tbuckley/cabot-search huggingface dataset:
MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients
Authors: S Harrach, C Schmidt-Lauber, T Pap, H Pavenstädt, E Schlatter, E Schmidt, W E Berdel, U Schulze, B Edemir, S Jeromin, T Haferlach, G Ciarimboli, J Bertrand
Journal: Blood Cancer Journal (2016)

Abstract Although imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), 25–30% patients do not respond or relapse after initial response. Imatinib uptake into targeted cells is crucial for its molecular response and clinical effectiveness. The organic cation transporter 1 (OCT1) has been proposed to be responsible for this process, but its relevance has been discussed controversially in recent times. Here we found that the multidrug and toxin extrusion protein 1 (MATE1) transports imatinib with a manifold higher affinity. MATE1 mainly mediates the cellular uptake of imatinib into targeted cells and thereby controls the intracellular effectiveness of imatinib. Importantly, MATE1 but not OCT1 expression is reduced in total bone marrow cells of imatinib-non-responding CML patients compared with imatinib-responding patients, indicating that MATE1 but not OCT1 determines the therapeutic success of imatinib. We thus propose that imatinib non-responders could be identified early before starting therapy by measuring MATE1 expression levels.
Update analysis: Thromboembolism in gastrointestinal tract cancer patients receiving chemotherapy.
Authors: Ayane Oba, Michio Nakamura, Taichi Murai, Chika Matsuda, Kazufumi Itaya, Yuta Koike, Ayana Endo, Yoko Tsukuda, Yuji Ono, Takahiko Kudo, Atsushi Nagasaka, Shuji Nishikawa
Journal: Journal of Clinical Oncology (2016)

e15156 Background: We previously reported that TE incidence (TEi) was 14 % among Japanese gastrointestinal tract cancer (GTC) patients (pts) receiving chemotherapy (CTx), and it was significantly higher in multiple primary (MP) pts compared with single primary (SP) pts (ASCO-GI 2016 Abst.541). We now update the results and report the associations between TEi and MP in a single organ (MPS) or MP in multiple organs (MPM), and the influence of TEi on overall survival (OS). Methods: All the patients received CTx for GTC in our institution from January 2008 to May 2015 were identified by reviewing electronic medical records. We extended the observation period and updated the TEi data. The associations between TEi and MPS or MPM were analyzed using Chi-square and Fisher’s exact tests. Kaplan-Meier analysis, Cox proportional hazards model, and log-rank test were used to assess the influence of TEi on OS. Results: Five hundred thirteen Japanese GTC pts were analyzed in this retrospective study. Patient characteristics were as follows; female/male 197/316, median age 69.3 (range 21.1 - 89.1), gastric cancer / colorectal cancer pts 213/30, MP/MPS/MPM/SP pts 52/25/29/461. Median follow-up period was 19 months (range 0 - 94). TEi was 32.0% (8/25) in MPS, 34.5% (10/29) in MPM, and 13.7 % (63/461) in SP, respectively. Compared with SP, TEi was significantly higher in MPS (p = 0.019) and MPM (p = 0.005), respectively. As for OS, there was no statistically significant difference between pts with and without TEi (31 v 33 months; HR, 0.78; p = 0.115). Conclusions: We found that MPS and MPM are associated with high TEi. Although several Western studies reported that TEi is associated with poor survival, we could not find the association in this retrospective analysis. Further prospective studies are required to assess the risk factors of TEi and its impact on OS in Asian cancer pts.
P1-250: Barriers for accrual to clinical trials in adult patients (pts) with non-small cell lung cancer
Authors: Maria Q. Baggstrom, Vamsidhar Velcheti, Mohsin Malik, Eve Gilstrap, Alesha Skelton, Kristen Lange, Debra Foersterling, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2007)
Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy
Authors: Stephen J. Blake, William C. Dougall, John J. Miles, Michele W.L. Teng, Mark J. Smyth
Journal: Clinical Cancer Research (2016)

