tbuckley/cabot-search huggingface dataset:
A pilot trial of a combination of therapeutic vaccines (GI-4000 and GI-6207) as adjunctive therapy with first-line therapy with bevacizumab plus either FOLFOX or FOLFIRI in stage IV patients with newly diagnosed Ras-mutant positive or negative metastatic colorectal cancer.
Authors: John Marshall, Jimmy J. Hwang, Michael J. Pishvaian, Aiwu Ruth He, Louis M. Weiner, Erin K. Sandene, James L. Gulley, Christopher Ryan Heery, Jeffrey Schlom, Sue Speyer, Joni Richman, John Ferraro, Claire Coeshott, Allen Cohn, David Apelian, Timothy C. Rodell
Journal: Journal of Clinical Oncology (2012)

TPS3638 Background: A promising approach for the treatment of cancer is the development of vaccines that target specific tumor antigens. In the metastatic CRC patient population, targeted and active immunotherapy may inhibit cancer progression and improve survival. This trial is designed to evaluate the efficacy, immunogenicity, and safety of GI-4000 plus standard therapy in patients with metastatic colorectal cancer. GI-4000 is a proprietary immunotherapy that uses whole, heat-killed recombinant Saccharomyces cerevisiae yeast (called Tarmogens = Targeted Molecular Immunogens). GI-4000 is designed to activate a cellular immune response to target cells with activating ras mutations. Tarmogens have been shown to elicit selective killing of target cells that express a number of cancer antigens, including mutated Ras, by activation of antigenspecific T cell mediated responses. Methods: The study population consists of subjects with metastatic colorectal cancer with an activating mutation in ras. Newly diagnosed subjects receive FOLFOX (or FOLFIRI) + bevacizumab (Bev) + GI- 4000; 3 weekly injections of GI-4000 are followed by 8 cycles of Bev + FOLFOX (or FOLFIRI); day 1 and 2 every 14 days. Doses of GI-4000 are administered on day 8 of each cycle. Upon completion of chemotherapy, GI-4000 continues along with Bev maintenance every 2 weeks for up to 5 years or until subjects experience intolerance, disease recurrence, or death. If Bev is stopped, GI-4000 may continue on the same maintenance schedule alone. Subjects that have already completed standard chemotherapy (FOLFOX or FOLFIRI) may enter the study and receive Bev + GI-4000 every 2 weeks for up to 5 years. Enrollment is ongoing and will continue up to 52 subjects.
Detection of the BCR-ABL Gene By the Real-Time PCR Method in Patients with Chronic Myeloid Leukemia in Rio Grande Do Norte, Brazil
Authors: Aldair Sousa Paiva, Hugo Diogenes De Oliveira Paiva, Geraldo Barroso Cavalcanti, Gioconda DR Leão, Marcos Dias Leão, Roberto C Vasconcelos, Andrea LAC Fernandes, Frank Bahia, Victor lima Soares, Erica Aires Gil, Geisa Januario, Karla Cristina Santos, Telma Araujo Lemos, Alessandra Suelen Jardim
Journal: Blood (2018)
Sequential first-line treatment for metastatic colorectal cancer with capecitabine, irinotecan, and bevacizumab: Capecitabine plus bevacizumab (Cape-Bev) versus capecitabine, irinotecan plus bevacizumab (CAPIRI-Bev): The AIO KRK 0110/ML22011 randomized, phase III trial.
Authors: Clemens Albrecht Giessen, Dominik Paul Modest, Sebastian Stintzing, Ludwig Fischer von Weikersthal, Ursula Vehling-Kaiser, Ernst Spaeth-Schwalbe, Jens Freiberg-Richter, Julia Mayerle, Markus Bangerter, Claudio Denzlinger, Markus Sieber, Christian Teschendorf, Bettina Peuser, Volker Heinemann
Journal: Journal of Clinical Oncology (2012)

