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Y Harima

Publications and source records attributed to Y Harima.

At least 19 recordsLinked to original sources
PubMed2001

Chromosome 6p21.2, 18q21.2 and human papilloma virus (HPV) DNA can predict prognosis of cervical cancer after radiotherapy.

Loss of heterozygosity (LOH) is one of the most important mechanisms for inactivation of tumor-suppressor genes. Studies of LOH in patients with cervical carcinoma have reported a high frequency of LOH on 3p21.3, 6p21.2, 17p13.1, and 18q21.2. Our study explored whether p53 status, human papilloma virus (HPV), and LOH on chromosome 3p21.3, 6p21.2, 17p13.1, and 18q21.2 are associated with treatment outcome in 65 patients with cervical cancer after radiotherapy. Tumors and normal DNA were analyzed by polymerase chain reaction (PCR) for genetic losses at 10 polymorphic microsatellite loci. The presence of HPV and its type were analyzed by PCR-based assay using the consensus primers for E6, E7, and L1 region. Mutations of the p53 gene were identified by a single-strand conformation polymorphism analysis. Chromosomes 3p21.3, 6p21.2, 17p13.1, and 18q21.2 were involved in the LOH in 23.1%, 41.5%%, 33.8%, and 23.1% of the tumors in our study, respectively. HPV-positive tumors were found in 73.8% of the patients and p53 mutation in 10.8%. The patients with LOH on chromosome 6p21.2 and 18q21.2 survived significantly shorter compared with those without LOH on chromosome 6p21.2 and 18q21.2 in both the overall survival (P = 0.006 and P = 0.007) and the disease-free survival (P = 0.005 and P = 0.008). The HPV-negative patients survived significantly shorter compared with the HPV-positive patients in both the overall survival (P = 0.01) and the disease-free survival (P = 0.04). According to multivariate analysis, HPV status (P = 0.0004, P = 0.01), LOH on 6p21.2 (P = 0.006, P = 0.02), and LOH on 18q21.2 (in both P = 0.01) is a significant predictor of both overall and disease-free survival time. The results of our study suggest that absence of HPV infection, LOH on 6p21.2, and LOH on 18q21.2 are the most important determinants of outcome of patients with cervical carcinoma after radiotherapy.

Adult↗
PubMed2001

Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women.

The WAF1 gene, located on chromosome 6p21.2, has been cloned and identified as a p53 mediator and an inhibitor of G1 cyclin-dependent kinases (CDKs). The present study was performed to investigate the possible role of the WAF1 gene in the pathogenesis of human cervical carcinoma. Matched venous blood and cancer tissues from 66 patients with cervical cancer were screened for WAF1 mutation by reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing. A polymorphism in the WAF1 gene involving a cytosine (C) to an adenine (A) transversion at the third base of codon 31 was observed in 52 of 66 (78.8%) patients with cervical carcinoma and 68 of 108 (63%) normal individuals (P=0.02). A total of 7 patients (10.6%) were found to have a change of the WAF1 gene at codon 31 on comparison of blood and tumor specimens. An A-->C transversion in 5 tumors and a C-->A transversion in 2 tumors, that were not found in matching normal specimens, were observed. In addition, the presence of loss of heterozygosity (LOH) on chromosome 6p21.2 in tumor and normal tissue DNA were analyzed by PCR at three polymorphic microsatellite loci (D6S276, D6S1624, D6S1583). In two cases, there was a change of Arg/Ser in blood to Ser/Ser in the tumor, which did not involve LOH on 6p21.2. Therefore, somatic mutation of the WAF1 gene was detected in 3% (2 of 66) of patients with cervical cancer in this series. In conclusion, the increased frequency of WAF1 polymorphism in the patients studied implied that codon 31 Arg allele of the WAF1 gene may be associated with a tendency to develop cervical carcinoma. To our knowledge, this is the first report of WAF1 somatic mutations in primary human cervical cancer.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed2001

Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy.

