tbuckley/cabot-search huggingface dataset:
Genomic analysis of circulating tumor cells to evaluate predictive biomarkers.
Authors: D. C. Danila, A. Anand, J. Yao, M. Gierszewska, M. Kramer, M. Fleisher, C. L. Sawyers, W. R. McCombie, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

38 Background: To estimate the association between molecular biomarkers detected in circulating tumor cells (CTC) and tumor sensitivity to treatment, robust assays are needed before qualification in prospective clinical trials. Methods: To address the limitations of the current FDA cleared technology, we focused on improving our ability to isolate more purified CTC populations based on fluorescence-activated cell sorting (FACS) to capture EpCAM+, CD45 − , DAPI − cells from patients with castration-resistant prostate cancer (CRPC). Androgen receptor (AR) and genes frequently mutated in CRPC have been selected from the integrative genomic profiling at MSK. We optimized the RainDance microfluidic PCR followed by targeted sequencing in low number of cancer cells, before proceeding to clinical samples. Results: On blood samples from124 patients with progressive CRPC, FACS method isolates an average 100-fold more EpCAM+ events compared to the current FDA cleared CellSearch assay. By FACS, &gt;10 or &gt;50 events were isolated in 88% or 58% of patients, compared to 32% or 10% of patients by CellSearch, respectively. FACS isolated cells express prostate-specific mRNAs (PSA, AR, TMPRSS2-ERG), as detected by an analytically validated multiplex RT-PCR, indicating that these EpCAM+ events are bona fide CTC. For genomic profiling, sufficient high quality DNA was obtained from as little as 50 CTC, with a recovery rate of 89% from FACS sorted samples and adequate sequencing coverage, and 1:4 detection threshold in a heterogeneous cell population. Selected missense mutations in AR, PIK3CA and TP53 found in CTC but not in WBC from same patient are further analyzed. Conclusions: Molecular alterations in CTC can potentially serve as predictive markers of sensitivity and clinical outcomes as surrogate tissue in clinical practice. We established standard operating procedures for specimen processing, and confirmed the sequencing coverage and polymorphism detection thresholds in a heterogeneous cell population. In the context of available samples collected from patients enrolled on AR-targeted therapies, we will generate data to qualify CTC as biomarkers under the Oncology Biomarker Qualification Initiative. [Table: see text]
Imatinib Mesylate Reduces Plexiform Neurofibromas by Targeting the Hematopoietic Microenvironment.
Authors: Feng-Chun Yang, David Ingram, Shi Chen, Kent Robertson, Xiohong Li, Jin Yuan, Scott Knoll, Whitney Horn, Gary Hutchins, L. Parada, David Wade Clapp
Journal: Blood (2007)
Prognostic Significance and Target Potential of Axl in Acute Myeloid Leukemia
Authors: Alexander Schultze, Isabel Ben-Batalla, Michael Heuser, Kristoffer Weber, Robert Erdmann, Sacha Holland, Stefanie Sawall, Helena Fritz, Marc Tjwa, Thomas Schmidt, Walter Fiedler, Boris Fehse, Bjorn Dahlback, Klaus Pantel, Jürgen Krauter, Arnold Ganser, Carsten Bokemeyer, Sonja Loges
Journal: Blood (2011)
A Phase II Study of the Safety and Efficacy of a Novel Oral fXa Inhibitor (LY517717) for the Prevention of Venous Thromboembolism Following TKR or THR.
Authors: Giancarlo Agnelli, Sylvia K. Haas, Kathryn A. Krueger, Alun W. Bedding, John T. Brandt
Journal: Blood (2005)
The incidence and preoperative detection of nodal metastases in resected pancreatic neuroendocrine tumors.
