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Biomedical subjects

A A Hakim

Publications and source records attributed to A A Hakim.

At least 19 recordsLinked to original sources
PubMed1989

Prognostic significance of mRNA-encoding estrogen receptor and epithelial growth factor receptor in breast carcinoma progression into lymph nodes: 1. Estrogen receptor encoding mRNA.

The main objective of this study was to differentiate between lymph nodes infiltrated by estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast carcinoma. Lymph nodes were obtained from 40 postmenopausal cancer patients, 10 from each disease stage. Six patients from each group had estrogen receptor-positive (BCaER+) and four estrogen receptor-negative (BCaER-) tumors. Both tumor-containing (T) and uninvolved (N) lymph nodes from the same patient were examined by the following parameters: magnitude of lymph node nucleic acid hybridization with cDNA probes from breast cancer MCF-7ER+ and MCF-7ER- cells; and binding capacity of 3H-estradiol, 125I-EGF, and 125I-PDGF binding and protein kinase C activities of the lymph nodes. Concomitant with the appearance of transformed cells, several events occur: Tumor cells induce stimulation of mononuclear cells and macrophages and evoke T- and B-cell proliferation, leading to the synthesis of tumor cell membrane-associated antibodies. In estrogen receptor-positive (ER+) breast carcinoma, estrogens and host hormonal modulatory mechanisms stimulate production and release of epithelial growth (EGF) and platelet-derived growth factors (PDGF). These factors are characterized by protein kinase C activities. There is infiltration of tumor cells into the lymph node and infiltration of leukocytes into the tumor site. In the lymph node, tumor progression depends on tumor cell proliferation rate and metastatic aggressiveness. The experiments described in this study document the changes that occur in lymph nodes, with differences between nodes infiltrated with BCaER+ and BCaER- breast carcinomas. Hybridization of 32P-cDNA from MCF-7ER+ cells with cellular RNA from BCaER+ involved (T) lymph nodes is greater than with cellular RNA from uninvolved (N) lymph nodes. The magnitude of hybridization correlated (P less than 0.005) with the disease stage.

Breast Neoplasms↗
PubMed1988

Peripheral blood lymphocytes from patients with cancer lack interleukin-2 receptors.

When tumor cells develop in healthy adults, they activate the cellular immune system--natural killer (NK) cells, antigen-specific cytotoxic lymphocytes (CTL), and the synthesis of antigen specific cytotoxic antibodies. These are aimed at killing the intruding cells. However, in cancer patients the tumor continues to grow. As tumor cells proliferate, they were shown to release factors that mediate the inactivation of the host immune defense systems. The study documented in this article examined peripheral blood lymphocytes, mononuclear cells (MNC), NK cells, T-helper cells (THC). This study confirmed the interaction of the released inhibitor factors with these mononuclear cells. NULL cells from healthy adults responding to interleukin-2 (IL-2) and NILL cells from patients with metastatic breast carcinoma nonresponsive to IL-2 were also isolated by the standard antibodies-pinning technique. The cells were obtained from age-matched subjects: ten healthy adults; ten patients each from Stage I, II, III, and IV metastatic breast carcinoma (BCa-I, BCa-II, BCa-III, and BCa-IV or MBCa); and ten patients with benign breast disease (BBD). The responsiveness of these THC, PBMNC, NK, NULL, and NILL cells in vitro to graded levels of phytohemagglutinin (PHA), Concanavalin A (Con A), and recombinant interleukin-2 (rIL-2) was examined. Responsiveness was monitored by 3H-thymidine (3H-TdR) uptake, production and release of IL-2, interleukin-2 receptor (IL-2R), and cytotoxic activities against K-562 cells and breast carcinoma short-term cell lines. A lack of functional IL-2R in peripheral blood lymphocytes from patients with metastatic breast carcinoma was confirmed by nonsignificant anti-Tac antibody binding. An elevation in the expression of cell surface antigen GP-120 has been observed to be associated with the activation in vitro of T-cells from healthy adults and from patients with benign breast disease, but not of T-cells from patients with breast carcinoma. Biochemical studies of the GP-120 using high performance liquid chromatography combined with nitrocellulose blotting confirmed that the glycoprotein was resistant to trypsin and chymotrypsin, but susceptible to pronase. It contained sialic acid and lactosaminoglycan as O-linked sugars. It could be labeled with pariodate/NaB(3H4) and is recognized by MAbT-305 monoclonal antibodies. It contained sialic acid linked (2---3) to galactose.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Peripheral blood lymphocytes from patients with cancer lack interleukin-2 (IL-2) receptor expression: isolation of mRNA encoding IL-2R.

