Cell Carcinoma In Men Research Articles

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998: reply from author

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998: reply from author

Physical variables in experimental photocarcinogenesis and quantitative relationships between stages of tumor development

Solar ultraviolet (UV) radiation is a prominent environmental carcinogen, but it does not penetrate any deeper than the skin. The UV-related skin cancers are by far the most common form of cancer among white Caucasians in the USA and Australia, and this poses a serious public health problem. Chronic UV exposure of hairless mice is a well established model for squamous cell carcinomas in man. It is important to identify the essential physical variables, and explore fully how photocarcinogenesis evolves in dependence of these variables. The 3 main physical variables in photocarcinogenesis are (i) the wavelength of the radiation, (ii) the exposure and (iii) time. A good quantitative description of tumor induction and precursing stages can be given in terms of these variables. An analysis of this description shows us that the early induction of clusters of epidermal cells that over-express mutant p53 ('p53 patches') are closely and, most likely, causally linked to the eventual tumors. These p53 patches may thus serve as early indicators of tumor risk. The induction of an immune-tolerance toward the UV-induced tumors precedes the actual occurrence of the tumors at high daily doses, but extrapolation indicates that this order of events may be reversed at low daily doses. This disparity between the dose-time relationships for the tumor tolerance and the tumors needs to be investigated further. It could imply a shift to non-immunogenic tumors at low daily doses.

Physical variables in experimental photocarcinogenesis and quantitative relationships between stages of tumor development.

Solar ultraviolet (UV) radiation is a prominent environmental carcinogen, but it does not penetrate any deeper than the skin. The UV-related skin cancers are by far the most common form of cancer among white Caucasians in the USA and Australia, and this poses a serious public health problem. Chronic UV exposure of hairless mice is a well established model for squamous cell carcinomas in man. It is important to identify the essential physical variables, and explore fully how photocarcinogenesis evolves in dependence of these variables. The 3 main physical variables in photocarcinogenesis are (i) the wavelength of the radiation, (ii) the exposure and (iii) time. A good quantitative description of tumor induction and precursing stages can be given in terms of these variables. An analysis of this description shows us that the early induction of clusters of epidermal cells that over-express mutant p53 ('p53 patches') are closely and, most likely, causally linked to the eventual tumors. These p53 patches may thus serve as early indicators of tumor risk. The induction of an immune-tolerance toward the UV-induced tumors precedes the actual occurrence of the tumors at high daily doses, but extrapolation indicates that this order of events may be reversed at low daily doses. This disparity between the dose-time relationships for the tumor tolerance and the tumors needs to be investigated further. It could imply a shift to non-immunogenic tumors at low daily doses.

A prospective study of a total material of lung cancer from a county in Sweden 1997–1999: gender, symptoms, type, stage, and smoking habits

The epidemiology of lung cancer is changing in many parts of the world. In the industrialized countries, there is a trend that the incidence in men is declining, while it is increasing for women. Also, adenocarcinomas are becoming relatively more common, especially among men. The purpose of this study was to investigate whether such trends also occur in Sweden and also to describe other aspects of an unselected lung cancer material today, such as symptoms, stage and smoking habits. In the county of Gaevleborg, Sweden, practically all patients with lung cancer are referred to the lung department, and thus a total material of lung cancer patients with only a minimal selection bias can be studied. All patients with lung cancer in the county from January 1, 1997 to December 31, 1999, were investigated prospectively regarding stage, type of cancer, and symptoms. In all, there were 364 patients, 237 (65.1%) men and 127 (34.9%) women. The mean age for men was 69.8 and for women, 68.1 years. 91.9% of the men and 78.6% of the women were smokers or ex-smokers. In general the men were heavier smokers than were the women ( P<0.0001). Adenocarcinoma was the most common subtype found in women and squamous cell carcinoma in men. The excess of adenocarcinoma in women was due to never-smoking women; for smoking and ex-smoking men and women, the proportion of adenocarcinomas was the same. In all, 240 patients (68.0%) were diagnosed at Stage IIIb (27.2%) or IV (40.8%), with no significant differences between the sexes. The most common first symptom was cough. Only 7.0% of patients were asymptomatic. In conclusion, the trend of an increasing proportion of adenocarcinoma in lung cancer is seen also in Sweden. A depressingly high percentage of patients present in late stages and are thus inoperable.

