PubMed Health⌕ Search

Biomedical subjects

S C Rubin

Publications and source records attributed to S C Rubin.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mutations of the BRCA2 gene in ovarian carcinomas.

Inherited mutations in the recently discovered BRCA2 gene are believed to be responsible for a significant fraction of early-onset hereditary breast cancers. Unlike BRCA1, however, which confers a high risk to both breast and ovarian cancer, the incidence of ovarian cancer appears to be much lower In BRCA2-linked families, causing uncertainty as to the relevance of BRCA2 to hereditary ovarian cancer. Numerous allelotype studies indicate that allelic deletions Including the BRCA2 locus on chromosome 13q are common in ovarian cancers in general, suggesting that somatic mutations of this gene may be involved in sporadic ovarian tumorigenesis. The purpose of this study was to test the hypothesis that germline or somatic mutations of BRCA2 are associated with hereditary and/or sporadic ovarian cancers, respectively. The entire 10.2-kb coding region of BRCA2 was screened for mutations in 130 consecutive ovarian tumors, the only selection criterion being a pathological diagnosis of epithelial ovarian carcinoma. Loss of heterozygosity at markers flanking BRCA2 was observed in 56% of the tumors. Four germline mutations and two somatic mutations were identified; two of the germline mutations are recurrent, having been previously described. Remarkably, the patients with germline mutations were late-onset cases with no medical or family histories suggestive of hereditary cancer. These data suggest that mutations of BRCA2 are rare in sporadic ovarian cancers, and that the proportion of ovarian cancers resulting from hereditary predisposition may be higher than previously suspected based on estimates derived from studies of highly penetrant genetic loci.

Aged↗
PubMed1996

OncoLink: a cancer information resource for gynecologic oncologists and the public on the Internet.

The Internet is a computer network accessible to over 30 million computers users worldwide. By default, it has become the "information superhighway" that is growing at an explosive rate of between 1 and 2 million new users per month. Internet contains thousands of information of interest to cancer patients and healthcare professionals. Identifying the outstanding "golden" resources from the chaos is difficult. To address this problem and to provide information specific to gynecologic oncology, we developed a cancer information server called "OncoLink" at our institution that is available at no cost 24 hr per day, 7 days per week to all Internet users. OncoLink has two major goals: (1) To provide quality, original content for cancer patients and healthcare professionals and (2) to provide well-organized, consistent access to existing Internet cancer resources. This service may be used by anyone with a Microsoft Windows, Apple Macintosh, or UNIX computer. The service is rich in multimedia content containing text, pictures, illustrations, sound, and video. The information includes (1) original content written by authors at our institution, (2) original content submitted by authors from other institutions and, (3) publicly available information from other resources. Patient-oriented articles, physician-oriented review articles, and NIH, NCI, and FDA documents are available. All content is reviewed by an Editorial Board prior to posting. We have kept a detailed log file of each time the system has been accessed by an Internet user. OncoLink went online in March 1994. During the first 18 months (542 days) of operation, the service received 4,051,901 request for information from 105,589 unique Internet addresses worldwide. There is tremendous public and professional demand for online cancer information via the Internet. We feel that the Internet is an outstanding vehicle for providing quality cancer information for gynecologic oncologist other healthcare professionals, and the public.

Computer Communication Networks↗
PubMed1996

Surgically documented responses to paclitaxel and cisplatin in patients with primary peritoneal carcinoma.

