tbuckley/cabot-search huggingface dataset:
Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study.
Authors: Davendra Sohal, Shiva Shrotriya, Katherine Glass, Robert James Pelley, Michael J. McNamara, Bassam N. Estfan, Marc A. Shapiro, Jane Wey, Sricharan Chalikonda, Gareth Morris-Stiff, Matthew Walsh, Alok A. Khorana
Journal: Journal of Clinical Oncology (2015)

414 Background: Overall survival after pancreatic cancer resection remains poor. A subgroup of patients die early (&lt;6 months) and understanding factors associated with early mortality may help identify high-risk patients. The Khorana Score, including baseline hemoglobin, leukocyte and platelet counts, and body mass index [Khorana et al, Blood, 2008], has been shown to be associated with early mortality in solid tumors [Ay et al; Kuderer et al]. We evaluated the role of this score and other prognostic variables in predicting early mortality following resection. Methods: We conducted a cohort study of consecutive patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013 and were followed at the Cleveland Clinic. Baseline (diagnosis +/- 30 days) parameters were used to define patients as high-risk (Score &gt;=3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) are presented. Results: The study population comprised 334 patients. Median age was 67 years; 50% were female; 86% were Caucasian. Pancreatic head was the primary site for 73%; 67% were T3 and 63% were N1 tumors. Median Khorana score was 2; 152 patients (47%) were high-risk. Adjunctive treatment included chemotherapy (70%) and radiation (40%). Post-operative (30-day) mortality was 0.9%. Six-month mortality for the entire cohort was 9.4%, with significantly higher rates for high-risk patients (13.4% vs. 5.6%, p=0.02). In univariable analyses, Khorana score, low hemoglobin, and elevated blood urea nitrogen (BUN) were associated with early mortality; T- and N-stage, as well as margin status (R0/R1), were not. In multivariable analyses (n=326), Khorana score (HR high-risk = 2.31, p=0.039) and elevated BUN (HR = 4.34, p&lt;0.001) were associated with early mortality. Conclusions: Patients at high risk for early mortality after resection of pancreatic adenocarcinoma can be identified using simple baseline patient-related clinical and laboratory parameters rather than tumor characteristics. Future studies could evaluate the benefit of pre-operative interventions targeting patients at high risk for early mortality.
Myelosuppression and "conventional" chemotherapy: what price, what benefit?
Authors: G P Canellos, G D Demetri
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8418220 Myelosuppression and "conventional" chemotherapy: what price, what benefit? G P CanellosxG P CanellosSearch for articles by this author , G D DemetrixG D DemetriSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.1.1 PDF "Myelosuppression and "conventional" chemotherapy: what price, what benefit?." Journal of Clinical Oncology, 11(1), pp. 1–2© 1993 by American Society of Clinical Oncology
Abstract 13979: Left Atrial Symmetry Changes in Atrial Fibrillation: Relation With Diastolic Dysfunction and Symptom Severity
Authors: Sotirios Nedios, Ole-A. Breithardt, Emmanuel Koutalas, Jedrzej Kosiuk, Philipp Sommer, Arash Arya, Sascha Rolf, Daniela Husser, Gerhard Hindricks, Andreas Bollmann
Journal: Circulation (2014)

Introduction: Atrial fibrillation (AF) progression has been associated with asymmetric left atrial (LA) dilatation and left ventricular diastolic dysfunction (LVDD). LVDD has been also correlated with symptom severity. Hypothesis: Aim of this study was to test the hypothesis that the pattern of LA asymmetry is associated to LVDD and symptom severity. Methods: In 104 patients (58±10 years old, 69% male) referred for AF ablation, CT data were used to determine the LA volume (LAV) after exclusion of the appendage and the pulmonary veins (PVs). A cutting plane, between the PV ostia and the appendage and parallel to the posterior wall, divided LAV into anterior- (LA-A) and posterior-LA (LA-P) parts. The ratio LA-A/LAV was defined as asymmetry index (ASI). LVDD was evaluated according to current guidelines and symptom severity was quantified using the European Heart Rhythm Association score. Results: Univariate linear regression revealed that ASI is associated with LVDD, LAV and mitral regurgitation. ASI was higher in patients with LVDD (n=35, 62±5% vs. 59±6%, p=0.013) and in patients with mitral regurgitation (n=67, 61±6% vs. 58±5%, p=0.025) than those without. LAV increase was associated with an ASI increase (r=0.26, p=0.008). Multiple linear regression analysis revealed that LAV (β=0.211, 95% CI: 0.003-0.071, p=0.033) and LVDD (β=0.207, 95% CI: 0.167-5.011, p=0.036) were the only independent predictors of ASI increase (adjusted r2=0.92, F=6.2, p=0.003). Patients with moderate-severe AF symptoms (n=61) had higher ASI (61±6% vs. 58±5%, p=0.012) and higher prevalence of LVDD (43% vs. 21%, p=0.034) than those with mild symptoms. Conclusions: LA symmetry changes are associated with dilatation and left ventricular diastolic dysfunction and correlate with symptom severity in AF.
Restarting antithrombotics after GI bleeding was linked to better outcomes in patients with AF
Authors: Geoffrey D. Barnes, James D. Douketis
Journal: Annals of Internal Medicine (2016)

