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Biomedical subjects

V V Baker

Publications and source records attributed to V V Baker.

At least 19 recordsLinked to original sources
PubMed2003

Inhibition of paclitaxel-induced apoptosis by the specific COX-2 inhibitor, NS398, in epithelial ovarian cancer cells.

OBJECTIVE: In vitro studies have revealed that treatment of various human cancer cell lines with specific cyclo-oxygenase 2 (COX-2) inhibitors induces apoptotic cell death. It is currently proposed that the combination of COX-2 inhibitors with chemotherapeutic agents improves the efficacy of cancer treatment. MATERIALS AND METHODS: In this study we sought to determine the effects of combining paclitaxel and the COX-2 inhibitor NS398 on apoptosis of epithelial ovarian cancer (EOC) cells. Two EOC cell lines, SKOV3 and MDAH2774, were exposed to increasing concentrations of paclitaxel (0.1, 10, and 100 microM) and NS398 (10, 100 microM) as well as a combination of both drugs. Apoptosis was evaluated by the Tunel assay. The fluorescein-labeled DNA was visualized directly by fluorescence microscopy and quantitated by flow cytometry. RESULTS: While NS398 did not significantly alter apoptosis of either EOC cell lines after 24 h of continuous exposure, treatment of both cell lines with paclitaxel resulted in a significant increase in the rate of apoptosis (60-70%). Concomitant treatment of both SKOV3 and MDAH2774 cells with paclitaxel and NS398 resulted in marked impairment of paclitaxel-induced apoptosis. Similarly, sequential treatment during which both cell lines were treated with NS398 for 4 h, triple-washed, and then exposed to paclitaxel for 24 h resulted in a significant inhibition of paclitaxel-induced apoptosis. Similar inhibition was seen when NS398 was replaced by aspirin. CONCLUSIONS: Combining COX-2 inhibitors and paclitaxel does not have an additive or synergistic tumoricidal effect. On the contrary, NS398 treatment markedly inhibited the apoptotic effects of paclitaxel in each of these two EOC cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[Synergistic efficacy of adenovirus-mediated bcl-Xs gene therapy and cisplatin in ovarian cancer cell].

OBJECTIVE: To observe the presence of synergistic efficacy between adenovirus-mediated bcl-Xs (Adv-bcl-Xs) gene therapy and cisplatin (CDDP) in ovarian cancer cell. METHODS: NuTu-19 cells were infected by different titers of Adv-bcl-Xs and treated with CDDP in the meantime. Percentage of cell proliferation was measured by methyl thiazolyl tetrazolium and cell cycles were measured by flow cytometry 3 days later. Graphical representations of the statistical analyses for their interaction in tumor cells. RESULTS: The statistical results and Graphical representations of the statistical modeling showed that the synergistic antiproliferative activity was present (P < 0.01). CONCLUSION: There was synergistic efficacy between Adv-bcl-Xs gene and CDDP for the inhibition of ovarian cancer cell.

Adenoviruses, Human↗
PubMed1998

Transforming growth factor-alpha and insulin-like growth factor-I, but not epidermal growth factor, elicit autocrine stimulation of mitogenesis in endometrial cancer cell lines.

OBJECTIVES: Endometrial carcinoma cell lines were evaluated for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor I (IGF-1) production and for autocrine stimulation. METHODS: Conditioned, serum-free media (CM) from cell lines RL95-2, KLE, HEC, and Ishikawa (ISH) were concentrated radioimmunoassayed (RIA). Samples for the IGF-1 assay were extracted with acid-ethanol to remove IGF-1 binding protein. Polymerase chain reaction (PCR) was used to validate the presence of mRNA for growth factors and receptors. Cells were incubated with Ab528, an antibody blocking EGF receptors, and alphaIR3, an antibody blocking IGF-1 receptors. Proliferation was quantified using [3H]thymidine incorporation. RESULTS: TGF-alpha was detected in CM: RL95-2 (0.4 +/- 0.001 ng/ml), KLE (0.7 +/- 0.003 ng/ml), HEC (0.8 +/- 0.01 ng/ml), ISH (1.2 +/- 0.05 ng/ml). No EGF was detected in CM. In extracted samples, IGF-1 was detected in CM: RL95-2 (0.8 +/- 0. 03 ng/ml), KLE (1.25 +/- 0.02 ng/ml), HEC (1.6 +/- 0.01 ng/ml), ISH (1.6 +/- 0.08 ng/ml). Unconditioned media served as the control. EGF, TGF-alpha, and IGF-1 mRNA was identified in all cell lines, as was the mRNA for EGF and IGF-1 receptors. Incubation with Ab528 or alphaIR3 resulted in significant inhibition of DNA synthesis in HEC 1A, KLE, and ISH. No inhibition was detected in the RL95-2 cell line. A control antibody did not inhibit the cell lines. CONCLUSION: Autocrine production and stimulation of endometrial carcinoma cell lines by TGF-alpha and IGF-1 are demonstrated in three of four endometrial cancer cell lines. No measurable EGF was produced by any of the cell lines.

