tbuckley/cabot-search huggingface dataset:
Assessment of tumor hypoxia in BEV resistant GBM using FMISO 18F-PET and MRI.
Authors: Yichu Liu, Eudocia Quant Lee, Shiliang Huang, Mark Muzi, David A. Reardon, Patrick Y. Wen, Andrew Jacob Brenner
Journal: Journal of Clinical Oncology (2017)

2045 Background: Glioblastoma (GBM) is the most common malignant brain tumor in adults, and is characterized by poor survival and marked resistance to treatment. Hypoxic volume is directly correlated with poor outcome in GBM, with structural and functional tumor vasculature changes regarded as a primary driver of tumor hypoxia. As part of an ongoing clinical trial with a hypoxia activated prodrug, we sought to explore the correlation between abnormal tumor vasculature and hypoxia in bevacizumab (BEV) resistant GBM. Methods: MRI and 18 F-FMISO PET scans were acquired at study entry. The MRI protocols include standard anatomical sequences as well as Dynamic Susceptibility Contrast (DSC/perfusion) imaging. Enhancing tumor ROIs were determined from Delta T1 maps, non-enhancing tumor ROIs were obtained from FLAIR images, ratio between enhancing and non-enhancing volumes were calculated, values from standardized rCBV maps were extracted from corresponding enhancing ROIs. Decay correction was applied to 18 F-FMISO images and converted to SUV units. After registration to MR images, cerebellar regions were used as surrogates for blood activity. The FMISO images were then normalized to generate tissue to blood ratio (TB). A threshold of TB &gt; 1.2 was used in discriminating the hypoxia volume (HV). Correlation between parameters was assessed using Pearson correlation. Results: 7 patients from University of Texas Health Science center and 7 patients from Dana-Farber Cancer Institute had evaluable MR and PET imaging. We compared MRI parameters (enhancing and non-enhancing tumor volumes, srCBV) with hypoxia (HV and maxSUV). There was a positive correlation between HV and enhancing volume (R = 0.732, p = 0.0029) as well as between HV and ratio (R = 0.644, p = 0.013. The correlation between other pairs were not statistically significant (HV vs srCBV: p = 0.862, T1 vs maxSUV p = 0.492, srCBV vs maxSUV: p = 0.393, ratio vs maxSUV = 0.178). Conclusions: The hypoxic volume following bevacizumab failure correlates with both the volume of enhancement and the fraction of enhancement within the mass. The clinical implications of this is being assessed in an ongoing phase 2 study. Clinical trial information: NCT02342379.
A nation-wide multicenter 10-year (1999-2008) retrospective study of chemotherapy in Chinese breast cancer patients.
Authors: Qiao Li, Zhao Yang, Jinhu Fan, Jianjun He, Bin Zhang, Hongjian Yang, Xiaoming Xie, Zhonghua Tang, Hui Li, Youlin Qiao, Pin Zhang
Journal: Journal of Clinical Oncology (2016)

