Showing papers on "Cancer published in 1990"

A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain

Abstract: To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.

A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer.

Abstract: Background. For patients with locally or regionally advanced non-small-cell lung cancer radiation is the standard treatment, but survival remains poor. We therefore conducted a randomized trial to determine whether induction chemotherapy before irradiation improves survival. Methods. All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging. Eligibility requirements included excellent performance status, minimal weight loss, and visible disease on radiography. Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy. Results. The eligible patients in group 1 (n = 7...

Increased cell division as a cause of human cancer

Abstract: Carcinogenesis research is increasingly focused on chemicals that are not genotoxic and yet, at high doses, can induce cancer, apparently by increasing cell proliferation. We hypothesize that increased cell division per se stimulated by external or internal factors is also associated with the development of many human cancers. Although this hypothesis is well substantiated in the experimental literature, it has not been generalized as an important mechanism for carcinogenesis in human populations. Under this increased cell division model, the pathogenesis of cancer may result from molecular genetic errors induced during the process of cell division and from altered growth control of malignant or premalignant cells. Molecular genetic analysis of human cancers has shown that tumor cells contain multiple genetic defects including mutations, translocations, and amplifications of oncogenes and are reduced to homozygosity for putative tumor suppressor genes; these phenomena all require cell division for their occurrence and fixation. Increased cell division increases the risk of such events occurring. An accumulation of a combination of such genetic errors leads to a neoplastic phenotype. Examples are discussed of human cancers in which increased cell division, which drives the accumulation of genetic errors and can lead to neoplastic transformation, is caused by hormones, drugs, infectious agents, chemicals, physical or mechanical trauma, and other chronic irritation.

Cancer statistics, 1990

Abstract: The American Cancer Societys Department of Epidemiology and Statistics reports its 24th annual compilation of cancer incidence survival and mortality data for the United States and around the world. (EXCERPT)

Western diet and Western diseases: some hormonal and biochemical mechanisms and associations.

Abstract: Breast cancer, prostate cancer, coronary heart disease and colon cancer belong to the so-called Western diseases and a general opinion is that diet is a significant or even the main factor increasing incidence and mortality of these diseases in the Western world. This review describes studies carried out in this department for about 10 years, many in collaboration with scientists abroad, and with the aim to clarify some of the connections between the diet and sex hormone, lipid and bile acid metabolism. A Western-type diet elevates plasma levels of sex hormones and decreases the sex hormone binding globulin concentration, increasing the bioavailability of these steroids. The same diet results in low formation of mammalian lignans and isoflavonic phytoestrogens. These diphenolic compounds seem to affect hormone metabolism and production and cancer cell growth by many different mechanisms making them candidates for a role as cancer protective substances. The precursors of these diphenols are to be found in ...

Family history and the risk of prostate cancer.

Abstract: A case-control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls. Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P < .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11–fold increased risk of developing prostate cancer. Recognizing that 9–10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease.

Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice.

Abstract: There are few reports describing experimental models of the growth and metastasis of human breast carcinomas. This article discusses the tumorigenic and metastatic properties of two estrogen receptor-negative breast carcinomas injected into nude mice. Tumor growth in the mammary fatpad (m.f.p.) and the subcutis was compared in female nude mice. The injection of 10(5) viable cells of two human breast carcinoma cell lines (MDA-MB-231 and MDA-MB-435) gave a 100% tumor take rate in the m.f.p., whereas only 40% of the s.c. injections produced tumors and these occurred several weeks after the appearance of the m.f.p. tumors. Thus, the m.f.p. of nude mice is a favorable site for the growth of human breast carcinomas. MDA-MB-435 tumors produced distant metastases in 80% to 100% of recipients. The most common sites for metastasis were the lymph nodes and lungs, with a lower incidence of metastases in muscle (chest wall and thigh), heart, and brain. New variant cell lines were isolated from metastases in the lungs, brain, and heart. All the cell lines were tumorigenic in the m.f.p., and the lung- and heart-derived metastasis lines produced slightly more lung metastases than the original cell line. However, the brain metastasis variant produced significantly fewer lung metastases. Intravenous inoculation of the spontaneous metastasis-derived cell lines produced few lung colonies. Only cell variants isolated from experimental lung metastases showed enhanced lung colonization potential when reinjected i.v. Our results suggest that the estrogen receptor-negative MDA-MB-435 cell line injected in the m.f.p. of nude mice could be a valuable tool for analysis of the cellular and molecular basis of the metastasis of advanced breast cancer.

