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Biomedical subjects

S Biran

Publications and source records attributed to S Biran.

At least 19 recordsLinked to original sources
PubMed1992

Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response.

We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.

Adolescent↗
PubMed1990

Second line hormonal therapy with aminoglutethimide in metastatic breast cancer.

One hundred and twenty patients with metastatic breast cancer, whose disease progressed on hormonal therapy with tamoxifen, were treated with aminoglutethimide. The overall response rate was 34% and the median duration of response 9.5 months. Response to aminoglutethimide was achieved in all metastatic sites except lung and brain. Even 25% of patients who had failed to respond to prior tamoxifen did respond objectively to aminoglutethimide. The actuarial survival for all patients at 30 months was 22%. Although initial toxicity was high (70%), side effects of aminoglutethimide were transient, and treatment had to be discontinued in only four patients. The results of this trial confirm that aminoglutethimide is an effective treatment in metastatic breast cancer.

Actuarial Analysis↗
PubMed1990

Radiation therapy for locally advanced breast cancer: prognostic factors and complication rate.

A retrospective analysis was carried out in 100 patients with locally advanced breast cancer without distant metastases treated by radiotherapy between 1960 and 1979. The primary tumor was irradiated to a total dose of 60 Gy in 76 patients and to doses ranging between 60 and 80 Gy in 24 patients. The regional lymphatics were treated with doses between 50 and 60 Gy. Following radiotherapy, chemotherapy was administered to 58 patients and hormonal therapy to 29, while 13 patients received no further therapy. Locoregional recurrences were documented in 29% and distant metastases in 49% of patients. The actuarial survival was 56% at 5 years, 21% at 10 years and 14% at 15 years. At 10 years 90% of the surviving patients had some degree of radiation damage.

Adult↗
PubMed1989

Cisplatin, bleomycin, and methotrexate (PBM) chemotherapy in locally advanced and metastatic head and neck cancer.

Twenty-two patients with locally advanced or metastatic head and neck tumors received a total of 84 courses of a combination of cisplatin, bleomycin, and Methotrexate (PBM) for a median of four courses per patient (range, 1-7). Among these 22 patients there were four patients (18%) who achieved complete remission (CR) and 13 patients (60%) who had a partial remission (PR). The overall remission rate (CR + PR) thus reached 78%; five patients (22%) progressed while on therapy. The mean duration of objective response (CR + PR) was 8 months; CR lasted a median of 18 months (range, 2-48). Survival was not influenced by tumor histology or by previous surgery. The presence of locoregional disease did adversely affect survival from the onset of chemotherapy (P = 0.1). The rate of survival was also affected by primary tumor site; patients with nasopharyngeal primaries survived longer than all other patients (22 vs. 11 months, P = 0.06). Toxicity to chemotherapy consisted mainly of nausea and vomiting and stomatitis. Three patients developed fever while leukopenic. One patient experienced irreversible renal damage, and another suffered from bleomycin-induced pulmonary fibrosis. The high response rate obtained in our group of patients did not have a substantial impact on overall survival. Aggressive, multimodality approaches should be considered in the treatment of these patients when possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study.

A clinical study was designed to evaluate the tolerance of cancer patients to liposome-associated doxorubicin (L-DXR). The liposomes used contain phosphatidylglycerol, phosphatidylcholine, cholesterol, and DXR intercalated in the lipid bilayer, and have a mean size in the range of 0.3-0.5 microns. Thirty-two patients, most of them with primary or metastatic liver cancer refractory to conventional therapy, were entered into the study. A total of 69 courses of therapy was administered by intravenous infusion of a suspension of L-DXR (0.5-2.0 mg DXR/ml) in physiologic saline at an approximate rate of 2 ml/min given on a 3-week intermittent schedule. The L-DXR and phospholipid doses were escalated from 20 mg/m2 and 0.3 g/m2 to 120 mg/m2 and 3.2 g/m2 respectively. Treatment was generally well tolerated and acute toxic effects such as nausea and vomiting were mild and infrequent. Chills and fever (greater than 38.0 degrees C) were observed in three patients during infusion of L-DXR and in seven patients 6-12 h after the end of infusion. Median WBC nadir counts were 2700, 2300 and 700/microliters at 85, 100 and 120 mg/m2 respectively. All three patients receiving 120 mg/m2 developed grade 4 leukopenia and fever requiring intravenous antibiotics, and, in two of them, severe stomatitis (grades 3 and 4) was observed. Significant hair loss was apparent in all patients receiving doses higher than 50 mg/m2. The maximal tolerated dose of L-DXR appears to be 120 mg/m2, with leukopenia and stomatitis being the dose-limiting factors. While the subacute toxicity of L-DXR appears to be qualitatively similar to that of free DXR, its tolerance exceeds the recommended dose of free DXR (75 mg/m2) in the standard 3-weekly schedule.