Source Citation Staerk L, Lip GY, Olesen JB, et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study. BMJ. 2015 Nov 16;351:h5876. 26572685
Abstract 17785: Eicosapentaenoic Acid Add-on to Atorvastatin Normalizes Pre-{beta}1-HDL Levels
Authors: Atsushi Nohara, Tohru Noguchi, Hayato Tada, Mika Mori, Chiaki Nakanishi, Masa-aki Kawashiri, Kunimasa Yagi, Akihiro Inazu, Junji Kobayashi, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2010)
Influence of Host Factors on Development and Type of Leukemia Induced in Mice by Graffi Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Luciano Fiore-Donati, Luigi Chieco-Bianchi
Journal: JNCI Journal of the National Cancer Institute (1964)

Cell-free extracts of leukemic tissues containing the Graffi virus were serially transmitted to newborn mice of the AKR, XVII, C57BL, DBA/2, C3Hf/Gs, and Swiss strains. In all the strains tested, leukemia developed with an incidence of approximately 90 percent, after latent periods ranging from 13 to 20 weeks. Although Graffi virus has been described as myelogenous, different types of leukemia, i.e., lymphatic, stem-cell, and myeloid, occurred in the various strains. In AKR mice inoculation of the virus caused lymphatic leukemia almost exclusively, which appeared after a median latent period of 14 weeks. When cell-free extracts of AKR lymphatic leukemia were passed in other strains of mice, such as C57BL and DBA/2, myeloid forms appeared in a significant number of the recipients. Induction of leukemia by the Graffi virus was also studied in C3Hf/Gs and AKR mice whose spleen or thymus gland had been removed. Splenectomy did not modify the incidence and type of leukemia. However, 76 percent of the C3Hf/Gs mice and 40 percent of the AKR mice that had been thymectomized developed myeloid leukemia. In the shamoperated controls, 8 percent of the C3Hf/Gs and 3 percent of the AKR mice developed a similar lesion. It is concluded that the environmental conditions of the recipient hosts significantly influence the type of neoplastic response induced by the Graffi virus.
Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: Results in six patients
Authors: A. Berruti, A. Roncari, G. Gorzegno, L. Dogliotti, P. Borasio, C. Mossetti
Journal: Annals of Oncology (1993)
Risk of stroke and transient ischaemic attack after herpes zoster
Authors: S.U. Kwon, S.-C. Yun, M.-C. Kim, B.J. Kim, S.H. Lee, S.-O. Lee, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-H. Kim
Journal: Clinical Microbiology and Infection (2016)
Telomerase vaccination of metastatic breast cancer patients induces antigen-specific tumor infiltrating lymphocytes and tumor necrosis
Authors: S. M. Domchek, K. R. Fox, A. Recio, L. M. Schuchter, R. Davidson, A. Demichele, M. D. Feldman, R. H. Vonderheide
Journal: Journal of Clinical Oncology (2005)