Abstract The receptors CD96 and TIGIT are expressed on the surface of T and natural killer (NK) cells, and recent studies suggest both play important inhibitory roles in immune function. CD96 has been shown to modulate immune cell activity in mice, with Cd96−/− mice displaying hypersensitive NK-cell responses to immune challenge and significant tumor resistance. TIGIT overexpression has been shown to reduce NK-cell–mediated cytotoxicity. TIGIT is also upregulated on T cells during cancer and chronic viral infection, with expression associated with effector T-cell exhaustion and increased regulatory T-cell suppression. The counterbalance between the putative inhibitory CD96 and TIGIT receptors and the activating receptor, CD226, offers unique strategies for immuno-oncology drug development. Blocking CD96 or TIGIT with mAbs has been shown to improve tumor control in mice, in particular when used in combination with PD-1/PD-L1 blockade. These results have highlighted these pathways as promising new targets for immune modulation. This review will examine the rationale behind targeting CD96 and TIGIT, and discuss the potential approaches in translating these preclinical findings into novel clinical agents. Clin Cancer Res; 22(21); 5183–8. ©2016 AACR.
P3-126: Erlotinib monotherapy for stage IIIB/IV non–small cell lung cancer: A prospective study by the Korean Cancer Study Group(KCSG)
Authors: Byeong-Bae Park, Myung-Ju Ahn, Sang We Kim, Heung-Tae Kim, Jong Seog Lee, Jin Hyung Kang, Jae Yong Cho, Hong Suk Song, Chang Hak Sohn, Keunchil Park
Journal: Journal of Thoracic Oncology (2007)
230TiP Phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly for patients with advanced gastric cancer (HGCSG1404; SNOW study)
Authors: Y. Kawamoto, Y. Komatsu, S. Yuki, K. Sawada, T. Muranaka, H. Nakatsumi, H. Fukushima, A. Ishiguro, M. Dazai, K. Hatanaka, M. Nakamura, I. Iwanaga, M. Uebayashi, S. Sogabe, T. Miyagishima, K. Ono, N. Sakamoto, Y. Sakata
Journal: Annals of Oncology (2015)
P2-249: A Phase I Trial of ABT-751 and carboplatin in patients with previously treated non-small cell lung cancer
Authors: Konstantin H. Dragnev, James R. Rigas, Wendye M. Disalvo, Sara A. Simeone, Ian Williams, Terri Leahy, Anne E. Hagey, Gary B. Gordon, Ethan Dmitrovsky
Journal: Journal of Thoracic Oncology (2007)
An Evidence That Murine Marrow-Derived CXCR4+ SSEA-1+ Oct-4+ Very Small Embryonic-Like (VSEL) Stem Cells Are Pluripotent and Express Several Primordial Germ Cell (PGC) Markers - Hypotesis for Developmental Deposition of PGC in Various Organs.
Authors: Magda Kucia, Ewa Zuba-Surma, Ryan Reca, Janina Ratajczak, Mariusz Ratajczak
Journal: Blood (2006)
First-in-class phase I trial of a selective Akt inhibitor, MK2206 (MK), evaluating alternate day (QOD) and once weekly (QW) doses in advanced cancer patients (pts) with evidence of target modulation and antitumor activity.
Authors: T. A. Yap, A. Patnaik, I. Fearen, D. Olmos, K. Papadopoulos, N. Tunariu, D. Sullivan, L. Yan, J. S. De Bono, A. W. Tolcher
Journal: Journal of Clinical Oncology (2010)

3009 Background: Akt mediates cell proliferation, survival, and angiogenesis and is deregulated in cancer. MK is a potent, allosteric Akt1/2/3 inhibitor, with wide preclinical antitumor activity and a predicted long terminal elimination half-life (t1/2). Methods: MK was initially given QOD; due to the observed long t1/2, a QW schedule was also evaluated. Archival tumor and circulating nucleic acid were analyzed for PTEN and PIK3CA aberrations. Pharmacodynamic (PD) analyses of AKT and downstream target phosphorylation (p) were conducted in tumor (mandatory biopsies at MTD), platelet-rich plasma (PRP) and hair follicles (HF). Circulating endothelial cell (CEC) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were conducted. Results: 70 pts (41 M; median age 60 yr; ECOG PS 0/1: 23/47) received MK. 55 pts received MK at 30, 60, 75 or 90 mg QOD; G3/4 rash (n=6) and G3 mucositis (n=1) were dose-limiting at 75 and 90 mg QOD. 15 pts received MK at 90, 135, 200 or 300 mg QW; G3 rash (n=3) was dose-limiting at 300 mg QW. Common reversible drug-related toxicities included rash (48.6%), nausea (20.0%), fatigue (17.1%) and hyperglycemia (12.9%). Pharmacokinetics were dose proportional; median Tmax was 6-8 hrs; mean t1/2 was 55-78 hrs. 9 pts at 60 mg QOD had serial tumor biopsies demonstrating pAKT inhibition following MK (>90% in 4/9; >70% in 7/9). This correlated with sustained falls in pAKT in PRP (p<0.001) and pPRAS40 in HF (p<0.05). A PTEN-negative (immunohistochemistry) pancreatic cancer pt (60 mg QOD) had 23% RECIST tumor shrinkage and 60% CA19-9 decline, with PD effects in tumor and HF. Minor tumor regressions (melanoma, neuroendocrine cancer), CA125 declines, PSA stabilization, tumor necrosis, and decreased ascites were seen following MK administration. Moreover, 18 of 23 (78.3%) evaluable pts had post-MK CEC declines of up to −100% (median change −69%); DCE-MRI studies (n≥12) are ongoing. Conclusions: MK has a long t1/2 and can be administered either on a QOD or QW schedule that is well tolerated and can induce sustained AKT blockade. MK also has antitumor activity and may be antiangiogenic. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Chemotherapy Foundation, Merck Merck
Characterizing The CpG Methylation Of Epstein-Barr Virus DNA In The Plasma Of Patients With Hodgkin Lymphoma and HIV-Associated Burkitt Lymphoma
Authors: Jennifer A. Kanakry, Meir Shamay, Yvette L. Kasamon, Hailun Li, Randy D. Gascoyne, Leo I. Gordon, Ariela Noy, Ethel Cesarman, Jeannette Y Lee, Sandra J. Horning, Richard F. Ambinder
Journal: Blood (2013)
Disparities found in perception of symptoms between patients and oncology team
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2016)

