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Biomedical subjects

B C Sheu

Publications and source records attributed to B C Sheu.

At least 19 recordsLinked to original sources
PubMed2001

Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer.

Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN-gamma in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-beta plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-beta Abs. IL-10 and TGF-beta are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF-beta in cancer-mediated immunosuppression.

Cytokines↗
PubMed2001

A novel role of metalloproteinase in cancer-mediated immunosuppression.

Depressed immune responses have been observed frequently in cancer patients. In a variety of human malignancies, the expression of interleukin-2 receptor alpha (IL-2R alpha) on activated tumor-infiltrating lymphocytes was down-regulated. Because IL-2R alpha plays a pivotal role in the development and propagation of functional T cells, its depressed expression may result in poor function of tumor-reactive cytotoxic lymphocytes. For elucidating the mechanism responsible for down-regulation of IL-2R alpha, a coculture model of in vitro mixed autologous lymphocytes and tumor cells was established. Kinetic analysis showed that cervical cancer cells down-regulated IL-2R alpha expression on encountered T cells. The amount of IL-2R alpha mRNA in tumor-infiltrating lymphocytes-derived CD8+ T cells was compatible with that in the corresponding activated CD8+ T cells. Additional evidence showed that cervical cancer cells could induce the release of soluble IL-2R alpha expression on encountered T cells. By using protease inhibition assays we demonstrated that tissue inhibitors of metalloproteinase abrogated the cancer-mediated IL-2R alpha proteolytic process and restored the T-cell proliferation function. Immunohistochemical stainings further revealed prominent metalloproteinase (MMP) expressions, including MMP-1, MMP-2, and MMP-9, in cervical cancer tissues. Additional in vitro studies showed that MMP-9 mediates cleavage of IL-2R alpha and down-regulates the proliferative capability of cancer-encountered T cells. Our findings suggest a new role of MMPs in tumor-mediated immunosuppression and provide a possible therapeutic potential for patients with cervical cancer.

Cervix Uteri↗
PubMed2001

Importance of urodynamic study before radical hysterectomy for cervical cancer.

OBJECTIVES: The aim of this study was to characterize the urodynamic findings in patients with cervical cancer before radical hysterectomy and to correlate the results with age, parity, menopausal status, and cancer stage. METHODS: All patients with cervical cancer before radical hysterectomy who underwent urodynamic study (UDS) from January 1996 through December 1998 were enrolled. Detailed history, physical examination, and multichannel UDS data including uroflowmetry, filling and voiding cystometry, stress urethral pressure profile, and 20-min pad test were obtained for each patient. The urodynamic findings of each patient were analyzed and correlated with age, parity, menopausal status, and cancer stage. RESULTS: A total of 210 patients with cervical cancer were included in the study. The mean age was 48.9 +/- 10.5 years with a mean parity of 3.3 +/- 1.7. Forty-two percent (n = 88) of patients were menopausal, and 88% (n = 184) belonged to stage IB while 10% (n = 20) were stage IIA and 2% (n = 6) stage IIB. Urodynamic study showed that only 17% (n = 37) of the 210 patients were normal, 10% (n = 21) had voiding dysfunction, 45% (n = 94) had storing dysfunction, and 28% (n = 58) had both voiding and storing dysfunctions. In addition, 51% (n = 106) had urinary incontinence and 37% (n = 78) had genuine stress incontinence (GSI), 8% (n = 16) detrusor instability (DI), and 6% (n = 12) GSI/DI. Age, parity, and cancer stage did not show any significant differences among these four groups. CONCLUSIONS: In this series, only 17% of patients with cervical cancer had normal urodynamic findings before radical hysterectomy.

Female↗
PubMed2000

Mid-trimester beta-hCG levels incorporated in a multifactorial model for the prediction of severe pre-eclampsia.

Pre-eclampsia remains a major cause of perinatal morbidity and mortality worldwide. Proposed predicting tests for early detection of pregnant women destined to develop pre-eclampsia remain unsatisfactory. The aim of this study was to investigate the clinical utility of combining mid-trimester maternal serum beta-human chorionic gonadotrophin (MShCG) levels with selected clinical determining factors as a multifactorial predictive test for pre-eclampsia. Thirty-nine cases with mild pre-eclampsia and 56 with severe pre-eclampsia were recruited as the study groups. Normotensive women (957) were enrolled as controls. Potential determining risk factors for severe pre-eclampsia were selected using a multiple logistic regression to build various combined prediction models. A receiver-operator characteristic curve was employed to assess the performance of each prediction test for pre-eclampsia. The prediction efficacy of each test was examined by the area under the curve (AUC). Our data show that mid-trimester MShCG levels significantly correlated with severity of pre-eclampsia (Spearman rank correlation coefficient=0.195, p<0.001). Women with mild pre-eclampsia had a 2.61-times greater chance, while women with severe pre-eclampsia had a 6.13-times greater chance of having MShCG exceeding 2.0 multiples of the median than did women with a normal pregnancy. A combined prediction model composed of MShCG levels, body mass index (BMI), parity, and age as a predictive test for severe pre-eclampsia was superior to MShCG levels alone (AUC 0.765 versus 0.648). The integrated multifactorial model could identify women at risk early on for developing severe pre-eclampsia, with a sensitivity of 70% and a specificity of 71%. Thus, we demonstrate a potentially effective and convenient method by which women at risk for developing severe pre-eclampsia can be identified early, based on a multifactorial predictive model composed of midtrimester MShCG levels, BMI, parity, and age.