Decreased erythropoietin response in patients with the anemia of cancer.

Abstract: Patients with solid tumors are often anemic even before they undergo cytotoxic therapy. Since the cause of the anemia of cancer is unknown, we examined the possible role of erythropoietin. Using a sensitive radioimmunoassay, we determined serum immunoreactive erythropoietin levels in 81 anemic patients with solid tumors. For any given degree of anemia, the serum concentration of immunoreactive erythropoietin was lower in this group of patients than in a group of control patients with iron-deficiency anemia (P = 0.0001). Furthermore, the expected inverse linear relation between serum levels of immunoreactive erythropoietin and of hemoglobin was absent in the group with cancer. The erythropoietin response was further decreased in patients receiving chemotherapy; it was not influenced by the presence or absence of cisplatin in the treatment regimen. The inability of the patients with cancer to produce erythropoietin was not absolute; if they had hypoxemia, adequate erythropoietin production was restored. We conclude that erythropoietin levels are inappropriately low in anemia associated with cancer, and that erythropoietin deficiency may contribute to the development of this form of anemia. Treatment of the anemia of cancer with erythropoietin may be of value.

Skin involvement as the presenting sign of internal carcinoma

Abstract: From tumor registry data of 7316 cancer patients, we found 367 cases (5.0%) with skin involvement. Skin involvement was present at the time of presentation in 92 patients (1.3%), only 26 of whom had remote metastases. Skin involvement was the first sign of cancer in 59 patients (0.8%); 22 had direct extension of their tumor into the skin, 20 had local metastases, and 17 had distal metastases. Direct invasion was most common with breast cancer and second most common with oral cavity cancer. Local metastases were also most frequently caused by breast cancer but occurred in surgical scars in three women with pelvic cancer and in perianal abscesses in one patient with rectal carcinoma as well. Except for metastases from unknown primary sites, distant metastases were rare as presenting signs, and their origins were widely distributed. Our data show that internal cancer uncommonly presents with skin involvement. Nevertheless, an index of suspicion should be maintained and biopsy performed, particularly for nonhealing ulcers, persistent indurated erythema, and unexplained skin nodules.

Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy

Abstract: A hospital-based case-control study of upper aerodigestive tract tumors was conducted between June 1986 and June 1989 in Northern Italy. One hundred fifty-seven male cases of oral cavity cancer, 134 of pharyngeal cancer, 162 of laryngeal cancer, and 288 of esophageal cancer, and 1272 male inpatients with acute conditions unrelated to tobacco and alcohol were interviewed. Odds ratios for current smokers of cigarettes were 11.1 for oral cavity, 12.9 for pharynx, 4.6 for larynx, and 3.8 for esophagus. For all 4 sites, the risk increased with increasing number of cigarettes and duration of smoking habits and, with the exception of esophageal cancer, decreased with increasing age at the start of and years since quitting smoking. Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers. Significantly increased risks emerged also in heavy drinkers (odds ratio greater than 60 versus greater than or equal to 19 drinks/week = 3.4, 3.6, 2.1, and 6.0 for oral cavity, pharynx, larynx, and esophagus, respectively), deriving predominantly from wine consumption.

Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation.

Abstract: To study the mechanism of regression of human prostatic cancer following androgen ablation, the androgen-responsive PC-82 human prostatic adenocarcinoma xenograft was used as a model system Castration of male nude mice bearing PC-82 xenografts results in a 50% tumor regression by 2 wk following androgen ablation This regression is due to a sequence of biochemical and morphological events that results in both the cessation of cell proliferation and activation of programmed death or apoptosis of the androgen-dependent prostatic cancer cells Associated with this response are an enhanced expression of the transforming growth factor beta 1 gene, a potent inhibitor of cell proliferation, and testosterone-repressed prostatic message 2 (designated TRPM-2), a programmed cell death-associated gene Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that preceded the dramatic reduction in tumor volume following androgen ablation These results suggest that androgen-dependent human prostatic cancer cells, like normal prostatic cells, retain the ability to inhibit proliferation and to activate programmed cell death in response to androgen ablation Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even androgen-independent human prostatic cancer

Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials.

