Patients With Dementia Less Likely To Receive Chemotherapy for Colon Cancer

MedicalResearch.com Interview with:

Yingjia Chen, M.Sc, MPH, Ph.D. Postdoctoral Fellow University of California, San Francisco

Dr. Chen

Yingjia Chen, M.Sc, MPH, Ph.D.
Postdoctoral Fellow
University of California, San Francisco 

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

Response: Both colon cancer and dementia are prevalent among the elderly and have a high risk of co-occurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of pre-existing dementia was associated with worse survival for stage III colon cancer patients, and that post-operative chemotherapy was on the causal pathway.

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Periodontal Disease is Associated with Higher Risk of Cancer in Postmenopausal Women

MedicalResearch.com Interview with:

Jean Wactawski-Wende, PhD Dean, SUNY Distinguished Professor Professor, Department of Epidemiology and Environmental Health School of Public Health and Health Professions University of Buffalo

Dr. Wactawski-Wende

Jean Wactawski-Wende, PhD
Dean, SUNY Distinguished Professor
Professor, Department of Epidemiology and Environmental Health
School of Public Health and Health Professions
University of Buffalo

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

Response: There has been a growing interest in the role of periodontal disease in system chronic diseases, including cancer. We explored the association of periodontal disease history and incident cancer in the women’s health initiative study of postmenopausal women. We found that women reporting periodontal disease history were at increased risk of developing cancer overall. In addition they were found to have significant increased risk of specific cancers including cancers of the lung, breast, esophagus, gallbladder and melanoma. The risk persisted after control for many other factors. In addition, the risk was seen in women regardless of their smoking history. Both ever smokers and never smokers were found to have increased risk of cancer associated with periodontal disease history.

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Phase III Study of Stivarga (Regorafenib) For Progressed Hepatocellular Carcinoma

MedicalResearch.com Interview with:

Dr. Jordi Bruix, MD Professor of Medicine University of Barcelona Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit Hospital Clinic of Barcelona

Dr. Bruix

Dr. Jordi Bruix, MD
Professor of Medicine
University of Barcelona
Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit
Hospital Clinic of Barcelona

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

Response: The RESORCE Phase III pivotal trial is an international, multicenter, placebo-controlled trial which investigated the efficacy of Stivarga (regorafenib) in adults with Child-Pugh A and Barcelona Clinic Liver Cancer Stage Category B or C hepatocellular carcinoma (HCC) who had documented disease progression following first-line treatment with Nexavar (sorafenib).

Trial participants were administered a daily oral 160mg dose (three weeks on/ one week off) of regorafenib plus best supportive care (BSC), or placebo plus BSC.

Results from the trial demonstrated that participants treated with regorafenib experienced a statistically significant and clinically meaningful improvement in the study’s primary endpoint—overall survival (OS). Participants treated with regorafenib demonstrated a median overall survival of 10.6 months vs. 7.8 months with placebo.

At ASCO 2017, an exploratory analysis evaluated the impact of baseline alpha-fetoprotein (AFP) and c-Met as predictors of poor prognosis in patients enrolled in the RESORCE trial (Abstract #4078).

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Circulating Cell Scoring System Identifies High Risk Prostate Cancer

MedicalResearch.com Interview with:

Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON

Dr. Yong-Jie Lu

Dr. Yong-Jie Lu MBBS, MD, PhD
Reader in Medical Oncology
Centre for Molecular Oncology
Barts Cancer Institute – a CR-UK Centre of Excellence
Queen Mary University of London
John Vane Science Centre, Charterhouse Square
London

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

Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials.

Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.

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Preclinical Study Finds Cancer Stem Cell Inhibitor Sensitizes Colon Cancer Cells To Immunotherapy

MedicalResearch.com Interview with:
Dr. Yuan Gao

Assistant Investigator at Boston Biomedical

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

Response: Colorectal cancer (CRC) is the third most commonly diagnosed malignant disease and third most frequent cause of cancer-related death in the United States. Standard treatment for unresectable metastatic CRC currently includes first and second line 5-fluorouracil (5-FU)-based chemotherapy regimens. However, CRC patients often develop chemoresistance. Recently, immunotherapy has emerged as a revolutionary new treatment for CRC. However, with the exception of a small percentage of CRC patients that display microsatellite instability (MSI), the vast majority of colorectal cancer patients have been found to be resistant to immune checkpoint therapies.

Cancer stem cells (CSCs), a highly malignant tumor cell subpopulation capable of self-renewal, are considered to be fundamentally responsible for malignant growth and tumor recurrence. Emerging evidence indicates that CSCs and cancer stemness pathways, such as STAT3, beta-Catenin, CD44 and Nanog, are involved in the immune evasion of cancers. BBI-608 (napabucasin) is an orally-administered first-in-class cancer stemness inhibitor that works by targeting STAT3. In this study, we investigated the effect of cancer stemness inhibition on sensitizing colorectal cancer to immune checkpoint inhibitors in preclinical models.