Intra-abdominal carcinomatosis indistinguishable from ovarian cancer may occur after removal of the ovaries or in association with surface ovarian involvement. Because its histologic pattern and behavior approximate those of ovarian cancer, this entity, known as primary peritoneal carcinoma, has been treated in a similar fashion--cytoreductive surgery followed by systemic chemotherapy. This review was undertaken to assess the efficacy of combination chemotherapy with paclitaxel and cisplatin, the current front-line chemotherapeutic regimen for ovarian cancer, in patients with primary peritoneal carcinoma. Sixteen patients diagnosed between January 1989 and July 1994 with primary peritoneal carcinoma were treated at the Hospital of the University of Pennsylvania. The records of the three patients whose initial chemotherapeutic regimen included paclitaxel and cisplatin were reviewed. An additional case from the Robert Wood Johnson Medical Center, Camden, New Jersey, was included. Pathologic review of all cases was conducted at the time of clinical management and again as part of this study. Reassessment laparotomy was performed in all patients after the completion of chemotherapy. Complete clinical information was available on all patients. All four patients presented with intra-abdominal carcinomatosis, and large volume (> 1 cm) residual disease was present following initial cytoreduction. Following chemotherapy, second-look laparotomy documented one complete pathologic response and three partial (>50% tumor volume reduction), but marked, responses. Combination chemotherapy with paclitaxel and cisplatin produces surgically documented responses in patients with primary peritoneal carcinoma.

Antineoplastic Agents↗
PubMed1996

Expression of A, B, and H blood group antigens in epithelial ovarian cancer: relationship to tumor grade and patient survival.

The expression of A, B, and H blood group antigens in epithelial ovarian cancer was evaluated in 137 patients with advanced disease by staining frozen sections with specific monoclonal antibodies using an indirect immunoperoxidase method. Expression of blood group antigens was observed in a proportion of ovarian carcinomas and in some areas of ovarian surface epithelium. Forty-eight percent of the tumors tested from 130 blood group A, B, or 0 individuals showed no expression of the appropriate blood group antigen, 32% had heterogeneous antigen expression, and 20% had strong expression. In the 7 blood group AB patients studied, no expression, heterogeneous expression of both antigens, or absence of one, but not the other antigen, was observed. No tumor showed A, B, or H antigen expression that was not compatible with the patient's blood group type. Histologic Grade 3 tumors showed absence of blood group antigen expression more often than did Grade 2 tumors. The presence or absence of A, B, or H antigen expression did not correlate with survival in this group of patients. This is in contrast to studies in other epithelial tumor types in which the normal epithelium synthesizes blood group antigens and loss of ABH antigen expression is observed in the corresponding tumors.

Aged↗
PubMed1996

Arterial occlusion complicating treatment of gynecologic cancer: a case series.

The objective in this paper is to describe the severity and outcome of arterial occlusion complicating treatment of women with gynecologic cancer. A series of six patients who underwent amputation were identified. Acute arterial occlusions were seen in three patients. One patient suffered extensive thrombosis of the hand and wrist resulting in amputation 3 weeks after cytoreductive surgery and chemotherapy for Fallopian tube cancer. She had a history of pulmonary embolism and deep-vein thrombosis. This patient was thought to have thrombophilia. One elderly patient with known arteriosclerosis developed sepsis following radical deep excision and groin dissection for vulvar cancer and lost two digits presumably due to microemboli. One patient developed thrombosis of the femoral artery on the second day following cytoreductive surgery for ovarian cancer. She responded to anticoagulation therapy; however, necrosis remained in portions of the heel and toes. Three patients underwent amputation of a lower extremity when they developed chronic arterial insufficiency after pelvic radiotherapy. The patients were irradiated at the ages of 28, 30, and 35 years for cervix cancer in two patients and a low-grade retroperitoneal sarcoma in one patient. Two received neutron beam therapy and one received conventional photon beam therapy. All three had extensive late radiation morbidity to the bladder and rectum and had multiple prior surgeries. The amputations occurred at the ages of 48, 48, and 55 due to accelerated arteriosclerosis. Two patients died as a result of this complication. Acute and chronic arterial occlusions are rare yet dramatic complications of therapy for gynecologic cancer. This series illustrates the predisposing factors, presentation, and management of these unusual events.

Adult↗
PubMed1996

Adenovirus-mediated gene therapy of ovarian cancer in a mouse model.

