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Biomedical subjects

C A Chen

Publications and source records attributed to C A Chen.

At least 55 records · Page 3Linked to original sources

Systematic relationships within the Anthozoa (Cnidaria: Anthozoa) using the 5'-end of the 28S rDNA.

Systematic relationships among the subclasses of Anthozoa, and especially among the orders Scleractinia, Actiniaria, and Corallimorpharia of subclass Zoantharia, were investigated by applying parsimony and distance methods of analysis to nucleotide sequence data obtained for the 5' end of the 28S rDNA. Exhaustive parsimony analysis indicates that the Ceriantipatharia are most representative of the ancestral Anthozoa. When applied to a wide range of scleractinians (nine taxa), actiniarians (seven taxa), and corallimorpharians (six taxa), both parsimony and distance analyses resolve three groups, one being the Scleractinia and the others containing both actiniarians and corallimorpharians. This indicates an unclear relationship between Actiniaria and Corallimorpharia and gives no support for Hand's hypothesis of scleractinian ancestry of actiniarians and corallimorphians; the monophyly of the Scleractinia, which is strongly supported by our analyses, is evidence to the contrary.

Animals↗

Vascular patterns of gestational trophoblastic tumors by color Doppler ultrasound.

BACKGROUND: Destruction of uterine vasculature is a common phenomenon in gestational trophoblastic tumors. The authors categorized such uterine vasculature by color Doppler ultrasound and studied its clinical significance. METHODS: Color Doppler ultrasound was performed in 28 patients with gestational trophoblastic tumors. The vascular morphologic manifestations were recorded, and the peak systolic velocity and resistance index of uterine artery were calculated. Serum beta-human chorionic gonadotropin (hCG) levels were measured periodically to monitor chemotherapy response. Seventeen uneventful postmole uteri were used as controls. Two-tailed Student's t-test and Fisher's exact test were used for statistical analysis. RESULTS: The gestational trophoblastic tumors were categorized as diffuse type (N = 7), lacunar type (N = 16), and compact type (n = 5) according to their vascular patterns. The mean serum beta-hCG level at diagnosis in diffuse type lesions (6608 +/- 6320 mIU/mL) was significantly lower than in the lacunar type (40462 +/- 39735 mIU/mL; P = 0.04) and compact type (212114 +/- 205126 mIU/mL; P = 0.02), whereas the level in compact type lesions was significantly higher than in the lacunar type (P = 0.003). Lacunar type lesions exhibited a significantly lower uterine artery resistance index (0.51 +/- 0.13) than diffuse type (0.66 +/- 0.10; P = 0.03) or compact type lesions (0.70 +/- 0.06; P = 0.02). All lesions exhibited significantly higher peak systolic velocity than control subjects (P < 0.001); however, no significant difference was observed among them. Brief courses (< 5 cycles) of chemotherapy cured more diffuse type (6 of 7) than lacunar type (3 of 15, P = 0.006) or compact type lesions (0 of 5, P = 0.008). Histopathologic diagnosis was available for 11 lesions. They were invasive mole in seven lacunar type lesions and choriocarcinoma in four compact type lesions. CONCLUSION: Vascular morphologic patterns of gestational trophoblastic tumors by color Doppler ultrasound correlated well with beta-hCG levels, uterine hemodynamics, chemotherapy response, and possibly the histopathologic diagnosis.

Arteries↗

Cell kinetics and radiosensitivity of cervical squamous cell carcinoma.

Flow cytometry analyses of tumors from 12 patients with cervical squamous cell carcinoma under radiotherapy were performed in this preliminary study. Six patients with a high (> 10%) G2/M fraction before treatment showed greater than 50% tumor reduction after initial 2000 cGy radiotherapy. Only two out of six patients with a low (< 10%) G2/M fraction before treatment responded favorably and three of them already had recurrence during the follow-up period of 33-40 months. Hyperploidy (DNA index > 1.1) was observed in 5 patients; all of them responded well to radiotherapy in contrast to three out of seven diploid tumors.

Carcinoma, Squamous Cell↗

The genotypes and prognostic significance of human papillomaviruses in cervical cancer.

