PubMed Health⌕ Search

Biomedical subjects

L Israel

Publications and source records attributed to L Israel.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Accelerated genetic destabilization and dormancy: two distinct causes of resistance in metastatic cells; clinical magnitude, therapeutic approaches.

Several years of clinical chemotherapy have shown that, despite modern refinements, cytotoxic agents are not able to eradicate metastases of most adult solid tumors but only to prolong survival by achieving a cell kill that is not 100 per cent. Among the possible causes of this phenomenon, two are discussed in detail. The first one is cell autonomy. It is shown that the numbers of generations reached by a metastatic clone until clinical detection is largely in excess of 100, which allows for a considerable number of mutations, and that in addition genetic destabilization leading to autonomy proceeds much more rapidly than anticipated by a random mutation process. Adaptative changes by genetic amplification in response to toxic injury add to this acceleration effect, accounting for the fact that most metastatic cells are totally resistant very early in the natural history of a human tumor. On the other hand, it is shown that dormant metastatic cells do exist, due either to lack of autocrine growth factors or to inhibiting agents secreted by other metastases. These cells can survive chemotherapy and then re-enter a proliferative state due to some mechanisms that are analyzed, accounting for semi-late and late failures. These obstacles call for other strategies of metastases management, such as arresting or differentiating agents, some of which have been successfully tested by the author's group, such as antiprostaglandins, antithrombin, somatostatin, hyaluronidase, and retinoic acid. It remains to study their optimal combinations, and the appropriate timing, in order to achieve, if not eradication, growth suppression for very long periods without toxicity.

Cell Division↗
PubMedDate not supplied

Blood transfusion in liver transplantation.

Liver transplantation is a relatively new procedure in which unusually large quantities of blood are used. Blood use in 68 adult and 49 pediatric liver transplants was reviewed. The median (range) intraoperative red cell use for adults and children was 28.5 (3-251) and 11 (2-55), respectively. Blood use closely correlated with the patient's primary diagnosis. Adult patients with primary biliary cirrhosis and carcinoma used about one-half as much blood as those with a diagnosis of sclerosing cholangitis, hepatitis, or cirrhosis. Patients in the former diagnostic groups also had better survival rates. Total red cell use for the patient's entire hospitalization was about twice that used during surgery. Fresh-frozen plasma use paralleled red cell transfusions, but platelet use was modest. These data can serve as a baseline in helping other hospital transfusion services prepare for the advent of liver transplantation in their institutions.

Adult↗
PubMedDate not supplied

Inhibitory effects of dextran derivatives in vitro on the growth characteristics of premalignant and malignant human mammary epithelial cell lines.

The effects of two dextran derivatives (CMDBS-6 and CMDBS-12) on the growth rates of three human mammary epithelial cell lines (HBL100,HH9 and MCF7) were studied. CMDBS-6 markedly inhibited the growth of all lines, while CMDBS-12 and native dextran T40 had no effect on the growth of all lines. This inhibition was dose-dependent, reversible and inversely related to the concentration of fetal calf serum. The inhibitory effect of CMDBS-6 is cytostatic but not cytotoxic. Moreover, CMDBS-6 appears to have a stronger effect on HBL100 cells which are non-tumorigenic in nude mice. In contrast, the growth of HH9 cells, which are highly tumorigenic in nude mice, is less inhibited by CMDBS-6. Whereas CMDBS-6 inhibited the HBL100 cell anchorage, that of HH9 cells was not affected. By analysing the cell distribution in the various phases of the cell cycle, we have observed that CMDBS-6 arrested HBL100 and MCF7 cell mainly in the G0/GI phase. In contrast, HH9 cells were accumulated in the G2/M phase. When treated with CMDBS-6, human mammary cells slightly increased their granularities. These results demonstrate an antiproliferative activity of CMDBS-6 which could not be explained by an inactivation of mitogens provided by the serum but suggest that this compound could exert its cytostatic effects via a cell-specific mechanism.

Amides↗
PubMedDate not supplied

Different susceptibility of lung cell lines to inhibitors of tumor promotion and inducers of differentiation.