Adult↗
PubMed1999

Reversed CD4/CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma.

BACKGROUND: To investigate the clinical significance of tumor-infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix. METHODS: A total of 30 patients with Stage Ia-IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual-color flow cytometry. Bulky tumor was defined as tumor size >4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics. RESULTS: The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4(+) T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4(+) T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P < 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001). CONCLUSIONS: Decreased proportions of tumor-infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression.

Adenocarcinoma↗
PubMed1999

Lipoleiomyoma of the uterus.

Uterine lipoleiomyoma may associate with certain concomitant metabolic disorders. The possible clinical correlates and the potential implications on the pathogenesis are elaborated.

Female↗
PubMed1999

Comparison of treatment outcomes for imipramine for female genuine stress incontinence.

OBJECTIVE: To assess the efficacy of imipramine as a treatment of genuine stress incontinence and to explore the possible determining factors for treatment success and failure. DESIGN: A prospective study. SETTING: University department of obstetrics and gynaecology. PARTICIPANTS: Forty women with genuine stress incontinence were enrolled. METHODS: Each woman was treated with 25 mg imipramine three times a day for three months. MAIN OUTCOME MEASURES: Each woman had a 20-minute pad test and urodynamic study including uroflowmetry, both filling and voiding cystometry, and stress urethral pressure profile before and after treatment. RESULTS: After treatment, 35% (n = 14) were cured, 25% (n = 10) improved by > or = 50% and in the remaining 40% (n = 16) treatment failed. The efficacy of successful treatment was 60% (95% CI 44.8-75.2). The median age and parity, as well as menopausal status, showed no statistical differences between the two groups. The pre-treatment data including pad weight, functional urethral length, maximal urethral pressure, bladder compliance at urgency, bladder capacity, and average and maximal flow rates showed no statistical differences between the two groups except urethral closure pressure (P = 0.001). Besides, the functional urethral length and urethral closure pressure were significantly improved in the treatment success group. After medication, the median functional urethral length was 3 cm (intraquantile range [IQR] 2.3-3) in the treatment success group vs 2.3 cm (IQR 2-3) in the treatment failure group (P = 0.028). The urethral closure pressure was 77 cmH2O (IQR 61-105) for the treatment success group vs 40 cmH2O (IQR 34-53) in the treatment failure group (P < 0.0001). CONCLUSIONS: The efficacy of imipramine for genuine stress incontinence was 60% (95% CI 44.8-75.2). The pre-treatment high urethral closure pressure may serve as a predictor for treatment success.

Adrenergic Uptake Inhibitors↗
PubMed1999

T lymphocytes and cytokine production in ascitic fluid of ovarian malignancies.

The activation status of T lymphocytes and the presence of various cytokines in ascitic fluid were examined to test peritoneal immunity in women with ovarian malignancies. Peripheral blood and peritoneal fluid were collected from 12 patients with primary ovarian cancer with ascites and 27 normal control subjects during laparoscopic examination. Lymphocyte subpopulations and the expression of activation markers on T lymphocytes were analyzed by dual-color flow cytometry. The concentrations of various cytokines and soluble interleukin (IL)-2 receptor-alpha were measured. CD8 T lymphocytes were the main component of peritoneal lymphocytes. CD69 and HLA-DR, but not CD25, were highly expressed on peritoneal T lymphocytes compared to those in peripheral blood. In ascitic fluid of ovarian malignancies, CD4 T lymphocyte concentrations were further decreased, resulting in a decreased CD4/CD8 ratio. Decreased expression of CD69 and CD25 was also noted on T lymphocytes from ascites compared with T lymphocytes in normal peritoneal fluid. IL-1b, tumor necrosis factor-alpha, IL-6, and soluble IL-2 receptor-alpha concentrations were increased significantly in the ascitic fluid of women with ovarian cancer. The decrease in activation markers on T lymphocytes is suggestive of an immunosuppressive state, despite the presence of abundant stimulatory cytokines. The immunosuppression may be multifactorial, attributed, in part, to the increased concentrations of soluble IL-2 receptor-alpha and other inhibitors.

Ascitic Fluid↗
PubMed1999

Tumor immunology--when a cancer cell meets the immune cells.

