Medical Sciences Commons^™

Omega-3 Fatty Acids To Augment Cancer Therapy, W. Hardman

Elaine Hardman Ph.D.

The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include 1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor; 2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion; 3) inducing differentiation of cancer cells; 4) suppressing nuclear factor--kB activation and bcl-2 expression, …

Three Percent Dietary Fish Oil Concentrate Increased Efficacy Of Doxorubicin Against Mda-Mb 231 Breast Cancer Xenografts, W. Hardman, C. Reddy Avula, Gabriel Fernandes, Ivan Cameron

Elaine Hardman Ph.D.

Omega 3 polyunsaturated fatty acids (the type of fat found in fish oil) have been used to kill or slow the growth of cancer cells in culture and in animal models and to increase the effectiveness of cancer chemotherapeutic drugs. An AIN-76 diet containing 5% corn oil (CO) was modified to contain 3% w/w fish oil concentrate (FOC) and 2% CO to test whether a clinically applicable amount of FOC is beneficial during doxorubicin (DOX) treatment of cancer xenografts in mice. Compared with the diet containing 5% CO, consumption of FOC increased omega 3 polyunsaturated fatty acids and lipid peroxidation …

Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta

Elaine Hardman Ph.D.

Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …

Dietary Walnut Suppressed Mammary Gland Tumorigenesis In The C(3)1 Tag Mouse, W. Hardman

Elaine Hardman Ph.D.

Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor …

Consumption Of An Omega-3 Fatty Acids Product, Incell Aafa Tm , Reduced Side-Effects Of Cpt-11 (Irinotecan) In Mice, W. Hardman, M. Moyer, Ivan Cameron

Elaine Hardman Ph.D.

INCELL AAFA™, an omega-3 polyunsaturated fatty acid product containing a high concentration of long chain fatty acids, was tested for its ability to ameliorate the harmful side effects of CPT-11 chemotherapy including: leukopenia, anaemia, asthenia, weight loss and liver involvement. Four groups of mice were fed an AIN-76 diet modified to contain: 10% w/w corn oil (CO), 0% AAFA™; 9% CO, 1% AAFA™; 8% CO, 2% AAFA™; or 7% CO, 3% AAFA™. After 2 weeks on the diets, half of the mice received CPT-11 chemotherapy (60 mg kg-1 q 4 days, i.v.) the rest of the mice received vehicle for …

Ybx1 Expression And Function In Early Hematopoiesis And Leukemic Cells, Jasjeet Bhullar, Vincent Sollars

Vincent E Sollars

Hematopoietic transcription factors play a critical role in directing the commitment and differentiation of hematopoietic stem cells along a particular lineage. Y-box protein (YBX1) is a transcription factor which is widely expressed throughout development and is involved in erythroid cell development; however, its role in early hematopoietic differentiation is not known. This study aims to investigate the role of YBX1 expression in early hematopoietic differentiation and leukemia. Here, we show that YBX1 is highly expressed in mouse erythroid myeloid lymphoid-clone 1 (EML), a hematopoietic precursor cell line, but is down-regulated in myeloid progenitors and GM-CSF-treated EML cells during the course …

Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles

Vincent E Sollars

Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-β2 (RAR-β2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-β2. There was not a strict correlation between DNA methylation of RAR-β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-β gene promoter was higher in cells expressing RAR-β2. All trans retinoic acid treatment of …

Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles

Richard M Niles

Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-β2 (RAR-β2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-β2. There was not a strict correlation between DNA methylation of RAR-β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-β gene promoter was higher in cells expressing RAR-β2. All trans retinoic acid treatment of …

Expression And Function Of Cd9 In Melanoma Cells, Jun Fan, Guo-Zhang Zhu, Richard Niles

Richard M Niles

CD9, a member of the tetraspanin family, functions as an organizer in “tetraspanin webs,” through interacting with other cell adhesion molecules. It plays a role in differentiation, fertilization, and cell migration. We investigated the expression and function of CD9 in melanoma. CD9 protein expression in B16 mouse melanoma and six human melanoma cell lines was decreased compared to normal melanocytes. B16F1 clones stably overexpressing CD9 had reduced ability to form colonies in soft agar; however, paradoxically these overexpressing clones had increased ability to invade Matrigel. Similarly, transient overexpression of CD9 in the human metastatic melanoma cell line WM9 dramatically decreased …

Resveratrol Is Rapidly Metabolized In Athymic (Nu/Nu) Mice And Does Not Inhibit Human Melanoma Xenograft Tumor Growth, Richard Niles, Carla Cook, Gary Meadows, Ya-Min Fu, Jerry Mclaughlin, Gary Rankin

Richard M Niles

Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 μmol/L or 263 μmol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10–100 mg resveratrol were implanted into the mice, next to newly palpated …

Pparα/Γ Expression And Activity In Mouse And Human Melanocytes And Melanoma Cells, Linda Eastham, Caroline Mills, Richard Niles

Richard M Niles

Purpose. We examined the expression of PPARs and the effects of PPARα and PPARγ agonists on growth of mouse and human melanocytes and melanoma cells.

