Cancer Research

25 Mar

Posted at 23:57h in Author Interviews, Cancer Research, JAMA, Pediatrics
MedicalResearch.com Interview with: [caption id="attachment_22870" align="alignleft" width="200"]Lee J. Helman, MD Senior Investigator Pediatric Oncology Branch Head, Molecular Oncology Section Acting Director, Center for Cancer Research and CCR Scientific Director for Clinical Research National Cancer Institute Bethesda, Maryland Dr. Lee Helman[/caption] Lee J. Helman, MD Senior Investigator Pediatric Oncology Branch Head, Molecular Oncology Section Acting Director, Center for Cancer Research and CCR Scientific Director for Clinical Research National Cancer Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Helman: It was known that most gastrointestinal stromal tumors (GISTS) that occur in children and young adults do not contain cKIT or PDGFRA mutations that drive more than 90% of adult GIST tumors.  Since GISTs are quite rare in the pediatric and young adult population, we decided to establish a clinic at NIH that would allow us to study the most patients to try to define these tumors both clinically and molecularly. We were able to bring both patients and physicians interested in pediatric GIST from around the country to the NIH to begin to collect and study these patients. Of the 95 patients in this cohort study that lacked cKIT or PDGFRAmutations, 84 were found to have succinate dehydrogenase (SDH) deficient (SDH-deficient) GIST (75% due to SDH A, B, C, or D mutations, and 25% due to SDHC promoter hypermethylation. Since these tumors are driven by SDH loss and not due to KIT or PDGFR mutations, they do not generally respond to standard treatments for GIST that target these kinases. The mechanism of SDH-deficiency is important, since SDH mutations are commonly germ line and therefore require genetic counseling and family testing, while the SDHC promoter methylation is not a germ line alteration and therefore does not require genetic counseling.  Finally, any patient with SDH-deficient GIST is also at risk for development of paraganglioma and should be screened on a regular basis for these tumors. 

21 Mar

Posted at 19:35h in Annals Internal Medicine, Author Interviews, Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_22799" align="alignleft" width="161"]Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 Dr. Joann Elmore[/caption] Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Elmore: Our team began studying diagnostic agreement among pathologists while interpreting breast biopsies in 2009. Early findings from the Breast Pathology Study (B-Path) were published in March 2015 in the Journal of the American Medical Association and indicated strong agreement among pathologists when diagnosing invasive breast cancer or benign breast tissue. Agreement, however, was much lower for ductal carcinoma in situ (DCIS) and atypia. Results from this study raised concerns that a high percentage of breast biopsies may be inaccurately diagnosed. These concerns were amplified in the media with statements like “as many as one-in-four biopsies are incorrectly diagnosed.” Statements like this inaccurately depicted the results of our study, which included a test set weighted heavily with DCIS and atypia cases. It is important to consider the percentage that each outcome category contributes to the overall number of biopsies in the U.S. population as we found that the agreement rate of pathologists varies drastically across these diagnostic categories. Atypia in Breast Tissue Elmore Image In the new work published in Annals of Internal Medicine, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates, In an effort to help physicians and patients better understand what the B-Path results mean for women, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates. When adjusted using population-based predictive value estimates, the B-Path results indicate that pathologists’ overall interpretations of breast biopsies would be confirmed by an expert panel 92 out of 100 biopsies, with more of the initial diagnoses over-interpreted rather than under-interpreted. Of concern, our results noted that among 100 breast biopsies given an initial diagnosis of atypia, less than half of these cases would be given a diagnosis of atypia after review by a panel of three experienced breast pathologists. Over half of the biopsies would be downgraded from atypia to a diagnosis of benign without atypia after review.

