MicroRNAs: short non-coding players in cancer chemoresistance.

Chemoresistance is one of the main problems in the therapy of cancer. There are a number of different molecular mechanisms through which a cancer cell acquires resistance to a specific treatment, such as alterations in drug uptake, drug metabolism and drug targets. There are several lines of evidence showing that miRNAs are involved in drug sensitivity of cancer cells in different tumor types and by different treatments.

Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

Purpose: Local failure rates after radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined.

AMP-activated protein kinase (AMPK) beyond metabolism: a novel genomic stress sensor participating in the DNA damage response pathway.

AMP-activated protein kinase (AMPK), an established metabolic stress sensor, has gained popularity in cancer biology due to its ability to control cellular growth and mediate cell cycle checkpoints in cancer cells in response to low energy levels. AMPK is a key effector of the tumor suppressor liver kinase B 1 (LKB1) which inhibits the cellular growth mediator mammalian target of rapamycin (mTOR) and activates checkpoint mediators such as p53 and the cyclin dependent kinase inhibitors p21(cip1) and p27(kip1). However, recent work describes a novel function for AMPK as a sensor of genomic stress and a participant of the DNA damage response (DDR) pathway.

Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK.

Background: We examined the potential of metformin (MET) to enhance non-small cell lung cancer (NSCLC) responses to ionising radiation (IR).

Methods: Human NSCLC cells, mouse embryonic fibroblasts from wild-type and AMP-activated kinase (AMPK) α1/2-subunit(-/-) embryos (AMPKα1/2(-/-)-MEFs) and NSCLC tumours grafted into Balb/c-nude mice were treated with IR and MET and subjected to proliferation, clonogenic, immunoblotting, cell cycle and apoptosis assays and immunohistochemistry (IHC).

Results: Metformin (2.

Metformin: On Ongoing Journey across Diabetes, Cancer Therapy and Prevention.

Cancer metabolism is the focus of intense research, which witnesses its key role in human tumors. Diabetic patients treated with metformin exhibit a reduced incidence of cancer and cancer-related mortality. This highlights the possibility that the tackling of metabolic alterations might also hold promising value for treating cancer patients.

Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cells.

Background: The sestrin family of stress-responsive genes (SESN1-3) are suggested to be involved in regulation of metabolism and aging through modulation of the AMPK-mTOR pathway. AMP-activated protein kinase (AMPK) is an effector of the tumour suppressor LKB1, which regulates energy homeostasis, cell polarity, and the cell cycle. SESN1/2 can interact directly with AMPK in response to stress to maintain genomic integrity and suppress tumorigenesis.

Ionizing radiation regulates the expression of AMP-activated protein kinase (AMPK) in epithelial cancer cells: modulation of cellular signals regulating cell cycle and survival.

Purpose: To analyze the (i) expression of AMPK in a variety of epithelial cancer cells, (ii) regulation of AMPK subunit expression by ionizing radiation (IR) and (iii) impact of AMPK on signaling pathways regulating cell cycle and survival.

Methods And Materials: Human lung, prostate, and breast normal and cancer cells were treated with 0 or 8 Gy IR and mRNA and protein levels of AMPK were evaluated by RT-PCR and immunoblotting 24 or 48 h later. Untreated and radiated wild type (WT) and AMPKα(-/-) mouse embryonic fibroblasts (MEFs) were analyzed by immunoblotting using total- and phosphorylation-specific antibodies.

Lovastatin sensitizes lung cancer cells to ionizing radiation: modulation of molecular pathways of radioresistance and tumor suppression.

Introduction: In this study, we investigated the effect of the 3-hydroxy-3-methylgutaryl-CoA reductase inhibitor lovastatin, as a sensitizer of lung cancer cells to ionizing radiation (IR).

Methods: A549 lung adenocarcinoma cells were treated with 0 to 50 μM lovastatin alone or in combination with 0 to 8 Gy IR and subjected to clonogenic survival and proliferation assays. To assess the mechanism of drug action, we examined the effects of lovastatin and IR on the epidermal growth factor (EGF) receptor and AMP-activated kinase (AMPK) pathways and on apoptotic markers and the cell cycle.

Chronology of the radiographic appearances of the calcium sulphate-calcium phosphate synthetic bone graft composite following resection of bone tumours--a preliminary study of the normal post-operative appearances.

Objective: To describe the normal chronological radiographic appearances of the calcium sulphate-calcium phosphate (CaSO(4)/CaPO(4)) synthetic graft material following bone tumour resection during the processes of graft resorption and new bone incorporation into the post-resection defect.

