Medicine and Health Sciences Commons^™

Targeting Urokinase And The Transferrin Receptor With Novel, Anti-Mitotic N-Alkylisatin Cytotoxin Conjugates Causes Selective Cancer Cell Death And Reduces Tumor Growth, K Vine, V. Indira Chandran, J Locke, L Matesic, J Lee, D Skropeta, J Bremner, M Ranson

Danielle Skropeta

Tumor-specific delivery of ligand-directed prodrugs can increase the therapeutic window of chemotherapeutics by maintaining efficacy whilst decreasing toxic side effects. We have previously described a series of synthetic N-alkylated isatin cytotoxins that destabilize microtubules and induce apoptosis with 10-fold greater potency than conventional anti-mitotics in vitro. Here, we report the characterization, in vitro cytotoxicity and in vivo efficacy of a lead compound, 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin (N-AI) conjugated via an esterase-labile linker (N-AIE) to two proven targeting ligands, transferrin (Tf) and plasminogen activator inhibitor type 2 (PAI-2/serpinB2). N-AI was released from N-AIE and the targeting ligands Tf/PAI-2 in an esterase-dependent manner at 37 …

Self-Reported Side Effects Of Breast Cancer Treatment: A Cross-Sectional Study Of Incidence, Associations, And The Influence Of Exercise, Sheridan A. Gho, Julie R. Steele, Sandra C. Jones, Bridget J. Munro

Sandra Jones

Purpose Side effects as a result of breast cancer treatment may have a lasting detrimental impact on quality of life. Exercise has been shown to be an effective intervention in post-treatment care. This study aimed to gain a better understanding of breast cancer treatment-related side effects through identifying potential patient characteristic associations, including current levels of exercise. Methods Four hundred and thirty-two breast cancer patients completed an online survey covering their treatment and demographic background, current exercise levels, and self-reported treatment side effects. Side effects were considered in a binary logistic regression against age, surgery, currently undergoing treatment, and exercise …

Male Reproductive Health And Yoga, Pallav Sengupta

Pallav Sengupta, PhD

Now-a-days reproductive health problems along with infertility in male is very often observed. Various Assisted Reproductive Technologies have been introduced to solve the problem, but common people cannot afford the cost of such procedures. Various ayurvedic and other alternative medicines, along with regular yoga practice are proven to be not only effective to enhance the reproductive health in men to produce a successful pregnancy, but also to regulate sexual desire in men who practice celibacy. Yoga is reported to reduce stress and anxiety, improve autonomic functions by triggering neurohormonal mechanisms by the suppression of sympathetic activity, and even, today, several …

Counterfactual Thinking In Response To Hypothetical Breast Cancer Scenarios: A Pilot Study, Amy Y. Chan, Sandra C. Jones, Karen T. Rich

Sandra Jones

This paper examined womens counterfactualthoughts in response to hypothetical scenarios aboutearly versus late breast cancer diagnoses.Womenaged 50 and over (N=29) read hypotheticalscenarios about the experience of fictitious womenof mammography screening age and completedcounterfactual statements from the protagonistsperspective.In two scenarios, the protagonist failedto attend mammography screening regularly andwas diagnosed with advanced breast cancer; thethird scenario depicted a woman who hadmammograms biennially and received an early-stagebreast cancer diagnosis.Consistent with pastliterature on counterfactual thinking, participantsgenerated exclusively upward counterfactuals fromthe two late-diagnosis scenarios, and predominantlydownward counterfactuals from the early-diagnosisscenario.Furthermore, participants primarilyfocussed on what the protagonist could personallyhave done differently to lead to a differentoutcome.Hence …

Wnt/Ss-Catenin/Lef-1 Signaling In The Uterus And Its Implications In Uterine Gland Formation And Cancer Development, Dawne N. Shelton, Michael J. Goodheart

Michael J. Goodheart

Wnt/b-catenin signaling appears to be important in a multitude of cancers. This review article details current knowledge of the Wnt/b-catenin/Lef1 pathway in generalized gland regulation and formation in addition to endometrial cancer. Wnt signaling is critical for the development of the female urogenital system, in particular mullerian duct formation. Dysregulation of this signaling pathway at multiple nodes has been observed in numerous tumor types, including endometrial cancer. In particular, nuclear accumulation of b-catenin correlates with tumor severity. As such, therapeutic modulation of Wnt signaling represents an emerging avenue for the treatment of cancers that rely on this pathway.