21 Mar

Posted at 16:29h in Author Interviews, Cancer Research, Imperial College
MedicalResearch.com Interview with: [caption id="attachment_22816" align="alignleft" width="149"]Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK Dr. Olivier Pardo[/caption] Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pardo: Metastatic dissemination, the ability of tumour cells to go and colonise organs distant from the primary disease site, is the principal cause for failing to cure patients with cancer. This is particularly true in the case of breast cancer where resection of local disease offers good chances of cure but metastatic dissemination that may appear at a later stage carries very poor prognosis. Surgical resection is also the only true curative strategy for localised lung cancer. Hence, a better understanding of the mechanisms controlling the dissemination of tumour cells is likely to propose novel targets for combination therapy that will improve the survival of cancer patients. Here, we showed that an enzyme, named MARK4, controls the ability of lung and breast cancer cells to move and invade. When we lower MARK4 levels, it prevents cancer cells from moving by changing their internal architecture, making them unfit to invade. Consequently, these cells were unable to efficiently form metastasis in mouse cancer models. Confirming the role of this enzyme in cancer, we show that breast and lung cancer patients with increased levels of MARK4 in their tumours have poorer prognosis. We found that what controls the levels of MARK4 in cells is miR-515-5p, a small oligonucleotide sequence called a microRNA. When present in the cells, miR-515-5p prevents the expression of MARK4. Incidentally, the loss of miR-515-5p correlates with increased metastasis and poorer prognosis in mouse cancer models and patients, respectively.

20 Mar

Posted at 00:48h in Author Interviews, Biomarkers, Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_22795" align="alignleft" width="133"]Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA Dr. Lan Ko[/caption] Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer. Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them.

19 Mar

Posted at 04:16h in Author Interviews, Cancer Research
MedicalResearch.com Interview with: Douglas.A. Lauffenburger PhD Ford Professor of Biological Engineering, Chemical Engineering, and Biology Head, Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA 02139  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lauffenburger: We aimed to advance understanding concerning causes of tumor resistance to kinase inhibitor drugs, which limits effectiveness for many therapeutics even when indicated by specific genetic mutations in the new ‘personalized medicine’ paradigm.  We discovered a new mechanism underlying this resistance at least for a number of otherwise promising drugs currently in clinical use as well as further clinical trials.  Our discovery was based on realizing that the same oncogenic signaling driving tumor cell proliferation and invasiveness at the same time activates proteolytic shedding of receptor tyrosine kinases not involved in the targeted oncogenic pathway, shutting down additional signaling inputs.  Thus, when the targeted pathway is inhibited by the intended drug, this shedding is concomitantly diminished — now permitting “bypass" pathways to be activated downstream of these alternative receptor inputs.  Moreover, we showed that measurement of a set of key shed receptors (primarily AXL and MET, in our examined case of MEK pathway inhibitors for melanoma and triple-negative breast tumors) in patient blood serum samples could predict effectiveness of these inhibitors: when the shed levels were high, the drugs were less effective because of the correspondingly great potential for bypass signaling upon drug treatment.  In follow-up mouse experiments, we demonstrated increased effectiveness of a MEK inhibitor when combined with either an AXL inhibitor or a proteolysis inhibitor, thereby confirming the mechanism and proving an avenue for overcoming it.

18 Mar

Posted at 21:45h in Author Interviews, Breast Cancer, Lancet
MedicalResearch.com Interview with: [caption id="attachment_22766" align="alignleft" width="136"]Professor Jack Cuzick, PhD, FMedSci, FRCP(hon) Director, Wolfson Institute of Preventive Medicine and Head, Centre for Cancer Prevention Queen Mary University of London. Prof. Jack Cuzick[/caption] Professor Jack Cuzick, PhD, FMedSci, FRCP(hon) Director, Wolfson Institute of Preventive Medicine and Head, Centre for Cancer Prevention Queen Mary University of London. MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cuzick: Ductal carcinoma in situ (DCIS) is a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year. Our IBIS-II DCIS trial looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery. The two groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant. The similar NSABP B-35  trial found a 29% reduction with anastrozole and the combined analysis of the two trials indicated a significant 21% reduction. The key difference between the two groups were in the side effects of the medication. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However more fractures and musculoskeletal side effects were seen among those receiving anastrozole.

