Rashid Latif Medical College

Lahore, Pakistan

Rashid Latif Medical College

Lahore, Pakistan
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Fayyaz S.,Rashid Latif Medical College | Aydin T.,Agri Ibrahim Cecen University | Cakir A.,Kilis Aralik University | Gasparri M.L.,University of Rome La Sapienza | And 2 more authors.
Current Topics in Medicinal Chemistry | Year: 2016

Cancer is a multifaceted and genomically complex disease. Rapidly accumulating preclinical and clinical studies are emphasizing on wide ranging molecular mechanisms that underpin cancer development, progression and metastasis. Intratumor heterogeneity, loss of apoptosis, rapidly developing resistance against molecular therapeutics and off-target effects are some of the deeply studied resistance mechanisms. Data obtained through high-throughput technologies has considerably enhanced our understanding of the intracellular signaling cascades frequently dysregulated spatio-temporally. There is an ever-expanding list of synthetic and natural agents reported to activate tumor suppressor genes and inhibit oncogenes in cancer cells. Markedly reduced tumor growth has also been documented in xenografted mice administered with phytochemicals. Oleuropein is a bioactive ingredient isolated from various sources and there is evidence of complete regression of tumors in 9- 12 days in mice orally administered with Oleuropein. In this review we summarize recent developments in use of Oleuropein as an anticancer agent. Extraction and isolation of Oleuropein and how it modulates intracellular signaling network to induce apoptosis in cancer cells. Human epidermal growth factor receptor 2 (HER2) frequently overexpressed in breast cancer cells is inhibited by Oleuropein. Interestingly, trastuzumab efficacy was notably enhanced in Oleuropein treated breast cancer cells. There is still insufficient information related to Oleuropein mediated microRNA regulation in cancer cells. We still do not have information about regulation of different signaling cascades by Oleuropein which are deregulated in cancer. Future studies must converge on a deeper analysis of target molecular network of Oleuropein and its efficacy as a tumor growth inhibitor in xenografted mice. © 2016 Bentham Science Publishers.

Farooqi A.A.,Rashid Latif Medical College | ur Rehman Z.,Kohat University of Science and Technology | Muntane J.,University of Seville | Muntane J.,CIBER ISCIII
OncoTargets and Therapy | Year: 2014

There is increasing progress in translational oncology and tremendous breakthroughs have been made as evidenced by preclinical and clinical trials. Data obtained from high-throughput technologies are deepening our understanding about the molecular and gene network in cancer cells and rapidly emerging in vitro and in vivo evidence is highlighting the role of antisense agents as specific inhibitors of the expression of target genes, thus modulating the response of cancer cells to different therapeutic strategies. Much information is continuously being added into various facets of molecular oncology and it is now understood that over expression of antiapoptotic proteins, oncogenes, oncogenic microRNAs (miRNA), and fusion proteins make cancer cells difficult to target. Delivery of antisense oligonucleotides has remained a challenge and technological developments have helped in overcoming hurdles by improving the ability to penetrate cells, effective and targeted binding to gene sequences, and down regulation of target gene function. Different delivery systems, including stable nucleic acid lipid particles, have shown potential in enhancing the delivery of cargo to the target site. In this review, we attempt to summarize the current progress in the development of antisense therapeutics and their potential in medical research. We partition this multi component review into introductory aspects about recent breakthroughs in antisense therapeutics. We also discuss how antisense therapeutics have shown potential in resensitizing resistant cancer cells to apoptosis by targeted inhibition of antiapoptotic proteins, oncogenic miRNAs, and BCR-ABL. © 2014 Farooqi et al.

Nogueira-Librelotto D.R.,Federal University of Santa Maria | Codevilla C.F.,Federal University of Santa Maria | Farooqi A.,Rashid Latif Medical College | Rolim C.M.B.,Federal University of Santa Maria
Current Pharmaceutical Design | Year: 2017

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research. © 2017 Bentham Science Publishers.

Zahoor A.,Institute of Biomedical and Genetic Engineering IBGE | Zahoor A.,International Islamic University, Islamabad | Mansoor Q.,Institute of Biomedical and Genetic Engineering IBGE | Farooqi A.A.,Institute of Biomedical and Genetic Engineering IBGE | And 3 more authors.
Cellular and Molecular Biology | Year: 2015