Key Points The prevalence and importance of pain and fatigue in patients with cancer continue to be underestimated by oncology physicians and nurses. Clinicians need to assess symptoms of fatigue and pain carefully at each encounter. An increased awareness of patient‐reported outcomes and education for HCPs is needed to improve patients' QOL.
Long Term Follow-up and IWG-MRT Response Assessment for 50 Myelofibrosis (MF) Patients Treated with Thalidomide-Prednisone Based Regimens
Authors: Prakash Thapaliya, Ayalew Tefferi, Animesh Pardanani, David P. Steensma, John Camoriano, Wenting Wu, Susan Geyer, Ruben A. Mesa
Journal: Blood (2010)
P1-132: Phase II study of erlotinib plus bevacizumab in patients with previously treated malignant pleural mesothelioma
Authors: David M. Jackman, Hedy L. Kindler, Panagiotis Fidias, Ravi Salgia, Joan Lucca, Patricia Ostler, Linda K. Morse, Thomas J. Lynch, Bruce E. Johnson, Pasi A. Janne
Journal: Journal of Thoracic Oncology (2007)
Selective Internal Radiation Therapy (SIRT) as Conversion Therapy for Unresectable Primary Liver Malignancies
Authors: Alessandro Cucchetti, Alberta Cappelli, Giorgio Ercolani, Cristina Mosconi, Matteo Cescon, Rita Golfieri, Antonio Daniele Pinna
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Background: &lt;/i&gt;&lt;/b&gt;Many patients with primary liver cancers are not candidates for surgery, and systemic therapies are seldom effective. Selective internal radiation therapy (SIRT) has been shown to obtain partial and even complete response in unresectable primary tumors. As a “side effect”, SIRT can induce contra-lateral liver hypertrophy. Tumor response to SIRT can be sufficient to allow disengagement from normal vital structures whose involvement is the cause of the initial unresectability. The contra-lateral hypertrophy can thereby increase the future liver remnant (FLR) volume to over the safe threshold so that extended hepatectomy can be performed. &lt;b&gt;&lt;i&gt;Summary: &lt;/i&gt;&lt;/b&gt;A review of the available literature was performed to assess the tumor response and liver hypertrophy that can be expected after SIRT, in order to delineate whether SIRTcan play a role in conversion therapy for resectability of primary liver malignancies. &lt;b&gt;&lt;i&gt;Key Message: &lt;/i&gt;&lt;/b&gt;Available data suggest that SIRT in unresectable hepatocellular and cholangiocellular carcinomas can provide a considerable down-sizing of the tumors to possibly allow resection. Hypertrophy of the contra-lateral lobe represents a favorable collateral effect that can help in achieving safer subsequent major hepatectomy. In patients whose FLR volume represents the only surgical concern, portal vein embolization remains the treatment of choice.
Outcomes of Haploidenitical Stem Cell Transplants for De Novo Acute Myeloid Leukemia, Myelodysplastic Syndrome and Acute Myeloid Leukemia Arising from MDS: The MD Anderson Experience
Authors: Reshma Ramlal, Sameh Gaballa, Julianne Chen, Gabriela Rondon, Betul Oran, Sairah Ahmed, Qaiser Bashir, Katayoun Rezvani, David Marin, Amin M. Alousi, Partow Kebriaei, Muzaffar Qazilbash, Chitra Hosing, Uday R. Popat, Elizabeth J Shpall, Richard Champlin, Stefan O. Ciurea
Journal: Blood (2015)
Whole Exome Sequencing in a Large Pedigree with DCM Identifies a Novel Mutation in RBM20
Authors: Tomas Robyns, Johan Van Cleemput, Rik Willems, Shalini Jhangiani, Donna Muzny, Richard Gibbs, James R Lupski, Jeroen Breckpot, Koenraad Devriendt, Gert Matthijs, Anniek Corveleyn
Journal: Circulation (2015)
Pharmacoeconomic analysis of Capecitabine in the adjuvant setting. Results from the X-ACT trial comparing capecitabine with 5-FU/LV in patients with Dukes' C colon cancer
Authors: Douillard J-Y., C Twelves, J McKendrick, O Bertetto, F Coxon, E Diaz-Rubio, P Dufour, T Maughan, W Scheithauer, H Burris
Journal: Annals of Oncology (2004)
Pediatric gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Guideline Executive summary
Authors: Andrea Tringali, Mike Thomson, Jean-Marc Dumonceau, Marta Tavares, Merit Tabbers, Raoul Furlano, Manon Spaander, Cesare Hassan, Christos Tzvinikos, Hanneke Ijsselstijn, Jérôme Viala, Luigi Dall’Oglio, Marc Benninga, Rok Orel, Yvan Vandenplas, Radan Keil, Claudio Romano, Eva Brownstone, Štěpán Hlava, Patrick Gerner, Werner Dolak, Rosario Landi, Wolf Huber, Simon Everett, Andreas Vecsei, Lars Aabakken, Jorge Amil-Dias, Alessandro Zambelli
Journal: Endoscopy (2016)

