Shamima Yeasmin

Shimane University, Matsue-shi, Shimane-ken, Japan

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Publications (25)76.15 Total impact

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    ABSTRACT: This study examined the biological and clinical significance of NAC1 (nucleus accumbens associated 1) expression in both cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. Using immunohistochemistry, the frequency of positive NAC1 expression in adenocarcinomas/adenosquamous carcinomas (31.0%; 18/58) was significantly higher than that in squamous cell carcinomas (16.2%; 12/74) (P = .043). NAC1 gene amplification was identified by fluorescence in situ hybridization in 5 (7.2%) of 69 squamous cell carcinomas. NAC1 amplification was not identified in the adenocarcinomas (0%; 0/58). Positive NAC1 expression was significantly correlated with shorter overall survival in squamous cell carcinomas (P < .0001). A multivariate analysis showed that positive NAC1 expression in squamous cell carcinomas was an independent prognostic factor for overall survival after standard radiotherapy (P = .0003). In contrast to squamous cell carcinomas, positive NAC1 expression did not correlate with shorter overall survival in adenocarcinomas/adenosquamous carcinomas (P = .317). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in the cervical cancer cell lines TCS and Hela P3, which normally lack NAC1 expression. These findings indicate that NAC1 overexpression is critical to the growth and survival of cervical carcinomas irrespective of histologic type. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, cervical carcinoma patients with NAC1 expression may benefit from a targeted therapy irrespective of histologic type.
    Human pathology 08/2011; 43(4):506-19. · 3.03 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the patterns of epidermal growth factor receptor (EGFR) overexpression, EGFR gene amplification, and the presence of activating mutations in the tyrosine kinase domain of this gene in squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas of the uterine cervix. The EGFR expression, amplification, and mutation in cervical carcinomas were assessed by immunohistochemistry, fluorescence in situ hybridisation, and PCR-SSCP, respectively, and correlated with clinical data collected by a retrospective chart review. A functional assessment was performed by inactivating EGFR in cervical cancer cells with the potent inhibitor AG1478. Immunohistochemical analysis revealed that 6 out of 59 (10.2%) cervical squamous cell carcinomas showed significant amplification of the EGFR locus, whereas none of the 52 adeno/adenosquamous cell carcinomas had detectable EGFR amplification (P<0.05). The EGFR amplification significantly correlated with shorter overall survival (P=0.001) in cervical squamous cell carcinomas. Multivariate analysis showed that EGFR gene amplification was an independent prognostic factor for overall survival (P=0.011). None of the squamous cell carcinomas (0%: 0 out of 32) had detectable oncogenic mutations in EGFR exons 18 through 21. The frequencies of KRAS and BRAF mutations were very low in both squamous and adeno/adenosquamous cell carcinomas. Sensitivity of cervical cancer cells to AG1478 depended on the presence of EGFR overexpression. AG1478-induced EGFR inactivation in cell lines with EGFR overexpression significantly suppressed tumour development and progression in a mouse xenograft model. Our data suggest that EGFR signalling is important in a subset of cervical squamous cell carcinomas and that anti-EGFR therapy may benefit patients who carry the 7p11.2 amplicon in their tumours.
    British Journal of Cancer 07/2011; 105(3):420-7. · 5.08 Impact Factor
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    ABSTRACT: Ovarian endometrioid adenocarcinomas (OEAs) frequently exhibit constitutive activation of canonical WNT signaling, usually as a result of oncogenic mutations that stabilize and dysregulate the β-catenin protein. In previous work, we used microarray-based methods to compare gene expression in OEAs with and without dysregulated β-catenin as a strategy for identifying novel β-catenin/TCF target genes with important roles in ovarian cancer pathogenesis. Among the genes highlighted by the microarray studies was MSX2, which encodes a homeobox transcription factor. We found MSX2 expression was markedly increased in primary human and murine OEAs with dysregulated β-catenin compared with OEAs with intact β-catenin regulation. WNT pathway activation by WNT3a ligand or GSK3β inhibitor treatment potently induced MSX2 and ectopic expression of a dominant negative form of TCF4 inhibited MSX2 expression in ovarian cancer cells. Chromatin immunoprecipitation studies demonstrated that β-catenin/TCF directly regulates MSX2 expression via binding to TCF binding elements in multiple regions of the MSX2 gene. Notably, ectopic MSX2 expression was found to promote neoplastic transformation of the rodent RK3E model epithelial cell line and to enhance the invasiveness of immortalized human ovarian epithelial cells in vitro and ovarian carcinoma cells in vivo. Inhibition of endogenous MSX2 expression in ovarian endometrioid cancer cells carrying a β-catenin mutation using shRNA approaches inhibited neoplastic properties of the cells in vitro and in vivo. Expression of MSX2 in selected ovarian carcinoma cells induced changes suggestive of epithelial-mesenchymal transition (EMT), but based on analysis of ovarian cell lines and primary tumor tissues, effects of MSX2 on EMT appear to be complex and context-dependent. Our findings indicate MSX2 is a direct downstream transcriptional target of β-catenin/TCF and has a key contributing role in the cancer phenotype of OEAs carrying WNT/β-catenin pathway defects.