OBJECTIVE: Our purpose was to test the feasibility of adenovirus-mediated gene therapy of ovarian cancer. STUDY DESIGN: Ovarian cancer cell lines were exposed to an adenovirus vector expressing a reporter gene (lacZ) and to the same vector bearing the herpes simplex virus thymidine kinase gene (Ad.RSVtk) followed by ganciclovir. lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injected intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSVtk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests. RESULTS: Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSVtk all cell lines showed significant (p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established subcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSVtk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Additionally, no intraperitoneal tumors were observed in treated mice. CONCLUSIONS: Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSVtk. These data support the development of this method for human clinical trials.

Adenoviridae↗
PubMed1996

Expression and mutational analysis of P53 in stage IB and IIA cervical cancers.

OBJECTIVE: This study evaluates overexpression of the p53 protein and point mutation in the P53 gene in a group of patients with stage IB and IIA cervical cancer. STUDY DESIGN: We reviewed the medical records of all patients who underwent radical hysterectomy for the treatment of stage IB and IIA cervical cancer between 1980 and 1985 at Memorial Sloan-Kettering Cancer Center. Overexpression of p53 protein was determined with the use of immunohistochemistry on fixed and paraffin-embedded tissue. Two blocks were selected for each tumor, and tissue sections from each block were tested with both monoclonal (Ab-6) and polyclonal (CM-1) anti-p53 antibodies. Molecular analysis for determination of specific P53 gene mutations was performed with single-strand conformation polymorphism analysis. A group of 132 patients was identified for inclusion in the study. RESULTS: Fifty-eight of 132 tumors (44%) showed overexpression of the p53 protein and were subjected to molecular analysis. Discrepancy between pairs of blocks (7/132, 5.3%) and between antibodies for the same block (5/264, 1.9%) was uncommon. High-level overexpression was rare (5/132, 3.8%). No difference in survival was found on the basis of overexpression of p53 protein. Only one of the 58 cases (1/58, 1.7%) that showed overexpression of the p53 protein exhibited a point mutation (exon 8) in P53 by single-strand conformation polymorphism. This case had a low level of overexpression of p53 protein on immunohistochemistry. CONCLUSIONS: Low levels of overexpression of p53 were frequently seen in early cervical cancers (40/132, 30%). However, mutation of the P53 gene was rarely seen in these tumors. Overexpression of p53 protein as detected by immunohistochemistry is not predictive of a somatic mutation in the P53 gene in cervical cancer. Molecular analysis is required for confirmation of P53 mutations in these tumors.

Female↗
PubMed1996

Racial differences in survival from gynecologic cancer.

OBJECTIVE: To determine whether survival from gynecologic cancer is different between African-American and white patients at an inner-city hospital with both a large clinic and a private service. METHODS: We studied 538 patients (89 African American, 449 white) diagnosed with cervical, uterine, or ovarian cancer at a single institution from January 1, 1989 through December 31, 1993. Information was obtained on age, stage, site of disease, histology, and type of health insurance (public or commercial). Insurance coverage was used as a proxy for socioeconomic status. Overall survival was estimated by the method of Kaplan and Meier and compared by the log-rank test. Cox proportional hazard modeling was used to evaluate the effects of multiple factors on survival. RESULTS: African-American patients were significantly older and were more likely to have cervical cancer and public insurance than white patients. Overall survival was worse for African-American patients than for white patients (P < .05). However, stage for stage, there was no significant difference in survival between the groups. There was also no difference when patients were grouped by insurance status. African Americans had a significantly worse survival for cervical cancer than whites, and African-American patients older than 65 years had a worse survival than whites of similar age. On multivariate analysis, only stage and insurance coverage were significant predictors of survival. CONCLUSIONS: African-American patients with gynecologic cancer at our institution have worse overall survival than white patients. The survival difference seems to be due predominantly to differences in socioeconomic status and stage at diagnosis.

Black People↗
PubMed1995

Expression and mutation analysis of the p53 gene in uterine papillary serous carcinoma.