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998.

One single report from the U.S. 16-centre-trial indicated that psoralen and ultraviolet A radiation (PUVA) therapy may induce an increased risk of genital tumours in men, and protection of the genital area is, therefore, recommended. To evaluate the relevance of this risk in routine clinical practice. Two groups of patients were included in a 1978-98 retrospective study. Case records of men with genital squamous cell carcinoma (SCC) identified from the Cancer Registry of the Doubs area of France were examined for a history of PUVA therapy, topical tar treatment, psoriasis, human papillomavirus infection or genital dermatitis. In addition, all the dermatologists of the Doubs area (in public and private practice) using PUVA therapy were asked to provide information on the number of patients having received PUVA therapy and whether the genital area was exposed during treatment. Between 1978 and 1998, among the 48 men who had developed a genital SCC in the Doubs area, only one had a history of intensive PUVA therapy. About 150,000 treatments with PUVA therapy had been performed by 15 dermatologists in the Doubs area for 5400 patients since 1978. No case of genital SCC had been reported, despite the fact that the genital area had not been protected during UVA exposure. Although retrospective, our study demonstrates that the occurrence of genital SCC in men treated with PUVA therapy is a very rare event in common dermatological practice.

Renal Toxicity and Carcinogenicity of Trichloroethylene: Key Results, Mechanisms, and Controversies

The discussion on renal carcinogenicity of trichloroethylene adresses epidemiological, mechanistic, and metabolic aspects. After trichloroethylene exposure of rats, renal cell tumors were found increased in males, and an increased incidence of interstitial cell tumors of the testes was reported. Studies on the metabolism of trichloroethylene in rodents and in humans support the role of bioactivation reactions for the development of tumors following exposure to trichloroethylene. Epidemiological cohort studies addressing the carcinogenicity of trichloroethylene with respect to the renal or urothelial target sites have been conducted, and no clear evidence for an elevated renal or urinary tract cancer risk in trichloroethylene-exposed groups was visible in exposed populations. However, a cohort study of 169 male workers having been exposed to unusually high levels of trichloroethylene in Germany within the period between 1956 and 1975 supported a nephrocarcinogenic effect of trichloroethylene in humans. The results of this study were discussed in the literature with considerable reserve; criticism was based mainly on the choice of the study group, which had been recruited from personnel of a company in which a cluster of four renal tumors was observed previously. Hence, a further case-control study was conducted in the same region. This study confirmed the results of the previous cohort study, supporting the concept of involvement of prolonged and high-dose trichloroethylene exposures in the development of renal cell cancer. Further investigations on patients with renal cell carcinoma and with histories of high trichloroethylene exposures, on the basis of excretion of marker proteins in the urine, pointed to toxic damage to the proximal renal tubules by trichloroethylene. The hypothesis of implication of a glutathione transferase-dependent bioactivating pathway of trichloroethylene, established in experimental animals, seems at least also plausible for humans. Apparently, the occurrence of renal cell carcinomas in man follows high-dose exposures to trichloroethylene that are also accompanied by damage to tubular renal cells. Development of renal cell carcinomas has been related to mutations in the vonHippel-Lindau (VHL) tumor suppressor gene. Renal cell carcinoma tissues of persons with histories of prolonged high-dose exposure to trichloroethylene were investigated for the occurrence of mutations of the vonHippel-Lindau (VHL) tumor suppressor gene. VHL gene mutations were found in the majority of renal cell tumors associated with high-level exposure to trichloroethylene. A specific mutational hot spot at the VHL nucleotide 454 was addressed as a unique mutation pattern of the VHL tumor suppressor gene. A synopsis of all experimental, clinical, and epidemiological data suggests that reactive metabolites of trichloroethylene, with likely involvement of dichlorovinyl-cysteine (DCVC), exert a genotoxic effect on the proximal tubule of the human kidney. This constitutes a tumor-initiating process of genotoxic nature, the initial genotoxic effect apparently being linked with mutational changes in the VHL tumor suppressor gene. However, there is compelling evidence that the full development of a malignant tumor requires continued promotional stimuli. Repetitive episodes of high peak exposures to trichloroethylene over a prolonged period of time apparently led to nephrotoxicity, visualized by the excretion of tubular marker proteins in the urine. This critical process of development of tubular damage by trichloroethylene must follow a “conventional” dose-dependence, implying a practical threshold. This view is much corroborated by the fact that the occurrence of human renal cell cancer is obviously confined to cases of unusually high trichloroethylene exposures in the past, with special characteristics of very high and repetitive peak exposures. Current instruments of regulation should be adjusted to allow adequate consideration of such carcinogenic effects of chemicals that are practically relevant at very high doses only.

