Trunk and Branch Drivers Distinguish Early vs Late Mutations in Hepatocellular Carcinoma

MedicalResearch.com Interview with:
Sara Torrecilla Recio

PhD Student
Mount Sinai Liver Cancer Program – Division of Liver Diseases Icahn School of Medicine at Mount Sinai
New York, NY

MedicalResearch.com: What is the background for this study?

Response: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which represents the second-leading cause of cancer related death worldwide. The landscape of molecular alterations in HCC has been thoroughly explored using next-generation sequencing technologies in single biopsies of tumors. However, in the recent years it has been demonstrated that not all the regions of a tumor harbor the same molecular alterations. This intra-tumor heterogeneity may lead to a misinterpretation of the molecular landscape of the malignancy since not all the molecular alterations would be captured by single-biopsies.

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Model of RAF Inhibitor Action Provides Roadmap For Resistant Colon and Thyroid Cancer Treatment

MedicalResearch.com Interview with:

Poulikos I. Poulikakos, PhD Assistant Professor Department of Oncological Sciences Department of Dermatology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai

Dr. Poulikakos

Poulikos I. Poulikakos, PhD
Assistant Professor
Department of Oncological Sciences
Department of Dermatology
The Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study?

Response: Mutations in the oncoprotein kinase BRAF are found in about 8% of human tumors, including more than 50% of melanomas. Small molecule RAF inhibitors prolonged survival of melanoma patients with mutant-BRAF tumors, but resistance limits their effectiveness. Further, RAF inhibitors showed only modest efficacy in patients with colorectal and thyroid mutant-BRAF tumors. Previous studies have suggested that the complex biochemical mechanisms of action of RAF inhibitors account for both sensitivity and major mechanisms of resistance to these drugs. Recently, a number of next generation RAF inhibitors have entered preclinical or clinical development, but the most appropriate clinical context for their use remained elusive.

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Effect of Centralization on Health Disparities in Lung and Bladder Cancer Surgery

MedicalResearch.com Interview with:

Emanuela Taioli MD PhD Professor, Population Health Science and Policy, and Thoracic Surgery Director, Institute for Translational Epidemiology Director, Center for the Study of Thoracic Diseases Outcome Director, Division of Social Epidemiology Icahn Medical Institute, New York, NY 10029

Dr. Taioli

Emanuela Taioli MD PhD
Professor, Population Health Science and Policy, and Thoracic Surgery
Director, Institute for Translational Epidemiology
Director, Center for the Study of Thoracic Diseases Outcome
Director, Division of Social Epidemiology
Icahn Medical Institute,
New York, NY 10029 

MedicalResearch.com: What is the background for this study?

Response: Extensive literature documenting the relationship between hospital volume and clinical outcomes has resulted in the centralization of cancer care advocating patients to seek cancer surgical procedures at high-volume (HV) hospitals. Lung resection and cystectomy have been specifically recommended for centralization, but improvements in outcomes are not shared equally among racial groups. It has also been reported that black patients more commonly undergo surgery at low-volume and lower-quality hospitals, despite living in close proximity to higher quality hospitals.

We investigated the effects of centralization on HV hospital utilization and surgical outcomes for lung (n = 28,047 White; n = 2,638 Black) and bladder (n = 7,593 White; n = 567 Black) cancer patients over a 15 year time span (1997-2011) in New York State. We hypothesized that centralization has improved utilization of HV hospitals and outcomes for both black and white patients, but significant disparities remain between black and white patients.

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Diabetes Drug Reverses Aging Medium That Promotes Melanoma

MedicalResearch.com Interview with:

Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA

Dr. Behera

Reeti Behera, Ph.D.
Postdoctoral fellow in the Weeraratna lab
The Wistar Institute
Philadelphia PA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance.

Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.

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False Positive Mammograms Can Lead Women To Delay or Skip Next Exam

MedicalResearch.com Interview with:

Mammogram showing small lesion - Wikipedia

Mammogram showing small lesion
– Wikipedia

Firas Dabbous, PhD
Manager, Patient Centered Outcomes Research
Russell Institute for Research & Innovation
Advocate Lutheran General Hospital
Park Ridge, IL 

MedicalResearch.com: What is the background for this study?

Response: When women are told that there is something abnormal on their screening mammogram that can cause stress and worry while undergoing additional testing, even when they are later told that there is nothing wrong. We wanted to know if receiving a false positive screening mammogram would cause women to think twice before getting their next screening mammogram, and maybe delay coming back for their next screen. This is important because patients who have a false positive experience may have higher chance to develop breast cancer at a later point in time. Therefore, it is important to understand their screening patterns to better educate and inform them about the importance of adhering to mammography guidelines and emphasize the importance of returning on schedule for their next screens.