Authors: James M. Lindberg, Dustin M Walters, Edward B Stelow, Reid B Adams, Todd W. Bauer
Journal: Journal of Clinical Oncology (2012)

178 Background: Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of rare malignancies in which surgical resection remains the only curative therapy. The optimal surgical approach (enucleation vs. pancreatectomy) is controversial. This study aims to determine the 1) incidence, 2) predictors, and 3) preoperative detection of lymph node (LN) metastases in resected pNETs to help guide surgical management. Methods: A retrospective review of prospectively collected data was performed for all patients with pancreatic neuroendocrine tumors who underwent surgical resection at the University of Virginia between 1991 and 2010. The electronic medical record, radiology reports and pathology reports were used to identify patient demographics, surgical procedure, tumor functional status, type, size, location, and LN status. Results: In all, 76 patients were identified. Most tumors were non-functioning (71%) with insulinomas (13%) and gastrinomas (5%) representing the largest groups of functioning pNETs. Nineteen tumors (25%) had LN metastases at the time of resection. LN-positive tumors were significantly larger than LN-negative tumors (4.0 ± 0.4 cm vs. 2.8 ± 0.2 cm, p=0.01). Five (11%) of 46 tumors ≤ 3 cm and one (14%) of 7 tumors ≤ 1 cm had LN metastases. There were no significant relationships between LN status and either tumor type or location (head/uncinate vs. body/tail). Of patients with LN-positive tumors, preoperative CT or MRI detected the LN metastases in only 19%. Conclusions: Twenty-five percent of pNETs are associated with LN metastasis. The only predictor of LN metastasis was tumor size, but even smaller tumors were associated with LN metastasis. The sensitivity of preoperative CT and MRI is quite poor in detecting LN metastasis. Thus, formal resection with lymphadenectomy should be considered the standard of care for pNETs. [Table: see text]
A Novel Synthetic Lethal Approach Targeting SIRT6 in Acute Myeloid Leukemia
Authors: Michele Cea, Antonia Cagnetta, Davide Lovera, Raffaella Grasso, Nicoletta Colombo, Micaela Bergamaschi, Sara Aquino, Fabio Guolo, Paola Minetto, Filippo Ballerini, Letizia Canepa, Sophia Adamia, Alessio Nencioni, Ivana Pierri, Marino Clavio, Maurizio Miglino, Marco Gobbi, Roberto Massimo Lemoli
Journal: Blood (2015)
Effect of CPAP on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial.
Authors: Martínez-Cerón E, Barquiel B, Bezos Am, Casitas R, Galera R, García-Benito C, Hernanz A, Alonso-Fernández A, Garcia-Rio F
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Abstract Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in diabetic patients. To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels ≥ 6.5% were randomized to CPAP (n=26) or no CPAP (control; n=24), while their usual medication for diabetes remained unchanged. HbA1c levels, scores of the Homeostasis Model Assessment (HOMA) and Qualitative Insulin Sensitivity Check Index (QUICKI), systemic biomarkers and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6 and adiponectin also improved in the CPAP group compared with the control group after 6 months. In the patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related with 6-month change in HbA1c levels (r2=0.510, P=0.002). Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months, when compared to a control group, resulted in improved glycemic control and insulin resistance. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01801150.
A phase I study of salvage photodynamic therapy (PDT) using talaporfin sodium and a diode laser for local failure of esophageal carcinoma (EC) after chemoradiotheapy (CRT).
