tbuckley/cabot-search huggingface dataset:
Abstract 17288: Green Tea Catechin Consumption Affects Metabolic Syndrome in Japanese Overweight and Obese Adults
Authors: Masao Takeshita, Kazuhiro Otsuka, Koichi Yasunaga, Yoshihisa Katsuragi
Journal: Circulation (2013)

Introduction:  Metabolic syndrome (MetS), a cluster of cardiovascular risk factors, increases the risk of type-2 diabetes mellitus and cardiovascular disease (CVD) worldwide. Accumulating evidence indicates that catechins (flavan-3-ols) abundant in green tea improve fat metabolism; however, health benefits of catechins consumption on the chronic metabolic disorder have yet to be elucidated.   Hypothesis:  Our aim was to assess the effect of long-term consumption of catechins on MetS among Japanese overweight and obese adults.   Methods:  The study was a multicenter, randomized, double-blind, placebo-controlled, parallel study. After a 4-week run-in period, 166 Japanese overweight and obese men and women (mean BMI: 28.3 kg/m 2 , M 101/F 65) consumed a 350-mL bottle of green tea containing either 554 mg of catechins with 84 mg of caffeine (catechin group, n=83) or 87 mg of catechins with 84 mg of caffeine (control group, n=83) per day for 12 weeks. Data on all subjects were analyzed on an intention to treat basis.   Results:  At the end of the study, body weight (-1.3 kg vs. -0.1 kg, p 2  vs. -0.3 cm 2 , p   Conclusions:  Daily consumption of a catechin-rich beverage may be useful for managing MetS accompanied by insulin resistance-related obesity, linked to type-2 diabetes mellitus and CVD.
Type, intensity, and duration of chemotherapy (CHT) and their correlation with prognosis of localized soft tissue Ewing tumors (STET): Experience of the Cooperative Weichteilsarkomstudiengruppe (CWS).
Authors: Ewa Koscielniak, Monika Scheer, Monika Sparber-Sauer, Erika Hallmen, Ivo Leuschner, Bernarda Kazanowska, Gustaf Ljungman, Felix Niggli, Ruth Ladenstein, Stefan S. Bielack, Marc W. Muenter, Thekla von Kalle, Simone Feuchtgruber, Thomas Klingebiel
Journal: Journal of Clinical Oncology (2017)

10527 Background: The optimal type and intensity of CHT in the treatment of STET is still a matter of debate. The CWS group has treated STET similar to rhabdomyosarcoma. We have analyzed the prognosis of STET in relation to the CHT regimens used in three consecutive CWS studies CWS-91, -96 and CWS- 2002P. Methods: 243 pts with localized STET were included. Their median age was 12 (range 0.1-29) yrs. In the CWS-91 pts with primary tumor resection (IRSG I and II) were treated with VACA (vincristine (VCR), actinomycin D (Act D), cyclophosphamide (CYC), doxorubicin (DOX), for 10 or 20 weeks. All other CWS-91 pts (high risk group, HRG) received EVAIA (ifosfamide (IFO) instead of CYC plus VP16) for 37 weeks. In the CWS-96 and CWS-2002P all STET pts were allocated to the HRG. In CWS-96 therapy was randomized: VAIA (IFO, DOX, Act D, VCR) vs. CEVAIE (Epi-DOX instead of DOX, plus carboplatin and VP16), for 25 weeks. In CWS-2002P VAIA (25 weeks) plus maintenance CHT with CYC and vinblastine (VBL) for 26 weeks were used. The cumulative doses varied: IFO 24-72 g/m², CYC 4.8-7.35 g/m², DOX 120-360 mg/m², Act D 3-9 mg/m², VP16 1.8-5.4 g/m². Irradiation was stratified depending on results of the primary or secondary resection and response. Results: 5 yr event free (EFS) and overall survival (OS) were 64% and 73%. The median observation time of survivors was 9 yrs. 5yr EFS and OS by study were: CWS-91 64 % and 72 %, CWS-96 57% and 70 %, CWS-2002P 78 % and 86 % respectively (n.s.). 5 yr EFS and OS for VACA arm were 79% and 90%. 5 yr EFS and OS by CHT for HRG were: EVAIA 57% and 65%, VAIA 64% and 80%, CEVAIE 45% and 54%, VAIA with CYC/VBL 84% and 87%, respectively (p = 0 .003). 5yr EFS and OS for irradiated (n = 181) vs. not irradiated (n = 48) patients were 63 % and 72% vs. 63% and 79%, respectively. Conclusions: The outcomes between CHT arms differed significantly: CEVAIA correlated with the worst outcome while VAIA with CYC/VBL showed the best results. A small group of low risk patients have an excellent prognosis with substantially reduced CHT. Ewing tumors are biologically heterogeneous and more diversification in therapy stratification is warranted to avoid overtreatment.
Immunological effect of hydrogen gas.
Authors: Junji Akagi
Journal: Journal of Clinical Oncology (2018)