In healthy adults, tumor cells stimulate the cellular immune defense mechanisms: natural killer (NK), antigen-specific cytotoxic lymphocytes (CTL), and synthesis of antigen-specific cytotoxic antibodies, all aimed at the destruction of the intruding tumor cells. The experiments described in this study examined responsiveness of peripheral blood lymphocyte mononuclear (MNC) cells, natural killer (NK) cells, T-helper (THC) cells, and NILL (cells obtained from patients with advanced breast cancer) cells from 10 of each age-matched subjects from 10 healthy adults and patients, 10 with benign breast diseases (BBD), and 10 from patients from each of the breast carcinoma pathological stage BCa PS I, BCa PS II, BCa PS III, and BCa PS IV. Cellular responsiveness to graded levels of phytohemagglutinin (PHA), concanavalin A (Con A), and recombinant interleukin-2(r IL-2) was monitored by 3H-thymidine (3H-TdRO) uptake, production, and release of interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R) and cytotoxic activities against K-562 and breast carcinoma (BCa) short-term cell lines. Suppressed cellular responsiveness is caused by the lack of functional IL-2R in peripheral blood lymphocytes with metastatic breast carcinoma (MBCa). This is confirmed by suppression of the anti-Tac antibodies binding and lack of cellular mRNA encoding IL-2R.

Adult↗
PubMed1987

Ulcerative colitis and familial polyposis oncologic transformation to colon carcinoma: changes in carcinoembryonic antigen release.

During cell proliferation, several "factors" are released into the microenvironment, or culture medium. The experiments described sought and examined agents that may cause or support malignant cell transformation. The response of colon cells from patients with ulcerative colitis (UC), familial polyposis coli (FPC) and colon carcinoma (CCC) to these agents was monitored by carcinoembryonic antigens (CEA) released into the medium during cell proliferation in a serum-free hormone-defined (SFHDM) medium, oncogenicity in athymic mice and colonigenicity, i.e. the ability of the cells to form colonies in soft agar. When cultured on the extracellular matrix (EM), i.e. footprints from colon carcinoma cells (short term or established cell lines), and in SFDHM, colon cells from patients with UC and FPC showed significant (P = 0.001) increases in all the three parameters. Analyses indicated that EM from cultures of [35S]methionine-labelled normal epithelial colon cells (NCE) differed from those left by UCC, FPC and CCC cell cultures. EM from NCE cell cultures did not contain [35S]methionine-labelled glycoproteins resistant to collagenase action which were not fragments of fibronectin, and which were present in EM from CCC cells. It is concluded that the extracellular matrix from malignant colon cells contains agents that support colon cell oncogenic transformation.

Adenomatous Polyposis Coli↗
PubMed1986

Human embryonic liver cell differentiation. I. Changes in specific mRNA synthesis correlates with parameters signaling oncologic alterations.

When incubated in preconditioned medium, i.e. spent media from the hepatocellular carcinoma (PLC/PRF/5) cell cultures, human embryonic liver (HEL) cells differentiate and acquire oncologic phenotypes. This is caused by transcriptional alterations in fetal gene expression. This occurs when hepatocytes are proliferating rapidly and secreting alpha fetoprotein (AFP), and later when the quiescent state is reached with secretion of albumin (ALB). The present studies examined the parameters signaling oncologic transformation during liver cell differentiation in the conditioned medium. mRNAs coding for AFP, ALB and HBsAg were isolated from HEL, adult liver cells (ADLC) and from PLC/PRF/5 cells, respectively. cDNA molecules complementary to these polysomal mRNA molecules were constructed and labeled with 32P. These tracers were used to quantitate changes in cellular mRNA X AFP, mRNA X ALB and mRNA X HBsAg directly by DNA molecular hybridization during HEL cells cultivation in the preconditioned medium. Under these conditions, the changes in cellular mRNA X HBsAg and mRNA X AFP correlated with an increased tumorigenicity in athymic Nu/Nu mice, membrane galactosyltransferase and phospho-tyrosine kinase activities.

Albumins↗
PubMed1985

Cytotoxicity of human peripheral blood T-lymphocyte clones activated by hepatitis B virus surface antigen.

The present studies examined the cytotoxic activities of peripheral blood lymphocytes (PBL) from volunteers with (sero-positive) and without (sero-negative) circulating antibodies to hepatitis B virus surface antigen before and 30 days after vaccination with hepatitis B virus surface antigen (HBsAg). Long-term culture of monospecific hepatitis B surface (HBsAg)-responsive T-lymphocytes were isolated and grown in large numbers. The mechanism of T-cell mediated cytolysis, and the identification of the carbohydrate determinants on the surface of these effector cells responsible for the killing effect, are being examined.

Carbohydrates↗
PubMed1979

Correlation of immunogenicity with suppression of lymphocyte adenosine 3',5'-monophosphate-dependent protein kinase.

