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Biomedical subjects

P H Wang

Publications and source records attributed to P H Wang.

At least 19 recordsLinked to original sources

Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats.

Sprague-Dawley rats with unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine showed marked decrease in the expression of dopamine D1 and D2 receptors in the prefrontal cortex. Simvastatin (10 mg/kg/day for 4 weeks) restored receptor expression to control levels. Given the association of dopaminergic dysfunction in the prefrontal cortex and cognitive deficits in Parkinson's disease, these findings may have implication in the treatment of cognitive decline in advanced Parkinson's disease.

Animals↗

The effect of dietary docosahexaenoic acid on the expression of porcine lipid metabolism-related genes.

To study the effect of dietary docosahexaenoic acid (DHA) on the expression of adipocyte determination and differentiation-dependent factor 1 (ADD1) mRNA in pig tissues, weaned, crossbred pigs (30 d of age) were fed either 2% (as-fed basis) tallow or DHA oil for 18 d. Body weight of the pigs was not affected by different dietary fatty acid (FA) compositions. The plasma and liver FA composition reflected the composition of the diet. The adipose tissue and skeletal muscle FA composition only partially reflected the diet, indicating either a slower FA turnover or that a greater proportion of the FA in these tissues is from endogenous FA synthesis. The ADD1 is an important transcription factor that modulates transcription of FA synthase to regulate the endogenous FA synthesis in the liver and adipose tissue. The ADD1 mRNA was decreased (P < 0.05) in the liver of DHA-treated pigs compared with that of the tallow-treated pigs. The diets did not have an effect on the ADD1 mRNA in pig adipose tissue. The ADD1 transcript was not detected in pig skeletal muscle. These results indicate that significant enrichment of liver DHA content inhibits the expression of ADD1 mRNA. Such an effect is similar to that reported in porcine differentiating adipocytes cultured with DHA. The liver and muscle acyl CoA oxidase mRNA concentration was increased (P < 0.05) by DHA oil treatment, suggesting that DHA treatment may increase peroxisomal fatty acid oxidation in these two tissues. Our present observations demonstrate that dietary DHA enrichment not only affects tissue DHA concentration but also mildly modifies the expression of genes related to fatty acid metabolism in the porcine liver and skeletal muscle.

Acyl-CoA Oxidase↗

Androgens and ovarian cancers.

Ovarian cancer is one of the most lethal malignancies in women. Numerous studies indicate that the steroid hormones have been implicated in the etiology and/or progression of epithelial ovarian cancer and support a role for androgens, including: 1) androgen receptor (AR) is present in primate ovaries at almost all stages of the menstrual cycle and involve folliculogenesis and ovulation; 2) high androgen serum levels show high risk of ovarian cancer and ovarian cancer occurring after menopause when the balance of ovarian steroid production shifts from estrogens to androgens; 3) ovarian cancer tissue shows a 90% AR positive rate and is associated with favorable outcomes; 4) androgens promote or inhibit ovarian cancer cell growth; 5) chemotherapy decreases androgen production from cancer cells. This review seeks to summarize our current understanding about the roles of androgens, AR and AR coregulators in the initiation and/or progression of ovarian cancers.

Androgen Antagonists↗

Is direct large loop electric excision for the transformation zone reasonable in the investigation of high-grade squamous intraepithelial lesions in cervical smears?