Estrogen treatment enhances hereditary renal tumor development in Eker rats.

Hormonal influences are known to affect the development of renal cell carcinoma in man and laboratory animal models. We tested the hypothesis that estrogen treatment or ovariectomy of rats modulates renal tumor development using tuberous sclerosis 2 (Tsc2) heterozygous mutant (Eker) rats in which a germline mutation predisposes the animals to renal cell tumor development. Two-month-old female wild-type and Eker rats were ovariectomized or sham-operated and treated with placebo or 5 mg 17beta-estradiol in s.c. pellets for 6 or 10 months. Rats were examined at 8 or 12 months of age, at which time the numbers of renal tumors and preneoplastic foci were quantitated and the severity of nephropathy was assessed. In contrast to what may have been expected, prolonged estrogen treatment enhanced the development of hereditary renal cell tumors, with a 2-fold greater number of preneoplastic and neoplastic renal lesions compared with untreated Eker rats. Ovariectomized Eker rats had 33% fewer renal lesions than the unmanipulated control group. No tumors or preneoplastic lesions were present in wild-type rats at either time point. Estrogen treatment increased the severity of nephropathy in both wild-type and Eker rats, whereas ovariectomy was protective against nephropathic changes. Although estrogen is not a rat renal carcinogen, it enhanced the development of hereditary renal cell tumors when administered to Eker rats. Eker rats heterozygous for a mutation in the Tsc2 locus provide a good model in which to study how genetic and hormonal factors contribute to the development of renal cell tumors and to understand the influence genetic susceptibility has on the development of renal cell carcinoma.

Lung cancer in women compared with men: stage, treatment, and survival

Background. In cardiac disease there appears to be a difference in the treatment of men and women, and thus an advantage in survival in men. This study aimed to determine whether these differences exist in lung cancer. Methods. We undertook a retrospective cohort study in a university hospital. The study population consisted of 104 consecutive women and 104 consecutive men with newly diagnosed lung cancer between March 1988 and June 1990. The following information was collected: sex, age, presenting symptoms, investigations, histology, stage, treatment, and survival. Results. The location of the tumor, presenting symptoms, investigations, and stages were similar in men and women. There was a difference in the distribution of the various histologic types of lung cancer: Small cell lung cancer was more frequent in women (25% versus 11.5% in men) and squamous cell carcinoma more frequent in men (38% in women versus 51% in men). The overall survival was similar among the two sexes, but there was a survival advantage in women when adjusted for stage. Conclusions. There was a higher incidence of small cell carcinoma in women and squamous cell carcinoma in men. There was evidence of a difference in the survival rate of lung cancer in favor of women according to stage.

Elevated concentrations of gamma-enolase in renal cell tumors in rats: similarity to renal cell carcinoma in man.