Materials And Methods: Retrospective review of our oncology database identified patients who had undergone serial radiographic assessment after treatment with the CaSO(4)/CaPO(4) synthetic graft following bone tumour resection. Post-operative radiographs were assessed for (1) partial resorption of graft material with partial ingrowth of new bone at the graft site and (2) complete resorption of graft material with complete incorporation of new bone into the graft site.

Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells.

Purpose: Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells.

A novel surgical approach to lipomatous tumours of the deltoid region.

Resection of large lipomatous tumours in the subdeltoid region remains technically challenging due to the risk of injury to the axillary neurovascular bundle. We describe a novel deltoid release and reinsertion technique for resection of large lipomatous tumours of the sub-deltoid region and report the functional and oncologic outcomes of six patients who underwent this procedure. Three cases were diagnosed histologically as atypical lipoma and three cases were diagnosed as lipoma.

Colorectal cancer in young adults.

Colorectal cancer (CRC) is rare in young adults. It presents more frequently with stage 3 or 4 disease, underscoring its relevance in this population. Prognosis, matched for stage of disease at presentation, is likely similar to that in older adults, although survival is clearly lower for the youngest subgroups within this population.

Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma.

Clinical trials have validated the importance of mammalian target of rapamycin (mTOR) as a targeted mechanism in the treatment of renal cell carcinoma (RCC). Temsirolimus, an mTOR inhibitor that is approved for treatment of advanced RCC, has demonstrated both overall survival benefits and progression-free survival benefits versus interferon-alpha as first-line treatment for patients with poor prognostic features. Exploratory subset analyses indicated that temsirolimus benefits patients with RCC regardless of tumor histology or nephrectomy status.

An empirical model of electronic portal imager response implemented within a commercial treatment planning system for verification of intensity-modulated radiation therapy fields.

Quality assurance (QA) of an intensity-modulated radiation therapy (IMRT) plan is more complex than that of a conventional plan. To improve the efficiency of QA, electronic portal imaging devices (EPIDs) can be used. The major objective of the present work was to use a commercial treatment planning system to model EPID response for the purpose of pre-treatment IMRT dose verification.

Hypoxia-induced lactate dehydrogenase expression and tumor angiogenesis.

The aim of this review is to discuss the basic science of tumor angiogenesis and recent clinical trial results with angiogenic inhibitors. Colorectal cancer (CRC) continues to be a major cause of all new cancer cases and cancer-related deaths in North America. Although advances in chemotherapy have increased overall survival for patients suffering from metastatic CRC, the survival rate continues to be poor.

Practitioner feedback on lung cancer practice guidelines in Ontario.

Purpose: Practitioner feedback (PF) surveys are sent to practitioners who care for lung cancer patients as each new practice guideline is completed. In this study, the PF was reviewed to assess the frequency of response to the surveys, the respondents' characteristics, the nature of the feedback, and the intention to adopt the guideline in practice.

Methods: Fourteen practice guidelines (PGs) were sent to Ontario practitioners treating lung cancer, and feedback on the PGs was obtained through either an eight- or 21-item survey.

Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia.

Purpose: Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC).

Patients And Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted.

Integrative oncology in North America.

Integrative oncology is an evolving evidence-based specialty that uses complementary therapies in concert with medical treatment to enhance its efficacy, improve symptom control, alleviate patient distress and reduce suffering. In North America the evolution of research into complementary therapies was delayed by the narrow focus of the Flexner Report. A government-funded research agenda and incorporation of complementary therapies into medical school curricula have been driven by early evidence of efficacy and patient demand.

ets-1 is transcriptionally up-regulated by H2O2 via an antioxidant response element.

Expression of the transcription factor Ets-1 is increasingly associated with the progression of several human cancers. A tumor-derived factor is expected to be involved in the inappropriate up-regulation of ets-1 in tumor and surrounding cells. A link between hydrogen peroxide (H2O2) and increased Ets-1 expression has also been suggested, leading to the proposal that this reactive oxygen species (ROS) may be an important factor in directly regulating the expression of ets-1 in tumor cells.

Estimating per patient funding for cancer clinical trials: an Ontario based survey.

The financial implications of conducting clinical trials in oncology have not been well researched from a perspective that would facilitate the negotiation of appropriate reimbursement. A better understanding of the resources required to conduct clinical trials is central to this process. Summaries of two hypothetical clinical trials were circulated to the clinical trials departments of the nine regional cancer centres of Cancer Care Ontario (CCO), in the Province of Ontario, Canada.