Authors: Kengo Nagai, Manabu Muto, Yasumasa Ezoe, Takashi Yamamoto, Miyuki Niimi, Kenichi Yoshimura, Yusuke Yoda, Tomonori Yano, Koji Higashino, Hiroyasu Iishi, Yoshinobu Yamamoto, Hogara Nishizaki
Journal: Journal of Clinical Oncology (2012)

123 Background: We recently reported that porfimer sodium (Photofrin)-based PDT was a less invasive, curative treatment option for carefully selected patients with locally residual EC after CRT (Endoscopy 2011:43:657-63). However, porfimer sodium-based PDT has some problems (long light shielding and skin phototoxicities). Conversely, talaporfin sodium (Laserphyrin)-based PDT using a diode laser system can overcome these problems. Therefore, we conducted a phase I study to establish the recommended dose of laser irradiation and to evaluate safety of talaporfin sodium-based PDT as a salvage treatment after CRT. (UMIN000003970). Methods: We recruited patients with residual or recurrent EC at primary site and who were treated with more than 50 Gy of (chemo)radiotherapy. To determine the dose limiting toxicity (DLT) according to the energy of the diode laser, dose escalation was set at three energy levels (50,75 and 100J/cm 2 ). The DLT was defined as follows; 1) severe pain, 2) ≥ grade 2 CTC-AE fever, 3) esophageal fistulae or stenosis, 4) ≥ grade 3 CTC-AE hemorrhage, and 5) ≥ grade 4 CTC-AE non-hematologic toxicity. Results: Between Oct. 2010 and May 2011, a total of 9 patients (9 men, median age of 72 y-o) were recruited and were treated using up to the third energy level in groups of three individuals. The initial T stage was T1/T2/T3(4/2/3) and recurrent T stage was T1/T2(6/3). None of the patients experienced DLT at all energy levels. A complete response was achieved in 5 of 9 patients (56%). Conclusions: Based on the results of our phase I study, we concluded that irradiation at 100J/cm 2 appeared to be a recommended dose for talaporfin sodium-based PDT as a salvage treatment for locally residual esophageal carcinoma after CRT. We are currently running a phase II part of the study to investigate efficacy of salvage talaporfin sodium-based PDT.
Rituximab Maintenance Therapy in CD20+ B-Cell Non-Hodgkin’s Lymphoma.
Authors: Sanja A. Trajkova, Lidija A. Cevreska, Irina Z. Panovska-Stavridis, Aleksandra Pivkova, Borce Georgievski, Oliver B. Karanfilski, Aleksandar T. Stojanovic
Journal: Blood (2005)
Statin Use and Prognosis in Patients with Follicular Lymphoma (FL) and Diffuse Large B Cell Lymphoma (DLBCL)
Authors: Grzegorz S. Nowakowski, Matthew J. Maurer, Thomas M. Habermann, Stephen M. Ansell, William R. Macon, Kay M. Ristow, Cristine Allmer, Susan L. Slager, Thomas E. Witzig, James R Cerhan
Journal: Blood (2008)
The Pre-Transplant Mantle Cell Lymphoma International Prognostic Index Predicts Overall and Progression-Free Survival Following High-Dose Therapy and Autologus Stem Cell Transplant for Mantle Cell Lymphoma
Authors: Leslie A Thompson, Katherine A Guthrie, Lihua Elizabeth Budde, Brian G. Till, Oliver W. Press, Thomas Chauncey, John M. Pagel, Stephen H. Petersdorf, William I Bensinger, Leona Holmberg, Andrei R. Shustov, Damian J. Green, David G. Maloney, Ajay K. Gopal
Journal: Blood (2011)
Phase II Study of VNP40101M (Cloretazine®) in Elderly Patients with De Novo Poor Risk Acute Myelogenous Leukemia (AML).
Authors: Gary J. Schiller, Daniel J. DeAngelo, Arnaud Pigneux, Norbert Vey, Jonathan Kell, Scott R. Solomon, Robert K. Stuart, Bonny L. Johnson, Susan O’Brien, Francis J. Giles
Journal: Blood (2007)
Preliminary results from a comparative effectiveness study of breast cancer survivorship care: A University of California (UC) ATHENA Breast Health Network project.