e15546 Background: In cancer patients, the affected microenvironment causes metabolic insufficiency of terminal CD8+ T cells, characterized by persistent loss of mitochondrial function and mass, typically following progressive loss of PPAR-gamma co-activator 1 alpha (PGC-1α). Consequently, terminal CD8+T cells become exhausted CD8+ T cells expressing PD-1 molecule. According to recent reports, nivolumab may not be effective for the exhausted CD8+ T cells with mitochondrial dysfunction. Hydrogen gas is reported to activate PGC-1α and enhance mitochondrial function, thereby potentially restoring the exhausted CD8+ T cells and improving the clinical efficiency of nivolumab. Methods: Using flow cytometry, we investigated PD-1 expression in CD8+ T cells in the peripheral blood of 55 patients with stage IV colorectal carcinoma, before and after hydrogen gas treatment. Further, we compared the progression-free survival (PFS) and overall survival (OS), using Cox and Kaplan-Meier survival analyses, between 12 patients treated with nivolumab only, and 14 patients treated with nivolumab + hydrogen gas. Results: Hydrogen gas reduced the number of terminal PD-1+CD8+ T cells in 35 of 55 patients and increased terminal PD-1−CD8+ T cells in 39 of 55 patients. Multivariate analyses demonstrated that the ratio of terminal PD-1+CD8+ T cells before and after treatment with hydrogen gas (terminal PD-1+CD8+ T cell ratio) was an independent predictor of PFS [hazard ratio (HR) 6.459, 95 % confidence interval (CI) 2.384–17.50, p < 0.0001] and OS (HR 2.957, 95 % CI 1.185–7.378, p = 0.020). Additionally, patients with higher terminal PD-1+CD8+ T cell ratio had shorter survival rates than those with lower ratio (log rank test, p < 0.0001 for PFS, p = 0.004 for OS), whereas the high terminal PD-1−CD8+ T cell ratio corresponded to longer survival rates than the lower ratio (log rank test, p = 0.004 for PFS, p = 0.024 for OS). Patients treated with nivolumab + hydrogen gas showed a significantly longer OS than those treated with nivolumab only. Conclusions: These results suggest that hydrogen gas restored terminal PD-1+CD8+ T cells to improve PFS and OS in patients with colorectal carcinomas and to enhance clinical effects in those treated with nivolumab, possibly by activating mitochondrial function.
Anti-PD1 treatment to induce M1 polarization of tumor infiltrating macrophages in a 3D ex vivo system of lung cancer patients.
Authors: Melanie Mediavilla-Varela, Melba Marie Page, Jenny Kreahling, Scott Joseph Antonia, Soner Altiok
Journal: Journal of Clinical Oncology (2017)