TPS3639 Background: Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question in bevacizumab-based first-line treatment including escalation- and de-escalation strategies. Methods: The AIO KRK 0110/ML22011 trial (ClinicalTrials.gov NCT01249638) is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of Cape-Bev versus CAPIRI-Bev in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, ECOG PS 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m 2 bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m 2 BID for 14d (d1-14), irinotecan 200 mg/m 2 (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumor tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are ORR, OS, PFS, safety and quality of life. Conclusion: The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with CAPIRI-Bev and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary. By January 2012, 79 of planned 516 patients have been enrolled.
The Efficacy and Toxicity of Blinatumomab in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia: Russian Multicenter Experience
Authors: Sergey N. Bondarenko, Alexey A Maschan, Elena N. Parovichnikova, Tatiana V Shelekhova, Vadim A Doronin, Elena N Bogatyreva, Kamil D Kaplanov, Natalia Miakova, Andrey N Sokolov, Ivan S Moiseev, Elena I Darskaya, Irina V Samorodova, Anna G Smirnova, Olesya V Paina, Tatjana A Bykova, Bella I Ayubova, Aleksandr D Kulagin, Ludmila S Zubarovskaya, Axel R Zander, Boris V Afanasyev
Journal: Blood (2017)
Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung
Authors: Arunava Ghosh, Raymond D. Coakley, Andrew J. Ghio, Marianne S. Muhlebach, Charles R. Esther, Neil E. Alexis, Robert Tarran
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Proteolysis is a key aspect of the lung’s innate immune system. Proteases, including neutrophil elastase and MMPs (matrix metalloproteases), modulate cell signaling, inflammation, tissue remodeling, and leukocyte recruitment via cleavage of their target proteins. Excessive proteolysis occurs with chronic tobacco use and is causative for bronchiectasis and emphysema. The effect of e-cigarettes (vaping) on proteolysis is unknown.Objectives: We used protease levels as biomarkers of harm to determine the impact of vaping on the lung.Methods: We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers), and determined protease levels in BAL. In parallel, we studied the effects of e-cigarette components on protease secretion in isolated human blood neutrophils and BAL-derived macrophages. We also analyzed the nicotine concentration in induced sputum and BAL.Measurements and Main Results: Neutrophil elastase, MMP-2, and MMP-9 activities and protein levels were equally elevated in both vapers’ and smokers’ BAL relative to nonsmokers. In contrast, antiprotease levels were unchanged. We also found that exposure of isolated neutrophils and macrophages to nicotine elicited dose-dependent increases in protease release. After vaping, measurable levels of nicotine were detectable in sputum and BAL, which corresponded to the half-maximal effective concentration values for protease release seen in immune cells.Conclusions: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease–antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.
Insulin-like growth factor receptor signaling pathways and resistance to tarceva (erlotinib) in non-small cell lung cancer cells
Authors: Floriana Morgillo, Jong K. Woo, Waun K. Hong, Ho Y. Lee
Journal: Cancer Research (2005)

1697  Purpose: The Epidermal Growth Factor Receptor (EGFR) is an important target for anticancer therapy. However, not all NSCLC cells respond to treatment with EGFR inhibitors, and the mechanism of resistance to EGFR inhibitors is poorly understood. Therefore, we studied the molecular mechanism that interferes with the activities of tarceva (Erlotinib), a selective EGFR tyrosin kinase inhibitor that has shown antitumor activities in patients with NSCLC as second / third line therapy. Methods: The effects of tarceva and its combination with inhibitors of IGF-1R signaling components on proliferation and apoptosis were assessed in a subset of NSCLC cell lines in vitro and in vivo, by using the MTT assay, anchorage-independent growth assay in soft agar, clonogenic survival assay, a flow cytometry-based TUNEL assay, western blot analyses, and a NSCLC xenograft tumor model. Results: Tarceva treatment exhibited an activation of IGF-IR signaling components, such as IGF-1R, Akt, and MAPK, in the resistant NSCLC cell lines, but not in the sensitive cell lines. Dual targeting of EGFR and IGF-1R signaling pathways through combined treatment of tarceva and inhibitors of upstream and downstream of IGF-1R signaling components showed enhanced antiproliferative activities in NSCLC cells in vitro and in vivo. Conclusion: The combination of tarceva and inhibitors of IGF-1R signaling components induced enhanced antiproliferative activities in NSCLC cells via increased apoptosis in vitro and in vivo. These results suggest that activation of IGF-1R signaling pathway confer resistance to tarceva treatment in NSCLC cells, and that simultaneous treatment with inhibitors of IGF-1R and EGFR signaling pathways might be an effective therapeutic strategy against NSCLC. Supported in part by the DAMD17-01-1-0689 from the Department of Defense (to W. K. Hong); W81XWH-04-1-0142-01-VITAL from the Department of Defense (to W. K. Hong); National Institutes of Health Grants R01 CA109520-01 (to H-Y. Lee) and CA100816-01A1 (to H-Y. Lee), National American Cancer Society, RSG-04-082-01-TBE 01(to H-Y. Lee)
Venous and arterial leg ulcers
Authors: Joseph E Grey, Keith G Harding, Stuart Enoch
Journal: BMJ (2006)

Venous leg ulceration is due to sustained venous hypertension, which results from chronic venous insufficiency. In the normal venous system, pressure decreases with exercise as a result of the action of the calf muscle pump. When the muscles relax, the valves in the perforating veins connecting the superficial to the deep venous circulation prevent reflux and the pressure remains low. The venous pressure remains high, however, in a system where the valves are incompetent.

