Laboratory for Translational Oncology and Personalized Medicine

Pakistan

Laboratory for Translational Oncology and Personalized Medicine

Pakistan
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Qadir M.I.,Bahauddin Zakariya University | Ali M.,Bahauddin Zakariya University | Muhammad S.A.,Bahauddin Zakariya University | Hanif M.,Bahauddin Zakariya University | And 2 more authors.
Reviews in Medical Microbiology | Year: 2015

AIDS is a disease, caused by the HIV belonging to the retroviral family, transmitted through blood, body fluids and unprotected sexual contact that may involve a number of complications of immune, cardiovascular and pulmonary systems. Antiretroviral drugs are usually used in treatment. Mild bone loss occurs with the start of antiretroviral treatment. Bone mass seems to be constant and improved in prolonged use of antiretrovirals. Oral and parenteral bisphosphonates are useful in patients, and they are referred to first-line treatment to prevent frailty and bone rupture. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Saleem M.,The University of Faisalabad | Abbas K.,The University of Faisalabad | Manan M.,The University of Faisalabad | Ijaz H.,The University of Faisalabad | And 5 more authors.
Pakistan Journal of Pharmaceutical Sciences | Year: 2015

Epigenetics means the study of alterations in the genetic material that affect the phenotype but does not affect the genotype. Epigenetics cause alterations in cell properties, which are inherited; but it does not cause alterations in DNA sequence. Epigenetic mediated silencing of gene is of four types, which are DNA methylation, histone deacetylation, RNA associated silencing and Genomic imprinting. Other factors (environmental and xenobiotics) can also cause gene silencing but DNA methytlation and changes in histones of chromatin are two important changes, which are responsible for malignant diseases. Two groups of drugs are under development, which corrects the epigenetic alterations. These are histone deacetylation (HDAC) inhibitors and DNA methytransferase (DNMT) inhibitors. These drugs may be used in cancer because in cancer, hypermethylation of cancer suppressor gene causes gene silencing. Epigenetic therapy scope is likely to increase in future. © 2015, Pakistan Journal of Pharmaceutical Sciences. All rights reserved.


PubMed | The University of Faisalabad, Bahauddin Zakariya University and Laboratory for Translational Oncology and Personalized Medicine
Type: Journal Article | Journal: Pakistan journal of pharmaceutical sciences | Year: 2015

Epigenetics means the study of alterations in the genetic material that affect the phenotype but does not affect the genotype. Epigenetics cause alterations in cell properties, which are inherited; but it does not cause alterations in DNA sequence. Epigenetic mediated silencing of gene is of four types, which are DNA methylation, histone deacetylation, RNA associated silencing and Genomic imprinting. Other factors (environmental and xenobiotics) can also cause gene silencing but DNA methytlation and changes in histones of chromatin are two important changes, which are responsible for malignant diseases. Two groups of drugs are under development, which corrects the epigenetic alterations. These are histone deacetylation (HDAC) inhibitors and DNA methytransferase (DNMT) inhibitors. These drugs may be used in cancer because in cancer, hypermethylation of cancer suppressor gene causes gene silencing. Epigenetic therapy scope is likely to increase in future.


Farooqi A.A.,Laboratory for Translational Oncology and Personalized Medicine | Yaylim I.,Istanbul University | Ozkan N.E.,Istanbul University | Zaman F.,RLMC | And 3 more authors.
Archivum Immunologiae et Therapiae Experimentalis | Year: 2014

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. © 2014, L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.


Farooqi A.A.,KRL Hospital | Li K.-T.,Kaohsiung Medical University | Fayyaz S.,Laboratory for Translational Oncology and Personalized Medicine | Chang Y.-T.,National Sun Yat - sen University | And 6 more authors.
Tumor Biology | Year: 2015

Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy. © 2015, The Author(s).