e23090 Background: Nivolumab and pembrolizumab treatment targeting the PD1/PD-L1 axis has demonstrated increased survival benefit in subpopulations of patients with advanced non-small cell lung cancer (NSCLC). The impact of these therapeutics on tumor immune microenvironment is not fully understood. Classical M1 macrophages are critical components involved in the inflammatory response and antitumor immunity. In this study, we evaluated the effect of PD1/PD-L1 blockade on M1 polarization of tumor-associated macrophages (TAMs) and activation of cytotoxic T-cells in a 3D ex vivo system of NSCLC. Methods: Fresh tumor tissues obtained from consented patients with NSCLC at the time of surgical resection were utilized in a 3D ex vivo tumor miscrosphere assay. 3D tumor microspheres were treated with nivolumab or pembrolizumab at 10 mg/ml for 36 hours within an intact tumor microenvironment. Flow cytometry analysis was performed to evaluate treatment-mediated TAM polarization, activation of T-cells and changes in CD4 and CD8 subpopulations. A multiplex human cytokine assay was used to simultaneously analyze the differential secretion of cytokines. Additionally, a NanoString platform containing probes to quantitate 770 immune function genes was used to determine potential positive or negative associations between expression of immune function genes and TIL activation by ex vivo treatment. Results: Both nivolumab and pembrolizumab treatment increased population of M1 macrophages (CD68+, CD80+, CD163-) and simultaneous release of MIP1b, IFN-ɣ, TNF-a, and GM-CSF cytokines as well as expression of genes related to the M1 phenotype that was accompanied by activation of CD8 cells assessed by Ki67 and CD107a expression and increased expression of genes involved in the IFNg pathway. Conclusions: Our studies showed that anti PD1/PD-L1 treatment leads to M1 macrophage polarization and T-cell activation in subgroups of NSCLC patients emphasizing the importance of comprehensive analysis of tumor immune microenvironment for a better understanding of the mechanism of action of immuno-oncology drugs that may help developing rationale combination treatments in NSCLC.
Impact of oncologists’ attitudes toward end-of-life care on Patient’s access to palliative care.
Authors: Eduardo Bruera, Maria Agustina Cerana, Minjeong Park, Kenneth R. Hess, David Hui
Journal: Journal of Clinical Oncology (2016)

e21644 Background: It is unclear how oncologists’ attitudes toward end-of-life (EOL) care affect their patients' access to primary and specialists/secondary palliative care.This study examined the association between oncologists’ EOL care attitudes and (1) timely specialist palliative care referral, (2) provision of primary palliative care, and (3) EOL cancer treatment decisions. Methods: We randomly surveyed 240 oncology specialists at our tertiary care cancer center to assess their attitudes toward EOL care using a composite score derived a priori based on a qualitative conceptual framework (Jackson et al. 2008; where 0 = uncomfortable, 8 = highly comfortable with EOL care). We determined the association between this composite score and the clinicians’ rating of their own specialist palliative care referral, provision of supportive care, and EOL cancer treatment decisions using the Mann-Whitney test and the Spearman correlation test. Results: Among the 182 respondents (response rate 76%), the median composite EOL care score was 6 (interquartile range 5-7). A higher composite EOL care score was significantly associated with solid tumor oncology (median 7 vs. 6 for hematologic oncology, P < 0.001), a greater willingness to refer patients with newly diagnosed cancer to specialist palliative care (median 7 vs. 6, P = 0.01), greater comfort with symptom management (median 6 vs. 5, P = 0.01) and provision of counseling (median 7 vs. 4, P < 0.001), but not recommendations for cancer treatments at the EOL. We observed a significant gradient effect with higher composite scores associated with a greater proportion of patients with advanced cancer being referred to palliative care (scores 0-4 = 27%; 5 = 31%, 6 = 32%, 7 = 35%, 8 = 45%; P = 0.007). Conclusions: A majority of oncology specialists at our institution considered themselves to be comfortable with EOL care. Greater comfort withEOL care was associated with higher rates of specialist palliative care referral and self-reported primary palliative care delivery. More support and education are needed for oncologists who were less comfortable with EOL care, whose patients may receive lower levels of both primary and secondary palliative care.
TCT-338 Comparison of Re-Do transcatheter aortic valve replacement with valve-in-valve for failed surgical aortic bioprostheses: a multicenter analysis of clinical and long-term outcome
Authors: Matthias Raschpichler, Felix Woitek, Tarun Chakravarty, Chetana Singh, Mohammad Kashif, Chinar Patel, Jasminka Stegic, Stephan Haussig, Philipp Kiefer, Norman Mangner, David Holzhey, Axel Linke, Holger Thiele, Michael Borger, Raj Makkar
Journal: Journal of the American College of Cardiology (2018)
Utilization of the 21-gene RS test among Medicare beneficiaries with breast cancer in 2011.
Authors: Julie Ann Lynch, Brygida Berse, Nicole Coomer, John Kautter
Journal: Journal of Clinical Oncology (2016)

