Implications of the use of eukaryotic translation initiation factor 5A (eIF5A) for prognosis and treatment of hepatocellular carcinoma

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Pelvic organ prolapse symptoms in relation to POPQ, ordinal stages and ultrasound prolapse assessment

Adequate staging of pelvic organ prolapse is important in clinical practice and research. The ability of the POPQ, ordinal stages and ultrasound prolapse assessment were evaluated for their ability to discriminate between women with and without prolapse symptoms. The leading edge of the predominant compartment in the three assessment systems was used for the calculation of receiver operating characteristics curves. Two hundred and sixty five (265) consecutive women were evaluated. The area under the receiver operating characteristics curve for the three staging systems ranged from 0.715 to 0.783. POPQ staging and ordinal staging performed equally well in the prediction of prolapse symptoms (p = 0.780), and both performed better as compared with ultrasound prolapse assessment (p = 0.048 and p = 0.015, respectively). Prolapse staging can equally be performed by the POPQ and ordinal stages systems as far as the discrimination between women with and without prolapse symptoms is concerned. The ultrasound prolapse assessment does not perform better as compared with these two systems

Anti-cadherin-17 antibody modulates Beta-catenin signaling and tumorigenicity of hepatocellular carcinoma

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Tumorigenic properties of serine peptidase inhibitor, Kazal type 1 (SPINK1) in hepatocellular carcinoma

Poster & abstractTheme: Integration and Collaboration - the Way Forwar

Targeting Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) as a Potential Treatment for Hepatocellular Carcinoma

Poster PresentationBackground: Hepatocellular carcinoma (HCC) ranks fourth as the most common cancer worldwide with high prevalence in Southeast Asia and Africa and the number of new cases in America and Europe is on the rise. HCC patients usually have poor prognosis partly due to the limitations of current treatments. For instance, surgical resection as the mainstream treatment for HCC patients is not suitable for those with advanced disease and poor liver functions. In addition, a subgroup of HCC patients suffers from post-treatment recurrence. All these factors make HCC as the third leading cause of cancer-related mortality. To address this clinical dismal, it is important to research for new therapeutic targets for HCC. Our previous gene profiling analysis implicated a secretory trypsin inhibitor named serine peptidase inhibitor, Kazal type 1 (SPINK1) as a potential molecular target for HCC because of its high expression in liver tumors. Other studies also revealed high serum level of SPINK1 in patients with cancers of various types including HCC. In view of these observations, this study aims to study the role of SPINK1 in liver tumorigenesis. Objectives: To study the role of SPINK1 in liver tumorigenesis Methods: High expression of SPINK1 was validated using quantitative polymerase chain reaction (qPCR) in tumor (T) and adjacent non-tumor (NT) tissues of 60 HCC patients. In examining the involvement of SPINK1 in HCC, loss-of-function approach by short hairpin RNA (shRNA)-based RNA interference (RNAi) was performed to suppress SPINK1 expression in HCC cells. Tumorigenic phenotypes like proliferation, migration and colony formation of these SPINK1-suppressed cells were examined using various in vitro assays. The abilities of these cells to form subcutaneous tumors in nude mice were also assessed. Finally, the downstream signaling pathway associated with SPINK1 suppression was delineated. Results: qPCR results demonstrated the up-regulation of SPINK1 (T/NT ≥ 2) in 68% (41/60) of HCC cases. Such high expression was positively correlated with poor tumor differentiation (Edmondson grading, p = 0.034) and late tumor stage (pTNM staging, p = 0.046). This clinical analysis revealed the involvement of SPINK1 in severe HCC condition. When SPINK1 was suppressed in HCC cells using shRNA, a reduction in proliferation, migration and colony formation ability of these cells was demonstrated. When these cells were used to inoculate into nude mice to form subcutaneous tumors, tumor xenografts derived from SPINK1-suppressed cells did not associate with growth advantage. These reduced tumorigenic properties and tumorigenicity of HCC cells after SPINK1 suppression led to an inactivation of Raf/MEK/ERK pathway, such that a down-regulation of the phosphorylated forms of Raf, MEK, ERK and Akt was observed in SPINK1-suppressed cells. Conclusion: High expression of SPINK1 in human liver tumors indicates severe tumor progression. Suppressing SPINK1 expression in HCC cells alleviates tumor phenotypes and tumorigenicity in vitro and in vivo. Findings reported here support SPINK1 as a potential biotherapeutic for HCC and implicate knockdown of its expression as a treatment for this liver disease

Oncofetal Molecules as Biomarkers and Drug Targets for Hepatic Cancer

Hepatocellular carcinoma (HCC) is a major type of liver cancer prevalent in Asia and Africa, with a global increase in numbers in western countries. Despite decades of efforts in improving management of this malignancy, prognosis of patients still remains suboptimal. Frontline surgical treatments and traditional diagnostic methods suffer from own limitations. To alleviate this clinical dismal, research for alternated and supplemental methods are imperative. Different studies have discovered a panel of molecules related to tumorigenesis. Among them, a class of oncofetal molecules, characterized by their abundance in fetal livers and HCC but not in adult healthy livers, seems to serve as biomarkers and therapeutic targets for HCC. Tumorigenesis and embryogenesis share common characteristics and undergo similar processes in terms of proliferation, division, plasticity, motility, and convergence of mechanistic pathways. This chapter reviews several oncofetal molecules of livers including alpha-fetoprotein (AFP), glypican-3 (GPC3), insulin-like growth factor II mRNA binding protein 3 (IMP3), survivin, Golgi protein 73 (GP73), cadherin-17 (CDH17), and granulin-epithelin precursor (GEP) for their diagnostic and prognostic values. In addition, how these molecules can be used for developing therapies for HCC is also discussed. Most of the mentioned oncofetal molecules are found associating with poor disease conditions, while some of them have been studied for their potential capability in treating tumors in preclinical animal models. In summary, oncofetal molecules belong to an emerging class of candidates with potential application in improving current methods of diagnosis, prognosis, and treatment of HCC