View this table:

Risk factors for venous ulceration



Up to 10% of the population in Europe and North America has valvular incompetence, with 0.2% developing venous ulceration. Forty to fifty per cent of venous ulcers are due to superficial venous insufficiency and/or perforating vein incompetence alone with a normal deep venous system.

There are many risk factors for venous ulceration. Recurrent venous ulceration occurs in up to 70% of those at risk. Many venous ulcers are painful, so appropriate pain relief and advice should be given.

### Examination

Ninety five per cent of venous ulceration is in the gaiter area of the leg, characteristically around the malleoli. Ulceration may be discrete or circumferential. The ulcer bed is often covered with a fibrinous layer mixed with granulation tissue, surrounded by an irregular, gently sloping edge. Ulcers occurring above the mid-calf or on the foot are likely to have other origins.

Pitting oedema is often present and may predate the ulcer. It is often worse towards the end of the day. Extravasation of erythrocytes into the skin occurs, resulting in the deposition of haemosiderin within macrophages, which stimulates melanin production, pigmenting the skin brown. In long term venous insufficiency, lipodermatosclerosis occurs. This …
Expression of caveolin-1 in renal neoplasms
Authors: M. Zhou, I. Tamaskar, L. Sercia, B. I. Rini, R. M. Bukowski
Journal: Journal of Clinical Oncology (2006)

14509 Background: Caveolin-1 is the major structural and functional component of caveolae, which are specialized lipid raft microdomains on cell membrane important for signaling pathways related to cell adhesion, growth and survival. Studies have shown that clear cell renal cell carcinoma (CCRCC) expressed caveolin-1 and that the over-expression correlated with adverse pathological findings and poor outcomes. The expression of caveolin-1 in other types of renal tumors has not been studied. Methods: A tissue microarray (TMA) was constructed from 60 normal kidneys, 22 CCRCC, 20 papillary renal cell carcinomas (PRCC), 16 chromophobe renal cell carcinomas (ChRCC), and 19 oncocytomas (ONC). The TMA was immunostained for caveolin-1 protein. Membranous caveolin-1 expression was scored using the internal vascular endothelial cells as positive control. Results: Membranous caveolin-1 expression was detected in 19/22 (86.4%) CCRCC, in 1/20 (5%) PRCC, 0/16 (0%) ChRCC, and 1/19 (5.3%) ONC. Cytoplasmic caveolin-1 was detected in 16/22 (72.7%) CCRCC, 13/20 (65%) PRCC, 8/16 (50%) ChRCC and 13/19 (68.4%) ONC. Membranous caveolin-1 expression correlated with tumor size (Pearson correlation = 0.266, p = 0.043). There was no correlation between membranous or cytoplasmic caveolin-1 expression and other pathological parameters, including Fuhrman nuclear grade, or TNM stage. Conclusion: Caveolin-1 exhibits distinct subcellular localization in different renal tumors. Membranous caveolin-1 is most commonly detected in CCRCC, rarely found in PRCC and ONC, and is absent in ChRCC. This finding suggests that caveolin-1 may play an important role in the pathogenesis of CCRCC. [Table: see text]
ABC of conflict and disaster: Humanitarian assistance: standards, skills, training, and experience
Authors: Marion Birch, Simon Miller Parkes
Journal: BMJ (2005)

### The Sphere Project

Those affected by catastrophe and conflicts often lose basic human rights. Recognising this, a group of humanitarian non-governmental organisations and the Red Cross movement launched the Sphere Project in 1997. The aim of this project was to improve the quality of assistance and enhance the accountability of the humanitarian system in disaster response by developing a set of universal minimum standards in core areas and a humanitarian charter.

The charter, based on international treaties and conventions, emphasises the right of people affected by disaster to life with dignity. It identifies the protection of this right as a quality measure of humanitarian work and one for which humanitarian actors bear responsibilities.

### What does the Sphere Project cover?

The Sphere handbook provides minimum standards common to all five key sectors of humanitarian aid

The Sphere Project was launched in response to concern about inconsistencies in aid provided to people affected by disaster, and the frequent lack of accountability of humanitarian agencies to their beneficiaries, their membership, and their donors. The project attempts to identify and define the rights of populations affected by disasters in order to facilitate effective planning and implementation of humanitarian relief.

### People in Aid: human resources management

People in Aid was founded with two main aims - to highlight the importance of human resources management in the effective achievement of an organisation's mission, and to offer support to humanitarian and development agencies wishing to improve human resources management.