Methods. PPARα,β, and PPARγ mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARα mRNA levels were determined by QuantiGene assay. PPARα and PPARγ protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter …

Stereotactic Ablative Radiotherapy For Comprehensive Treatment Of Oligometastatic Tumors (Sabr-Comet): Study Protocol For A Randomized Phase Ii Trial., Michael Lock

Michael Lock

No abstract provided.

Long-Term Outcome Of Breast Cancer Patients With One To Two Nodes Involved-Application Of Nodal Ratio, Patricia Tai, Kurian Joseph, Ali El-Gayed, Edward Yu

Edward Yu

Abstract: Nodal ratio (NR) is defined as the number of involved nodes to the number of nodes examined. There is limited information on the application of NR on population data. Previous reports in breast cancer generally analyzed one to three positive axillary nodes as a single group. This study investigates whether one to three positive axillary nodes is a homogeneous group in prognosis by comparing one to two positive nodes to three positive nodes. The population-based registry of a Canadian province from 1981 through 1995 was searched. As the reliability of nodal assessment depends on the number of nodes sampled, …

Mesothelioma - Epidemiology And Management, Patricia Tai, Edward Yu, Avi Assouline, Kurian Joseph

Edward Yu

Mesothelioma is an uncommon tumor. It has a latency period of 20-40 years. The most important risk factor is asbestos exposure. Prognosis of mesothelioma is generally poor with high case-fatality rate, and research to improve the outcome of this disease is on-going worldwide. Due to its rarity, management by a multidisciplinary team with experience is recommended. Carefully selected patients may benefit from tri-modality (surgery, radiotherapy and chemotherapy) treatment. The management of pleural and peritoneal mesothelioma is summarized in this review. Recent advances in chemotherapy and biologic response modifiers are promising.

Lung Cancer Epidemiology – A Global View, Patricia Tai, Edward Yu, Rashmi Koul, Arbind Dubey

Edward Yu

Smoking, air pollution and radon exposure are causally related to lung cancer. This review analyzes trends of smoking habits by age, sex and ethnicity and their correlation with incidence and mortality of lung cancer. Unfortunately the use of tobacco by adolescents is on the rise. Most developed countries are still showing the rising trend of mortality in female smokers. In Asia, cigarette smoking has become a major health risk with one in three of all cigarettes in the world today are smoked in China. Estimated one hundred million young ( < 29 years old) Chinese smokers will eventually die from lung …

Lung Cancer Brachytherapy: Robotics-Assisted Minimally Invasive Approach, Edward Yu, Craig Lewis, Ana Trejos, Rajni Patel, Richard Malthaner

Edward Yu

New technological concepts have been evolving to manage the relative poor prognosis of lung cancer. Brachytherapy is becoming an option for both unresectable and early resectable lung cancer. Three-dimensional ultrasound (US) of lung tumours and image-guided minimally invasive robotics-assisted brachytherapy are feasible for dosimetry planning and management of lung tumours. The present article reviews the current knowledge of lung brachytherapy and discusses its potential in future management of lung cancer.

The Impact Of Post-Mastectomy Radiation Therapy On Male Breast Cancer Patients--A Case Series, Edward Yu, Hiromichi Suzuki, Jawaid Younus, Tarek Elfiki, Larry Stitt, Gary Yau, Olga Vujovic, Francisco Perera, Michael Lock, Patricia Tai

Edward Yu

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: …

Pillows For Pain, Michael Lock

Michael Lock

No abstract provided.

