Biomedical subjects

Kevin Holcomb

Publications and source records attributed to Kevin Holcomb.

4 recordsLinked to original sources

PubMed2005

Hormonally active nontransformed human ovarian cell culture from oophorectomy specimens: methods of development and initial characterization.

We repeatedly established a nontransformed steroidogenically active human ovarian cell culture derived from oophorectomy specimens. The cells maintained steroidogenic activity for 3-5 passages (6-8 weeks) and responded to stimulation by insulin and gonadotropin. With pregnenolone as substrate, LH stimulated progesterone production up to 124% and FSH up to 121%. Insulin alone stimulated progesterone production up to 135%, in the presence of LH up to 191%, and in the presence of FSH up to 170%. With dehydroisoandrosterone (DHA) as substrate, insulin alone stimulated testosterone production up to 117%, and in the presence of LH (but not FSH) up to 125%. With androstenedione as substrate, insulin alone stimulated estradiol production up to 133%, FSH alone up to 188%, and LH with insulin up to 217%. With progesterone as substrate and in the presence of LH (but not FSH), 17-alpha-hydroxylase activity was stimulated up to 131%. With DHA as substrate and in the presence of LH, 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) activity was stimulated up to 139%. With androstenedione as substrate, insulin alone stimulated aromatase activity up to 202%, LH up to 208%, and FSH up to 251%. Under the same conditions, in the presence of LH and insulin, aromatase activity was stimulated up to 342%, and in the presence of FSH and insulin, up to 318%. With testosterone as substrate, insulin alone stimulated aromatase activity up to 122%. With testosterone as substrate, in the presence of LH and insulin, aromatase activity was stimulated up to 136%, and in the presence of FSH and insulin, up to 156%. Immunocytochemistry studies directly confirmed presence of aromatase and 3-beta-HSD in these cultured cells. We conclude that a steroidogenically active nontransformed long-term human ovarian cell culture can be repeatedly established from oophorectomy specimens, providing uninterrupted supply of cultured human ovarian cells for a variety of studies of ovarian physiology.

3-Hydroxysteroid Dehydrogenases↗

PubMed2005

Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production.

CONTEXT AND OBJECTIVE: Hyperinsulinemia contributes to the pathogenesis of ovarian dysfunction in insulin-resistant states, including polycystic ovary syndrome (PCOS). Peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists [thiazolidinediones (TZDs)] ameliorate hyperandrogenism in polycystic ovary syndrome presumably because they reduce systemic hyperinsulinemia. Direct effects of TZDs in the ovary, however, cannot be excluded. We explored direct effects of TZDs in cultured human ovarian cells. METHODS: Human ovarian cells, obtained from oophorectomy specimens, were cultured in the presence or absence of rosiglitazone or pioglitazone, insulin, and gonadotropins. Steroid hormone and IGF-binding protein-1 (IGFBP-1) concentrations were measured in conditioned tissue culture medium. RESULTS: Rosiglitazone or pioglitazone stimulated progesterone production up to 156% (P < 0.001) and 131% (P < 0.001) of baseline, respectively. Pioglitazone but not rosiglitazone, inhibited baseline and FSH-stimulated estradiol production by 20% (P < 0.001) and 50% (P < 0.001), respectively. Both rosiglitazone and pioglitazone abolished insulin-dependent stimulation of estradiol production in the presence of FSH. Rosiglitazone and pioglitazone inhibited testosterone production by 10% (P < 0.012) and 15% (P < 0.023), respectively, and abolished insulin-induced stimulation of testosterone production. In the absence of insulin, pioglitazone or rosiglitazone stimulated IGFBP-1 production up to 160% (P < 0.001) and 125% (P < 0.036) of baseline, respectively. Pioglitazone and rosiglitazone enhanced insulin-induced inhibition of IGFBP-1 production by 13% and 20%, respectively (P < 0.001). CONCLUSIONS: PPAR-gamma agonists directly stimulate progesterone and IGFBP-1 production, inhibit estradiol and testosterone production, abolish insulin-induced stimulation of testosterone production and insulin-dependent stimulation of estradiol production in the presence of FSH, and enhance insulin-induced inhibition of IGFBP-1 production in human ovarian cells. PPAR-gamma represents a novel system of ovarian regulation.

Adult↗

PubMed2005

Cervical cancer screening.

Cervical cytology has proved to be one of the most successful examples of cancer screening and has resulted in significant decreases in incidence and mortality from invasive cervical cancer in regions in which comprehensive programs have been instituted. A standardized system of reporting abnormal cervical cytology, the Bethesda System has been developed and revised to reflect our current understanding of HPV-related precancers. The Pap smear has been the backbone of cervical cancer screening programs in North America over the past five decades; however, recent advances, including liquid-based cytology, HPV typing, and direct visualization techniques, are proposed to address the inherent weaknesses of cytologic screening in women who are screened. The problem of unscreened and underscreened women exists and accounts for most cases of invasive cancer. Widespread screening hopefully one day will lead to a significant decrease in the mortality of cervical cancer, the second most common female malignancy worldwide. Another means of preventing this disease involves HPV vaccines, which are in development but are not ready for use outside of a clinical trial.

Colposcopy↗

PubMed2002

E-cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium.

OBJECTIVE: To compare the frequency and pattern of E-cadherin expression in endometrioid, papillary serous, and clear cell carcinomas of the endometrium. METHODS: E-cadherin expression was examined in 76 endometrial carcinomas by immunohistochemistry using a monoclonal antibody to E-cadherin and was correlated with poor prognostic indicators such as depth of myometrial invasion, lymph node status, and intraperitoneal spread. The frequency of expression was compared between endometrioid, papillary serous, and clear cell carcinomas by the Fisher exact test. Logistic regression was used to examine the simultaneous effect of histological type and tumor grade on E-cadherin expression. RESULTS: Sixty-three endometrioid, nine papillary serous, two clear cell, and two carcinomas of mixed histology were examined. E-cadherin negative tumors were more likely to be poorly differentiated (P <.01), have cervical extension (P =.02), have positive peritoneal cytology (P <.01), and have adnexal spread (P =.01) when compared with E-cadherin positive tumors. Papillary serous and clear cell carcinomas were significantly less likely to express E-cadherin than endometrioid carcinoma (38% versus 95%, P <.001). Tumor grade and histological type were identified as significant predictors of E-cadherin expression in univariable analysis; however, only histological type remained significant in multivariable analysis (P =.01). When grade was controlled, endometrioid carcinoma remained 23 times more likely to express E-cadherin than papillary serous and clear cell carcinomas. CONCLUSION: Papillary serous and clear cell carcinomas are significantly less likely to express E-cadherin than endometrioid tumors. This difference may account for the more aggressive behavior of papillary serous and clear cell carcinomas.

Adenocarcinoma, Clear Cell↗