tbuckley/cabot-search huggingface dataset:
A randomized phase II study of a novel antigen-presenting cell-targeted hCG-β vaccine (the CDX-1307 regimen) in muscle-invasive bladder cancer.
Authors: D. A. Bradley, M. Morse, T. Keler, J. A. Green, T. A. Davis, B. A. Inman
Journal: Journal of Clinical Oncology (2010)

TPS228 Background: hCG-β is frequently expressed and correlates with poor prognosis in a number of common epithelial cancers (Iles 2007). Patients (pts) with invasive bladder cancer and elevated hCG-β levels are much more likely to develop metastasis and die earlier (Iles 1996). We have developed a dendritic cell-targeted vaccine, CDX-1307, by genetically coupling hCG-β to a human monoclonal antibody targeting mannose receptors. CDX-1307 efficiently stimulates both MHC-I and II hCG-β-specific T-cell responses in vitro (Ramakrishna 2004/2007). CDX-1307 has completed a phase I study to define an immunogenic regimen and safety profile for phase II studies. The study design included administration in combination with GM-CSF (GM), the TLR3 agonist Poly-ICLC (PIC), and/or the TLR7/8 agonist resiquimod (R), in pts with advanced cancers known to frequently express hCG-β (Morse, iSBTc 2009). Treatment was well tolerated with no DLT. Significant hCG-β–specific cellular and humoral immune responses were detected in pts receiving the combination with all 3 adjuvants. Indications of clinical benefit (disease stabilization and/or reduction in tumor markers) were seen in a subset of patients. These data support further evaluation in newly diagnosed, resectable, hCG-β+ bladder cancer pts, who may have greatest potential for response to immunologic intervention. Methods: A phase II, multicenter trial randomizes (1:1) 60 chemo-naive pts with newly diagnosed, nonmetastatic, resectable, muscle invasive, hCG-β+ bladder cancer to (a) neoadjuvant gemcitabine/cisplatin chemotherapy (GC) or (b) CDX-1307 (2.5 mg) with GM, PIC and R (the CDX-1307 regimen), both with neoadjuvant GC and in the adjuvant setting to prolong immunity. The primary efficacy objective is to estimate the 2-year PFS (95% confidence interval extending ≤18.5% about the point estimate). Besides safety and immune response (during neoadjuvant GC and adjuvantly), additional antitumoral effect will be assessed including radiographic and pathologic tumor response to neoadjuvant vaccination, immune response at the tumor site and persistence of hCG-b expression. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celldex Therapeutics Celldex Therapeutics Celldex Therapeutics
Final report of phase I clinical, pharmacokinetic (PK), pharmacodynamic (PD) study of PF-00562271 targeting focal adhesion kinase (FAK) in patients (pts) with solid tumors.
Authors: N. C. Dhani, H. A. Burris, L. L. Siu, D. R. Camidge, L. R. Mileshkin, H. Xu, K. J. Pierce, N. R. Fahey, H. J. Fingert, S. M. Shreeve
Journal: Journal of Clinical Oncology (2010)

3028 Background: FAK is a non-receptor tyrosine kinase that transduces signaling from integrins and growth factor receptors to modulate cell invasion, migration, metastasis and survival. PF-00562271 is a potent ATP-competitive inhibitor of FAK that also inhibits the related protein proline-rich tyrosine kinase (Pyk2). Methods: Phase I dose escalation study of PF-00562271 given as continuous oral dosing in 21 day cycles. Endpoints include safety, PK including CYP3A interaction, PD by FDG-PET imaging, and response by RECIST. Results: 99 pts received doses ranging from 5 mg to 105 mg BID or 125 mg to 225 mg QD without food, or 100 mg to 150 mg BID with food. Demographics: M:F 56:43, median age 60 yrs (range 25–83). Primary sites: colorectal 21, pancreatic 15, head neck 13, lung 7, breast 5, prostate 5, sarcoma 5, ovary 3, others 25. 