The Use Of Ct Density Changes At Internal Tissue Interfaces To Correlate Internal Organ Motion With An External Surrogate, Stewart Gaede, Gregory Carnes, Edward Yu, Jake Van Dyk, Jerry Battista, Ting-Yim Lee

Edward Yu

The purpose of this paper is to describe a non-invasive method to monitor the motion of internal organs affected by respiration without using external markers or spirometry, to test the correlation with external markers, and to calculate any time shift between the datasets. Ten lung cancer patients were CT scanned with a GE LightSpeed Plus 4-Slice CT scanner operating in a ciné mode. We retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s reconstructions at 0.1 s intervals to increase image sampling. We defined regions of interest containing tissue interfaces, including tumour/lung interfaces that move due to breathing …

Post-Operative Extended Volume External Beam Radiation Therapy In High Risk Esophageal Cancer Patients: A Prospective Experience, E. Yu, P. Tai, J. Younus, R. Malthaner, P. Truong, L. Stitt, G. Rodrigues, R. Ash, R. Dar, B. Yaremko, A. Tomiak, B. Dingle, M. Sanatani, M. Vincent, W. Kocha, D. Fortin, R. Inculet

Edward Yu

Background and purpose: Extended volume external beam radiation therapy (RT) following esophagectomy is controversial. This prospective study evaluates the feasibility of extended volume RT treatment in high-risk esophagectomy patients with cervical anastomosis receiving post–operative combined chemo-radiation therapy. Patients and methods: From 2001-2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study, to evaluate the adverse effects of extended volume RT. Eligibility criteria were pathologically proven esophageal malignancy, T3-4, N0-1, disease amenable to surgical resection and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All …

The Effect Of Timing Of Radiotherapy After Breast-Conserving Surgery In Patients With Positive Or Close Resection Margins, Young Age, And Node-Negative Disease, With Long Term Follow-Up, Olga Vujovic, Anil Cherian, Edward Yu, A. Dar, Larry Stitt, Francisco Perera

Edward Yu

Purpose: The aim of this study was to determine the effect of timing of radiotherapy after conservative breast surgery on local recurrence in women with positive resection margins and young age, treated without systemic therapy. Methods and materials: A total of 568 patients with T1 and T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, between January 1, 1985, and December 31, 1992, at the London Regional Cancer Centre. 63 patients (11.1%) had positive/close resection margins (< 2 mm) and 48 patients (8.4%) were age < or = 40 years. For patients with positive resection margins, the time intervals from breast surgery to breast irradiation used for analysis were, 0 to 8 weeks, > 8 to 12 weeks and > 12 weeks. For patients < or = 40 years, the intervals used for analysis were 0 to 8 weeks and > 8 weeks. Results: Median follow up was 11.2 years. For patients …

Comparative Planning Evaluation Of Intensity-Modulated Radiotherapy Techniques For Complex Lung Cancer Cases, Slav Yartsev, Jeff Chen, Edward Yu, Tomas Kron, George Rodrigues, Terry Coad, Kristina Trenka, Eugene Wong, Glenn Bauman, Jake Van Dyk

Edward Yu

Background and purpose: Lung cancer treatment can be one of the most challenging fields in radiotherapy. The aim of the present study was to compare different modalities of radiation delivery based on a balanced scoring scheme for target coverage and normal tissue avoidance. Patients and methods: Treatment plans were developed for 15 patients with stage III inoperable non-small cell lung cancer using 3D conformal technique and intensity-modulated radiotherapy (IMRT). Elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to …

Does Sex Influence The Impact That Smoking, Treatment Interruption And Impaired Pulmonary Function Have On Outcomes In Limited Stage Small Cell Lung Cancer Treatment?, Gregory Videtic, Pauline Truong, Robert Ash, Edward Yu, Walter Kocha, Mark Vincent, Anna Tomiak, A Dar, Frances Whiston, Larry Stitt

Edward Yu

PURPOSE: To look for survival differences between men and women with limited stage small cell lung cancer (LS-SCLC) by examining stratified variables that impair treatment efficacy. METHODS: A retrospective review of 215 LS-SCLC patients treated from 1989 to 1999 with concurrent chemotherapy-radiotherapy modelled on the 'early-start' thoracic radiotherapy arm of a National Cancer Institute of Canada randomized trial. RESULTS: Of 215 LS-SCLC patients, 126 (58.6%) were men and 89 (41.4%) were women. Smoking status during treatment for 186 patients (86.5%) was: 107 (58%) nonsmoking (NS) (76 [71%] male [M]; 31 [29%] female [F]) and 79 (42%) smoking (S) (36 M …