Cyclic-AMP-dependent protein kinase activity was depressed in whole spleen as well as in isolated splenic lymphocytes from 3-methylcholanthrene (MCA), R3230 AdCa mammary adenocarcinoma, N-hydroxy-2-acetylaminofluorene, and 4-dimethylaminoazobenzene (DMAAB) tumor-bearing Fischer rats as compared to control animals. The magnitude of depression increased with the immunogenicity of the tumor. The depressed enzyme activity was the result of a reduced Vmax for adenosine 3',5'-monophosphate (cAMP)-stimulated histone phosphorylation.

Animals↗
PubMed1979

Enzymatic modulation of the cell surface in malignant transformation of normal human mammary epithelial cells and in conversion of mammary carcinoma cells.

The effect of treatment with trypsin and neuraminidase on morphology, proliferation pattern, adhesiveness and ultrastructure of human normal mammary and carcinoma cell lines has been investigated. These criteria were chosen because they reflect on the cell surface function. Active enzymes were required to produce changes. If trypsinized and then allowed to grow in culture media supplemented with 'fibroblast growth-promoting factor', human normal mammary epithelial cells proliferated in a disorganized pattern with cells overlapping and piling up and developing ultrastructural characteristics of neoplastic cells. On the other hand, if treated with neuraminidase and then permitted to grow in presence of the 'fibroblast growth-promoting factor', mammary carcinoma cells proliferated in an organized pattern, forming one-cell-thick, fibroblast-like monolayers and ultrastructural characteristics of normal epithelial cells.

Breast↗
PubMed1979

Enzymically-modified human mammary carcinoma cells: modulators of macrophage functions.

Human mammary carcinoma cells (HMCC), vibrio cholera neuraminidase (VCN) treated HMCC(VCN-HMCC); glutaraldehyde fixed VCN-HMCC(Glut-VCN-HMCC), normal mammary epithelial cells (HMEC), VCN treated HNEC (VCN-HNEC) and glutaraldehyde fixed VCN-HNEC (Glut-VCN HNEC) were prepared and injected into separate groups of mice. Intraperitoneal injection of phytohemagglutinin (PHA) produced a delayed type of inflammatory reaction characterized by an accumulation of macrophages. Injection of HNEC, VCN-HNEC, and Glut-VCN-HNEC had no effect, HMCC inhibited, and VCN-HMCC and Glut-VCN-HMCC increased both the number and the tumoricidal activity of peritoneal macrophages. Cell-free media (CFM) harvested from cultures of HMCC alone or mixed with lymphocytes from patients with mammary carcinoma inhibited, whereas CFM from mixed cultures of HMCC and lymphocytes from normal subjects had no effect on, the chemotactic response and migration of normal peritoneal macrophages. CFM was passes through a series of Amicon membranes, the active principle passed through membrane PM-10 but was retained by PM-5 suggesting a molecular weight of less than 10,000. In culture, HNEC, VCN-HNEC and VCN-HMCC proliferated as sheets of single cell monolayers, whereas HMCC began to spread as a monolayer, but as cellular density increased it formed cell foci, cell colonies and cell clusters packed into solid tissuelike masses.

Animals↗
PubMed1979

Long-term cultivation of human mammary carcionoma: proliferation and differential biochemical properties of the cultured cells.

Human mammary carcinoma cell cultures proliferated from primary explants in Eagle's essential medium (MEM) supplemented with insulin, fetal calf serum (FCS) and/or human alpha-a1-antitrypsin. Human mammary carcinoma cells differed from normal mammary epithelial cells by the following catalytic activities: a. Thymidine uptake into the carcinoma cells was 6 to 10 fold greater, whereas thymidine conversion to CO2 was half to one fifth that of normal cells. b. The nucleolytic activity patterns of the mammary carcinoma cells preferred polycytydylic acid and double helical polynucleotides, whereas those of the normal mammary cells preferred polyuridylic acid and had no effect on double helical polynucleotides. c. The polymerase activity most evident in mammary carcinoma cells is a hybrid-dependent DNA polymerase which is guided by the ribo-strand of the template poly (rA) . poly(dT). In contrast the all-ribo template poly (rA) . poly(rU) showed little activity. d. There was slight or statistically non-significant difference between the amino acid composition of material cleaved from mammary carcinoma cells prepared from tumor tissues and from cells cultivated 10 months in vitro. e. There was no difference between the molar proportions of the carbohydrate components of the cell membrane from fresh tumor tissue and long term in vitro cultivated cells. f. The granules from long term in vitro cultured mammary carcinoma cells contained high collagenolytic, caseinolytic, fibrinolytic and esterolytic activities.

Amino Acids↗
PubMed1978

Isolation of a growth-stimulating agent from human skin fibroblast cultures.

Cell-free supernatants were harvested from cultures of human skin fibroblasts, were applied on to DEAE-cellulose columns, and the first fraction eluted with phosphate-buffered saline contained the growth-stimulating agent. The eluted fraction was then passed through a series of amicon membranes. After passing through PM-10, the filtrate stimulated growth of bovine vascular endothelial, canine myocardial, and human mammary carcinoma cells.

Blood Vessels↗