This Executive summary of the Guideline on pediatric gastrointestinal endoscopy from the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) refers to infants, children, and adolescents aged 0 – 18 years. The areas covered include: indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; endoscopic management of corrosive ingestion and stricture/stenosis; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease (IBD) have been dealt with in other Guidelines and are therefore not mentioned in this Guideline. Training and ongoing skill maintenance will be addressed in an imminent sister publication.
Gastric Anisakiasis
Authors: Uichiro Fuchizaki, Masahi Nishikawa
Journal: New England Journal of Medicine (2016)

A previously healthy 36-year-old woman presented with a 2-day history of severe chest pain and epigastric pain associated with nausea and vomiting. The patient reported that she had consumed uncooked salmon approximately 2 hours before the chest pain developed.
PPARγ mediated PTEN transcription via rosiglitazone stimulation
Authors: Robert A. Johnson, Brijesh Patel, Adrian Canutescu, Josephine Hoh, Roland Dunbrack, Kathleen Scotto
Journal: Cancer Research (2005)

4620  Germline mutations in the PTEN tumor suppressor gene predisposes to heritable breast cancer. In addition, somatic alterations of PTEN have also been observed in many human malignancies, including breast cancer. Its protein product, PTEN, is a dual specificity phosphatase, with both lipid and protein phosphatase activities, that induces apoptosis and/or G1 cell cycle arrest. Moreover, PTEN is a constitutively active protein regulated by its transcription and degradation. Recently, a putative binding domain for the transcriptional factor PPARγ has been identified within the PTEN promoter, but its biological significance has yet to be determined. We therefore examined the ability of the therapeutic PPARγ agonists, Rosiglitazone (Rosi), Pioglitazone, Ciglitazone and Troglitazone, to induce PTEN expression in vivo. We demonstrated that only Rosi has the ability to induce increased PTEN levels in both a dose- and time -dependent manner. PTEN levels increased at 48 hours after stimulation and resulted in a maximal 2.5-fold increase at 30 μM. In contrast, Pioglitazone, Ciglitazone and Troglitazone had no effect on PTEN levels, even at varied concentrations and time. Concomitant with PTEN expression, exposure to Rosi resulted in a decrease in Akt phosphorylation. Additionally, Rosi stimulation resulted in a 2.8-fold increase in PTEN mRNA levels. Stimulation with Cmpd-66, an inactive form of Rosi, resulted in minimal induction of PTEN protein (1.2-fold) and mRNA (1.1-fold). These data indicate that the increase in PTEN observed by Rosi stimulation is due to PPARγ-mediated transcription. To further confirm these data, MCF-7 cells were co-transfected with a plasmid containing a PPARγ response element (PPRE) tagged with luciferase, with either wild-type PPARγ, dominant negative PPARγ or empty vector. Cells were then stimulated with either Rosi or Cmpd-66. Rosi stimulation resulted in a ∼900-fold induction of luciferase activity in cells transfected with wildtype PPARγ, compared to empty vector. In contrast, there was little activity in stimulated cells transfected with a dominant negative PPARγ. Stimulation with Cmpd-66 resulted in minimal luciferase activity. Taken together, our data indicates that PPARγ can regulate PTEN at the transcriptional level. Furthermore, since PTEN is constitutively active, it may be worthwhile to examine the effects of Rosi as a mechanism to increase PTEN protein expression for both the treatment and prevention of cancer.
Can ultrasound imaging predict the development of Achilles and patellar tendinopathy? A systematic review and meta-analysis
Authors: Seán McAuliffe, Karen McCreesh, Fiona Culloty, Helen Purtill, Kieran O'Sullivan
Journal: British Journal of Sports Medicine (2016)

