tbuckley/cabot-search huggingface dataset:
Conditioned medium from human mesenchymal stem cells restores both amiloride sensitive sodium transport and epithelial permeability to protein across alveolar epithelial cell monolayers in an in vitro model of alveolar injury
Authors: Arnaud Goolaerts, Nadia Randrianarisson, Jérôme Larghero, Valérie Vanneaux, Carole Planes, Michael Matthay, Christine Clerici
Journal: European Respiratory Journal (2011)

Patients with acute lung injury (ALI) have a decreased capacity to reabsorb alveolar edema. Alveolar fluid clearance results from the electro-osmotic gradient created by active sodium (Na) transport across alveolar epithelium. In various models of ALI, MSCs reduce pulmonary edema and increase survival in mice, but in some studies, MSC conditioned medium (MSC-CM) was as effective as MSCs themselves. However, the mechanisms of MSC-CM beneficial effects remain unclear. Thus, in this study our objective was to test the effects of human MSC-CM on vectorial ion transport and epithelial permeability in injured alveolar epithelial cells (AEC). After 18 h of exposure to both hypoxia (3% O2) and 25 ng/ml cytomix (IL-1β, TNFα and INFγ) (CYT-HYX), there was an increase in epithelial permeability measured by radio-labeled albumin over 12 h (1.6±0.40 vs 4.7±2.3%, p<0.05) and a marked decrease in transepithelial Na transport (4.2±0.3 vs 1.7±0.1 μA.cm2), (p<0.05). After permeabilization of the basolateral or apical membrane, we showed no change in Na,K-ATPase activity. We then tested the effect of MSC-CM and found that AEC that were exposed to CYT-HX in the presence of MSC-CM (i) completely prevented CYT-HX-induced increase in protein permeability; (ii) restored the amiloride sensitive-Isc, and iii) increased ENaC activity in the apical membrane. Taken together, these findings indicate that MSC-CM exerts beneficial effects on the injured alveolar epithelium through the preservation of epithelial barrier function and by restoring amiloride-sensitive sodium transport.
Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.
Authors: R Zucali, L Mariani, E Marubini, R Kenda, L Lozza, F Rilke, U Veronesi
Journal: Journal of Clinical Oncology (1998)

The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data.Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%).Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors.Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.
Abstract 12731: MicroRNAs 196b-5p and 411-5p Are Associated With Post-Operative Atrial Fibrillation
Authors: Menhel Kinno, Nada Esa, Raghava S Velagaleti, Amir Y Shaikh, Kahraman Tanriverdi, Honghuang Lin, Divakar Mandapati, Stanley Tam, Okike N Okike, John F Keaney, Jane E Freedman, J. Kevin Donahue, David D McManus
Journal: Circulation (2014)

Introduction: Post-operative atrial fibrillation (POAF) develops in 1/3 of patients undergoing cardiac surgery and is associated with significant morbidity and mortality. MicroRNAs (miRs) are gene regulators linked to pathological atrial remodeling. Although genetic factors are implicated in susceptibility to POAF, no studies, to our knowledge, have examined atrial miR expression in relation to POAF. Hypothesis: Changes in miR expression (estimated as fold difference in the delta cycle threshold compared to global mean) in human atria can be associated with POAF. Methods: Atrial tissue (26 from right atrium; 2 from left atrium) was obtained from 28 participants with no history of atrial fibrillation undergoing elective cardiac surgery (36% coronary artery bypass grafting, 50% valve replacement and 14% combined surgeries or others). Based on pilot data and prior literature, the expression of 82 miRs was quantified using high-throughput quantitative reverse-transcriptase polymerase chain reaction. We used l...
Antiemetic prescriptions and understanding in patients with cancer receiving chemotherapy
Authors: E. C. Smyth, O. S. Breathnach
Journal: Journal of Clinical Oncology (2008)