An integrated study on the role of human papillomaviruses (HPV) in cervical cancer has been conducted. Out of a total of 433 cases of cervical cancer, HPV-DNA was detected in 342 (79%) using the polymerase chain reaction (PCR). The incidence of HPV infection was not significantly related to histological types, although a lower incidence was noted in adenocarcinoma cases. The incidence of lymph node (LN) metastasis in adenosquamous carcinoma (55.6%) was significantly higher than in squamous cell carcinoma (SCC) and adenocarcinoma. HPV 16 was detected significantly more often in SCC than in adenocarcinoma. In contrast, HPV 18 was detected more often in adenocarcinoma than in SCC. As a whole, pelvic LN metastases were found in 24.3% of HPV+ cases, significantly higher than 11% of HPV- cases. However, the significant association of HPV-DNA with LN metastasis was only noted in stage I but not stage II. As far as histological types were concerned, the incidence of positive LN was: HPV+ SCC > HPV- SCC (p < 0.01), whereas HPV- adenocarcinoma > HPV+ adenocarcinoma (p = 0.12). Genotypes of HPV did not have any effect on nodal status. The presence of types of HPV were not associated with tumor size and distribution of clinical stage. Our results suggest that the prognostic significance of HPV-DNA on nodal status is dependent on histological types while the genotypes of HPV cannot account for prognostic significance in cervical cancer.

Adult↗

Human papillomavirus DNA and p53 status in stage IB bulky cervical cancer.

We used the polymerase chain reaction (PCR) to study the presence and typing of human papillomavirus (HPV) DNA, and PCR/single-strand confirmation polymorphism to survey the mutations of the p53 gene in exons 5-9 in 26 bulky stage IB cervical cancers. The HPV DNA was present in 20 out of the 21 (95%) squamous-cell carcinoma tissues, including 13 cases of HPV-16, 0 case of HPV-18, and 7 cases of other HPV types. In the other 5 adenocarcinoma tissues, 3 had HPV type-18 DNA and 2 had no detectable HPV DNA. The distribution of HPV DNA in bulky tumors was not statistically different from that in the other 228 squamous-cell carcinomas and 23 adenocarcinomas of smaller size operated upon during the same period. Out of the 26 patients, 9 (35%) had lymph node metastasis at the time of operation. During the follow-up period ranging from 19 to 48 months, 9 patients had recurrence and 7 of them died of disease. The distribution of HPV types was not related to the prognosis in these patients. There were no p53 mutations detected in all the 26 samples. Thus, HPV type and the status of p53 could not serve as additional prognostic factors in stage IB bulky cervical cancers.

Adenocarcinoma↗

Infrequent mutation in tumor suppressor gene p53 in gestational trophoblastic neoplasia.

In order to determine the p53 status of gestational trophoblastic neoplasia, 24 cases of molar pregnancies and two choriocarcinoma cell lines (JAR and JEG-3) were evaluated for the presence of mutations. The evaluation involved the whole coding sequence (i.e. exons 2-11) of the p53 gene with polymerase chain reaction (PCR) amplification of genomic DNA, followed by single strand conformation polymorphism (SSCP) and sequencing. Only one case of hydatidiform mole was found to have a missense point mutation (codon 295, CCT-->CTT, i.e. proline to leucine) of the p53 gene. The results suggest that p53 mutation is rarely involved in the pathogenesis of gestational trophoblastic neoplasia.

Base Sequence↗

Correlation of uterine hemodynamics with chemotherapy response in gestational trophoblastic tumors.

OBJECTIVE: To assess the uterine hemodynamics in gestational trophoblastic tumors and to correlate them with response to chemotherapy. METHODS: Using transvaginal color Doppler ultrasound, we measured the peak systolic velocity and the resistance index (RI) of the uterine arteries in 23 women with gestational trophoblastic tumors before each course of chemotherapy. Fifty-five nonpregnant women and another 15 women who had uneventful molar evacuation were enrolled as controls. Two-tailed Student t test was used for statistical analysis. RESULTS: A hyperdynamic uterine circulation was noticed at diagnosis in all gestational trophoblastic tumors, manifested as higher peak systolic velocity (mean +/- standard deviation 57.5 +/- 20.4 cm/second) of the uterine arteries compared to nonpregnant (28.3 +/- 3.41 cm/second; P < .0001) and uneventful post-mole uteri (26.8 +/- 3.08 cm/second; P < .0001). The RI values of the uterine arteries in gestational trophoblastic tumors at diagnosis ranged from 0.21-0.80. However, the mean value (0.56 +/- 0.19) was lower than those of nonpregnant (0.80 +/- 0.05; P < .0001) and post-mole uteri (0.75 +/- 0.06; P < .0001). A higher pre-treatment uterine artery RI (mean 0.71 +/- 0.09) was noted in ten patients with gestational trophoblastic tumors requiring fewer than five courses of chemotherapy, compared with the mean in 13 patients requiring longer courses of treatment (0.47 +/- 0.14; P < .0001). There was a marked decrease of peak systolic velocity during the first three courses of treatment in the former group (54.2 to 23.6 cm/second; P < .001), in contrast to no change in the latter group (60.1 to 60.5 cm/second). CONCLUSION: Uterine hemodynamic characteristics assessed by color Doppler ultrasound might predict and monitor the response to chemotherapy in gestational trophoblastic tumors.