Adult↗
PubMed1989

Methylprednisolone and chlorpromazine in patients receiving cancer chemotherapy: a prospective non-randomized study.

Seventy-six consecutive patients receiving chemotherapy were evaluated for the antiemetic efficacy and side-effects of the combination of chlorpromazine (CPM) and methylprednisolone (MPN). All patients had previously received the same chemotherapy with metoclopramide in conventional dosage and experienced severe emesis. A significant antiemetic response was achieved in 70% of the patients, and in 28% of them the antiemetic protection was complete. The most common side effects were drowsiness, dry mouth and headache. The combination of CPM and MPN is effective, well tolerated and is recommended for outpatients receiving chemotherapy for cancer.

Adolescent↗
PubMed1989

Methylprednisolone versus metoclopramide as antiemetic treatment in patients receiving adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy: a randomized crossover blind study.

Nineteen women receiving their first cycle of adjuvant chemotherapy for early breast cancer were randomized between two antiemetic drugs: methylprednisolone (MPN) 125mg and metoclopramide (MCP) 20mg, both given by intravenous push as a single dose. The chemotherapy included: cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The total response rates for MPN and MCP were: complete protection 11% versus 0% and partial protection 63% versus 11% of the patients, respectively (P = 0.007). Eighteen patients (95%) preferred MPN over MCP. Common side effects with both drugs were: drowsiness, headache and diarrhea. MPN is recommended as an antiemetic in patients receiving CMF adjuvant chemotherapy.

Adult↗
PubMed1989

5-Fluorouracil, doxorubicin (adriamycin) and mitomycin-C (FAM) in advanced gastric cancer: observations on response, patient characteristics, myelosuppression and delivered dosage.

Forty-four patients with advanced gastric adenocarcinoma were treated with the fluorouracil, adriamycin and mitomycin-C (FAM) regimen. One was excluded from response evaluation. Partial (PR) and minor (MR) response rates were 7 and 9% respectively. These patients enjoyed remission for a median of 7.0 months. Stabilization (S) occurred in 25% and lasted a median of 6.0 months. No response (NR) was associated with a median survival of 3 months (p less than 0.001). The predominant pretreatment factors to affect survival were diagnosis to treatment interval and initial CEA serum level. Performance status influenced survival less markedly. Toxicity was mainly myelosuppression, which resulted in death of one patient. 'Responders' had marrow suppression more frequently than NR. Comparison of PR + MR, PR + MR + S and NR patient groups showed median minimum WBC counts of 1.4 x 10(3), 2.6 x 10(3) and 4.3 x 10(3) per mm3 respectively. Leukopenia (less than 3,000/mm3) was associated with a median survival advantage of 9.5 versus 3.5 months (p less than 0.05) and did not depend significantly on given FAM dosage. The median dosage of FAM agents delivered to nonresponders was reduced. A trend of dose-response (including dose-survival) relationship was found but was inconclusive statistically.

Adult↗
PubMed1989

Chlorpromazine and dexamethasone versus high-dose metoclopramide and dexamethasone in patients receiving cancer chemotherapy, particularly cis-platinum: a prospective randomized crossover study.

Sixty-nine patients with malignant tumors receiving cancer chemotherapy, 90% including cis-platinum, were evaluated in a randomized crossover study for the antiemetic efficacy and the side effects of two antiemetic regimens: chlorpromazine (CPM) 2.5 mg/kg in 5 doses plus dexamethasone (DXM) 0.2 mg/kg in 2 doses, and high-dose metoclopramide (HD-MCP) 10 mg/kg in 5 doses plus the same dose of DXM. In 69% of 173 courses of chemotherapy, antiemetic response was achieved, and in 26% emesis was completely prevented. There was no statistical difference in the response to the antiemetic regimens, but 65% of the patients who completed 3 courses of chemotherapy preferred HD-MCP plus DXM. The main side effects of the treatment were drowsiness, nervousness, diarrhea and extrapyramidal reactions. HD-MCP plus DXM is recommended as a first line antiemetic treatment in patients receiving cancer chemotherapy. Patients resistant to this treatment should receive CPM plus DXM treatment.

