tbuckley/cabot-search huggingface dataset:
A mechanistic radiographic and biologic phase II single-agent study of sunitinib in relapsed/refractory esophageal (E) and gastroesophageal (GE) cancers.
Authors: A. S. Bhinder, J. S. Rose, X. Li, S. Tahiri, D. Clark, S. Sammet, K. Foy, S. Rawale, P. Kaumaya, T. Bekaii-Saab
Journal: Journal of Clinical Oncology (2010)

e14650 Background: There is no established standard for patients (pts) with advanced refractory E or GE cancer. Given the scientific evidence supporting the development of strategies targeting angiogenesis in these cancers we performed a prospective study evaluating the efficacy and safety of sunitinib in pts with refractory/relapsed E and GE cancers. Our study includes hybrid imaging protocol using PET/CT/3T-MRI and other angiogenic markers to help predict for early response or resistance to sunitinib. Methods: Eligibility criteria include advanced E or GE cancer, PS 0-1, adequate organ function and no significant cardiac disease. The primary endpoint is PFS at 24 weeks (wk) using RECIST criteria. Using a single stage Fleming phase II design, enrollment of 25 pts was planned. Pts received sunitinib at 37.5 mg PO daily continuously. In addition to staging CT scans pts get PET/CT/3T-MRI, serum VEGF, VEGFR-1, -2 and PlGF measurement at baseline, 2, 6, and 12 wks as well as tumor biopsy before and 6 wk post treatment to assess the mean vessel density. Results: 11 pts were enrolled at The Ohio State University so far. Median age was 60 yrs (range 38-75). 11/11 pts had metastatic disease at baseline. 11/11 pts received prior therapy. 9/11 pts had > 1 prior chemotherapy, 7/10 had prior radiation and 6/10 had prior surgery. 1 pt had partial response at 12 wk and 3 pts had SD. The median time to progression is 45 days. Grade 3 AE's included: lymphopenia (3), lower GI bleeding (1) and fatigue (1). Grade 1/2 AEs included fatigue, AST elevation, leucopenia, nausea and dysgeusia. There was an upward trend in both VEGF and PlGF levels and downward trend in the VEGFR and contrast enhancement, illustrated by low Amp on 3T Dynamic contrast enhanced (DCE) MRI and low SUV on PET/CTfrom baseline to wk 2 measurements. Conclusions: Preliminary analysis suggests sunitinib is safe with evidence of interesting activity in previously treated relapsed/refractory E and GE cancer pts. Preliminary PET/CT/3T-MRI data suggests a role for this modality in predicting early progression on sunitinib. Accrual is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Preliminary evaluation of radioimmunotherapy with Tenarad, a I-131 labeled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin lymphoma.
Authors: L. Aloj, L. D'Ambrosio, M. Aurilio, R. Marreno, D. Neri, H. D. Menssen, L. Giovannoni, F. Di Gennaro, C. Caraco, M. Arcamone, F. Frigeri, A. Pinto, S. Lastoria
Journal: Journal of Clinical Oncology (2011)

8063 Background: The extra-domain A1 (ED-A1) of tenascin-C is a highly expressed component of the tumor extracellular matrix and constitutes a valuable target for radionuclide therapy. Tenarad is a human antibody which is capable of recognizing ED-A1, has been labeled with I-131 and is expressed as small immunoprotein (SIP) for improving its biodistribution properties. Previous phase I/II studies with a similar compound (131I-L19SIP) have shown efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad is administered to patients with progressive Hodgkin lymphoma refractory to conventional treatment. Methods: Eight patients (4 M, 4 F, 19-41 yo) have been enrolled between April and December 2010. All patients had undergone at least three lines of chemotherapy; seven pts had prior external beam radiation therapy and six had prior autologous bone marrow or stem cell transplantation. All patients presented with nodal disease and some had involvement of the bone (n=3), lung (n=2) or liver (n=2). Baseline assessments included whole body FDG-PET with contrast enhanced CT, bone marrow biopsy and SPECT. If Tenarad uptake, measured by SPECT, in tumor areas was 4 times higher than in muscle, patients were considered eligible to receive the therapeutic dose of the drug (2.05 GBq/m2). Results: All patients were eligible for the therapeutic dose of Tenarad. At the first tumor assessment (4-6 weeks from therapy), two patients showed a very good partial response, both of which were confirmed at second assessment (8-10 weeks), and five showed disease stabilization, three of which with reduced lesion number and/or size. One patient developed grade 4 platelet and leukocyte toxicity, which required hospitalization and intervention. Other patients had grade 3 or lower hematologic toxicity, which resolved spontaneously. Conclusions: In this heavily pretreated patient population with poor prognosis, the application of Tenarad showed acceptable toxicity and resulted in some objective responses. Further studies are being planned to better define effective Tenarad treatment schemes in patients with Hodgkin lymphoma.
Groupwise connectivity-based parcellation of the whole human cortical surface using watershed-driven dimension reduction
Authors: Sandrine Lefranc, Pauline Roca, Matthieu Perrot, Cyril Poupon, Denis Le Bihan, Jean-François Mangin, Denis Rivière
Journal: Medical Image Analysis (2016)

Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri.
Lenalidomide and pomalidomide strongly enhance tumor cell killing <i>in vitro</i> during antibody-dependent cellular cytotoxicity (ADCC) mediated by trastuzumab, cetuximab and rituximab
Authors: J. B. Bartlett, L. Wu, M. Adams, P. Schafer, G. Muller, D. Stirling
Journal: Journal of Clinical Oncology (2007)

3023 Background: Potential mechanisms of action of lenalidomide and pomalidomide (CC-4047) include anti-angiogenic, anti- proliferative and immunomodulatory activities, e.g., enhancement of T cell and NK cell function. Both drugs appear to enhance T cell activation and Th1-type cytokines in cancer patients. Also, both drugs have been shown to enhance rituximab-mediated protection in a mouse lymphoma model. Methods: We have utilized an in vitro ADCC system to assess the ability of these drugs to enhance human NK cell function in response to the approved therapeutic antibodies trastuzumab, cetuximab and rituximab. Results: Pre-treatment of NK cells with either pomalidomide or lenalidomide greatly enhanced IFN-γ production by NK cells in response to IgG in the presence of either IL-2 or IL- 12. In a series of functional ADCC assays, Her2/neu overexpressing breast cancer cells (SKBR3 &amp; MCF-7) pre-coated with trastuzumab, EGFR positive colorectal cancer cells (HCT-116) pre-coated with cetuximab and NHL cell lines (Namalwa, Farage &amp; Raji) pre-coated with rituximab, were exposed to NK cells pre-treated with pomalidomide, lenalidomide or thalidomide. Both pomalidomide and lenalidomide synergistically increased (up to 6-fold) NK cell-mediated killing of antibody coated tumor cells in a dose-dependent manner. Thalidomide had no effect in this system. There was minimal tumor cell killing by antibody alone or in the absence of antibody. The presence of IL-2 or IL-12 was required to see enhanced killing by either drug. Enhanced ADCC was associated with increased signaling in NK cells, specifically with inhibition of the negative regulator SHIP-1. Other downstream effects on signaling pathways are also being investigated. Monocyte-mediated tumor cell ADCC was also enhanced by both drugs. Conclusions: We have shown that pomalidomide and lenalidomide (but not thalidomide) strongly enhance the ability of therapeutic antibodies to induce ADCC via NK cell/monocyte-mediated killing of tumor cells in vitro. These results provide a strong rationale for combination of either lenalidomide or pomalidomide with antibodies to tumor-specific surface antigens in cancer patients. No significant financial relationships to disclose.
Disease expression in patients with primary ciliary dyskinesia (PCD), CF and pancreatic sufficiency (CF-PS) and insufficiency (CF-PI)
Authors: Malena Cohen-Cymberknoh, Natalia Simanovski, Nurith Hiller, Alex Gileles Hillel, David Shoseyov, Eitan Kerem
Journal: European Respiratory Journal (2011)

In both CF and PCD, lung disease is caused by impaired mucociliary clearance. In CF it is a result of airway surface liquid depletion and in PCD, of ciliary defects in the structure and/or function. CF-PS patients are diagnosed at a later age, have better nutritional status and survival compared to CF-PI. PCD patients do not have PI and are diagnosed at a later age than patients with CF-PI; hence, are expected to have a disease similar to CF-PS.   Aim:  To correlate clinical status, microbiological, FEV 1 , and HRCT-Total Brody Score (CT-TBS) between patients with PCD, CF-PI and CF-PS.   Methods:  Patients with CF-PI, CF-PS and PCD were included. Data on FEV 1 , HRCT, sputum cultures and BMI were collected as part of their routine assessment.   Results:  Overall, 145 patients (79-CF-PI, 43-CF-PS, 23-PCD) participated in this study. The age of the CF-PS group was markedly higher compared to the other groups. BMI was notably lower in the PCD group compared to both CF groups. FEV 1  had a strong negative correlation with age in the CF groups, not in the PCD group. Sputum colonization rates of  P. aeruginosa  (PA) were similar in the CF-PI and PCD groups, lower in the CF-PS group. CT-TBS showed the most severe structural disease in CF-PI, followed by the PCD and the CF-PS group. In both CF groups there was a strong negative correlation between TBS and FEV 1 , not observed in the PCD group.   Conclusion:  In PCD, FEV 1  does not correlate with age, BMI, rate of PA infection and CT-TBS. Therefore, opposed to CF, in PCD, FEV 1  is not a reliable predictor of severity of lung disease. Further studies are needed to delineate the pathogenesis and progression of lung disease in PCD
Induction cetuximab (C) followed by C, paclitaxel (P), carboplatin (CP) and concurrent radiation (RT) for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: A. E. Birnbaum, T. T. Johnson, R. Rathore, H. Khurshid, M. Puthawala, K. Radie Keane, C. Ruhl, H. Wanebo, T. Kennedy, N. Ready
Journal: Journal of Clinical Oncology (2007)

