Saskatoon, Canada
Saskatoon, Canada

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Tai P.,Saskatchewan Cancer Agency | Assouline A.,Center Clinique Of La Porte Of Saint Cloud | Joseph K.,University of Alberta | Stitt L.,Clinical Research Unit | Yu E.,University of Western Ontario
Clinical Lung Cancer | Year: 2013

Background: Previous clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. Patients and Methods: The Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). Results: There were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P =.0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P =.0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P <.0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P =.02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P =.05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P =.32 and 0.39, respectively). Conclusions: Patients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation. © 2013 Elsevier Inc. All rights reserved.


Cranmer-Sargison G.,Saskatchewan Cancer Agency | Cranmer-Sargison G.,University of Leeds | Charles P.H.,Queensland University of Technology | Trapp J.V.,Queensland University of Technology | And 2 more authors.
Radiotherapy and Oncology | Year: 2013

Purpose The goal of this work was to set out a methodology for measuring and reporting small field relative output and to assess the application of published correction factors across a population of linear accelerators. Methods and materials Measurements were made at 6 MV on five Varian iX accelerators using two PTW T60017 unshielded diodes. Relative output readings and profile measurements were made for nominal square field sizes of side 0.5 to 1.0 cm. The actual in-plane (A) and cross-plane (B) field widths were taken to be the FWHM at the 50% isodose level. An effective field size, defined as FSeff=A·B, was calculated and is presented as a field size metric. FSeff was used to linearly interpolate between published Monte Carlo (MC) calculated kQclin,Qmsr fclin,fmsr values to correct for the diode over-response in small fields. Results The relative output data reported as a function of the nominal field size were different across the accelerator population by up to nearly 10%. However, using the effective field size for reporting showed that the actual output ratios were consistent across the accelerator population to within the experimental uncertainty of ±1.0%. Correcting the measured relative output using kQclin,Qmsrfclin, fmsr at both the nominal and effective field sizes produce output factors that were not identical but differ by much less than the reported experimental and/or MC statistical uncertainties. Conclusions In general, the proposed methodology removes much of the ambiguity in reporting and interpreting small field dosimetric quantities and facilitates a clear dosimetric comparison across a population of linacs. © 2013 Elsevier Ireland Ltd. All rights reserved.


Duggleby W.,University of Alberta | Doell H.,Saskatchewan Cancer Agency | Cooper D.,Regina QuAppelle Health Region | Thomas R.,University of Ottawa | Ghosh S.,University of Alberta
Cancer Nursing | Year: 2014

Background: The quality of life of male spouses of partners with breast cancer may determine the support they are able to give their wives. Little is known about the factors associated with their quality of life. Objective: The purpose of this study was to examine the relationship of the quality of life of male spouses of partners with breast cancer with the following factors: (a) demographic variables of male spouses and their partners, (b) levels of hope of male spouses and their partners, (c) self-efficacy and loss and grief of male spouses, and (d) quality of life of partners with breast cancer. Methods: Six hundred surveys were mailed to women with breast cancer (stage 1-3) and their male spouses. A total of 110 surveys were completed. Results: With the use of generalized linear modeling, participating male spouses with higher quality of life scores: (a) were older (P = .01), (b) had higher hope scores (P = .01), (c) had lower feelings of guilt scores (P < .01) (subscale of loss and grief), (d) had higher general self-efficacy scores (P < .01), and (e) had partners with breast cancer with higher quality of life scores (P < .01). Conclusions: Hope, self-efficacy, feelings of guilt, age, and their partners' quality of life were significantly related to quality of life of the male spouses of women with breast cancer. Implications for practice: The findings underscore the importance of assessing for and fostering hope and self-efficacy as well as decreasing guilt in male spouses of women with breast cancer to improve their quality of life. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Duggleby W.,University of Alberta | Ghosh S.,University of Alberta | Cooper D.,Regina quAppelle Health Region | Dwernychuk L.,Saskatchewan Cancer Agency
Journal of Pain and Symptom Management | Year: 2013