18 Mar

Posted at 19:06h in Alcohol, Author Interviews, Breast Cancer, Genetic Research, PLoS
[caption id="attachment_22760" align="alignleft" width="133"]Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) 3517 Cullen Blvd, Rm 3018 Houston, TX 77204-5056 Dr. Chin Yo Lin[/caption] MedicalResearch.com Interview with: Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) Houston, TX 77204-5056  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers.

14 Mar

Posted at 12:50h in Author Interviews, Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_22492" align="alignleft" width="124"]Professor Nigel Bundred MD, FRCS Professor of Surgical Oncology Institute of Cancer Sciences University Hospital of South Manchester Dr. Nigel Bundred[/caption] Professor Nigel Bundred MD, FRCS Professor of Surgical Oncology Institute of Cancer Sciences University Hospital of South Manchester MedicalResearch.com: What is the background for this study? Dr. Bundred: HER-2 is a cancer-causing gene which is expressed in some cells by having more copies of the gene and predicts for early relapse and metastasis from the tumour. Despite this, even in the absence of anything other than local treatment, some 50% of patients still survive for five years without relapse. Herceptin was discovered and licensed for use in 2006 because it improved survival when given with chemotherapy after surgery, from 66% at five years to 90% at five years. The use of Herceptin and chemotherapy before surgery to shrink the tumour indicates that around 30% of patients have a complete pathological response with this treatment. Combination of dual anti-HER-2 therapies and  Neoadjuvant chemotherapy given for six months before surgery has been shown to increase pCR rate to 50% and a single study utilising the combination of pertuzumab and trastuzumab (two anti-HER-2 monoclonal antibodies) given for four months revealed a 16.8% pCR rate.

14 Mar

Posted at 12:15h in Author Interviews, Cancer, Cancer Research, Cost of Health Care
MedicalResearch.com Interview with: [caption id="attachment_22590" align="alignleft" width="93"]Hrishikesh Kale School of Pharmacy Virginia Commonwealth University Hrishikesh Kale[/caption] Hrishikesh Kale School of Pharmacy Virginia Commonwealth University MedicalResearch.com: What is the background for this study? What are the main findings? Response: The cost of cancer care in the United States is extremely high and escalating every year. Because of increased cost sharing, patients are paying higher out-of-pocket costs for their treatments. Along with high medical expenses, cancer survivors face problems such as loss of employment and reduced productivity. It has been well-established in the literature that because of high out-of-pocket costs, many cancer survivors forgo or delay medical care and mental health-related services and avoid filling prescriptions. This puts their physical and mental health at risk. A related issue is the growing number of cancer survivors in the U.S. As of January 2014, there were approximately 14.5 million cancer survivors in the U.S. By 2024, this number is expected to reach 19 million as a result of improved survival among patients with cancer along with an aging population. Therefore, we decided to investigate the prevalence and sources of financial problems reported by a nationally representative sample of cancer survivors from the 2011 Medical Expenditure Panel Survey. We also studied the impact of cancer-related financial burden on survivors’ health-related quality of life and psychological health.

11 Mar

Posted at 21:48h in Author Interviews, Prostate Cancer, Surgical Research
MedicalResearch.com Interview with: [caption id="attachment_22580" align="alignleft" width="166"]Naveen Pokala, MD Division of Urology University of Missouri Columbia, MO 65212 Dr.Naveen Pokala[/caption] Naveen Pokala, MD Division of Urology University of Missouri Columbia, MO 65212 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pokala: The main purpose of the study was to determine survival outcome following salvage prostatectomy in men that fail radiation therapy. Radiation and surgery are the main modalities utilized to treat localized prostate cancer. When patients fail radiation treatment, traditionally, only hormonal treatment was offered. With refinements in surgical techniques, a select few of these patients that have recurrence after radiation may benefit with salvage surgery. Salvage prostatectomy is a complex procedure because prior radiation makes this procedure tenuous, but this procedure is offered in most major tertiary medical centers.

