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Biomedical subjects

I Jahan

Publications and source records attributed to I Jahan.

10 recordsLinked to original sources

Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers.

BACKGROUND: The ligand ephrinB2 and the corresponding receptor EphB4 contribute to tumor growth in various human tumors. This prompted us to study the expression and localization of ephrinB2 and EphB4 in uterine endometrial cancers to analyze the ephrinB2/EphB4 functions against clinical backgrounds. MATERIALS AND METHODS: We carried out immunohistochemistry and real-time RT-PCR to determine the histoscores and messenger RNA (mRNA) levels of ephrinB2 and EphB4, respectively, in 68 uterine endometrial cancers and 16 normal endometrium tissue samples. Patient prognoses were analyzed with a 60-month survival rate. RESULTS: The localization of ephrinB2 and EphB4 was dominantly in the cancer cells of uterine endometrial cancer of all cases given. EphrinB2 and EphB4 histoscores were highly correlated with ephrinB2 and EphB4 mRNA levels, respectively (r = 0.864 and r = 0.615, P < 0.01). Both the histoscores and mRNA levels of ephrinB2 and EphB4 significantly increased with clinical stages (I < II < III, P < 0.01), dedifferentiation (G(1) < G(2) < G(3), P < 0.01) and myometrial invasion (A < B < C, P < 0.01 for ephrinB2 and P < 0.05 for EphB4) in uterine endometrial cancers. The 60-month survival rates of the 34 patients with high ephrinB2 and EphB4 expression were poor (59% and 62% respectively), while for the other 34 patients with low ephrinB2 and EphB4 expression, they were significantly higher (85% and 82%, respectively). CONCLUSIONS: EphrinB2 and EphB4 were overexpressed during the tumor advancement as dedifferentiation and myometrial invasion. Therefore, ephrinB2/EphB4 might work on tumor advancement and may be recognized as a novel prognostic indicator for uterine endometrial cancers.

Adult↗

Suppression of the accumulation of triosephosphates and increased formation of methylglyoxal in human red blood cells during hyperglycaemia by thiamine in vitro.

The accumulation of triosephosphates and the increased formation of the potent glycating agent methylglyoxal in intracellular hyperglycaemia are implicated in the development of diabetic complications. A strategy to counter this is to stimulate the anaerobic pentosephosphate pathway of glycolysis by maximizing transketolase activity by thiamine supplementation, with the consequent consumption of glyceraldehyde-3-phosphate and increased formation of ribose-5-phosphate. To assess the effect of thiamine supplementation on the accumulation of triosephosphates and methylglyoxal formation in cellular hyperglycaemia, we incubated human red blood cell suspensions (50% v/v) in short-term culture with 5 mM glucose and 50 mM glucose in Krebs-Ringer phosphate buffer at 37 degrees C as models of cellular metabolism under normoglycaemic and hyperglycaemic conditions. In hyperglycaemia, there is a characteristic increase in the concentration of the triosephosphate pool of glycolytic intermediates and a consequent increase in the concentration and metabolic flux of the formation of methylglyoxal. The addition of thiamine (50-500 microM) increased the activity of transketolase, decreased the concentration of the triosephosphate pool, decreased the concentration and metabolic flux of the formation of methylglyoxal, and increased the concentration of total sedoheptulose-7-phosphate and ribose-5-phosphate. Biochemical changes implicated in the development of diabetic complications were thereby prevented. This provides a biochemical basis for high dose thiamine therapy for the prevention of diabetic complications.

Deoxyglucose↗

Effects of okadaic acid on cell growth, anchorage-independent growth, and co-cultures of normal (KMS-6), immortalized (KMST-6), and neoplastically transformed (KMST-6T and KMST-6/RAS) human fibroblasts.

The effects of okadaic acid (OA) on normal human (KMS-6), its immortalized (KMST-6) and neoplastically transformed (KMST-6T and KMST-6/RAS) cells were investigated as a model of two stage carcinogenesis. The presence of OA inhibited cell growth of the normal and immortalized cells but not that of the neoplastic KMST-6T cells. In contrast, cell growth of the other neoplastic KMST-6/RAS cells transformed with the Ha-ras oncogene was inhibited by OA. OA enhanced colony formation of KMST-6T cells in soft agar, but it suppressed that of KMST-6/RAS cells. Co-cultures of KMST-6T cells with normal KMS-6 cells showed an increase in focus formation of KMST-6T cells in the presence of OA, whereas focus formation of KMST-6/RAS cells decreased. These results indicate that OA has growth-promoting effects on certain types of transformed human cells.