Concentrations of enolase isozymes in normal kidney and renal cell tumors in rats were determined using a highly sensitive enzyme immunoassay, and the isozymes were immunohistochemically localized in tissue sections. Levels of alpha-enolase in renal cell tumors were significantly lower than in normal kidney, whereas those of gamma-enolase were significantly elevated (mean +/- SD: 211 +/- 129 ng/mg protein, n = 15, as compared to 27.1 +/- 2.9 ng/mg protein, n = 7). The proportion of gamma-enolase in the total enolases in the tumor tissues (1.6 +/- 0.5%) was significantly higher than in normal kidney (0.15 +/- 0.05%). Immunohistochemistry revealed epithelial cells of all nephron segments to be positive for the alpha-isozyme, whereas gamma-enolase staining was strongly positive only in the loops of Henle, being faint in the distal tubules and absent in the proximal tubules. Both alpha- and gamma-enolases demonstrated positive immunostaining in all of the seven renal cell tumors studied. These findings indicate that an isozyme switch from alpha- to gamma-enolase occurs during rat kidney carcinogenesis, taking into account the derivation from proximal tubules, consistent with the findings for renal cell carcinomas in man.

The variation of cell type distribution in lung cancer: a study of 10,910 cases at a medical center in Taiwan between 1970 and 1993.

The rise in the incidence of lung cancer has been associated with shifts in histologic distribution. A study was conducted to investigate changes in the cell type distribution in lung cancer in relation to age, sex, and smoking history, based on a retrospective analysis of 10,910 proven cases of lung cancer at the Veterans General Hospital-Taipei during the period from 1970 to 1993. The diagnosis in each case was substantiated by histologic samples from the original tumor site in the lung. Detailed smoking histories were obtained by personal interview at the time of the first admission. Adenocarcinoma (38.3%) was the most common type of lung cancer, followed by squamous cell carcinoma (37.1%) and small cell carcinoma (12.2%). Over the study period, the incidence of squamous cell carcinoma decreased from 46.4% to 36.2% in men (P < 0.005), adenocarcinoma increased from 30% to 36% in men (P = 0.001) and 50.7% to 64.8% in women (P = 0.008), and small cell carcinoma increased from 7% to 14% in men but showed no significant change in women. Adenocarcinoma exhibited a marked increase in both men and women, and surpassed squamous cell carcinoma as the most frequent type of lung cancer. Lung cancer among younger men, and among non-smoking older men and women, was more often adenocarcinoma. Small cell carcinoma showed a significant increase among males, differing from the trend for squamous cell carcinoma in men, though both are strongly associated with smoking. These findings suggest factors other then cigarette smoking could influence the development and distribution of lung cancer.

Wood dust and sino-nasal cancer: pooled reanalysis of twelve case-control studies.

In order to examine the relationship between wood dust and sino-nasal cancer, data from 12 case-control studies conducted in seven countries were pooled and reanalyzed. The relative risks associated with wood-related jobs and with exposure to wood dust, measured using a job exposure matrix based on occupation and industry titles, were examined using logistic regression. The combined data set consisted of 680 male cases, 2,349 male controls, 250 female cases, and 787 female controls. A high risk of adenocarcinoma among men was associated with employment in wood-related occupations (odds ratio [OR] = 13.5, 95% confidence interval [CI] = 9.0-20.0) and the risk was greatest among men who had been employed in jobs with the highest wood dust exposure (OR = 45.5, 95% CI = 28.3-72.9) and increased with duration of exposure. The risk of adenocarcinoma also appeared elevated among women employed in wood-related jobs (OR = 2.5, 95% CI = 0.5-12.3), but the small number of exposed cases precluded detailed analysis. Women in wood dust-exposed jobs appeared to have an excess of squamous cell carcinoma (OR = 2.1, 95% CI = 0.8-5.5) which increased with duration of exposure. An increased risk of squamous cell carcinoma in men was seen only among those employed for 30 or more years in jobs with exposure to fresh wood (OR = 2.4, 95% CI = 1.1-5.0). The results of this analysis provide strong support to the association between exposure to wood dust in a variety of occupations and the risk of sino-nasal adenocarcinoma and are consistent with the results of individual participating studies, although the magnitude of the excess risk varied. The evidence in regard to squamous cell carcinomas was ambiguous and there was a great deal of heterogeneity observed in individual study results. This may be due to differences in risk associated with exposure to hardwoods and softwoods or with other, as yet to be identified, aspects of exposure.