11 Mar

Posted at 12:22h in Author Interviews, Cancer Research, JAMA
MedicalResearch.com Interview with: [caption id="attachment_22567" align="alignleft" width="133"]Joseph Unger, PhD, MS SWOG Statistical Center Assistant Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center Affiliate Assistant Professor, Health Services Research, University of Washington Seattle, WA 98109-1024 Dr. Joseph Unger[/caption] Joseph Unger, PhD, MS SWOG Statistical Center Assistant Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center Affiliate Assistant Professor, Health Services Research, University of Washington Seattle, WA  98109-1024 MedicalResearch.com: What is the background for this study? Dr. Unger: The rate at which trials are positive has previously been examined, and the relationship between trial results and publication rates in the context of publication bias has also been studied. But the comparative scientific impact of positive vs negative clinical trials using citation data has not been investigated We used the phase III trial database of SWOG, a major national cooperative clinical trials group, in combination with its trial publication database and citation data from Google Scholar, to compare the scientific impact of positive vs negative phase III cancer clinical treatment trials.

09 Mar

Posted at 20:25h in Author Interviews, Breast Cancer, Diabetes
MedicalResearch.com Interview with: Dr. Zorana Andersen Department of Public Health Center for Epidemiology and Screening University of Copenhagen  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Andersen: Diabetes is associated with increased risk of breast cancer, but exact mechanisms are unknown. The role of insulin has been debated. High mammographic density (MD) is one of the strongest predictors and a biomarker of breast cancer risk. Few studies have linked diabetes to mammographic density, finding none or weak inverse associations, but none had data on diabetes treatment. We examined whether diabetes and diabetes treatment are associated with mammographic density in a prospective cohort study of Danish women above age of 50 years. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Andersen: Women with diabetes, as well as clinicians working with diabetes and breast cancer and breast cancer screening, would have interest to know how different diabetes treatment can affect breast density, and hereby possibly breast cancer risk. For example, diabetic women taking insulin may possibly benefit from informing radiologists at breast cancer screening about their insulin use, due to increased breast density and increased risk of masking bias.

09 Mar

Posted at 17:03h in Author Interviews, BMJ, Cancer Research, Colon Cancer, Psychological Science
[caption id="attachment_22507" align="alignleft" width="164"]Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) Benedicte Kirkøen[/caption] MedicalResearch.com Interview with: Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) MedicalResearch.com: What is the background for this study? Response: Randomised controlled trials have demonstrated that screening for colorectal cancer (CRC) can reduce CRC related mortality, but the total benefit and harm of national cancer screening programmes are under debate. Saving relatively few lives requires a large number of people to be screened. Most people who attend screening will never develop cancer, but may be exposed to potential psychological stress by participation. Cancer is one of the largest threats to peoples’ health, and participating in screening for cancer might therefore cause anxiety. In Norway, colorectal cancer incidence has nearly tripled since the 1950s, and currently a large randomised pilot study of a national screening programme (Bowel Cancer Screening in Norway) is investigating the effect of screening on reduction in CRC incidence and mortality. As part of an evaluation of the benefits and harms of the pilot, we investigated the psychological effect of screening participation in a large group of participants. Of particular interest to us were participants who received a positive screening result and were referred to colonoscopy.

09 Mar

Posted at 15:06h in Author Interviews, Biomarkers, Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_22386" align="alignleft" width="150"]Michele Orditura Dr. Michele Orditura[/caption] Michele Orditura MD, PhD Associate Professor in Medical Oncology Faculty of Medicine, Second University of Naples Naples Italy  MedicalResearch.com: What is the background for this study? Prof. Orditura: In the last few years increasing evidence suggests that cancer-related inflammatory response plays a crucial role in the development and progression of several malignancies. Neutrophil to lymphocyte ratio (NLR), calculated as the neutrophil count divided by the lymphocyte count , may represent an easily measurable and inexpensive marker of systemic inflammation. Several studies have reported NLR as an unfavourable prognostic indicator for patients with gastrointestinal, lung, renal and gynaecological cancers. In the breast cancer setting, the results of published trials evaluating the relationship between NLR and outcome are controversial, and a recent meta-analysis including eight trials published between 2012 and 2014 has shown that elevated NLR is strongly associated with poor survival. In addition, the available data mainly concern women of Asian race and only three papers have included patients of Europe race. The main aim of this study was to clarify the correlation between pre surgery NLR and distant metastasis-free survival in a series of 300 Italian patients with early breast cancer. The propensity score-matched analysis was chosen for statistical evaluation to avoid risk of confounding bias.