In the syngeneic microsatellite stable (MSS) tumor model, CT26, an anti-PD-1 antibody delivered as a monotherapy, produced low level and temporary antitumor activity with rapid development of complete resistance to anti-PD-1 treatment. The anti-PD-1 antibody-treated CT26 tumors exhibited increased p-STAT3 activation and overexpression of a variety of stemness factors, as well as enrichment of sphere-forming stemness-high cancer cells. Napabucasin was able to reduce basal as well as anti-PD1-induced STAT3 activation and other CSC features within CT26 tumors. The combination of a stemness inhibitor – napabucasin – with the anti-PD-1 antibody led to tumor complete response (CR) in all treated CT26 tumors, with 40 percent of the mice remaining tumor-free for 30 days following treatment termination. This combination also had a synergistic effect on the influx of tumor infiltrating CD8+ T cells, which likely contributed to the rapid tumor regression. Finally, mice CR-induced by napabucasin and the anti-PD-1 antibody were able to reject CT26 tumors upon re-challenge, but not the unrelated breast cancer 4T1 tumors.

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

Response: Our data suggest cancer stemness pathways contribute to immunotherapy resistance in MSS CRC, a subtype representing the vast majority of colorectal cancer cases. Furthermore, inhibition of cancer stemness by BBI-608 sensitizes colorectal cancer to immune checkpoint inhibition, producing striking regression in a large proportion of the tumors treated.

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

Response: This study provides compelling preclinical evidence to support the investigation of the combination of napabucasin with immune checkpoint inhibitors in CRC. While this study specifically investigated the combination with anti-PD-1, the combination with other immunotherapies could be studied as well.

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

Citation: AACR 2017 Abstract

Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Gene-silencing RNAs Targeting CTNNB1 and PD-L1 May Attack a Variety of Cancers

MedicalResearch.com Interview with:
Dr. Youzhi Li

Vice President at Boston Biomedical 

MedicalResearch.com: What are the main findings?

Response: RNAi (RNA interference) technology has the potential to target any genes causing disease, including conventionally “undruggable” targets in cancer. One particularly interesting RNAi target in oncology is the CTNNBI oncogene, which encodes the β-Catenin protein whose nuclear form acts as a transcription factor promoting tumorigenesis. Aberrant β-Catenin signaling has been demonstrated in 90 percent of colorectal carcinomas, 40 percent of hepatocellular carcinoma, and 90 percent of non-ductal pancreatic carcinomas. Recent research also suggests active β-Catenin contributes to tumor immune evasion and to the recurrence of melanoma in patients post the check-point blockage immunotherapy.

However, the direct blockade of β-Catenin activity has proved difficult with conventional approaches. While the application of traditional RNAi technology has the potential to block this pathway, in clinical cancer therapy, this approach has proven challenging due to the difficulty in systemic delivery of RNAi to tumor sites located in various organs.

We have recently developed BBI-801, a lipid-based nanoparticle that encapsulates therapeutic aiRNAs targeting CTNNB1 and PD-L1 to simultaneously target immune evasion via both these pathways. Here, we investigate the in vivo delivery and anti-tumor activity of BBI-801.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

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

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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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

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Polyomaviruses May Raise Risk of Skin Cancer In Patients of Risk of Squamous Cell Carcinoma

MedicalResearch.com Interview with:
Anala Gossai BSc, MPH PhD candidate
Department of Epidemiology
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
and co-authors

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

Gossai et al: Polyomaviruses (PyV) are potentially tumorigenic viruses in humans. However, limited data exists on the population seroprevalence or longitudinal serostability of PyVs, and individual characteristics that relate to seropositivity. Further, PyVs may be associated with the occurrence of cutaneous squamous cell carcinoma (SCC) – one of the most common malignancies in humans with increasing incidence reported in the US.

In a US nested case-control study, BK and JC seroreactivity was measured on 113 SCC cases and 229 matched controls who had a prior keratinocyte cancer. Repeated serum samples from controls, and both pre- and post-diagnosis samples from a subset ofsquamous cell carcinoma cases, were also assayed. Antibody response against each PyV type was measured using multiplex serology of recombinantly expressed VP1 capsid proteins. Among controls, BK and JC seroreactivity was stable over time, and there was little evidence of seroconversion following SCC diagnosis among cases. Odds of squamous cell carcinoma  associated with seropositivity to each PyV type were estimated using conditional logistic regression. JC seropositivity prior to diagnosis was associated with an elevated risk of SCC (OR=2.5, 95% CI: 1.2-5.2). 
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Segregated Black Patients Less Likely To Receive Lung Cancer Surgery

MedicalResearch.com Interview with:

Asal Mohamadi Johnson, PhD, MPH Assistant Professor of Epidemiology, Integrative Health Science Stetson University DeLand, FL 32723

Dr. Asal Mohamadi Johnson

Asal Mohamadi Johnson, PhD, MPH
Assistant Professor of Epidemiology, Integrative Health Science
Stetson University
DeLand, FL 32723

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

Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation.

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Monitoring Circulating Tumor Cells May Further Personalized Cancer Treatment

MedicalResearch.com Interview with:

Dr. Elodie Sollier
Chief Scientific Officer at Vortex Biosciences

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

Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response.