TRAIL mediated signaling in cancer cells has emerged as one amongst the most deeply studied molecular phenomenon. Data obtained through genetic studies has highlighted highly polymorphic nature of DR4 and in accordance with this concept, we aimed to investigate the association between Colorectal cancer and polymorphisms in TRAIL and DR4 gene. We selected 100 patients with colorectal cancer and 100 healthy, sex and age matched volunteers randomly. C626G and A1322G in DR4 gene were analyzed using Polymerase Change Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) and Amplification Refractory Mutation System (ARMS) techniques. PCR-RFLP was used to study TRAIL 1595 C>T. TRAIL gene 1595 C>T genotypes percentage in colorectal cancer patients was statistically non-significant. CC was 43% in patients and 50% in controls. CT was 45% in patients and 43% in controls. TT was 12% in patients and 7% in controls. C allele was 0.655% in cancer patients and 0.715% in controls. T allele was 0.345% in patients and 0.285% in controls. DR4 gene 626 C>G genotypes percentage analysis indicated that CC was 28% in patients and 2% in controls. GC was 42% in patients and 40% in controls. GG was 30% in patients and 58% in controls. CC was statistically significant (p=0.00000207) in cancer patients. C allele was 0.49% in patients and 0.22% in controls. G allele was 0.51% in patients and 0.78% in controls. For DR4 A1322G, homozygous GG genotype was 36% in the patients and in controls. There was statistically insignificant difference (p> 0.05). The heterozygous GT genotype was 30% in patients and 29% in controls. This difference was statistically insignificant (p value > 0.05). Similarly, the homozygous genotype TT of the minor allele was (35%) in controls and patients (34 %). This difference was also statistically insignificant (p value > 0.05). C allele was 0.51% in patients and 0.5% in controls. T allele was 0.49% in patients and 0.495% in controls. Future studies must converge on a larger sample size, sporadic mutations of DR4 and TRAIL and expression profiling. © 2015.

Farooqi A.A.,Rashid Latif Medical College | De Rosa G.,University of Naples Federico II
Applied Microbiology and Biotechnology | Year: 2013

Disruption of spatiotemporal behavior of intracellular signaling cascades including tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling in prostate cancer has gained tremendous attention in the past few years. There is an increasing effort in translating the emerging information about TRAIL-mediated signaling obtained through experimental and preclinical data to clinic. Fascinatingly, novel targeting approaches are being developed to enhance the tissue- or subcellular-specific delivery of drugs with considerable focus on prostate cancer. These applications have the potential to revolutionize prostate cancer therapeutic strategies and include the accumulation of drugs in target tissue as well as the selection of internalizing ligands for enhanced receptor-mediated uptake of drugs. In this mini-review, we outline outstanding developments in therapeutic strategies based on the regulation and/or targeting of TRAIL pathway for the treatment of prostate cancer. Moreover, microRNAs (miRNAs), with potential transcriptional and posttranscriptional regulation of gene expression, will be presented for their potential in prostate cancer treatment. Emphasis has been given to the use of delivery approaches, especially based on nanotechnology. Considerably, enhanced information regarding miRNA regulation of TRAIL-mediated signaling in prostate cancer cells may provide potential biomarkers for the characterization of patients as responders and nonresponders of TRAIL-based therapy and could provide rationalized basis for combination therapies with TRAIL death receptor-targeting drugs. © 2013 Springer-Verlag Berlin Heidelberg.

Farooqi A.A.,Rashid Latif Medical College | Butt G.,Phycology Research Laboratory | Razzaq Z.,Rawal Institute of Health science
Cancer Cell International | Year: 2012

There is an overwhelmingly increasing trend of analysis of naturally occurring ingredients in treatment of prostate cancer. Substantial fraction of information has been added that highlights activity at various levels and steps of deregulated cellular proliferation, metastasis and apoptosis. Among such ingredients, algae extracts and jasmonates are documented to have anti-cancer activity in vitro and in vivo and induce growth inhibition in cancer cells, while leaving the non-transformed cells intact. In this short review we outline systematically, how these ingredients predispose prostate cancer cells to undergo apoptosis. © 2012 Farooqi et al.; licensee BioMed Central Ltd.

Jamil A.Z.,Rashid Latif Medical College | Ahmed A.,LRBT Eye Hospital | Mirza K.A.,LRBT Eye Hospital
Journal of the College of Physicians and Surgeons Pakistan | Year: 2014

Objective: To evaluate the effect of intracameral dexamethasone on corneal endothelium. Study Design: Quasi experimental study. Place and Duration of Study: Layton Rehmatulla Benevolent Trust Eye Hospital, Lahore, from May 2011 to January 2012. Methodology: Study subjects were adults of either gender with senile cataract who underwent phacoemulsification. They were divided in two groups, each had 110 patients. Group-A received subconjunctival injection of dexamethasone (2 mg/0.5 ml) at the end of surgery while group-B received intracameral injection of dexamethasone (0.4 mg/0.1 ml) at the end of surgery. Endothelial cell count was performed by specular microscopy pre-operatively and postoperatively at first week, first month and three months. Outcome measures included changes in endothelial cell count. Results were compared using t-test for means. Results: There were 55 (50%) males and 55 (50%) females in group-A and 44 (40%) males and 66 (60%) females in group-B. In group-A, there were 66 (60%) right and 44 (40%) left eyes while group-B had 62 (56.36%) right and 48 (43.63%) left eyes. Mean age in group-A was 55.17 ± 5.93 years and 54.87 ± 5.55 years in group-B. Mean phacoemulsification time in group-A was 1.92 ± 0.63 minutes and 1.82 ± 0.54 minutes in group-B. After 3 months, in group-A, there was 7.55 ± 1.19% endothelial cell loss while in group-B, there was 7.63 ± 1.10% endothelial cell loss. The difference between the two groups was not statistically significant (p=0.614). Conclusion: Use of intracameral dexamethasone at the end of cataract surgery is safe for corneal endothelium.

