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R S Berkowitz

Publications and source records attributed to R S Berkowitz.

At least 145 records · Page 8Linked to original sources
PubMed1986

Immunobiology of complete molar pregnancy and gestational trophoblastic tumor.

The unique curability of gestational trophoblastic tumors may in part be attributable to a host immunologic response. The occurrence of rapidly progressive and fatal choriocarcinoma may be favored by histocompatibility between patients and their partners. However, histocompatibility is not a prerequisite for the development and persistence of gestational choriocarcinoma. The expression of HLA by choriocarcinoma cells in culture is enhanced following incubation with gamma-interferon and this may be of both biologic and clinical significance. Complete molar pregnancy is a complete allograft because all molar chromosomes are of paternal origin. Patients with complete mole are sensitized to paternal HLA antigen which is expressed in molar tissue. Other polymorphic antigen systems including trophoblast-leukocyte common antigens and placental-type alkaline phosphatase are also expressed in molar tissue. We have studied the immunopathology of the molar implantation site to investigate possible humoral and cellular immune responses. The relationships among normal placenta, complete mole and choriocarcinoma are not clearly understood. The pattern of expression of oncofetal antigens in these three gestational tissues may be used to assess trophoblastic differentiation. In studies to date, molar trophoblast has the same pattern of expression of oncofetal antigens as normal placental trophoblast. We will review recent advances in our understanding of the immunobiology of gestational trophoblastic disease and suggest new directions for further research.

Alkaline Phosphatase↗
PubMed1986

Expression of trophoblast-leukocyte common antigens and placental-type alkaline phosphatase in complete molar pregnancy.

The current study was undertaken to determine the localization of trophoblast-leukocyte common antigens and placental-type alkaline phosphatase in complete molar pregnancy with the use of rabbit antiserum and murine monoclonal antibodies in immunofluorescence assays. Trophoblast-leukocyte common antigens were expressed on all normal villous trophoblast (8 to 38 weeks' gestation) and on all complete moles studied. Placental-type alkaline phosphatase was not expressed on villous trophoblast before 20 weeks' gestation in either normal placentas or complete moles. In contrast, there was strong expression of placental-type alkaline phosphatase on villous trophoblast of normal placentas of more than 20 weeks' gestational age. The expression of polymorphic antigens such as trophoblast-leukocyte common antigens and placental-type alkaline phosphatase on molar trophoblast may be important in the immunobiologic features of gestational trophoblastic disease.

Alkaline Phosphatase↗
PubMed1986

Ten year's experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease.

Methotrexate and folinic acid was administered as primary therapy in 185 patients with gestational trophoblastic disease between 1974 and 1984. Methotrexate and folinic acid induced complete remission in 147 (90.2%) of 163 patients with nonmetastatic disease and in 15 (68.2%) of 22 patients with low-risk metastatic disease. Sustained remission was achieved in 132 (81.5%) patients following only one course of chemotherapy. All patients with methotrexate resistance subsequently achieved remission with Actinomycin D or combination chemotherapy. Methotrexate when administered with folinic acid was associated with granulocytopenia, thrombocytopenia, and hepatotoxicity in 11 (5.9%), 3 (1.6%), and 26 (14.1%) patients, respectively. The human chorionic gonadotropin (hCG) regression curve served as a reliable guide for the administration of chemotherapy and enabled the attainment of a high remission rate while limiting chemotherapy exposure. Methotrexate and folinic acid achieves an excellent therapeutic outcome with limited chemotherapy exposure and effectively limits systemic toxicity.

Adolescent↗
PubMed1986

Hormonal measurements in patients with theca lutein cysts and gestational trophoblastic disease.

Concentrations of human chorionic gonadotropin (HCG), human placental lactogen (HPL), prolactin (PRL), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) were measured in serum and fluid from ovarian theca lutein cysts (TC) in patients with gestational trophoblastic disease (GTD). Either intact hydatidiform mole (HM) or persistent GTD was present. The values were compared to serum hormone concentrations in ten GTD patients whose ovaries were not enlarged. In the presence of intact HM and TC, significant elevations in the mean serum concentration of HCG, PRL, P and E2 were observed when compared to levels in GTD patients with normal-sized ovaries (P less than .01). Serum FSH and HPL were not elevated in either control or TC patients. The mean concentration of P in cyst fluid from patients with intact HM was higher than that in patients with persistent GTD (P less than .05). From both groups of GTD patients with TC, the mean concentrations of P in cyst fluid were higher than those in the sera. These findings suggest that besides the markedly elevated HCG levels generally seen in TC patients, other hormones, such as P, PRL and E2 are elevated and may be involved in the formation and/or maintenance of TC.