Autocrine Communication↗
PubMed1997

Transforming growth factor-beta negatively modulates proliferation and c-fos expression of the human endometrial adenocarcinoma cell line HEC-1-A.

Growth factor regulation of normal and cancerous cell proliferation has been well-documented and may be mediated by proto-oncogene activity. The purpose of this study was to assess changes in proliferation and mitogen-induced c-fos mRNA expression of an endometrial carcinoma cell line, HEC-1-A, in response to TGF-beta, a potent growth-inhibitory peptide. HEC-1-A cells were incubated in the presence or absence of TGF-beta. Mitogen-stimulated cells were additionally treated with epidermal growth factor (EGF). Changes in proliferation were measured by [3H]thymidine uptake assays. Alterations in EGF-induced c-fos expression following TGF-beta pretreatment were assessed by Northern blot using a 32P-labeled human c-fos probe. Finally, chloramphenicol acetyltransferase assays were performed to evaluate c-fos promoter activity in response to treatment conditions. Basal and EGF-stimulated proliferation was inhibited by TGF-beta in a dose- and time-dependent manner. TGF-beta also reversibly decreased EGF-induced c-fos mRNA expression in a dose- and time-dependent manner. Sequences in the c-fos promoter that were stimulated by EGF showed suppressed activity when preincubated with TGF-beta. These results show that TGF-beta negatively modulates EGF-induced c-fos expression, which may be related to the observed inhibition of carcinoma cell proliferation.

Adenocarcinoma↗
PubMed1997

Molecular profile of advanced-stage transitional cell carcinoma of the ovary.

OBJECTIVES: Our purpose was to determine the molecular profile of advanced-stage transitional cell carcinoma in terms of immunostaining for p53, epidermal growth factor receptor and HER-2/neu, deoxyribonucleic acid index, and S-phase fraction and to analyze the prognostic significance of these markers. STUDY DESIGN: Archival paraffin-embedded tissue blocks from 29 advanced stage transitional cell carcinomas were obtained. Selected sections of the primary tumors were immunostained for p53, epidermal growth factor receptor, and HER-2/neu; deoxyribonucleic acid ploidy and S-phase fraction were determined with use of flow cytometry. Clinical information was abstracted from the medical records. Survival times were analyzed according to the life-table methods of Kaplan and Meier, and the statistical significance of the various factors was tested with the log-rank test. The proportional hazards model of Cox was used to identify prognostic factors. RESULTS: Positive immunostaining was observed for p53 in 13 cases (45%), for epidermal growth factor receptor in 14 cases (50%), and for HER-2/neu in 19 cases (65%). Tumors were diploid in 16 cases (55%) and aneuploid in 13 (45%). The S-phase fraction was < or = 15% (mean) in 13 cases (45%) and > 15% in 16 cases (55%). The median survival for the entire group was 52 months. None of the above variables had a significant effect on survival time. CONCLUSION: Neither immunostaining for p53, epidermal growth factor receptor, and HER-2/neu nor deoxyribonucleic acid ploidy nor S-phase fraction allowed us to distinguish transitional cell carcinoma from other more common epithelial ovarian cancers. In addition, no prognostic significance was associated with these biomarkers. A study of larger numbers of cases may be more elucidative.

Adult↗
PubMed1996

Expression of estrogen receptor variants in normal and neoplastic human uterus.

Estrogen receptor variants lacking internal exons and representing dominant positive and negative activity may be involved in the initiation and/or progression of endocrine dependent tumors. To assess the role of estrogen receptor in uterine disease, we have analyzed both normal and neoplastic uterine samples for the presence of variant estrogen receptors using the sensitive technique of RT-PCR and direct automated DNA sequencing of the amplified products. Our analysis was conducted to determine the presence of spliced variants lacking exons 3 through exon 8. We demonstrate that both the normal and neoplastic human uterus contains a number of spliced variants of the estrogen receptor that co-exist with the wild type receptor. Variants lacking exons 4, 5 and 7 but not exons 3 and 6 were detected. Also, a novel partial deletion in exon 8 was detected in both the normal and neoplastic tissues, although a total deletion of this exon was not observed. In addition another region of exon 8 deletion was found to be present in one tumor tissue which also contained an insertion within this region, however, other tumors did not contain this variant. In addition, double exon deletion variants were observed lacking exons 3 and 4, exons 4 and 5, and exon 7 with part of exon 8. Although our data represents a limited number of samples it suggests that splicing of the estrogen receptor message occurs in the normal physiological setting. There does not appear to be any association between the presence or absence of spliced variants of estrogen receptor and uterine tumor formation at the mRNA level.

