Showing papers on "Cancer published in 1992"

Fruit, vegetables, and cancer prevention: A review of the epidemiological evidence

Abstract: Approximately 200 studies that examined the relationship between fruit and vegetable intake and cancers of the lung, colon, breast, cervix, esophagus, oral cavity, stomach, bladder, pancreas, and ovary are reviewed. A statistically significant protective effect of fruit and vegetable consumption was found in 128 of 156 dietary studies in which results were expressed in terms of relative risk. For most cancer sites, persons with low fruit and vegetable intake (at least the lower one-fourth of the population) experience about twice the risk of cancer compared with those with high intake, even after control for potentially confounding factors. For lung cancer, significant protection was found in 24 of 25 studies after control for smoking in most instances. Fruits, in particular, were significantly protective in cancers of the esophagus, oral cavity, and larynx, for which 28 of 29 studies were significant. Strong evidence of a protective effect of fruit and vegetable consumption was seen in cancers of the pancreas and stomach (26 of 30 studies), as well as in colorectal and bladder cancers (23 of 38 studies). For cancers of the cervix, ovary, and endometrium, a significant protective effect was shown in 11 of 13 studies, and for breast cancer a protective effect was found to be strong and consistent in a meta analysis. It would appear that major public health benefits could be achieved by substantially increasing consumption of these foods.

Manual for Staging of Cancer

Abstract: Part 1 General information on cancer staging and end-results reporting: purposes and principles of staging reporting of cancer survival and end results. Part 2 Staging of cancer at specific anatomic sites: lip and oral cavity, pharynx (including base of tongue, soft palate, and uvula) larynx maxillary sinus salivary glands (including parotid, submandibular, and sublingual), thyroid gland digestive system sites - oesophagus, stomach, small intestine, colon and rectum, anal canal, liver (including intrahepatic bile ducts), gallbladder, extrahepatic bile ducts, ampulla of vater, exocrine thorax - lung, pleural mesothelioma musculoskeletal sites - bone, soft tissue, carcinoma of the skin (excluding eyelid, vulva, and penis), melanoma of the skin (excluding eyelid), breast gynaecologic sites - cervix uteri, corpus uteri, ovary, vagina, vulva genitourinary sites - prostate, testis, penis, urinary bladder, kidney, renal pelvis and ureter, urethra ophthalmic tumours - carcinoma of the eyelid, melanoma of the eyelid, carcinoma of the conjunctiva, melanoma of the conjunctiva, melanoma of the uvea, retinoblastoma, sarcoma of the orbit, carcinoma of the lacrimal gland, brain lymphomas - Hodgkin's disease, non-Hodkin's lymphoma paediatric cancers - nephroblastoma (Wilms' tumour), neuroblastoma, soft-tissue sarcoma - paediatric. Part 3 Personnel of the american joint committee on cancer.

APC mutations occur early during colorectal tumorigenesis.

Abstract: HUMAN tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumour suppressor genes1–3 But in no common adult cancer have the mutations that are critical in the early stages of the tumorigenic process been defined We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from small benign tumours (adenomas) to larger malignant tumours (carcinomas) over the course of several decades Here we report that sequence analysis of 41 colorectal tumours revealed that the majority of colorectal carcinomas (60%) and adenomas (63%) contained a mutated APC gene Furthermore, the APC gene met two criteria of importance for tumour initiation First, mutations of this gene were found in the earliest tumours that could be analysed, including adenomas as small as 05 cm in diameter Second, the frequency of such mutations remained constant as tumours progressed from benign to malignant stages These data provide strong evidence that mutations of the APC gene play a major role in the early development of colorectal neoplasms

Combined Chemotherapy and Radiotherapy Compared with Radiotherapy Alone in Patients with Cancer of the Esophagus

Abstract: Background. The efficacy of conventional treatment with surgery and radiation for cancer of the esophagus is limited. The median survival is less than 10 months, and less than 10 percent of patients survive for 5 years. Recent studies have suggested that combined chemotherapy and radiation therapy may result in improved survival. Methods. This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus. The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received chemotherapy and radiation therapy. Results. The median survival was 8.9 months i...

Tumor Angiogenesis: A New Significant and Independent Prognostic Indicator in Early-Stage Breast Carcinoma

Abstract: BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.

A case-control study of screening sigmoidoscopy and mortality from colorectal cancer.