2505 Background: The telomerase reverse transcriptase hTERT represents a promising target for cancer immunotherapy because of its near universal expression in cancer and its critical role in oncogenesis. CD8+ T lymphocytes recognize peptides derived from hTERT and kill hTERT+ tumors cells of multiple histologies in vitro. Methods: We report the immunologic and biologic effects of vaccinating metastatic BrCa patients with hTERT peptide. Fourteen HLA-A2+ women with metastatic BrCa were vaccinated sq with 10 ug (n=6), 100 ug (n=5), or 1000 ug (n=3) of hTERT I540 peptide in adjuvant with GM-CSF for up to 8 vaccinations. Results: Most patients experienced Grade 1 and 2 injection site reactions and a syndrome of tumor pain or tumor-site itchiness after vaccination. One patient had a minor response following regression chest wall lesions. Three patients had stable disease after completing all 8 vaccinations. Peptide/MHC tetramer analysis of PBMC showed that 7 of 14 patients responded immunologically to the vaccine, including all those with clinical benefit. In freshly isolated PBMC, tetramer+ CD8+ cells were observed after (but not before) vaccination (0.1% to 2.0% of CD8+ T cells, median 0.86%). These cells secreted IFN-gamma in response to hTERT peptide and importantly, secreted IFN-gamma in response to telomerase-positive, HLA-A2+ (but not HLA-A2-negative) wild-type carcinoma cells. For 3 patients undergoing tumor biopsy, hTERT-specific CD8+ tumor infiltrating lymphocytes (TILs) were observed by tetramer analysis after, but not before, vaccination, measuring between 5%–12% tetramer+ cells among CD8+ T cells. By immunohistochemistry, tumor infiltrating lymphocytes observed after vaccination included both CD8+ and CD4+ T cells. TILs were associated in 2 patients with tumor necrosis involving 50%–80% of the biopsy specimens. Conclusions: Vaccination of metastatic BrCa patients against hTERT induces hTERT-specific T cells that are readily identifiable in blood and infiltrate tumors without major clinical toxicity. Tumor regression and tumor necrosis was observed after vaccination. These results suggest that hTERT can serve as a tumor rejection antigen in novel vaccines. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dana-Farber Cancer Institute Patent Application Pending
“Birth of a Culture”-Source of Postpartum Anomalies1
Authors: M. Edward Kaighn
Journal: JNCI Journal of the National Cancer Institute (1974)

Current procedures for the preparation of cell suspensions from tissues as well as nutrient media for growth are empirically seiected. Methods for the seiection or separation of different kinds of cells are generally more sophisticated and based on sound physical or biochemical principles, although their application to cultures of differentiated cells needs to be more thoroughly explored. Isolation of such cells by cloning has definite advantages. Because basic knowledge about the nutritional requirements and intercellular matrices of both normal and cancer cells is at best fragmentary, the following lines of investigation were recommended for the immediate future: 1) improvement in procedures for cell dissociation; 2) determination of nutritional requirements for newly isolated, differentiated cells (media-promoting optimal growth and function are needed); and 3) development of standardized reagents for cell culture. With this information, the prospects of developing model culture systems from normal and cancer cells derived from various organ parenchyma would be realistic.
Abstract 14916: Assessing Right Ventricular to Pulmonary Circulation Reserve During Exercise in Heart Failure Patients With Depressed Right Ventricular Function at Rest Provides Relevant Clinical Insights
Authors: Francesco Bandera, Marta Pellegrino, Greta Generati, Valeria Donghi, Eleonora Alfonzetti, Andrea Garatti, Marco Guazzi
Journal: Circulation (2013)
Spatiotemporal control of cardiac anisotropy using dynamic nanotopographic cues
Authors: Paulos Y. Mengsteab, Koichiro Uto, Alec S.T. Smith, Sam Frankel, Elliot Fisher, Zeid Nawas, Jesse Macadangdang, Mitsuhiro Ebara, Deok-Ho Kim
Journal: Biomaterials (2016)
Preexposure tenofovir–emtricitabine reduced HIV infection in men who have unprotected anal sex with men
Authors: Henry S. Sacks
Journal: Annals of Internal Medicine (2016)

Source Citation McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2015 Sep 9. [Epub ahead of print] 26364263
Treatment of acquired immunodeficiency syndrome-related Kaposis sarcoma with lymphoblastoid interferon.
Authors: Rios A, Mansell Pw, Newell Gr, Reuben Jm, Hersh Em, Gutterman Ju
Journal: Journal of Clinical Oncology (1985)

