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Biomedical subjects

J S Berek

Publications and source records attributed to J S Berek.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cytokine-induced modulation of tumor suppressor gene expression in ovarian cancer cells: up-regulation of p53 gene expression and induction of apoptosis by tumor necrosis factor-alpha.

OBJECTIVE: Our purpose was to determine the effect of tumor necrosis factor-alpha on anti-oncogene expression and to investigate the relationship between the up-regulation of the p53 tumor suppressor gene and tumor necrosis factor-alpha-mediated apoptosis in epithelial ovarian cancer cell lines. STUDY DESIGN: By means of Northern blot techniques p53 messenger ribonucleic acid expression was assayed in ovarian cancer cells. Tumor cells explanted from patients into Balb/c nude mice were exposed to supernatants from activated monocytes, activated T cells, or the recombinant cytokines interleukin-6 and tumor necrosis factor-alpha. Time- and dose-dependence of p53 up-regulation was measured. Induction of programmed cell death (apoptosis) by tumor necrosis factor-alpha was quantitated by means of a deoxyribonucleic acid fragmentation assay. RESULTS: Detectable levels of messenger ribonucleic acid for p53 were seen in ovarian cancer cells. Tumor necrosis factor-alpha induced a significant up-regulation of p53 messenger ribonucleic acid levels in ovarian cancer cells grown in nude mice and in vitro, whereas interleukin-6 did not. The maximum level of induction was 8 hours, and the up-regulation of p53 was dose dependent. In addition, tumor necrosis factor-alpha induced a dose-dependent increase in deoxyribonucleic acid fragmentation. CONCLUSION: Tumor necrosis factor-alpha induced up-regulation of p53 tumor suppressor gene expression in epithelial ovarian cancer cell lines, together with the induction of cell death by apoptosis.

Apoptosis↗
PubMed1994

Advances in the biology of gynecologic cancer.

This review discusses recent insights into the roles of the p53 tumor-suppressor gene and growth factors in the development of ovarian cancer and describes the genes implicated in familial ovarian cancer syndromes related to the MSH2 (Lynch II) and BRCA1 (breast and ovarian cancer) genes. Evidence of the monoclonality of ovarian cancer, which contrasts with data supporting the polyclonal origin of primary peritoneal carcinoma, is presented. Finally, the roles of the human papillomavirus and the HIV virus in the etiology of cervical cancer are analyzed in view of the growing importance of this HIV-associated cancer and the poor outcome in these patients.

Female↗
PubMed1994

A multicenter study of laparoscopic management of selected cystic adnexal masses in postmenopausal women.

BACKGROUND: The objective of this study was to determine the ability to predict benign adnexal masses in postmenopausal women and to evaluate the effectiveness of laparoscopic management in selected patients. STUDY DESIGN: Postmenopausal women found to have an adnexal mass were prospectively evaluated with clinical examination, sonography, and serum CA-125 levels. Women with cystic masses greater than 3 cm but less than 10 cm, with distinct borders, without solid parts or septations greater than 2 mm, without ascites or matted bowel, and with serum CA-125 levels less than 35 IU per mL were operated upon by laparoscopy. RESULTS: Sixty-one women gave consent for the study. Cyst size ranged from 3 to 10 cm. All masses were accurately predicted to be benign. Fifty-eight (95 percent) women were successfully managed by operative laparoscopy and three required laparotomy. For the patients managed by laparoscopy, the mean operative time was 63 minutes, the mean postoperative hospitalization period was 12 hours, and the mean return to normal activity was 5.6 days. CONCLUSIONS: The combination of clinical examination, sonographic appearance and serum CA-125 levels can accurately predict benign masses in postmenopausal women. Operative laparoscopy is acceptable for these patients and provides for a short period of hospitalization and a rapid recovery.

Adnexal Diseases↗
PubMed1994

Laparoscopic management of the adnexal mass.

Careful preoperative evaluation of women found to have an adnexal mass may select patients for whom operative laparoscopy is appropriate. The role of ultrasonography and serum tumor markers in patient selection is discussed. Operative techniques for the laparoscopic management of the adnexal mass are also presented.

Adnexa Uteri↗
PubMed1994

Molecular and biologic factors in the pathogenesis of ovarian cancer.

The development and progression of epithelial ovarian cancer can be correlated with various biologic and molecular factors. Tumor growth has been associated with aberrant and dysfunctional expression and mutation of various genes. These genetic defects include oncogene overexpression, amplification or mutation, aberrant tumor suppressor gene expression or mutation, and the inappropriate expression of cytokines and growth factors and/or the cellular receptors for these molecules. Dysregulation of host immune responses may also play a permissive role in the pathogenesis of the disease. Since ovarian cancer has been associated with the frequency of ovulation, the repeated proliferation of epithelial cells may increase the chance of a genetic accident that could contribute to the activation of an oncogene or inactivation of a suppressor gene. These events, combined with the inherent ability of ovarian epithelial cells to respond to and produce various cytokines and growth factors, could promote oncogenesis.