Adult↗

Serum neuron-specific enolase levels in patients with small cell carcinoma of the uterine cervix.

Serum neuron-specific enolase (NSE) is a tumor marker for neuroendocrine tumors or tumors of neuroepithelial origin. While the clinical application of NSE in small cell lung cancer has been established, its role in small cell carcinoma of the uterine cervix is unknown. We examined serum NSE in six patients with cervical small cell carcinoma and 13 patients with cervical squamous cell carcinoma. Elevated serum NSE was noted in four of six patients (67%) with small cell carcinoma, but none of the 13 patients with squamous cell carcinoma. An extremely high NSE serum level (154.7 ng/mL) was found in one patient with recurrence of small cell carcinoma, suggesting its correlation with disease extension. Although further studies to evaluate its relevance to prognosis, treatment effect, and early detection of recurrence are in progress, this preliminary result seems promising.

Adult↗

In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428.

[11C]WIN 35,428 was evaluated as a specific in vivo radioligand for the dopamine transporter site by PET scanning in nonhuman primates and humans. In studies with a baboon (Papio anubis), [11C]WIN 35,428 accumulated in brain regions containing dopamine transporters, i.e., the striata. This accumulation was partially blocked by prior administration of (-)cocaine (4 mg/kg, i.v.). Placement of a unilateral lesion of dopamine-containing nerve terminals with MPTP resulted in a unilateral reduction in [11C]WIN 35,428 accumulation in the striatum on the side of the lesion. Imaging of D2 dopamine receptors with [11C]NMSP in the same MPTP-treated animals showed much less reduction in the postsynaptic D2 dopamine receptors as compared to the much larger reduction in the dopamine transporters labeled with [11C]WIN 35,428. A total of ten normal human volunteers (five males and five females) with ages ranging from 19 to 81 years were studied. The caudate/cerebellar and putamen/cerebellar ratios ranged from 4.4 to 5.7 90 min after injection of the tracer. Preliminary kinetic modeling with arterial plasma sampling resulted in an average binding potential (k3/k4) of 4.98 in the caudate nucleus and 5.13 in putamen. To demonstrate in vivo blockade with dopamine reuptake inhibitors, two subjects received prior oral doses of 6 mg mazindol. Subject 5 had significant reductions of 29% in the caudate/cerebellar ratio at 90 min, 35% in the putamen/cerebellar ratio at 90 min, 45% in the caudate k3/k4 ratio from 6.7 to 3.7, and 46% in the putamen k3/k4 from 4.7 to 2.5. Subject 8 had significant reductions of 20% in both the caudate/cerebellar ratio and the putamen/cerebellar ratio at 90 min. During the human PET studies, a number of neuropsychological tests and physiological measurements were performed. No significant changes were found after administration of the [11C]WIN 35,428 alone. Taken together, these data indicate that [11C]WIN 35,428 is a promising radioligand for future studies of neuropsychiatric disorders that involve the dopamine transporter site.

Adult↗

The state of p53 in primary human cervical carcinomas and its effects in human papillomavirus-immortalized human cervical cells.

Wild-type (wt) p53 acts as a tumor suppressor, while certain mutant type (mt) p53 may exhibit 'oncogenic' function. We have recently demonstrated that human papillomavirus type 18 (HPV-18) E6 can partially overcome the growth-suppressive effects of wt p53, but it remains unclear what role p53 plays in cervical carcinogenesis. In this report, we have examined nine HPV-immortalized human cervical epithelial cell lines and 13 HPV-positive and two HPV-negative primary cervical cancers for p53 mutations by polymerase chain reaction--single-strand conformation polymorphism (PCR-SSCP). None of them contained p53 mutations in exons 5-9 where most p53 mutations in human tumors have been found. The entire p53-coding region of the two HPV-negative cervical cancers was sequenced and no mutations were noted. In order to examine the effects of wt p53 and mt p53 on HPV-immortalized human cells, we transfected HPV-immortalized cell lines with wt p53 and a mt p53 (mtp53Val-135). The results indicate that HPV-immortalized cells cannot tolerate large amounts of exogenous wt p53, while mt p53Val-135 can enhance transformation of these cells. The results support the notion that inactivation of wt p53 by E6 may be important for HPV-associated transformation and also suggests that mt p53 can act as an oncogene in HPV-immoralized human cells.