    Oncogene 04/2011; 30(40):4152-62. · 8.56 Impact Factor
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    ABSTRACT: Our previous studies indicate that loss of MKK4 expression is associated with the progression of ovarian cancer. However, direct evidence that MKK4 inhibits the malignant phenotype of ovarian cancer cells is limited. In the current study, we investigated the mechanism relating loss of MKK4 expression to the development of ovarian cancer. Using cell growth and anchorage-independent assays, we determined that both the growth and colony-forming ability of MKK4-transfected TOV-21G cells, a line with a homozygous deletion of MKK4, were significantly reduced compared to control vector-transfected cells. Overexpression of the MKK4 gene in TOV-21G cells resulted in reduced proliferative activity and increased apoptosis. To confirm that MKK4 expression related to tumor suppress function, we used two independent but complementary approaches. MKK4 gene knockdown in OVK18#2 and MDAH2774 cells, which overexpressed MKK4, increased proliferation activity. Additionally, the engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOV-21G. Similar results were produced in tumor xenografts in nude mice. These results indicated that MKK4 acts as a tumor suppressor and may represent an important therapeutic target for the treatment of ovarian cancer.
    Tumor Biology 04/2011; 32(4):661-70. · 2.52 Impact Factor
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    ABSTRACT: To compare microwave endometrial ablation (MEA) using a new curved applicator with conventional surgical procedures in 26 patients with menorrhagia. Ten patients received MEA and 16 patients received conventional surgical procedures. Using a visual analog scale (VAS). MEA patients rated their menorrhagia, dysmenorrhea, and feelings of satisfaction from the procedure. The patients' intraoperative blood loss, operating time, and length of hospital stay were compared. Following MEA, the VAS scores were significantly decreased in the MEA patients for menorrhagia (p < 0.0001) and dysmenorrhea (p = 0.0002). The average VAS score regarding feelings of satisfaction for MEA was 8.9 (full score = 10). Mean blood loss, operating time, and mean length of hospital stay were significantly decreased in the MEA group compared to the conventional surgical procedure group (p < 0.0001). MEA successfully controlled menorrhagia and achieved a high rate of satisfaction among patients.
    Clinical and experimental obstetrics & gynecology 01/2011; 38(1):33-7. · 0.38 Impact Factor
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    ABSTRACT: This study examined the biological and clinical significance of NAC1 expression in ovarian cancer and assessed whether NAC1 has the potential to be a therapeutic target. NAC1 expression and gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected by a retrospective chart review. NAC1 gene knockdown using silencing RNA and a NAC1 gene transfection system were used to assess NAC1 function in ovarian cancer tissue samples. The frequency of positive NAC1 expression in serous adenocarcinomas (50.0%:22/44) was significantly higher than that in the other histological subtypes (33.3%: 10/30). NAC1 gene amplification was identified in seven (9.5%) of 74 ovarian carcinomas. Positive NAC1 expression significantly correlated with shorter disease-free and overall survival (P = 0.002, P = 0.0048). A multivariate analysis showed that positive NAC1 expression was an independent prognostic factor for disease-free and overall survival after standard platinum-taxane chemotherapy (P = 0.0027, P = 0.0302). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in ovarian cancer cell lines KF28 and TOV-21G, which normally lacked NAC1 expression. These findings indicate that NAC1 over-expression is critical to the growth and survival of ovarian cancers. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, NAC1-targeted therapy may benefit ovarian cancer patients with NAC1 expression.