Ultrasound (US) imaging is commonly used to visualise tendon structure. It is not clear whether the presence of structural abnormalities in asymptomatic tendons predicts the development of future tendon symptoms in the Achilles or patellar tendon.To perform a systematic review and meta-analysis investigating the ability of US imaging to predict future symptoms of patellar or Achilles tendinopathy.Prospective studies that performed US imaging of Achilles OR patellar tendon structure among asymptomatic patients at baseline and a clinical measure of pain and/or function at follow-up were included. Study quality was assessed using the Critical Appraisal Skills Programme tool by two independent reviewers, and predictive ability of US was assessed using meta-analyses.The majority of participants in the review were from sporting populations. Meta-analysis revealed that tendon abnormalities on US are associated with future symptoms of both patellar and Achilles tendinopathy (RR=4.97, 95% CI 3.20 to 7.73). Subgroup analysis indicated that tendon abnormalities at baseline were associated with an increased risk of both Achilles (RR=7.33, 95% CI 2.95 to 18.24) and patellar (RR=4.35, 95% CI 2.62 to 7.23) tendinopathy.This systematic review and meta-analysis indicates that tendon abnormalities visualised using US in asymptomatic tendons are predictive of future tendinopathy and are associated with at least a fourfold increased risk.Identification of at-risk athletes using screening tools such as US may allow preventative programmes to be implemented. However, it is clear that other factors beyond tissue structure are involved in the development of lower limb tendinopathy.
P3-157: Correlation of EGFR mutation status between primary tumor and metastases in NSCLC
Authors: Ar Kalikali, A Voutsina, A Koutsopoulos, A Pallis, M Trypaki, J Souglakos, E Stathopoulos, D Mavroudis, V Georgoulias
Journal: Journal of Thoracic Oncology (2007)
Association Between User-Generated Commuting Data and Population-Representative Active Commuting Surveillance Data — Four Cities, 2014–2015
Authors: Geoffrey P. Whitfield, Emily N. Ussery, Brian Riordan, Arthur M Wendel
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Creating environments that support all types of physical activity, including active transportation, is a public health priority (1). Public health surveillance that identifies the locations where community members walk and bicycle (i.e., engage in active transportation) can inform such efforts. Traditional population-representative active transportation surveillance incurs a considerable time lag between data collection and dissemination, and often lacks geographic specificity (2). Conversely, user-generated active transportation data from Global Positioning System (GPS)-based activity tracking devices and mobile applications can provide near real-time information, but might be subject to self-selection bias among users. CDC analyzed the association between GPS-based commuting data from a company that allows tracking of activity with a mobile application (Strava, Inc., San Francisco, California) and population-representative commuting data from the U.S. Census Bureau's American Community Survey (ACS) (3) for four U.S. cities. The level of analysis was the Census block group. The number of GPS-tracked commuters in Strava was associated with the number of ACS active commuters (Spearman's rho = 0.60), suggesting block groups were ranked similarly based on these distinct but related measurements. The correlation was higher in high population density areas. User-generated active transportation data might complement traditional surveillance systems by providing near real-time, location-specific information on where active transportation occurs.
G-quadruplex structures mark human regulatory chromatin
Authors: Robert Hänsel-Hertsch, Dario Beraldi, Stefanie V Lensing, Giovanni Marsico, Katherine Zyner, Aled Parry, Marco Di Antonio, Jeremy Pike, Hiroshi Kimura, Masashi Narita, David Tannahill, Shankar Balasubramanian
Journal: Nature Genetics (2016)