Improvement in management of advanced cervical cancer after radiotherapy requires a better understanding of its biological behavior. PTEN/MMAC/TEP(PTEN), a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be frequently mutated in several different types of human tumors. In contrast, rare mutations of the PTEN gene have been reported in cervical cancer. The aim of this study was to determine whether mutation of PTEN leads to increased genomic alteration in advanced cervical carcinoma, and to identify the correlation between mutation of PTEN and patient outcome after radiotherapy. We examined 50 primary advanced cervical carcinomas (37 patients of Stage IIIB, 13 patients of Stage IVA) treated with definitive radiotherapy using a PCR-based assay followed by SSCP and direct sequencing. The PTEN gene was mutated in 8 of the 50 (16%) patients (2 of Stage III, and 6 of Stage IV). There was a significant difference in Stage III versus IV between the wild-type PTEN patients and mutant PTEN patients (P=0.002). The tumor size was 6+/-2.1 cm in the wild-type PTEN tumors versus 8.5+/-2 cm in the mutant PTEN tumors (P=0.009). In addition, there was a significant difference in survival between the wild-type PTEN patients and mutant PTEN patients (P=0.009). The results of this study suggest that the PTEN gene mutation rate increases with tumor progression, and that the PTEN gene may play a role in both progression of cervical carcinoma and treatment outcome.

Adult↗
PubMed2000

Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in stage IIIB cervical carcinoma.

BACKGROUND: The relative amounts of Bcl-2 and Bax proteins determine cell survival or death following an apoptotic stimulus. To clarify the molecular mechanism of cell death after radiotherapy or thermoradiotherapy and its relation to the response of AJCC/UICC Stage IIIB cervical carcinomas, the expression of Bax and Bcl-2 proteins was investigated both before and in the course of treatment given during this study. METHODS: Thirty-seven patients with Stage IIIB carcinoma of the uterine cervix were treated with external beam irradiation to the pelvis combined with iridium-192 high-dose-rate intracavitary brachytherapy. All patients were randomized to one of the following two groups: the radiotherapy (RT) group of 19 patients who were given radiotherapy alone, and the thermoradiotherapy (TRT) group of 18 patients who were given 3 sessions of hyperthermia in addition to RT. Specimens of the cervical tumors were obtained by punch biopsy both before and in the course of the treatment (after a total dose of 10.8 grays ¿Gy for the RT group or after 10.8 Gy plus 1 session of hyperthermia for the TRT group). The tumor sections were stained with anti-Bax and anti-Bcl-2 monoclonal antibody. On the basis of the percentage of immunopositive cells, both pretreatment and posttreatment samples were scored. Furthermore, relative changes in protein expression were determined by comparing the pretreatment scores with those in the course of treatment. In addition, treatment response was evaluated. RESULTS: A complete response was achieved in 52.6% (10 of 19) of the RT group versus 83. 3% (15 of 18) of the TRT group (P = 0.049). Better tumor control was accompanied by increased Bax expression, i.e., 10.5% (2 of 19) of the RT group versus 44.4% (8 of 18) of the TRT group (P = 0.02). The respective number of patients who partially responded (PR) or did not respond to treatment (NC) was 26.3% (5 of 19) and 21.1% (4 of 19) of the RT group versus 11.1% (2 of 18) and 5.6% (1 of 18) of the TRT group (P = 0.2 for both the PR and NC subgroups). CONCLUSIONS: TRT was found to result in better treatment responses than RT for patients with Stage IIIB cervical carcinoma. An additive or synergistic antitumor effect of TRT is likely to occur through induction of apoptosis involving one of the bax pathways.

Aged↗
PubMed2000

Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer.

Cervical carcinomas develop as a result of multiple genetic alterations, and specific alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p is one of those most frequently involved in a loss of heterozygosity (LOH) in patients with cervical carcinoma. The aim of this study was to identify the correlation between the LOH on chromosome 6p21.2 and the recurrence of cervical cancer after radiotherapy. A total of 62 patients with cervical cancer (stage I, 4 patients; stage II, 9 patients; stage III, 37 patients; and stage IV, 12 patients) were included in this study. All patients were treated with definitive radiotherapy. We analyzed specimens from the tumors and venous blood of all patients. Tumors and normal DNA were analyzed by PCR for genetic losses at three polymorphic microsatellite loci (D6S276, D6S1624, and D6S1583). Chromosome 6p21.2 is involved in the LOH in 46.8% (29 of 62) of the informative carcinomas. Ten patients had a local recurrence, 4 had distant metastases, and 13 had both local recurrence and distant metastases after radiotherapy. To evaluate the relationship between the recurrence after radiotherapy and LOH on chromosome 6p21.2, we divided the patients into those with cancer recurrence (n = 27) and those without recurrence (n = 35). LOH on chromosome 6p21.2 was correlated with recurrence after radiotherapy (P = 0.006). The tumors in patients with recurrence were significantly larger than those in patients without recurrence (P = 0.003). However, there was no correlation between the sizes and stages of tumors and the LOH on chromosome 6p21.2. In addition, both overall survival and relapse-free survival were significantly worse for the patients with LOH as compared with those without LOH (P = 0.02 and P = 0.002, respectively). The results of this study suggest that LOH on 6p21.2 is correlated with recurrence of cervical carcinoma after radiotherapy.

