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ABSTRACT: Adenosine triphosphate cell viability assay (ATP-CVA) was used previously to evaluate chemotherapy in uterine cancer cell lines. In this study, we have performed the ATP-CVA on endometrial cancer patients to study the feasibility of using ATP-CVA in endometrial cancer to determine the intrinsic chemosensitivity of the cytotoxic drugs.
Thirty-three patients with endometrial adenocarcinoma who presented for a staging operation were recruited. Endometrial cancer samples were obtained at the time of operation. In vitro ATP-CVA and chemosensitivity testing was performed using cisplatin, carboplatin, paclitaxel, etoposide, doxorubicin, 4-epidoxorubicin, and topotecan.
Thirty-two of the 33 endometrial cancer samples were evaluable for SF50 (survival fraction at 50% of the peak plasma concentration [PPC]) using ATP-CVA. The median SF50 of carboplatin (0.33) was significantly less than the median SF50 of cisplatin (0.71), topotecan (0.93), paclitaxel (0.68), doxorubicin (1.0), etoposide (0.70), or 4-epidoxorubicin (0.88) (Wilcoxon signed rank test, P <.001).
This study showed the feasibility of using the ATP-CVA in endometrial cancer to determine the intrinsic chemosensitivity of cytotoxic drugs.
Journal of the Society for Gynecologic Investigation 11/2006; 13(7):518-22. · 2.26 Impact Factor
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ABSTRACT: Comparative genomic hybridization has frequently detected amplification of chromosome 5p in cervical cancer, but candidate cancer genes within the region are rarely known. Therefore, we pursued to identify potential candidate gene related to cervical cancer development.
A series of 128 cervical tumor samples were examined by semi-quantitative fluorescent differential PCR for copy number changes on three candidate genes (PRKAA1, CTNND2 and POLS) mapped to chromosome 5p and one gene (ERBIN) mapped to chromosome 5q12.3. The impact of gene copy number was later analyzed in relation to HPV infection, tumor stage or tumor radiosensitivity.
DNA copy numbers of PRKAA1, CTNND2 and ERBIN were significantly different from normal controls (P < 0.05). DNA copy number changes did not correlate with HPV infection, tumor stages or tumor radiosensitivity. Using RT-PCR, PRKAA1 mRNA expression in seven tumor samples with known 5p amplification was amplified from 3- to 15-fold. Over-expression of PRKAA1 was further confirmed by immunohistochemical staining on 125 paraffin-embedded cervical cancer tissues. The expression level in cervical tumor was significantly higher than that in normal epithelium (P < 0.001).
PRKAA1 gene codes for the catalytic alpha 1 subunit of the AMP-activated protein kinase which is an important cellular metabolic stress regulator. It might assist tumor cells growth under stress. Thus, PRKAA1 may be one of the potential candidate genes for cervical carcinogenesis.
Gynecologic Oncology 10/2006; 103(1):219-25. · 3.89 Impact Factor
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ABSTRACT: Cervical and vulvar cancers are diseases of the female lower genital tract, and high-risk human papillomavirus (HPV) infection is the most important risk factor for the development of both cancers. However, it is clear that additional genetic events are necessary for tumor progression, particularly in HPV-negative cases. We detected the presence of high-risk HPV16 and HPV18 genomes by gene-specific polymerase chain reaction and searched for common genetic imbalances by comparative genomic hybridization (CGH) in 28 cervical and 8 vulvar tumor samples and 7 cancer cell lines. The presence of the HPV genome was detected in 25/28 (89%) cervical tumors and 6/8 (75%) vulvar tumors. CGH of cervical and vulvar tumor samples revealed a consistent pattern of genetic changes in both cancers. Frequent gains were found in 1q, 3q, 5p, and 8q, and less consistent losses were detected in 2q, 3p, 4p, and 11p. Notably, a high-level amplification of 3q was found in 9/28 (32%) cervical tumors and 1/8 (12.5%) vulvar tumors, indicating a pivotal role of gain of 3q in cervical and vulvar carcinogenesis. Furthermore, gains of 5p identified in 9/28 (32%) cervical tumors and 3/8 (37.5%) vulvar tumors were seldom described, particularly in vulvar tumors. Our findings suggest that cervical and vulvar carcinomas bear similar chromosomal alteration hot spots that largely coincide with common genomic lesions during tumor progression, besides the initiation by infection and integration of oncogenic HPV.