Carcinogens↗

Lipid profile of Helicobacter spp.: presence of cholesteryl glucoside as a characteristic feature.

The lipid and fatty acid profiles of eight Helicobacter spp. (H. nemestrinae, H. acinonyx, H. canis, Helicobacter sp. strain CLO-3, "H. rappini" [Flexispira rappini], H. pametensis, Helicobacter sp. strain Bird-B, and Helicobacter sp. strain Bird-C) and the fatty acid profiles of five additional species (H. pylori, H. felis, H. muridarum, H. mustelae, and H. fennelliae) were analyzed and compared. A heterologous fatty acid profile was observed among the Helicobacter spp., and on that basis the species could be divided into two groups. Group A had 19-carbon cyclopropane fatty acid (19:0cyc) and tetradecanoic acid (14:0) as the major fatty acids, and group B characteristically lacked the 19:0cyc and had hexadecanoic acid (16:0) and octadecenoic (18:1) acids as the major fatty acids. The species of group A are primarily gastric colonizers, and those of group B are primarily intestinal colonizers. Seven of the eight species studied showed the unusual and characteristic presence of cholesteryl glucosides (CGs), and most of these seven showed a very large amount (9.7 to 27.4% of the weight of total extractable lipid). The types of CGs and their distribution in different species were as follows: cholesteryl-6-O-acyl-alpha-D-glucopyranoside (cholesteryl-6-O-tetradecanoyl-alpha-D-glucopyranoside in H. nemestrinae and mainly cholesteryl-6-O-dodecanoyl-alpha-D-glucopyranoside in "H. rappini"), cholesteryl-alpha-D-glucopyranoside (H. nemestrinae, H. acinonyx, H. canis, Helicobacter sp. strain CLO-3, and "H. rappini"), and cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside (H. nemestrinae, H. acinonyx, H. canis, and Helicobacter sp. strain CLO-3). Besides this, we could also detect cholesteryl acyl glucoside in H. acinonyx, cholesteryl glucoside in Helicobacter sp. strains Bird-B and -C, and cholesteryl phosphatidyl glucoside in "H. rappini" and Helicobacter sp. strain Bird-C. A selective accumulation of free cholesterol was observed in the neutral lipid fractions. On the basis of the detection of CGs in 11 of the 13 species studied so far, the presence of CGs appears to be a characteristic feature of the genus Helicobacter. In view of this and also because of a simple and rapid detection method described herein, the CGs can be used as a valuable chemotaxonomic marker.

Cholesterol↗

Human fibroblasts (KMST-6/RAS cell line) transformed with 60Co gamma-rays and c-Ha-ras oncogene produce a large amount of granulocyte colony-stimulating factor (G-CSF); production is enhanced by cAMP, theophylline, and butyrate.

Human fibroblasts (KMST-6/RAS cell line), which was malignantly transformed in vitro with 60Co gamma-rays and the c-Ha-ras oncogene, produced a large amount of granulocyte colony-stimulating factor (G-CSF). The production was greater during the logarithmic growth phase than during the stationary phase. cAMP and theophylline, alone or in combination, and butyrate significantly enhanced G-CSF production, but dexamethasone or 5-azacytidine did not. Enhanced production of G-CSF by these agents was regulated at the posttranscriptional level. Neither the expression of the ras oncogene nor the tumorigenicity of the cells correlated with the production of G-CSF.

Butyrates↗

Karyotypic analysis in the process of immortalization of human cells treated with 4-nitroquinoline 1-oxide.

The establishment of a model system of neoplastic transformation of normal human cells has been attempted with a chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO). In the course of these experiments, it was noticed that immortalization of human cells is a multi-step process involving several mutational genetic events. Thus, chromosomal changes which occurred during the process of immortalization of human fibroblasts were examined. To accomplish immortalization, fibroblasts obtained from an embryo were repeatedly treated with 10(-6) M 4NQO from primary culture to passage 51 (59 treatments in total). Before immortalization, some chromosomes (especially, chromosomes 2, 6, 8, 10, 11, 12, 15, 19, and 20), were lost at a relatively high frequency. After immortalization, the chromosomes distributed so broadly in the triploid to hypotetraploid region without a distinct modal number or without marker chromosomes that it was difficult to identify the specific chromosomes related to the immortalization of human cells. No specific structural chromosomal changes were detected. Although the significance of such chromosome changes in relation to immortalization is not clear, the loss of some specific chromosomes suggests that genes which are involved in cellular aging and which suppress immortalization may have been lost in the immortalization process.

