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Biomedical subjects

S Biran

Publications and source records attributed to S Biran.

At least 37 records · Page 2Linked to original sources
PubMed1987

Prevention of human bladder tumor cell implantation in an in vitro assay.

The high recurrence rate of bladder tumors can be reduced by prevention of tumor cell reimplantation on denuded urothelium following transurethral resection. This can be achieved by intravesical chemotherapy immediately after the resection of the bladder tumors. We have demonstrated, in an in-vitro system, the process of human bladder tumor cell implantation on a naturally produced extracellular matrix (ECM) which simulates the exposed bladder basement membrane and submucosa. Using this model we examined the efficacy of various cytotoxic agents in preventing tumor cell adhesion to the ECM. Human bladder tumor cell implantation was prevented following exposure of the cells to distilled water, epodyl or mitomycin C, and significantly reduced following one hour incubation in cisplatinum and doxorubicin. The maximal effect for each of these cytotoxic agents was reached within 30 to 60 minutes of treatment. Mitomycin C reached maximal effect within 10 minutes. In contrast, thiotepa did not cause a significant reduction in cell adherence to ECM as compared to untreated control cells.

Antineoplastic Agents↗
PubMed1987

High-dose metoclopramide and dexamethasone as an antiemetic in outpatients receiving chemotherapy for breast cancer. Second study.

Forty-six outpatients with breast cancer who had experienced severe emesis as a result of chemotherapy were evaluated for the antiemetic efficacy of high-dose metoclopramide (HD-MCP) and dexamethasone (DXM). Chemotherapy consisted of: cyclophosphamide 600, methotrexate 40 and 5-fluorouracil 600 mg/m2 (CMF) given intravenously every 3 weeks. The dosage of antiemetic drugs was MCP 2 mg/kg and DXM 0.2 mg/kg given by slow intravenous drip 0.5 h before the administration of chemotherapy. 138 courses of combined chemotherapy--HD-MCP and DXM--were administered, with a mean of 3 courses and a range of 1-10 courses per patient. Complete protection--no nausea and no vomiting--was achieved in 17.7% of the courses. Partial protection--no vomiting with mild nausea or 1-3 episodes of vomiting--in 45.3% of the courses. The total antiemetic efficacy was 63%. The most common side effects were: drowsiness, dry mouth, restlessness and diarrhea. Sixteen patients (35%) refused to continue the antiemetic regimen because of the side effects. HD-MCP and DXM have antiemetic efficacy, but because of these side effects, further studies are required to determine the optimal dose of each of these drugs.

Adult↗
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

Interleukin 1 inhibitory activity secreted by a human myelomonocytic cell line (M20).

Culture supernatants from a myelomonocytic cell line (M20) were found to inhibit interleukin 1 (IL 1) activity in vitro. The factor, isolated from these supernatants, inhibited augmentation of phytohemagglutinin response of mouse thymus cells induced by IL 1 derived from several established cell lines. Various IL 1-dependent activities such as lymphocyte and fibroblast proliferation in vitro were also inhibited by the factor. The factor did not inhibit IL 2-induced or other proliferative responses not related to IL 1. Preliminary biochemical characterization of the factor indicated that the activity resides in a protein with a molecular mass of 52 kDa.

Cell Division↗
PubMed1986

Parameters affecting the in vitro maturation of human monocytes to macrophages.

In vitro maturation of human monocytes to macrophages was characterized by morphological criteria, cell size and lysosomal enzymes activity. Purified populations of monocytes were maintained in culture at either adherent or nonadherent conditions and their maturation to macrophages was observed in both cases. The addition of external factors such as hydrocortisone and vitamin D3 inhibited monocyte maturation. In the absence of external factors, nonadherent monocytes were inhibited in their maturation for up to 10 days when plated at crowded cell concentrations. In addition, the presence of human serum in the culture media had a higher inhibitory activity than similar concentrations of fetal calf serum. Supernates from crowded macrophages were also inhibitory for monocyte maturation. We suggest the possibility that cell crowding, as well as soluble factors found in the serum and probably secreted by macrophages, participate in the regulation of monocyte development by inhibiting their maturation. Once released from this inhibitory signal or environment, the monocytes mature to macrophages.

Adolescent↗
PubMed1986

Adriamycin, vinblastine and mitomycin C as second-line chemotherapy in advanced breast cancer.