Cancer Genetics and Cytogenetics 03/2005; 157(1):42-8. · 1.39 Impact Factor
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ABSTRACT: The presence of liver metastasis will be staged as IV in the FIGO 1992 Gestational Trophoblastic Tumor (GTT) staging. This study was to determine the role of hepatic arteriogram (HAG) in the management of GTT. It is a retrospective analysis of 309 patients treated from 1981 to 2001. Patients were restaged according to the FIGO 1992 classification with or without taking into account the HAG result. Outcome measures including mortality, drug resistance and recurrence of disease, as well as treatment with and without the HAG result were compared. Eighty-one (26.2 percent) patients had HAG and 11 (3.6 percent) also had ultrasound (USG) features of liver metastasis. Interval between diagnosis and treatment were significantly different between USG and HAG positive groups (Mann-Whitney U test, P < 0.05). Seventeen (5.5 percent) of the 309 patients died of the disease and 7 (41.2 percent) of them had liver metastasis. Three (27.3 percent) of the 11 patients who had USG features of liver metastasis died of the disease; mortality is significantly higher than those without USG features of metastasis (Chi-square test, P < 0.05). Patients classified as medium to high risk with or without taking HAG as a feature of liver metastasis were associated with higher mortality and recurrent rate (Chi-square test, P < 0.05). On the other hand, the chance of drug resistance was higher in the medium to high risk group after reclassifying all HAG positive patients as negative for liver metastasis (Chi-square test, P < 0.05). HAG evidence of liver metastasis did not correlate with patient mortality. HAG was not an appropriate investigation in the management of GTT.
Cancer Investigation 02/2005; 23(8):677-82. · 1.85 Impact Factor
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ABSTRACT: Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy. By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy (P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients (P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression (P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.
Clinical Cancer Research 05/2004; 10(10):3309-16. · 7.74 Impact Factor
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Human Mutation 09/2003; 22(2):173-4. · 5.69 Impact Factor
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ABSTRACT: We have previously demonstrated the presence of human papillomavirus (HPV) DNA in several gynecological cancers using conventional PCR. In the present study, to further understand the role of HPV in malignant transformation of these cancers, the infection rates and viral loads of HPV 16 and 18 in gynecological cancers were analyzed using real-time quantitative PCR (qPCR). HPV 16 DNA was detected in 61.0% (58/95), 15.2% (7/46) and 32.1% (18/56) of cases of cervical, endometrial and ovarian cancers, respectively. On the other hand, HPV 18 DNA was detected in 23.2% (22/95) of cervical cancers, 1.8% (1/56) of ovarian cancers, and in no cases of endometrial cancer. Thus, HPV 16 is much more prevalent than HPV 18 in malignancies of the female genital tract. We also found that both HPV 16 and 18 were significantly (p < 0.05) less frequently present in endometrial and ovarian cancers than in cervical cancer. The median copy numbers of HPV 16 DNA in endometrial and ovarian cancers were 3,500 and 7,590 copies/microg DNA, respectively. These amounts were also significantly (p < 0.05) lower than HPV 16 DNA in cervical cancer (492,800 copies/microg DNA). Thus, HPV 16 could be detected in all three types of gynecological cancer, whilst HPV 18 is extremely rare in endometrial and ovarian cancers. The lower HPV 16 infection rates and lower copy numbers when compared with cervical cancer tend to suggest that HPV plays a less essential role in the development of endometrial cancer and ovarian cancer.
Tumor Biology 24(6):310-6. · 1.94 Impact Factor
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ABSTRACT: Objective. The aim of this study was to investigate the feasibility of using DNA in the circulation as a diagnostic tool for cervical cancer.Methods. We used PCR followed by Southern hybridization to detect human papillomavirus (HPV) DNA in serum samples taken from patients of cervical cancer before treatment.Results. A total of 60 samples were analyzed. In a set of 40 samples, without knowledge of the HPV DNA status in the corresponding cervical carcinomas, we could detect 8 (20%) positive samples, of which 7 (17.5%) were HPV 16 and 1 (2.5%) was HPV 18. In another set of 20 samples, known to be HPV 16 infected in the corresponding cervical carcinomas, we detected only 4 (20%) HPV-16-positive samples. The occurrence of HPV DNA in sera of cervical cancer patients seems sporadic.Conclusion. The low incidence indicates that serum HPV DNA has limited application in the diagnosis of cervical cancer.
Gynecologic Oncology.
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ABSTRACT: Objective. The aims of this study were to assess the cost/benefit ratio for interinstitution pathology consultation (IPC) and to identify the types of specimens with little or no risk of diagnostic error in order to reduce the cost.Methods. All gynecologic oncology referrals having IPC from 1993 to 1998 were reviewed. Each case was evaluated by comparing both the original and the consulted pathology reports. A discrepancy was major if it led to treatment alteration. A minor discrepancy was defined as differences without clinical consequences. Consultation error was determined by comparison with the final diagnosis and clinical data obtained from the records. The cost per review was adjusted to 1998 dollars for all cases over the 5-year study period. Statistical data were obtained by Fisher's exact test and Pearson's correlation test.Results. Five hundred sixty-nine pathology specimens from 498 patients were analyzed in this study. The major discrepancy rate was 6.5% and the minor discrepancy rate was 12.5%. Cytological specimens accounted for no major discrepancy and 13 minor discrepancies compared to 37 major and 58 minor discrepancies in histological specimens. The difference was statistically significant (P = 0.003). Consultation errors occurred in 5 cases with no alteration of clinical care. By excluding cervical and vaginal smears and cervical biopsy specimens in cases with clinically gross tumors, the cost can be reduced by 25% with no detriment to the clinical management.Conclusions. The types of specimens that do not need consultative pathology review include (1) cervical biopsy specimens in those patients with gross tumors and (2) cervical and vaginal smears.
Gynecologic Oncology.