e18078 Background: The numbers of genomic tests and indications for testing are rapidly expanding. By identifying patients’ response to treatment, genomic risk stratification tools can improve health outcomes, while decreasing costs and toxicities of ineffective treatments. The 21-gene recurrence score test predicts 10-year risk of recurrence and chemotherapy benefit in early-stage, estrogen receptor (ER) positive breast cancer patients. We evaluated utilization of this test among Medicare beneficiaries and analyzed clinical, demographic, and regional factors that predict testing. Methods: Using 2011 Medicare claims data, we conducted a retrospective cohort study of fee-for-service beneficiaries diagnosed with breast cancer who had undergone tissue collection. Independent variables expected to predict testing were patient age, gender, race, Medicaid status, clinical characteristics, and the hospital referral region (HRR). Results: Among the 114,624 beneficiaries analyzed, 11,934 (12%) had a claim for the 21-gene test. HRR was the strongest predictor of testing, odds ratios ranging from 0.21 (CI .0.07 – 0.62) for Rochester, Minnesota HRR to 3.61 (CI 1.66-7.87) for Slidell, Louisiana. ER-positive patients had an OR of 2.58, CI 2.48-2.69. White patients were more likely to be tested than minorities (OR 1.42, CI 1.33-1.51). Medicaid patients were less likely to be tested (OR 0.75, CI 0.71-0.80). For every tenth point increase in the weighted average risk score, there was a 5% decrease in likelihood of testing. The likelihood decreased with beneficiaries’ age, by 4% per year (OR 0.96, CI 0.96-0.96). Conclusions: Despite widespread implementation of the 21-gene test, some minorities and Medicaid patients have less access to testing. We also identified patients for whom the appropriateness of testing was questionable due to comorbid medical conditions or advanced age.Our data illustrate the need to improve coding to ensure that reimbursement of genomic tests is tied to appropriate use and to discourage overutilization.
Surveillance of cancer survivors: Results from a survey of primary care physicians working in the Spanish National Health System.
Authors: Begoña Graña, Ana Martinez, Manuel Lado, Maria Forjan, Rosario Garcia Campelo, Joaquin Mosquera, Aurea Molina, Martin Deben
Journal: Journal of Clinical Oncology (2016)

e21562 Background: Caring for a growing number of cancer survivors is a worldwide challenge for health systems.There is a paucity of evidence for effective ways to monitor cancer survivors, but Primary Care seems to take a greater role and responsibility. In Spain, there is no data about the state of cancer survivors’ surveillance by Primary Care. Methods: In June 2015, an online anonymous survey was sent to 1,860 Primary Care physicians working in Galicia (NW Spain), who provide universal health coverage to a population of 2,750,000 inhabitants. The questionnaire consisted of 13 items that included questions about professional experience, characteristics of the work place, identified obstacles to take care of cancer survivors, and proposals to improve cancer survivors’ follow up. Results: 332 physicians answered the survey (response rate 17.8%).Their average age was 52 years, 57% were women, and 72.3% had more than 20 years of professional practice. Most responders (51%) considered it was very important to work with cancer survivors, and 48% of them regarded it a competence of Primary Care. Professional expertise to follow up cancer survivors was qualified as average by 55.1% of responders. The main obstacles to adequately follow up cancer survivors were lack of training (81.6%), lack of time and absence of guidelines (82.9%). Overall, all groups of respondents assessed the proposals for improvement of cancer survivors’ follow-up as favorable. Women have statistically significant differences compared to male colleagues when assessing continuing education (X2 = 20.8; p < 0,0001, DF = 4) and rotations in Oncology services by Primary Care fellows in training (X2 = 23.2; p < 0,0001,DF = 4). Conclusions: This is the first study about surveillance of cancer survivors conducted in Spain which collects the opinion of Spanish Primary Care physicians working for the public National Health System. Cancer survivor surveillance was considered a competence of Primary Care by survey responders. The main obstacles identified were lack of training, time and guidelines. The main proposal to improve surveillance of cancer survivors is to promote training and education in this area of knowledge.
P01.010 Patterns of care in glioma patients surviving beyond ten years
Authors: C Marosi, M Stacherl, B Flechl, K Dieckmann, A Wöhrer, J Hainfellner, G Widhalm, B Kiesel, M Preusser
Journal: Neuro-Oncology (2018)