e12513 Background: We aimed to evaluate factors associated with receipt of chemotherapy, and to describe trends of chemotherapeutic regimens and agents in Chinese females with breast cancer. Methods: We retrospectively analyzed demographic and pathological data along with chemotherapeutic information of 4211 breast cancer patients randomly selected from representative hospitals of 7 traditional areas in China between 1999 and 2008. Results: Among the 4211 cases, a total of 3271 cases (77.7%) received adjuvant chemotherapy (ACT), 558 (13.3%) received neoadjuvant chemotherapy (NACT), and 392 (9.3%) received chemotherapy for metastatic disease. In adjuvant settings, age, stage, HR and HER2 status were independent factors affecting the use of ACT (P < 0.001). Frequencies of ACT in stage I, II and III cases were 69.1%, 83.2% and 93.9%, respectively. Frequencies of ACT in age groups of ≤ 39, 40-49, 50-59, 60-69 and ≥ 70 years were 84.2%, 81.9%, 79.5%, 65.6% and 28.3%, respectively. The percentage of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in ACT decreased from 51.2% to 1.3% between 1999 and 2008, and the use of regimens containing both anthracyclines and taxanes increased from 14.4% to 45.4% during the same period, while anthracycline-based (without taxanes) regimens increased during the first 5 years (from 15.3% to 54.5%) and decreased to 26.8% in 2008. Compared to earlier stage, more locally advanced patients received NACT (24.1% vs. 9.2%, p < 0.001). The percentage of NACT regimens containing both anthracyclines and taxanes increased from 2.4% to 43.8% between 1999 and 2008, while anthracycline-based (without taxanes) regimens increased in the first 6 years (from 24.4% to 70.4%) and decreased to 30.0% in 2008. In first-line chemotherapy, 87.5% of cases received combined chemotherapy. Among them, most received anthracyclines and taxanes (34.9%), followed by taxanes plus platinum (21.7%) and vinorelbine plus platinum (16.5%). Conclusions: Major changes have taken place in chemotherapy for early and metastatic breast cancer patients in China during this 10-year interval, which reflected the incorporation of key evidence and guidelines into Chinese medical practice.
An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG)
Authors: B. Kasper, C. Baumgarten, J. Garcia, S. Bonvalot, R. Haas, F. Haller, P. Hohenberger, N. Penel, C. Messiou, W.T. van der Graaf, A. Gronchi, S. Bauer, J.Y. Blay, F. van Coevorden, P. Dileo, H.R. Dürr, M. Fiore, V. Grünwald, R. Jones, I. Judson, C. Kettelhack, K. Kopeckova, A. Lazar, L.H. Lindner, J. Martin-Broto, P. Rutkowski, S. Stacchiotti, E. Stoeckle, C. Valverde, K. Verhoef, E. Wardelmann, M. Wartenberg
Journal: Annals of Oncology (2017)

Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals' AND patients' expertise following a round table meeting bringing together sarcoma experts from the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group with patients and patient advocates from Sarcoma PAtients EuroNet. In this paper, we focus on new findings regarding the prognostic value of mutational analysis in desmoid-type fibromatosis patients and new systemic treatment options.
Breast cancer in male veterans: The Veterans Affairs (VA) informatics and computing infrastructure (VINCI) big data analysis.
Authors: Anita Aggarwal, David Maron, Steven H. Krasnow
Journal: Journal of Clinical Oncology (2017)

1559 Background: Male breast cancer (MBC) management from diagnosis to treatment is generalized from female breast cancer (FBC) because of its rarity and paucity in literature. VINCI is a unique database for cross sectional and longitudinal analysis. The objective of this retrospective analysis was to compare characteristics and outcome of MBC with FBC in veterans. Methods: Detailed demographics, diagnosis, treatment and outcome of all patients diagnosed with breast cancer between 1998 and 2016 at 152 VA medical centers were obtained and analyzed with Chi-square and t-test univariate statistics. Results: In total 9765 patients' records were reviewed, 1613 MBC were compared with 8152 FBC. The mean age at diagnosis is 68.5 and 57.3 years for MBC and FBC, respectively (Table1). After a median follow up of 3.5 years, 48% MBC and 22% FBC died. Breast cancer mortality is 18% and 9% in MBC and FBC, respectively. A cox regression survival analysis indicates that males were 33% (Hazard Ratio 1.33, P=&lt;0.0001) more likely to die from breast cancer than females. Conclusions: This is the largest comparison series of MBC with FBC to date in the Veteran population to author’s knowledge. Males have higher breast cancer specific mortality than females most likely because of older age and higher stage at the time of diagnosis. Differences in the biology and pathology may be contributing factors which needs further prospective studies. [Table: see text]
Impact of patient-provider race/ethnicity and gender concordance on cancer screening: Findings from medical expenditure panel survey.
Authors: Jyoti Malhotra, David Rotter, Jennifer Tsui, Adana Llanos, Bijal A Balasubramanian, Kitaw Demissie
Journal: Journal of Clinical Oncology (2017)