    Gynecologic Oncology 12/2010; 119(3):469-78. · 3.93 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the role of NAC1 in the development of endometrial cancer. NAC1 expression and localization were assessed with immunohistochemistry in the normal cyclic human endometrium, hyperplastic endometrium, and endometrial cancer. Expression of NAC1 in the glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases, endometrial hyperplasia, and endometrial carcinoma. NAC1 expression was down-regulated during endometrial carcinogenesis. There were significant correlations between positive NAC1 expression and pathological grade (P=0.037). No significant associations were found between NAC1 expression and the other clinicopathological characteristics including patient age, FIGO staging, depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, menopause, or body mass index. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and JHEM2 cell lines, all of which overexpressed NAC1. Ectopic overexpression of the NAC1 gene stimulated cell proliferation in the HEC1B, and JHEM1 endometrial cancer cell lines, which have lower endogenous NAC1 expression. Endometrial carcinomas with NAC1 overexpression are clinically aggressive, high-grade carcinomas. Therefore, detection of NAC1 overexpression in endometrial cancers may identify patients who will benefit from NAC1 targeted therapy.
    International Journal of Oncology 05/2010; 36(5):1097-103. · 2.66 Impact Factor
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    ABSTRACT: To asses the effectiveness of microwave endometrial ablation (MEA) using a new curved applicator for the emergent control of uterine hemorrhage. Seven patients received emergency MEA. Three out of seven patients were treated with MEA as their primary procedure, and four out of seven patients were treated for an intraoperative hemorrhage. In all three patients treated preoperatively, MEA was highly effective and successfully controlled acute uterine hemorrhage. Four out of seven patients were treated with MEA for a hemorrhage following resection of a submucosal myoma or polyp. MEA successfully controlled bleeding in all four patients, thereby preventing them from undergoing hysterectomy. Our results suggest that emergency MEA is a promising way to control a life-threatening uterine hemorrhage.
    Archives of Gynecology 05/2010; 283(5):1065-8. · 0.91 Impact Factor
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    ABSTRACT: Malignant transformation of an ovarian mature cystic teratoma is very rare; it arises in about 1-2% of all dermoid cysts. No standard treatment has been established for advanced and recurrent disease. In Case 1, a 78-year-old woman was diagnosed with squamous cell carcinoma arising from a mature cystic teratoma of the ovary after undergoing right salpingo-oophorectomy (RSO). She was treated with chemotherapy(TC), but the carcinoma recurred 2 months after completing first-line chemotherapy. She began second-line chemotherapy (PEC: CBDCA+PEP+etoposide), but became disoriented on the second day of treatment, and could not complete the schedule. She died 2 months after the recurrence. Case 2 was a 60-year-old woman diagnosed with stage Ic disease when she underwent a computed tomography scan during chemotherapy for breast cancer recurrence in her liver. She underwent bilateral salpingo-oophorectomy (BSO), and was treated with chemotherapy (TC+trastuzumab). She received 5 courses, but the breast cancer metastases enlarged and her chemotherapy regimen was changed. Five months later, after completing 5 courses of TC+trastuzumab, she had disseminated recurrence in the pelvis and also had a mass. She developed ileus and underwent a colostomy. She then underwent transcatheter arterial embolization via the inferior mesenteric artery and received cisplatin (100 mg/body) as second-line chemotherapy. The tumor was reduced in size about 30%, for a partial remission. However, her breast cancer recurrence was exacerbated and she died. The results of TAE, however, showed that it may be an effective second-line therapy for recurrent squamous cell carcinoma arising from a mature cystic teratoma.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2010; 37(4):747-52.
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    ABSTRACT: In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase 4 (MKK4) expression to development of ovarian cancer. Over-expression of the MKK4 gene in TOV-21 G cells, a line with homozygous deletion of MKK4, resulted in morphologic changes in which cells growing in a scattered, fibroblast-like pattern formed tightly packed colonies. Based on a wound healing assay and a Matrigel invasion assay, we determined that both motility and invasiveness of MKK4-transfected TOV-21G cells were significantly reduced compared to control vector-transfected cells. To confirm that MKK4 expression related to tumor invasion resulted from an epithelial to mesenchymal transition (EMT)-like morphological change, we used 2 independent but complementary approaches. MKK4 gene knockdown in MDAH 2774 cells over-expressing MKK4 increased invasion activity. Additionally, engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOVG-21G. Interestingly, we found that MKK4 upregulation caused downregulation of phosphorylated NF-κB and Twist, as well as upregulation of E-cadherin, in TOVG-21G and SKOV3 cells. Reciprocal results were obtained in MDAH 2774 cells with MKK4 knockdown. Our results suggest that MKK4 downregulation causes increased phosphorylation NF-κB. This promotes Twist over-expression, resulting in E-cadherin downregulation that induces EMT in ovarian cancer.