08 Mar

Posted at 18:26h in Author Interviews, BMJ, Prostate, Prostate Cancer, Urology
MedicalResearch.com Interview with: [caption id="attachment_22465" align="alignleft" width="120"]Robert Nam, MD, FRCSC Ajmera Family Chair in Urologic Oncology Professor of Surgery University of Toronto Head, Genitourinary Cancer Site Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto, Ontario Dr. Robert Nam[/caption] Robert Nam, MD, FRCSC Ajmera Family Chair in Urologic Oncology Professor of Surgery University of Toronto Head, Genitourinary Cancer Site Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto, Ontario MedicalResearch.com: What is the background for this study? Response: Prostate cancer treatment is associated with a number of complications including erectile dysfunction and urinary incontinence. Two years ago, we published a paper examining other, previously undescribed complications. The most controversial finding was a significantly increased risk of secondary cancers among men treated with radiotherapy. We therefore wanted to assess this in a meta-analysis, examining all the research currently available on the topic. MedicalResearch.com: What are the main findings? Response: We found that, for patients with prostate cancer, radiotherapy treatment was associated with significantly increased rates of bladder cancer, colorectal cancer and rectal cancer. There wasn't an increased risk for other cancers such as lung and blood system cancer. However, the absolute rates of these cancers remained low (1-4% of patients).

08 Mar

Posted at 14:16h in Author Interviews, Brigham & Women's - Harvard, Melanoma, Ophthalmology
MedicalResearch.com Interview with: Ines Laines MD and Deeba Husain MD Associate Professor Ophthalmology Harvard Medical School Investigator Angiogenesis Laboratory Retina Service Massachusetts Eye and Ear Infirmary Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Uveal melanoma (UM) is the most common malignant tumor of the eye in adults. More than half of the patients are long-term survivors. It is well established for other malignancies that cancer survivors are especially prone to developing independent second primary neoplasms (SPNs) and that their characteristics vary according to the site of the first primary tumor. Multifactorial causes seem to be involved, including environmental exposures and genetic risk factors. The relevance of the treatment modalities applied to the first tumor also seem to play a role, in particular radiation therapy, which is currently the gold-standard treatment for most uveal melanoma. This risk is most pronounced in the organs within the irradiated fields, but has also been described in sites not directly exposed to radiation. Despite growing knowledge about treatment-induced effects on the occurrence of SPNs in patients with other malignancies, data is insufficient for uveal melanoma. We present a population-based analysis of the Surveillance, Epidemiology, and End Results (SEER) database, which is a well-validated public database with a case ascertainment rate of 98%. In this study, we evaluated whether patients with UM demonstrate an increased incidence of  second primary neoplasms compared to the general population, including an analysis on whether radiation therapy is associated with a higher risk of thesesecond primary neoplasms.