Chorionic Gonadotropin↗
PubMed1985

Intraperitoneal immunotherapy of epithelial ovarian carcinoma with Corynebacterium parvum.

Corynebacterium parvum was administered intraperitoneally to 21 patients with epithelial ovarian cancer. Nineteen patients had surgically measurable disease and two received adjuvant therapy. Surgically confirmed responses were documented in six of 19 patients (31.6%), with two complete responses (10.5%) and four partial responses (21.1%). Three patients (15.8%) had stable disease, and 10 patients (52.6%) had disease progression. The mean survival of the patients who had a complete response was 35.5 months; the four patients who had a partial response the mean survival was 26.6 months, and of the nonresponders the mean survival was 12.6 months (p less than 0.02). The mean survival of the entire group was 18.2 months. Initial response and patient survival correlated with the amount of disease pretreatment. Thus six responding patients had less than or equal to 5 mm maximum diameter tumors, that is, minimal residual disease. Toxicity in the 86 courses of therapy included abdominal pain in 78% of cases, fever in 56%, nausea in 40%, and vomiting in 22%. Stimulation of cytotoxic lymphocytes resulted from the administration of C. parvum, which induced a significant increase of both intraperitoneal natural killer lymphocyte cytotoxicity and antibody-dependent cell-mediated cytotoxicity in six of nine patients tested; these two types of cytotoxicity correlated with response to therapy and may be partially responsible for the surgically documented tumor regression. While the clinical usefulness of intraperitoneal C. parvum is limited because of its toxicity, intraperitoneal immunotherapy may prove useful in patients with minimal residual ovarian cancer when more refined agents become available.

Adenocarcinoma, Mucinous↗
PubMed1985

Risk factors for complete molar pregnancy from a case-control study.

Demographic, reproductive, and dietary histories for 90 white women with complete molar pregnancy were compared in a multivariate analysis with those of 90 parous controls matched to cases by residence, birth year, and race. Women with molar pregnancy were more likely to have been born outside North America (relative risk = 1.9, p = 0.05), were more likely to have been past age 30 at time of their molar pregnancy (relative risk = 1.6, p = 0.05), and were more likely to have diets deficient in the vitamin A precursor carotene. Women with dietary scores for carotene above the control median had a relative risk for molar pregnancy of 0.6 (p = 0.02). In addition, there was a significant trend for decreasing risk for molar pregnancy with increasing consumption of carotene. Although other nutritional deficiencies in patients with complete molar pregnancy may exist, carotene is a biologically plausible candidate for a nutritional risk factor that could explain the geographic distribution of molar pregnancy.

Adult↗
PubMed1985

Implantation site in complete molar pregnancy: a study of immunologically competent cells with monoclonal antibodies.

The nature and intensity of inflammatory cellular infiltrate in the implantation sites of 10 complete molar pregnancies were evaluated by immunohistochemical staining of frozen tissue sections with monoclonal antibodies. As compared to the implantation site in normal pregnancy, there was an increase in the number of infiltrating inflammatory cells in the molar implantation site. Most of the inflammatory cells were T cells with predominance of T4+ (Leu-3a+) cells over T8+ cells. Inflammatory cells were not detected in the molar vesicles. The possible implications of these findings in molar pregnancy are discussed.

Antibodies, Monoclonal↗
PubMed1985

Localization of transferrin receptor in the chorionic villi of complete molar pregnancy.

Transferrin receptors have been identified on the villous trophoblast of normal chorionic villi by immunohistochemical techniques. The current study investigated the expression of transferrin receptors on molar chorionic villi by using a monoclonal antibody in immunofluorescence assays. The villous trophoblast of molar chorionic villi was brightly positive for transferrin receptor in the immunofluorescence assay. The presence of transferrin receptors on molar villous trophoblast may influence the immunologic relationship between molar and host tissues.

Antibodies, Monoclonal↗
PubMed1985

Reactivity of anti-human sperm monoclonal antibodies with normal placenta, hydatidiform mole, and gestational choriocarcinoma.

