Please cite this paper as: Mahmud G, Zaman F, Jafarey S, Khan RL, Sohail R, Fatima S. Achieving Millennium Development Goals 4 and 5 in Pakistan. BJOG 2011;118 (Supp. 2):69–77. Pakistan is a signatory of many international development strategies including the Millennium Development Goals, and the government is committed to achieving a reduction in infant mortality rate from 72 to <55 per 1000 live births, the newborn mortality rate from 55 to <40 per 1000 live births and the maternal mortality rate from 276 per 100 000 to 140 per 100 000 live births by 2015. Maternal, newborn and child health play a key role in reducing poverty and promoting social and economic development. Improvement in maternal and child health is a priority agenda of the Government of Pakistan.
HPV encoded proteins can elicit ectopic protein–protein interactions that re-wire signaling pathways, in a mode that promotes malignancy. Moreover, accumulating data related to HPV is now providing compelling substantiation of a central role played by HPV in escaping immunosurveillance and impairment of apoptotic response. What emerges is an intricate network of Wnt, TGF, Notch signaling cascades that forms higher-order ligand–receptor complexes routing downstream signaling in HPV infected cells. These HPV infected cells are regulated both extracellularly by ligand receptor axis and intracellularly by HPV encoded proteins and impair TRAIL mediated apoptosis. We divide this review into different sections addressing how linear signaling pathways integrate to facilitate carcinogenesis and compounds that directly or indirectly reverse these aberrant interactions offer new possibilities for therapy in cancer. Although HPV encoded proteins mediated misrepresentation of pathways is difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can target dysregulated pathways in HPV infected cervical cancer cells, thus setting the stage for preclinical models and clinical trials.
Ovarian cancer has emerged as a multifaceted and genomically complex disease. Genetic/epigenetic mutations, suppression of tumor suppressors, overexpression of oncogenes, rewiring of intracellular signaling cascades and loss of apoptosis are some of the deeply studied mechanisms. In vitro and in vivo studies have highlighted different molecular mechanisms that regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis in ovarian cancer. In this review, we bring to limelight, expansion in understanding systematical characterization of ovarian cancer cells has led to the rapid development of new drugs and treatments to target negative regulators of TRAIL mediated signaling pathway. Wide ranging synthetic and natural agents have been shown to stimulate mRNA and protein expression of death receptors. This review is compartmentalized into programmed cell death protein 4, platelet-derived growth factor signaling and miRNA control of TRAIL mediated signaling to ovarian cancer. Mapatumumab and PRO95780 have been tested for efficacy against ovarian cancer. Use of high-throughput screening assays will aid in dissecting the heterogeneity of this disease and increasing a long-term survival which might be achieved by translating rapidly accumulating information obtained from molecular and cellular studies to clinic researches.
Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine.
Urinary stone disease or nephrolithiasis, the third most common disease of the urinary tract, is a major health issue due to its high prevalence, occurrence, and recurrence. The hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh. Stone size influences the rate of spontaneous stone passage.Our aim was to compare the efficacy & the frequency of stone-free patients after intervention at 1 week after extracorporeal shock wave litho-tripsy (ESWL) and ureterorenoscopic (URS) manipulation for proximal ureteric stone (10–15 mm size).This randomized control trial was done in the department of Urology, KRL Hospital Islamabad from 18th Nov 2019 to 18th May 2020. After meeting the inclusion criteria, 100 patients were enrolled and were divided into two groups. The first group was treated with ESWL and the other with URS. Then, procedures were done. Follow-up was noted after 1 week in the stone clinic.The average age of the patients was 39.71 ± 10.17 years. Efficacy in the ESWL group was found in 68% cases while in the URS group, efficacy was noticed in 76% cases (P > 0.05). Male patients were three times at a higher risk of recurrence as compared to females.This study concluded that both ESWL and URS are equally effective statistically in terms of the frequency of stone-free patients at 1 week for proximal ureteric stone (10–15 mm size).
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