Abstract: About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.

Allelic loss of chromosomes 16q and 10q in human prostate cancer.

Abstract: Recent advances in understanding the molecular genetics of common adult tumors have indicated that multiple genetic alterations including the activation of oncogenes and the inactivation of tumor suppressor genes are important in the pathogenesis of these tumors. Loss of heterozygosity is a hallmark of tumor suppressor gene inactivation and has been used to identify chromosomal regions that contain these genes. We have examined allelic loss in the most common tumor in men, prostate cancer. Twenty-eight prostate cancer specimens have been examined for loss of heterozygosity at 11 different chromosomal arms including 3p, 7q, 9q, 10p, 10q, 11p, 13q, 16p, 16q, 17p, and 18q. Fifty-four percent (13/24) of clinically localized tumors and 4 of 4 metastatic tumors showed loss of heterozygosity on at least one chromosome. Chromosomes 16q and 10q exhibited the highest frequency of loss of heterozygosity with 30% of tumors showing loss at these chromosomes. These data demonstrate that allelic loss is a common event in prostate cancer and suggest that chromosomes 16q and 10q may contain the sites of tumor suppressor genes important in the pathogenesis of human prostate cancer.

Development of Antiestrogens and Their Use in Breast Cancer: Eighth Cain Memorial Award Lecture

Abstract: This paper describes the laboratory discovery and clinical testing of the first nonsteroidal antiestrogen, MER-25 (ethamoxytriphetol). The compound blocks estrogen action in all species tested and has only slight but transient estrogenic effects. No other antisteroidal actions are noted. MER-25 is antiestrogenic in primates and was investigated in the clinics in a wide range of gynecological conditions, including breast and endometrial cancer. Unfortunately toxic side effects (hallucinations, etc.) precluded further investigation. A derivative of triphenylethylene, clomiphene, has some partial agonist (estrogen-like) actions in laboratory animals and following clinical evaluation is now an established agent for the induction of ovulation in subfertile women. Although clomiphene is active in advanced breast cancer, it was not developed further. In the late 1960s a related compound, tamoxifen, was evaluated to treat a number of estrogen-responsive disorders but was successfully introduced in the 1970s for the treatment of advanced breast cancer. Although there was only modest initial interest in the palliative use of tamoxifen, an enormous increase in basic and applied studies with antiestrogens resulted in a definition of the target site-specific and tumoristatic actions of tamoxifen. Close cooperation between laboratory and clinical evaluation has guided the subsequent development of tamoxifen which is now available to treat all stages of breast cancer. Long-term adjuvant tamoxifen therapy, a concept developed in the laboratory, is currently the treatment strategy of choice. The considerable success of tamoxifen has focused attention on new antiestrogens with different pharmacological properties for other potential clinical applications.

Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review.

Abstract: A search of the literature using National Library of Medicine databases and individual cancer journal articles yielded over 500 compounds with published chemopreventive activity in animals. From these, an initial 16 agents or agent combinations have been evaluated in the following animal tumor models: mouse skin papillomas/carcinomas induced by 7,12-dimethylbenz( a )anthracene/12- O -tetradecanoylphorbol-13-acetate; rat breast adenocarcinoma induced by N -methyl- N -nitrosourea or 7,12-dimethylbenz( a )anthracene; hamster lung carcinoma induced by N -methyl- N -nitrosourea or diethylnitrosamine; mouse bladder papillary carcinoma induced by N -butyl- N -(4-hydroxybutyl)nitrosamine; and rat and mouse colon cancer induced by azoxymethane/methylazoxymethanol acetate. Some of the most interesting positive results observed include 4-hydroxyphenyl retinamide plus tamoxifen in breast cancer, piroxicam in colon cancer, dimethylfluoroornithine in breast and bladder cancer, oltipraz in lung cancer, dehydroepiandrosterone in colon cancer, and molybdate in bladder cancer. Eighteen human intervention trials in progress are described that involve the following agents: β-carotene (eight trials). Retinol/retinoic acid (seven trials), vitamins C and E (three trials), 4-hydroxyphenyl retinamide (one trial), piroxicam (one trial), and calcium (one trial). By organ site these studies involve cancer of the lung (six studies), skin (five studies), colon (four studies), breast (one study), and uterine cervix (two studies).