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New Technology Can Detect Circulating Colon Cancer Cells In Less Than an Hour

MedicalResearch.com Interview with:
Dr. Elodie Sollier PhD
Chief Scientific Officer at Vortex Biosciences

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

Response: Vortex Biosciences has developed a fast and simple way to isolate and collect intact circulating tumor cells (CTCs) directly from whole blood in less than an hour using a process based on microfluidics. To better understand the utility of the technology for the clinical setting, PCR-based Sanger sequencing was used to profile the mutations of CTCs isolated from blood from metastatic Colorectal cancer patients. The mutations were compared to primary tumor biopsies, secondary tumor biopsies and ctDNA. There are 3 primary take-aways:

  1. The Vortex technology captures CTCs with enough purity to perform sensitive and accurate PCR-based Sanger sequencing.
  2. Mutations present in primary and secondary tumors can be identified in both CTCs and ctDNA making liquid biopsies a valuable alternative to tissue biopsies.
  3. While there is general consistency of mutations identified, some mutations are only identified in CTCs while others only in ctDNA demonstrating how these are indeed complimentary.

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Genetic Variants May Raise Risk of Breast Cancer In Pediatric Radiation Therapy Patients

MedicalResearch.com Interview with:

Lindsay M. Morton, PhD Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic National Cancer Institute Bethesda, Maryland

Dr. Lindsay Morton

Lindsay M. Morton, PhD
Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic
National Cancer Institute
Bethesda, Maryland

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

Dr. Morton: We know that childhood cancer survivors, particularly those who received radiotherapy to the chest, have strongly increased risk of developing breast cancer. We studied about 3,000 female survivors of childhood cancer to identify whether inherited genetic susceptibility may influence which survivors go on to develop breast cancer.

MedicalResearch.com: What are the main findings?

Dr. Morton: In this discovery study, we found that specific variants in two regions of the genome were associated with increased risk of breast cancer after childhood cancer among survivors who received 10 or more gray of chest radiotherapy. A variant at position q41 on chromosome 1 was associated with nearly two-fold increased risk and one at position q23 on chromosome 11 was associated with a more than three-fold increased risk for each copy of the risk alleles. However, the variant alleles didn’t appear to have an effect among survivors who did not receive chest radiotherapy.

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Prostate Cancer Mortality May Be Reduced By Moderate Physical Activity

MedicalResearch.com Interview with:

Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303

Dr. Ying Wang

Ying Wang, PHD | Senior Epidemiologist
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303

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

Dr. Wang: Although evidence is still limited, previous studies suggest that vigorous activity and brisk walking after prostate cancer diagnosis might be associated with lower risk of prostate cancer progression and disease-specific mortality. We still don’t know if physical activity before diagnosis is associated with the risk or not. This is also important because reverse causation is a concern in the analysis of post-diagnosis physical activity, especially for vigorous activity, that men with advanced diseases may reduce their activity level. In contrast, pre-diagnosis physical activity is less subject to reverse causation and may represent a long-term behavior. When walking, the most common type of physical activity, was examined separately in previous studies, it was not evaluated in the absence of other activities. No study has examined sitting time in relation to mortality among prostate cancer survivors, although previous study suggests longer sitting time is associated with higher risk of all-cause mortality in healthy populations. So in our study, we aimed to examine physical activity, walking only, and sitting time both before and after diagnosis in relation to prostate cancer-specific mortality.

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High Dietary Saturated Fat Associated With Prostate Cancer Aggressiveness

MedicalResearch.com Interview with:

Emma Helen Allott, PhD University of North Carolina at Chapel Hill Chapel Hill, NC

Dr. Emma Allott

Emma Helen Allott, PhD
University of North Carolina at Chapel Hill
Chapel Hill, NC

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

Dr. Allott: Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in Western countries. This large international variation is due in part to differences in screening practices between countries, but dietary factors may also play a role. Unlike other macronutrients, dietary fat intake varies more than fivefold worldwide, and individuals in Western countries are among the highest consumers of saturated fat. High dietary saturated fat content contributes to raised blood cholesterol levels, and evidence from population-based studies supports an adverse role for serum cholesterol and a protective role for cholesterol-lowering statins in prostate cancer. Our hypothesis in this study was that high saturated fat intake would drive prostate tumor aggressiveness via raising serum cholesterol levels.

MedicalResearch.com: What are the main findings?

Dr. Allott: Using the North Carolina-Louisiana Prostate Cancer Project, a study of 1,854 men with newly-diagnosed prostate cancer, we show that high dietary saturated fat content is associated with increased tumor aggressiveness. We found a slightly weaker effect of saturated fat on prostate cancer aggressiveness in men using statins to control serum cholesterol levels, suggesting that that statins may counteract, but do not completely negate, the effects of high saturated fat intake on prostate cancer aggressiveness. We also found an inverse association between high dietary intake of polyunsaturated fatty acids (PUFAs) and prostate cancer aggressiveness.

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PD-L1 Status Can Not Be Used To Determine Immunotherapy Eligibility for Melanoma Treatment

MedicalResearch.com Interview with:

Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering

Dr. Michael Postow

Michael A. Postow, MD
Medical Oncologist
Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK)
Memorial Sloan Kettering

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

Dr. Postow: Pembrolizumab has been shown to improve overall survival for patients with advanced melanoma compared to ipilimumab.  Patients with PD-L1 negative tumors still respond to pembrolizumab.  Responses to pembrolizumab were higher when patients had more PD-L1 in the tumor.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Postow: PD-L1 status cannot be used to select patients with melanoma to receive pembrolizumab vs. ipilimumab or even to be used to determine eligibility for immunotherapy in general.  PD-L1 “positivity” is a difficult definition and various cutoff points have been used in various studies to determine positivity.  We need more research to determine the significance of various cutoff definitions of “positive.”