Defining Genetic Intra-Tumor Heterogeneity: A Chronological Annotation Of Mutational Pathways, Wentao Luo, Fan Wu, Susan R. Atlas, Gavin Pickett, Kimberly K. Leslie, Donghai Dai

Donghai Dai

Tumor heterogeneity is believed to be important in tumor progression and its response to therapies. However, despite numerous mutations being reported in human tumors, genetic intra-tumor heterogeneity remains poorly defined. We have developed a novel strategy to provide a chronological annotation of mutational events in a tumor. We used an endometrial tumor from a patient and transplanted it into athymic mice to create many tumor xenografts. While the patient tumor xenografts were initially responsive to raloxifene treatment, xenografts created with cancer cell clones isolated from the same patient tumor showed dramatic differences in response to raloxifene, indicating existence of intra-tumor …

Environmental And Occupational Interventions For Primary Prevention Of Cancer: A Cross-Sectorial Policy Framework, Carolina Espina, Miquel Porta, Joachim Schüz, Ildefonso Hernández Aguado, Robert V. Percival, Carlos Dora, Terry Slevin, Julietta Rodriguez Guzman, Tim Meredith, Philip J. Landrigan, Maria Neira

Robert Percival

Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low and middle-income countries. A substantial portion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. The objective of this study was to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. The study concluded that opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens.

Defining Genetic Intra-Tumor Heterogeneity: A Chronological Annotation Of Mutational Pathways, Wentao Luo, Fan Wu, Susan R. Atlas, Gavin Pickett, Kimberly K. Leslie, Donghai Dai

Kimberly K. Leslie

Tumor heterogeneity is believed to be important in tumor progression and its response to therapies. However, despite numerous mutations being reported in human tumors, genetic intra-tumor heterogeneity remains poorly defined. We have developed a novel strategy to provide a chronological annotation of mutational events in a tumor. We used an endometrial tumor from a patient and transplanted it into athymic mice to create many tumor xenografts. While the patient tumor xenografts were initially responsive to raloxifene treatment, xenografts created with cancer cell clones isolated from the same patient tumor showed dramatic differences in response to raloxifene, indicating existence of intra-tumor …

Global Quantitative Assessment Of The Colorectal Polyp Burden In Familial Adenomatous Polyposis Using A Web-Based Tool, Patrick M. Lynch, Jeffrey S. Morris, William A. Ross, Miguel A. Rodriguez-Bigas, Juan Posadas, Rossa Khalaf, Diane M. Weber, Valerie O. Sepeda, Bernard Levin, Imad Shureiqi

Jeffrey S. Morris

Background: Accurate measures of the total polyp burden in familial adenomatous polyposis (FAP) are lacking. Current assessment tools include polyp quantitation in limited-field photographs and qualitative total colorectal polyp burden by video.

Objective: To develop global quantitative tools of the FAP colorectal adenoma burden.

Design: A single-arm, phase II trial.

Patients: Twenty-seven patients with FAP.

Intervention: Treatment with celecoxib for 6 months, with before-treatment and after-treatment videos posted to an intranet with an interactive site for scoring.

Main Outcome Measurements: Global adenoma counts and sizes (grouped into categories: less than 2 mm, 2-4 mm, and greater than 4 mm) were …

Physical Activity And Quality Of Life Of Cancer Survivors: A Lack Of Focus For Lifestyle Redesign, Jia Ern Lee Ms, Siew Yim Loh Assoc Prof

Siew Yim Loh

Physical activity is a component of lifestyle activity and one that has been increasingly seen as 'the medicine' to cure chronic diseases, including certain types of cancer. Physical activity has potent impact on mortality but only if it is well incorporated as lifestyle activity may it allow a better outcome of the quality of life of cancer survivors. This paper presents a review on the evidence of physical activity being actively promoted as lifestyle activity amongst cancer survivors, for the last five years. MATERIALS AND METHODS: Electronic databases were systematically searched for randomized controlled trials incorporated as lifestyle activity through …

Effectiveness Of A Patient Self- Management Program For Breast Cancer As A Chronic Illness: A Non- Randomised Controlled Clinical Trial, Siew Yim Loh Assoc Prof, Tanya Packer Prof, Karunthan Chinna Assoc Prof, Kia Fatt Quek Assoc Prof

Siew Yim Loh

Purpose Patient self-management enables living with a chronic disease effectively. This study examines the effectiveness of a 4-week self-management programme to enable self-management of the numerous after-effects and with breast cancer as a chronic disease. Methods Upon ethical approval, 147 multiethnic survivors (stages I–III breast cancer) received either a 4-week self-management intervention (n=68) or usual care (n=78) on a controlled clinical trial in a medical centre. The facilitator led group intervention provides self-management support and skills for managing the medical, emotional and role tasks. Survivors completed the pre- and post-intervention measures on quality of life, distress and participation inventory. Results …

An Intervention To Improve Adherence And Symptoms For Oral Oncolytics, Sandra Spoelstra

Sandra L. Spoelstra, PhD, RN, FGSA, FAAN

Feasibility Of Text Messaging To Improve Oral Anti-Cancer Adherence In Older Cancer Patients, Sandra Spoelstra

Sandra L. Spoelstra, PhD, RN, FGSA, FAAN