20692 Background: Poor control of chemotherapy induced nausea and vomiting (CINV) may lead to decreased compliance with treatment and impaired quality of life for cancer patients (pts). Education regarding anti-emetic regimens may decrease this occurrence. This study aims to assess levels of patients’ anti-emetic awareness and impact on levels of CINV in that population. Methods: Pts attending an Irish tertiary referral centre for chemotherapy (chemo) from Feb-Mar 2007 participated, answering a short anonymous questionnaire. Factors assessed included age, primary diagnosis, duration of chemo, knowledge of anti-emetic medications (AEM), sources of education on AEM utilised, and frequency of CINV. Results: Fifty-five pts participated. The mean age was 62.4 years (y) (range 28- 88y). Numbers for both sexes were equivalent. The most common cancers treated were colorectal (25%), breast (16%), lymphoma (12%) and lung (9%). Mean duration of attendance was 9.5 months (mo). 62% were educated by physicians on medication, half of whom received information from physicians only. 64% were educated by nursing staff, 33% received information from nurses only. 28% received education from both. 53% received written information. Nurses were twice as likely to give written information (78% vs. 35% RR 2.2 p=0.02). Pts educated by both were more likely to know their AEM than those educated by nurses alone (RR 4.3 p=0.04). 91% self administered their medication. 78% were aware of the purpose of these drugs. 71% could name their tablets. 47% named an AEM as part of their prescription. 22% did not recognise the name of any routinely prescribed AEM. 85% of those <70y could name their AEM vs. 52% of those >70y (p=0.029). 57% treated for <3mo could name their AEM, increasing to 88% for those attending up to 6mo and 100% at >1y (RR 1.8 p=0.005). There was no significant difference in CINV between patients who knew their AEM and those who did not. Conclusions: Pts knowledge regarding AEM varies and is derived from many sources. Older patients exhibited less knowledge regarding their medication intake. Knowledge of AEM increased with duration of treatment. None of these factors appeared to significantly affect CINV in this population. Additional research is needed to evaluate optimal methods of pt education and its impact on CINV. No significant financial relationships to disclose.
The Safe Use of Propofol
Authors: Richard M. Pino
Journal: JAMA Internal Medicine (2016)

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Rescue of experimental intrathecal methotrexate overdose with carboxypeptidase-G2.
Authors: P C Adamson, F M Balis, C L McCully, K S Godwin, J D Bacher, T J Walsh, D G Poplack
Journal: Journal of Clinical Oncology (1991)

The carboxypeptidase G class of enzymes rapidly hydrolyze methotrexate (MTX) into the inactive metabolites 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate. This study evaluated the use of carboxypeptidase-G2 (CPDG2) as a potential intrathecal (IT) rescue agent for massive IT MTX overdose. The CSF pharmacokinetics of MTX with and without CPDG2 rescue was studied in adult rhesus monkeys (Macaca mulatta) using a nontoxic IT 5 mg dose (equivalent to 50 mg in humans). Without CPDG2 rescue, peak CSF MTX concentration was 2,904 +/- 340 mumol/L. Within 5 minutes of administration of 30 U IT CPDG2, CSF MTX concentrations decreased greater than 400-fold to 6.55 +/- 6.7 microM. Subsequently, groups of three monkeys received either 25 mg IT MTX (equivalent to 250 mg in humans) followed by 150 U IT CPDG2 or 50 mg IT MTX (equivalent to 500 mg in humans) followed by 300 U IT CPDG2. All animals survived without neurotoxicity. Our studies suggest that CPDG2 may prove to be an important addition to the currently recommended strategy for the management of IT MTX overdose.
Treatment of diffuse histiocytic lymphoma (DHL) with COMLA (cyclophosphamide, oncovin, methotrexate, leucovorin, cytosine arabinoside): a 10-year experience in a single institution.
Authors: E R Gaynor, J E Ultmann, H M Golomb, D L Sweet
Journal: Journal of Clinical Oncology (1985)