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Inflammation Factors in How Obesity Influences Prostate Cancer Progression

MedicalResearch.com Interview with:

Charnita Zeigler-Johnson, Ph.D., M.P.H. Assistant Professor Division of Population Sciences Department of Medical Oncology Thomas Jefferson University Philadelphia, PA 19107

Dr. Zeigler-Johnson

Charnita Zeigler-Johnson, Ph.D., M.P.H.
Assistant Professor
Division of Population Sciences
Department of Medical Oncology
Thomas Jefferson University
Philadelphia, PA 19107

Medical Research: What is the background for this study?

Dr. Zeigler-Johnson: Obesity has been associated with poor prostate cancer outcomes, included advanced disease at diagnosis, increased risk for cancer recurrence, and risk for mortality. One possible link in the relationship between obesity and prostate cancer progression is inflammation. Obesity produces a state of systemic chronic low-grade inflammation which may contribute to the underlying biology of the tumor microenvironment. The presence of immune cells (T-cells and macrophages) in the tumor microenvironment may indicate aggressive tumors that are likely to metastasize. The goal of this study was to examine prostate cancer tissue to characterize differences in immune cells within the tumor microenvironment by obesity status and cancer severity. We studied tumor samples from 63 non-obese and 36 obese prostate cancer patients.

Medical Research: What are the main findings?

Dr. Zeigler-Johnson: We found that T-cell and macrophage counts in the tumor did not differ by patient obesity status. However, macrophage (CD68) counts were higher among men diagnosed with higher tumor grade (Gleason Score 7-10). We also found that T-cell (CD8) counts were associated with quicker time to prostate cancer recurrence (indicated by detectable prostate specific antigen levels after treatment.)

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Study Targets Obesity Genes That May Raise Risk of Kidney Cancer

MedicalResearch.com Interview with:

Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas

Dr. Xifeng Wu

Dr. Xifeng Wu, MD PhD
Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences
Director, Center for Translational and Public Health Genomics
Professor, Department of Epidemiology
Division of Cancer Prevention and Population Sciences
The University of Texas MD Anderson Cancer Center, Houston, Texas

Medical Research: What is the background for this study? What are the main findings?

Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms.

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Study Evaluates Obesity-Related Factors Leading to Pancreatic Cancer Progression

MedicalResearch.com Interview with:

Joao Incio MD Research Fellow in Radiation Oncology Harvard Medical School/MGH Boston, MA

Dr. Joao Incio

Joao Incio MD
Research Fellow in Radiation Oncology
Harvard Medical School/MGH
Boston, MA

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

Dr. Incio: With  the  current  epidemic  of  obesity,  the  majority  of  pancreatic  cancer  patients  are  overweight  or  obese  at  diagnosis.  Importantly, obesity  worsens treatment  outcomes  in  pancreatic  cancer  patients.  Therefore,  understanding  the  mechanisms  that  underlie  the  poorer  prognosis  of  obese  cancer  patients  is  of  paramount importance.  Obesity  causes  inflammation  and  fibrosis  in  the  normal  pancreas  due  to  the  accumulation  of  dysfunctional  hypertrophic  adipocytes.  Importantly,  desmoplasia  -­  a fibroinflammatory  microenvironment  -­  is  a  hallmark  of  pancreatic  ductal  adenocarcinoma  (PDAC),  and  we  have  shown  that  activation  of  pancreatic  stellate  cells  (PSCs)  via angiotensin-­II  type  1  receptor  (AT1)  pathway  is  a  major  contribution  to  tumor  desmoplasia.  Whether  obesity  affects  desmoplasia  in  PDACs,  and  interferes  with  delivery  and response  of  chemotherapeutics,  was   the focus of our study.

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Good Overall Agreement Among Three PD-L1 Diagnostic Assays

MedicalResearch.com Interview with:

Marianne J. Ratcliffe, PhD Associate director of diagnostics AstraZeneca Alderley Park, UK

Dr. Mariann Ratcliffe

Marianne J. Ratcliffe, PhD
Associate director of diagnostics
AstraZeneca
Alderley Park, UK

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

Dr. Ratcliffe: PD-L1 status is informative when considering monotherapy treatment and of growing importance when we consider that treatment decision will, in the near future also include combination therapy, an area of focus for AstraZeneca. The Ventana SP263 test has been developed with AstraZeneca, to support selection of PD-L1 testing within the Durvalumab programme, with full analytical validation at a 25% cut point derived from clinical data indicating this cut point best identifies patients more likely to respond to Durvalumab. The Ventana SP263 assay is commercially available in the US and the EU as a Class I device. The Dako 22C3 test has been approved as companion diagnostic for Pembrolizumab, and the Dako 28-8 has been released as a complementary diagnostic as an aid to physicians considering treatment with Nivolumab. What we didn’t know before our study was whether the three assays identify the same patients, and particularly how to cross compare patients identified with the different cut points specified for the different assays. It was therefore an important question to be addressed through a very thorough scientific assessment.

MedicalResearch.com: What are the main findings?