Thirty-six evaluable patients with metastatic measurable breast carcinoma previously treated with CMF or CMFVP were given second-line chemotherapy with Adriamycin, vinblastine, and mitomycin C (AVM), as follows: Adriamycin 20 mg/m2 and vinblastine 6 mg/m2 by i. v. push on days 1, 8, and 15, and mitomycin C 10 mg/m2 i. v. on day 1, every 6 weeks. Ten patients (28%) achieved partial remission (PR) lasting a median of 10 months, and eight patients (22%) experienced improvement of a lesser level than PR. An additional nine patients (25%) had disease stabilization; in the remaining nine patients (25%), persistent disease progression was observed. The median survival from the onset of AVM was 7 months for all patients; patients with PR survived a median of 13 months. Myelotoxicity was substantial and frequently interfered with the optimal administration of AVM, especially in patients with skeletal metastases; four patients were hospitalized with leukopenia and fever; all recovered promptly; one death was probably related to thrombocytopenia and CNS bleeding. Our results with AVM are similar to the average response rate published in the literature with the use of Adriamycin as a single agent in previously treated patients with advanced breast cancer.

Adult↗
PubMed1986

The effect of estradiol on human myelomonocytic cells. II. Mechanism of enhancing activity of colony formation.

Elevated proportions of monocytes have previously been found in the blood of healthy women during the ovulation period as well as in other conditions associated with increased blood estradiol (E2). This phenomenon was explained, in part, by an augmenting effect which physiological concentrations of E2 may have on the development of granulocyte-macrophage (GM) colonies derived from normal peripheral blood mononuclear cells. To analyze this effect, we tested possible alternatives for the interaction between E2, colony-stimulating factor (CSF) and GM colony progenitor cells. E2 was found not to interact synergistically with CSF, but pre-treatment of the progenitor cells with E2 resulted in higher numbers of colonies in response to CSF. Moreover, E2 did not induce higher secretion of CSF but treatment with anti-CSF antibodies abolished the enhancing effect of E2. Based on these results, we suggest that the augmenting effect of E2 on GM colony formation is mediated by inducing the colony precursor cells to be more responsive to CSF. These findings may help to elucidate some of the complex relationships between estrogens, immune responses and hemopoiesis.

Adult↗
PubMed1986

In vitro differentiation and establishment of cell lines derived from human myelomonocytic leukemia cells.

Primary cultures of cells derived from 13 patients with acute myelomonocytic leukemia (AMML) were studied with particular emphasis on in vitro proliferation, cell differentiation and the mode for establishment of cell lines. Using irradiated human macrophage monolayers to assist cell growth, we obtained four new cell lines of myelomonocytic origin. All the cell lines were characterized for cytochemical markers and response to phorbol esters (TPA), a differentiation inducing agent. In the absence of any inducing agent, spontaneous differentiation of blast cells into mature macrophages-like cells occurred in 8 out of the 13 primary cultures. Thus, maturation induction by agents such as TPA is not always required in order to obtain leukemic cell differentiation in vitro. The regulation of cell proliferation and differentiation by cellular interactions and by extrinsic soluble products is discussed in detail, in the light of these findings.

Cell Differentiation↗
PubMed1986

The mechanism of human bladder tumor implantation in an in vitro model.

Implantation of tumor cells in the bladder following transurethral resection of superficial bladder tumors is believed to be one factor in the etiology of bladder tumor recurrences. Using an in vitro model system we have studied the initial interaction between bladder carcinoma cells and a naturally produced basement membrane-like substrate. Minced explants of superficial low grade human bladder tumors from 10 patients were plated into culture dishes coated with a naturally produced extracellular matrix (ECM). This ECM has been shown to resemble the human urothelial basement membrane and submucosa in its macromolecular composition and ultrastructural appearance. It was found that a firm attachment of the human bladder tumor cells occurred within one hour, reached a maximal value within 24 hours and was followed by flattening and proliferation of the plated cells. These results indicate that prevention of tumor implantation should be initiated in the first hour after transurethral resection of the bladder tumors. This assay can be used for the investigation of various treatments to prevent tumor implantation.

Basement Membrane↗
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↗
PubMed1986

Detection of different interleukin-1 activities in human monocytes and monocytic cell lines.