Attar R.,Yeditepe University | Tabassum S.,Islamic University | Fayyaz S.,Laboratory For Translational Oncology and Personalized Medicine | Ahmad M.S.,Pmas Arid Agriculture University | And 7 more authors.
Cellular and Molecular Biology | Year: 2015

Cancer is a multifaceted and genomically complex disease. Research over the years has gradually provided a near complete resolution of cancer landscape and it is now known that genetic/epigenetic mutations, inactivation of tumor suppressors, Overexpression of oncogenes, spatio-temporally dysregulated intracellular signaling cascades, epithelial to mesenchymal transition (EMT), metastasis and loss of apoptosis are some of the most extensively studied biological mechanisms that underpin cancer development and progression. Increasingly it is being realized that current therapeutic interventions are becoming ineffective because of tumor heterogeneity and rapidly developing resistance against drugs. Considerable biological activities exerted by bioactive ingredients isolated from natural sources have revolutionized the field of natural product chemistry and rapid developments in preclinical studies are encouraging. Viscum album has emerged as a deeply studied natural source with substantial and multifaceted biological activities. In this review we have attempted to provide recent breakthroughs in existing scientific literature with emphasis on targeting of protein network in cancer cells. We partition this review into different sections, highlighting latest information from cell culture studies, preclinical and clinically oriented studies. We summarized how bioactive ingredients of Viscum album modulated extrinsic and intrinsic pathways in cancer cells. However, surprisingly, none of the study reported stimulatory effects on TRAIL receptors. The review provided in-depth analysis of how Viscum album modulated Endoplasmic Reticulum Stress in cancer cells and how bioactive chemicals tactfully targeted cytoskeletal machinery in cancer cells as evidenced by cell culture studies. It is noteworthy that Viscum album has entered into various phases of clinical trials, however, there are still knowledge gaps in our understanding regarding how various bioactive constituents of Viscum album modulate intracellular signaling cascades in cancer. Better and deeper comprehension oncogenic signaling cascades will prove to be helful in getting a step closer to individualized medicine. © 2015.


Mansoor Q.,Institute of Biomedical and Genetic Engineering | Fayyaz S.,Laboratory for Translational Oncology and Personalized Medicine | Farooqi A.A.,Laboratory for Translational Oncology and Personalized Medicine | Bhatti S.,The University of Lahore | Ismail M.,Institute of Biomedical and Genetic Engineering
Journal of experimental therapeutics & oncology | Year: 2013

Cancer is a life threatening complicated diseasethatarises because of wide-ranging environmental and cellular factors. These external and internal stresses disrupt the spatio-temporally controlled mechanisms of the cellular signalings. Accumulating evidence suggests that signal transductions are misrepresented in carcinogenesis and FGFR4 is reported to be involved in carcinogenesis. Although there is considerable evidence emphasizing the relationship between FGFR4 (G388R) mutation and carcinogenesis however rapidly accumulating data cannot be extrapolated to Pakistani population due to intra- and inter-ethnic variability. The study is focused on the trans-membrane mutation G388R of FGFR4 genes among different types of cancers diagnosed in local population in Pakistan. 103 breast cancer patients, 56 Lung cancer patients (both Small Cell and Non Small Cell) and 45 control subjects participated in this study. Sample of 5-ml venous blood was taken from participants with informed consent. DNA was extracted and PCR-RFLP analysis was done for G388R mutation in FGFR4 gene using site specific primers and restriction enzyme. The results were statistically evaluated in SPSS14. The genotypes of G388R in FGFR4 gene were in Hardy-Weinberg equilibrium. The percentage of normal homozygotes GG was found to be (48.5%) in breast cancer, (51.8%) in lung cancer. Glycine/arginine was (36.9%) in breast cancer, (42.9%) in lung cancer. We were unable to find a possible correlation between FGFR4 G388R mutation and different cancers in local population.


Halim T.A.,RLMC | Farooqi A.A.,Laboratory for Translational oncology and Personalized Medicine | Zaman F.,RLMC
Cancer Cell International | Year: 2013

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. © 2013 Halim et al.; licensee BioMed Central Ltd.


PubMed | Laboratory for Translational Oncology and Personalized Medicine
Type: Journal Article | Journal: Archivum immunologiae et therapiae experimentalis | Year: 2014

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.


PubMed | Autonomous University of Guerrero, Institute of Biomedical and Genetic Engineering IBGE, GCU, Laboratory for Translational Oncology and Personalized Medicine and 2 more.
Type: Journal Article | Journal: Archivum immunologiae et therapiae experimentalis | Year: 2016

It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with stem cell like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as cancer stem cells. Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network.

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