BACKGROUND: The status of p53 protein expression was determined by immunohistochemistry and correlated with genetic analysis and clinical outcome in patients with uterine papillary serous carcinoma (UPSC). METHODS: Twenty-two patients with UPSC were identified and immunohistochemical staining of p53 protein was performed. Staining was analyzed by quantitating nuclear reactivity in 500 randomly counted cells per specimen. DNA analysis was performed on the tumors using single-strand conformation polymorphism (SSCP) analysis of exons 4-10 of the p53 gene, followed by DNA sequencing of all variants. Clinical data and patient status were ascertained from chart reviews. RESULTS: Sixteen of the 22 (73%) tumors were scored as p53-overexpressing as determined by immunohistochemical analysis. Patients whose tumors overexpressed p53 had a statistically significant shorter survival than those whose tumors did not (P < 0.022). DNA analysis of the 22 tumors revealed five with mutations of the p53 gene. Only three of these mutations were observed in tumors that overexpressed p53. CONCLUSIONS: A relatively large percentage of UPSC tumors exhibited high p53 immunoreactivity. Overexpression is correlated with poor prognosis. Positive immunohistochemistry for p53 protein in UPSC is not necessarily indicative of a genetic mutation.

Aged↗
PubMed1995

The accuracy of a frozen section diagnosis of borderline ovarian malignancy.

While the accuracy of frozen section in the diagnosis of invasive ovarian neoplasms has been previously addressed, the frozen section diagnosis of borderline ovarian tumors has been less well characterized. The distinction between benign and borderline lesions is critical to the proper operative management of these patients. The records of 48 patients that had a frozen section diagnosis of borderline ovarian malignancy during surgical exploration between 1986 and 1993 were reviewed. Thirty-one patients were Stage I, 2 patients were Stage II, 10 patients were Stage III, and 5 patients were unstaged. Clarifying phrases were used frequently in the frozen section report, and these terms were categorized as "rule out" borderline tumor, borderline tumor, and "at least" borderline tumor. Of 33 cases with a frozen section report of borderline or at least borderline malignancy, no case were subsequently found to be benign. Errors in the intraoperative management could have occurred in 3 of 48 cases (6.25%), when benign neoplasms were thought to be of borderline malignancy on frozen section. However, in each of these cases, the clarifying term rule out was used, indicating the equivocal nature of the frozen section findings. Thirteen of the 48 patients (27.1%) were found to have a focus of invasive cancer within a borderline tumor on final pathologic review; the primary tumors in these 13 cases ranged in maximal diameter from 5 to 26 cm and were of varying histologic types. The level of experience of the pathologist responsible for the frozen section did not influence the accuracy of frozen section determination noted in this study. A frozen section evaluation identifying a borderline ovarian malignancy is accurate in excluding the presence of benign pathology. It is crucial to understand the meaning of specific clarifying terms used in frozen section diagnoses.

Adult↗
PubMed1995

Cytoreductive surgery in ovarian carcinoma patients with a documented previously complete surgical response.

Recurrent ovarian cancer after negative findings at second-look laparotomy is common. A retrospective review of 57 patients who developed recurrent tumor after a negative second-look laparotomy was undertaken to evaluate treatment efficacy and prognostic factors. All patients received primary platinum-based chemotherapy. Recurrences occurred in the abdomen or pelvis (40 patients), lymph nodes (7), liver (4), lungs (3), and vagina (3). Recurrent disease was diagnosed at a mean interval of 20 months after second-look surgery. Of the 38 patients who underwent laparotomy for recurrence, 36 (95%) had > 0.5 cm disease. After cytoreductive surgery 14 patients (37%) were left with minimal (< 0.5 cm) residual disease. Intestinal resection or bypass was performed on 10/38 patients (26%) with one requiring a colostomy. There was no operative mortality and one complication (small bowel obstruction). Treatment after recurrence consisted of platinum-based chemotherapy (88%), with the remaining patients receiving irradiation or hormonal therapy. At a mean follow-up from recurrence for the entire group of 20 months, 18/38 (47%) explored patients are alive. All 19 patients who were not explored died with a median survival time from recurrence of 9 months. Patients who underwent a laparotomy and patients with < 0.5 cm residual disease had a significant survival advantage (P < 0.0001). Initial stage, grade, disease-free interval, and disease found at laparotomy did not influence survival. Recurrent ovarian carcinoma after platinum-based chemotherapy is associated with a grave prognosis when the patient is deemed inoperable or when distant metastasis are found. Patients with disease reduced to < 0.5 cm showed a significant survival advantage.

