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Griffin C.,University of Windsor | Hamm C.,Windsor Regional Cancer Center | McNulty J.,McMaster University | Pandey S.,University of Windsor
Cancer Cell International | Year: 2010

Background: Pancratistatin, a natural compound extracted from Hymenocallis littoralis, can selectively induce apoptosis in several cancer cell lines. In this ex vivo study, we evaluated the effect of pancratistatin on peripheral blood mononuclear cells obtained from 15 leukemia patients prior to clinical intervention of newly diagnosed patients, as well as others of different ages in relapse and at various disease progression states.Results: Mononuclear cells from healthy volunteers and leukemia patients were exposed to 1 μM pancratistatin for up to 48 h. Irrespective of leukemia type, pancratistatin induced apoptosis in the leukemic samples, with minimal effects on non-cancerous peripheral blood mononuclear control cells.Conclusion: Our results show that pancratistatin is an effective and selective anti-cancer agent with potential for advancement to clinical trials. © 2010 Griffin et al; licensee BioMed Central Ltd.


Ovadje P.,University of Windsor | Hamm C.,Windsor Regional Cancer Center | Pandey S.,University of Windsor
PLoS ONE | Year: 2012

Background: Chronic Myelomonocytic Leukemia (CMML) is a heterogeneous disease that is not only hard to diagnose and classify, but is also highly resistant to treatment. Available forms of therapy for this disease have not shown significant effects and patients rapidly develop resistance early on in therapy. These factors lead to the very poor prognosis observed with CMML patients, with median survival duration between 12 and 24 months after diagnosis. This study is therefore centered around evaluating the selective efficacy of a natural extract from dandelion roots, in inducing programmed cell death in aggressive and resistant CMML cell lines. Methodology/Principal Findings: To confirm the induction of programmed cell death in three human CMML cell lines, nuclear condensation and externalization of the phosphatidylserine, two main characteristics of apoptosis, were detected using Hoechst staining and annexin-V binding assay. The induction of another mode of cell death, autophagy, was determined using a monodansylcadaverine (MDC) stain, to detect the formation of autophagy vacuoles. The results from this study indicate that Dandelion Root Extract (DRE) is able to efficiently and selectively induce apoptosis and autophagy in these cell lines in a dose and time dependent manner, with no significant toxicity on non-cancerous peripheral blood mononuclear cells. More importantly, we observed early activation of initiator caspase-8, which led to mitochondrial destabilization and the induction of autophagy, suggesting that DRE acts through the extrinsic pathway of apoptosis. The inability of DRE to induce apoptosis in dominant-negative FADD cells, confirms the mechanism of action of DRE in in vitro models of CMML. Conclusion: The results from this study indicate that natural products, in particular Dandelion Root Extract, have great potential, as non-toxic and effective alternatives to conventional modes of chemotherapy available today. © 2012 Ovadje et al.


Ovadje P.,University of Windsor | Chochkeh M.,University of Windsor | Akbari-Asl P.,University of Windsor | Hamm C.,Windsor Regional Cancer Center | Pandey S.,University of Windsor
Pancreas | Year: 2012

OBJECTIVES: Pancreatic cancer has a 100% mortality rate; the aim of this study is to evaluate the efficacy of dandelion root extract (DRE) in inducing apoptosis and autophagy in aggressive and resistant pancreatic cancer cells. METHODS: The effect of DRE was evaluated using WST-1 (4-[3-(4-iodophenyl)-2-(4- nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assay. Apoptotic cell death was confirmed by nuclear condensation by Hoechst staining and externalization of phosphatidylserine to the outer leaflet of the plasma membrane by Annexin-V binding assay. Loss of mitochondrial membrane potential was observed using the JC-1 (5,5′,6, 6′-tetrachloro-1,1′,3, 3′ tetraethylbenzimidazolylcarbocyanine iodide) dye. The induction of autophagy was detected using a monodansylcadaverine assay and this was confirmed by immunofluorescence for light chain 3-II. RESULTS: BxPC-3 and PANC-1 pancreatic cells were sensitive to aqueous DRE. This extract induces selective apoptosis in a dose- and time-dependent manner. Dandelion root extract caused the collapse of the mitochondrial membrane potential, leading to prodeath autophagy. Normal human fibroblasts were resistant at similar doses. CONCLUSIONS: We demonstrate that DRE has the potential to induce apoptosis and autophagy in human pancreatic cancer cells with no significant effect on noncancerous cells. This will provide a basis on which further research in cancer treatment through DRE can be executed. ABBREVIATIONS: DRE - dandelion root extractLC3-II - light chain 3-IIMDC - monodansylcadaverine Copyright © 2012 by Lippincott Williams & Wilkins.