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ER-beta May Identify Breast Cancer Patients For Whom Chemotherapy is Sufficient

MedicalResearch.com Interview with:
Helena Jernström, PhD
Associate Professor in Experimental Oncology
Study Coordinator for Graduate studies Division of Oncology and Pathology
Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University
Division of Oncology and Pathology, Department of Clinical Sciences, Lund
Lund University Cancer Center/Kamprad
Lund, Sweden

MedicalResearch.com: What is the background for this study?

Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated.

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Novel microRNA Regulatory Network Has Important Therapeutic Implications in Rhabdomyosarcoma

MedicalResearch.com Interview with:
Riccardo Taulli, PhD
Assistant Professor of Biochemistry
Dept. of Oncology, University of Turin
Via Santena 5, 10126
Torino, Italy

MedicalResearch.com: What is the background for this study?

Response: Rhabdomyosarcoma is a muscle-derived pediatric cancer for which therapeutic options have not improved significantly over the past decades, especially for its metastatic form. MicroRNAs are small regulatory molecules that control gene expression at the post-transcriptional level, fine tuning a wide number of cellular mechanisms, processes and behaviors. In our work, we underwent a large microRNA isolation and sequencing effort using human samples of the three major rhabdomyosarcoma subtypes, along with cell lines and normal muscle, to identify novel molecular circuits with therapeutic potential.
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President of AACR Discusses Sixth Annual Cancer Progress Report

MedicalResearch.com Interview with:

Nancy Davidson, MD President of the American Association for Cancer Research (AACR) and Director, University of Pittsburgh Cancer Institute

Dr. Nancy Davidson

Nancy Davidson, MD
President of the American Association for Cancer Research (AACR) and
Director,  Cancer Institute
University of Pittsburgh

Dr. Davidson discusses the 2016 AACR Cancer Progress Report. “The report serves as an educational document for both Congress and the public, alike. The report is a call to action, designed to urge Congress and the American public to stand firm in their commitment to the conquest of cancer”.

MedicalResearch.com: What is the background and goals for this report?

Dr. Davidson:

  • This is the sixth edition of our annual Cancer Progress Report.
  •  The annual report is the cornerstone of the AACR’s educational and advocacy efforts:
  • The report outlines efforts to increase public and Congressional understanding of cancer and the importance of cancer research to public health and
  • Efforts to advocate for increased federal funding for the NIH, NCI, FDA, and other federal agencies that are vital for fueling progress against cancer
  • The first report was written in 2011, the year that marked the 40th anniversary of the signing of the National Cancer Act of 1971, to commemorate the advances in cancer research that had been made to date and to paint a picture of where the science was leading us.

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RANK signaling-blockade reduces breast cancer recurrence by inducing tumor cell differentiation

MedicalResearch.com Interview with:

Eva Gonzalez Suarez, PhD Group Leader Transformation and Metastasis lab. Cancer Epigenetics and Biology Program-PEBC Institut d'Investigació Biomédica de Bellvitge-IDIBELL Hospital Duran i Reynals Avinguda Gran Via de l'Hospitalet, L'Hospitalet de Llobregat-Barcelona-Spain

Dr. Eva Gonzalez Suarez

Eva Gonzalez Suarez, PhD
Group Leader Transformation and Metastasis lab.
Cancer Epigenetics and Biology Program-PEBC
Institut d’Investigació Biomédica de Bellvitge-IDIBELL
Hospital Duran i Reynals Avinguda Gran Via de l’Hospitalet,
L’Hospitalet de Llobregat-Barcelona-Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Thousands of cancer patients worldwide are taking RANKL inhibitors for the management of bone metastasis, based on the key role of RANKL and its receptor, RANK, driving osteoclastogenesis. RANK signaling pathway acts as a paracrine mediator of progesterone in mouse and human mammary epithelium. RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remained unknown.

Complementary genetic and pharmacological approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation and enhances sensitivity to chemotherapy in mouse models that closely resemble the clinical disease. Mechanistically, genome wide expression analyses showed that anti-RANKL therapy promotes differentiation of tumor cells into milk-producing cells, as observed during pregnancy.

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Math Algorithm Helps Predict Recurrence of Prostate Cancer


MedicalResearch.com Interview with:  

Ilaria Stura PhD

Università degli Studi di Torino
Turin, Piedmont, Italy


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Man has always tried to predict the future, especially to prevent catastrophes, diseases and death. In this case, we want to prevent the ‘personal catastrophe’, i.e. the spread of the disease (recurrence of prostate cancer) in the patient. Our work therefore belongs to the so-called ‘personalized medicine’, a very important and innovative clinical approach.