Abstract: Background The efficacy of sigmoidoscopic screening in reducing mortality from colorectal cancer remains uncertain. A randomized trial would be ideal for clarifying this issue but is very difficult to conduct. Case–control studies provide an alternative method of estimating the efficacy of screening sigmoidoscopy. Methods Using data on the 261 members of the Kaiser Permanente Medical Care Program who died of cancer of the rectum or distal colon from 1971 to 1988, we examined the use of screening by rigid sigmoidoscopy during the 10 years before the diagnosis and compared it with the use of screening in 868 control subjects matched with the case subjects for age and sex. Results Only 8.8 percent of the case subjects had undergone screening by sigmoidoscopy, as compared with 24.2 percent of the controls (matched odds ratio, 0.30; 95 percent confidence interval, 0.19 to 0.48). Adjustment for potential confounding factors increased the odds ratio to 0.41 (95 percent confidence interval, 0.25 to 0.69)...

Principles and Practice of Gynecologic Oncology

Abstract: Epidemilogy of gynaecologic cancers genetics of gynaecologic cancer basic biology and biochemistry of gynaecologic cancer tumour invasion and metastases oncogenes and antioncogenes immunology of gynaecologic cancers tumour markers cancer prevention hormonal interactions in gynaecologic malignancies biostatistics and clinical trials surgery in gynaecologic oncology perioperative and critical care biologic and physical aspects of radiation oncology principles of chemotherapy in gynaecologic cancer pharmacology and therapeutics in gynaecologic cancer gynaecologic oncology for the general obstetrician gynaecologist cancer in the pregnant patient management of infections in gynaecologic cancer patients management of pain quality of life and psychosocial aspects of gynaecologic cancer care sexual rehabilitation - surgical and psychological approaches nutrition in gynaecologic cancer patients diagnostic imaging techniques in gynaecologic oncology management of late effects of treatment AIDS and women pathogenesis and diagnosis of preinvasive lesions of the lower genital tract vulva vagina uterine cervix corpus - epithelial tumours corpus - mesenchymal tumours epithelial ovarian cancer ovarian germ cell tumours stromal tumours of the ovary carcinoma of the fallopian tube gestational trophoblastic disease breast cancer.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group.

Abstract: Data collected from 2,197 white ovarian cancer patients and 8,893 white controls in 12 US case-control studies conducted in the period 1956-1986 were used to evaluate the relation of invasive epithelial ovarian cancer to reproductive and menstrual characteristics, exogenous estrogen use, and prior pelvic surgeries. Clear trends of decreasing risk were evident with increasing number of pregnancies (regardless of outcome) and increasing duration of breast feeding and oral contraceptive use. Ovarian dysfunction leading to both infertility and malignancy is an unlikely explanation for these trends for several reasons: 1) The trends were evident even among the highly parous; 2) risk among nulliparous women did not vary by marital status or gravidity; and 3) risk among ever-married women showed little relation to length of longest pregnancy attempt or history of clinically diagnosed infertility. Risk was increased among women who had used fertility drugs and among women with long total duration of premenopausal sexual activity without birth control; these associations were particularly strong among the nulligravid. No consistent trends in risk were seen with age at menarche, age at menopause, or duration of estrogen replacement therapy. A history of tubal ligation or of hysterectomy with ovarian conservation was associated with reduced ovarian cancer risk. These observations suggest that pregnancy, breast feeding, and oral contraceptive use induce biological changes that protect against ovarian malignancy, that, at most, a small fraction of the excess ovarian cancer risk among nulliparous women is due to infertility, and that any increased risk associated with infertility may be due to the use of fertility drugs.

Screening Sigmoidoscopy and Colorectal Cancer Mortality

Abstract: Background Sigmoidoscopy may reduce colorectal cancer mortality by identifying both cancers and precursor lesions (including polyps) for treatment; however, evidence regarding the efficacy of this technique as a screening procedure is extremely limited. Purpose In the absence of data from randomized controlled trials, we performed a retrospective case-control study to determine if sigmoidoscopy screening is associated with a reduction in colorectal cancer mortality. Methods The medical records of 66 members of the Greater Marshfield Community Health Plan (GMCHP) who died of large-bowel cancer from 1979 to 1988 were reviewed for history of screening for colorectal cancer (case subjects). For comparison, the records of 196 GMCHP members of similar gender, age, and enrollment duration were randomly selected for review (control subjects). Results History of screening sigmoidoscopy was much less common among case subjects (10%) than among control subjects (30%). Risk for death from colorectal cancer was reduced among individuals having had a single examination by screening sigmoidoscopy (odds ratio = 0.21; 95% confidence interval = 0.08-0.52), compared with the risk for those who never had one. The reduction in risk appeared to be limited to tumors in the rectum and distal colon. Neither fecal occult blood testing nor digital rectal examination was associated with a reduction in colorectal cancer mortality. Conclusions These results suggest that screening sigmoidoscopy can substantially reduce mortality from cancers of the rectum and distal colon.

Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years

Abstract: OBJECTIVES: To evaluate the efficacy of the combination of annual screening with mammography, physical examination of the breasts and the teaching of breast self-examination in reducing the rate of death from breast cancer among women aged 40 to 49 years on entry. DESIGN: Individually randomized controlled trial. SETTING: Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. PARTICIPANTS: Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or usual care after an initial physical examination (UC group). The 50,430 women enrolled from January 1980 through March 1985 were followed for a mean of 8.5 years. DATA COLLECTION: Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients9 physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. MAIN OUTCOME MEASURES: Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size, and rates of death from all causes and from breast cancer. RESULTS: Over 90% of the women in each group attended the screening sessions or returned the annual questionnaires, or both, over years 2 to 5. The characteristics of the women in the two groups were similar. Compared with the Canadian population, the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 3.89 per 1000 in the MP group and 2.46 per 1000 in the UC group; more node-positive tumours were found in the MP group than in the UC group. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.26 in the MP group and 1.02 in the UC group. Of the women with invasive breast cancer through to 7 years, 191 and 157 women in the MP and UC groups respectively had no node involvement, 55 and 43 had one to three nodes involved, 47 and 23 had four or more nodes involved, and 38 and 49 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 28 in the UC group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 1.36 (95% confidence interval 0.84 to 2.21). The survival rates were similar in the two groups. The highest survival rate occurred among women whose cancer had been detected by mammography alone. CONCLUSION: The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography and physical examination of the breasts detected considerably more node-negative, small tumours than usual care, but it had no impact on the rate of death from breast cancer up to 7 years9 follow-up from entry.

Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water.

Abstract: In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.

Risk of cancer in patients with dermatomyositis or polymyositis. A population-based study.

Abstract: Background. An association between polymyositis and cancer was first proposed in 1916, but the existence of the association has been disputed. An association between dermatomyositis and cancer is better accepted, but its magnitude is not known. Methods. We undertook a study to provide accurate estimates of the risk of cancer in patients with dermatomyositis or polymyositis. We studied the incidence of cancer and the rate of mortality from cancer in a population-based cohort of 788 patients with dermatomyositis or polymyositis in Sweden from 1963 through 1983. The results were compared with those for the general population. Results. Among the 396 patients with polymyositis, 42 cancers were diagnosed at the same time or after polymyositis was diagnosed in 37 patients (9 percent). The relative risk of cancer was 1.8 (95 percent confidence interval, 1.1 to 2.7) in the male patients and 1.7 (95 percent confidence interval, 1.0 to 2.5) in the female patients. Eighty-four males and 85 females died, and ...

Deep-Vein Thrombosis and the Incidence of Subsequent Symptomatic Cancer

Abstract: Background. In contrast to the established relation between overt cancer and subsequent venous thromboembolism, it is unclear whether symptomatic deep-vein thrombosis is associated with a risk of subsequent overt malignant disease. Methods. Two hundred sixty consecutive patients with symptomatic, venographically proved deep-vein thrombosis were enrolled in a study, of whom 250 were followed during a two-year period. Among those assessed during follow-up, the incidence of subsequently detected cancer in the 105 patients with secondary venous thrombosis (i.e., thrombosis associated with a well-recognized risk factor other than cancer) was compared with the incidence of cancer in the 145 patients with idiopathic venous thrombosis. Results. Routine examination at the time of diagnosis of the venous thrombosis revealed cancer in 5 of the 153 enrolled patients with idiopathic venous thrombosis (3.3 percent) and in none of the 107 enrolled patients with secondary venous thrombosis. During follow-up, ove...

The "retinoic acid syndrome" in acute promyelocytic leukemia

Abstract: ▪Objective:To describe a novel complication of therapy with all-trans retinoic acid in patients with acute promyelocytic leukemia. ▪Design:Case series. ▪Setting:Comprehensive cancer center...

Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation.

Abstract: Background. Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men, The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer. Methods. Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses. Results. The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer. Conclusions. These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer.

Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer.

Abstract: E-cadherin is a Ca2+-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52: 2916–2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87: 8751–8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215–220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nonmalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.