Planning Evaluation Of Radiotherapy For Complex Lung Cancer Cases Using Helical Tomotherapy, Tomas Kron, Grigor Grigorov, Edward Yu, Slav Yartsev, Jeff Chen, Eugene Wong, George Rodrigues, Kris Trenka, Terry Coad, Glenn Bauman, Jake Van Dyk

Edward Yu

Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used …

Radiation Treatment Of Lung Cancer--Patterns Of Practice In Canada, Patricia Tai, Edward Yu, Jerry Battista, Jake Van Dyk

Edward Yu

BACKGROUND AND PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat lung cancers. PATIENTS AND METHODS: A questionnaire detailing different aspects of radiation treatment of lung cancer was mailed to all radiation oncologists treating lung cancer in Canada. Seventy-two percent (74/103) of radiation oncologists who treat lung cancer from all 34 Canadian cancer centres replied to the questionnaire. RESULTS: (a) Radiotherapy regimens in Canadian cancer centres are in accordance with several major randomised studies. There is still some variation in treatment practice that may be due to unresolved controversies or limited resources. The most frequently used …

Improving The Consistency In Cervical Esophageal Target Volume Definition By Special Training, Patricia Tai, Jake Van Dyk, Jerry Battista, Edward Yu, Larry Stitt, Jon Tonita, Olusegun Agboola, James Brierley, Rashid Dar, Christopher Leighton, Shawn Malone, Barbara Strang, Pauline Truong, Gregory Videtic, C. Wong, Rebecca Wong, Youssef Youssef

Edward Yu

PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 …

Monte Carlo Simulations Of Dna Damage From Incorporated Cold Iodine Following Photoelectrically Induced Auger Electron Cascades, V. Moiseenko, S. Karnas, E. Yu, J. Battista

Edward Yu

Radiation-induced damage in nucleosomal DNA from Auger electron cascades due to incorporated cold IUdR has been modelled through Monte Carlo simulations. Probabilities of DNA double strand break (DSB) production following a vacancy in the K, L, M and N shells of iodine are estimated. DSB complexity from the base damage accompanying a break was also estimated. Multiple DSB events were analysed for correlated breaks due to nucleosome periodicity. The probability of an Auger cascade causing at least one DSB strongly depended on the shell in which the initial vacancy was produced. This probability was approximately 0.35 for K and L …

Monte Carlo Simulations And Measurement Of Dna Damage From X-Ray-Triggered Auger Cascades In Iododeoxyuridine (Iudr), S. Karnas, V. Moiseenko, E. Yu, P. Truong, J. Battista

Edward Yu

We investigated the DNA damage from Auger electrons emitted from incorporated stable iodine (127I), following photoelectric absorption of external x-rays. The effectiveness of the Auger electrons in producing DNA double-strand breaks (DSB) was determined theoretically, using Monte Carlo simulations of the radiation physics and chemistry, and was shown to be in reasonable agreement with DNA damage measured using the comet assay. The DSB yields were measured in CHO cells for 60Co (as a non-Auger-promoting radiation) and for tungsten-filtered 100 kVp x-rays capable of producing Auger electron emission. The theoretical study showed that on average, 2.5 Auger electrons were emitted for …

Using Treatment Interruptions To Palliate The Toxicity From Concurrent Chemoradiation For Limited Small Cell Lung Cancer Decreases Survival And Disease Control, Gregory Videtic, Karen Fung, Anna Tomiak, Larry Stitt, A. Dar, Pauline Truong, Edward Yu, Mark Vincent, Walter Kocha

Edward Yu

BACKGROUND AND PURPOSE: We analyzed the impact on survival outcomes of treatment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radiotherapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years. MATERIALS AND METHODS: From 1989 to 1999, 215 patients received treatment for LSCLC, consisting of six cycles of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine (CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, …

Radiation Treatment For Cervical Esophagus: Patterns Of Practice Study In Canada, 1996, Patricia Tai, Jake Van Dyk, Edward Yu, Jerry Battista, Matthew Schmid, Larry Stitt, Jon Tonita, Terry Coad

Edward Yu

PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat esophageal cancers, using a trans-Canada survey, completed at the end of 1996. METHODS AND MATERIALS: One of 3 case presentations of different stages of cervical esophageal cancer was randomly assigned and sent to participating radiation oncologists by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline target volumes for the boost phase of radiotherapy. Radiation oncologists from 26 of 27 (96%) of all Canadian centers participated. RESULTS: High-energy X-rays (>/= 10 MV) were employed by 68% of the respondents in part …