Authors: E. E. Hahn, P. A. Ganz, M. E. Melisko, J. P. Pierce, M. M. Von Friederichs-Fitzwater, K. Lane, R. A. Hiatt
Journal: Journal of Clinical Oncology (2011)

212 Background: The ATHENA Breast Health Network collaboration is a large scale, UC system-wide project initiated with the intent to drive innovation in breast cancer prevention, screening and treatment. An IRB approved research protocol was developed to examine survivorship care across Network sites, which includes key informant interviews at each site and patient/survivor surveys. This abstract presents preliminary analyses from the key informant interviews. Methods: Investigators at each site conducted semi-structured interviews with oncology specialists and primary care providers (PCPs). Interviews used case study examples and open and closed-ended questions on the delivery of post-treatment breast cancer care. Informant responses were manually recorded by the interviewer, compiled in a database, then coded and analyzed using NVIVO9 software. Results: There were 39 key informants across five participating UC sites: 14 medical oncologists, 7 radiation oncologists, 11 surgeons, 3 oncology nurses, and 4 PCPs. Care coordination is a major unprompted theme identified in the interviews. 85% of all participants reported using shared care coordination between PCP and oncology for post-treatment follow-up. 49% report the need for greater care coordination in general, and 28% report the need for greater care coordination within oncology, particularly to help avoid duplication of follow-up care and services. The responses demonstrate wide variability among provider types and institutions (Table). Additional analyses from this study will be updated in our presentation. Conclusions: These preliminary results identify the need for focus on care coordination during the post-treatment phase of breast cancer care within the UC system. [Table: see text]
Molecular profiling of metastatic breast cancer in body cavity fluids.
Authors: R. Ashfaq, E. Fong
Journal: Journal of Clinical Oncology (2011)

61 Background: The diagnosis of malignant effusion signifies disease progression and is associated with a worse prognosis regardless of tumor origin. The cancer cells in fluids have unique genotypic and phenotypic characteristics that are uniquely different from the primary tumor. Therapeutic guidance should be based on the evaluation of tumor cells in effusions. This study reports the feasibility of molecular profiling for breast cancer metastasis in pleural and peritoneal fluids. Methods: A computer search was conducted to retrospectively identify malignant fluid samples or cell blocks for molecular profiling. A cell-block was either prepared or available for testing for all samples. An H&amp;E slide was prepared from the cell- block and reviewed by a pathologist before any testing. Malignant cell percentages were determined for purpose of DNA microarray analysis and Sequencing. Appropriate clusters and malignant cells were marked for FISH. The results were reviewed and data compiled to calculate the yield of various molecular predictive tests. Results: We studied 172 fluid of which 28 were metastatic breast cancer (16.2%). Of the 28 breast cases, 10 IHC biomarkers could be performed in 20 (71.4 %), 1-9 in 1 (3.5 %), while 7 (25%) were insufficient. DNA microarray analysis was done in 10 (35.7%), FISH for EGFR 7 (25%), Her2 Neu FISH 11(39%), cMYC FISH 5 (17.8%) and TOPO2a by FISH 3 (10.7%). Combined IHC/FISH/MA data was available in 10, IHC and FISH data in 11 and IHC and MA data in 10 cases. Combined results of predictive markers provided information on therapeutic guidance in 21 of 28 cases. Conclusion: Molecular profiling of malignant fluids offers additional opportunities for testing those patients where other tissue samples such as needle core biopsy or resection samples are not available. Molecular profiling provides insight into the molecular characteristics of malignant cells in body cavity fluids and associated expression of unique therapeutic targets.
Imer Blocks Phosphorylation of the β3 Integrin, Decreasing Platelet Activation Responses and Protecting Mice From Arterial Thrombosis
Authors: Brian R. Branchford, Susan Sather, Gary Brodsky, Tara C White-Adams, Deborah DeRyckere, Keith B Neeves, Katina M Wilson, Steven R. Lentz, Douglas K. Graham, Jorge A Di Paola
Journal: Blood (2011)
A phase III clinical trial of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus
Authors: H. Yang, J. Fu, M. Liu, Y. Chen, Z. Chen, C. Zhu, H. Yang, W. Fang, J. Wang, Z. Yu, Q. Pang, W. Mao, X. Zheng, J. Xiang, H. Yang, Y. Han
Journal: Annals of Oncology (2016)
Management and outcomes for primary cardiac sarcomas (PCS): A retrospective study of the French Sarcoma Group (FSG).