PURPOSE OF INVESTIGATION: To evaluate women with cytological high-grade squamous intraepithelial lesions (HGSIL) who received standard colposcopic evaluation and direct diagnostic large loop electric excision for the transformation zone (LLETZ) to determine the feasibility of using LLETZ alone (ie, skipping the colposcopic examination). METHODS: From May 1999 to May 2001, 70 women, with the mean age of 49.58 years (range, 20-82 years) and with cervical HGSIL categorized by the Bethesda system were all evaluated by colposcopic evaluation and LLETZ. Cases with a satisfactory colposcopy examination were classified as group A and those with an unsatisfactory colposcopy examination were classified as group B. "Over-treatment" was determined if the women did not need further LLETZ for evaluation or management. "Under-treatment" was determined if treatment might be potentially inadequate or invasive cancer could be ruled out during a satisfactory colposcopic evaluation. RESULTS: Group A consisted of ten women who were evaluated satisfactorily by colposcopy and group B consisted of 30 women who were not evaluated satisfactorily by colposcopy. Overall 8.6% of the patients (6/70) were considered "over-treated". The rate of over-treatment was 10.0% (4/40) in group A compared with 6.7% (2/30) in group B. In contrast, overall 10% of the patients (7/70) were considered "under-treated". The rate of under-treatment was 10% (1/40) in group A compared with 10% (3/30), in group B. The positive predictive values of group A and B were 90.6% and 88.0%, respectively. The negative predictive values were 33.2% and 40%, respectively. CONCLUSION: Direct diagnostic and therapeutic LLETZ for the management of cervical HGSIL may be a better alternative to colposcopy. This method of treatment avoids the possibility of under-treatment and is associated with an acceptable over-treatment rate, especially for postmenopausal women with cytological HGSIL. LLETZ has a good diagnostic accuracy with minimal morbidity and, most importantly, may help reduce patient anxicty, although further studies are needed to directly examine this effect.

Adult↗

Use of polymerase chain reaction to detect the soft rot pathogen, Pythium myriotylum, in infected ginger rhizomes.

AIMS: The aims are to establish a polymerase chain reaction (PCR)-based method for detecting Pythium myriotylum in the rhizome of ginger and diagnosing ginger soft rot and screening health seed ginger. METHODS AND RESULTS: A booster PCR method was established for detection of P. myriotylum using a specific primer selected from rDNA ITS1 region coupled with universal primer ITS2. It successfully applied to the detection of P. myriotylum in naturally infected ginger rhizomes but not from DNA of ginger rhizomes collected from field without target fungus. CONCLUSIONS: A specific method for detecting P. myriotylum was achieved. SIGNIFICANCE AND IMPACT OF THE STUDY: The new PCR method has allowed us to monitor ginger for the presence of P. myriotylum as a way of disease diagnosis or healthy seed ginger examination.

Zingiber officinale↗

Detection of the low-germination-rate resting oospores of Pythium myriotylum from soil by PCR.

AIMS: To establish a sensitive and specific polymerase chain reaction (PCR)-based method for detecting Pythium myriotylum in soils. METHODS AND RESULTS: Oospores of P. myriotylum were separated from large soil particles by flotation in sucrose solution. The thick-walled oospores were disrupted by vortex with sea sand and its DNA was extracted by the Cetyl trimethyl Ammonium Bromide (CTAB) method. The recovered DNA was verified by PCR amplification of a 150-bp target sequence of P. myriotylum. Samples of 10 g of soil were assayed; thus, the detection limit by PCR-based method was 10 oospores per gram soil. The method was successfully applied for the detection of P. myriotylum in soils collected in March, prior to planting of ginger crops. CONCLUSIONS: A PCR-based method for detecting P. myriotylum from soil was achieved. SIGNIFICANCE AND IMPACT OF THE STUDY: The PCR method has allowed us to monitor the presence of P. myriotylum in soil prior planting season as a way of reducing or eliminating disease.

DNA, Fungal↗

Species-specific PCR primers for Pythium developed from ribosomal ITS1 region.

AIMS: To develop a specific method for distinguishing and detecting Pythium species. METHODS AND RESULTS: Twenty PCR primers were designed from the sequences of the rDNA internal transcribed spacer 1 (ITS1) region from 34 Pythium species. The specificity of these forward primers paired with ITS2 or ITS4 and reverse universal primers was tested. Five species-specific primers were obtained, other primers showed different specificity to Pythium species. The specific amplifications enabled nine Pythium species to be differentiated. Specific detection of Pythium aphanidermatum from infested plants and P. dimorphum from soil was demonstrated. CONCLUSIONS: A method for identifying nine Pythium species using specific PCR amplification was achieved. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its rapidness and ease, the results of PCR amplified with different primers can be a powerful method for identifying Pythium species and detecting or monitoring the target fungus directly from plant material, soil and water samples.