Symptom prevalence and control during cancer patients' last days of life.

Abstract: The lack of control of physical suffering among cancer patients in the last days or hours of life is a common medical problem but it is rarely discussed in an open fashion. We carried out a prospective study of the dying of 120 terminal cancer patients assisted by a home care team. We documented how long it was before death that physical symptoms, unendurable to the patient and controlled only by sedation-inducing sleep, appeared. In 63 patients (52.5%), unendurable symptoms due to tumor progression or irreversible acute organic phenomena appeared, on average two days before death. Of the 63 patients, 47 had only one uncontrollable symptom, 15 had two symptoms and one patient had three symptoms. The most common symptoms included dyspnea (33 patients), pain (31), delirium (11), and vomiting (5). The most frequent symptoms were dyspnea in lung and head and neck disease; pain in breast, gastrointestinal tract, colon-rectum, and male genitourinary tract cancer; and vomiting in female genitourinary tract malignancies. Data reported emphasize the clinical relevance of physical symptoms in the last days of life in terminal cancer patients and how these serve to indicate imminent death. More than 50% of these patients die with physical suffering that is controllable only by means of sedation.

Histologic differentiation, cancer volume, and pelvic lymph node metastasis in adenocarcinoma of the prostate

Abstract: The Gleason grading system for prostate cancer was applied quantitatively to analysis of entire tumors in 209 radical prostatectomy specimens from patients with clinical Stage A and Stage B carcinoma. Percentage of poorly differentiated tumor (Gleason histologic pattern 4 and/or 5) was related to quantitated cancer volume, cancer location within the prostate, and presence or absence of pelvic lymph node metastasis. A strong correlation was found between cancer volume, percentage of poorly differentiated cancer, and nodal metastasis. Twenty-two of 38 patients with more than 3.2 cc of Gleason histologic pattern 4-5 cancer had nodes with positive results, compared with one of 171 patients with less than 3.2 cc of pattern 4-5 cancer. Gleason histologic patterns 1 and 2 cancer was found mainly in a small subgroup of tumors whose site of origin was in the anatomic transition zone and whose volume was less than 1 cc. Gleason "cribriform" histologic pattern 3 cancer was thought to represent mainly intraductal carcinoma. Its increase in area with increasing cancer volume paralleled the increase in pattern 4 cancer and was counter to the decrease in other types of pattern 3 cancer.

Isoenzyme(s) of glutathione transferase (class Mu) as a marker for the susceptibility to lung cancer: a follow up study

Abstract: Glutathione transferase are divided into three classes: Alpha, Mu and Pi. Isoenzyme(s) from one of these classes, class Mu, is dominantly inherited and can be determined by activity measurements directed towards the substrate trans-stilbene oxide. The frequency of this phenotype has been measured in patients with bronchial carcinoma and in control subjects matched for age and smoking history. After combining an earlier study from our laboratory (Carcinogenesis, 7, 751-753, 1986) with the additional material presented here (control smokers, n = 114, lung cancers, n = 125) non-cancer smokers had an increased number of subjects who expressed class Mu isoenzymes (58.3% of total n = 192) compared with lung cancer patients (36.6% of total n = 191; P less than 0.0001). The pathology of lung tumors related to the lack of class Mu isoenzymes which occurred most frequently in patients with adenocarcinomas. It is concluded that the gene expressing class Mu isoenzymes may be a host determinant of genetic susceptibility to lung cancer among smokers.

Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study.

Abstract: A cohort of 17,633 white males age 35 and older responded to a mailed epidemiological questionnaire in 1966 and was followed until 1986 to determine the risk of cancer associated with diet, tobacco use, and other factors. During the 20-year follow-up, 149 fatal prostate cancer cases were identified. Relative risks for prostate cancer were significantly elevated among cigarette smokers (relative risk, 1.8; 95% confidence interval, 1.1–2.9) and users of smokeless tobacco (relative risk, 2.1; 95% confidence interval, 1.1–4.1). No significant associations were found with frequency of consumption of meats, dairy products, fruits, or vegetables. There were no overall significant associations between consumption of vitamin A from animal sources (retinol) and provitamin A from plant sources (carotene) and risk, but positive trends were seen for ages under 75, while inverse associations were found at older ages. Beverage consumption, including drinking coffee and alcohol, was unrelated to risk. Marital status, education, rural/urban status, and farming residence were also unrelated to the risk of fatal prostate cancer. The findings add to limited evidence that tobacco may be a risk factor for prostate cancer, but fail to provide clues to dietary or other risk factors.

Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment.

Abstract: Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma. Canine osteosarcoma is a malignant aggressive bone tumor with a 90% metastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers. Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies. Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches. Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers. Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers. This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology.

The prostate: An increasing medical problem

Abstract: The prostate gland is the major site of medical problems in the U.S. male. Surgery for benign prostatic hyperplasia is the most common surgical procedure performed in males, and the total cost for this surgery exceeds 1 billion dollars per year. The incidence of and mortality from prostate cancer are increasing yearly. Prostate cancer now exceeds lung cancer as the most commonly diagnosed cancer in males and is the second leading cause of male cancer deaths. Of all tumors, the prevalence of prostate cancer increases the most rapidly with age. A shift in age distribution favoring an older population will lead to an increase in the number of patients diagnosed with prostate cancer in the United States. It is estimated that by the year 2000 there will be a 37% increase in prostate cancer deaths per year and a 90% increase in prostate cancer cases per year. Although the factors responsible for the development and progression of prostate cancer to a clinically manifest form are not known, there is evidence that environmental factors may play a role. It will be important for the future to focus on the etiological factors that may lead to a decrease in the prevalence of prostatic tumors.

Insulin-like Growth Factor Receptor Expression and Function in Human Breast Cancer

Abstract: The insulin-like growth factors IGF-I and IGF-II are potent mitogens for several breast tumor cell lines in culture. Additionally, both IGF-I and IGF-II mRNAs are easily detected in the majority of breast tumor specimens examined, while no breast cancer epithelial cell lines we have studied express authentic IGF-I mRNA, and few lines express IGF-II mRNA. Although receptors for insulin, IGF-I, and IGF-II have been described, there is significant cross-reactivity between the various receptors and ligands in the insulin/insulin-like growth factor family, and it is not clear which receptor or receptors are responsible for the biological effects of these growth factors in this system. Using an RNase protection assay, we examined breast tumor specimens and breast cancer epithelial cell lines for expression of mRNA encoding the type I and type II IGF receptors as well as the insulin receptor. Virtually all of the specimens examined expressed mRNA for all three receptors. We then examined estrogen-dependent MCF-7 cells for the mitogenic effects of IGF-I and II in the presence of antibodies to both the type I and type II receptors. alpha IR-3, a monoclonal antibody which blocks the type I receptor, abolished the mitogenic effects of both IGF-I and IGF-II. It did not, however, block the mitogenic effects of insulin. We conclude that type I and type II IGF receptors are ubiquitously expressed in breast cancer, and our experiments with MCF-7 cells suggest the mitogenic effects of both IGF-I and IGF-II are mediated via the type I IGF receptor.

Allelic losses of chromosomes 9, 11, and 17 in human bladder cancer.

Abstract: Twenty-five human bladder tumors were examined for loss of heterozygosity of markers on chromosomes 6p, 9q, 11p, 14q, and 17p. These studies show that all of the markers were reduced to homozygosity in at least some of the tumors. They also confirmed earlier studies by Fearon et al. [Nature (Lond.), 318: 377-380, 1985] that approximately 40% of bladder tumors were reduced to homozygosity for markers on chromosome 11p. However, the greatest frequency of allelic loss was seen for chromosomes 9q (67% of informative cases) and 17p (63% of informative cases) with both chromosomes being lost concordantly in 10 out of 20 informative tumors. Allelic loss of chromosome 9q has not been previously observed with other human cancers; however, deletions of 17p have been reported in breast, lung, and colorectal carcinomas. The data raise the interesting possibility that allelic losses of specific chromosomes might be a feature of cancer in a particular differentiated cell type whereas loss of other chromosomes harboring more generally acting tumor suppressor genes might be a common feature of human cancers.