Adult↗
PubMed2000

Determination of p53-mediated transactivational ability in radiation-treated cervical cancer.

To establish a new predictor of human cervical cancer radioresponse, we investigated the transactivational ability of p53 gene in tumor tissue for use as a marker of both pretreatment and postirradiation levels of mRNA of its downstream gene, WAF1. A total of 38 wild-type p53-bearing patients with histologically proved uterine cervical cancer were treated with definitive radiotherapy. Their p53 status was investigated using a single-strand conformation polymorphism analysis, and human papilloma virus 16, 18, 33, and 58 E6 was determined by polymerase chain reaction in pretreatment biopsy specimens. WAF1 mRNA was estimated by reverse transcriptase-polymerase chain reaction in both pretreatment specimens and those obtained after the administration of 10.8 Gy. Undetectable or low pretreatment levels of WAF1 mRNA were associated with complete response in the majority of cases, whereas only a few patients with a high pretreatment WAF1 level responded to treatment (P = .03). The increase in the postirradiation level of WAF1 mRNA positively correlated with better treatment response and long survival (P = .02). Although the human papilloma virus infection did not change the radiation response directly, it decreased the inducibility of WAF1. Consequently, the lower inducibility of WAF1 resulted in a poor treatment response. This is the first clinical report showing that the transactivational ability of p53 may be a determinant of the efficacy of cervical cancer radiotherapy.

Biopsy↗
PubMed1999

Interhospital network system using the worldwide web and the common gateway interface.

We constructed an interhospital network system using the worldwide web (WWW) and the Common Gateway Interface (CGI). Original clinical images are digitized and stored as a database for educational and research purposes. Personal computers (PCs) are available for data treatment and browsing. Our system is simple, as digitized images are stored into a Unix server machine. Images of important and interesting clinical cases are selected and registered into the image database using CGI. The main image format is 8- or 12-bit Joint Photographic Experts Group (JPEG) image. Original clinical images are finally stored in CD-ROM using a CD recorder. The image viewer can browse all of the images for one case at once as thumbnail pictures; image quality can be selected depending on the user's purpose. Using the network system, clinical images of interesting cases can be rapidly transmitted and discussed with other related hospitals. Data transmission from relational hospitals takes 1 to 2 minutes per 500 Kbyte of data. More distant hospitals (e.g., Rakusai Hospital, Kyoto) takes 1 minute more. The mean number of accesses our image database in a recent 3-month period was 470. There is a total about 200 cases in our image database, acquired over the past 2 years. Our system is useful for communication and image treatment between hospitals and we will describe the elements of our system and image database.

CD-ROM↗
PubMed1999

Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer.

Chromosome 17 alterations are found in more cancers than those of any other chromosome, and frequently involve the p53 gene on 17p13. The aim of this study was to identify the correlations between the presence of loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosome 17p13 in patients with cervical cancer and the patients' response to radiotherapy. A total of 50 patients were treated with definitive radiotherapy. We performed biopsies and took specimens from the tumour and venous blood of all patients. Tumour and normal DNAs were analysed by polymerase chain reaction for genetic losses and instability at three polymorphic microsatellite loci mapped to 17p13. Nineteen of the 50 tumours (38%) displayed a genetic alteration (GA) on 17p13, 16 (32%) were found to have LOH, and three (6%) showed MI. The sizes of the tumours of the GA-positive patients were significantly greater than those of the GA-negative patients (P = 0.009). The mean tumour diameter of all patients was 6 +/- 2.4 cm. We divided the patients into those with tumours smaller than 6 cm in diameter (n = 26) and those with tumours equal to or greater than 6 cm in diameter (n = 24). The former group survived significantly longer compared to the latter group (P = 0.0002). Among the patients with < 6 cm tumours, all six GA-positive patients are alive with no evidence of disease (NED), whereas of the 20 GA-negative patients, 18 have NED and two are alive with disease (AWD) or suffered cancer-caused death (CD). Thus, there was no correlation between GA and radiotherapy response in the tumours smaller than 6 cm. However, among the patients with > or = 6 cm tumours, two of the GA-positive patients have NED and 11 are AWD/CD, whereas seven of the GA-negative patients have NED and four are AWD/CD. Among the patients with > or = 6 cm tumours, the response to radiotherapy of the GA-positive patients were significantly poorer than those of the GA-negative patients (P = 0.02). In addition, the GA-negative patients survived significantly longer compared to the GA-positive patients (P = 0.026). The results of this study suggest that GA increases with tumour growth. Improved success in the management of bulky cervical cancer requires a better understanding of its biological behaviour.