08 Mar

Posted at 02:35h in Author Interviews, Chemotherapy, Lancet
MedicalResearch.com Interview with: Dr Christina H Ruhlmann PhD Department of Oncology Odense University Hospital, Denmark  MedicalResearch.com: What is the background for this study? Response: The background for the GAND-emesis study is the result of a phase II study in patients with gynecological cancer receiving fractionated radiotherapy and concomitant weekly cisplatin 40 mg/m2. In that study, patients received weekly antiemetic prophylaxis with palonosetron and prednisolone, and we found that 57% of patients were continuously free from emesis (sustained no emesis) during 5 weeks of treatment. We hypothesized that the addition of a NK1 receptor antagonist could increase the number of patients with sustained no emesis, and we therefore planned the GAND-emesis study: a multinational, randomised, placebo-controlled, double-blind study that has recently been published. MedicalResearch.com: What are the main findings? Response: In the GAND-emesis study we compared efficacy of weekly antiemetic prophylaxis with fosaprepitant, palonosetron, and dexamethasone to placebo, palonosetron, and dexamethasone during 5 weeks of radiotherapy and concomitant weekly cisplatin 40 mg/m2 for cervical cancer. The primary endpoint was sustained no emesis during 5 weeks of treatment (competing risk analysis). We found that the proportion of patients with sustained no emesis was 48.7% for the placebo group compared with 65.7% for the fosaprepitant group, and the treatments were well tolerated. To our knowledge, this is the first study to investigate the efficacy of a NK1 receptor antagonist during 5 weeks of chemoradiotherapy.

07 Mar

Posted at 06:21h in Author Interviews, Breast Cancer, FASEB
MedicalResearch.com Interview with: Michelle L. Halls BBiomedSci(Hons), PhD NHMRC Career Development Fellow Drug Discovery Biology Theme Monash Institute of Pharmaceutical Sciences Monash University Parkville Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Halls: Stress causes an increase in the release of hormones including adrenaline. Previous studies have found a link between stress and metastases in triple negative breast cancer. However, what occurs inside a cancer cell in response to adrenaline to drive cancer progression was not known. We have found that adrenaline can directly act on triple negative breast cancer tumour cells via a cell surface receptor called the beta2-adrenoceptor. We identified changes in signalling within the cell that make the tumour cell highly invasive by mapping the signalling pathways that were activated in these cells in response to stress. We found that different signalling pathways converge to amplify the final signal. This ‘positive signalling loop’ was linked to the increased invasion of these cells in response to stress, and was not identified in less aggressive breast cancer cells. This may allow future research to identify new ways to intervene and slow cancer progression. New therapies are important for triple negative breast cancer, as it is particularly aggressive and currently has limited treatment options.

07 Mar

Posted at 05:22h in Author Interviews, Biomarkers, Cleveland Clinic, Genetic Research, Personalized Medicine, Prostate, Prostate Cancer, Urology
MedicalResearch.com Interview with: [caption id="attachment_22405" align="alignleft" width="132"]Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic Dr. Eric Klein[/caption] Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Klein: Prostate cancer is an enigma. While this tumor is the second leading cause of cancer death among American men, most newly diagnosed disease detected by PSA screening is biologically indolent and does not require immediate therapy. Currently, the main clinical challenge in these men is to distinguish between those who can be managed by active surveillance from those who require curative intervention. Current clinical and pathological tools used for risk stratification are limited in accuracy for distinguishing between these scenarios. An abundance of research in the last decade has provided evidence that genomics can offer meaningful and clinically actionable biological information to help inform decision making, and current National Comprehensive Cancer Network (NCCN) guidelines on prostate cancer endorse the use of commercially available genomic tools for men considering active surveillance.[1] It has been previously shown that the 22-gene genomic classifier, Decipher, accurately predicts the likelihood of metastasis and prostate cancer specific mortality when measured on tissue from radical prostatectomy specimens.[2] In multiple validation studies, it performed with higher accuracy and discrimination compared to clinical risk factors alone. The current study[3] is the first to examine whether the use of Decipher might aid decision making when measured on biopsy tissue at the time of diagnosis. Men with available needle biopsy samples were identified from a study cohort that previously had Decipher performed on their matched radical prostatectomy tissue. In this cohort of mixed low, intermediate and high risk men, Biopsy Decipher predicted the risk of metastasis 10 years post RP with high accuracy, outperforming NCCN clinical risk categorization, biopsy Gleason score and pre-operative PSA. Furthermore, this study showed that Decipher reclassified 46% of patients into lower or higher risk classification compared to NCCN classification alone. The study also showed that Biopsy Decipher can identify men that are at high risk for adverse pathology as defined by the presence of primary Gleason pattern 4 or greater.

