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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.

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.

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.

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.

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.

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