75% of pts had ≥ 3 prior treatments. Adverse events (AEs) possibly related to PF-00562271 in over 10% pts: nausea, vomiting, headache, fatigue, diarrhea, peripheral edema, dizziness, anorexia, hypotension, dysgeusia. AEs were typically CTCAE grades 1/2 and reversible. At maximum administered dose, 150 mg BID with food, dose limiting toxicities were headache, nausea, vomiting and facial swelling, all reversible. Weekly step-up dosing mitigated headache. PF-00562271 displays time- and dose-dependent non-linear PK, and inhibits CYP3A at the recommended phase II dose (RP2D). Doses over 30 mg/day led to average trough concentrations exceeding the minimal efficacious concentration (45 ng/mL) predicted pre- clinically, and to PD effects measured by PET with decreased (18–48%) SUV in lesions from 7 of 14 evaluable pts treated in the expansion cohort. In 20 response-evaluable patients with progressive colorectal carcinoma, 7 had SD, 2 over 24 weeks. One patient with adenoid cystic carcinoma had SD for 1 yr. Conclusions: PF-00562271 has a manageable safety profile. The RP2D was 125 mg BID with food, and continuous treatment was tolerable for 6–12 mos in some pts with sustained disease control. Clinical safety, PK, PD, and antitumor activity support further development. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Merck, Millenium Pfizer Bayer, Bristol-Myers Squibb, Novartis; Cyclacel; Roche; Merck; Pfizer; Bayer; Regeneron
The Epithelial‐to‐Mesenchymal Transition‐Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation
Authors: Isabele C. Iser, Mariana B. Pereira, Guido Lenz, Márcia R. Wink
Journal: Medicinal Research Reviews (2016)

Abstract Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer due to its highly invasive nature that impedes the surgical removal of all tumor cells, making relapse inevitable. However, the mechanisms used by glioma cells to invade the surrounding tissue are still unclear. In this context, epithelial‐to‐mesenchymal transition (EMT) has emerged as a key regulator of this invasive state and although the real relevance of this program in malignant glioma is still controversial, it has been strongly associated with GBM malignancy. EMT is a very complex process regulated by several families of transcriptional factors through many signaling pathways that form a network that allows cancer cells to acquire invasive properties and penetrate the neighboring stroma, resulting in the formation of an advantageous microenvironment for cancer progression and metastasis. In this systematic review, we focus on the molecular mechanisms of EMT including EMT‐factors, drug resistance, miRNA, and new therapeutic strategies. In addition, we address controversial questions about mesenchymal shift in GBMs with a bioinformatics analysis to show that in terms of epithelial and mesenchymal phenotype, the majority of GBMs samples analyzed have a profile more mesenchymal than epithelial. If induced, this phenotype can be shifted toward an even more mesenchymal phenotype in an EMT‐like process in glioma cells. A better understanding of the molecular regulation of the EMT during tumor spreading will help to provide potential therapeutic interventions to target this program when treating GBM.
Cancer Treatment and Research Under the Affordable Care Act
Authors: Charlie Schmidt
Journal: JNCI Journal of the National Cancer Institute (2016)

For decades, U.S. policymakers have tried to offer health insurance to the entire country.Although politicians made progress, through Medicare and Medicaid and most recently through the Affordable Care Act (ACA), the main goal continues to be elusive.The ACA implemented reforms designed to improve the accessibility, affordability, and quality of health care.Last April, health care experts convened for a panel discussion at the annual meeting of the American Association for Cancer Research of how the law affects cancer research and treatment.Their assessments were mixed.Although the ACA has improved access to cancer treatment, prevention services, and clinical trials, they agreed, it has done so unevenly, and many people still grapple with insufficient coverage."The ACA is taking us in a positive direction, said panelist Ernest Hawk, M.D., M.P.H., vice president for cancer preven-
Physical Activity (PA) and Physical Fitness (PF) in Lymphoma Patients before during and after Chemotherapy (PAFILP): A Prospective Observational Pilot-Study
Authors: P. Wolter, N. Vermaete, D. Dierickx, A. Janssens, P. Schöffski, G. Verhoef, R. Gosselink
Journal: Annals of Oncology (2012)
Epstein-Barr Viral Load in Post Renal Transplant Lymphoproliferative Disease: Elevated EBV DNA Levels at Diagnosis and Clearence after Rituximab Therapy.