Dr. Ratcliffe: Our data, generated in 500 commercial samples, demonstrates that three commercially available PD-L1 tests achieved overall percentage agreement of >90%. This was achieved at multiple assay cut-offs. These results indicate that it may be possible to extrapolate the results from one test to that of another test. Further work is required to confirm this finding.
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Some SPF30 Sunscreens Protect Better Than Others

MedicalResearch.com Interview with:
Christin E. Burd, Ph.D.
Assistant Professor
Departments of Molecular Genetics, and Molecular Virology, Immunology and Medical Genetics
The Ohio State University
James Comprehensive Cancer Center
Columbus, OH 43210

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

Dr. Burd: Many melanomas develop from benign moles and exposure to ultraviolet sunlight is thought to play a major role in this process.

Initially, we were interested in determining how ultraviolet sunlight might cooperate with gene mutations found in moles to initiate melanoma. To examine this, we exposed melanoma-prone mice to a single, non-burning dose of ultraviolet (UV) light.  Our findings were quite unexpected. While the untreated mice naturally developed melanoma at 26 weeks of age, UV-treated subjects got melanoma at just 5 ½ weeks of age.

This striking result suggested to us that our model might provide a superior way to test sunscreens. SPF ratings are currently based upon the ability of a sunscreen to protect against skin burning. We know that sunburns are associated with melanoma risk, but whether protection from skin burning is enough to prevent cancer was unclear.

By applying a number of commercially available SPF30 sunscreens to our mice before UV exposure, we were able to show that the animals were protected from melanoma. However, we noticed that some SPF30 sunscreens worked better than others. In fact, many SPF30 sunscreens out-performed the one SPF50 sunscreen tested in our initial study. So while all sunscreens protect against melanoma, SPF does not predict which ones are the best. Continue reading

Immunotherapy Drug Nivolumab May Help Some Aggressive HPV-Induced Anal Cancers

MedicalResearch.com Interview with:

Dr. Van K. Morris, MD Assistant Professor, GI Medical Oncology The University of Texas MD Anderson Cancer Center

Dr. Van Morris

Dr. Van K. Morris, MD
Assistant Professor, GI Medical Oncology
The University of Texas MD Anderson Cancer Center

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

Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past.

Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer.

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High Glycemic Index May Raise Lung Cancer Risk Especially in Never Smokers

MedicalResearch.com Interview with:

Xifeng Wu, M.D., Ph.D Professor of Epidemiology

Dr. Xifeng Wu

Xifeng Wu, M.D., Ph.D
Professor of Epidemiology and

Dr. Stephanie Claire Melkonian PhD Epidemiologist, Postdoctoral Research Fellow

Dr. Melkonian

Dr. Stephanie Claire Melkonian  PhD
Epidemiologist, Postdoctoral Research Fellow
The University of Texas MD Anderson Cancer Center

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

Response: Glycemic index (GI) assigns foods an indexed value to show how quickly and how much carbohydrates in the food cause blood glucose levels to rise after eating and is a measure of overall carbohydrate quality. Glycemic load (GL) is a related measure that is calculated by multiplying Glycemic index by the amount of carbohydrates in grams in that specific food and by the amount consume, then dividing by 100. Previous studies have investigated the association of GI and GL with certain types of cancer, including colorectal, stomach, and pancreatic cancer, but there has been limited research into the association with lung cancer.

We conducted a study using patients and control subjects from an ongoing case-control study of lung cancer conducted at MD Anderson. The patients were newly diagnosed and had not received treatment other than surgery. The healthy control subjects were selected from patient lists at Kelsey-Seybold Clinics, a large physician group in the Houston area. The study results encompass 1,905 cases and 2,413 controls. Using data collected from in-person interviews regarding health histories and dietary behaviors, we were able to categorize the study subjects according to their dietary Glycemic index and GL.

What we found was that individuals in the highest category of GI were at an almost 50% increased risk for developing lung cancer as compared to those in the lowest group. This association was different based on different subtypes of cancer. Most interestingly, however, among those individuals that never smoked, high Glycemic index was associated with an almost 2 fold increased risk of lung cancer. In other words, we found a more profound association between GI and lung cancer in never smokers in this study.

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Experimental 3DNA Nanocarrier Used to Target and Treat Ovarian Tumor Cells

MedicalResearch.com Interview with:

Janet A. Sawicki, Ph.D. Deputy Director and Professor Lankenau Institute for Medical Research 100 Lancaster Ave. Wynnewood, PA 19096

Dr. Janet Sawicki

Janet A. Sawicki, Ph.D.
Deputy Director and Professor
Lankenau Institute for Medical Research
100 Lancaster Ave.
Wynnewood, PA 19096

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

Dr. Sawicki: This study addresses the need for a more effective therapy for ovarian cancer. HuR is an RNA-binding protein that is present in high amounts in ovarian tumor cells compared to amounts in normal cells. HuR regulates the expression of thousands of genes that promote the survival of tumor cells. Thus, it is an ideal therapeutic target to suppress ovarian tumor growth. In this study, we used a small interfering RNA (siRNA) to investigate the impact of suppressing HuR expression on ovarian tumor growth in an ovarian cancer mouse model. We made use of the ability to conjugate a novel DNA dendrimer nanocarrier, 3DNA®, to both siHuR and a tumor-targeting moiety to suppress HuR expression specifically in tumor cells following systemic administration while avoiding toxicity in healthy cells. Systemic administration of siHuR-conjugated FA-3DNA to ovarian tumor-bearing mice suppressed tumor growth and ascites development, and significantly prolonged lifespan. Gene expression analysis identified multiple HuR-regulated genes in tumor cells as evidenced by changes in their expression upon HuR inhibition. These HuR-regulated genes function in multiple essential cellular molecular pathways, a finding that sets this therapeutic approach apart from other therapies that target a single gene.