Base Sequence↗

The effects of cyclosporin A on the lysis of ovarian cancer cells by cisplatin or adriamycin.

The major limitation to curative therapy for ovarian cancer is the development of drug resistance. Cyclosporin A (CsA), an immunosuppressive agent that has been used extensively in organ transplantation, also has been shown to decrease the resistance of cancer cells to some chemotherapeutic agents. Since cisplatin (CDDP) is the most common drug used for the treatment of ovarian cancer, we evaluated the potential of CsA to decrease resistance to CDDP in ovarian cancer cells selected for resistance to CDDP (A2780-CDDP). Although CsA significantly increased the sensitivity of A2780-CDDP cells to cytolysis by CDDP it did not increase CDDP sensitivity in the CDDP-sensitive parent cells (A2780), that is, CsA did not decrease basal resistance to CDDP. Both A2780-CDDP and A2780 are sensitive to cytolysis by Adriamycin (ADR). CsA significantly decreased the basal resistance of both cell lines to ADR. Interestingly, the effect of the protein synthesis inhibitors, emetine and cycloheximide, was similar to that of CsA, suggesting that CsA decreased selected resistance to CDDP and decreased basal resistance to ADR by affecting a protein synthesis-dependent resistance mechanism(s). In contrast to CsA and protein synthesis inhibitors, buthionine sulfoximine, an inhibitor of glutathione synthesis, decreased basal resistance of both cell lines to cytolysis by CDDP but not ADR, while verapamil, an inhibitor of P-glycoprotein, had no effect on cytolysis in either cell line. These results suggest that CsA may not decrease resistance to CDDP or ADR-mediated cytolysis by reducing glutathione or by inhibiting P-glycoprotein.

Antimetabolites, Antineoplastic↗

Secondary ovarian malignancy of extragenital origin: clinical analysis of 42 cases.

Forty-two patients with secondary ovarian cancer from extragenital sites encountered in the past 14 years at the National Taiwan University Hospital were retrospectively analyzed. They accounted for 11.6% (42/362) of all ovarian cancers. The mean age was 43.7 years, and 32 patients were premenopausal. Gastric cancer was the most frequent primary malignancy (50.0%); other sites of extragenital primaries were colon (23.8%), breast (11.9%), rectum (4.8%), and indeterminate (9.5%). Bilateral ovarian involvement was found in 78.6% of patients. The most common presenting symptom was abdominal distension (52%). All patients received surgical intervention as the primary treatment; 30 patients had subsequent chemotherapy and four patients had postoperative radiotherapy. However, the outcome was poor; more than half of the patients died within one year, with a two-year survival rate of 22.5%.

Adult↗

Malignant mixed müllerian tumor of the fallopian tube.

Malignant mixed Müllerian tumor (MMMT) of the fallopian tube is an extremely rare neoplasm with a poor prognosis. To date, only 37 cases have been reported. The primary treatment for this tumor is surgery. Chemotherapy has been used with some success. The role of radiotherapy is less clear. A case of malignant mixed Müllerian tumor of the fallopian tube occurring in a 63- year- old woman, presenting with postmenopausal vaginal spotting for 7 months, is reported.

Fallopian Tube Neoplasms↗

Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody.

The effect of stimulating normal type 1 murine T cell clones with anti-CD3 antibody was examined in vitro. In the absence of accessory cells, anti-CD3 antibody immobilized on plastic plates stimulated inositol phosphate production, suboptimal proliferation, IL-2 and IL-3 production, and maximal IFN-gamma production. Addition of accessory cells augmented lymphokine production and proliferation when the effects of "high-dose suppression" were relieved by removing the T cells from the antibody-coated plates. Exposure of type 1 T cell clones to immobilized anti-CD3 antibody alone rapidly induced long-lasting proliferative unresponsiveness (anergy) to Ag stimulation that could be prevented by accessory cells. This anergic state was characterized by a lymphokine production defect, not a failure of the T cells to respond to exogenous IL-2 or to express surface Ti/CD3 complexes. In addition, anergy could not be induced in the presence of cyclosporine A. These results suggest that under certain conditions anti-CD3 antibodies may have potent immunosuppressive effects independent of Ti/CD3 modulation. Furthermore, our results support a two-signal model of type 1 T cell activation in which Ti/CD3 occupancy alone (signal 1) induces anergy, whereas Ti/CD3 occupancy in conjunction with a costimulatory signal (signal 2) induces a proliferative response.

