Biomedical subjects

Long Jin

Publications and source records attributed to Long Jin.

42 records · Page 3Linked to original sources

PubMed1998

Analysis of TGF-B and TGF-B-RII in Thyroid Neoplasms from the United States, Japan, and China.

Transforming growth factor B (TGF-B) has an inhibitory effect on cell proliferation in various cells and tumors, so loss of TG-B-receptor (TGF-B-R) may lead to increase proliferative activity in these tumors. We compared the expression of TGF-B and TGF-B-Rll in a group of thyroid neoplasms from the United States, Japan, and China to determine if there were differences in the expression of this growth factor or its receptors in various tumor types from different countries. A total 108 neoplastic thyroids from the United States, 42 from Japan, and 46 from China were analyzed for TGF-B1, TGF-B3, and TGF-B-Rll by in situ hybridization with riboprobes. TGF-jB-RII expression was also examined by immunohistochemistry. TGF-B1 mRNA was expressed in all neoplastic thyroids from all three countries except for one anaplasti carcinoma (ACA). TGF-B3 expression was lowest in follicular carcinomas (FCA) from all three countries (30/42; 71%). TGF-B-RII was much lower in FCA from Japan (112; 50%) and China (6/11; 55%) compared to cases from the United States (26/29; 90%). TGF-B-RII expression in papillary carcinoma (PCA) was also lower in carcinomas from Japan (21/28; 75%) and China (23/30; 77%) compared to the United States (24/25; 96%). Most ACA from the United States (25/30; 83%) and from China (3/3; 100%) were positive for TGF-B-Rll. Immunohistochemical analysis for TGF-B-RII protein expression showed the highest levels in follicular adenomas (FA) (38/38; 100%) with decreased immunoreactivity in FCA (36142; 86%). PCA (66/83; 80%), and ACA (14/33; 42%). These findings suggest that loss of TGF-B--RII may be important in thyroid tumor progression and that environmental/geographic factors may play a role in the variable expression of TGF-B--RII in thyroid malignancy.

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PubMed1998

Remodeling of Hyperplastic Pituitaries in Hypothyroid us-Subunit Knockout Mice After Thyroxine and 1713-Estradiol Treatment: Role of Apoptosis.

Hyperplasia of pituitary thyrotrophs is often associated with hypothyroidism. In this study. the effects of thyroxine and 1 7B-estradiol on thyrotroph hyperplasia was analyzed using a hypothyroid mouse model resulting from targeted disruption of the glycoprotein hormone a-subunit (aSU) gene, which leads to lack of functional thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and underdevelopment of the thyroid and gonads. Thyroxine replacement for 2 mo resulted in a decrease in the relative percent of thyrotrophs and an increase of lactotrophs and somatotrophs numbers to normal values. A twofold increase in the relative percent of gonadotrophs was observed compared to wild-type mouse pituitary. Treatment for 2 mo with 17B-estradiol led to an increase in lactotroph numbers to normal levels, but had no influence on thyrotroph hyperplasia. Rearrangement of the hyperplastic pituitary phenotype after hormonal replacement proceeded without any evidence of pituitary cell necrosis. A slight increase in apoptotic cell death was observed in hormone-treated pituitaries, and this was localized to TSH cells by double-labeling experiments. Chronic thyroxine treatment resulted in increased expression of Bcl-2 protein in hypertrophied pituitary cells, whereas 17f3-estradiol increased expression of Bad protein in prolactin cells. These results suggest that apoptotic cell death is involved in reversal of thyrotroph hyperplasia in the presence of thyroid hormone. Thyroxine and 17-estradiol may influence cell death in this model by regulating expression of the Bcl-2 protein family in a celltype specific manner.

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PubMed1997

TGF-B and Estrogen Regulate P27(Kip1) and Cyclin D(1) in Normal and Neoplastic Rat Pituitary Cells.

Pituitary hyperplasia and tumor growth are regulated by various hormones and growth factors. Estrogen (E(2)) stimulates pituitary cell proliferation and prolactin (PRL) production. Estrogen also regulates transforming growth factor-B (TGF-B) effects in the pituitary. IGF-B in turn regulates various cell cycle proteins including p15 and p27(Kip1) (p27). To better understand the regulatory role of growth factors and hormones in the cell cycle we analyzed cyclin D(1), cyclin E, and p27 expression in normal and neoplastic rat pituitary cells. An in vitro analysis using cultured normal pituitary cells and GH(3) tumor cells and an in vivo analysis of estrogen-treated normal pituitary and implanted GH(3) cells were performed. Semiquantitative RT-PCR was used to analyze mRNA expression for cyclin D(1) cyclin E, and p27 in cultured pituitary cells and E(2)-treated pituitaries in vivo, Cyclin D(1) and p27 were localized in the nuclei of normal pituitary cells by immunocytochemistry (ICC). Very weak or absent immunostaining for cyclin D(1) and p27 was present in GH(3) cells. Both normal pituitary and GH(3) cells had strong nuclear staining for cyclin E. Normal pituitary had a 20-fold greater amount of cyclin D mRNA and a 3-fold greater amount of p27 mRNA compared to GH cells, whereas GH cells had slightly (1.5-fold) more cyclin E than normal pituitary cells. Treatment in vivo stimulated cell proliferation and decreased cyclin D(1) mRNA levels in normal pituitary. GH(3) tumor cells, implanted subcutaneously in the same animal, showed increased proliferation after E(2) treatment, but there was no change in cyclin B(1) mRNA in GH(3) cells. Cyclin E and p27 mRNA levels did not change significantly in normal pituitary or in GH(3) cells after E(2) treatment in vivo. Treatment of normal pituitary cells with 10(-9)M TGF-B1 for 3 d in vitro led to significant decreases in cyclin B(1) and p27 mRNAs (p < 0.05 ), whereas cyclin E levels were unchanged. These results indicate that cyclin B(1) and p27 mRNAs are present at significantly higher levels in normal pituitary compared to GH(3) cells, and that both E(2) and TGF-B1 can down-regulate cyclin B(1) mRNA levels in normal pituitary cells, suggesting that these factors regulate G1 to S phase transition in pituitary cells. The lower levels of specific cell cycle regulators in GH cells may explain the decreased regulatory control by E(2) in GH(3) tumor cells.