Tumor immunology consists of two essential concepts: immune surveillance, which specifies the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. Effective antitumor immunity by the host immune surveillance is supposed to be dependent on the identification of tumor antigens. In the process of malignant transformation, genetic mutations with aberrant expression of cancer-related genes and protein products are potentially immunogenic, which may serve as rejection antigens. Several scenarios are proposed to be responsible for tumor immune-escape mechanisms. The elucidation of the immune deficit against cancer progression has been a difficult task and no solitary mechanism explains the complicated cancer-host immune interactions. Cancer cells may overcome immune surveillance through a common but effective pathway, either by changing the polarity of effector cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells within the tumor milieu is of importance for further clinical applications of immunotherapy in cancer treatment.

Antigens, Neoplasm↗
PubMed1998

Abnormal urodynamic findings after radical hysterectomy or pelvic irradiation for cervical cancer.

OBJECTIVE: To assess urodynamic study results in patients with cervical cancer who had received radical hysterectomy or pelvic irradiation or radical hysterectomy with pelvic irradiation. METHODS: Forty-two patients with stage IB cervical cancer after radical hysterectomy (group A), 11 patients at stage IB or IIA after pelvic irradiation (group B), 15 patients at stage IB or IIA after both radical hysterectomy and pelvic irradiation (group C) and 17 patients at stage IB before treatment (group D) as control were recruited for urodynamic examination. The evaluations for each case included a 20-min pad test, uroflowmetry, both filling and voiding cystometry, and stress urethral pressure profile. ANOVA method with Bonferroni test and Pearson chi2-test were utilized for statistical analysis. RESULTS: The mean ages in sequential groups A, B, C and D were 52.9 +/- 10.2, 62.5 +/- 13.5, 49.8 +/- 11.7 and 49.4 +/- 12.5 years (P = 0.02), respectively. The occurring frequency of either detrusor instability or low bladder compliance was 57%, 45%, 80% and 24%, respectively. Each group revealed decreased bladder capacity as 268.4 +/- 102.8, 164.1 +/- 62.9, 233.5 +/- 73.9 and 293.0 +/- 47.2 ml (P < 0.0001). However, the frequency of abdominal strain voiding was 100% in groups A, B and C as compared to 0% in group D (P < 0.01), and the frequency of abnormal residual urine (> 50 ml) was 41%, 27%, 40% and 24%. Although each case showed a poor pressure transmission ratio (< 100%), the frequency of positive pad test in each group was 81%, 46%, 100% and 18% (P < 0.001). The functional urethral length decreased in each group and was 2.6 +/- 0.8, 2.3 +/- 0.8, 2.5 +/- 0.8 and 2.9 +/- 0.6 cm, but there were no significant differences in maximal urethral pressure or urethral closure pressure among the four groups. CONCLUSIONS: Our data show that abnormal urodynamic findings pre-exist in patients with cervical cancer before treatment especially in bladder storing function, and that these findings may worsen, or that new abnormal findings may happen after radical hysterectomy or pelvic irradiation, or both.

Combined Modality Therapy↗
PubMed1998

Maternal age-specific risk of Down syndrome in an Asian population: a report of the Taiwan Down Syndrome Screening Group.

This study is a novel approach in establishing the maternal age-specific risk for Down syndrome screening in an Asian population. The relative frequency by one-year maternal age interval in women who had live births in the Taiwan area between 1975 and 1995 was used as the age-specific distribution of women who had unaffected pregnancies. Data about Down syndrome live births were obtained from the Taiwan Down Syndrome Association to establish the age distribution of women who had Down syndrome live births. The relative frequencies and the likelihood ratio by one-year maternal age interval was calculated and smoothed by running median and moving average smoothing methods. The age-specific risk was established by multiplying the total population risk by the likelihood ratio of the specific maternal age. The total live births in the Taiwan area between 1975 and 1995 were 7,232,689. A total of 527 cases of Down syndrome live births were registered in the Taiwan Down Syndrome Association. A total of 466 cases (88.43 per cent) of Down syndrome live births occurred before age 35, which was higher than occidental reports. This study established the first sizeable database of maternal age-specific risk for Down syndrome in an Asian population.

Adolescent↗
PubMed1997

Adenomyosis in the broad ligament and tamoxifen: report of a case.

Adenomyosis confined to the broad ligament is extremely rare. Herein we present a case of adenomyosis in the broad ligament with unusual gross features. This 41-year-old woman had been on tamoxifen therapy for 3 years due to breast cancer. Ten months after discontinuing tamoxifen, she underwent exploratory laparotomy for a right adnexal mass suspected as ovarian malignancy. At laparotomy, the mass was located in the right broad ligament with a fibrous stalk connecting to the uterus. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathologic examination revealed adenomyosis with cyst formation and an unusual thick capsule. The possible effects of tamoxifen upon the uterus are discussed in this article, in view of reports of tamoxifen associated with endometrial carcinoma and endometriosis.