1547 Background: Racial/ethnic minority groups experience lower rates of cancer screening compared to non-Hispanic (NH) whites. Previous studies evaluating the role of patient-provider race/ethnicity and gender concordance in cancer screening have been inconclusive. Methods: We conducted a cross-sectional study of 18,690 patient-provider pairs using the 2003-2010 Medical Expenditure Panel Survey (MEPS) data. We assessed association between patient-provider race/ethnicity and gender concordance and, screening adherence for breast, cervical, and colorectal cancer using American Cancer Society guidelines. Separate multivariable logistic regression adjusting for demographics, self-reported health and MEPS survey year were conducted to examine relationships of interest. Results: Seventy percent of patients were NH-white, 15% were NH-black and 15% were Hispanic. Patients adherent to cancer screening were more likely to be non-Hispanic, better educated, married, wealthier, and privately insured. Among NH-black and NH-whites, patient-provider racial/ethnic concordance was not associated with screening adherence. Among Hispanics, patient-provider racial/ethnic discordant pairs had higher colorectal cancer screening rates as compared to concordant pairs (OR 1.48; 95% CI 1.28-1.71). This association was significant even on adjusting for gender concordance and survey language (English vs. Spanish). Conversely, patient-provider gender discordance was associated with lower rates of breast (OR 0.81; 95% CI 0.74-0.89), cervical (OR 0.79; 95% CI 0.72-0.87) and colorectal cancer (OR 0.86; 95% CI 0.80-0.93) screening adherence in all patients. This association was also significant on restricting analysis to racial/ethnic concordant pairs. Conclusions: Patient-provider gender concordance positively impacts adherence to cancer screening and this finding may guide future interventions. Patient-provider racial/ethnic concordance is not associated with screening adherence among whites and blacks but Hispanic patients seen by Hispanic providers have lower colorectal cancer screening rates. This counter-intuitive finding requires further study.
Abstract P153: Role of Nonreceptor Tyrosine Kinases in Cardiac Fibrosis in a Mouse Model of Pressure Overload Hypertrophy
Authors: Sundaravadivel Balasubramanian, Harinath Kasiganesan, Lakeya Quinones, Yuhua Zhang, Amy Bradshaw, Dhandapani Kuppuswamy
Journal: Circulation Research (2011)

During prolonged hypertrophic insult to the myocardium, while the function of cardiomyocytes needs to be protected, the hyperactivation of cardiac fibroblasts has to be curbed to prevent fibrosis. Previously, we showed that integrin-mediated non-receptor tyrosine kinase (NRTK) activation is required for normal functioning of both cardiac fibroblasts and cardiomyocytes. We hypothesized that inhibition of NRTKs in cardiac fibroblasts without affecting cardiomyocytes would be beneficial to the stressed myocardium. Our initial studies using kinase inactive forms of Src, Pyk2 and FAK expressed adenovirally in isolated primary cardiac fibroblasts showed that the pro-fibrotic signaling events as studied by fibronectin and collagen deposition are downregulated. Our in vivo studies in mouse transverse aortic constriction (TAC) model suggest that dasatinib, a multikinase NRTK inhibitor administration via a peritoneally implanted mini-osmotic pump is able to preserve ventricular geometry and function and reduce the accumulation of fibrotic extracellular matrix (ECM) proteins upon 4 wk pressure overload. Data obtained from cell culture experiments with kinase inactive NRTKs and dasatinib suggest that NRTK inhibition is able to reduce the proliferation, migration and mitogenic signaling in cardiac fibroblasts without affecting the cell survival pathways in cardiomyocytes. These data indicate that NRTKs play a significant pro-fibrotic role in cardiac fibroblasts and curbing the activity of NRTKs could be a potential therapeutic approach to treat fibrosis in hypertrophic heart diseases.
Effect of PectaSol-C modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in patients (pts) with nonmetastatic, biochemically relapsed prostate cancer (BRPC): Results of the interim analysis of a prospective phase II study.
Authors: Daniel Keizman, Moshe A. Frenkel, Todd Michael Edwards, Eli Rosenbaum, David Margel, David Sarid, Victoria Neiman, Maya Gottfried, Natalie Maimon, Ilan Leibovitch, Hadas Dresler, Isaac Eliaz
Journal: Journal of Clinical Oncology (2017)