Cytokines↗
PubMed1994

Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma.

OBJECTIVE: To determine the incidence of uterine sarcoma in patients operated on for symptomatic uterine leiomyomas or "rapidly growing" leiomyomas. METHODS: We reviewed the medical records of 1332 women admitted to either of two community hospitals between 1988-1992 for hysterectomy or myomectomy for uterine leiomyomas. The incidence of leiomyosarcoma, endometrial stromal sarcoma, and mixed mesodermal tumor was calculated. Patient ages, admitting symptoms, and operative and pathologic findings were analyzed. The study included 371 women (28%) operated on for rapidly growing leiomyomas. All patients operated on during the same interval and found to have a uterine sarcoma were reviewed. RESULTS: One of the 1332 patients operated on for presumed leiomyoma was found to have a leiomyosarcoma. This women was the only patient found to have a sarcoma among 371 women operated on for rapid growth of the uterus. None of 198 patients who met a published definition of rapid growth had a uterine sarcoma. Two women (0.15%) had endometrial stromal sarcoma, but none had a mixed mesodermal tumor. During the same interval, nine additional patients were found to have uterine sarcomas, and for these women, the preoperative diagnosis was sarcoma in four, endometrial cancer in three, ovarian cancer in one, and prolapsed uterus in one. CONCLUSIONS: The total incidence of uterine sarcoma (leiomyosarcoma, endometrial stromal sarcoma, and mixed mesodermal tumor) among patients operated on for uterine leiomyoma is extremely low (0.23%). The incidence of sarcoma among patients having surgery for "rapidly growing" leiomyoma (0.27%) or among those who met published criteria for rapid growth (0%) does not substantiate the concept of increased risk of sarcoma in these women.

Adult↗
PubMed1994

Papillary serous cystadenocarcinoma arising in benign glandular inclusion cysts in pelvic and inguinal lymph nodes.

BACKGROUND: Benign glandular inclusion cysts occurring within lymph nodes have been well described in the literature. However, the malignant potential of these glands is unknown. One previous case report described an adenoacanthoma arising within one of these glands. CASE: A 65-year-old woman was previously diagnosed with papillary serous cystadenocarcinoma in the inguinal and pelvic lymph nodes. She had no tumor involving the ovaries or peritoneal surfaces at the time of initial diagnosis. She presented to us 9 years later with a recurrence of this tumor in the obturator fossa and along the vaginal sidewall. Treatment consisted of surgery, radiation, and chemotherapy. CONCLUSION: Although rare, müllerian tumors can occur in the lymph nodes without simultaneous ovarian or peritoneal involvement, and most likely arise de novo within lymph node inclusion cysts.

Aged↗
PubMed1993

Constitutive production of macrophage colony-stimulating factor and interleukin-6 by human ovarian surface epithelial cells.

Normal and neoplastic epithelial cells produce growth factors that can affect cells from different lineages. Epithelial ovarian cancers produce M-CSF and IL-6. In the present study, production of these cytokines has been measured in the apparently normal epithelial cells from which epithelial ovarian neoplasms are thought to arise. Epithelial cells from the surface of premenopausal human ovaries were established in short-term cultures. The cells bound anti-cytokeratin antibodies and exhibited characteristic epithelial morphology by light and transmission electron microscopy. M-CSF and IL-6 were detected in supernatants from cultures of these cells, using assays specific for each factor. Cytokine levels were comparable to those in supernatants from ovarian and breast cancer cell lines. M-CSF expression could also be demonstrated by immunohistochemical analysis with specific rabbit heteroantiserum. Thus, M-CSF and IL-6 are produced constitutively by normal as well as by neoplastic ovarian epithelium.

Cells, Cultured↗
PubMed1993

Sensitivity of drug-resistant human ovarian tumor cell lines to combined effects of tumor necrosis factor (TNF-alpha) and doxorubicin: failure of the combination to modulate the MDR phenotype.