Context: Hope is important to cancer patients as it helps them deal with their diagnosis. Little is known about hope in newly diagnosed cancer patients. Objectives: Based on the Transcending Possibilities conceptual model of hope, the purpose of this study was to examine the relationship of hope with pain, energy, and psychological and demographic characteristics in newly diagnosed adult oncology outpatients. Methods: Data from 310 New Patient Assessment Forms from cancer outpatients' health records were collected. Health records from the first six months of 2009 were reviewed and data were collected on hope, energy, pain, depression, anxiety, feeling overwhelmed, and demographic variables. A generalized linear modeling approach was used to study the relationship of hope scores with these variables. Hypothesized variables and variables that were significant at the P = 0.01 level from the univariate analysis were entered into the multivariate model, with hope scores as the dependent variable. Results: Hope scores were significantly negatively related to age (P = 0.02). More specifically, oncology patients who were 65 years of age or older had significantly less hope than those under the age of 65 years (P = 0.01). Gender (P = 0.009) also was a significant factor, with men having higher hope scores than women. No other variables were significant. Conclusion: Older adults comprise the majority of persons in Canada with cancer. The lower hope scores found in this age group compared with their younger counterparts underscore the importance of further research. This study provides a foundation for future research in this important area for oncology patients. © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.


Mellor P.,University of Saskatchewan | Mellor P.,Saskatchewan Cancer Agency | Furber L.A.,University of Saskatchewan | Nyarko J.N.K.,University of Saskatchewan | And 2 more authors.
Biochemical Journal | Year: 2012

The p85α protein is best known as the regulatory subunit of class 1A PI3Ks (phosphoinositide 3-kinases) through its interaction, stabilization and repression of p110-PI3K catalytic subunits. PI3Ks play multiple roles in the regulation of cell survival, signalling, proliferation, migration and vesicle trafficking. The present review will focus on p85α, with special emphasis on its important roles in the regulation of PTEN (phosphatase and tensin homologue deleted on chromosome 10) and Rab5 functions. The phosphatidylinositol-3-phosphatase PTEN directly counteracts PI3K signalling through dephosphorylation of PI3K lipid products. Thus the balance of p85α-p110 and p85α-PTEN complexes determines the signalling output of the PI3K/PTEN pathway, and under conditions of reduced p85α levels, the p85α-PTEN complex is selectively reduced, promoting PI3K signalling. Rab5 GTPases are important during the endocytosis, intracellular trafficking and degradation of activated receptor complexes. The p85α protein helps switch off Rab5, and if defective in this p85α function, results in sustained activated receptor tyrosine kinase signalling and cell transformation through disrupted receptor trafficking. The central role for p85α in the regulation of PTEN and Rab5 has widened the scope of p85α functions to include integration of PI3K activation (p110-mediated), deactivation (PTEN-mediated) and receptor trafficking/signalling (Rab5-mediated) functions, all with key roles in maintaining cellular homoeostasis. © The Authors Journal compilation © 2012 Biochemical Society.


Das U.,University of Saskatchewan | Kumar S.,University of Saskatchewan | Kumar S.,Saskatchewan Cancer Agency | Dimmock J.R.,University of Saskatchewan | And 2 more authors.
Current Cancer Drug Targets | Year: 2012

N-myristoyltransferase (NMT) is an essential eukaryotic enzyme which catalyzes the transfer of the myristoyl group to the terminal glycine residue of a number of proteins including those involved in signal transduction and apoptotic pathways. Myristoylation is crucial for the cellular proliferation process and is required for the growth and development in a number of organisms including many human pathogens and viruses. Targeting the myristoylation process thus has emerged as a novel therapeutic strategy for anticancer drug design. The expression/activity of NMT is considerably elevated in a number of cancers originating in the colon, stomach, gallbladder, brain and breast and attenuation of NMT levels has been shown to induce apoptosis in cancerous cell lines and reduce tumor volume in murine xenograft models for cancer. A focus of current therapeutic interventions in novel cancer treatments is therefore directed at developing specific NMT inhibitors. The inhibition of the myristoyl lipidation process with respect to cancer drug development lies in the fact that many proteins involved in oncogenesis such as src and various kinases require myristoylation to perform their cellular functions. Inhibiting NMT functions to control malignancy is a novel approach in the area of anticancer drug design and there are rapidly expanding discoveries of synthetic NMT inhibitors as potential chemotherapeutic agents to be employed in the warfare against cancer. The current review focuses on developments of various chemical NMT inhibitors with potential roles as anticancer agents. © 2012 Bentham Science Publishers.


