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Biomedical subjects

S Biran

Publications and source records attributed to S Biran.

At least 55 records · Page 3Linked to original sources
PubMed1985

Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis.

Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. This requires adhesion of blood-borne cells to the luminal surface of the vascular endothelium, invasion through the endothelial cell layer and local dissolution of the subendothelial basement membrane. Platelets may participate in each of these steps and thus play a role in the pathogenesis of tumor cell metastasis. To learn more about the possible involvement of platelets we studied the interaction of platelets and tumor cells with cultured vascular endothelial cells and their secreted basement membrane-like extracellular matrix (ECM). Whereas the apical surface of the vascular endothelium lacks adhesive glycoproteins and hence protect the vessel wall against platelet and tumor cell adhesion, the underlying ECM constitute a highly adhesive and thrombogenic surface. Interaction of platelets with this ECM was associated with platelet activation, aggregation and degradation of heparan sulfate in the ECM by means of the platelet heparitinase. The activity of a similar enzyme has been previously correlated with the metastatic potential of various tumor sublines. Biochemical and scanning electron microscopy (SEM) studies have demonstrated that platelets may detect even minor gaps between adjacent endothelial cells and degrade the ECM heparan sulfate. This may expose a larger area of the subendothelium and facilitate subsequent adhesion of blood borne tumor cells. Platelets were also shown to recruit lymphoma cells into minor gaps in the vascular endothelium, that otherwise do not constitute a preferential site of invasion. It is suggested that the platelet heparitinase is involved in the impairment of the integrity of the vessel wall and thus play a role in tumor cell metastasis.

Animals↗
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↗
PubMed1984

Procarbazine, CCNU and vincristine (PCV) combination chemotherapy for brain tumors.

12 patients with brain tumors were treated with a combination of procarbazine, CCNU (bis-2-chloroethyl-3-cyclohexyl-1-nitrosourea) and vincristine. 3 of 8 patients (37.5%) with primary brain tumors responded to chemotherapy, with a mean duration of 9.3 months. The mean survival of responders was 11.7 months, versus 3.6 months for nonresponders. 4 patients with metastatic brain tumors were also treated with the same combination chemotherapy; only 1, suffering from a lymphoma of the brain, responded partially.

Adult↗
PubMed1984

Treatment of advanced soft tissue sarcomas with a modified CYVADIC protocol.

33 consecutive patients with metastatic or locally recurrent soft tissue sarcoma were treated with a modification of the CYVADIC (cyclophosphamide, vincristine, Adriamycin, dacarbazine) protocol. In an attempt to enhance the response rate without increasing the toxicity, the dose of Adriamycin was raised to 60 mg/m2 and the dose of cyclophosphamide to 600 mg/m2 in each cycle. The dose of dacarbazine was decreased to 150 mg/m2/day for 5 days. Of 31 evaluable patients there were 4 complete responses (13%) and 9 partial responses for a total response rate of 39%. 11 patients (33%) had minimal response or stable disease. The response achieved with our dose modification was no better than that achieved in several series with conventionally dosed CYVADIC.

Adult↗
PubMed1983

High-density lipoprotein and extracellular matrix promotes growth and plating efficiency of normal human mammary epithelial cells in serum-free medium.

A routine procedure has been developed for the establishment in culture of normal primary and secondary human mammary epithelial cells. The high (80-100%) rate of success resulted from the combined use of a serum-free medium supplemented with high-density lipoprotein (HDL) and of cell plating on a naturally produced extracellular matrix (ECM). Plating on ECM greatly improved cell attachment, plating efficiency and initial outgrowth. HDL supported epithelial cell proliferation and prevented their detachment and degeneration while the omission of serum prevented the growth of stromal fibroblasts. Under these conditions we obtained from each specimen, and regardless of the patient's age, pure and actively dividing epithelial cell cultures forming a tightly packed and non-overlapping cell monolayer covering the entire area of the culture dish. These epithelial cultures could be easily dissociated and subcultured at a split ratio of 1:10. The described procedure will promote studies on the role of hormones and growth factors in the proliferation and differentiation of human mammary epithelial cells and on the susceptibility of human breast epithelial cells to various transforming agents and anti-cancer treatments.

Blood↗
PubMed1983

Levels of fibrinogen/fibrin degradation fragment E and related substances in sera and effusions of patients with malignant disease.