In particular this study may potentially improve the quality of life of the patients and help the clinicians, since it could give valuable information to the urologist, for example reporting that the growth velocity of the tumor is increasing and that a relapse is expected within few months. With this information, the clinician could chose the best therapy for the patient (e.g. hormone or radio therapy) in order to stop the spread of the disease or, conversely, the use of drugs can be delayed if not necessary.

Obviously clinicians already try to do this, based on their experience, but our method provides further confidence in their ‘investigation’ work, since the algorithm is validated on data coming from a database much larger than his/her personal experience.

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French Grape Seed Extract May Help Eliminate Cancer Stem Cells

MedicalResearch.com Interview with:
Ajay Goel, Ph.D.
Professor, and Director of Center for Epigenetics and Cancer Preventio
Baylor Scott & White Research Institute
Baylor University Medical Center, Dallas, TX

MedicalResearch.com: What is the background for this study?

Dr. Goel: One of the areas in which I am interested is examining the activity of natural compounds as it relates to cancer prevention, progression, and treatment. Polyphenols have known antioxidant and anti-cancer activity, but it is important that we better understand the mechanisms of action. I have found in my research on curcumin and boswellia that these plants contain compounds that work on an epigenetic level and can influence microRNA in ways that chemotherapeutic agents cannot. MicroRNA is important because it is like a master control panel that turns on and off a multitude of genetic “switches.” Influencing the activity of microRNA influences a wide array of genetic expression. If you tell the general of the army what to do, it has a much greater impact than directions given to a private, because the general influences so many more soldiers.

Because grape seed extract contains oligomeric proanthocyanidins (OPC) that are also quite active in influential cancer mitigating genetic pathways, I wanted to determine its effects more exactly. I chose specifically tannin-free, low molecular weight OPCs because there is some evidence that the larger sized OPCs are not absorbable.

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Adolescent Diet High in Saturated Fats Linked to Breast Density in Adulthood

MedicalResearch.com Interview with:
Seungyoun Jung, ScD, Fellow and
Joanne F. Dorgan Ph.D., M.P.H., Professor

Department of Epidemiology & Public Health
Division Director Of Cancer Epidemiology
University of Maryland

MedicalResearch.com: What is the background for this study?

Response: Despite the strong evidence from the animal and experimental studies, the lack of association between fat intake and breast cancer has been observed in epidemiologic studies of adult women. However, the development of breast tissue, which induces rapid structural changes and makes breasts vulnerable to exposures, mostly occurs during adolescence. The effect of dietary fat intake on the breasts, therefore, might be greater at younger than older ages. However, only a few prospective cohort studies have examined the role of fat intake during adolescence in relation to the possible risk of breast cancer later in adulthood. Therefore, we examined the association between adolescent intakes of dietary fat and breast tissue composition as measured by breast density, a strong risk factor for breast cancer, measured among young women in the Dietary Intervention Study in Children 2006 Follow-up (DISC06) study.

MedicalResearch.com: What are the main findings?

Response: We observed that higher intake of saturated fat and lower intake of mono- and polyunsaturated fat during adolescence are associated with higher breast density measured approximately 15 years later.

MedicalResearch.com: What should readers take away from your report?

Response: The take home message from our results, if confirmed, is that the diet consumed in early life is important and may confer risk or protective benefits for breast cancer later in adulthood. In particular, adherence to a healthy diet higher in healthy unsaturated fats and lower in saturated fats during youth may contribute to lower breast density, and possibly decreased breast cancer risk.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: As a future direction of our study, it will be important to see if our results are replicated in a large prospective cohort study and are not attributable to other components in major food sources of different types of fat, and to identify possible underlying mechanism.

MedicalResearch.com: Is there anything else you would like to add?

Response: Breast cancer is the most common cause of cancer incidence and cancer death among women worldwide. However, the established known risk factors for breast cancer, such as age at menarche, age at first full term pregnancy and age at menopause, are not readily modifiable. Although further research is warranted, our result is important as it suggests the promising role of dietary modification during adolescence for promotion of breast health as well as prevention of diabetes, cardiovascular disease and other chronic diseases in adulthood.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Seungyoun Jung, Olga Goloubeva, Catherine Klifa, Erin S. LeBlanc, Linda G. Snetselaar, Linda Van Horn, and Joanne F. Dorgan. Dietary Fat Intake During Adolescence and Breast Density Among Young Women. Cancer Epidemiology, Biomarkers & Prevention, May 2016 DOI:10.1158/1055-9965.EPI-15-1146

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