07 Mar

Posted at 04:59h in Author Interviews, Chemotherapy, Pancreatic, Vanderbilt
MedicalResearch.com Interview with: [caption id="attachment_22400" align="alignleft" width="129"]Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN Dr. Alexander Parikh[/caption] Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN MedicalResearch.com: What is the background for this study? Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease. The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival. MedicalResearch.com: What are the main findings? Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival.

06 Mar

Posted at 01:25h in Author Interviews, Breast Cancer, Cancer Research, Genetic Research
MedicalResearch.com Interview with: [caption id="attachment_22440" align="alignleft" width="100"]Rong Li, Ph.D., Professor Holder of the Tom C. & H. Frost Endowment Department of Molecular Medicine Institute of Biotechnology Co-Leader, Cancer Development and Progression Program Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio Dr. Rong Li[/caption] Rong Li, Ph.D., Professor Holder of the Tom C. & H. Frost Endowment Department of Molecular Medicine Institute of Biotechnology Co-Leader, Cancer Development and Progression Program Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Li: The breast cancer susceptibility gene BRCA1 is well known for its function in double strand break DNA repair. However, the ubiquitous role of BRCA1 in DNA repair may not be sufficient to explain its tissue-specific tumor suppressor function in vivo. Using the “awesome power” of mouse genetics, we identified a previously unappreciated crosstalk between BRCA1 and a transcription regulator in mammary gland development. Importantly, we provide compelling evidence that this BRCA1 function is independent of its well-established DNA repair activity. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Li: The newly identified DNA repair-independent function of BRCA1 may provide new tools and targets for early prevention of BRCA1-associated breast cancer.

05 Mar

Posted at 14:58h in AACR, Author Interviews, Cancer Research, Lung Cancer, MD Anderson, Nutrition, Sugar
MedicalResearch.com Interview with: [caption id="attachment_22379" align="alignleft" width="98"]Xifeng Wu, M.D., Ph.D Professor of Epidemiology Dr. Xifeng Wu[/caption] Xifeng Wu, M.D., Ph.D Professor of Epidemiology and [caption id="attachment_22380" align="alignleft" width="150"]Dr. Stephanie Claire Melkonian PhD Epidemiologist, Postdoctoral Research Fellow Dr. Melkonian[/caption] 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.

04 Mar

Posted at 18:01h in Author Interviews, Cancer Research, Lancet, Leukemia, OBGYNE, Pediatrics
MedicalResearch.com Interview with: [caption id="attachment_22359" align="alignleft" width="180"]Erin Marcotte, Ph.D. Assistant Professor Division of Epidemiology and Clinical Research Department of Pediatrics University of Minnesota Dr. Erin Marcotte[/caption] Erin Marcotte, Ph.D. Assistant Professor Division of Epidemiology and Clinical Research Department of Pediatrics University of Minnesota MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Marcotte: Recently there have been several studies that indicate a higher risk of immune-related disorders, such as type-I diabetes, asthma, and allergies, among children born by cesarean delivery. Our analysis used pooled data from 13 independent studies of childhood leukemia that were conducted in 9 different countries. We used data on over 33,000 children to investigate the relationship between birth by cesarean delivery and risk of childhood leukemia. We did not find an association between cesarean delivery overall and childhood leukemia. However, when we looked at emergency cesarean deliveries and pre-labor (planned) cesarean deliveries separately, we found a 23% increase in risk of acute lymphoblastic leukemia among children born by pre-labor cesarean delivery.

04 Mar

Posted at 01:43h in Author Interviews, Breast Cancer, Chemotherapy, Lancet
MedicalResearch.com Interview with: [caption id="attachment_22319" align="alignleft" width="200"]Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611 Dr. Massimo Cristofanilli[/caption] Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity. 