The current study was undertaken to examine reactivity patterns of well-characterized anti-human sperm monoclonal antibodies with normal placenta, complete hydatidiform mole (HM), and gestational choriocarcinoma (CCA). Two anti-human sperm monoclonal antibodies (MA2 and MA7) out of a panel of 14 reacted with human CCA cell lines but did not react with the trophoblast of 4 HM or 4 normal placentas from 13 weeks to term gestation in immunofluorescence and absorption tests. Therefore, in terms of expressing these sperm-embryonic antigens, the trophoblast of HM is more like normal placental trophoblast than CCA. The relationships among normal placenta, HM, and CCA may be better understood by continued studies on the pattern of expression of additional embryonic antigens in these three gestational tissues.

Antibodies, Monoclonal↗
PubMed1985

Localization of stage-specific embryonic antigens in hydatidiform mole, normal placenta, and gestational choriocarcinoma.

Murine stage-specific embryonic antigens (SSEA-1, SSEA-3) are well characterized oncofetal antigens and have been identified in several human tumors. The current study was undertaken to determine the localization of SSEA-1 and SSEA-3 in hydatidiform mole, normal human placenta, and gestational choriocarcinoma. SSEA-3 did not react with any cellular components in hydatidiform moles, normal placentas, or choriocarcinoma cell lines. SSEA-1 was detectable in two human gestational choriocarcinoma cell lines, but not in the trophoblastic cells of 10 hydatidiform moles or in nine normal placentas between 6 weeks and term gestation. Therefore, according to this oncofetal marker system, the trophoblast in hydatidiform mole is more like normal trophoblast than gestational choriocarcinoma.

Antigens, Neoplasm↗
PubMed1985

The issue of microinvasive squamous cell carcinoma of the vulva: an evaluation of the criteria of diagnosis and methods of therapy.

Current literature on definition, metastatic potential, and treatment of microinvasive squamous cell carcinoma of the vulva is reviewed. There is marked disparity among the various reports about the features of this lesion that are most crucial in predicting the propensity to recur or metastasize. Nonuniformity of the techniques for measuring stromal invasion is noted among many of them as well. The issue of conservative versus more aggressive surgical treatment of microinvasive squamous cell carcinoma of the vulva is discussed within the context of the reviewed data. One should exercise prudence in determining which affected patients are appropriate candidates for conservative surgical therapy.

Carcinoma in Situ↗
PubMed1985

Natural history of partial molar pregnancy.

Between January 1979 and August 1984, 81 patients with partial molar pregnancy were observed at the New England Trophoblastic Disease Center. The preevacuation clinical diagnosis in 74 (91.3%) patients was either missed or incomplete abortion. The uterine size was either small or appropriate for gestational age in 78 (96.3%) patients. Only five (6.2%) patients presented with excessive uterine size or toxemia and were thought to have a molar pregnancy. Preevacuation human chorionic gonadotropin (hCG) levels exceeded 100,000 mIU/mL in only two (6.6%) of 30 patients. No patient had prominent theca lutein cysts. After evacuation, eight (9.9%) patients developed nonmetastatic gestational trophoblastic disease. Patients with partial moles usually do not present with the clinical features that are characteristic of complete molar pregnancy. The diagnosis of partial mole is generally only considered after histologic review of curettage specimens.

Abortion, Incomplete↗
PubMed1985

Gamma-interferon enhances expression of Class I MHC antigens in the weakly HLA+ human choriocarcinoma cell line BeWo, but does not induce MHC expression in the HLA- choriocarcinoma cell line Jar.

PHA-activated lymphocyte supernatants and high doses of affinity-purified human gamma-interferon enhance the expression of apparently normal Class I histocompatibility antigens in a malignant human trophoblast cell line that expresses low amounts of these antigens under normal culture conditions. Another human choriocarcinoma cell line, Jar, which is normally HLA-, did not respond to this treatment. This system provides a model in which to study further the regulation and effects of MHC antigen expression in cells of trophoblastic origin.

Antibodies, Monoclonal↗
PubMed1984

Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole.