Farooqi A.A.,Rashid Latif Medical College | Sarkar F.H.,Barbara Ann Karmanos Cancer Institute
Cancer Cell International | Year: 2015

In the past decades, the field of prostate cancer (PCa) biology has developed exponentially and paralleled with that has been the growing interest in translation of laboratory findings into clinical practice. Based on overwhelming evidence of high impact research findings which support the underlying cause of insufficient drug efficacy in patients progressing on standard androgen deprivation therapy (ADT) is due to persistent activation of the androgen receptor (AR) signaling axis. Therefore, newer agents must be discovered especially because newer ADT such as abiraterone and enzalutamide are becoming ineffective due to rapid development of resistance to these agents. High-throughput technologies are generating massive and highly dimensional genetic variation data that has helped in developing a better understanding of the dynamic repertoire of AR and AR variants. Full length AR protein and its variants modulate a sophisticated regulatory system to orchestrate cellular responses. We partition this multicomponent review into subsections addressing the underlying mechanisms of resistance to recent therapeutics, positive and negative regulators of AR signaling cascade, and how SUMOylation modulates AR induced transcriptional activity. Experimentally verified findings obtained from cell culture and preclinical studies focusing on the potential of natural agents in inhibiting mRNA/protein levels of AR, nuclear accumulation and enhanced nuclear export of AR are also discussed. We also provide spotlight on molecular basis of enzalutamide resistance with an overview of the strategies opted to overcome such resistance. AR variants are comprehensively described and different mechanisms that regulate AR variant expression are also discussed. Reconceptualization of phenotype- and genotype-driven studies have convincingly revealed that drug induced resistance is a major stumbling block in standardization of therapy. Therefore, we summarize succinctly the knowledge of drug resistance especially to ADT and potential avenues to overcome such resistance for improving the treatment outcome of PCa patients. © 2015 Farooqi and Sarkar.

Farooqi A.A.,Rashid Latif Medical College | Attar R.,Yeditepe University | Gasparri M.L.,University of Rome La Sapienza
Asian Pacific Journal of Cancer Prevention | Year: 2014

There have been overwhelming advances in molecular oncology and data obtained through high-throughput technologies have started to shed light on wide ranging molecular mechanisms that underpin cancer progression. Increasingly it is being realized that marine micro-organisms and the biodiversity of plankton are rich sources of various anticancer compounds. Marine derived compounds play major roles in inducing apoptosis in cancer cells. More importantly, various agents have been noted to enhance TRAIL induced apoptosis in cancer cells by functionalizing intrinsic and extrinsic pathways. In this commentary, a list of marine derived compounds reported to induce apoptosis is discussed.

Fayyaz S.,Rashid Latif Medical College | Farooqi A.A.,Rashid Latif Medical College
Immunogenetics | Year: 2013

Oncogenic fusion proteins belong to an important class that disrupts gene expression networks in a cell. Astonishingly, fusion-positive prostate cancer cells enable the multi-gene regulatory capability of miRNAs to remodel the signal transduction landscape, enhancing or antagonizing the transmission of information to downstream effectors. Accumulating evidence substantiates the fact that miRNAs translate into dose-dependent responsiveness of cells to signaling regulators in transmembrane protease serine 2:ETS-related gene (TMPRSS2-ERG)-positive cells. Wide ranging signaling proteins are the targets for the degree of quantitative fluctuations imposed by miRNAs. miRNA signatures are aberrantly expressed in fusion-positive cancer cells, suggesting that they have a cumulative effect on tumor aggressiveness. It seems attractive to note that TMPRSS2:ERG fusion has a stronger effect as tumors positive for the oncogenic TMPRSS2:ERG have dysregulated oncomirs and tumor suppressor miRNA signature. It is undeniable that a comprehensive analysis of the prostate cancer microRNAome is necessary to uncover novel microRNAs and pathways associated with prostate cancer. Moreover, the identification and validation of miRNA signature in TMPRSS2-ERG-positive prostate cancer cells may help to identify novel molecular targets and pathways for personalized therapy. © 2013 Springer-Verlag Berlin Heidelberg.

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