12 homosexual patients with Kaposis sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon Burroughs Wellcome Research Triangle Park NC).  They were given a dose of 20 x 10(6) U/m2 intramuscularly daily for approximately 2 months.  Responders continued their treatment on a maintenance schedule of 20 x 10(6) U/m2 3 times a week.  4 patients experienced complete remissions and 4 experienced partial remissions that resulted in a total response rate of 67%.  The median duration of treatment was 14 weeks (7 to 28+ weeks) and the median response duration was 28+ weeks (19 to 29+ weeks).  Of the 4 patients in complete remission 1 relapsed at 25 weeks and 1 at 26 weeks; the other 2 remained in complete remission at 28 and 29 weeks.  The clinical toxicity consisted of chills fever fatique and asthenia.  Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia.  Asthenia a condition present in all 12 patients was severe in 50%.  A minimal tumor burden the absence of circulating interferon before treatment and a performance status of or =90% on the Karnofsky scale were related to an improved response rate.  Measurement of immunologic parameters showed significant declines in the already impaired T cell levels lymphocyte blastogenic response to concanavalin A monocyte-mediated antibody-dependent cellular cytotoxicity and monocyte-adherence.  Activations of natural killer cells was not noted and no life-threatening infections occurred during treatment.  These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposis sarcoma and its use warrants further study in a larger number of patients.  (authors)
Elucidation of the Roles of Tumor Integrin β1 in the Extravasation Stage of the Metastasis Cascade
Authors: Michelle B. Chen, John M. Lamar, Ran Li, Richard O. Hynes, Roger D. Kamm
Journal: Cancer Research (2016)

Tumor integrin β1 (ITGB1) contributes to primary tumor growth and metastasis, but its specific roles in extravasation have not yet been clearly elucidated. In this study, we engineered a three-dimensional microfluidic model of the human microvasculature to recapitulate the environment wherein extravasation takes place and assess the consequences of β1 depletion in cancer cells. Combined with confocal imaging, these tools allowed us to decipher the detailed morphology of transmigrating tumor cells and associated endothelial cells in vitro at high spatio-temporal resolution not easily achieved in conventional transmigration assays. Dynamic imaging revealed that β1-depleted cells lacked the ability to sustain protrusions into the subendothelial matrix in contrast with control cells. Specifically, adhesion via α3β1 and α6β1 to subendothelial laminin was a critical prerequisite for successful transmigration. β1 was required to invade past the endothelial basement membrane, whereas its attenuation in a syngeneic tumor model resulted in reduced metastatic colonization of the lung, an effect not observed upon depletion of other integrin alpha and beta subunits. Collectively, our findings in this novel model of the extravasation microenvironment revealed a critical requirement for β1 in several steps of extravasation, providing new insights into the mechanisms underlying metastasis. Cancer Res; 76(9); 2513-24. ©2016 AACR.
Should the treatment of advanced lepidic adenocarcinoma be adapted to the pathological subtype?
Authors: Marianne Paesmans
Journal: European Respiratory Journal (2015)

In 2011, the pathological classification of lung adenocarcinoma was jointly revised by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society [1]. The former terminology adenocarcinoma with bronchiololalveolar features was recategorised as nonmucinous lepidic predominant adenocarcinoma (NM L-ADC) or mucinous variant (M L-ADC). The reason for this subclasssification was the identification of multiple differences: clinical, radiological, pathological and genetic. In particular, although bronchioloalveolar (BAC) features are overall an independent predictive factor for EGFR (epidermal growth factor receptor) mutation in a non-Asian population with an odds ratio of 2.84 (95% CI: 1.98–4.06) [2] compared with other types of lung adenocarcinoma, it was shown that NM tumours more frequently exhibit KRAS (Kirsten Ras) mutations and lack of EGFR mutations while M tumours are more likely to be EGFR mutated [3]. The creation of these two subcategories gives a rationale to investigate further whether the M or NM characteristic might be a new target for tailoring treatment of those patients with advanced lepidic adenocarcinoma. Increased sensitivity to chemotherapy/TKI of mucinous variant in advanced L-ADC should be tested in a phase III trial <http://ow.ly/TkWXi>
Facilitated Allergen Binding (FAB) Is a Meaningful Immunological Biomarker for Monitoring Immediate Clinical Efficacy in Short-Term Peptide Allergen Immunotherapy
Authors: Silke Allekotte, Mohamed H. Shamji, Gregor V. Zadoyan, Elena M. Kasche, Kija Shah-Hosseini, Anatoli Astvatsatourov, Sabine Pirotton, Adrian Caplanusi, Stephen R. Durham, Ralph Mosges
Journal: Journal of Allergy and Clinical Immunology (2016)
Does endoscopy accurately predict response to chemoradiation in patients undergoing esophagectomy?
Authors: I. S. Sarkaria, N. Rizk, M. Bains, R. Flores, B. Park, D. H. Ison, B. D. Minsky, V. W. Rusch
Journal: Journal of Clinical Oncology (2006)