e16588 Background: 30% of pts with localized PC will have a biochemical relapse post local tx. The optimal tx of these pts remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long term benefit on survival remain undefined, and it is associated with significant cumulative toxicities.Thus evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, which is known to be involved in cancer pathogenesis. Preliminary pre-clinical and clinical data suggest that P-MCP is active in PC. We aimed to evaluate the safety and PSA dynamics of tx with P-MCP in pts with BRPC. Methods: Pts with non-castrate non metastatic BRPC were enrolled in a prospective phase 2 study of tx with oral P-MCP, at 4.8 grams X 3/day. Pts that did not progress clinically, biochemically (PSA), and radiologically, at 6 months (mos), were treated for subsequent 12 mos. Sample size provided 85% power to assess a decrease in PSA progression rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. We report here first results of a pre-planned interim analysis after ≤ 50% of planned enrolled pt completed 6 mos of tx. Results: The study was initiated in June 2013. We report here the 6 mos data of the first 35 pts enrolled. Median age was 74 years. Treatment of the primary tumor consisted of surgery in 11% (n = 4), radiation in 69% (n = 24), and both in 20% (n = 7). No pt had tx related grade 3/4 toxicity. One patient withdrew his consent after 1 mos. Of the 34 pts analysed, 18% (n = 6) had grade 1 toxicity. 62% (n = 21) had a stabilization/decrease of PSA, and negative scans, at 6 mo, and entered into the second 12 mos tx phase. A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of pts. Disease progression at 6 mos was noted in 38% (n = 13: PSA only 29%, n = 10; PSA and scans 9%, n = 3). A future final report will include full tx data (18 mos) and correlative analysis. Conclusions: The interim analysis of the present study suggests a potential benefit of P-MCP tx on progression of BRPC. P-MCP tx is safe. Final analysis is pending. Clinical trial information: NCT01681823.
Small RNA Activity in Archeological Barley Shows Novel Germination Inhibition in Response to Environment
Authors: Oliver Smith, Sarah A. Palmer, Alan J. Clapham, Pamela Rose, Yuan Liu, Jun Wang, Robin G. Allaby
Journal: Molecular Biology and Evolution (2017)

The recovery of ancient RNA from archeological material could enable the direct study of microevolutionary processes. Small RNAs are a rich source of information because their small size is compatible with biomolecular preservation, and their roles in gene regulation make them likely foci of evolutionary change. We present here the small RNA fraction from a sample of archeological barley generated using high-throughput sequencing that has previously been associated with localized adaptation to drought. Its microRNA profile is broadly similar to 19 globally distributed modern barley samples with the exception of three microRNAs (miRNA159, miRNA319, and miR396), all of which are known to have variable expression under stress conditions. We also found retrotransposon activity to be significantly reduced in the archeological barley compared with the controls, where one would expect the opposite under stress conditions. We suggest that the archeological barley’s conflicting stress signals could be the result of long-term adaptation to its local environment.
Progesterone receptor, a novel risk factor for paclitaxel-induced peripheral neuropathy.
Authors: Zohreh Ghoreishi, Ali Esfahani, Mohammad Asghari Jafarabadi, Hormoz Ayromlou
Journal: Journal of Clinical Oncology (2016)

e12031 Background: Peripheral neuropathy is the main dose-limiting complication of paclitaxel. In this study, the association between clinical characteristics of the patients with breast cancer, disease pathology and paclitaxel-induced peripheral neuropathy (PIPN) was evaluated. Methods: In patients with node positive breast cancer who were candidate for chemotherapy with paclitaxel, the associations between age, body mass index (BMI), tumor histological grading, tumor size, metastasis status, the number of involved nodes, estrogen/progesterone receptors status, Her2 and P53 status and incidence and severity of PIPN were studied. PIPN was measured by “reduced Total Neuropathy Score/ rTNS”, a composite score including clinical and electrophysiological assessments. Analysis was performed on data of trial NCT01049295. Results: Fifty-seveneligible breast cancer patients completed the study. In Univariate analysis, there was a significant association between age, BMI, and progesterone receptor positive (Pr+) breast cancer and incidence of PIPN, ((OR = 1.08, .95% CI = (1.01- 1.14), p = 0.015; (OR = 1.07, .95% CI = (1.00- 1.15), p = 0.041); (OR = 5.78, .95% CI = (1.57- 21.26), p = 0.008), respectively). Similar results were found between these parameters and severity of PIPN, ((B = .07, .95% CI = (.02- .11), p = 0.010; (B = .08, .95% CI = (.02- .14), p = 0.012); ((B = 1.58, .95% CI = (.39- 2.76), p = 0.009)). In multivariate analysis, progesterone receptor positive breast cancer was found as an independent risk factor for incidence and severity of PIPN after adjusting for intervention effect (OR = 5.83, .95% CI = (1.39- 24.40), p = 0.016; B = 1.23, .95% CI = (.03- 2.42), p = 0.045), so that patients with Pr+ tumors were nearly 6 times more likely to develop PIPN. Conclusions: The progesterone receptor positive breast cancer was found for the first time as an independent risk factor for incidence and severity of PIPN. These data provide a possible role for progesterone in the pathogenesis of PIPN. More studies with larger sample size are warranted. Clinical trial information: NCT01049295.
Using Viral Gene Sequences to Compare and Explain the Heterogeneous Spatial Dynamics of Virus Epidemics
Authors: Simon Dellicour, Rebecca Rose, Nuno Rodrigues Faria, Luiz Fernando Pereira Vieira, Hervé Bourhy, Marius Gilbert, Philippe Lemey, Oliver G. Pybus
Journal: Molecular Biology and Evolution (2017)