Adnexal Diseases↗
PubMed1997

The potential of serum levels of soluble tumour necrosis factor receptor I as a biochemical marker in cervical cancer.

OBJECTIVES: To investigate the significance of serum levels of soluble tumour necrosis factor receptor I (sTNF-RI) as a potential biochemical marker in women with cervical cancer. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Seventy-one women with cervical cancer and 33 women with myoma were enrolled in this study. METHODS: Pre-operative serum levels of sTNF-RI were measured with a standard enzyme-linked immunosorbent assay utilising murine monoclonal antibody against sTNF-RI. MAIN OUTCOME MEASURES: All data in both groups were evaluated and correlated with the pre-operative serum levels of sTNF-RI. Data analysis was carried out using ANOVA with multiple comparison and linear regression. RESULTS: The mean serum level of sTNF-RI in the cervical cancer group was significantly lower than that in the myoma group (P < 0.001). The sTNF-RI levels decreased sequentially with disease progression from Stage Ia to IIb in women with cervical cancer. The mean serum level of sTNF-RI was also significantly lower in women with positive lymph node (P < 0.05) or recurrent cancer (P < 0.001). A negative correlation was observed between serum levels of sTNF-RI and tumour size (r = -0.622, P < 0.0001). CONCLUSIONS: Decreased pre-operative serum levels of sTNF-RI are observed in women with cervical cancer. The results do not support that the use of sTNF-RI as a biochemical marker for cervical cancer.

Adult↗
PubMed1995

Prenatal detection of limb defects after chorionic villus sampling.

Prenatal sonographic diagnoses of two cases of severe limb defects after first-trimester chorionic villus sampling (CVS) are presented. Pathological examination after elective termination correlated well with the prenatal sonographic findings. Although the relationship between CVS and limb defects remains controversial, careful ultrasound examination for possible limb defects in cases receiving CVS is recommended.

Adult↗
PubMed1995

Synchronous primary carcinomas of the endometrium and ovary.

OBJECTIVES: Synchronous carcinomas of the endometrium and ovary may indicate either independently developing neoplasms or metastatic disease. The clinical implications and prognosis of these two categories are quite different. The objectives of this study were to identify and evaluate the empirical criteria and significant therapeutic implications. METHOD: The National Taiwan University Hospital Cancer Registry records and pathological reports from 1977 to 1994 were reviewed. Empirical criteria were used to identify synchronous primary cancers. RESULTS: A total of 322 patients had endometrial cancer and 421 patients had ovarian cancer in our Cancer Registry records. Eleven patients had simultaneous cancer involvement of both the endometrium and ovary. Six cases fulfilled the criteria of synchronous primary carcinomas of the endometrium and ovary. Of these, five were alive and free of disease for 35-144 months (median 94.2 months). The disease-free survival rates between patients with synchronous primary and metastatic cancers of different histologic types showed a statistically significant difference (P = 0.013). No statistical significance was noted for different histologic types (P > 0.5). CONCLUSIONS: The empirical criteria used here were useful in identifying synchronous primary cancers of the endometrium and ovary. The favorable clinical outcome may relate to early detection of early-stage disease and low-grade malignancy with an indolent growth rate. Surgical management with or without adjuvant therapy has a satisfactory outcome in our experience.

Adult↗
PubMed1995

Limb defects after chorionic villus sampling.

OBJECTIVE: To clarify the association between limb defects and chorionic villus sampling (CVS). METHODS: Questionnaires were sent to 165 major obstetric units in Taiwan to survey the incidence of limb defects with and without CVS exposure during 1991. Limb defects with CVS exposure from September 1990 to June 1992 were also surveyed. The spectrum of limb defects in CVS-exposed and general populations were compared by the Poisson test. RESULTS: The incidence of limb defects in the surveyed general population in 1991 was 0.032% and that with CVS exposure was 0.294%, a statistically significant difference (P < .001). The incidence of severe limb defects in the general population was 0.0026% and that with CVS exposure was 0.22%, also statistically significant (P < .001). Twenty-nine cases of limb defects after CVS were reported from September 1990 until June 1992: 19 cases with transverse limb reduction, two with mid-palm reduction, seven with adactyly or hypodactyly, and one with syndactyly. Four cases also had oromandibular-limb hypogenesis syndrome. CONCLUSIONS: The incidence of limb defects, especially the severe types, was increased after CVS. The spectrum of limb defects with CVS exposure was more severe than the limb defects seen in the general population and showed a specific pattern ranging from hypodactyly, adactyly, and transverse limb reduction, to oromandibular-limb hypogenesis. A correlation between the severity of limb defects and the timing of CVS was suggested.

Abnormalities, Multiple↗