Authors: Otávio C.G. Baiocchi, Otávia L. Caballero, André L. Vettore, Adriana Bulgarelli, Marcello F. Franco, Antonio C. Alves, José O.M. Pestana, Gisele W.B. Colleoni, José O. Bordin
Journal: Blood (2004)
R-FND Followed by Radioimmunotherapy for High-Risk Follicular Lymphoma
Authors: Peter McLaughlin, Sattva Neelapu, Michelle Fanale, Maria Rodriguez, Ana Ayala, Barbara Pro, F.B. Hagemeister, Anas Younes, Susan Neel, Nathan Fowler, Mark Hess, Larry W. Kwak
Journal: Blood (2008)
Phase I Clinical Trial of a Novel, Long-Acting Antithrombotic Drug: A Human Monoclonal Antibody Partially Inhibiting FVIII Activity.
Authors: Peter Verhamme, Steve Pakola, Marc Jacquemin, Jean Marie Saint-Remy, Jean Marie Stassen, Desire Collen, Rikke Riisbro, Thomas Jensen, Steven Glazer
Journal: Blood (2007)
Vascular Function and Uric Acid-Lowering in Stage 3 CKD
Authors: Diana I. Jalal, Emily Decker, Loni Perrenoud, Kristen L. Nowak, Nina Bispham, Tapan Mehta, Gerard Smits, Zhiying You, Douglas Seals, Michel Chonchol, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2016)

Hyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus. We measured vascular endothelial function by brachial artery flow-mediated dilation. No significant differences existed between groups at baseline; 61% of the participants had diabetes mellitus in both groups. The placebo and the allopurinol groups had baseline serum uric acid levels (SDs) of 8.7 (1.6) mg/dl and 8.3 (1.4) mg/dl, respectively, and baseline flow-mediated dilation values (SDs) of 6.0% (5.0%) and 4.8% (5.0%), respectively. Compared with placebo, allopurinol lowered serum uric acid significantly but did not improve endothelial function. In participants without diabetes mellitus, allopurinol associated with a trend toward improved flow-mediated dilation (+1.4% [3.9%] versus −0.7% [4.1%] with placebo), but this was not statistically significant ( P =0.26). Furthermore, we did not detect significant differences between groups in BP or serum levels of markers of inflammation and oxidative stress. In conclusion, allopurinol effectively and safely lowered serum uric acid levels in adults with stage 3 CKD and asymptomatic hyperuricemia but did not improve endothelial function in this sample of patients.
Targeted Therapy of B Cell Lymphoma with a Direct Inhibitor of the NF-κB Subunit c-Rel
Authors: Yusuke Shono, Andrea Z. Tuckett, Hsiou-Chi Liou, Samedy Ouk, Ekaterina Doubrovina, Mikhail Doubrovin, Enrico Derenzini, Mary I. Scallion, Jennifer J. Tsai, Odette M. Smith, Anas Younes, Richard J. O'Reilly, Marcel R.M. van den Brink, Johannes L. Zakrzewski
Journal: Blood (2014)
P2-090: Expression of cellular retinol binding protein-1 is associated with poor prognosis of stage I non-small cell lung cancer
Authors: Moo Suk Park, Yoon Soo Chang, Shin Myung Kang, Jae Ho Chung, Chang Hoon Hahn, Young Sam Kim, Joon Chang, Sung Kyu Kim, Se Kyu Kim
Journal: Journal of Thoracic Oncology (2007)
Results Of a Phase I Study Of Clofarabine and 2 Gy Total Body Irradiation (TBI) As a Non-Myeloablative Preparative Regimen For Hematopoietic Stem Cell Transplantation (HSCT) In High Risk Children With Hematologic Malignancies: A Multi-Center TACL Study
Authors: Sandeep Soni, Hisham Abdel-Azim, Elena Eckroth, Ccrc Ccrc, Jeanette van der Geissen, Ccrp Ccrp, Meghann Pine McManus, Eneida R. Nemecek, Richard Sposto, Blythe Thompson, Ann E Woolfrey, Haydar A Frangoul
Journal: Blood (2013)
P1-186: Usefulness of autofluorescence bronchoscopy for detecting bronchial premalignant lesions
Authors: Ju Ock Kim, Yeun Seun Lee, Yu-Jin Lee, Mi-Kyong Joung, Jeong Eun Lee, Hee Sun Park, Sung Soo Jung, Sun Young Kim
Journal: Journal of Thoracic Oncology (2007)
P1-279: The impact of bisphosphonates therapy in survival of lung cancer patients with bone metastasis
Authors: Kostas Zarogoulidis, Efimia Boutsikou, Theodoros Kontakiotis, Klio Eleftheriou, Ellada Eleftheriadou, Pavlos Zarogoulidis
Journal: Journal of Thoracic Oncology (2007)
P2-088: Analysis of the correlation between HLA phenotype and prognosis of non-small cell lung cancer patients in Japan
Authors: Yoshika Nagata, Koji Kuroda, Yoshiki Shigematsu, Tetsuro Baba, Takashi Fukuyama, Makiko Mizukami, Tetsuya So, Yoshinobu Ichiki, Masakazu Sugaya, Manabu Yasuda, Tomoko So, Mitsuhiro Takenoyama, Takeshi Hanagiri, Kenji Sugio, Akira Nagashima, Kosei Yasumoto
Journal: Journal of Thoracic Oncology (2007)
Prediction of disease-free nipple-areola complex in patients with extended DCIS by computer-assisted detection in breast MRI.
