Publications (265) View all
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Article: Doxycycline in mitochondrial mediated pathway of apoptosis: a systematic review.
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ABSTRACT: Tetracyclines have been long known for their antimicrobial role. They are one of the most widely used antibiotics in clinical practice since last 5 decades. Recently their role as matrix metalloproteinase inhibitor and in apoptosis has widely attracted attention in biological field. Of them, doxycycline is one with long duration of actions and has recently been shown to have various anti-cancer properties, especially cytotoxic and anti-proliferative activities. Here, we systematically reviewed the role of doxycycline in the mitochondrial mediated apoptosis in various tissues. MEDLINE and EMBASE databases were searched using a formal search strategy with definite inclusion and exclusion criteria. Data extraction was performed for each included study using a custom designed data extraction form. A total of 81 references were identified through MEDLINE and 5 were identified through EMBASE. 74 references from MEDLINE and all 5 in EMBASE were excluded through reading titles, abstracts and full text. In total, 7 studies fulfilled inclusion criteria. Following systematic review of these studies, we concluded that doxycycline induces apoptosis through mitochondrial mediated pathway in different tissue cells however it may be cell specific. The caspase independent apoptosis as one of the mechanisms of actions of doxycycline needs further studies for better understanding.Anti-cancer agents in medicinal chemistry 09/2010; 10(7):556-63. -
Article: Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells.
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ABSTRACT: BACKGROUND: Arachidonic acid metabolite, generated by cyclooxygenase (COX), is implicated in the colorectal cancer (CRC) pathogenesis. Inhibiting COX may therefore have anti-carcinogenic effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only COX have been conflicting. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX) pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2). Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells. METHODS: Three colorectal cancer cell lines (HCA7, HT-29 & LoVo) expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor) and rofecoxib (COX-2 selective) on prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA) content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay. RESULTS: COX inhibitors suppressed PGE2 production but enhanced LTB4 secretion in COX-2 expressing cell lines (P <0.001). The level of COX-2 expression in colorectal cancer cells did not significantly influence the anti-proliferative and pro-apoptotic effects of COX inhibitors due to the shunting mechanism. CONCLUSIONS: This study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors.World Journal of Surgical Oncology 09/2012; 10(1):200. · 1.12 Impact Factor -
Article: A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration.
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ABSTRACT: Management of intestinal failure remains a clinical challenge and total parenteral nutrition, intestinal elongation and/or transplantation are partial solutions. In this study, using a detergent-enzymatic treatment (DET), we optimize in rats a new protocol that creates a natural intestinal scaffold, as a base for developing functional intestinal tissue. After 1 cycle of DET, histological examination and SEM and TEM analyses showed removal of cellular elements with preservation of the native architecture and connective tissue components. Maintenance of biomechanical, adhesion and angiogenic properties were also demonstrated strengthen the idea that matrices obtained using DET may represent a valid support for intestinal regeneration.Biomaterials 04/2012; 33(12):3401-10. · 7.40 Impact Factor -
Article: Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study.
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ABSTRACT: Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 μg/kg) and epoetin beta (40,000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome. European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.The Lancet 11/2011; 378(9808):1997-2004. · 38.28 Impact Factor -
Article: Quantum dots and carbon nanotubes in oncology: a review on emerging theranostic applications in nanomedicine.
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ABSTRACT: Cancer is one of the main causes of death in the world, and according to the WHO it is projected to continue rising. Current diagnostic modalities for the detection of cancer include the use of x-rays, magnetic resonance imaging and positron emission tomography, among others. The treatment of cancer often involves the use (or combination) of chemotherapeutic drugs, radiotherapy and interventional surgery (for solid and operable tumors). The application of nanotechnology in biology and medicine is advancing rapidly. Recent evidence suggests that quantum dots (QDs) can be used to image cancer cells as they display superior fluorescent properties compared with conventional chromophores and contrast agents. In addition, carbon nanotubes (CNTs) have emerged as viable candidates for novel chemotherapeutic drug delivery-platforms. The unique photothermal properties of CNTs also allow them to be used in conjunction with near infrared radiation and lasers to thermally ablate cancer cells. Furthermore, mounting evidence indicates that it is possible to conjugate QDs to CNTs, making it possible to exploit their novel attributes in the realm of cancer theranostics (diagnostics and therapy). Here we review the current literature pertaining to the applications of QDs and CNTs in oncology, and also discuss the relevance and implications of nanomedicine in a clinical setting.Nanomedicine 08/2011; 6(6):1101-14. · 5.05 Impact Factor