In view of the controversy regarding the role of human chorionic gonadotropin as the stimulator of thyroid function in patients with trophoblastic tumors, especially hydatidiform mole, we conducted studies to explore whether a correlation between serum human chorionic gonadotropin levels and thyroid function was demonstrable in such patients. Among 47 patients studied, only one was clinically hyperthyroid, although 10 had serum total thyroxine values exceeding those found in normal pregnancy (8 to 17 micrograms/dl). Among 34 patients in whom free thyroxine indices could be calculated, 18 had elevated values for the free thyroxine index (greater than 10.6), and nine had elevated values for both total thyroxine and free thyroxine index. Serum total 3,5,3'-triiodothyronine concentrations were also measured in 17 patients, and only one of them had a value (400 ng/dl) above the normal limit for pregnancy (greater than 350 ng/dl). Among the 13 patients for whom free 3,5,3'-triiodothyronine indices were calculated, three had values above the normal range (greater than 215). A weakly positive correlation (r = 0.35, p less than 0.05, n = 47) between the serum human chorionic gonadotropin levels and serum total thyroxine concentrations was observed in these patients. However, no correlation was found between serum human chorionic gonadotropin levels and free thyroxine index values (r = 0.32, p greater than 0.05, n = 34). Also there was no correlation between serum human chorionic gonadotropin levels and either serum total 3,5,3'-triiodothyronine concentrations (r = 0.32, p greater than 0.1, n = 17) or free 3,5,3'-triiodothyronine index values (r = 0.27, p greater than 0.1, n = 13). chi 2 Analysis revealed no significant relationship between elevations of serum human chorionic gonadotropin concentration and abnormally high values of the free thyroxine index. These studies do not support the premise that human chorionic gonadotropin per se is the thyroid stimulator of molar pregnancy and suggest that a substance or substances, distinct from human chorionic gonadotropin and elaborated by the gestational trophoblastic tissue, are responsible for thyrotoxicosis observed in patients with trophoblastic tumors.

Adolescent↗
PubMed1984

Choriocarcinoma following term gestation.

The current study reviews post-term choriocarcinoma at the New England Trophoblastic Disease Center (NETDC) in order to expand knowledge of its clinical features. Between June 1965 and June 1981, 366 patients with persistent gestational trophoblastic disease were managed at the NETDC and 15 (4.1%) of these patients had choriocarcinoma following term pregnancy. Post-term choriocarcinoma has a propensity for early metastasis with frequent involvement of the liver and brain. Metastases were detected in 13 (86.7%) patients with post-term choriocarcinoma at the time of diagnosis. Seven patients (53.8%) with metastatic post-term choriocarcinoma had hepatic and/or cerebral involvement. Complete remission was achieved in both patients with nonmetastatic disease and in 8 (61.5%) patients with metastatic disease. When the time interval from the antecedent term delivery to diagnosis was less than 4 months, 7 (87.5%) of 8 patients achieved complete remission. The 5 patients who died from post-term choriocarcinoma all had hepatic and/or cerebral involvement. Patients with post-term choriocarcinoma should undergo a meticulous metastatic evaluation and if metastases are detected these patients should be treated with primary combination chemotherapy and with the selective use of irradiation and surgical therapy.

Brain Neoplasms↗
PubMed1984

Histocompatibility antigens (HLA-A,B,C) are not detectable in molar villous fluid.

Cell-free villous fluid from healthy and necrotic molar villi did not contain detectable soluble HLA Class I (HLA-A,B,C) antigens; therefore, HLA sensitization of the maternal host is probably not attributable to shedding of HLA antigens by viable or degenerating HLA-positive stromal cells. The method developed for this study, a combination of immunoprecipitation and Western blot techniques, employed specific antibodies for positive identification of the HLA heavy chain. The pathogenesis of complete molar pregnancy may be better understood through further study of the mechanisms of HLA sensitization of the maternal host and the host's response to these foreign antigens.

Female↗
PubMed1984

Modified triple chemotherapy in the management of high-risk metastatic gestational trophoblastic tumors.

Modified triple chemotherapy (MAC III: methotrexate with citrovorum factor, actinomycin D, and cyclophosphamide) was administered as primary treatment to 14 patients with high-risk metastatic gestational trophoblastic tumors (GTT). Ten (71.4%) patients attained complete remission with 1 to 4 courses of MAC III (mean = 2.7 courses). Three of the remaining patients subsequently achieved remission with the modified Bagshawe regimen or vinblastine, bleomycin, and cis-platinum. Following 38 courses of MAC III, moderate hepatotoxicity (SGOT greater than or equal to 150 U) developed after 1 (2.6%) course. Marked thrombocytopenia (platelets less than 50,000/mm3) and marked granulocytopenia (granulocytes less than 500/mm3) developed after 7 (18.4%) and 19 (50%) of the courses, respectively. Platelet transfusions were administered after 4 (10.5%) courses of MAC III and no patient required granulocyte transfusions. MAC III is an effective alternative treatment for patients with high-risk metastatic GTT.

Adolescent↗