16504 Background: C is an IgG1 chimerized, monoclonal antibody that binds specifically to the epidermal growth factor receptor, which is expressed in 90–100% of HNC. We conducted a phase II study to evaluate the toxicity and efficacy of induction C followed by concurrent C with chemoRT for patients (pts) with SCCHN. Methods: Eligible pts had untreated stage III or IV, SCCHN. All pts received induction, single agent, C, 400 mg/m 2 week 1, followed by 250 mg/m 2 weeks 2, 3, and 4. Potentially operable pts then received C, 250 mg/m 2 , P 40 mg/m 2 and CP AUC=1, weekly x 5 wks, with 45 Gy RT then underwent endoscopic biopsy. If the biopsy was negative, pts received 3 additional weekly doses of C, P, CP and 22–27 Gy boost RT. Inoperable pts received 8 weeks of C, P and CP and 66.6–72 Gy RT. All pts then received maintenance C 250 mg/m 2 /week x 24 weeks. Results: 29 pts have been enrolled. Male:Female 18:11. Median age = 55 (38–75). Primary sites included oral cavity (10 pts), oropharynx (1), larynx (12), hypopharynx (2), and glottis (4). The tumor stages were III (10 pts), IV (19). Toxicity data are available for 23 pts. 2 of 23 (9%) had grade (G) 4 toxicities (hypokalemia =1, ischemic colitis=1) however there were no treatment related deaths. G 2 toxicities included rash (52%), dysphagia (35%), mucositis (43.5%) and hypomagnesemia (9%). G 3 toxicities included rash (9%), dysphagia (44%), mucositis (26%) and XRT dermatitis (18%). Induction C responses by RECIST criteria were SD (14 pts) 61%, PR (7) 30%, and CR (1) 4%. Conclusion: C can be safely administered with chemoRT (CRT) for pts with HNC. C increases cutaneous toxicity but does not increase in-field CRT side effects. There were no unexpected high-grade adverse events. Preliminary single agent activity of C in untreated SCCHN is promising. No significant financial relationships to disclose.
Time-Dependent Relevance of Steroid Receptors in Breast Cancer
Authors: Danila Coradini, Maria Grazia Daidone, Patrizia Boracchi, Elia Biganzoli, Saro Oriana, Gianluigi Bresciani, Cinzia Pellizzaro, Gorana Tomasic, Giovanni Di Fronzo, Ettore Marubini
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To analyze the time-dependent prognostic role of the investigated variables, considered, when appropriate, on a continuous scale, for the purpose of evaluating and describing the interrelationships between clinically relevant patient and tumor characteristics (age, size and histology, and estrogen receptor [ER] and progesterone receptor content) and the risk of new disease manifestation. PATIENTS AND METHODS: We applied a flexible statistical model to a case series of 1,793 patients with axillary lymph node–negative breast cancer with a minimal potential follow-up of 10 years. To avoid a potential confounding effect of adjuvant treatment, only patients given local-regional therapy until relapse were considered. RESULTS: ER content and tumor size (adjusted for all the other covariates) showed a time-dependent relationship with the risk of new disease manifestations. In particular, ER content failed to show a prognostic effect within the first years of follow-up; thereafter, a positive association with risk of relapse was observed. For tumor size, within the first years of follow-up, the risk of relapse was directly related to size for only tumors up to 2.5 cm in diameter; thereafter, the impact on prognosis progressively decreased. CONCLUSION: The availability of a long follow-up on a large breast cancer series, as well as the use of innovative statistical approaches, allowed us to explore the functional relation between steroid receptors and clinical outcome and to generate a hypothesis on the involvement of ER in favoring long-term metastasis development.
Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus
Authors: Argyro Syngelaki, Kypros H. Nicolaides, Jyoti Balani, Steve Hyer, Ranjit Akolekar, Reena Kotecha, Alice Pastides, Hassan Shehata
Journal: New England Journal of Medicine (2016)

Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin.In this double-blind, placebo-controlled trial, we randomly assigned pregnant women without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35 to receive metformin, at a dose of 3.0 g per day, or placebo (225 women in each group) from 12 to 18 weeks of gestation until delivery. The BMI was calculated at the time of study entry (12 to 18 weeks of gestation). The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD (equivalent to a 50% reduction, from 20% to 10%, in the incidence of large-for-gestational-age neonates). Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia, as well as the incidence of adverse neonatal outcomes. Randomization was performed with the use of computer-generated random numbers. The analysis was performed according to the intention-to-treat principle.A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], P<0.001), as was the incidence of preeclampsia (3.0% vs. 11.3%; odds ratio, 0.24; 95% confidence interval, 0.10 to 0.61; P=0.001). The incidence of side effects was higher in the metformin group than in the placebo group. There were no significant between-group differences in the incidence of gestational diabetes, large-for-gestational-age neonates, or adverse neonatal outcomes.Among women without diabetes who had a BMI of more than 35, the antenatal administration of metformin reduced maternal weight gain but not neonatal birth weight. (Funded by the Fetal Medicine Foundation; ClinicalTrials.gov number, NCT01273584; EudraCT number, 2008-005892-83.).
포스터발표 : 컨벤션홀 특설 발표장 ; 역행성 경정맥 위정맥류 폐색술 후 위정맥류 재출혈에 관한 장기간 관찰 결과
Authors: 이순학, 조한진, 장선익, 오종댁, 이응갑, 배락천, 박수영, 정민규, 전성우, 조창민, 탁원영, 김성국, 최용환, 권영오
Journal: Clinical and Molecular Hepatology (2008)
Inferior vena cava filters in cancer patients: indications and outcome.
Authors: R E Schwarz, A M Marrero, K C Conlon, M Burt
Journal: Journal of Clinical Oncology (1996)

Our experience with inferior vena cava (IVC) filter placement to prevent pulmonary emboli (PE) in cancer patients with deep vein thromboses (DVT) was reviewed to identify indications, patient characteristics, complications, and long-term outcome.Charts of 182 patients with cancer were retrospectively analyzed. All patients had received an IVC filter in our institution between January 1980 and April 1992.Of 182 patients, 103 were men and 79 were women. Median age was 59 years (range, 15 to 88). Eight patients (4%) had stage I disease, 22 patients (12%) stage II, 37 patients (20%) stage III, and 115 patients (63%) stage IV. A DVT was diagnosed in 97 patients (53%), a PE in 46 patients (25%), and a combination in 39 patients (21%). Indications for IVC filter placement were DVT or PE in the presence of contraindications to anticoagulation therapy (perioperative, n = 58; CNS metastases, n = 20; thrombocytopenia, n = 7; bleeding, n = 61; others, n = 24; total, N = 170) or anticoagulation failure (recurrent PE, n = 6; recurrent DVT; n = 6; total N = 12). Filter placement complications (n = 6, 3%) included malposition (n = 3), migration (n = 1), arrhythmia (n = 1), and wound infection (n = 1), but no deaths. After filter placement, four patients developed a recurrent PE, and 11 patients developed a recurrent DVT. No significant postthrombotic complications were observed.IVC filter placement patients with advanced cancer and thrombotic complications is safe, well tolerated, and can offer effective therapy/prophylaxis with a low incidence of treatment failure.
Ebola vaccine R&amp;D: Filling the knowledge gaps
Authors: Donata Medaglini, Ali M. Harandi, Tom H. M. Ottenhoff, Claire-Anne Siegrist, VSV-EBOVAC Consortium, Selidji Todagbe Agnandji, Rafi Ahmed, Jenna Anderson, Floriane Auderset, Luisa Borgianni, Jessica Brosnahan, Annalisa Ciabattini, Olivier Engler, Marielle C. Haks, Gray Heppner, Alice Gerlini, Peter Gottfried Kremsner, Stephen Leib, Thomas Monath, Francis Ndungu, Patricia Njuguna, Mark Page, Gianni Pozzi, Rino Rappuoli, Francesco Santoro
Journal: Science Translational Medicine (2015)

With an emphasis on systems analyses, the VSV-EBOVAC project harnesses state-of-the-art technologies that illuminate mechanisms behind the observed immunogenicity and reactogenicity of the rVSV-ZEBOV vaccine and ensures that such information is shared among stakeholders.
THE JOURNAL OF INFECTIOUS DISEASES.
Journal: JAMA (1904)

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