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Breast and Pancreatic Cancer: Pathway Identified That Accelerates Tumors in Obese Patients

MedicalResearch.com Interview with:

Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal

Dr. Joao Incio

Joao Incio, MD
Edwin L. Steele Laboratory for Tumor Biology
Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A
Department of Internal Medicine | Hospital S. Joao | Porto, Portugal

 Medical Research: What is the background for this study? What are the main findings?

Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression.

We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects.

Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients.

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Socioeconomic Factors Influence Survival in Youth Hodgkin Lymphoma

MedicalResearch.com Interview with:

Theresa Keegan, PhD, MS Associate Professor Division of Hematology and Oncology UC Davis Comprehensive Cancer Center Sacramento, California 95817

Dr. Theresa Keegan

Theresa Keegan, PhD, MS
Associate Professor
Division of Hematology and Oncology
UC Davis Comprehensive Cancer Center
Sacramento, California 95817

Medical Research: What is the background for this study? What are the main findings?

Dr. Keegan: This study expanded upon our earlier work examining survival among the young population diagnosed with Hodgkin lymphoma, which can be cured about 90 percent of the time with it is diagnosed at its earliest stages.  We tracked 9,353 patients ages 15-39 who were diagnosed with Hodgkin lymphoma between 1988 and 2011. Using California Cancer Registry data, we examined the impact on survival of socio-demographic characteristics such as race/ ethnicity, neighborhood socioeconomic status (SES), health insurance, the types of treatment patients received and whether they were diagnosed with subsequent cancers.

We found that insurance coverage, neighborhood socioeconomic status (SES) and the types of treatment provided patients all played a role in survival.  Young adults diagnosed with early-stage Hodgkin lymphoma were twice as likely to die if they resided in a lower SES neighborhood. They were also twice as likely to die if they had public health insurance or were uninsured, whether they were diagnosed at an early stage or late stage.

While there were improvements in survival over time, disparities in survival persisted for some racial/ethnic groups. African American patients were 68 percent more likely to die of their disease than non-Hispanic white patients, regardless of stage at diagnosis. Hispanic AYA patients diagnosed at a late stage were 58 percent more likely than non-Hispanic white patients to die of Hodgkin lymphoma; there was not a significant disparity for Hispanic patients diagnosed at an early stage.

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Genetic Markers Help Individually Identify Melanoma Patients At Risk For Metastases

Tomas Kirchhoff, PhD Assistant Professor, Departments of Population Health and Environmental Medicine NYU Langone Medical Center Member, Laura and Isaac Perlmutter Cancer Center NYU Langone

Dr. Thomas Kirchhoff

MedicalResearch.com Interview with:
Tomas Kirchhoff, PhD
Assistant Professor, Departments of Population Health and Environmental Medicine
NYU Langone Medical Center
Member, Laura and Isaac Perlmutter Cancer Center
NYU Langone 

Medical Research: What is the background for this study?
Dr. Kirchhoff: Melanoma is the deadliest form of skin cancer, and the cause of approximately 80% of all skin cancer patients annually. One factor that can help reverse this negative trend is efficient prediction of which patients at early melanoma stage will likely progress to more advanced metastatic disease. Current clinical predictors of patient survival, based on tumor characteristics, are important, but are relatively non-specific to inform melanoma prognosis to an individual patient level. It is critical to identify other factors that can serve as more personalized markers of predicting the course of melanoma.

Medical Research: What are the main findings?

Dr. Kirchhoff: In our study, we found that inherited genetic markers that impact activity of certain immune genes correlate with melanoma survival. More specifically, our findings show that patients with more frequent forms of these genetic markers (genotypes) have, on average, a five-year shorter survival than patients with less common genotypes. We suggest that these genetic markers are independent of the current tumor surrogates and, as such, can serve as novel personalized markers of melanoma prognosis.

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Preventable Colon Cancer Deaths Take Large Fiscal Toll In Poor Communities

Hannah K. Weir, PhD, MSc Senior Epidemiologist CDC

Dr. Weir

MedicalResearch.com Interview with:
Hannah K. Weir, PhD, MSc
Senior Epidemiologist
CDC

Medical Research: What is the background for this study? What are the main findings?

Dr. Weir: Colorectal cancer (CRC) is one of the leading causes of cancer related deaths in the United States.

We know that the risk of dying from colorectal cancer  is not the same across all communities – people living in poorer communities have a higher risk of dying from colorectal cancer than people living in wealthier, better educated communities.

In this study, we estimated the number of potentially avoidable CRC deaths between 2008 and 2012 in poorer communities.  Then we estimated the value of lost productivity that resulted from these deaths. Lost productivity includes the value of future lost salaries, wages, and the value to household activities such as cooking, cleaning, and child care.