Base Sequence↗

Detection of HPV infection by analyzing the changes in structure of peripheral blood lymphocytes specifically induced by HPV E7 antigen.

PURPOSE: Detection of human papilloma virus (HPV) infection in clinical practice was examined based on the observation that peripheral blood lymphocytes exposed in vitro to antigenic or mitogenic stimulation change their intracellular structures as measured by polarization of fluorescent light emitted by labeled cells. MATERIALS AND METHODS: A total of 47 women were enrolled in this study. They were classified into four groups based on the results of HPV-DNA detection in cervical tissues by the Hybrid Capture II kit (Digene, Gaithersburg, MD, USA) and pathological examination. Ten women with no HPV-DNA detection were used as a normal control group. Fifteen women without pathological diagnosis in the cervical tissues had HPV-DNA detection. Ten women with CIN lesions had 80% HPV-DNA detection. Twelve women with invasive squamous cell carcinoma had 100% HPV detection. Peripheral blood lymphocytes derived from all women were collected and then exposed to HPV-E7 antigen and PHA mitogen. RESULTS: The positive response rate of HPV-E7 antigen was ten percent (1/10) in the normal control group, 73.3% (11/15) in the HPV infectious women, 50% (5/10) in the CIN women, and 91.7% (11/12) in the cervical cancer patients. The overall sensitivity rate of blood tests was 77.1% and the specificity rate was 57.8% when the Hybrid Capture II HPV Test kit was used as the standard detection method for cervical tissue. CONCLUSIONS: The results showed that peripheral blood lymphocytes derived from patients with cervical lesions might be another choice to be used as a screening method to detect HPV infection compared with conventional methods.

Carcinoma, Squamous Cell↗

Tamoxifen-induced endometrial cancer.

OBJECTIVE: Tamoxifen-induced endometrial changes in postmenopausal women with breast carcinoma are well-known. Due to the popularity of postoperative chemotherapy for breast cancer, chemotherapy-induced early menopause in women with breast cancer on tamoxifen treatment needs more attention, because these women have higher risk for endometrial cancers than premenopausal women. SUBJECT: From May 1995 to May 1997, three premenopausal women aged 46, 43, and 39 with breast cancer were treated in our center. All patients received standard surgery for their breast cancers followed by six courses of adjuvant chemotherapy and 5-year tamoxifen treatment. All patients were regularly followed-up at the Breast Cancer Center and evaluated annually at the gynecological clinics including pelvic examination, Pap smear and transvaginal sonography. RESULTS: All patients became menopausal after six courses of chemotherapy ranging from three months to 14 months. The endometrial cancers occurred at 36 months, 28 months, and 33 months, respectively, after initial treatment for the breast cancers. Their last gynecologic examinations performed at six months, eight months and five months before the diagnosis of endometrial cancer showed nothing remarkable. Only one patient complained of vaginal spotting before diagnosis and the other two patients only complained of increasing purulent vaginal discharge. All patients received standard treatment for endometrial cancer and none of them died of their disease but one patient died of recurrent breast cancer 52 months later. CONCLUSION: Women with breast cancer on tamoxifen treatment need more attention and frequent evaluation of their reproductive organs, especially postmenopausal (either spontaneous or chemotherapy induced) women, although the American College of Obstetricians and Gynecologists (ACOG) comments that no more than annual pelvic exams with Pap smears are needed in asymptomatic women.

Adult↗

Both TPA and SCC-Ag levels are prognostic even in high-risk stage Ib-IIa cervical carcinoma as determined by a stratification analysis.