Gorey K.M.,University of Windsor | Haji-Jama S.,University of Windsor | Bartfay E.,University of Ontario Institute of Technology | Luginaah I.N.,University of Western Ontario | And 2 more authors.
BMC Health Services Research | Year: 2014

Background: Despite evidence of chemotherapy's ability to cure or comfort those with colon cancer, nearly half of such Americans do not receive it. African Americans (AA) seem particularly disadvantaged. An ethnicity by poverty by health insurance interaction was hypothesized such that the multiplicative disadvantage of being extremely poor and inadequately insured is worse for AAs than for non-Hispanic white Americans (NHWA). Methods. California registry data were analyzed for 459 AAs and 3,001 NHWAs diagnosed with stage II to IV colon cancer between 1996 and 2000 and followed until 2011. Socioeconomic data from the 2000 census categorized neighborhoods: extremely poor (≥ 30% of households poor), middle (5-29% poor) and low poverty (< 5% poor). Participants were randomly selected from these poverty strata. Primary health insurers were Medicaid, Medicare, private or none. Chemotherapy rates were age and stage-adjusted and comparisons used standardized rate ratios (RR). Logistic and Cox regressions, respectively, modeled chemotherapy receipt and long term survival. Results: A significant 3-way ethnicity by poverty by health insurance interaction effect on chemotherapy receipt was observed. Among those who did not live in extremely poor neighborhoods and were adequately insured privately or by Medicare, chemotherapy rates did not differ significantly between AAs (37.7%) and NHWAs (39.5%). Among those who lived in extremely poor neighborhoods and were inadequately insured by Medicaid or uninsured, AAs (14.6%) were nearly 60% less likely to receive chemotherapy than were NHWAs (25.5%, RR = 0.41). When the 3-way interaction effect as well as the main effects of poverty, health insurance and chemotherapy was accounted for, survival rates of AAs and NHWAs were the same. Conclusions: The multiplicative barrier to colon cancer care that results from being extremely poor and inadequately insured is worse for AAs than it is for NHWAs. AAs are more prevalently poor, inadequately insured, and have fewer assets so they are probably less able to absorb the indirect and direct, but uncovered, costs of colon cancer care. Policy makers ought to be cognizant of these factors as they implement the Affordable Care Act and consider future health care reforms. © 2014 Gorey et al.; licensee BioMed Central Ltd.


Pandey S.,University of Windsor | Chatterjee S.J.,University of Windsor | Ovadje P.,University of Windsor | Mousa M.,University of Windsor | Hamm C.,Windsor Regional Cancer Center
Evidence-based Complementary and Alternative Medicine | Year: 2011

Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25-29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS) generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells. © 2011 S. J. Chatterjee et al.


Whelan T.J.,McMaster University | Pignol J.-P.,Odette Cancer Center | Levine M.N.,McMaster University | Julian J.A.,McMaster University | And 10 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown. METHODS: We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group). RESULTS: The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, -6.9 to 9.8). CONCLUSIONS: Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.) Copyright © 2010 Massachusetts Medical Society.


Yu E.,London Health Sciences Center | Suzuki H.,Seirei Hamamatsu General Hospital | Younus J.,London Health Sciences Center | Elfiki T.,Windsor Regional Cancer Center | And 6 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Objective: To assess the impact of radiation management on male breast cancer (MBC) at London Regional Cancer Program (LRCP). Methods and Materials: Men with a diagnosis of breast cancer referred to LRCP were reviewed. The seventh American Joint Committee on Cancer staging system was used. Patients treated with and without post-mastectomy radiation therapy (PMRT) were analyzed. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. Survival estimates were obtained using Kaplan-Meier methodology. Results: From January 1977 to December 2006, 81 men had invasive ductal carcinoma. The median age was 65 (range, 35-87 years). There were 15 Stage I, 40 Stage II, 20 Stage III, and 6 Stage IV patients. Median follow-up time was 46 months (range, 1-225 months). Of the 75 patients treated with curative intent, 29 did not receive PMRT and 46 completed PMRT. Patients who received PMRT demonstrated no benefit in overall survival (p = 0.872) but significantly better local recurrence free survival (p < 0.001) compared with those who did not receive RT. There was trend toward improving locoregional recurrence with PMRT in patients with high-risk features (node-positive, advanced stage, and ≤2 mm or unknown surgical margin). The median, 5-year, and 10-year disease-free survival and overall survival for the 75 patients were 77.7 months, 66.3%, 32.7%, and 91.2 months, 73.9%, and 36.6%, respectively. Conclusion: The experience at LRCP suggests that high-risk MBC patients should consider PMRT to improve their chance of local recurrence-free survival. © 2012 Elsevier Inc.