After the Rwanda crisis, research showed that aid workers saw organisational and management issues as prime stressors in their work. From this research, the People in Aid Code of Good Practice was developed. The code focuses on the organisational decisions that affect aid workers - such as including human resources in plans and budgets, …
Statins (ASIs) may improve the outcome of erlotinib as second line treatment (tx) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC).
Authors: Natalie Maimon, Daniel Keizman, Maya Gottfried
Journal: Journal of Clinical Oncology (2012)

e18108 Background: The EGFR inhibitor erlotinib is a standard second line tx for mNSCLC. Statins are used in the tx of hyperlipidemia. Pre-clinical and clinical studies in several cancer types have shown that they may inhibit tumor growth. Their effect on the outcome of erlotinib as second line tx in mNSCLC is poorly defined. We aimed to study the effect of statins on the outcome of erlotinib as second line tx for mNSCLC. Methods: We performed a retrospective study of an unselected cohort of pts with mNSCLC, who were treated continuously with 150mg of oral erlotinib. Pts were divided into 2 groups: (1) statins users and (2) statins naive. The effect of statins use on objective response, progression free survival (PFS) and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chisquare test and partial likelihood test from cox model. Results: Between 2005-2011, 107 pts with mNSCLC were treated with second line erlotinib. There were 51 statins users (group 1) and 56 nonusers (group 2). All users started statins before erlotinib tx initiation. The groups were balanced regarding the following known clinical prognostic factors: female gender, ECOG performance status, active smoking, anemia, adenocarcinoma histology type, EGFR mutation (positive vs negative + unknown). Objective response in group 1 vs 2 was partial response (PR) 41% vs 29% (p=0.15), stable disease (SD) 41% vs 25% (p=0. 11), and progressive disease (PD) 18% vs 46% (OR=2.5, p=0.07). Median PFS was 12 vs 3 ms (HR 0.44 in statins users, p=0.02). Median OS was 35 vs 19 ms (HR 0.63, p=0.1). Conclusions: Statins may improve the outcome of pts with mNSCLC that are treated with erlotinib as second line tx. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials.
Whole Grains and Risk of Hepatocellular Carcinoma—Missing the Forest for the Trees?
Authors: Alain Braillon
Journal: JAMA Oncology (2019)

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Recommendations for rosacea diagnosis, classification and management: update from the global <scp>ROS</scp> acea <scp>CO</scp> nsensus 2019 panel
Authors: M. Schaller, L.M.C. Almeida, A. Bewley, B. Cribier, J. Del Rosso, N.C. Dlova, R.L. Gallo, R.D. Granstein, G. Kautz, M.J. Mannis, G. Micali, H.H. Oon, M. Rajagopalan, M. Steinhoff, E. Tanghetti, D. Thiboutot, P. Troielli, G. Webster, M. Zierhut, E.J. Zuuren, J. Tan
Journal: British Journal of Dermatology (2019)

A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups.
PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express targetable activating and inhibitory receptors
Authors: Guillaume Beyrend, Esmé van der Gracht, Ayse Yilmaz, Suzanne van Duikeren, Marcel Camps, Thomas Höllt, Anna Vilanova, Vincent van Unen, Frits Koning, Noel F. C. C. de Miranda, Ramon Arens, Ferry Ossendorp
Journal: Journal for ImmunoTherapy of Cancer (2019)

The clinical benefit of immunotherapeutic approaches against cancer has been well established although complete responses are only observed in a minority of patients. Combination immunotherapy offers an attractive avenue to develop more effective cancer therapies by improving the efficacy and duration of the tumor-specific T-cell response. Here, we aimed at deciphering the mechanisms governing the response to PD-1/PD-L1 checkpoint blockade to support the rational design of combination immunotherapy.Mice bearing subcutaneous MC-38 tumors were treated with blocking PD-L1 antibodies. To establish high-dimensional immune signatures of immunotherapy-specific responses, the tumor microenvironment was analyzed by CyTOF mass cytometry using 38 cellular markers. Findings were further examined and validated by flow cytometry and by functional in vivo experiments. Immune profiling was extended to the tumor microenvironment of colorectal cancer patients.PD-L1 blockade induced selectively the expansion of tumor-infiltrating CD4+ and CD8+ T-cell subsets, co-expressing both activating (ICOS) and inhibitory (LAG-3, PD-1) molecules. By therapeutically co-targeting these molecules on the TAI cell subsets in vivo by agonistic and antagonist antibodies, we were able to enhance PD-L1 blockade therapy as evidenced by an increased number of TAI cells within the tumor micro-environment and improved tumor protection. Moreover, TAI cells were also found in the tumor-microenvironment of colorectal cancer patients.This study shows the presence of T cell subsets in the tumor micro-environment expressing both activating and inhibitory receptors. These TAI cells can be targeted by combined immunotherapy leading to improved survival.