Adenocarcinoma↗
PubMed1996

Vulvar intraepithelial neoplasia and vulvar cancer.

Vulvar carcinoma is a rare cancer. It is more frequent among older women, but the incidence is increasing among younger women. The incidence of VIN may be rising in younger women as well. Different factors have been associated with an increased risk for vulvar cancer (HPV, age, smoking, education, diet, genital infections, infrequent pelvic examinations, socioeconomic status, immunosuppressive diseases); however, conclusive epidemiologic evidence is lacking. More studies with larger sample sizes are needed to understand more fully the role of these and other as yet unknown factors in the etiology of vulvar cancer. At present, studies of the molecular risk assessment for VIN and vulvar cancer focus mostly on HPV. The treatments for VIN are painful, and the disease has a high risk of recurrence. The treatments for vulvar cancers are morbid, even though radical vulvectomy is being replaced by the less morbid wide local excision and unilateral groin lymph node dissection. Therefore, VIN and vulvar cancer benefit from early detection, and their morbidity is decreased by early treatment. Screening should be performed by the primary care practitioner and should focus on women with HPV; women who smoke; and women who have other preinvasive disease of the cervix, vagina, or perianal area. Chemoprevention and an HPV vaccine may eventually be promising, but no studies have yet been performed. Patients should be educated about performing vulvar self-examination stopping smoking, being persistent about insisting on a biopsy if symptoms persist, and avoiding exposure to HPV.

Biomarkers, Tumor↗
PubMed1996

Vaginal intraepithelial neoplasia and vaginal cancer.

Vaginal cancer is infrequent, but the morbidity associated with treatment is high. Delays in diagnosis account for presentations in advanced stages. Screening is probably not warranted given the low incidence, but inspection of the vagina should be performed at the time of Pap smear screening. No molecular markers are currently promising. Chemoprevention with retinoids may be feasible.

Carcinoma in Situ↗
PubMed1996

Cervical intraepithelial neoplasia and cervical cancer.

Cervical cancer remains an important health problem for women worldwide, despite its decline in countries where organized screening programs are in place. The morbidity of treatment and the mortality for advanced lesions are high, a frustrating situation because the cervix is accessible and a good screening test, the Pap smear, exists. HPV is an important risk factor, and the molecular evidence for its role is overwhelming. Molecular markers may soon help us decide which lesions are at highest risk of progression to invasion and which invasive lesions are likely to recur. Chemoprevention of precursor lesions is promising. An HPV vaccine could be effective in eradicating this cancer.

Biomarkers, Tumor↗
PubMed1996

Endometrial hyperplasia and endometrial cancer.

Endometrial cancer is the most frequently seen gynecologic neoplasm, but it fortunately has low mortality, which is due largely to its presentation with abnormal bleeding and its subsequent early diagnosis. The morbidity associated with therapy for early lesions is moderate. Hyperplasia with atypia should be treated as early cancers. Many molecular markers are currently under study. Markers may soon help us identify invasive lesions at higher risk of recurring and thus more suitable for adjunct therapy. Screening in the general population is not recommended, but a high-risk group that is more suitable for screening could be identified, including obese and nulliparous women, those treated with unopposed estrogen or tamoxifen, or those with family or past histories of breast or colon cancer. Development of chemoprevention with an oral contraceptive during the reproductive years is under way, and there may be a role for chemoprevention in the reversal of hyperplasias.

Biomarkers, Tumor↗
PubMed1996

Uterine sarcoma.

Sarcomas are rare tumors with unpredictable prognosis. They are treated similarly to endometrial cancers. Little is known of epidemiologic risk factors for sarcoma; similarly, little work has been performed assessing molecular alterations in sarcomas. Because of their rarity, uterine sarcomas are not suitable for screening. Chemoprevention studies might target those at risk for recurrence or a second neoplasm.

Biomarkers, Tumor↗
PubMed1996

Ovarian intraepithelial neoplasia and ovarian cancer.