Little is known about patterns of care during long term follow-up of patients with glioma Patients and Methods: By retrospective chart review, patterns of care of patients surviving at least for ten years were analyzed Results: 57 patients (30 men, 27 women, aged 18 to 73, in median 36 years at diagnosis) with gliomas that were followed for a minimum of ten years (10 to 25y) were identified. First histological diagnosis was diffuse glioma in fifteen patients, oligo-astrocytoma in WHO grade II in nine, and WHO grade III in six, oligodendroglioma WHO grade II in six, WHO grade III in five, anaplastic astrocytoma in six and glioblastoma in 8 patients respectively. The patients underwent 1–7 surgical procedures. Fifty (80%) of patients were treated with radiotherapy, fourteen (28%) patients received salvage radiation therapy and five patients radiosurgery in relapse. All patients were treated with alkylating chemotherapy, 36 (63%)patients had at least one and up to seven drug therapy lines for relapsing gliomas (alkylating drugs n= 46, anti-angiogenic treatment n=16, Imatinib n=16, Thalidomide 50 mg n=14) Seven patients (12.3%) developed a secondary glioblastoma, fifteen patients (26%) progressed from WHO grade II to WHO grade III gliomas. However, fifty-two patients showed a KPS ≥70 during 75% of their respective survival time. Fifty-four (95%) had at least three years without any therapy and twenty -one (37%) still survive recurrence free after first line therapy. Thirty six patients (63%) remained professionally active after first line treatment and forty-one (72%) were still alive at the end of study. this highly selected cohort represents the right end of the Gaussian curve of outcomes for long term surviving glioma patients
p63-Dependent Dickkopf3 Expression Promotes Esophageal Cancer Cell Proliferation via CKAP4
Authors: Chihiro Kajiwara, Katsumi Fumoto, Hirokazu Kimura, Satoshi Nojima, Keita Asano, Kazuki Odagiri, Makoto Yamasaki, Hayato Hikita, Tetsuo Takehara, Yuichiro Doki, Eiichi Morii, Akira Kikuchi
Journal: Cancer Research (2018)

Dickkopf3 (DKK3) is a secretory protein that belongs to the DKK family, but exhibits structural divergence from other family members, and its corresponding receptors remain to be identified. Although DKK3 has been shown to have oncogenic functions in certain cancer types, the underlying mechanism by which DKK3 promotes tumorigenesis remains to be clarified. We show here that DKK3 stimulates esophageal cancer cell proliferation via cytoskeleton-associated protein 4 (CKAP4), which acts as a receptor for DKK3. DKK3 was expressed in approximately 50% of tumor lesions of esophageal squamous cell carcinoma (ESCC) cases; simultaneous expression of DKK3 and CKAP4 was associated with poor prognosis. Anti-CKAP4 antibody inhibited both binding of DKK3 to CKAP4 and xenograft tumor formation induced by ESCC cells. p63, a p53-related transcriptional factor frequently amplified in ESCC, bound to the upstream region of the DKK3 gene. Knockdown of p63 decreased DKK3 expression in ESCC cells, and reexpression of DKK3 partially rescued cell proliferation in p63-depleted ESCC cells. Expression of ΔNp63α and DKK3 increased the size of tumor-like esophageal organoids, and anti-CKAP4 antibody inhibited growth of esophageal organoids. Taken together, these results suggest that the DKK3-CKAP4 axis might serve as a novel molecular target for ESCC.Significance: In esophageal cancer, findings identify DKK3 as a poor prognostic indicator and demonstrate CKAP4 inhibition as an effective therapeutic strategy. Cancer Res; 78(21); 6107-20. ©2018 AACR.
MicroRNAs associated with small bowel neuroendocrine tumors and their metastases.
Authors: Justin Stebbing, Adam Enver Frampton, Helen C Miller, Anna Malczewska, Silvia Ottaviani, Euan A Stronach, Rashpal Flora, Daniel Kaemmerer, Gerd Schwach, Roswitha Pfragner, Omar Faiz, George Hanna, Leandro Castellano, Andreja Frilling
Journal: Journal of Clinical Oncology (2016)

11598 Background: Novel molecular analytes are needed in small bowel neuroendocrine tumors (SBNETs) to better determine disease aggressiveness and predict treatment response. In the present study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumor progression for use as potential biomarkers. Methods: Two independent miRNA profiling experiments were performed (n = 90), including primary SBNETs (n = 28), adjacent normal small bowel (NSB; n = 14), matched lymph-node (LN) metastases (n = 24), normal LNs (n = 7), normal liver (n = 2) and liver metastases (n = 15). We then evaluated potentially targeted genes by performing integrated computational analyses. Results: We discovered 39 miRNAs significantly deregulated in SBNETs compared to adjacent NSB. The most up-regulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly down-regulated in LN and liver metastases compared to primary tumors. Furthermore, we identified up-regulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Conclusions: Our study represents the largest global miRNA profiling of SBNETs using matched primary tumor and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms, and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.