Intraoral squamous cell carcinoma in human immunodeficiency virus infection: A clinicopathologic study

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal cell carcinoma and thiazide use: a historical, case-control study (California, USA)

Renal cell carcinoma has been linked to hypertension and antihypertensive medications. We investigated the association between renal cell carcinoma and the use of thiazide in a case-control study of 167 men and 90 women. Subjects were members of the Kaiser Permanente Medical Care Program in northern California (United States) who had taken a multiphasic health check-up from 1964 through 1988 and who were evaluated for cancer until the end of 1989. Control subjects received the same check-up, were matched by gender, year of check-up, and age at check-up, and had to be in the health plan until the date on which renal cell carcinoma was diagnosed. Data on known and potential risk factors, including hypertension, body mass index (BMI), and smoking status, were collected from the record of the check-up. Thiazide use was abstracted from the medical chart, which was reviewed from the date of the first entry until the date on which the cancer was diagnosed or the equivalent date for control subjects. The mean follow-back to check-up was 11.3 years. Among women, we found a significantly elevated risk of 4.0 (95 percent confidence interval [CI] 1.5-10.8) associated with ever having used thiazide after we adjusted for smoking, BMI, hypertension, and history of kidney infection at check-up. We did not find a statistically significantly elevated risk in men. Smoking was related to renal cell carcinoma in men (odds ratio [OR] 2.5, CI = 1.1-5.4) for those who smoked at least one pack per day compared with those who had never smoked, but was not related in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Monoclonal Antibodies as Prognostic Indicators in Patients with Squamous Cancer of the Oral Cavity and Oral Pharynx

Prior work in our laboratory has shown that the expression of an epithelial antigen identified by the monoclonal antibody A9 is amplified in squamous carcinoma cell lines and that the intensity of expression is related to aggressive cell growth in vitro and in the nude mouse (1). To determine if alterations in expression of normal epithelial antigens are related to the biological behaviour of squamous cell carcinoma in man, the expression of the A9 antigen and of normal A, B and H blood group antigens in primary tumor tissue sections from 41 patients with cancer of the oral cavity and oral pharynx was analyzed. The majority of these patients had stage III (19/41) or stage IV (17/41) tumors. Antigen expression was analyzed with respect to traditional histologic features and disease-free survival. Median follow-up was 13 months (range 1—53 months). Disease-free survival was decreased (median 8.7 months) in patients with tumors that had high A9 expression compared to patients with low A9 expression (p =. 132...

Risk of lung cancer by histologic type among smokers in Miyagi Prefecture.

Smoking habits of the 827 lung cancer patients aged 40 years or over who were treated in the Sendai Kosei Hospital from 1977-82 were compared with those in the general population of a non-metropolitan district in northern Japan, which we recently surveyed by mail questionnaire. The relative risks of lung cancer by histologic type adjusted by age and area of residence were as follows: 1.9 for adenocarcinoma, 4.3 for squamous cell carcinoma, 3.9 for small cell carcinoma and 3.4 for large cell carcinoma in men, and 2.9, 6.4, 4.5 and 4.0 for these histologic types, respectively, in women. These elevated risks were all statistically significant (p less than 0.05). These findings suggest that smoking habits should be carefully considered when studying the etiology of any cell type of lung cancer, even adenocarcinoma, which often has been thought to be unrelated to smoking habits.