Abdominal Neoplasms↗
PubMed1995

The effect of renal function on serum levels of CA 125.

OBJECTIVE: Serum assays for CA 125 are used to monitor disease status in patients undergoing treatment for epithelial ovarian cancer. While a number of benign gynecologic as well as benign and malignant nongynecologic conditions are associated with CA 125 elevations, the established "normal" range describes a healthy population of women. The metabolism and clearance of CA 125 is not well understood. Because mild degrees of renal impairment frequently occur in ovarian cancer patients, we investigated the effect of impaired renal function on basal CA 125 in a population of female dialysis patients. METHODS: Twenty-five women on hemodialysis were selected at random. Patients ranged in age from 29 to 87 years. Renal disease was secondary in most cases to diabetes mellitus or hypertension. The creatinine clearance was less than 10 cc/min for all patients. The duration of dialysis ranged from 3 months to 14 years. Serum levels of CA 125 were measured using monoclonal antibodies in an immunoradiometric assay. RESULTS: The mean of duplicate determinations for 23 of 25 (92%) patients fell within the normal range for otherwise healthy women (< 35 U/ml). There was no apparent correlation between CA 125 level and age, menopausal status, BUN, serum creatinine, adequacy of dialysis, or primary underlying diagnosis. Of the 2 patients (8%) with CA 125 levels above the normal range, 1 was premenopausal and the other was postmenopausal; their CA 125 elevations were marginal (49.81 and 50.51). CONCLUSIONS: The results of this study demonstrate that even marked renal insufficiency is not itself associated with significant elevations of CA 125 above the normal range selected for otherwise healthy women. The development of renal insufficiency during treatment for ovarian cancer should not alter the interpretation of serum levels of CA 125.

Adult↗
PubMed1995

Advances in surgery for gynecologic malignancies.

Surgery has a significant role in the management of most gynecologic cancers. Recent developments in the diagnosis and management of ovarian, cervical, endometrial, and vulvar cancer are worthy of addressing in this review. Significant advances have occurred in the understanding of molecular genetic lesions, leading to a predisposition for ovarian cancer that may have a profound influence on prophylactic oophorectomy. Interval debulking surgery may provide a survival advantage for patients with advanced ovarian cancer. The loop electrosurgical excision procedure has become an integral part of the management of preinvasive disease of the cervix. Advances in the application of surgical stapling devices may lead to reduced operative time and blood loss for radical hysterectomy. Recent studies have addressed the adequacy of endometrial biopsy for the evaluation of postmenopausal bleeding. Advances in lymphatic mapping techniques have led to a novel application to the intraoperative identification of the sentinel node in vulvar cancer.

Endometrial Neoplasms↗
PubMed1994

Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that can be produced by human ovarian cancer cells. Elevated IL-6 levels have been found in the serum and ascites of patients with ovarian cancer, but its role in this disease has not been clearly established. METHODS: The authors studied the relationship between IL-6 levels in serum and ascites, various tumor parameters, and survival in 70 patients with newly diagnosed, untreated epithelial ovarian cancer. Ascites and serum specimens were obtained at the time of initial surgery, and IL-6 levels were determined using the B9 bioassay. RESULTS: All patients underwent platinum-based chemotherapy after initial surgery. The median age of the group was 62 years (range, 28-87 years), and the median follow-up time was 13 months (range, 12-59 months). Significantly higher IL-6 levels were detected in patients' ascites (median, 49,612 pg/ml [range, < 1 to 680,330 pg/ml]) compared with serum (median, 10 pg/ml [range, < 1 to 1221 pg/ml]) (P < 0.0001). IL-6 levels in ascites correlated significantly with the volume of ascites (P < 0.0001) and nearly so with the size of tumor found at initial surgery (P = 0.05). Serum and ascites IL-6 levels did not correlate statistically with overall survival time, tumor stage, grade, histologic findings, residual tumor volume after debulking, and serum CA 125 levels. Although not statistically significant, patients who responded to chemotherapy tended to have lower ascites IL-6 levels (median, 21,102 pg/ml) compared with patients who did not respond to chemotherapy (median, 40,200 pg/ml). CONCLUSIONS: IL-6 is present in very high amounts in the ascites of patients with epithelial ovarian cancer. IL-6 levels in ascites correlated significantly with ascites volume and initial tumor size. IL-6 levels in ascites and serum did not correlate statistically with other tumor parameters or with survival time.