4024 Background: Endoscopic biopsy after chemoradiation therapy (CRT) for esophageal cancer has been used to determine response to treatment. To test the validity of this methodology, we conducted a study to determine if endoscopic biopsy can accurately establish evidence of local pathologic complete response (pCR), defined as no residual local disease in the esophagus, in patients undergoing esophagectomy after CRT. Methods: We retrospectively queried a prospectively maintained database for patients seen at Memorial Sloan-Kettering Cancer Center from 1996 to the present who underwent, 1) CRT for esophageal cancer with the intent to proceed to esophagectomy post-treatment, and 2) post-CRT endoscopic biopsy. Data points included the pathology of the post-CRT endoscopy and resected surgical specimens, tumor histology, mean time from end of CRT to endoscopic biopsy, and mean time from endoscopic biopsy to surgery. Correlations were analyzed by the chi-square test and one way analysis of variance. Results: One-hundred thirty seven patients meeting our search criteria were identified. Ninety-percent of patients received cisplatin based chemotherapy and 5040 cGy of radiation. One-hundred four patients had a negative pathology on endoscopic biopsy. A negative pathology at endoscopic biopsy was a poor predictor of pCR (Positive Predictive Value = 37.5%), with 65% of these patients having residual local disease at esophagectomy. This result was not influenced by mean time from completion of CRT to endoscopy (p=0.5), or by mean time from endoscopy to surgery (p=0.47). A positive pathology at endoscopic biopsy was highly predictive of residual disease (p&lt;0.001). When analyzed by histology, a negative endoscopic biopsy better predicted response for squamous cell carcinomas versus adenocarcinomas (p&lt;0.001). Conclusions: Although improved for squamous cell cancers versus adenocarcinomas, a disease free endoscopic biopsy does not appear to be a useful predictor of a complete pathologic response after CRT. Neither the time to endoscopy after CRT, nor the time to surgery after endoscopy, influence this finding. No significant financial relationships to disclose.
Tumor molecular correlates of unresectable, locally advanced head and neck squamous cell carcinoma (SCCHN) response to concurrent radiation (RT), cisplatin (DDP), and cetuximab (C225) in a phase II trial (ECOG 3303).
Authors: A. M. Egloff, J. Lee, A. E. Vaezi, C. J. Langer, A. A. Forastiere, H. Quon, B. Burtness, J. R. Grandis
Journal: Journal of Clinical Oncology (2010)

5537 Background: The molecular characteristics of SCCHN associated with response to C225 alone or in combination with RT and DDP are unknown. We evaluated tumor HPV status, EGFR gene amplification, and EGFR, P16, ERCC1, and XPF tumor protein levels and their association with overall survival (OS) and progression-free survival (PFS) in a cohort of 69 unresectable SCCHN patients (pts) treated on ECOG 3303 with RT/DDP/C225; toxicity and response data were previously reported (ASCO 2008, #6006). Methods: Tissue microarrays (TMAs) were made from baseline tumor cores from 34 eligible pts who received treatment. HPV status was determined using an HPV pan-specific DNA probe and bright field in situ hybridization (ISH). EGFR gene amplification status was determined using dual color EGFR/CEP7 fluorescence-ISH (FISH); positive EGFR FISH was defined as gene amplification or high polysomy. Tumor protein levels were determined by pathologist interpretation of immunohistochemical (IHC) staining. ERCC1 levels were determined using the highly specific FL-297 antibody. OS and PFS differences by biomarker status were assessed using log rank tests. Results: HPV DNA was detected in 59% (10/17) of oropharyngeal tumors; all other successfully evaluated tumors (n=12) were HPV negative. Pts with HPV (+) tumors had significantly longer OS and PFS compared to patients with HPV (-) tumors (p=0.004 and p=0.036, respectively). High P16 tumor levels, defined by the median value, were associated with longer OS (p=0.006), and there was a trend for longer PFS (p=0.067). Patients with high EGFR IHC tumor scores had shorter PFS (p=0.018). ERCC1, XPF and EGFR FISH were not associated with OS. Conclusions: SCCHN biomarkers previously identified as favorable prognostic indicators, HPV positivity, high P16 and low EGFR protein expression levels, were found to be associated with improved survival in this ECOG 3303 cohort. No other biomarker evaluated was associated with either OS or PFS. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Bristol-Myers Squibb Bristol-Myers Squibb