Chagpar R.B.,University of Saskatchewan | Links P.H.,Saskatchewan Cancer Agency | Pastor M.C.,University of Saskatchewan | Furber L.A.,University of Saskatchewan | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is deregulated in many human diseases including cancer, diabetes, obesity, and autoimmunity. PI3K consists of a p110 catalytic protein and a p85α regulatory protein, required for the stabilization and localization of p110-PI3K activity. The p110-PI3K enzyme generates the key signaling lipid phosphatidylinositol 3,4,5-trisphosphate, which is dephosphorylated by the PI3-phosphatase PTEN. Here we show another function for the p85α regulatory protein: it binds directly to and enhances PTEN lipid phosphatase activity. We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner. We also show epidermal growth factor dependent coimmunoprecipitation of endogenous p85 and PTEN proteins in HeLa cells. Thus p85 regulates both p110-PI3K and PTEN-phosphatase enzymes through direct interaction. This finding underscores the need for caution in analyzing PI3K activity because anti-p85 immunoprecipitations may contain both p85:p110-PI3K and p85:PTEN-phosphatase enzymes and thus measure net PI3K activity. We identify the N-terminal SH3-BH region of p85α, absent in the smaller p55α and p50α isoforms, as the region that mediates PTEN binding and regulation. Cellular expression of p85ΔSH3-BH results in substantially increased magnitude and duration of pAkt levels in response to growth factor stimulation. The ability of p85 to bind and directly regulate both p110-PI3K and PTEN-PI3-phosphatase allows us to explain the paradoxical insulin signaling phenotypes observed in mice with reduced PI3K or PTEN proteins. This discovery will impact ongoing studies using therapeutics targeting the PI3K/PTEN/Akt pathway.


Paul J.M.,University of Saskatchewan | Templeton S.D.,University of Saskatchewan | Baharani A.,University of Saskatchewan | Freywald A.,University of Saskatchewan | And 2 more authors.
Trends in Molecular Medicine | Year: 2014

The most commonly used therapies for cancer involve delivering high doses of radiation or toxic chemicals to the patient that also cause substantial damage to normal tissue. To overcome this, researchers have recently resorted to a basic biological concept called 'synthetic lethality' (SL) that takes advantage of interactions between gene pairs. The identification of SL interactions is of considerable therapeutic interest because if a particular gene is SL with a tumor-causing mutation, then the targeting that gene carries therapeutic advantages. Mapping these interactions in the context of human cancer cells could hold the key to effective, targeted cancer treatments. In this review, we cover the recent advances that aim to identify these SL interactions using unbiased genetic screens. © 2014 Elsevier Ltd.


Ahmed S.,Saskatchewan Cancer Agency | Ahmed S.,University of Saskatchewan | Shahid R.K.,University of Saskatchewan
Current Oncology | Year: 2012

Canada is facing cancer crisis. Cancer has become the leading cause of death in Canada. Despite recent advances in cancer management and research, growing disparities in cancer care have been noticed, especially in socio-economically disadvantaged groups and under-served communities. With the rising incidence of cancer and the increasing numbers of minorities and of social disparities in general, and without appropriate interventions, cancer care disparities will become only more pronounced. This paper highlights the concepts and definitions of equity in health and health care and examines several health determinants that increase the risk of cancer. It also reviews cancer care inequity in the high-risk groups. A conceptual framework is proposed and recommendations are made for the eradication of disparities within the health care system and beyond. © 2012 Multimed Inc.


Ahmed S.,Saskatchewan Cancer Agency | Ahmed S.,University of Saskatchewan | Johnson K.,University of Saskatchewan | Ahmed O.,University of Saskatchewan | And 2 more authors.
International Journal of Colorectal Disease | Year: 2014

Background: Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide and the fourth leading cause of cancer-related deaths. This article reviews the epidemiology, risk factors, pathogenesis, and prognosis of CRC with special emphasis on advances in the management of CRC over the past decade. Methods: A review of the published English literature was conducted using the search engines PubMed, Medline, EMBASE, and Google Scholar. A total of 127 relevant publications were identified for further review. Results: Most CRC are sporadic and are due to genetic instability and multiple somatic mutations. Approximately 80 % of cancers are diagnosed at the early stage and are curable. The pathologic stage at presentation is the most important predictor of outcome after resection of early stage cancer. Surgery is the primary treatment modality for localized CRC. Advances in (neo)adjuvant chemotherapy and radiation have reduced the disease recurrence and increased survival in high risk diseases. Although recent advancements in combination chemotherapy and target agents have increased the survival of incurable CRC, it is remarkable that only selected patients with advanced CRC can be cured with multimodality therapy. Conclusion: Over the past decade, there has seen substantial progress in our understanding of and in the management of CRC. © 2014 Springer-Verlag.

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