Adult↗
PubMed1994

Prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer.

BACKGROUND: Although expression of the HER-2/neu oncogene may be of some prognostic importance in advanced ovarian cancer, its role in early-stage disease has not been established. The current study examined the prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer. METHODS: The authors analyzed the expression of HER-2/neu on frozen tumor specimens from 40 patients with early epithelial ovarian cancer using the indirect immunoperoxidase technique with monoclonal antibodies that detect epitopes on the extracellular domain of the HER-2/neu protein. All patients underwent comprehensive surgical staging. HER-2/neu expression was graded as negative, weak, moderate (1+ to 2+), or strong (3+). Complete clinical data and long-term follow up were available for all patients. RESULTS: The distribution of patients by stage was as follows: Stage IA, 6; IB, 0; IC, 14; IIA, 4; IIB, 6; IIC, 10. The mean patient age was 53 years. Fourteen patients had serous tumors; nine, endometrioid; eight, clear cell; eight, mucinous; and one, undifferentiated. Intratumoral heterogeneity of HER-2/neu expression was observed with most specimens. In eight specimens (20%), some areas of the tumor showed strong (3+) expression, beyond the level that can be seen in normal ovarian epithelium. Twenty-eight specimens (70%) showed moderate (1+ to 2+) staining, whereas four specimens (10%) showed negative or weak staining. At a mean follow-up time among surviving patients of 32 months, 15 patients (37%) have had cancer recurrence. No statistically significant relationship was found between HER-2/neu expression and survival, disease-free survival, stage, or grade. A significant increase was found in 3+ expression of HER-2/neu in clear cell tumors. CONCLUSION: Consistent HER-2/neu overexpression occurs infrequently in early ovarian cancer, making it unlikely that such overexpression is a general early event in ovarian carcinogenesis. HER-2/neu expression does not appear to be a strong prognostic marker in early epithelial ovarian cancer.

Adult↗
PubMed1994

Image analysis of the distribution of intraperitoneally administered fluids in patients with ovarian cancer.

Patients are selected for intraperitoneal chemotherapy based on the condition of the peritoneal cavity and the volume of residual disease, as determined by second-look surgery. Several techniques have been described to assess the distribution of intraperitoneal fluids. They rely on point, as opposed to area, measurements. We performed serial radionuclide scans of 15 patients undergoing intraperitoneal chemo for ovarian cancer. Scans were performed following intraperitoneal administration of 500-1000 ml of 99Tc-labeled human serum albumin in normal saline. Each patient underwent three scans at least 4 weeks apart. Radionuclide scans were digitized for computerized analysis. Area in picture elements (pixels) and optical density (mass) of the 99Tc-labeled regions were determined and analyzed for similarities in the pattern of distribution. Area analysis was used to divide the patients into two groups. Group 2 patients (n = 7) had more patients with < 0.5 cm of residual disease (P = .051) and no evidence of disease (P = 0.1) compared with group 1 patients (n = 8). No differences in overall survival were found (P = 0.21). No objective measurement of distribution of intraperitoneally administered fluids exists. Computer image analysis may be an improvement over static scoring techniques to assess non-invasive imaging studies.

Antineoplastic Combined Chemotherapy Protocols↗