Authors: N. A. Boehm, I. Laemmer-Skarke, S. Paepke, V. R. Jacobs, M. Kiechle, E. J. Rummeny, A. Artmann
Journal: Journal of Clinical Oncology (2010)

e11103 Background: Important preoperative information to decide for skin-sparing mastectomy (SSM), a surgical option in selected patients with extended ductal carcinoma in situ (DCIS), is a disease-free nipple-areola complex (NAC). Breast MRI can be used to detect patients with disease in ductal tissue behind the NAC. The purpose of this study was to evaluate the impact of computer-assisted detection (CAD) with breast MRI as an additional diagnostic tool in the prediction of preoperative tumor extension with respect to the NAC. Methods: A routine case series of 28 patients with extended DCIS underwent 3D (Gd)-enhanced 1.5T MR mammography preoperatively using a T1-w FLASH pulse sequence. Two radiologists assessed the images in consensus reading for non-mass enhancement with segmental or ductal distribution. According to the enhancement distance towards the NAC 3 groups were defined: Group (1): NAC reached; (2): ≥4-6mm (intraoperative assessment of surgical margins required) and (3): ≥6mm (disease-free). Histopathological analysis served as standard of reference. Results: Contrast uptake was in 84% ductal and in 16% segmental. Without CAD n=2 false-positive cases for retroareolar tumor involvement were found in group (1), a marginal disease-free NAC of n=9/28 was in group (2); n=17/28 were categorized disease-free in group (3). With additional CAD n=20/28 were now classified (2) (+32.1%), n=1 re-classified from (1) to (2) and n=10 re-classified from (3) to (2). The CAD-supported findings confirmed a more accurate tumor extension and diameters in correlation with microscopic margins of resection. Conclusions: Preoperative CAD-assisted MRI enables detailed evaluation of the subnipple ductal tissue and prediction of disease-free NAC. This breast imaging modality is important for the preoperative decision making process between prophylactic mastectomy and SSM in patients with extended DCIS. For the oncological safety of SSM breast MRI with additional CAD can show NAC involvement, an important information for preoperative surgical planning in extended DCIS patients. No significant financial relationships to disclose.