The choice of treatment of single brain metastasis should be based on extracranial tumor-activity and age

Abstract: Purpose: To determine if in patients with single brain metastasis the addition of neurosurgery to radiotherapy leads to lengthening of survival or to better quality of life. Methods and Materials: From 1985 to 1990, 66 patients with single brain metastasis from a solid tumor were entered in a randomized trial of neurosurgery plus radiotherapy vs. radiotherapy alone. Patients were stratified for lung cancer vs. other sites of cancer and for progressive vs. stable systemic cancer. Radiotherapy was given to the whole brain by a novel scheme of two fractions of 2 Gy per day for a total dose of 40 Gy in 2 weeks, to obtain a relatively high total dose and short overall time, with minimal risk of late damage to normal tissue in long-term survivors. Results: In the whole group of 63 evaluable patients, both with lung cancer as with other tumors, the combined treatment led to a better duration of survival (median 10 vs. 6 months; p = 0.04). The largest difference between both treatment arms was observed in patients with inactive extracranial disease (median 12 vs. 7 months; p = 0.02). Patients with active extracranial disease had an equal median survival of only 5 months, irrespective of given treatment. Age proved to be a strong and independent prognostic factor: patients older than 60 years had a hazard ratio of dying of 2.74 (p = 0.003) compared with younger patients. Following treatment, most patients remained functionally independent until a few weeks before death. In the majority of patients the cause of death was systemic tumor progression. Conclusion: Patients with single brain metastasis and with controlled or absent extracranial tumor activity should be treated with surgery and radiotherapy, especially when they are younger than 60 years. For patients with progressive extracranial disease, radiotherapy alone seems to be sufficient. The accelerated radiotherapy scheme of 40 Gy in 2 weeks to the whole brain is tolerated well and should also be considered for patients in a good performance status with surgically unaccessible single metastasis or even with multiple brain metastases.

Insulin-like growth factors and cancer.

Abstract: The insulin-like growth factors (IGFs). also known as somatomedins, have been identified as a result of three separate lines of research carried out over the last 30 years (Van Wyk & Underwood, 1978). First, IGFs promote incorporation of 35-sulphate into cartilage, hence 'sulphation' factor (Salmon & Daughaday, 1957). Secondly, they mediate the mitogenic activity of serum (Pierson & Temin, 1972) and medium conditioned by rat hepatocytes (multiplication stimulating activity, MSA; Dulak & Temin. 1973). Thirdy. IGFs have insulin-like activity which is not inhibited by anti-insulin antibodies (non-suppressive insulin-like activity, NSILA: Froesch et al., 1963). Sequence analysis revealed that these functions are subserved by two main peptide: IGF-I, also known as somatomedin-C (Klapper et al.. 1983) and IGF-II. of which the rat form is MSA (Rinderknecht & Humbel. 1978; Marquardt et al.. 1981). The IGF terminology is now preferred as there is no somatomedin designation for IGF-II (Daughaday et al.. 1987). IGF-I (70 residues, MW 7649) and IGF-II (67 residues. MW 7471) are single chain peptides with around 70% sequence homology, and 50% homology with pro-insulin. Mature IGFs have A and B domains where the homology with proinsulin is highest, a C-peptide domain which has no sequence homology with proinsulin. and a carboxyterminal D domain (Daughaday & Rotwein. 1989). The IGF-I gene is located on chromosome 12q, and the IGF-II gene is on chromosome llp, contiguous with the insulin gene (Barreca & Minuto. 1989). In the mouse, the IGF-II gene is imprinted. that is. there is a difference in expression between the maternal and paternal genes. Specifically, it is the paternal IGF-II gene which is active (Willison. 1991). IGF-I is synthesised by the liver and also by other viscera including kidney and lung (D'Ercole et al., 1984). Hepatic synthesis, which largely determines serum levels, is regulated by growth hormone (GH) and also varies with liver function and nutritional status (Underwood et al., 1986; Zapf & Froesch. 1986). In endocrine-sensitive tissues. IGF-I gene expression may be regulated by hormones other than GH. Notably in rat uterus, IGF-I expression is enhanced by oestrogen, and is repressed to a small extent by GH (Murphy & Friesen, 1988). In vitro, IGF-I is a potent mitogen for normal cells including chondrocytes and other mesenchymal derivatives (Clemmons & Van Wyk, 1981). In vivo, IGF-I has acute insulin-like anabolic effects on adipose tissue, muscle and liver (Zapf & Froesch, 1986; Guler et al.. 1987). However its most important physiological role is as the primary regulator of growth, especially of mesenchymal tissues including bone and cartilage (Schoenle et al., 1982; Van Buul-Offers et al.. 1986; Mathews et al., 1988). IGF-II has metabolic and mitogenic effects experimentally, but its physiological function is unclear. Serum concentrations are less dependent on GH. and it causes less growth promotion in hypophysectomised animals (Schoenle et al., 1983). IGF-II mRNA is expressed in foetal tissues of mesenchymal origin, including kidney, liver

Studies of human tumors by MRS: a review.

