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Problem: To determine the role of inactivated GSK3β with respect to Wnt/β-catenin pathway activation in HPV-16/18-associated cervical cancer., Method of Study: The expression of active (pGSK3β-Try(216)), inactive (pGSK3β-Ser(9)), and c-Myc as well as HPV-16/18 infection was analyzed in cervical intra-epithelial neoplasia (CIN), squamous cell carcinoma (SCCs) and normal by immunohistochemistry and multiplex PCR. The proteins level was also compared with β-catenin and APC expression., Results: The dramatic decrease of pGSK3β-Try(216) expression but ectopic overexpression of pGSK3β-Ser(9) and c-Myc was observed both in CIN and SCCs samples compared to normal tissues. 57/67 CIN and 132/153 SCCs showed HPV-16 infection, while 3/67 CIN and 4/153 SCCs were harbored with HPV-18 infection. Both the proteins were significantly upregulated in HPV-16 infected cases (P = 0.0001; P = 0.001) and also positively correlated with nuclear β-catenin (P = 0.0001; P = 0.0001)., Conclusion: The process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3β inactivation and overactivation of Wnt/β-catenin pathway., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: To study the innate immune response -TLR2 TLR 4 and iNOS expression in female genital Chlamydia trachomatis infection., Method: TLR 2, TLR 4, and iNOS expression was evaluated by real-time PCR in C. trachomatis-infected asymptomatic, mucopurulent cervicitis (MPC), and fertility disorders (FD) women. Expression of TLR signaling pathway genes was checked in vivo in C. trachomatis-infected cervical monocytes. Further, inos gene expression and nitric oxide release was assessed in vitro in THP-1 cell line upon chlamydial infection., Results: TLR2, TLR4, and iNOS expression was significantly (P < 0.05) higher in C. trachomatis-positive women with FD, MPC, and asymptomatic women, respectively, than in control. Chlamydial infection significantly upregulates CD86, TLR4, MyD88, IRAK2, nF-κB, IL-1,β and IL-12 genes. Expression of iNOS gene was found to be significantly (P < 0.05) high 12 hrs post-infection., Conclusions: Chlamydia trachomatis stimulates innate immune cells by activation of TLR2/TLR 4. Overall data indicate that recognition by TLR4 helps in initiation of immune response while recognition by TLR2 leads to secretion of inflammatory cytokines while iNOS-induced nitric oxide production helps in clearing Chlamydia. These results are first to provide initial insights into how innate immune response operates in human cervical monocytes upon chlamydial infection., (© 2011 John Wiley & Sons A/S.)

Problem: Despite of advances in diagnosis and staging, the prognosis of hydatidiform mole (HM) remains intricate. HM possesses the substantial risk of developing persistent trophoblastic disease (PTD), which is considerably high for complete hydatidiform moles (CHMs). Significance of serum soluble Fas (sFas) and soluble FasL (sFasL) has been observed in various malignancies; however, there is no report till date on HM., Method of Study: The serum levels of sFas and sFasL were measured using enzyme-linked immunosorbent assay in 62 patients with CHMs and 64 healthy controls. The protein concentrations were also correlated with clinicopathological parameters, β-hCG level, and clinical outcome., Results: The serum sFas and sFasL levels in patients with CHM were significantly higher than those in control group (mean±SD: 703.497±491.759 versus 348.141±175.24; P<0.004 and 31.17±18.758 versus 18.802± 6.775; P<0.0001, respectively). Patients who progressed to PTD demonstrated higher sFas and sFasL concentrations than those who regressed spontaneously (794.211±415.892 versus 446.69±161.382; P<0.046 and 37.55±20.337 versus 22.763±6.52; P<0.011, respectively). Furthermore, significant associations were observed among sFas, sFasL, and β-hCG levels (P<0.0001 for all associations)., Conclusion: Production of sFas and sFasL may play a crucial role in progression of CHM and may serve both as prognostic tool and therapeutic target in improving the clinical outcome., (© 2011 John Wiley & Sons A/S.)

Problem: Hydatidiform mole (molar pregnancy) is the commonest form of Gestational Trophoblastic Disease, with the risk of undergoing malignant transformation. The molecular pathway leading to pathogenesis and progression of molar pregnancy is barely understood. The study focuses on Fas/FasL system which represents one of the main apoptotic pathways controlling placental morphogenesis., Method of Study:   Placental tissues from 52 patients with complete hydatidiform moles (CHMs) and 55 age-matched controls were examined for Fas and FasL expression using immunohistochemistry, immunofluorescence and Western blotting. The protein expression was also correlated with trophoblast apoptosis (assessed by M30 Cyto DEATH), clinico-pathological parameters and disease progression., Results:   Immunohistochemistry and immunofluorescence revealed both cytoplasmic and membranous expression of Fas in villous syncytiotrophoblast as well as cytotrophoblast but FasL was confined merely to the cytoplasm of syncytiotrophoblast. Both Fas (cytoplasm and membrane) and FasL were significantly upregulated in syncytiotrophoblast of CHMs (P = 0.004, P < 0.0001 and P < 0.0002 respectively) and showed a positive association between them (P = 0.019). However, none of the proteins reveal any correlation with M30 index. The results were revalidated using Western blotting., Conclusion: This study demonstrated differential expression of Fas and FasL in CHMs and its implications in the pathogenesis of molar pregnancy has been discussed., (© 2010 John Wiley & Sons A/S.)

Problem: Chlamydial infections are often associated with various fertility-related disorders. Serological prediction of these has limitations, as they do not differentiate between past and current infections. Thus, we looked for local markers that could predict more precisely women at higher risk of developing severe complications., Method of Study: A total of 320 Chlamydia trachomatis positive women with or without fertility disorders were tested for the prevalence of immunoglobulin A antibodies to synthetic peptides of chlamydial heat-shock protein 60 (cHSP60) and cHSP10 along with cervical interferon-gamma (IFN-gamma) and serum C-reactive protein (CRP) levels., Results: Positive IFN-gamma level was the single best predictor for fertility disorder [odds ratio (OR) 15.4]. The predictive value of IFN-gamma could be significantly improved only by the addition of CRP test (OR 37.9)., Conclusion: Positive IFN-gamma levels in cervical washes along with elevated CRP levels could be used to predict women who are at higher risk of developing fertility disorders.