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PubMed1997

TGFB, TGFB Receptors, Ki-67, and p27(Kip)l Expression in Papillary Thyroid Carcinomas.

Although most papillary thyroid carcinomas behave as low-grade neoplasms and are generally associated with a good prognosis, some subgroups of these neoplasms represent more aggressive variants. In order to determine if differences in the behavior of these papillary carcinomas were related to expression of growth factors or cell-cycle proteins, we analyzed a series of papillary carcinomas including the conventional or usual type (n = 27), tall cell (n = 27), diffuse sclerosing (n = 5), and columnar cell (n = 2) variants for expression of transforming growth factor beta (TGB), TGB receptors (TGB-RI and II, the proliferation marker Ki-67, and for the cell-cycle inhibitory protein p27(Kip)1 (p27). All groups of thyroid tumors expressed TGFB and TGFB-RI and RlI by immunohistochemical staining. There was a marked increase in the Ki-67 labeling index after staining with antibody MIB-1 in the columnar cell tumors compared to the other groups, but this difference was not significant because of the small number of tumors in this group. The cell-cycle inhibitory protein p27 was expressed in all groups and was not significantly different between groups. Normal thyroid cells had a higher labeling index for p27 compared to papillary carcinomas. These results indicate that TGFB and TGFB receptors I and II are commonly expressed in the usual and in variant forms of papillary thyroid carcinomas, and that there is decreased expression of p27 protein in all of these neoplasms compared to normal thyroid. The biological basis for the more aggressive behavior of these variants of papillary thyroid carcinoma remains uncertain.

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PubMed1996

Expression and Regulation of Transforming Growth Factor B1 in Cultured Normal and Neoplastic Rat Pituitary Cells.

Pituitary prolactin (PRL) cell gene expression and proliferation are regulated by hormones and growth factors. Transforming growth factor beta (TGFB) and blast growth factor (bFGF) have been implicated in the regulation of antenor pituitary function. To study the roles of TGFB and bFGF in anterior pituitary cell function, we analyzed normal and neoplastic pituitary cells in serum-free media. The various isoforms of TGFB and TGFB receptor types I, II, and III were also analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in pituitary cells. Transforming growth factor beta 1 (TGFB1) stimulated PRL expression and PRL cell proliferation in normal pituitary. TGFB1 stimulated PRL expression, but inhibited proliferation in the growth hormone (GH) and PRL-producing GH(3) cells. Estradiol 17 B (E(2)) and bFGE stimulated PRL gene expression in normal pituitary and GH(3) cells, whereas E(2) inhibited and bFGF stimulated TGFB1 mRNA levels in normal pituitary PRL cells, but not in GH(3) cells. Both normal pituitary and GH(3) cells expressed the mRNAs for TGFB1, TGFB2, and TGFB3 isoforms and for TGFB receptors I, II, and III. These results indicate that there is a relative loss of regulatory control by growth factors in neoplastic GH(3) cells compared to normal pituitary PRL cells.

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PubMed1995

Immunohistochemical Analysis of the Cell Cycle-Associated Antigens Ki-67 and Retinoblastoma Protein in Parathyroid Carcinomas and Adenomas.

The morphologic distinction between parathyroid carcinoma and adenoma can be a difficult diagnostic problem. We analyzed nuclear immunoreactivity for the cell cycle-associated antigen Ki-67 with monoclonal antibody (MAb) MIB-1 and for retinoblastoma (RB) protein with two polyclonal antisera in 24 parathyroid carcinomas and 35 adenomas, which were formalin fixed and paraffin embedded to determine if these antibodies could assist in distinguishing between carcinomas and adenomas. In addition, 10 cases of parathyroid hyperplasia and 5 cases of normal parathyroids were examined as control tissues. The Ki-67 labeling index was significantly higher in parathyroid carcinomas compared to adenomas (7.1 +/- 1.0% vs 2.4 +/- 0.2%, p <0.001). No patient with a parathyroid adenoma, parathyroid hyperplasia, or normal parathyroid gland had a Ki-67 labeling index >5.3%. Analysis of the primary tumors from patients with recurrent carcinomas and from those with nonrecurrent carcinomas showed a higher mean Ki-67 labeling index (7.8 +/- 1.5% vs 5.2 +/- 1.1%) in the former group. Although these differences were not statistically significant, the RB protein immunoreactivity was not useful in distinguishing between parathyroid carcinomas and adenomas in paraffin-tissue sections. These results indicate that nuclear immunoreactivity for the cell cycle-associated antigen Ki-67 may be another useful method to assist in distinguishing parathyroid carcinomas from adenomas.

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