We focused on the age group 50 to 74 years because this is the age group where routine CRC screening is recommended. We estimated that more than 14,000 CRC deaths in poorer communities could have been avoided and that these CRC deaths resulted in a nearly $6.5 billion dollars loss in productivity.

This is tragic – for the person who died, their family and for their community. This loss in productivity contributes to the economic burden of these already disadvantaged communities.

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Repositioning Bazedoxifene For Use Against Pancreatic Cancer

Jiayuh Lin, Ph.D. Associate Professor, College of Medicine, The Ohio State University

Dr. Lin

MedicalResearch.com Interview with:
Jiayuh Lin, Ph.D.

Associate Professor,
College of Medicine,
The Ohio State University

Medical Research: What is the background for this study? What are the main findings?

Dr. Jiayuh Lin: Pancreatic cancer is one of the most serious forms of cancer.  Because of the poor response to chemotherapy as conventionally used, patients with any stage of pancreatic cancer may appropriately be considered candidates for clinical trials using novel agents.

IL-6 signaling plays an important role in oncogenesis and high serum IL-6 levels is a poor prognostic factor for overall survival in pancreatic cancer. Therefore, IL-6 is considered as a viable target for pancreatic cancer therapy.  We utilized a drug discovery method with Multiple Ligand Simultaneous Docking and drug repositioning to identify an existing FDA-approved drug Bazedoxifene with previously unknown biological function as an IL-6/GP130 inhibitor.  Bazedoxifene can inhibit cell viability of pancreatic cancer cells expressing IL-6 and suppressed pancreatic tumor growth in vivo.

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Health Diet May Reduce Ovarian Cancer Risk in African American Women

Bo (Bonnie) Qin, PhD Postdoctoral associate at Rutgers Cancer Institute of New Jersey

Dr. Qin

MedicalResearch.com Interview with:
Bo (Bonnie) Qin, PhD

Postdoctoral associate at Rutgers Cancer Institute of New Jersey

Medical Research: What is the background for this study? What are the main findings?

Response:  Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments.

We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women.

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New Enzyme Inhibitor Shows Modest Effect Against Relapsed Lymphoma

Dr. Jatin J. Shah, MD Associate Professor, Department of Lymphoma/Myeloma Assistant Professor, Lymphoma/Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Houston, TX

Dr. Shah

MedicalResearch.com Interview with:
Dr. Jatin J. Shah, MD
Associate Professor, Department of Lymphoma/Myeloma
Assistant Professor, Lymphoma/Myeloma
Division of Cancer Medicine
The University of Texas, MD Anderson Cancer Center
Houston, TX 

Medical Research: What is the background for this study? What are the main findings?

Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells.

The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma.

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Plasma cfDNA Can Monitor Response To Metastatic Colon Cancer Treatment

Van K. Morris, M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030

Dr. Morris

MedicalResearch.com Interview with:
Van K. Morris,  M.D.
Assistant Professor, GI Medical Oncology
University of Texas – M.D. Anderson Cancer Center
Houston, TX 77030 

Medical Research: What is the background for this study? What are the main findings?

Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy.

For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples.

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Some Triple Negative Breast Cancers Show Response To New Drug Conjugate

Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114

Dr. Bardia

MedicalResearch.com Interview with:
Aditya Bardia MD, MPH
Attending Physician, Massachusetts General Hospital Cancer Center,
Assistant Professor, Harvard Medical School,
Boston, MA 02114 

Medical Research: What is the background for this study? What are the main findings?

Dr. Bardia: Triple negative breast cancer (TNBC) represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20% of all invasive breast cancers and is more prevalent in young and African-American women.Triple negative breast cancer characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. Trop-2 is a protein present in limited amounts in normal human tissues but widely found in many human cancers. It is expressed in more than 80 percent of Triple negative breast cancer, making it an attractive therapeutic target.

Sacituzumab govitecan (IMMU-132) is a first-in-class ADC developed by Immunomedics, Inc. by linking moderately-toxic drug, SN-38, to an antibody that binds to the Trop-2 target found in many solid cancers. We conducted a clinical trial with this drug for patients with advanced tumors, including patients with TNBC who either had failed their previous treatments for Triple negative breast cancer or their cancer had returned.

We have found that even though patients who participated in this trial had very advanced stages of the disease, approximately 30% of these patients responded with 30% or more tumor shrinkage. The response rate to standard agents is usually 10 to 20 percent, while the response rate with IMMU-132 was approximately 30 percent. If you include patients with stable disease, the clinical disease control rate, which is complete response [CR] + partial response [PR] + stable disease, was about 75 percent.

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Smoked, Charred Meat Raises Increases Carcinogens, Risk of Kidney Cancer

MedicalResearch.com Interview with:
Xifeng Wu, M.D., Ph.D
, Professor, Epidemiology
Stephanie Melkonian, Ph.D
University of Texas M. D. Anderson Cancer Center

Medical Research: What is the background for this study? What are the main findings?