Histologically distinct lung tumor and normal cell lines were treated with a variety of potential inhibitors of cell growth such as inducers of cell differentiation, inhibitors of protein kinase C and inhibitors of tumor promotion. The response was assessed by 3H thymidine incorporation and cloning efficiency. Both phorbol retinoate acetate and mezerein stimulated growth in lung normal cell lines (human fibroblastic PEH cells and rat epithelial TP9 cells) while inhibiting growth in lung tumor cell lines (human small-cell cancer-derived cell line IRSC-10M and adenocarcinoma-derived cell line A549). Likewise, the hydrophobic peptide melittin did not inhibit growth and cloning efficiency of normal cells at 1 microM, a concentration which prevented proliferation in tumor cells. Protein kinase C inhibitors, chlorpromazine, trifluoperazine and 1-(5 isoquinolinylsulfonyl) 2-methylpiperazine, were much more effective on proliferation of IRSC-1OM than of A549 cells. In contrast, the latter cells were more susceptible to anti-promoters such as glycyrrhetic acid, an anti-inflammatory agent, and 3,4',2', 4'-tetrahydroxychalcone or 2,3,5-trimethyl-6 (12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone, two inhibitors of lipoxygenase, a key enzyme in arachidonate metabolism. Our results provide evidence that small-cell carcinoma-derived cells, in contrast with adenocarcinoma-derived cells, are growth-inhibited by protein kinase C inhibitors and poorly dependent on the arachidonate metabolism. This difference in responsiveness suggests that different growth signalling pathways are preferentially triggered in these histologically distinct lung tumor cell lines. As a consequence, the proper susceptibility of tumor cells to phenotype modifiers has to be taken into account in cancer therapy.

Arachidonic Acid↗
PubMedDate not supplied

Primary cultures of human benign mastopathies and mammary carcinomas; growth factor requirements.

Primary cultures of non malignant human breast tissues, benign mastopathies and breast carcinoma were performed in defined culture conditions. Epithelial cells from these primary cultures were characterized for mammary epithelial cell specific markers, for in vitro cell proliferation, for steroid receptors and hormone sensitivity (estradiol, progesterone and prolactin) and for EGF sensitivity. We show that although some mastopathies have estradiol and progesterone receptors, they did not respond to hormone treatment. Human prolactin had no effect on the proliferation of one mastopathy but stimulates the cell growth of another fibrocystic mastopathy. EGF was capable of stimulating the three types of primary cultures. As regards growth characteristics, steroid hormone receptors and prolactin sensitivity, phenotypes of mastopathy cells differ from each other; some are similar to non malignant cells, whereas others are comparable to tumor cells.

Adenocarcinoma↗
PubMedDate not supplied

[Long survival periods after therapy for metastatic or reccurrent cancer (author's transl)].

Out of 671 cases of various cancers, first seen for growing metastases and or recurrences (resectable cases being excluded) the 3 years survival rate has been 18 per cent (121 cases). This result was obtained by various combinations of chemotherapy and radiotherapy. It follows that advanced cases should not be abandoned without any attempt at control, and that earlier treatments in cases being at high risk for metastases would probably further increase such results.

Adenocarcinoma↗
PubMedDate not supplied

Steroid hormone receptors and tumorigenicity of sublines from breast tumor metastatic MDA-MB 231 cell line.

Ten cell sublines the MDA-MB 231 human breast cell line were analyzed for their phenotypic diversity: morphology, karyotype, growth rate, clonogenicity in semisolid medium, tumorigenicity in nude mice, number and affinity of nuclear receptors for oestradiol, progesterone and glucocorticoids. Karyotypic analysis showed different aneuploidies from 50 to 120 chromosomes and variable chromosomal rearrangements in the analyzed subclones. All except two of the ten subclones were tumorigenic when injected subcutaneously or intraperitoneally into nude mice. Although the parental cell line has no receptor, all except two of the tested subclones contained various amounts of high affinity oestradiol and progesterone receptors ranging from 3,000 to 33,000 per cell. Seven subclones contained either high affinity oestradiol or progesterone receptors in nuclei. The diversity found in different subclones derived from one breast carcinoma cell line might represent variabilities acquired and selected continuously in culture.

Aneuploidy↗