We have examined four human ovarian tumor lines (A2780, AD10, OVC-8, and SKOV-3) selected for their sensitivity and/or resistance to the recombinant human tumor necrosis factor alpha (TNF-alpha) and the chemotherapeutic drug doxorubicin (DOXO). The tumor lines were either sensitive to both agents, resistant to one or the other, or resistant to both. Of the four lines examined only the DOXO-resistant line AD10 exhibited the multidrug-resistance (MDR) phenotype. Enhanced cytotoxicity was seen with the combination of TNF-alpha and DOXO in each line regardless of their sensitivity or resistance patterns and, thus, demonstrates that drug resistance due to the expression of the MDR phenotype or its absence can be overcome by TNF-alpha and DOXO. We then examined whether TNF-alpha or TNF-alpha and DOXO modulated the MDR phenotype in AD10 as a possible mechanism of overcoming drug resistance. TNF-alpha had no effect on either DOXO intake or efflux as measured by flow cytometry. Further, TNF-alpha treatment showed no effect on the level of MDR-1 mRNA. These results suggest that the enhanced cytotoxicity seen with the combination of TNF-alpha and DOXO is not the result of any modulation of drug influx or efflux levels by TNF-alpha. Overall, these findings suggest that combination treatment with TNF-alpha and DOXO can overcome resistance inflicted by different mechanisms.

Doxorubicin↗
PubMed1993

Solitary recurrent metastasis of epithelial ovarian cancer in the spleen.

In epithelial ovarian cancer, solitary metastasis to and recurrences in the parenchyma of the spleen are rare in the absence of apparent disease in other sites. We report four patients who developed isolated, solitary splenic parenchymal recurrences of their epithelial ovarian adenocarcinomas and underwent a splenectomy to remove the recurrent disease. They had undergone optimal cytoreductive surgery for stage III grades 2-3 serous cystadenocarcinoma of the ovary, followed by six to nine cycles of cisplatin and cyclophosphamide chemotherapy and a negative second-look laparotomy. Evidence of relapse developed 2, 4, 6, and 10 years after initial treatment. In two patients, a rising CA-125 heralded the recurrence that was subsequently documented by computed tomography (CT) of the abdomen and pelvis with a single defect noted only in the splenic parenchyma. Two others had only a defect on CT scan. Based on these findings, the otherwise healthy women underwent an exploratory laparotomy, each had a single focus of recurrent poorly differentiated disease that was found in the splenic parenchyma and a splenectomy was performed. Multiple biopsies and cytologies revealed no other evidence of microscopic disease. There was no major postoperative morbidity. Subsequently, one woman was treated with intraperitoneal cisplatin, two with intravenous carboplatin, and one declined further therapy. Three women are alive and free of disease at 6 months to 3 years. The fourth woman is alive with recurrent disease near the site of the resected spleen found 10 months postsplenectomy. Thus, splenic recurrence of epithelial ovarian cancer can occur in the absence of other demonstrable metastasis, and it can be preceded by elevation of CA-125 and an abnormal CT scan. Based on this limited experience with selected patients, splenectomy may have a role in the management of this unusual recurrence.

Aged↗
PubMed1993

Primary leiomyosarcoma of the ovary in a perimenarchal female.

A case of primary leiomyosarcoma of the ovary in a perimenarchal female is presented. Previous to this report, ovarian leiomyosarcoma was thought to arise predominantly in postmenopausal women and, indeed, this is the first reported case in a pubertal adolescent. The sarcoma was associated with bilateral cellular ovarian leiomyomas, suggesting malignant degeneration of such tumors. After complete resection, the patient is alive without evidence of recurrent disease 20 months after diagnosis. A review of the literature suggests that chemoradiation is of unproven benefit and aggressive surgical management is recommended.

Cerebellar Neoplasms↗
PubMed1993

Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides.

In previous work, we saw that interleukin-6 (IL-6), a multifunctional cytokine, is produced by epithelial ovarian cancer cells and that ovarian cancer cells express the IL-6 receptor. Here, we examined the possibility that IL-6 acts as an autocrine growth factor for ovarian cancer cells. Inhibition of IL-6 gene expression by exposure to IL-6 antisense oligonucleotides resulted in greatly decreased cellular proliferation. Exposure of ovarian cancer cell lines (CAOV-3, OVCAR-3, and OC-436), to 1-5 microM of a 15-base single-stranded antisense IL-6 oligodeoxynucleotide, specific for a sequence in the second coding exon of the IL-6 gene, resulted in decreased IL-6 production and a > 80-85% inhibition of cellular proliferation. However, the addition of exogenous IL-6 failed to restore the proliferation of the antisense-treated cells. Antibodies to IL-6 did not consistently inhibit cell growth nor did rIL-6 enhance precursor frequency in a limiting dilution analysis. These results suggest that IL-6 does not directly induce the proliferation of ovarian cancer cells although endogenous IL-6 production is needed for optimal cell growth. As the majority of epithelial ovarian cancers produce IL-6, the direct specific inhibition of IL-6 gene expression is of potential therapeutic value.