03 Mar

Posted at 12:18h in ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology
MedicalResearch.com Interview with: [caption id="attachment_22296" align="alignleft" width="200"]Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany Dr. Oleg Gluz[/caption] Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany MedicalResearch.com: What is the background for this study? Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients. For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk. MedicalResearch.com: What are the main findings? Dr. Gluz: The study has two major findings: We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67). Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up.

03 Mar

Posted at 00:12h in Author Interviews, Breast Cancer, Cancer Research, JNCI, Lymphoma
MedicalResearch.com Interview with: [caption id="attachment_22284" align="alignleft" width="200"]David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Dr. David Hodgson[/caption] David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Toronto, ON Canada   MedicalResearch.com: What is the background for this study? Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance. MedicalResearch.com: What are the main findings? Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have "false positive" tests - abnormal findings that are not really cancer.

02 Mar

Posted at 20:31h in Author Interviews, Dental Research, Esophageal, Infections
MedicalResearch.com Interview with: [caption id="attachment_22280" align="alignleft" width="160"]Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY Dr. Huizhi Wang[/caption] Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate. 

01 Mar

Posted at 22:43h in Author Interviews, Cancer Research, Diabetes, Diabetologia
MedicalResearch.com Interview with: [caption id="attachment_22195" align="alignleft" width="160"]Bendix Carstensen Bendix Carstensen[/caption] Bendix Carstensen Department of Clinical Epidemiology Steno Diabetes Center Gentofte Medical Research: What is the background for this study? What are the main findings? Response: It has long been known that all diabetes patients have elevated risk of cancer (10-15%). Patients on insulin slightly more (20-25%). Type 1 patients is only a small fraction (10%) of all diabetes patients, but they ALL take insulin. If insulin has a role in cancer occurrence it would be expected to be particularly pronounced in type 1 patients, and increasing by duration. But it is not, the risk of cancer is 15% elevated (if we disregard prostate, breast and other cancers only occurring in one of the sexes), and there is no increase in the excess risk by duration of insulin use. Breast cancer risk is 10% lower and prostate cancer risk some 40% lower. Overall there is very little increased cancer risk - 1% for men 7% for women.

01 Mar

Posted at 20:26h in Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer
MedicalResearch.com Interview with [caption id="attachment_22239" align="alignleft" width="169"]Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA Dr. Dingxiao Zhang[/caption] Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers. Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

01 Mar

Posted at 12:38h in Author Interviews, Biomarkers, Cancer Research, Melanoma, Ophthalmology
MedicalResearch.com Interview with: [caption id="attachment_22174" align="alignleft" width="130"]J. William Harbour, MD Professor & Vice Chairman Dr. Mark J. Daily Endowed Chair Director, Ocular Oncology Service Bascom Palmer Eye Institute Interim Associated Director for Basic Research Leader, Eye Cancer Site Disease Group Sylvester Comprehensive Cancer Center Member Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Biomedical Research Building, Room 824 Miami FL 33136 Dr. J. William Harbour[/caption] J. William Harbour, MD Professor & Vice Chairman Dr. Mark J. Daily Endowed Chair Director, Ocular Oncology Service Bascom Palmer Eye Institute Interim Associated Director for Basic Research Leader, Eye Cancer Site Disease Group Sylvester Comprehensive Cancer Center Member Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Biomedical Research Building, Room 824 Miami FL 33136 Medical Research: What is the background for this study? What are the main findings? Dr. Harbour: Gene expression profiling has become the predominant means of molecular prognostic testing in uveal melanoma, with primary tumors being divided into Class 1 (low metastatic risk, about two thirds of cases) and Class 2 (high metastatic risk, about one third of cases).  In this study, we identified a new biomarker for uveal melanoma that subdivides Class 1 tumors based on the mRNA expression of the oncogene PRAME. Class 1 tumors not expressing PRAME have an extremely low metastatic risk, whereas those expressing PRAME have an intermediate metastatic risk.