Adolescent↗
PubMed1986

Growth of human mammary carcinoma cells from biopsy specimens in serum-free medium on extracellular matrix.

A method developed for the initiation and maintenance in primary culture of human normal mammary epithelial cells was adopted for the growth of epithelial cells from 45 primary human breast tumors. The cells were grown on a naturally produced extracellular matrix (ECM) or on regular tissue culture plastic in a serum-free medium containing growth supplements and high-density lipoprotein (HDL). Successful enzymatic dissociation of the tumor biopsy into organoid structures and cell aggregates was crucial for subsequent cell attachment and growth. Fifty-five percent of the biopsy specimens were successfully dissociated and 87% of these gave rise to actively dividing epithelial cells forming monolayer cultures. In contrast, only 21% of the biopsies which were not optimally dissociated yielded growing cultures. Variations in sample size, duration of enzymatic digestion, and tumor composition affected the outcome of tumor dissociation. Omission of serum from the culture medium prevented the growth of fibroblasts, while plating on ECM greatly improved and in some cases was essential for cell attachment and subsequent outgrowth. The epithelial nature of the cells was verified by their cuboidal and closely apposed morphology and positive staining with antikeratin antibodies. The growth and subculture requirements and the expression of the B38.1 tumor marker were compared in human mammary epithelial cells derived from solid tumors, pleural effusion and normal breast tissue.

Antibodies, Neoplasm↗
PubMed1986

Immunofluorescent characterization of fibronectin, laminin, and keratin in normal and neoplastic human mammary epithelial cells in culture and in breast tissue sections.

Employing indirect immunofluorescent staining, primary and secondary serum-free cultures and frozen sections of human mammary tissue, normal and neoplastic, were examined for the presence and distribution of fibronectin (FN) and keratin, and frozen sections also for laminin (LM). The epithelial cell purity of the cultures was confirmed by the observation that all cells stained with anti-keratin antibody. In confluent cultures, FN was absent at the apical cell surface, and was seen as a fibrillar matrix exclusively beneath the epithelial monolayer, at the cell-substratum interface. No differences were noted between normal and neoplastic cells in vitro. In sections of normal breast tissue, FN was localized in the basement membrane zone (BMZ) and in the connective tissue stroma. A distinguishing feature of the neoplastic tissue was the considerably more intensive anti-FN immunofluorescence of the stroma. In normal tissue sections, LM was present exclusively in the BMZ, where it formed a continuous, well-delineated, smooth line; this line was found to be distorted, interrupted, and sometimes entirely absent in the neoplastic tissue. The cytoplasm of all cultured cells, neoplastic as well as normal, exhibited a dense network of keratin filaments that was especially prominent around the nucleus. In the sections, keratin was ubiquitously present in the epithelial cells, predominantly along the interior border of the surface membrane; in the neoplastic tissue, this pattern was markedly disorganized, and some of the cells failed to express the substance.

Breast↗
PubMed1985

Combined modality treatment for stage III ovarian carcinoma.

Thirty-eight Stage III ovarian carcinoma patients were treated with a combined modality protocol consisting of sequential initial surgery with a maximal tumor reduction, CHAD combination chemotherapy, second look reductive surgery and whole abdominal irradiation. Sixteen patients (42%) had minimal residual tumors (less than 2 cm) after initial surgery (Stage IIIA) and 22 (58%) had large residual tumors (greater than 2 cm) (Stage IIIB). The patients received 3-14 courses of CHAD combination chemotherapy, with a response rate (CR + PR) in the evaluable (Stage IIIB) patients of 91%. Twenty-eight patients had a second attempt of cytoreductive operation (10 Stage IIIA patients and 18 Stage IIIB patients). In 10 patients no residual tumor was found. In another 12 patients residual tumor (less than 2 cm) was found and completely resected, whereas in six patients a complete resection of large residual tumors (greater than 2 cm) was not possible. Twenty-one of the patients also completed a course of whole abdominal radiotherapy. Radiation was well-tolerated with the usual expected amounts of nausea, vomiting, diarrhea and transient leukopenia and thrombocytopenia. 11/21 (52%) of the patients relapsed within the first 18 months after completion of radiotherapy. The actuarial relapse-free survival at 36 months from completions of radiotherapy was 44%. The actuarial survival for the whole group from diagnosis was 43% at 3 years (70% for Stage IIIA and 41% for Stage IIIB). The data indicated that this combined modality protocol is both feasible and well-tolerated but its curative potential for patients with advanced ovarian carcinoma is as yet unknown.