4-Nitroquinoline-1-oxide↗

Neoplastic transformation and characterization of human fibroblasts by treatment with 60Co gamma rays and the human c-Ha-ras oncogene.

Human fibroblasts (KMST-6) immortalized by treatment with 60Co gamma rays were further neoplastically transformed by transfection of the c-Ha-ras oncogene from human lung cancer. The ras-transfected cells formed undifferentiated fibrosarcoma in nude mice. One of the tumors was recultured and a neoplastic human fibroblast line, KMST-6/RAS, was established. To analyze multistep carcinogenesis of human cells, the cellular characteristics of these genetically matched immortalized (KMST-6) and neoplastic (KMST-6/RAS) cell lines were studied in detail. KMST-6/RAS cells showed an increased saturation density, colony formation on confluent monolayers of normal human fibroblasts, proliferation in neomycin-containing medium, anchorage-independent growth, and enhanced expression of the transfected c-Ha-ras oncogene, whereas the immortalized cells did not demonstrate these characteristics. Unexpectedly, growth of KMST-6/RAS cells was serum-dependent, although they were neoplastic. Interestingly, the neoplastic cells did not show the criss-crossing or piling up growth pattern characteristic of transformed rodent fibroblasts.

Animals↗

Immortalization of normal human cells is a multistep process and a rate limiting step of neoplastic transformation of the cells.

Three normal human fibroblast strains were immortalized by treatment with either 4-nitroquinoline 1-oxide (SUSM-1 and OUMS-24F lines) or 60Co gamma rays (KMST-6 line). Immortalization of normal human cells with these agents required repeated treatments. Before immortalization, most of the cells treated with these mutagenic agents showed more or less chromosome aberrations, but immortalized cells appeared very rarely. This suggests that several mutational events are involved in the immortalization process itself. The immortalized cells showed polygonal or epithelial-like morphology, prominent numerical and structural abnormalities of chromosomes, requirement of serum growth factors for their growth, and no tumorigenicity. The immortalized KMST-6 and OUMS-24F were further transformed into neoplastic ones by the ras oncogene, but not by transfection with the mutant p53 gene. Normal human fibroblasts which are mortal were not immortalized nor neoplastically transformed with the ras oncogene or the mutant p53. These findings strongly indicate that the immortalization of human cells is prerequisite for neoplastic transformation of the cells.

4-Nitroquinoline-1-oxide↗

Reproductive function after reconstructive surgery on rat uterine horns.

OBJECTIVE: To assess the effectiveness of tuboplasty procedures employing fibrin glue. METHODS: Experimental tuboplasty operations were performed on 63 rats using biological glues (fibrin glue--"Beriplast" Behring; "FK-1", Russia) and microsuture materials. Uterine horn patency, adhesion formation, and other changes at the site of anastomosis, as well as pregnancy rate and embryonal characteristics, were assessed. CONCLUSIONS: We confirmed the effectiveness of fibrin glue application in reconstructive surgery on uterine horns, and documented no significant differences between microsuture and sutureless anastomoses with regard to pregnancy rates (80 and 83.3%, respectively).

Animals↗

Hormonal and immunologic methods in the diagnosis and treatment of patients with benign ovarian tumors and endometriotic cysts.

OBJECTIVE: To compare efficacy of various methods for characterizing endometriosis and benign ovarian tumors. DESIGN: Two parallel groups of patients, 54 with endometriotic ovarian cysts and 48 with benign tumors. SETTING: Central clinic. PATIENTS: Patients referred from all regions over a 5-year period. OUTCOME MEASURES: Estrogen Estrogen and progesterone receptor levels of endometrium and endometriotic foci, CA-125 concentration, and estradiol, progesterone, LH, and testosterone blood levels. RESULTS: LH levels elevated during follicular phase in patients; estradiol levels reduced; receptor levels abnormal in endometriosis, but not in benign ovarian cysts. CONCLUSIONS: Hormone therapy is adequate treatment for endometriotic cysts. CA-125 is not a reliable indicator for differential diagnosis.

Antigens, Tumor-Associated, Carbohydrate↗