Response: This study examines dietary intake of meat-cooking mutagens and genetic risk factors associated with kidney cancer in a population of 659 kidney cancer patients and 699 matched healthy control subjects from the community. We calculated the intake of several cancer-causing carcinogens that are produced when certain types of meat are cooked over an open flame and at high temperatures resulting in the burning, smoking or charring of the meat (for example, during barbequing or pan-frying). We found that kidney cancer patients consumed more red and white meat when compared to the healthy individuals, and also had higher intake of these cancer-causing chemicals created through the meat cooking process. These results suggest that meat intake, and the way we cook our meat, may potentially be linked to risk of kidney cancer. Additionally, we found that individuals with certain genetic variants were more likely to be susceptible to the harmful effects of the cancer-causing mutagens created during the process of cooking meat.

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Some Carotenoids May Have a Protective Effect on Breast Cancer

MedicalResearch.com Interview with:
Ying Wang, PHD | Senior Epidemiologist
American Cancer Society, Inc.
Atlanta, Georgia

Dr. Wang: Several epidemiologic studies and a recent large pooled analysis suggest that higher blood levels of carotenoids, a group of lipid-soluble pigments that are rich in colorful fruits and vegetables, are associated with lower breast cancer risk. What remains unclear is whether or not the effect of carotenoids on breast cancer differ by estrogen receptor status, tumor stage, BMI, and smoking status. We examined plasma carotenoids and breast cancer risk overall, and by aforementioned tumor and participant characteristics in a cohort of 992 postmenopausal women. We found that higher pre-diagnosis plasma α-carotene, but not other subtypes or total carotenoids, was significantly associated with lower invasive breast cancer risk. The inverse association of α-carotene with breast cancer risk seems stronger for estrogen receptor positive tumors than for estrogen receptor negative tumors. There is a suggestive inverse association of total plasma carotenoid levels and breast cancer among ever smokers but not among never smokers.

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Novel Combination Treatment May Help Some Patients With Ovarian and Triple-negative Breast Cancers

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with
Dr. Victoria L. Chiou, MD

Medical Oncology Fellow
Women’s Malignancies Branch
National Cancer Institute

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

Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers.

We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population. Continue reading

HPV Vaccine Still Valuable For Women Who Were Not Fully Vaccinated As Children

Jacqueline Hirth, PhD, MPH Assistant Professor andMedicalResearch.com Interview with:
Jacqueline Hirth, PhD, MPH
Assistant Professor and
Dr. Abbey B. Berenson MD, MMS, PhD Center for Interdisciplinary Research in Women's Health Obstetrics and Gynecology The University of Texas Medical Branch at Galveston TexasDr. Abbey B. Berenson MD, MMS, PhD
Center for Interdisciplinary Research in Women’s Health
Obstetrics and Gynecology
The University of Texas Medical Branch at Galveston Texas

Medical Research: What is the background for this study? What are the main findings?

Response: In this sample of young women, vaccination was effective at reducing prevalence of vaccine-type HPV (6,11,16,18) compared to women who were unvaccinated. We also found a dose response, with young women who received at least 2 doses of the 3 dose vaccine series having a lower rate of vaccine-type HPV compared to those who only received one dose (8.6% compared to 16.9%, respectively).

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Neuropeptide Level May Signal Neuroblastoma Prognosis

MedicalResearch.com Interview with:
Joanna Kitlinska, PhD
Assistant Professor
Georgetown University Medical Center
Department of Biochemistry and Molecular & Cellular Biology
Washington, DC 20057

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

Dr. Kitlinska: Neuroblastoma is a pediatric malignancy with extremely heterogeneous phenotypes, ranging from spontaneously regressing to aggressive, untreatable tumors. Consequently, treatment strategies vary significantly between patients, depending on the initial risk assessment. Given the severe late effects of anti-cancer treatment administered to infants and children, proper disease stratification is of utmost importance for neuroblastoma patients.

Due to their neuronal origin, neuroblastomas secrete neuropeptide Y (NPY), a small protein normally released from mature nerves. This, in turn, may result in elevated NPY levels in blood of neuroblastoma patients. We have found that serum NPY is particularly high in patients with aggressive, metastatic disease. Consequently, patients with elevated NPY levels have significantly worse survival. This finding is in agreement with our previous data indicating crucial role for NPY in stimulation of neuroblastoma tumor growth.

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Leveraging Big Data to Accelerate Drug Discovery

MedicalResearch.com Interview with: Neel S. Madhukar Graduate student in the lab of

Neel S. Madhukar

MedicalResearch.com Interview with:
Neel S. Madhukar
Graduate student in the lab of
Olivier Elemento, PhD, Associate Professor
Head, Laboratory of Cancer Systems Biology
Department of Physiology and Biophysics
Institute for Computational Biomedicine
Weill Cornell Medical College

Medical Research: What is the background for this study? What are the main findings?

Response: It takes on average 2.6 billion dollars and 10-15 years to develop a single new drug. Despite massive investment in drug discovery by pharmaceutical companies, the number of drugs obtaining FDA approval each year has remained constant over the past decade. One of biggest bottlenecks in the process of developing a new drug is to understand precisely how a drug works, that is, what it binds to in cells, how it binds, and what it does when it is bound. This process is collectively called target identification and characterization of mechanisms of action. At present, target identification is a slow and failure-prone process, driven by laborious experimentation. Every time we seek to develop a new drug, such laborious experimentation needs to be redone from scratch. We are not learning from data acquired from our past successes and failures.

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