Rabies is an important zoonotic disease distributed worldwide. A key question in rabies epidemiology is the identification of factors that impact virus dispersion. Here we apply new analytical methods, based on phylogeographic reconstructions of viral lineage movement, to undertake a comparative evolutionary-epidemiological study of the spatial dynamics of rabies virus (RABV) epidemics in different hosts and habitats. We compiled RABV data sets from skunk, raccoon, bat and domestic dog populations in order to investigate the viral diffusivity of different RABV epidemics, and to detect and compare the environmental factors that impact the velocity of viral spread in continuous spatial landscapes. We build on a recently developed statistical framework that uses spatially- and temporally-referenced phylogenies. We estimate several spatial statistics of virus spread, which reveal a higher diffusivity of RABV in domestic dogs compared with RABV in other mammals. This finding is explained by subsequent analyses of environmental heterogeneity, which indicate that factors relating to human geography play a significant role in RABV dispersion in domestic dogs. More generally, our results suggest that human-related factors are important worldwide in explaining RABV dispersion in terrestrial host species. Our study shows that phylogenetically informed viral movements can be used to elucidate the factors that impact virus dispersal, opening new opportunities for a better understanding of the impact of host species and environmental conditions on the spatial dynamics of rapidly evolving populations.
Abstract 17460: Anemia and Therapeutic Hypothermia Post-cardiac Arrest: Is There a Transfusion Threshold?
Authors: Nyal Borges, Michael N Young, Benjamin Holmes, Yanna Song, Emily Zern, John A McPherson
Journal: Circulation (2015)

Introduction: Profound anemia has been shown to have deleterious effects in critically ill patients (pts). Currently, no data exists regarding the effects of anemia on outcomes in pts post-cardiac arrest treated with therapeutic hypothermia (TH). We aim to evaluate whether a correlation between anemia and neurologic outcome exists in this high risk population. Methods: We performed a retrospective study of 260 consecutive comatose survivors of cardiac arrest treated with TH. Independent variables included hematocrit at time of admission, 24, 48 and 72 hrs post-admission as well as packed red blood cell transfusions. The outcome variable was Cerebral Performance Category (CPC) score at discharge. CPC scores 1-2 represented good neurologic outcomes while scores 3-5 represented poor outcomes. A Spearman correlation was computed between each of the above independent variables and discharge CPC, adjusting for the following risk factors: place of arrest, arrest rhythm, time to ROSC, witnessed arrest and presence of chronic kidney disease. Results: Of 260 pts, 101 (38.9%) had a good neurologic outcome (CPC≤2) at discharge. The mean hematocrit at admission for males and females was 40 ± 6.4 and 39.2 ±7 % respectively. The Spearman coefficient between hematocrit and CPC score at discharge was not statistically significant (Figure 1). Coefficient for hematocrit at admission and 72hrs with CPC score at discharge was 0.07 (p = 0.32) and 0.01 (p = 0.85) respectively. Coefficient for transfusions and CPC score was -0.11 (p =0.1). Conclusion: Our data suggest that neurological outcomes after cardiac arrest in pts treated with TH are unrelated to hematocrit levels or transfusions. Based on these findings, conservative transfusion strategies may be appropriate in this patient population.
Public’s distrust of medicines needs urgent action, says academy
Authors: Nigel Hawkes
Journal: BMJ (2017)

Only a third of the public trust the evidence from medical research, a survey for the Academy of Medical Sciences has found—half as many as trust what their friends and family tell them about medicines.1

John Tooke, who chaired the committee that commissioned the survey, called the finding “startling.” Speaking at a press conference at the Science Media Centre in London on 19 June, he noted an urgent need to act now to give patients clearer, more useful information about medicines, saying that otherwise they would not reap the full benefits of new drugs coming to the …