    International Journal of Cancer 03/2010; 128(1):94-104. · 6.20 Impact Factor
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    ABSTRACT: The aim of this study was to clarify the functional role of Notch3 in human cervical carcinomas. Notch3 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. We used dual-color fluorescence in situ hybridization (FISH) to analyze DNA copy number alterations in cervical cancer. Inactivation of Notch3 and knocking down Notch3 gene were done using gamma-secretase inhibitor and Notch 3 specific SiRNA to asses Notch3 function in cervical cancer either in vivo or in vitro. Immunohistochemical analysis revealed that Notch3 was significantly overexpressed in cervical squamous cell carcinomas compared with adenocarcinomas. In contrast to normal cervical tissue and cervical intraepithelial neoplasms [CINs], squamous cell carcinomas demonstrated higher nuclear Notch3 immunoreactivity. Notch3 amplification was not found in any cervical carcinomas using FISH analysis. Notch3 nuclear expression was significantly correlated with Jagged-1, a putative Notch3 ligand, and Pbx1b, a potential Notch3 downstream target (P<0.05).Patients with cervical carcinomas positive for nuclear Notch3 expression had significantly shorter overall survival than their peers whose tumors did not express nuclear Notch3. Inactivation of Notch3 decreased cell proliferation and induced apoptosis in ME180 and SKGIIIb cell lines that overexpressed Notch3. Injection of a gamma-secretase inhibitor into ME180 cell tumors established on mice, demonstrated a reduction in tumor growth. Our findings suggest that Notch3 might play important role for the proliferation and survival of Notch3 overexpressing tumors and that inactivation of Notch3 may represent a new therapeutic avenue for cervical squamous cell carcinomas.
    Gynecologic Oncology 03/2010; 117(3):409-16. · 3.93 Impact Factor
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    ABSTRACT: Exaggerated placental site is defined as a non-neoplastic trophoblastic lesion featuring exuberant infiltration into the endometrium and myometrium by intermediate trophoblasts and syncytiotrophoblasts. Exaggerated placental site can occur following normal or ectopic pregnancy, abortion, or hydatidiform mole. We encountered a case of reactive exaggerated placental site seven months following normal pregnancy that clinically mimicked placental site trophoblastic tumor. Few reports have described the clinical course, histopathology and differential diagnosis of exaggerated placental site; we present our patient's case together with histopathological observations and review of related literature.
    European journal of gynaecological oncology 01/2010; 31(5):586-9. · 0.58 Impact Factor
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    ABSTRACT: The extracellular-regulated kinase (ERK) signaling pathway plays an important role in regulating the malignant potential of a cancer cell. However, the effect of ERK signaling on cancer metastasis is not clearly understood. In the present study, we examined the status of ERK activation in 88 ovarian carcinomas in order to clarify the clinicopathological and prognostic significance of phosphorylated ERK1/2 (p-ERK1/2). p-ERK1/2 expression was identified in 37 (42%) of 88 ovarian carcinomas. There was no significant correlation between p-ERK1/2 expression and any of the clinicopathological factors tested. No significant correlation between p-ERK1/2 expression and overall survival was found in patients with ovarian carcinoma treated with platinum and taxane chemotherapy (P=0.426). Next, to clarify the role of ERK1/2 activation in ovarian cancers, we inactivated ERK1/2 in ovarian cancer cells using the MEK inhibitor, CI-1040, which prevents ERK1/2 activation. Based on simulated wound healing and invasion chamber assays, we found that the motility and invasion of ES2 and MPSC1 cells with p-ERK1/2 were significantly reduced (P<0.01) after treatment with CI-1040. By contrast, CI-1040 did not have any effect on KF28 cells, which were negative for p-ERK1/2. Twist was down-regulated simultaneously with p-ERK1/2 following treatment of ES2 and MPSC1 cells with CI-1040. Immunohistochemistry of ovarian carcinoma tissue revealed that the increased expression of p-ERK1/2 significantly correlated with Twist expression (P<0.01). The findings in this study provide new insight into the biological role of ERK signaling in ovarian carcinomas. Additionally, our observations have an important therapeutic implication for patients with ovarian cancers that express p-ERK1/2 as these patients may potentially benefit from CI-1040 therapy.