Aged↗
PubMed1998

Bax and Bcl-2 expressions predict response to radiotherapy in human cervical cancer.

PURPOSE: The ratio of Bcl-2 to Bax expression determines survival or death following an apoptotic stimulus. In order to establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expressions of the Bax and Bcl-2 proteins and the response to radiotherapy after the administration of 10.8 Gy. METHODS: A total of 44 patients with histologically proven carcinoma of the uterine cervix, including three with recurrent cervical stump carcinomas, were treated with definitive radiotherapy. The presence of mutations in exons 5-8 of the p53 gene was analyzed by a single-strand conformation polymorphism analysis and DNA sequencing. RESULTS: Forty patients were found to have wild-type p53, and the remaining four had mutant p53. The Bax and Bcl-2 protein expressions prior to radiotherapy did not correlate with response and survival. However, the Bax and Bcl-2 protein expressions after radiotherapy correlated with both response and survival. Bax-positive tumors showed significantly better responses than the Bax-negative tumors after 10.8 Gy radiation (P = 0.0002). In contrast, the Bcl-2-positive tumors showed significantly poorer responses than the Bcl-2-negative tumors after radiation (P = 0.002). Increased Bax expression after the 10.8 Gy radiotherapy was found to be correlated with good survival (P = 0.04). In contrast, increased Bcl-2 expression after such radiotherapy was correlated with poor survival (P = 0.002). CONCLUSION: The levels of Bax and Bcl-2 expression after 10.8 Gy radiotherapy are useful prognostic markers in patients with human cervical carcinoma.

Adult↗
PubMed1998

[Bax and Bcl-2 expression predict response to radiotherapy in human cervical cancer].

To establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expression of the Bax and Bcl-2 proteins and the response to radiotherapy after administration of 10.8 Gy. A total of 44 patients with uterine cervical carcinoma were treated with definitive radiotherapy. On univariate analysis, Bax and Bcl-2 protein expression prior to radiotherapy did not correlate with survival. Increased Bax expression after 10.8 Gy correlated with good survival (p = 0.003). In contrast, increased Bcl-2 expression after 10.8 Gy correlated with poor survival (p < 0.0001). On multivariate analysis, Bcl-2 expression after 10.8 Gy of radiation was the most important predictor of treatment outcome. The levels of Bax and Bcl-2 expression after 10.8 Gy of radiotherapy are useful prognostic markers in patients with human cervical carcinoma.

Adenocarcinoma↗
PubMed1996

Histopathological changes in rabbit uterus carcinoma after transcatheter arterial embolization using cisplatin.

The effects of chemoembolization with cisplatin on gynecological malignancy were investigated using rabbit uterine tumors. A group of 20 rabbits were subjected to inoculation of the uterus with 5 x 10(7) VX2 carcinoma cells and 4 weeks later were divided into four groups, each consisting of five rabbits: an untreated control group, a group given cisplatin intraarterially (IA), a group subjected to transcatheter arterial embolization (TAE) with Gelfoam particles and a group subjected to transcatheter chemoembolization (TACE) with Gelfoam particles plus 1 mg/kg cisplatin. All groups were examined histologically 2 days after treatment. The untreated control group was further investigated 4 weeks after inoculation. In the untreated control group, the tumor cell nuclei varied in size and were irregular in form, and multiple nuclei and nuclear division were also observed. No necrotic zones were found up to 4 weeks after inoculation. The IA group showed no necrosis, but a few apoptotic cells were scattered throughout the tumor. In the TACE group, necrosis was observed in the center of the tumors, but proliferating cells persisted at the periphery. In the TACE group, necrosis was observed in the central part with many apoptotic cells surrounding the necrotic region in layers. The proliferating cell nuclear antigen (PCNA) index was 95.88% in the untreated control group, 86.6% in the IA group, and 8.62% in the TACE group, indicating a significant reduction in cell proliferation in the TACE group. These findings suggest that TACE results in more effective cytotoxicity than the other two treatments in uterine cancer tumor transplants.