Glucose Utilisation by Pulmonary Squamous Cell Carcinomas in Man

Glucose Utilisation by Pulmonary Squamous Cell Carcinomas in Man

Treatment of carcinoma of the nasal cavity and paranasal sinuses.

The results of the radical treatment of 528 cases of carcinoma of the nasal cavity and paranasal sinuses are presented. These cases were analysed according to treatment modes of surgery of radiotherapy alone and surgery, radical or subradical, with radical radiotherapy. Of necessity the survey is retrospective but the results can be interpreted as demonstrating that while surgery without radiotherapy is appropriate to certain tumours near the nasal vestibule, to transitional cell carcinoma in men, and to some salivary carcinomas, for the remainder surgery, either radical or subradical with radiotherapy, is appropriate. No significant difference can be shown between radical and subradical surgery, when combined with radiotherapy. Radiotherapy alone appears inappropriate.

Increased CTP synthetase activity in cancer cells

AN insight into the biochemical strategy of cancer cells has been achieved by the conceptual and experimental approach provided by the molecular correlation concept1,2. Studies carried out using this approach with model systems of rat hepatomas and kidney tumours of different growth rates revealed a biochemical imbalance in cancer cells, which manifested itself in progressive changes in activities of key enzymes and overall metabolic pathways that correlated with tumour growth rate1,2. Some of these biochemical alterations have been shown to apply to human primary liver3 and kidney4 carcinomas. Those alterations in gene expression that are linked to the increase in the expression of malignancy are manifested in the increased activities of key glycolytic-, purine-, pyrimidine-, DNA- and polyamine-synthesising enzymes1–8. Concurrently, decreases occur in the activities of the key enzymes of gluconeogenesis, purine and pyrimidine catabolism and of the urea cycle1–5,9,10. In addition to such a progression-linked (growth-rate-linked) metabolic imbalance, the reprogramming of gene expression in cancer cells entails transformation-linked alterations that are present in all hepatomas irrespective of growth rate or extent of differentiation1,2,11–15.Here we report that CTP synthetase (UTP:L-glutamine amido ligase, EC 6.3.4.2) increased in all the hepatomas examined, the activity being highest in the rapidly growing tumours. Thus, in liver neoplasia the activity of this enzyme is both transformation- and progression-linked. CTP synthetase activity was also markedly increased in transplantable kidney tumours in the rat and in primary renal cell carcinomas in man.

Evaluation of chemotherapeutic agents in a new murine renal carcinoma model.

Vinblastine and 1-(2-chlorethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were evaluated in a murine renal cell carcinoma model. Both drugs significantly decreased tumor weight and the percentage of distant metastases and very significantly prolonged the survival of tumor-bearing animals. Both also exhibited a dose-related effect. The therapeutic index of vinblastine was limited by signs of systemic toxicity, while the dosage of CCNU might have been limited by its tendency to suppress host immune response to tumor, based on observations of this renal tumor model. Vinblastine may prove clinically useful in early or prophylactic treatment of resected renal tumors, whereas CCNU may be very useful in prolonging survival of patients with renal tumors which have already metastasized. Therefore, both drugs, either alone or combined, may have clinical value in the treatment of metastatic renal carcinoma. Vinblastine may serve best as initial postsurgical treatment, with the addition of CCNU if metastatic disease is documented or progressive. The 3 response criteria evaluated by this model were tumor growth, tumor spread, and prolongation of survival. These seemed most clinically relevant and this model appeared to resemble closely the clinical situation of disseminated renal cell carcinoma in man.

Mitomycin C in the treatment of metastatic transitional cell carcinoma of urinary bladder.

Mitomycin C was administered to 21 patients with metastatic transitional cell carcinoma of the urinary bladder. Of these, 19 patients were evaluable. Objective response occurred in four patients, or 21%. Hemopoietic depression was common and was dose related. Nephrotoxicity related to the drug was seen in one case. Mitomycin C does exhibit antitumor activity against transitional cell carcinoma in man.