OBJECTIVE: To determine the prognostic values of tissue polypeptide antigen (TPA), squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen (CEA) in the sera of cervical carcinoma patients, especially in those with a poor prognosis. METHODS: In this retrospective study, the preoperative serum SCC-Ag, TPA, and CEA were analyzed in 779 patients with cervical squamous cell carcinoma of stage Ib-IIa who received radical hysterectomy and pelvic lymph node dissection (RAH-PLND) between 1984 and 1994. RESULTS: Due to poor predictive value and poor correlation between serum CEA and clinico-pathological factors, CEA was abandoned in this study. Elevated TPA and SCC-Ag levels, pelvic lymph node metastasis (PLNM), lymphvascular space involvement (LVSI) and deep stromal invasion (DSI) were associated with poor survival time by univariate analysis. The correlation study showed that elevated serum TPA was significantly related to PLNM, LVSI, and DSI (p = 0.004, 0.008, and 0.021, respectively), and SCC-Ag was related to PLNM and bulky tumor size (p = 0.001 and 0.02, respectively). In the multivariate analysis, only PLNM and LVSI remained independently significant indicating poor survival. Further stratification studies by PLNM and LVSI showed that elevated TPA levels could even indicate higher recurrence rates in patients with PLNM (p = 0.045), as well as SCC-Ag in patients with LVSI (p = 0.038). CONCLUSIONS: The results suggest that both elevated TPA and SCC-Ag levels depicting poor prognosis in stage Ib-IIa cervical SCC, especially indicates a group of high-risk patients who may need more aggressive therapy.

Adult↗

Intraperitoneal cancer spread after laparoscopic cystectomy for mature teratoma with malignant transformation.

Laparoscopic surgery for ovarian dermoid cysts has been accepted. However, its potential limitations should be considered, including technique difficulty, intraoperative tumor spillage and malignant transformation. We report a case of ovarian dermoid cysts with malignant transformation that was initially treated using laparoscopic cystectomy, but was complicated by intraperitoneal tumor dissemination.

Adult↗

Radioimmunodetection of cervical carcinoma xenografts with (111)In-labeled MAb Cx-99 detected by a hand-held gamma detector.

PURPOSE: To establish a radioimmunodetection (RAID) system for localization of cervical cancer by labeling 111-indium ((111)In) to a monoclonal antibody against cytokeratin 19 (MAb Cx-99), and detecting it with a hand-held gamma detector in an animal model. METHODS: MAb Cx-99 was labeled with 111-Indium by the DTPA chelating method. From the second day to the seventh day after injection of this immunoconjugate into athymic nude mice bearing cervical cancer cell line CC7T xenografts, the biodistribution ratios of tumor and non-tumor radioactivity were detected by a hand-held gamma detector. Data were also correlated with the data detected by the conventional gamma counter. RESULTS: The labeling efficiency of this (111)In-labeled MAb Cx-99 and (111)In-labeled MOPC was 91.6% and 95.5%, respectively. After injection, the liver, kidney and lung were initially noticed to have high radioactivity, but the localization of tumor/tissue ratios increased progressively as time passed, indicating the effect of delayed detection for distinguishing tumor from non-tumor tissues. Except for the spleen, the range of tumor/tissue ratios was 1.18-32.7 and 1.14-39.35 for the fourth day and the seventh day, respectively. The tumor/spleen ratio remained low until the seventh day after injection, thus indicating that the spleen might have a different excretion rate. CONCLUSION: This study indicated the feasibility of a hand-held detection system in the localization of cervical cancer after injection of (111)In-labeled MAb Cx-99. The effect of delayed detection was obvious by the decreasing high bindings in the liver, spleen and kidney, with the applicable detection time being four to seven days after injection.

Animals↗

Different enzyme activities of sialyltransferases in gynecological cancer cell lines.