Animals↗
PubMed1996

Hepatitis in used syringes: the limits of sensitivity of techniques to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA, and antibodies to HBV core and HCV antigens.

Hepatitis virus infections are common among injecting drug users. Syringes containing hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were identified by polymerase chain reaction (PCR); syringes containing antibodies to HBV core antigen and HCV were identified by EIA. Syringe use was simulated to determine the sensitivity of these assays. The mean limits for PCR were 0.082 microliter of blood for HBV and 0.185 microliter for HCV; the mean limits for EIA were 0.185 microliter for HBV and 0.023 microliter for HCV. HBV PCR testing of 681 syringes returned to the needle exchange program in New Haven, Connecticut, revealed a decline from 7.8% HBV-positive at the program's outset to 2.6%. HCV antibodies were found in 12.1% of 207 syringes tested. Syringe testing can help estimate the prevalence and incidence of hepatitis virus infections when standard seroepidemiologic analyses cannot be applied.

Base Sequence↗
PubMed1991

[Long-term results of transcatheter arterial embolization therapy in cases of recurrent and advanced pelvic cancer].

From April 1983 through April 1989, transcatheter internal iliac arterial embolization therapy (TAE) using Gelfoam particles was performed in 64 cases of recurrent or advanced pelvic cancer. We report here 19 patients who survived for more than one year. After TAE, the patients were followed on an outpatient basis for an average of two years. The condition of the patients was generally good during this period of follow-up. Complete response (CR) to therapy was obtained in five cases, partial response (PR) in nine, minor response (MR) in one and no change (NC) in four. Among the five cases that showed complete response, one case had local control for over five years, two cases for over three years and two cases for over one year. Though the patients had cancer, there were no other complications during the long-term follow-up.

Adult↗
PubMed1990

[Transcatheter arterial embolization therapy in cases of recurrent and advanced pelvic cancer--estimation by Cox's proportional hazard model].

From April 1983 through September 1988, transcatheter internal iliac arterial embolization therapy (TAE) using Gelfoam particles was performed in 36 patients with recurrent pelvic cancer and 18 patients with advanced pelvic cancer. The tumor showed complete response (CR) to the therapy in seven patients, partial response (PR) in 18, minor response (MR) in five, and no change (NC) in 24 patients, with the response rate (CR + PR) of 46.3%. Univariate analysis, using Kaplan-Meier estimates and log-rank test, revealed that overall survival was related to performance status (p = 0.0001) and tumor reduction by TAE (p = 0.0008). Similarly, a multivariate analysis, using Cox's proportional hazard model, revealed a strong relationship between prognosis and performance status and tumor reduction by TAE. These results show that both good general condition and tumor reduction by TAE are significant characteristics for the prognosis of recurrent and advanced pelvic cancer treated by TAE.

Adult↗
PubMed1990

Advanced vulvar carcinoma treated with internal iliac arterial embolization therapy after radiotherapy.

Two patients with vulvar carcinoma are reported who were treated with internal iliac transcatheter arterial embolization and radiotherapy. Patient 1 had T3N3M0 vulvar carcinoma. The lesion remaining after radiotherapy was treated by bilateral internal iliac arterial embolization. Vulvectomy was then performed, and the resected specimen showed no residual malignant cells. This patient is alive without recurrence 4 years 7 months after operation. Patient 2 (T3N0M0 vulvar carcinoma) underwent radiotherapy, and the remaining malignant tumor disappeared after bilateral internal iliac artery embolization. This patient has remained disease free without vulvectomy for 3 years after treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Transcatheter arterial embolization therapy in cases of recurrent and advanced gynecologic cancer.

Transcatheter internal iliac arterial embolization therapy (TAE) using Gelfoam particles was performed in 24 patients with recurrent gynecologic cancer and ten patients with advanced gynecologic cancer who had previously undergone radiotherapy. The tumor showed complete response (CR) to the therapy in six patients, partial response (PR) in 12, minor response (MR) in three, and no changes (NC) in 13 patients, with the response rate (CR + PR) of 52.9% (18 of 34). No serious or prolonged side effects were encountered except for vesicovaginal fistula in three patients and renal failure in one. The median duration of survival was 299 days, and the 1-year cumulative survival rate was 32.5%. The factors that were associated with favorable outcome after TAE were good general condition, no distant metastases, tumors less than 5 cm in diameter, and responses to the therapy of PR or better. Thus, TAE appears useful for the treatment of recurrent and advanced gynecologic malignancies.

Adult↗