Authors: N. Isambert, I. L. Ray-Coquard, B. Bui Nguyen, M. Rios, P. Kerbrat, A. Blouet, L. Chaigneau, F. Duffaud, S. Piperno-Neumann, J. Kurtz, J. Thariat, N. Girard, O. Collard, E. Bompas, N. Penel, J. Bay, C. Guillemet, F. Collin, J. Blay, A. Le Cesne
Journal: Journal of Clinical Oncology (2011)

10093 Background: PCS are very rare tumors with poor prognosis. The current study aimed to evaluate clinico-pathological characteristics, treatment and survival in a cohort of patients (pts) referred to the FSG Network. Methods: From June 1977 to January 2010, 123 pts with PCS were identified. Medical records and clinicopathologic data were collected. Results: There were 54 men (44%) and 69 females (56%) with a median age of 47 years (range 3-82). Median time between first symptoms and diagnosis was 1 months (mo) (range 0-53). The most frequent revealing clinical signs were dyspnea (41%), thoracic pain (22%), heart failure (13%) and pericarditis (5%). The median tumor size was 60 mm (range 8-100). The pathological diagnoses included poorly differentiated sarcoma (S) (n=45), angioS (n=40), leiomyoS (n=16), synovialoS (n=7), rhabdomyoS (n=6), Ewing S (n=4), lipoS (n=3) and chondroS (n=2). At diagnosis, 99 pts (80%) had a localized disease and 24 pts had metastases in one site (n=14) or in multiple sites (n=10). The most frequent metastatic sites were lung (n=9), liver (n=7), bone (n=7), brain (n=4). Tumors were mainly located in the atrial cavities (right atrium n=47; left atrium n=44). Other localization included right ventricle (n= 6), left ventricle (n=9) and pericardium (n=3). In 11 cases, the tumor was multifocal. A surgical approach was considered in the majority of pts with localized disease. Resection alone or in combination with doxorubicin-containing chemotherapy (CT) or with a radiotherapy and CT regimen was undertaken in 18, 43 and 16 pts respectively. Among these pts, surgical approaches included wide excision (n=10), marginal excision (n=22), intralesional excision (n=31) and heart transplant (n=5). The median follow up was 13 mo (0-153), the median overall survival (OS) for those who underwent R0 excision was 39 mo (range 8-96) versus 17 mo (range 0-153) for those with R1 or R2 resection. The median OS of pts with initial metastatic disease treated with doxorubicin-containing CT was 11 mo (range 2-95). Conclusions: Complete surgical excision is associated with long-term survival. However, the poor prognosis of this malignancy requires extensive multidisciplinary research studies.
Outcomes of multivisceral resection of gastric gastrointestinal stromal tumors.
Authors: Sabha Ganai, Mitchell Posner, Vivek N. Prachand, John C. Alverdy, Eugene A. Choi, Irving Waxman, Marco G. Patti, Kevin K. Roggin
Journal: Journal of Clinical Oncology (2012)

10090 Background: Despite the recent introduction of imatinib and laparoendoscopic techniques to the management of gastric gastrointestinal stromal tumors (GISTs), outcomes remain uncertain in the setting of multivisceral involvement. Methods: We conducted a retrospective review of 73 consecutive patients who underwent resection of gastric GISTs from October 2002 through December 2011. Median follow-up was 22 months (interquartile range [IQR] 6-37). Results: Patients were 51% female, with a mean age of 65 ± 12 years and BMI of 30 ± 8 kg/m 2 . Patients undergoing multivisceral resection (n=14) had a longer interval from diagnosis to surgery (7.3 [IQR 1.9 – 15.0] vs. 1.3 [IQR 0.7-4.2] months, p&lt;0.01), greater use of neoadjuvant imatinib (64% vs. 3%, p&lt;0.0001), and greater preoperative tumor size (12 ± 8 vs. 4 ± 3 cm, p&lt;0.0001) in comparison to gastric-only resections (n=59). Patients were less likely to be managed laparoscopically (7% vs. 71%, p&lt;0.0001), had a longer operative time (310 ± 117 vs. 145 ± 62 min, p&lt;0.0001), and were less likely to be R0 (71% vs. 98%, p&lt;0.001). While patients undergoing multivisceral resection were more likely to have a pathological complete response to therapy (29% vs. 0, p&lt;0.001), they were also more likely to have metastatic disease present (29% vs. 0, p&lt;0.001). Hospital length of stay was greater (median 8 [IQR 6-9] vs. 3 [IQR 2-6] days, p&lt;0.0001). There were no significant differences in grade or mitotic index between groups. There was greater use of adjuvant imatinib (64% vs. 25%, p&lt;0.05). Overall survival was less in patients undergoing multivisceral resection (64% vs. 87% at 3 years, p&lt;0.05), as was disease-free survival (52% vs. 71% at 3 years, p&lt;0.05). Median overall and disease-free survival were 43 and 22 months after multivisceral resection for gastric GISTs. Controlling for tumor size, grade, resection status, and the use of neoadjuvant imatinib, multivisceral resection and use of adjuvant imatinib were both independent predictors of disease-free survival (p&lt;0.05). Conclusions: Multivisceral involvement is associated with tumors of greater size and, despite an increased use of neoadjuvant imatinib, it is associated with poor outcome for patients with gastric GISTs.
EC-18 (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) Exhibits the Immune Regulatory Role through HSC Differentiation of Bone Marrow Cells in Mice
Authors: Ha-Reum Lee, Su-Hyun Shin, Nina Yoo, Sun Young Yoon, Myung-Hwan Kim, Cheolwon Suh, Ki-Young Sohn, Heung-Jae Kim, Yong-Hae Han, Saeho Chong, Jae Wha Kim
Journal: Blood (2015)
Risk factors for complications of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass
Authors: Piotr Major, Michał Wysocki, Michał Pędziwiatr, Magdalena Pisarska, Jadwiga Dworak, Piotr Małczak, Andrzej Budzyński
Journal: International Journal of Surgery (2016)
End Piece: Sanitas sanitatum
Authors: Jeremy Hugh Baron
Journal: BMJ (2005)

There is a great mistake in the Vulgate.. .the Latin translation of the Holy Scriptures, and that instead of saying “Vanity of vanities, all is vanity” - Vanitas vanitatum, omnia vanitas, the wise and witty king really said, Sanitas sanitatum, omnia sanitas. Gentlemen, it is impossible to overrate the importance of the subject. After all, the first consideration of a Minister should be the health of the people.

Benjamin Disraeli, 1872. Cited by Sir Humphry Rolleston. The progress and pioneers of preventive medicine. Ann Med Hist 1934;6: 95
Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Jordi Bruix, Shukui Qin, Philippe Merle, Alessandro Granito, Yi-Hsiang Huang, György Bodoky, Marc Pracht, Osamu Yokosuka, Olivier Rosmorduc, Valeriy Breder, René Gerolami, Gianluca Masi, Paul J Ross, Tianqiang Song, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Masatoshi Kudo, Ann-Lii Cheng, Josep M Llovet, Richard S Finn, Marie-Aude LeBerre, Annette Baumhauer, Gerold Meinhardt, Guohong Han
Journal: The Lancet (2016)
High Concordance between Pharmacogenetic Analysis of Bone Marrow and Buccal Cell Samples in Acute Myeloid Leukemia.
Authors: Joli R. Weiss, Maria R. Baer, Christine B. Ambrosone, Javier G. Blanco, Alan Hutson, Laurie A. Ford, Kirsten B. Moysich
Journal: Blood (2006)
Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Bortezomib (B) in Patients (pts) with Relapsed Multiple Myeloma (MM): A Phase I/II Study in Japan.
Authors: Kensei Tobinai, Takashi Watanabe, Yoshiaki Ogawa, Michinori Ogura, Yasuo Morishima, Hironobu Minami, Kuniaki Itoh, Tomomitsu Hotta
Journal: Blood (2006)