Animals↗

Enhanced natural killer cell activity in patients with cervical carcinoma by postoperative PS-K immunotherapy.

The cell-mediated immunity in 19 patients with stage I and II cervical carcinoma was evaluated before and after postoperative PS-K immunotherapy. Lymphocyte subpopulations were enumerated using specific monoclonal antibodies (moAbs) of the Leu series (Leu2, Leullb, Leu15, and Leu19) and the OKT series (OKT3, and OKT4). A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell activity. Serum levels of interleukin-2 (IL-2), soluble interleukin-2 receptor (IL-2R), and tumor necrosis factor (TNF) were also determined before and after postoperative PS-K immunotherapy. The results showed that the number of cells carrying the marker of a non-major histocompatibility complex (MHC), restricted cytotoxic lymphocytes in the peripheral blood and NK activity at three different effector/target ratios increased significantly after postoperative PS-K immunotherapy. It is therefore concluded that postoperative PS-K immunotherapy enhanced the NK activity in patients with cervical carcinoma, in which NK activity tended to be lower. Further clinical investigation to assess the effectiveness of PS-K immunotherapy in improving the overall survival is in progress.

Adjuvants, Immunologic↗

Serum copper and zinc levels in patients with cervical cancer.

The serum copper (SCL) and zinc (SZL) levels were measured in 99 patients with cervical cancer and 50 patients with uterine myoma as controls. The mean SCL in the control group was 109.4 +/- 17.4 micrograms/ml as compared to 117.1 +/- 14.6 micrograms/dl and was not significant (NS) in 17 carcinoma in situ (CIS) patients, 142.3 +/- 14.2 micrograms/dl in 30 stage I patients (p less than 0.001), 159.0 +/- 16.6 micrograms/dl in 22 stage II patients (p less than 0.001), 171.6 +/- 25.7 micrograms/dl in 10 stage III or IV patients (p less than 0.001), and 166.2 +/- 32.2 micrograms/dl in 20 recurrent patients (p less than 0.001). The SCL returned to control level 2 weeks after surgical treatment for the stage I and II patients (mean 110.6 +/- 19.6 and 108.7 +/- 20.4 micrograms/dl, respectively, p less than 0.001). The SZL was 97.2 +/- 15.8 micrograms/dl in control patients and only showed a significant decrease in stage III or IV and recurrent patients (67.2 +/- 16.6 and 70.4 +/- 17.2 micrograms/dl, respectively). Concerning the copper/zinc ratio, the control group was 1.13 +/- 0.07 as compared to 1.17 +/- 0.07 in CIS (p = 0.06), 1.51 +/- 0.24 in stage I (p less than 0.001), 1.85 +/- 0.37 in stage II (p less than 0.001), 2.66 +/- 0.61 in stage III or IV (p less than 0.001), and 2.50 +/- 0.75 in recurrent patients (p less than 0.001). Taking mean +/- 2.5 SD of the control values as cut off points, the percentages of the recurrent patients with abnormal SCL, SZL, and a Cu/Zn ratio were 65, 30 and 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Decreased natural killer cell activity in patients with invasive cervical carcinoma.

The cell-mediated immunity in 21,12,14 and 12 patients with preinvasive, stage I and II invasive cervical carcinoma, and in controls respectively, was studied. Lymphocyte subpopulations were enumerated using specific monoclonal antibodies (moAbs) of the Leu series (Leu2, Leu3, Leu4, Leu11b, and Leu15). Double stain using fluorescein-isothiocyanate (FITC) conjugated Leu2 moAb and phycoerythrin (PE) conjugated Leu15 moAb was applied to distinguish cytotoxic T-cells from suppressor T-cells. A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell activity. The results showed that there was no significant difference in lymphocyte subpopulations among these 4 studied groups. However, the NK activity tended to be lower in patients with invasive cervical carcinoma (stage I and II) especially at a high effector/target ratio of 100. It is therefore concluded that functional cytotoxicity assay is more informative in evaluating the status of cell-mediated immunity against tumors than the enumeration of lymphocyte subsets.

Adult↗