Adenocarcinoma↗
PubMed1985

Synthesis and receptor-binding affinity of fluorotamoxifen, a possible estrogen-receptor imaging agent.

Aminotamoxifen was totally synthesized from p-nitrobenzoyl chloride via a Friedel-Crafts acylation. Then, by means of a Balz-Schiemann reaction, aminotamoxifen was converted into fluorotamoxifen. The triazene variation of this conversion, with a 25% yield, enables a rapid, one-step diazotization, incorporating a fluorine atom into the phenyl ring of the tamoxifen. This reaction may be useful for the preparation of low specific activity 18F-labeled tamoxifen, for distribution, and for estrogen-receptor studies. For these in vivo and in vitro studies, fluorotamoxifen was also synthesized from p-fluorobenzoyl chloride, and its chemical intermediates were compared with estradiol and hexestrol, for their receptor binding and competition, as well as for their uterotropic activity. It is demonstrated that tamoxifen and fluorotamoxifen are strong estradiol agonists and partial hexestrol agonists, while aminotamoxifen is a weak estradiol and hexestrol agonist.

Animals↗
PubMed1985

A new human ovarian carcinoma cell line: establishment and analysis of tumor-associated markers.

In the present study we describe the establishment and characteristics of a new human tumor cell line (OV-1063) positive for carcinoembryonic antigen (CEA) originating from ovarian metastatic tumor cells. Analysis of the cultured cells during their in vitro adaptation period revealed while the primary culture exhibited a low proportion of CEA-positive cells, this proportion increased with culture passages and eventually more than 90% of the cells in the established line were CEA-positive. Thus, during the period of adaptation to in vitro growth, a selection for CEA-positive cells took place but the amount of CEA secreted per each positive cell seemed to be constant. Several tumor-associated characteristics were found positive on the established OV-1063 cell line. The in vitro growing cell line exhibited an abnormal chromosome pattern with a near-trisomy karyotype for some chromosomes, colony formation in soft agar as well as positive staining with a monoclonal antibody B38.1. Culture supernatants of the OV-1063 cells contained significant amounts of CEA as well as CA-125 antigen which is an ovarian-carcinoma-associated antigen.

Agar↗
PubMed1985

Treatment of metastatic breast cancer with aminoglutethimide after progression on chemotherapy and/or hormonal therapy with tamoxifen.

Sixty patients suffering from metastatic breast cancer, whose disease progressed on chemotherapy and/or hormonal therapy with tamoxifen, were treated with aminoglutethimide. The overall objective response rate was 33%, including 3% complete responses. The median duration of response was 8 months. Even patients who failed to respond to prior treatment modalities responded objectively to aminoglutethimide. Objective response was observed in all metastatic sites, except for lung. Subjective improvement was achieved in 70% of the patients. Although initial toxicity was high (67%), side effects of aminoglutethimide were transient, and therapy had to be discontinued in only 3 patients. The results of this study indicate that aminoglutethimide in combination with hydrocortisone is a very effective treatment for metastatic breast cancer, especially in patients with positive hormone receptors.

Adult↗
PubMed1979

Development of carcinoma of the breast at the site of an implanted pacemaker in two patients.

We report here on two female patients who had permanent pacemakers implanted in their chests and who developed carcinoma of the breast subsequently. An association is suspected between the breast cancer and the pacemaker, which is implanted in an area which borders with the mammary gland or is even right within it. This suspicion led us lately to change in female patients the site of the subcutaneous pocket for the implantation of the pacemaker to a position higher in the chest than before. Moreover, we advocate frequent breast examinations in all female patients with implanted pacemakers.

Adenocarcinoma↗