Letter by Yang et al Regarding Article, “Use of Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation Who Have a History of Intracranial Hemorrhage”
Authors: Xinglong Yang, Ran An, Yanming Xu
Journal: Circulation (2016)

The research of Chao et al 1 based on the National Health Insurance Research Database shows that warfarin use may be beneficial for patients with atrial fibrillation (AF) with prior intracranial hemorrhage (ICH) who have a CHA 2 DS 2 -VASc score ≥6.It provides excellent evidence to guide the use of oral anticoagulants (OACs) in patients with AF with prior ICH.However, an unanswered question is how to decrease the risk of ischemic stroke in the AF patients with prior ICH who have a CHA 2 DS 2 -VASc score between 2 and 5.As recommended by the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline for the management of patients with AF, OACs should be applied to the patients with AF with a CHA 2 DS 2 -VASc score ≥2 to decrease the risk of ischemic stroke. 2 Thus, it is important to identify patients who may have a lower risk of ICH and have CHA 2 DS 2 -VASc scores between 2 and 5.We should not wait on the condition of these patients to deteriorate (eg, having an ischemic stroke) until they have a CHA 2 DS 2 -VASc score >6 and then initiate the anticoagulants.Several bleeding risk prediction schemes were proposed in patients with AF to predict the risk of bleeding.The HAS-BLED score was verified to be superior to the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), ORBIT (Outcomes Registry for Better Informed Treatment), and HEMORR 2 HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke) scores. 3In fact, in the research by Chao et al, because details on alcohol intake and the biochemical indexes of renal/liver function were not available in their database, it is hard to tell whether patients with a lower HAS-BLED score and a CHA 2 DS 2 -VASc score between 2 and 5 will benefit from OACs.It is of great significance to conduct research based on both the HAS-BLED and CHA 2 DS 2 -VASc scores to evaluate the risk and efficacy of OACs in these patients with AF with a lower bleeding risk but with a CHA 2 DS 2 -VASc score between 2 and 5. Besides, the non-vitamin K OACs have been verified to be more effective in decreasing stroke, ICH, and mortality than warfarin. 4More evidence should be gathered to validate the efficacy and safety of non-vitamin K OACs in treating patients with AF with prior ICH.Furthermore, the "local" strategy of left atrial appendage closure, which is noninferior to "systemic" anticoagulation with warfarin, may be an alternative for patients with a low CHA 2 DS 2 -VASc score and high bleeding risk. 5
Healing Responses After Bifurcation Stenting with the Dedicated TRYTON Side-Branch Stent in Combination with XIENCE V Stents: an Angiography and Optical Coherence Tomography Study
Authors: Christophe Dubois, Tom Adriaenssens, Giovanni Jacopo Ughi, Mark Coosemans, Bert Ferdinande, Peter Sinnaeve, Walter Desmet
Journal: Journal of the American College of Cardiology (2011)
P0911 : Characterization of clinical predictors of naturally occurring NS3/NS4A protease polymorphism in genotype 1 Hepatitis C virus infected patients
Authors: G. Lisboa Neto, C. Noble, J.R.R. Pinho, F.M. Malta, M.S. Gomes-Gouvêa, M.V. Alvarado-Mora, M.H. Silva, A.G. Leite, L.Z. Piccoli, F.J. Carrilho, M.C. Mendes-Correa
Journal: Journal of Hepatology (2015)
Retrospective clinico-pathologic review of gastric cancer in an inner city Canadian hospital.
Authors: C. W. Chung, C. Streutker, Y. J. Kim, T. P. Grantcharov, C. B. Brezden
Journal: Journal of Clinical Oncology (2010)

e14649 Background: Gastric cancer is the second leading cause of cancer death worldwide. Gastric carcinoma is divided histologically into intestinal and diffuse subtypes. The former is found among older patients, particularly in males from Asian descent; it is preferentially found in the gastric antrum. In contrast, the diffuse type is more frequently found in females, in the proximal stomach and is associated with a worse prognosis. The objective of this study is to delineate the clinical and pathologic pattern of gastric cancer in an inner city population. Methods: Searching within the pathology and clinical databases of St. Michael's Hospital from January 2000 to December 2009 yielded a total of 168 cases of gastric cancer. Pathologic (e.g., stage, pathologic subtype, etc) and clinical (e.g., age, sex, race, treatment, etc.) data were collected. Results: There was a higher incidence (68%) of the intestinal type with a total of 115 cases compared to 53 cases of the diffuse type. Patients with the intestinal type were older (mean age 70.1 vs 60.6) with 3:1 male to female ratio; 23.5% were of Southeast Asian background. The intestinal type was predominantly moderately (35.7%) to poorly (36.7%) differentiated and were found in the body or distal stomach (53.0%). The diffuse type had no gender preference and 22.6% were found in Asians. They were located in the body or distal stomach (62.3%). A greater proportion of patients with the diffuse type had stage 4 disease (32.1% vs. 23.5%) and shorter median survival (3 vs. 12 months). Conclusions: The inner city population in Toronto comprises of a larger immigrant population with a higher proportion of Asians, and this epidemiology data on the intestinal subtype is consistent with prior studies. However, it was surprising to find a high proportion of Asians among both subtypes; thus the diffuse type had no gender preference and was more commonly found in the distal rather than proximal stomach. Future studies are underway to determine the presence of HER2 overexpression and other oncogenes involved in molecular pathways of gastric cancer tumorigenesis for potential targeted therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche sanofi-aventis