    Experimental and therapeutic medicine 01/2010; 1(4):591-596. · 0.34 Impact Factor
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    ABSTRACT: Stage1a1 cervical cancer has been established to define a subset of the disease in patients who may safely be managed more conservatively and who have an excellent prognosis. Recently, however, a number of stage 1a1 cases with lymph node metastasis have been reported. Some of these cases had positive lymphovascular space invasion (LVSI), which some studies have identified as a negative prognostic factor. There is still, however, disagreement between the International Federation of Gynecology and Obstetrics (FIGO) and the Society of Gynecologic Oncologists (SGO) regarding whether LVSI may be used as a staging criterion. We report a 36-year-old patient with stage 1a1 cervical cancer who was diagnosed with multiple pelvic and parametrial lymph node metastases. Histopathology showed extensive LVSI. While stage 1a1 cases may still be managed conservatively, physicians must consider the possibility of lymph node metastasis, particularly in patients with positive LVSI, and counsel patients accordingly.
    International Journal of Clinical Oncology 12/2009; 14(6):564-7. · 1.41 Impact Factor
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    ABSTRACT: Primary osteosarcoma originating from the ovary is an exceedingly rare, highly malignant tumor. Only a few cases have been reported in the past few decades. We describe a 50-year-old postmenopausal woman who presented with a large abdominal mass. The clinical diagnosis was malignant ovarian cancer. Her disease was aggressive; she had no response to systemic chemotherapy and died within 1 month of presentation. A definitive diagnosis of primary ovarian osteosarcoma was made by histopathological examination of autopsy specimens. Although rare, primary ovarian osteosarcoma should be considered in the differential diagnosis of a large, rapidly progressing pelvic mass in a postmenopausal woman. Early diagnosis provides hope of a complete surgical resection, which is currently the only promising treatment.
    International Journal of Clinical Oncology 05/2009; 14(2):163-6. · 1.73 Impact Factor
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    ABSTRACT: Ovarian germ cell tumors are malignant tumors which commonly develop during childhood, and which are sensitive to chemotherapy. We have had a case of germ cell tumors which showed resistance to first-line PEP(BEP)chemotherapy. As second-line chemotherapy, VeIP therapy was used, because it is possible that this therapy is effective against recurrent testicular germ cell tumors. The patient was fourteen years old. She experienced acute abdominal pain and visited the hospital, where she was diagnosed with torsion of an ovarian tumor. An emergency laparotomy and right salpingoophorectomy were performed, the pathological diagnosis being stage Ia ovarian dysgerminoma G1. She was followed for two years until her serum hCG-CTP elevated to 1.4 mIU/mL. An MRI revealed an abnormal signal in the left ovary, so we diagnosed this as a recurrence of the dysgerminoma. Then she received chemotherapy PEP(BEP), but after eight months of PEP (BEP), her serum hCG-CTP was again elevated to 14.5 mIU/mL. A recurrence was detected with an MRI and PET-CT, and another laparotomy was performed. The recurrent region was detected in the left ovary. A left ovarian cystectomy was performed in which CDDP ip was used. After the operation, the patient again underwent chemotherapy. VeIP (vinblastine+ifosfamide+cisplatin)was chosen as the second-line regimen. After 6 courses of this therapy, she had a follow-up operation. No recurrence region was found in the pelvic area. She remains without recurrence of this disease 24 months after VeIP therapy. This case suggests that VeIP therapy might be an effective second-line therapy for patients with PEP(BEP)-resistant ovarian dysgerminoma.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2009; 36(3):513-7.
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    ABSTRACT: The purpose of this study was to investigate the expression and localization of NAC1, a member of the BTB/POZ gene family in the human cyclic endometrium. NAC1 expression in normal cyclic endometrium was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. To elucidate the molecular mechanisms of NAC1 expression in the normal endometrium endometrial carcinoma cell lines (Ishikawa, HHUA; ER+, PR+) and primary cultured normal endometria were tested in a sex steroid induction assay and a NAC1 knockdown assay using siRNA. Expression of NAC1 in glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases. Both NAC1 RNA and protein expression were up-regulated by treatment with 10 nmol/L 17beta-Estradiol (E2) in Ishikawa, HHUA and primary cultured normal endometrial cells. The estrogen receptor antagonist ICI 182,780 significantly attenuated E2-induced NAC1 expression. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and normal endometria, all of which expressed NAC1. Furthermore, NAC1 siRNA significantly abrogated estrogen-driven cellular proliferation in Ishikawa, HHUA, and primary cultured normal endometrial cells, whereas the control siRNA had no effect on cell growth in any of these cells. These findings suggest that NAC1 is functionally involved in E2-induced cell growth of the normal endometrial glandular cells. Because NAC1 is thought to have oncogenic potential, the current findings may provide new insight into the mechanism of estrogen induced endometrial carcinogenesis.