PURPOSE: Due to rarity of a relationship between sialyltransferase enzyme activities and gynecological cancers, we arranged the study to evaluate sialyltransferase enzyme activity in the various kinds of gynecological cancer cell lines. METHODS: Ten cell lines from various kinds of gynecological cancers and two cell lines from normal tissue were enrolled in this study. The activities of each subtype of sialyltransferases were detected using Gal beta1,3GalNAc-acetyl-lactosamine)-Obz1 (acceptor for ST2,3Gal I), Gal beta1,3GlcNAc beta1,3Gal beta1,4GlcNAc (acceptor for ST2,3Gal III), Gal beta1,4GlcNAc (acceptor for ST2,3Gal IV), asialo-bovine submaxillary mucin (acceptor for ST2,6GalNAc I), asialo-fetuin (acceptor for STalpha2,6GalNAc II), and fetuin (acceptor for ST2,6GalNAc III), respectively. The amounts of sialic acids were measured using fluorescein-conjugated Sambucus nigra agglutinin (SNA) specific for alpha2,6-sialic acids and fluorescein-conjugated Maackia Amurensis agglutinin (MAA) specific for alpha2,3-sialic acids. RESULTS: The activities of two sialyltransferase subtypes, ST3Gal I & ST6GalNAc II, were significantly higher in nearly all cell lines. More specifically, cervical cancer cell line-ME 180, ovarian cancer cell line-ES-2, and choriocarcinoma cell line-BeWo showed high levels of ST3Gal I enzyme activity; all gynecological cancer cell lines except endometrial cancer cell line-RL95-2 had high levels of ST6GalNAc II enzyme activity when compared with a normal control cell line--fibroblast cell line (CCD-966Sk). Cell lines tested in this study have diverse levels of surface alpha2,6-sialic acid sugar chains (enhanced SNA binding) when compared with alpha2,3-sialic acid sugar chains (enhanced MAA binding) but we found that some cell lines such as Ca Ski (cervical cancer cell line), CC7T (cervical cancer cell line), PA-I (ovarian cancer cell line), and BeWo showed significantly altered cell surface alpha2,6-sialic acid sugar chains. CONCLUSION: Increasing enzyme activity of ST3Gal I and ST6GalNAc II might be important in various kinds of gynecological cancers. More specifically, enhanced activity of sialyltransferases involving alpha2,6-sialic acid sugar chains might be more important in cancer development. Future studies will investigate whether the enzyme activity of these sialyltransferases can be helpful for clinical practice.

Female↗

Correlation of three-dimensional tumor volumetry with cervical cancer prognostic parameters.

OBJECTIVE: Estimation of tumor size by a single diameter is used in the current Federal International Gynecology Oncology (FIGO) cervical cancer staging system. However, the role of three-dimensional volumetry is rarely mentioned. In this study, three kinds of tumor volume estimations were performed and the relationship of these volume estimations among associated cervical cancer prognostic parameters were evaluated. METHODS: Thirty patients with newly diagnosed cervical cancer at Taipei Veterans General Hospital were enrolled in the study. Final pathology and associated parametric information was obtained by chart review. The original magnetic resonance (MR) image was reappraised by an experienced radiologist and the tumor volume was estimated using either three axial measurements or the longest axial measurement. The corresponding three-dimensional (3-D) volume was calculated by the integration of lesion areas in different images using volumetric software developed by engineers at National Central University, Taiwan. All data were analyzed separately for correlation with clinical staging, histological differentiation, pelvic lymph node metastasis and survival status. RESULTS: A statistically significant difference in tumor volume estimates was found between 3-D-integration and one-dimensional estimates among tumors with lymph nodes metastasis, cell differentiation and parametrial involvement. CONCLUSION: This study found that the parameters of lymph node metastasis, parametrial involvement and tumor differentiation are volume-dependent. 3D-tumor volumetry showed superior discrimination of these parameters compared to current single diameter evaluation suggesting its potential as a rapid method for initial prediction of prognostic factors in cervical cancer.

Adult↗

Sialyltransferase family members and cervix squamous cell carcinoma.