Ovarian cancer accounts for only 4% of cancers in women, but it is the leading cause of death from gynecologic malignancies in the United States. In the general population, a woman's lifetime risk of ovarian cancer is 1.4% but this risk can increase substantially in women with a strong family history of the disease. The high mortality rate from ovarian cancer is due primarily to the difficulty in detecting the disease in early stages; the disease tends to be asymptomatic until it is well advanced. The primary care physician needs to be alert to the possibility of an ovarian malignancy in all women with an intact ovary or ovaries who present with abdominal or pelvic complaints. There are no current recommendations for routine screening for ovarian cancer in the general population. Even in high-risk women, there are currently no convincing data to support extensive screening, although a number of studies looking at this issue are under way. Despite this lack of conclusive evidence, a consensus panel on ovarian cancer convened by the NIH recently issued guidelines for screening high-risk women. They recommend annual rectovaginal pelvic examination, testing of CA 125 level, and transvaginal ultrasonography. Color flow Doppler analysis of the ovarian vessels is also being studied as a possible screening modality. BRCA1 gene testing may soon play a role in women with a strong family history of the disease. Given its high mortality rate, primary prevention strategies for ovarian cancer should be used whenever possible. Oral contraceptive use appears to reduce the risk of ovarian cancer. Prophylactic oophorectomy may be suggested for women at particularly high risk of the disease. Here, too, the primary care physician can play an important role in helping a patient understand the risks and benefits of these options.

Biomarkers, Tumor↗
PubMed1996

Gestational trophoblastic disease.

GTD occurs in fewer than 1 in 1200 pregnancies in the United States, but it is much more common in Asia and Latin America, where its incidence may be as high as 1 in 200 pregnancies. Risk factors for GTD include advanced or young maternal age, low socioeconomic status, and prior hydatidiform mole. Early diagnosis and prompt treatment are key to a favorable outcome, and thus recognition of the signs and symptoms of the disease is important for all physicians. Because these diseases have low incidences and occur after reproductive events, screening for them in the general population is not worthwhile. No chemopreventive agents have yet been studied in women at risk for GTD, but the oral contraceptive is a good candidate.

Biomarkers, Tumor↗
PubMed1995

Potential criteria for cohort selection in chemoprevention trials of uterine adenocarcinoma.

Women at risk of uterine cancer include those with one or more of the following characteristics: obesity, nulliparity, late menopause, diabetes mellitus, prolonged unopposed estrogen use, and tamoxifen therapy. Risk is additionally increased by the presence of endometrial hyperplasia. The incorporation of biomarkers into the selection criteria of cohort groups at risk for developing endometrial cancer offers an innovative approach to the clinical design of chemoprevention trials of endometrial adenocarcinoma. Biomarkers that may be useful in cohort selection include nuclear morphometry, specific genetic abnormalities, and markers of proliferation and differentiation.

Adenocarcinoma↗
PubMed1995

Potential criteria for cohort selection in chemoprevention trials of epithelial ovarian cancer.

Epithelial ovarian cancer is a heterogeneous disease. Epidemiologic studies have identified risk factors for this disease including advanced age, nulliparity, history of infertility, early age at menarche, late age at menopause, and perhaps ovulation induction. Cohort selection that includes women who have potential precursor lesions and alterations of select biomarkers may prove useful in the design of chemoprevention trials of epithelial ovarian cancer. Nuclear morphometry, specific genetic alterations, and markers of proliferation and differentiation may be useful biomarkers to monitor the efficacy of specific interventions.

Biomarkers, Tumor↗
PubMed1995

Expression of apolipoprotein J in the uterus is associated with tissue remodeling.

The endometrium is a dynamic tissue that, in response to hormonal cues, undergoes cycles of growth and involution. Extracellular factors required for this remodeling are poorly understood. The potential role in endometrial turnover of apolipoprotein J (apoJ), a secretory glycoprotein that can bind lipids and membrane-active proteins, is proposed on the basis of its spatial and temporal patterns of expression during normal cycling, after ovariectomy, and in response to hormone manipulation. In the mouse, apoJ mRNA was expressed in uterine luminal and glandular epithelial cells coincident with the presence of apoJ protein. The apoJ gene was differentially expressed in the glandular and uterine luminal epithelial cells during the estrous cycle and following hormone depletion. Expression of apoJ was not induced in ovariectomized mice by estrogen, progesterone, or dexamethasone treatment alone. Progesterone administration after an initial estrogen pretreatment, however, resulted in dramatic induction of apoJ as the progesterone level declined. In contrast, apoJ was not induced when a long-lived progesterone analog, medroxyprogesterone, was substituted for progesterone. In the human menstrual cycle, apoJ was present in glandular lumens only during the late secretory phase. Declining progesterone levels, causing substantial tissue reorganization, are characteristic of the times of marked apoJ induction in uterine epithelial cells. These expression patterns are consistent with apoJ functioning as an extracellular cytoprotectant by mediating clearance of and/or neutralizing cytolytic tissue debris.

Animals↗