Morton G.,Sunnybrook Odette Cancer Center | Loblaw A.,Sunnybrook Odette Cancer Center | Cheung P.,Sunnybrook Odette Cancer Center | Szumacher E.,Sunnybrook Odette Cancer Center | And 9 more authors.
Radiotherapy and Oncology | Year: 2011

Background and purpose: High dose-rate (HDR) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy (EBRT). Our purpose is to compare outcomes with a single fraction HDR boost to that with a standard fractionated boost in intermediate risk prostate cancer. Materials and methods: Results of two sequential phase II clinical trials are compared. The Single Fraction protocol consists of 15 Gy HDR in one fraction followed by 37.5 Gy EBRT in 15 fractions over 3 weeks; the Standard Fractionation protocol consisted of two HDR fractions each of 10 Gy, 1 week apart, followed by 45 Gy EBRT in 25 fractions. Patients had intermediate risk disease, and were well balanced for prognostic factors. Patients were followed prospectively for efficacy, toxicity and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition, and by biopsy at 2 years. Results: The Single Fraction protocol accrued 123 patients and the Standard Fractionation protocol, 60. With a median follow-up of 45 and 72 months, respectively, the biochemical disease-free survival was 95.1% and 97.9% in the Single and Standard Fractionation trials (p = 0.3528). Two-year prostate biopsy was positive in only 4% and 8%, respectively. There was no difference in late urinary or rectal toxicity rates, or in health-related quality of life between the two protocols. Conclusions: The Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions, with significant savings in resources. While mature results with longer follow-up are awaited, a single 15 Gy may be considered as a standard fractionation regimen in combination with EBRT for men with intermediate risk disease. © 2011 Elsevier Ireland Ltd. All rights reserved.


Coroneos C.J.,Windsor Regional Cancer Center | Hamm C.,Windsor Regional Cancer Center | Hamm C.,Universities of Western Ontario and of Windsor
Current Oncology | Year: 2010

Ductal carcinoma in situ (dcis) in a young man is rarely reported. Our patient, a 25-year-old man, presented with apparent symptomatic unilateral gynecomastia. He has a strong history of cancer on both the maternal and paternal sides of his family, including breast and lung (maternal) and melanoma, colon, and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on paternal genetic testing. The patient was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gynecomastia and dcis were discovered. To date, only 4 cases of gynecomastia and dcis have been described in younger male patients. Because only 30%-50% of patients with dcis eventually develop invasive cancer in the subsequent 10-20 years, dcis prevalence in the general population may be higher than predicted. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be, and physicians must remain cautious of cancer in young men with gynecomastia.


PubMed | Windsor Regional Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

10686 Background: Wait times in the navigation of the diagnostic and therapeutic system of breast cancer have been increasingly investigated. It is inherently apparent that an earlier diagnosis would lead to an improved prognosis in breast cancer. In Ontario (Canada) Breast Screening Clinics (OBSC) allow direct access of patients to mammograms.A retrospective review of all breast cancer patients seen in the regional cancer centre in the year 2003 was performed. Wait times between the following events were recorded: first symptom to presentation to medical system, presentation to mammogram, mammogram to biopsy, biopsy to surgery, surgery to consultation at cancer centre.In 2003, 277 new cases of breast cancer were seen at the regional cancer centre. Identified median waiting times were as follows: mammogram to diagnostic biopsy - 18.5 days, diagnostic biopsy to definitive surgery - 28 days; surgical consultation to definitive surgery - 13 days; definitive surgery to oncology consultation - 31 days. Some wait times were longer in those patients who did not have close geographic access to OBSC and a regional cancer centre: mammography to diagnostic biopsy was doubled (17 to 34 days) and surgical consult to surgical date was doubled (12 vs 26.5 days). Eighty per cent (n = 27) of patients identified by OBSC presented with Stage I or less breast cancer vs 37% of all other patients. Seventeen per cent of patients seen at the regional cancer centre were less than 50 years of age and not eligible for the OBSC.The wait times reported are in keeping with the current experience in Ontario, Canada.[1] It is most likely that access to a breast-screening clinic allows self-selection of a more highly motivated population. This population of patients consistently presented with earlier stage and more curable disease. The challenge that remains is to increase the number of patients that access breast-screening clinics. Presently, only 13% of presenting patients seen at the regional cancer centre were identified by the OBSC. We are identifying barriers to the use of this very effective strategy. [1] Cancer Care Ontario. Ontario Wait Times Strategy. www.health.gov.on.ca. [Table: see text].

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