The potential molecular therapeutic approach in targeting ovarian clear cell carcinoma

EditorialOvarian Clear Cell Carcinoma (OCCC) is a distinctive subtype of Epithelial Ovarian Cancer (EOC). Compared with other subtypes of EOC, CCC has relatively poor in prognosis and bad outcome in current clinical management using maximal cytoreduction and platinum plus paclitaxel–based combined chemotherapy. Therefore, the investigation of molecular therapeutic approaches targeting at signaling pathways associated with chemoresistance is needed. This review describes some recent potential signaling pathway targets and also suggests putative small molecule kinase inhibitors as well as natural anti-cancer agents in combating this disease.published_or_final_versio

Down-regulation of Sox7 is associated with aberrant activation of Wnt/b-catenin signaling in endometrial cancer

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The prognostic and therapeutic potential of AMP-activated protein kinase in ovarian cancer

Topics 3 - Translational Research for Ovarian Cancer: no. 3-2Ovarian cancer is one of the leading causes of cancer-associated death in women. The high mortality is due to its poor prognosis as most cases are found in late stages. Therefore, searching reliable tumor markers is urgently needed for clinical management of this disease. Altered cellular metabolism is a crucial phenomenon for the development and progression of ovarian cancer. AMP-activated protein kinase (AMPK) acts as a key intracellular energy sensor and regulator for governing energy balance homeostasis. It also closely links with cancer cell metabolism. Others and we have reported that the activation of AMPK by pharmacological agents shows cytotoxicity to cancer cells, indicating that targeting AMPK could be a promising therapeutic approach. On the other hand, our study also demonstrated that the AMPK activity had an inversely correlation between tumor stage and/or high grade ovarian cancer. Import...postprin

PITX2 transcription factor is overexpressed and involved in the tumorigenicity of ovarian cancer

Free Paper Session - Biomedicine: abstract no. A2

Molecular detection of minimal residual disease for patients with leukemia and lymphoma

Although a complete clinical remission can often be achieved with chemotherapy for patients with leukaemia and lymphoma, relapses still occur. Residual tumour cells probably have survived therapy and account for subsequent disease relapse. The sensitivity of conventioned ways of detecting residual tumour cells, such as morphological studies, immunophenotyping, and cytogenetics, is only about 1% to 5% and may be inadequate. Polymerase chain reaction technology had provided a simple and highly sensitive means for the detection of minimal residual disease. The technology has been successfully applied to study biopsy samples obtained from patients with leukaemia and lymphpma. Its clinical usefulness, however, requires further evaluation by prospective clinical studies.published_or_final_versio

Mechanisms of Chemoresistance in Human Ovarian Cancer at a Glance

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Behavioral characteristics of chinese adolescents with dyslexia: The use of teachers' behavior checklist in Hong Kong

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Screening for Chinese children with dyslexia in Hong Kong: The use of the teachers' behaviour checklist

Primary school teachers rated the frequency of occurrence of 65 reading-related behavioural characteristics in a sample of 251 Grade 1 to Grade 6 Chinese school children in Hong Kong. These behavioural characteristics were in the areas of general performance, reading, dictation, writing, mathematics, language, memory, concentration, sequential ability, motor co-ordination, spatial orientation, and social/emotional adjustment. Of these 12 areas, 10 yielded scale scores that could distinguish children with dyslexia from those without dyslexia, identified on the basis of their performance in five domains of literacy and cognitive skills. Using a summary score derived from the 10 relevant scales, an optimal cut-off score was suggested to arrive at a balance between high sensitivity and an acceptable rate of false positives in screening for children with dyslexia. The need for cross-replication in screening children with dyslexia using the behaviour checklist with different samples of school students is emphasised.published_or_final_versio

Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer

AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-beta1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-beta1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-beta1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-beta1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-beta1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-beta1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-beta1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-beta1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer.published_or_final_versio

Epigenetic silencing of microRNA-199b-5p is associated with acquired chemoresistance via activation of JAG1-Notch1 signaling in ovarian cancer.

Epithelial ovarian cancer is a highly lethal and aggressive gynecological malignancy. The high mortality rate is due in part to the fact that many advanced cancer patients become refractory to current chemotherapeutic agents, leading to tumor recurrence and death. However, the underlying mechanisms leading to chemoresistance remain obscure. Here, we report that the loss of miR-199b-5p due to progressive epigenetic silencing leads to the activation of the JAG1-mediated Notch1 signaling cascade, thereby leading to the development of acquired chemoresistance in ovarian cancer. Using miRCURY LNATM microRNA array and Q-PCR analyses of two pairs of cisplatin-sensitive and -resistant ovarian cancer cell lines, we identified miR-199b-5p as significantly down-regulated in cisplatin-resistant ovarian cancer cells and confirmed that miR-199b-5p is clinically associated with advanced and poor survival ovarian cancers. Interestingly, the loss of miR-199b-5p could be restored by 5-Aza-dC-mediated demethylation, and methylated specific PCR (MS-PCR), bisulfite-sequencing and pyrosequencing revealed that the promoter region of miR-199b-5p was hypermethylated. Computational and mechanistic analyses identified JAG1 as a primary target of miR-199b-5p. Notably, the reduced expression of miR-199b-5p was found to be inversely correlated with the increased expression of JAG1 using an ovarian cancer tissue array. Enforced expression of miR-199b-5p sensitized ovarian cancer cells to cisplatin-induced cytotoxicity both in vitro and in vivo. Conversely, re-expression of miR-199b-5p and siRNA-mediated JAG1 knockdown or treatment with Notch specific inhibitor γ-secretase (GSI) attenuated JAG1-Notch1 signaling activity, thereby enhancing cisplatin-mediated cell cytotoxicity. Taken together, our study suggests that the epigenetic silencing of miR-199b-5p during tumor progression is significantly associated with acquired chemoresistance in ovarian cancer through the activation of JAG1-Notch1 signaling.published_or_final_versio