A radioimmunoassay (RIA) was developed and used to determine the level of fragment E [a fibrinogen/fibrin degradation product (FDP)] and of fragment-E-containing substances (FES) in sera and effusion fluids of patients with malignant diseases. Sera of patients with other diseases and sera of healthy individuals served as controls. Results were expressed as units/ml (U/ml), one unit being equivalent to 40 ng pure fragment E. Effusion fluids of both malignant and nonmalignant origin contained relatively high levels of fragment-E-containing substances, up to 7,500 U/ml. Normal sera had less than 30 U/ml, while sera of patients with a variety of neoplastic or nonneoplastic conditions contained larger amounts, reaching to hundreds and, in rare cases (some patients with rheumatoid arthritis), even thousands of U/ml. Some of the highest levels in the malignant sera were found in samples from patients with Burkitt's lymphoma and stomach cancer. About 10%-20% of the reactive material in effusions and 20%-40% in the sera consisted of fragment E. These results confirm earlier findings of high FDP levels in neoplasia. Given the higher accuracy of the radioimmunoassay and its suitability for large scale testing, it would appear worthwhile to continue such studies to explore the clinical usefulness of the RIA for fragment E.

Electrophoresis, Polyacrylamide Gel↗
PubMed1983

The use of carcinoembryonic antigen for identification of human tumor cells in malignant effusions.

A specific anti-carcinoembryonic antigen (CEA) antiserum was used to identify CEA-positive tumor cells in peritoneal and pleural effusions obtained from patients with various malignant neoplasia. In 7 out of 10 fluids in which tumor cells were detected by cytological examinations, cytoplasmic CEA-positive cells were also detected by an indirect immunofluorescence test. In addition, out of 11 fluid samples cytologically negative for tumor cells, CEA-positive cells were found in 8 cases. When both staining for cytoplasmic CEA and soluble fluid CEA levels were considered in combination, 81% of the samples were found to be positive by either one or both of these markers, whereas only 54% were positive by using cytological criteria. The data suggest that CEA marker may be used to identify tumor cells and to assess malignancy in pleural and peritoneal effusions in patients with certain types of cancer. The CEA marker was also used for identifying tumor cells grown in tissue cultures and for separating viable CEA-positive and CEA-negative cells from a mixed cell population using the fluorescence-activated cell sorter.

Ascitic Fluid↗
PubMed1981

Comparison of the response to PHA and suppressor macrophage function in different age groups of cancer patients and healthy controls.

The mitogenic response of peripheral blood lymphocytes was examined in 37 healthy individuals and in 44 patients with various malignant neoplasms. Tested individuals were divided into three major age groups (20-40; 40-60; and over 60 years of age). There was a significant decrease in Phytohemagglutinin (PHA) response with age in the normal controls, but no significant change with age was observed in the cancer patients. Comparison between the various age groups of cancer patients and their corresponding normal controls did not reveal a significant difference in mitogenic response of the young and middle age groups. However, the older cancer patients responded significantly better compared with their corresponding older normal controls. The reduced responsiveness of older normal controls was partially explained by a high activity of suppressor macrophages observed in this group. Reduction of the proportion of phagocytic cells improved their response to PHA. On the other hand, the activity of suppressor macrophages in the older cancer patients was much less prominent. These observations emphasize the importance of appropriate age grouping when immune function tests in cancer patients are compared with those performed in normal individuals and suggest the possibility of higher mitogen responsiveness in certain age groups of cancer patients.

Adult↗
PubMed1981

Vinblastine, cyclophosphamide and 5-fluorouracil (VEF) combination chemotherapy for metastatic hypernephroma.

10 evaluable patients with metastatic hypernephroma received vinblastine (6 mg/m2, i.v., on days 1 and 8), cyclophosphamide (100 mg/m2, p.o., on days 1-14), and 5-fluorouracil (600 mg/m2, i.v., on days 1 and 8), cycled every 29 days. 7 of the patients also received dexamethasone (16 mg/day, p.o), shortly before or during chemotherapy, in an attempt to improve their clinical status. No complete or partial responses were seen. 5 pairs (50%) remained stable (median duration, 4.5 months; medium survival, 6.5 months), and the remaining 5 patients progressed. A subjective response was observed in all stable patients, who also received dexamethasone. The side-effects of VEF chemotherapy were mild: 2/10 patients developed leukopenia (WBC below 3,000), 3/10 patients manifested thrombocytopenia (platelets below 100,000), and 3/10 patients alopecia.

Adenocarcinoma↗