Culture supernatants from normal human monocytes, monocyte hybrid cell lines, and myelomonoblastic cell lines were tested for human interleukin-1 (IL-1) activity. In the present study, we report the detection of IL-1 secreted by several cell lines of monocyte origin and compare their biological and biochemical characteristics. IL-1 activity was tested by the regular assay of phytohemagglutinin (PHA) response of mouse thymus cells. IL-1 was found to be constitutively secreted by U937 and the M20 cell lines, as well as by three of the monocyte hybrid cell lines. The activity was always augmented following dialysis and did not require the presence of serum for its secretion. We compared the IL-1 activity of the myelomonoblastic M20 and hybrid 1C4 cell lines to that of normal monocytes. We found differences in the kinetics of IL-1 secretion, the pattern of activity following dilution of concentrated supernatants, and augmentation of activity by various inducers. The differences described may be explained by concomitant secretion of IL-1 inhibitory factors, as well as the secretion of activities other than IL-1. Preliminary biochemical analysis showed that all three cell sources tested shared some species of molecules characterized by gel filtration and ion-exchange chromatography. However, some species of molecules expressing IL-1 activity were unique to the cell lines and were not found in normal monocytes.

Animals↗
PubMed1986

Pleural effusion in breast cancer: influence upon clinical course and survival.

The clinical course and outcome of 31 women suffering from breast carcinoma with documented pleural involvement was reviewed retrospectively. These 31 patients represent 14% of all patients with metastatic breast cancer seen in our Institution between 1977 and 1982. Most effusions were unilateral and ipsilateral to the affected breast, and the median interval from diagnosis of breast cancer to detection of pleural effusion was 32 months (range 0 to 84). In 55% of the patients, the effusion represented the first site of failure; in patients with known metastatic disease, the median interval from initial failure to the development of pleural effusion was 12 months. Local recurrence in the affected breast or chest wall very frequently preceded the onset of an ipsilateral effusion. Once pleural fluid developed, spread to other visceral organs was common. Treatment regimens were far from uniform and included systemic chemotherapy, hormone therapy or both, as well as intrapleural treatment; 10 of 22 patients (45%) given any form of therapy other than thoracentesis had a significant decrease in the amount of the effusion, including 3 patients with a complete response. The median survival of all patients from the onset of the effusion was 7 months (1-72); complete responders survived a median of 15 months whereas progressors had a median survival of 5 months only. Prognostic characteristics associated with a prolonged survival were: a unilateral effusion, ipsilateral to the primary tumor; effusion as first site of relapse, and mainly, an objective response to therapy. Although this is a small series, patients given both systemic and intracavitary treatment achieved best results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

High-dose metoclopramide as an antiemetic in patients receiving cis-platinum-based combination chemotherapy.

Thirty-seven patients with advanced malignancies, who received cis-platinum-based combination chemotherapy, were evaluated for the antiemetic efficacy of high-dose metoclopramide. Most of the patients suffered from ovarian carcinoma. The dose of metoclopramide was 7.5 or 10 mg/kg per course. A total of 69 courses were given to 37 patients and in 22% of the courses, nausea and vomiting were eliminated altogether. In an additional 48% of the courses, a partial protection from chemotherapy-induced emesis was evident. No serious side effects were observed. The administration of high-dose metoclopramide is recommended for prevention of cis-platinum chemotherapy-induced emesis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

The effect of estradiol on human myelomonocytic cells. 1. Enhancement of colony formation.

Cyclic changes were observed in the content of blood monocytes during the menstrual cycle of normal women. Elevated blood monocytes were found during the ovulation period as well as in other conditions which are associated with increased blood estradiol (E2). To understand the possible association between E2 and monocytosis, we analysed the in vitro effect of E2 on the development of myelomonocytic colonies in culture. E2 in physiological concentrations was found to increase the number of colonies developed from peripheral blood mononuclear cells (PBM) of both females and males. The optimal concentration for the augmenting effect on males' PBM was lower than that for females. Mononuclear cells derived from cord blood, which yielded much higher numbers of colonies than adult PBM, also responded to the stimulatory effect of E2. Estrone and estriol were less effective than E2 in adult PBM. In contrast, progesterone, diethylstilbestrol and testosterone did not affect the number of colonies at the range of physiological concentrations tested. The anti-estrogen Tamoxifen did not inhibit the stimulatory effect of E2. The augmenting effect of E2 on monomyelocytic colony formation may explain at least in part the increase in blood monocyte content of women with high E2 as well as other phenomena of macrophage and granulocyte changes associated with the menstrual cycle.

Adult↗