Abstract: The literature describing 31P, 1H, 13C, 23Na and 19F MRS in vivo in human cancers is reviewed. Cancers have typical metabolic characteristics in 31P and 1H MRS including high levels of phospholipid metabolites and a cellular pH more alkaline than normal. These alone are not specific for cancer but are diagnostic in appropriate clinical settings. Some metabolic characteristics appear to be prognostic indices and correlation with treatment response is emerging as an important potentially cost-effective use of MRS in oncology. 19F MRS examines pharmacokinetics of 5-fluorouracil and by demonstrating its retention predicts response of a cancer to treatment. Current needs include improvement of diagnostic specificity by use of techniques like multivoxel MRS, proton decoupling of 31P, short echo time and fat-suppressed 1H MRS, 13C MRS direct or via 1H-observe, and statistical analysis of multiple spectral features. Trials in large populations in well defined clinical settings are needed to determine if MRS can provide independent prognostic indices useful in cancer management.

Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines.

Abstract: Lack of estrogen receptor (ER) and presence of vimentin (VIM) associate with poor prognosis in human breast cancer. We have explored the relationships between ER, VIM, and invasiveness in human breast cancer cell lines. In the matrigel outgrowth assay, ER+/VIM- (MCF-7, T47D, ZR-75-1), and ER-/VIM- (MDA-MB-468, SK-Br-3) cell lines were uninvasive, while ER-/VIM+ (BT549, MDA-MB-231, MDA-MB-435, MDA-MB-436, Hs578T) lines formed invasive, penetrating colonies. Similarly, ER-/VIM+ cell lines were significantly more invasive than either the ER+/VIM- or ER-/VIM- cell lines in the Boyden chamber chemoinvasion assay. Invasive activity in nude mice was only seen with ER-/VIM+ cell lines MDA-MB-231, MDA-MB-435 and MDA-MB-436. Hs578T cells (ER-/VIM+) showed hematogenous dissemination to the lungs in one of five mice, but lacked local invasion. The ER-/VIM+ MCF-7ADR subline was significantly more active than the MCF-7 cells in vitro, but resembled the wild-type MCF-7 parent in in vivo activity. Data from these cell lines suggest that human breast cancer progression results first in the loss of ER, and subsequently in VIM acquisition, the latter being associated with increased metastatic potential through enhanced invasiveness. The MCF-7ADR data provide evidence that this transition can occur in human breast cancer cells. Vimentin expression may provide useful insights into mechanisms of invasion and/or breast cancer cell progression.

Fungal infections in cancer patients: an international autopsy survey.

Abstract: In an attempt to estimate the frequency of fungal infections among cancer patients, a survey of autopsy examinations was conducted in multiple institutions in Europe, Japan and Canada. Fungal infections were identified most often in leukemic patients and transplant recipients (25% each). Fifty-eight percent of fungal infections were caused by Candida spp. and 30% by Aspergillus spp. There was considerable variability in the frequency of fungal infections in different countries. Nevertheless, this study clearly demonstrates that fungal infections represent a common complication in cancer patients, especially in patients with leukemia.

Paraneoplastic cerebellar degeneration.: I.A clinical analysis of 55 anti‐Yo antibody‐positive patients

Abstract: We reviewed the clinical findings in 55 patients with cerebellar degeneration associated with the anti-Yo antibody (an anti-Purkinje cell antibody identified in this study by histochemistry and Western blot). The patients were all women, 26 to 85 years old. Fifty-two of them proved to have malignancies, almost exclusively breast or gynecologic cancers and usually confined to the involved organs and local lymph nodes. One woman had adenocarcinoma of the lung, and in three no malignancy has yet been identified. In 34 of 52 patients with cancer, the neurologic syndrome preceded the diagnosis of cancer and in many led to that diagnosis. Patients subacutely developed a pancerebellar disorder that was substantially disabling in most, with 37 of 48 assessable patients being unable to walk or sit unassisted. Laboratory evaluation revealed lymphocytic pleocytosis in 35 patients, with eventual cerebellar atrophy on imaging studies in seventeen. The disabling neurologic syndrome generally did not respond to treatment, but the cancer was often successfully treated. The presence of the anti-Yo antibody in patients with cerebellar symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer, as many are curable at the time neurologic symptoms develop.