Sialic acids including a number of their derivatives are ubiquitous at the terminal positions of the oligosaccharides of glycoproteins. The transfer of sialic acids from cystidine-5-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to the terminal position of the carbohydrate group of glycoproteins and glycolipids is catalyzed by a family of sialyltransferases (STs). There is a large body of evidence to suggest that tumor cells have altered surface properties from their normal counterparts, and that these changes are partially due to altered sialo-glycoconjugates expressed on the plasma membrane and that altered sialylation (change in glycoprotein expression), which occurs during certain pathological processes, such as oncogenic transformation, tumor metastases, and invasion, is associated with enhanced ST activity. In this report we attempt to review the important findings in studing sialyltransferases of cervix squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Developing a strategy to define the effects of insulin-like growth factor-1 on gene expression profile in cardiomyocytes.

Insulin-like growth factor (IGF)-1 activates intracellular signaling pathways and regulates myocardial structure and function. This study used DNA microarray to define the effects of IGF-1 on gene expression in cardiomyocytes. Despite DNA microarray becoming a popular tool for profiling gene expression, the specificity of DNA microarray results is rarely addressed. Our data showed that the specificity of a DNA microarray study can be increased by repetitive experiments and by excluding minimally expressed genes. In this study, the false-positive rates were reduced to <0.2%. Future DNA microarray studies should incorporate a proper strategy to minimize false-positive results. IGF-1 modulates the expression of genes in 17 functional categories, but most genes clustered around the regulation of intracellular signaling, cell cycle, transcription/translation, cellular respiration and mitochondrial function, cell survival, ion channels and calcium signaling, and humoral factors. To further explore whether extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI) 3 kinase specifically regulate different sets of genes, the effects of IGF-1 were inhibited with PD98059 or LY294002. The results showed that the majority of genes regulated by IGF-1 required activation of both ERK and PI 3 kinase. Thus, PI 3 kinase and ERK coordinately mediate the transcriptional regulatory effects of IGF-1 in cardiac muscle cells. These findings provide novel insight into how IGF-1 signaling modulates the programming of cardiac muscle gene expression.

Animals↗

Overexpression of 12-lipoxygenase causes cardiac fibroblast cell growth.

Evidence suggests that leukocyte type 12-lipoxygenase (12-LO) plays an important role in cell growth. However, the role of 12-LO in cardiac cell growth has not been tested. We have now stably overexpressed 12-LO cDNA in rat fetal cardiac fibroblasts to evaluate the role of the 12-LO pathway in cardiac cell growth. Overexpression of 12-LO increased cell [(3)H]leucine incorporation by 2.1+/-0.1-fold (P<0.01) and cell protein content by 2.2+/-0. 3-fold (P<0.01) over mock-transfected cells. These findings were confirmed in additional clones. Baicalein, a 12-LO enzyme inhibitor, dose-dependently inhibited serum-induced leucine incorporation in cardiac fibroblast cells as well as partially inhibited leucine incorporation in cells overexpressing 12-LO. 12-LO overexpression also caused cell [(3)H]thymidine incorporation to increase by 3.4+/-0.3-fold (P<0.01). Cell flow cytometry analysis showed that the size of 12-LO-overexpressing cells was markedly enlarged compared with that of mock-transfected cells. The fibronectin content of the 12-LO-overexpressing cardiac fibroblasts was also significantly increased. We next evaluated the effects of 12-LO RNA overexpression on kinase pathways linked to cellular growth. The overexpression of 12-LO enhanced extracellular signal-regulated kinase activity (4. 1+/-0.5-fold), c-Jun NH(2)-terminal kinase activity (2.9+/-0.5-fold), and p38 mitogen-activated protein kinase activity (2.2+/-0.3-fold). Pretreatment with SB202190 (100 nmol/L), a specific inhibitor of p38, prevented the increases in protein content of 12-LO-overexpressing cardiac fibroblast cells. These data clearly demonstrate that the overexpression of 12-LO causes cell growth of cardiac fibroblasts, thus supporting the role of 12-LO as a novel growth-promoting pathway in the heart.

Animals↗