    Clinical Cancer Research 03/2009; 15(3):804-11. · 7.84 Impact Factor
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    ABSTRACT: Ovarian tumors of low malignant potential (LMP) appear to be intermediate between adenomas and ovarian carcinomas. Such tumors are often associated with a significantly better prognosis than for ovarian carcinomas. However, a subset of LMPs can progress and become lethal even in patients with early-stage disease. In order to seek sensitive diagnostic tools to monitor patients after surgical therapy, we performed a genome-wide scan for LOH in 37 early-stage mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reported to be associated with ovarian carcinoma. Fractional allelic loss (FAL) values were calculated as (loci scored with LOH)/(total informative loci) for each sample. With respect to tumor recurrence, high FAL values were more frequent in recurrent tumors than in non-recurrent tumors. Using the screening markers, FAL values for recurrent tumors were significantly higher than for non-recurrent tumors (19.8% vs 6.3%, respectively, p < 0.0001). Similar results were obtained using the hotspot markers (22.2% vs 7.1%, respectively, p < 0.0001). A significant correlation between FAL values obtained using screening markers and those based on hotspot markers was observed (R = 0.460, p = 0.003). Our findings suggest that a specific type of genetic instability (i.e., chromosomal instability, CIN) may exist in mucinous LMPs, and that this instability may indicate tumors with an aggressive biological nature. Therefore, FAL values may represent a new biomarker for risk prediction in early-stage mucinous LMP tumors.
    European journal of gynaecological oncology 02/2009; 30(1):16-9. · 0.58 Impact Factor
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    ABSTRACT: Microwave endometrial ablation is a new, minimally invasive treatment option for menorrhagia. Its popularity in many countries is increasing due to its safety and simplicity. We treated menorrhagia due to submucosal myomas in two patients with a modified microwave endometrial ablation device. Surgery was contraindicated in the first patient secondary to medical co-morbidities and in the second patient because of acute hemorrhagic shock. In both cases, the operation was highly effective and each patient was satisfied with her treatment outcome. Given its safety, simplicity, and effectiveness, microwave endometrial ablation may be widely adopted for the emergent control of uterine bleeding in patients with poor surgical candidates.
    Archives of Gynecology 01/2009; 280(2):279-82. · 0.91 Impact Factor
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    ABSTRACT: This study examined the status of KRAS and BRAF mutations, in relation to extracellular signal-regulated protein kinase (ERK) activation in 58 ovarian carcinomas to clarify the clinicopathological and prognostic significance of KRAS/BRAF mutations. Somatic mutations of either KRAS or BRAF were identified in 12 (20.6%) out of 58 ovarian carcinomas. The frequency of KRAS/BRAF mutations in conventional serous high-grade carcinomas (4.0% : 1/25) was significantly lower than that in the other histological type (32.3% : 10/31). Phosphorylated ERK1/2 (p-ERK1/2) expression was identified in 18 (38.2%) out of 45 ovarian carcinomas. KRAS/BRAF mutation was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage I, II (P<0.001), and p-ERK1/2 (P<0.001). No significant correlations between KRAS/BRAF mutations or p-ERK1/2 expression and overall survival were found in patients with ovarian carcinoma treated with platinum and taxane chemotherapy (P=0.2460, P=0.9339, respectively). Next, to clarify the roles of ERK1/2 activation in ovarian cancers harbouring KRAS or BRAF mutations, we inactivated ERK1/2 in ovarian cancer cells using CI-1040. Cl-1040 is a compound that selectively inhibits MAP kinase kinase (MEK), an upstream regulator of ERK1/2, and thus prevents ERK1/2 activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated cancer cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. This was evident in both in vitro and in vivo studies. The findings in this study indicate that an activated ERK1/2 pathway is critical to tumour growth and survival of ovarian cancers with KRAS or BRAF mutations. Furthermore, they suggest that the CI-1040-induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian cancers. Therefore, ovarian cancer patients with KRAS or BRAF mutations may benefit from CI-1040 treatment.
    British Journal of Cancer 11/2008; 99(12):2020-8. · 5.08 Impact Factor