Glutathione Transferases and Cancer

Abstract: The glutathione transferases, a family of multifunctional proteins, catalyze the glutathione conjugation reaction with electrophilic compounds biotransformed from xenobiotics, including carcinogens. In preneoplastic cells as well as neoplastic cells, specific molecular forms of glutathione transferase are known to be expressed and have been known to participate in the mechanisms of their resistance to drugs. In this article, following a brief description of recently identified molecular forms, we review new findings regarding the respective molecular forms involved in carcinogenesis and anticancer drug resistance, with particular emphasis on Pi class forms in preneoplastic tissues. The rat Pi class form, GST-P (GST 7-7), is strongly expressed not only in hepatic foci and hepatomas, but also in initiated cells that occur at the very early stages of chemical hepatocarcinogenesis, and is regarded as one of the most reliable markers for preneoplastic lesions in the rat liver. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-responsive element-like sequences have been identified in upstream regions of the GST-P gene, and oncogene products c-jun and c-fos are suggested to activate the gene. The Pi-class forms possess unique enzymatic properties, including broad substrate specificity, glutathione peroxidase activity toward lipid hydroperoxides, low sensitivity to organic anion inhibitors, and high sensitivity to active oxygen species. The possible functions of Pi class glutathione transferases in neoplastic tissues and drug-resistant cells are discussed.

Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol

Abstract: SummaryCertain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the twol-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathioneS-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.

Clonal origin of bladder cancer.

Abstract: Background. Patients with cancer of the urinary bladder often present with multiple tumors, appearing at different times and at different sites in the bladder. This observation has been attributed to a "field defect" in the bladder that allows the independent transformation of epithelial cells at a number of sites. We tested this hypothesis using molecular genetic techniques. Methods. We examined 13 tumors from cystectomy specimens from four women, using a method that analyzes the pattern of X-chromosome inactivation to determine whether the tumors were derived from the same precursor cell. In addition, we analyzed allelic loss on autosomes to determine whether different tumors had the same genetic alterations. The alterations evaluated included the loss of chromosome 9q sequences (commonly found in superficial bladder tumors) and the loss of 17p and 18q sequences (usually found only in advanced tumors). Results. For each patient studied, all the tumors had inactivation of the same X chromosome, ...

Dietary intake of fiber and decreased risk of cancers of the colon and rectum: Evidence from the combined analysis of 13 case-control studies

Abstract: BACKGROUND Colorectal cancer is a major public health problem in both North America and western Europe, and incidence and mortality rates are rapidly increasing in many previously low-risk countries. It has been hypothesized that increased intakes of fiber, vitamin C, and beta carotene could decrease the risk of colorectal cancer. PURPOSE The objective of this study was to examine the effects of fiber, vitamin C, and beta-carotene intakes on colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. The study was designed to estimate risks in the pooled data, to test the consistency of the associations across the studies, and to examine interactions of the effects of the nutrients with cancer site, sex, and age. METHODS Original data records for 5287 case subjects with colorectal cancer and 10,470 control subjects without disease were combined. Logistic regression analysis was used to estimate relative risks and confidence intervals for intakes of fiber, vitamin C, and beta carotene, with the effects of study, sex, and age group being adjusted by stratification. RESULTS Risk decreased as fiber intake increased; relative risks were 0.79, 0.69, 0.63, and 0.53 for the four highest quintiles of intake compared with the lowest quintile (trend, P < .0001). The inverse association with fiber is seen in 12 of the 13 studies and is similar in magnitude for left- and right-sided colon and rectal cancers, for men and for women, and for different age groups. In contrast, after adjustment for fiber intake, only weak inverse associations are seen for the intakes of vitamin C and beta carotene. CONCLUSION This analysis provides substantive evidence that intake of fiber-rich foods is inversely related to risk of cancers of both the colon and rectum. IMPLICATIONS If causality is assumed, we estimate that risk of colorectal cancer in the U.S. population could be reduced about 31% (50,000 cases annually) by an average increase in fiber intake from food sources of about 13 g/d, corresponding to an average increase of about 70%.