Base Sequence↗
PubMed1993

Prognostic factors for groin node metastasis in squamous cell carcinoma of the vulva (a Gynecologic Oncology Group study)

From 1977 to 1984 the Gynecologic Oncology Group (GOG) conducted a prospective clinical and surgical staging protocol of squamous cell carcinoma of the vulva (n = 637). The patients with superficial (5 mm or less invasion) lesions were the subject of a previous report (n = 272). The subject of this report is on factors that predict groin node metastasis based on all 588 evaluable patients. Comparisons between the two reports are made. Almost half of this group (49.3%) had minimal tumor thickness (< or = mm). Almost one-third of patients had small vulvar lesions (< or = cm). Groin node metastasis was 18.9% for the < or = 2-cm diameter tumors and 41.6% for the > 2-cm diameter lesions. The inaccuracy of clinical palpation of the groin nodes (23.9% false negative) largely accounts for underestimation of extent of disease. Body weight was not related to the sensitivity of detecting positive groin nodes (P = 0.26). Using the logistic model, independent predictors of positive groin nodes were identified (in order of importance): less tumor differentiation by GOG criteria (P < 0.0001), suspicious or fixed/-ulcerated nodes (P < 0.0001), presence of capillary-lymphatic involvement (P < 0.0001), older age (P = 0.0002), and greater tumor thickness (invasion) (P = 0.03). Lesion size and location were not independent predictors of positive groin nodes.

Aged↗
PubMed1993

Impact of contraception on gynecologic cancers.

In considering the appropriate contraceptive method for a particular woman, the potential effect of that method on her risk of developing cancer of the breast, cervix, endometrium, or ovary is crucial. Among the most closely studied of the risk factors for gynecologic neoplasm has been the potential role of contraceptives, especially oral contraceptives, intrauterine devices, and injectable progestins. Physicians need to consider the potential impact of these agents on the disease process, therapy for the disease, future fertility, and the health of the fetus. Although much of the epidemiologic data is inconsistent and difficult to interpret, most studies find no association between oral contraceptive use and increased risk of breast cancer, except possibly in younger women (< 45 years of age) with prolonged use. Oral contraceptive use may also protect against benign breast disease. Data concerning oral contraceptive use and cervical neoplasm are confounded by several interacting variables, the most important of which is that oral contraceptive users tend to have more Papanicolaou smears than nonusers. Some studies have indicated an increased risk of two- to fourfold after 10 years of use. Oral contraceptive use provides clear protection against endometrial and ovarian cancer, an effect that persists for years after discontinuation. Less data have been collected regarding the relationship between intrauterine devices and injectable hormonal preparations and various types of cancer. No evidence suggests that the intrauterine device predisposes to the development of preneoplastic conditions of the cervix, nor to endometrial or ovarian cancer. A reliable form of contraception is indicated in women with cancer of any kind that may require chemotherapy or radiation, because these treatments can have adverse effects on the fetus, especially if given during the first trimester.

Breast Neoplasms↗
PubMed1993

Molecular and biological factors in the pathogenesis of ovarian cancer.

BACKGROUND: The classic prognostic parameters are insufficient for predicting the prognosis of the individual patient. Knowledge of molecular and biological factors which are responsible for the development and progression of ovarian cancer may improve the prediction of prognosis. MATERIALS AND METHODS: Recent data both on factors associated with the development and control of ovarian cancer cells and on DNA ploidy have been reviewed. RESULTS: Observations suggest that steroid and peptide hormones have a role in disease etiology and progression, and that peptide growth factors and cytokines, oncogenes and tumor suppressor genes, by their impact on mitosis and cell number may influence the rate of mutations, which could confer malignant transformation. DNA ploidy is an objective independent prognostic factor. DNA aneuploidy indicates high risk, diploidy low risk. Only tumours shown to be DNA diploid by flow-cytometry and image cytometry are considered diploid. S-phase fraction is currently not reliable. CONCLUSION: Understanding the mechanisms involved in ovarian cancer development and growth will allow opportunities for the rational design of effective anti-tumour treatment modalities. More objective and reproducible prognostic variables will improve the predictiveness of prognosis.

DNA, Neoplasm↗
PubMed1993

Advanced epithelial ovarian cancer: 1993 consensus statements.

BACKGROUND: Over the last few days of a 5-day international workshop held in June 1993, a group of specialists in the field of advanced epithelial ovarian cancer tried to reach consensus on a number of issues with implications for standard practice and for research. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, management recommendations, dose intensity, supportive care, drug resistance, second-line treatment, investigational drugs, and tumour markers. Discussing the management recommendations, the group attempted to arrive at answers to four questions: Is there in fact a cure rate for advanced ovarian carcinoma? Are there prognostic factors which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? In a plenary meeting these issues were discussed. RESULTS: Consensus statements were achieved on all topics mentioned above. This article reports on the statements written by the chairmen and approved by the consensus group.

Antineoplastic Agents↗