...

Laryngeal and hypopharyngeal cancer

Hypopharyngeal Cancer

Is cord fixation or extension of disease into the hypopharynx or when hypopharynx cancer causes fixation of the hemilar-ynx, total laryngectomy is usually required. Hypopharyngeal cancer requires partial or total pharyngectomy in addition to laryngectomy. Reconstruction of the pharyngeal defect is by regional myocutaneous flap (based on the latissimus dorsi or the pectoralis major muscle), free forearm flap (Fig. 20.14), free jejunal segment or gastric pull up. Extrathoracic gastric pull up or colon interposition is required to reconstruct the oesophagus when total oesophagectomy is carried out for upper cervical oesophageal disease (Fig. 20.18). Voice rehabilitation is by learning oesophageal speech, use of an elec-trolarynx or by creation of a tracheo-oesophageal fistula for insertion of a Blom-Singer prosthesis. Advanced stage laryn-geal hypopharyngeal cancer often requires concomitant neck dissection for a clinically positive neck followed by postoperative radiotherapy. Induction...

Mutational Theory Of Inherited And Spontaneous Sporadic Cancer

A reasonable solution to this dilemma was first proposed by Knudson (1971), who hypothesized a two-mutational (two-hit) theory of carcinogenesis. His theory was developed primarily to explain the epidemiological findings seen in hereditary retinoblastoma, in which nearly two-thirds of the hereditary cases were bilateral but all of the sporadic cases were unilateral. The former cases occurred in very young patients (mean age, 18 months), whereas the sporadic unilateral cases developed at an average of 30 months or more. On the assumption that mutational events occur at random and a relatively fixed rate, Knudson reasoned that at least two mutational events, now understood to be frequently in each allele of the same gene, were necessary to convert a normal cell into a neoplastic cell. If the first mutation or hit were postzygotic (spontaneous or sporadic), the progeny of this mutated cell would then be at an increased risk of developing into a neoplasm when one or more cells received a...

Videoassisted Thoracic Surgery for Lung Cancer

The majority of patients with pulmonary carcinoma present with extensive tumor burden that is centrally located. A minority of patients present with asymptomatic, peripheral tumors. Approximately 37 of solitary lung nodules represent primary lung carcinoma. Therefore these lesions require accurate histological diagnosis for effective treatment. The incidence of lung cancer increases with age and smoking habits. Early diagnosis is imperative as patients with solitary, peripheral lung lesions have the best outcomes following proper treatment. Most if not all operations performed through conventional thoracotomy are possible using VATS. Although technically more demanding initially, VATS is a reasonable surgical option for pulmonary carcinoma. Without 10-year survival data, many thoracic surgeons believe that VATS should be limited to patients with stage IA or IB tumors (T1N0 and T2N0, respectively). Stages I and II tumors are confined to lung parenchyma without mediastinal or...

Colorectal Cancer Background and aetiology

Each year colorectal cancer affects 32 000 people in the UK and is responsible for around 22 000 deaths. In males it is second only to lung cancer and in females it falls third behind lung and breast cancer. In the developed world, life-time risk of colorectal cancer is around 1 25 and this is increased by genetic predisposition and certain conditions such as chronic colitis. Colorectal cancer is mainly a disease of the elderly with a marked rise in incidence after age 70 years, however, 10 of individuals are under age 55 years at diagnosis. In 1972, Burkitt described the relationship between diet and incidence of bowel cancer he hypothesised that a diet rich in fibre was associated with regular bulky stools and reduced bowel carcinogenesis, perhaps by reducing exposure of colonic mucosa to dietary carcinogens. It does seem likely that the combination of high fibre and low fat may be protective against bowel cancer. Protection against colorectal carcino-genesis is also derived from...

Clinical Manifestations Of Colorectal Cancer

A major goal of global expression analysis is to provide information that supports an enriched system of classification, either alone or in conjunction with clinical and genetic data. To place this effort in perspective, we sketch the clinical behavior of colon cancer and outline the major clinical-pathological classification systems. Colorectal cancer principally affects those older than 40 yr of age, although it occurs occasionally in adolescents (18). Ninety percent of tumors are found in people older than 50 yr. The incidence rate varies about 20-fold in different parts of the world, with the highest in the West and the lowest in India (19). Migration from a low to a high incidence region is associated with an increase in disease risk. This suggests that the environment (probably the diet) can influence the incidence of colorectal cancer (20), although the occurrence of cancer predisposition syndromes (accounting for about 5 of all cases of colon cancer) such as familial...

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