Between March 1974 and December 1983, 83 patients with diffuse histiocytic lymphoma (DHL) were treated with COMLA (cyclophosphamide 1.5 g/m2 day 1; Oncovin (Lilly, Indianapolis) 1.4 mg/m2 days 1, 8, and 15; and cytosine arabinoside 300 mg/m2 and methotrexate 120 mg/m2 days 22, 29, 36, 43, 50, 57, 64, and 71; and leucovorin 25 mg/m2 every six hours X 4, beginning 24 hours after methotrexate). For the purpose of analysis, patients were divided into two groups. Group 1 (n = 54) included patients age 65 or under who had received no prior curative radiotherapy or chemotherapy. Group 2 (n = 29) included all patients over age 65 and patients who had received prior curative radiation therapy or prior minimal chemotherapy. The median time of follow-up for all patients was 28 months. Group 1 included 11 stage II, ten stage III, and 33 stage IV patients. Of 48 evaluable patients in this group, 21 (44%) achieved a complete remission (CR), eight (17%) achieved a partial remission (PR), and 19 (40%) showed no response (NR). Median survival of CR patients was 114+ months, PR patients, 42 months, and NR patients, 13 months. Six CR patients relapsed. The median disease-free survival of CR patients was 108+ months. Group 2 included nine stage II, seven stage III, and 13 stage IV patients. Of 24 patients evaluable for response, eight (33%) achieved a CR, six (25%) achieved a PR, and ten (42%) showed no response. The median survival of CR patients was 114+ months, that of PR patients was 17 months, and that of NR patients, 9 months. Two CR patients relapsed. The median disease-free survival of CR patients had not been reached at 102 months. The regimen was well tolerated in most patients and toxicity was acceptable. We conclude that COMLA is a well tolerated outpatient chemotherapy regimen capable of inducing durable CRs in some patients with DHL. Results achieved with COMLA, however, are inferior to those of more aggressive treatment programs; thus, the use of COMLA as first-line therapy in DHL should be limited to those patients unable to tolerate a more aggressive treatment program.
Three Year Trends of Ideal Cardiovascular Health Metrics Among Employees of a Large Health Care Organization: The Baptist Health South Florida Employee Study
Authors: Oluseye Ogunmoroti, Adnan Younus, Maribeth Rouseff, Ehimen Aneni, Sankalp Das, Don Parris, Leah Holzwarth, Henry Guzman, Thinh Tran, Omar Jamal, Shozab Ali, Rehan Malik, Rameez Ahmad, Emeka Osondu, Janisse Post, Arthur Agatston, Theodore Feldman, Michael Ozner, Emir Veledar, Khurram Nasir
Journal: Circulation (2015)
Poorly differentiated carcinoma of unknown primary site: clinical usefulness of immunoperoxidase staining.
Authors: J D Hainsworth, E P Wright, D H Johnson, B W Davis, F A Greco
Journal: Journal of Clinical Oncology (1991)

To assess the clinical utility of immunoperoxidase tumor-cell staining in patients with poorly differentiated carcinoma of unknown primary site, we performed a battery of stains on tumors from 87 patients treated between August 1978 and April 1983. Poorly differentiated carcinoma or poorly differentiated adenocarcinoma was diagnosed on the basis of light microscopic examination, and all patients were treated before the technology of immunoperoxidase staining was routinely used. Therefore, results of immunoperoxidase staining can be correlated with clinical outcome in this group of similarly treated patients with a long median follow-up. Immunoperoxidase staining confirmed the diagnosis of poorly differentiated carcinoma in 49 patients (56%) and yielded other diagnoses in 14 patients (16%): melanoma, eight; lymphoma, four; prostatic carcinoma, one; and yolk sac carcinoma, one. In 24 patients (28%) the immunoperoxidase staining pattern was inconclusive; electron microscopy was usually helpful in clarifying the diagnosis in these patients. Seventy-five patients (86%) received combination chemotherapy with a cisplatin-based regimen, and 24 patients (28%) had a complete response. Nine of these patients were later given specific diagnoses by immunoperoxidase staining (lymphoma, four; melanoma, four; yolk sac tumor, one). All patients with an immunoperoxidase diagnosis of lymphoma also had clinical features compatible with lymphoma and are long-term survivors. Patients with immunoperoxidase features suggesting melanoma were surprisingly responsive to chemotherapy, with three of seven complete responses and two long-term survivors. Patients with melanoma diagnosed by immunoperoxidase staining should not be excluded from a trial of cisplatin-based therapy. Immunoperoxidase staining is useful in the routine evaluation of metastatic poorly differentiated carcinoma of unknown primary site, as it can occasionally suggest the lineage of the tumor and have specific therapeutic implications.
A phase I clinical trial of combination therapy with gemcitabine and epitope peptides derived from human vascular endothelial growth factor receptor for patients with advanced pancreatic cancer.
Authors: D. Kim, S. Shiozawa, T. Usui, K. Yoshimatsu, K. Ogawa
Journal: Journal of Clinical Oncology (2010)

e13138 Background: Vascular endothelial growth factor receptors (VEGFR) were reported to be a promising target for antiangiogenic cancer immunotherapy. Therefore, a phase I clinical trial of combination therapy with gemcitabine and epitope peptides derived from VEGFR1 and VEGFR2 was conducted for patients with advanced pancreatic cancer. The aim of this study was to evaluate the safety, immunological response, and tumor response. Methods: Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. Epitope peptides derived from VEGFR1 (VEGFR1-1084) and VEGFR2 (VEGFR2-169) were subcutaneously injected on days 3, 10, 17, and 24 in a dose-escalation manner (doses of 0.5, 1, and 3 mg/body, three patients/one cohort). Results: Nine patients were enrolled in this trial. During the clinical course, no major adverse events of grade 4 or higher were observed. So no dose-limiting toxicity was found in this trial. Two patients who showed grade 2 reaction at the injection site were judged as having partial response of the tumor. The analysis of immunological parameters including measurement of the specific cytotoxic T lymphocytes is now in progress. Conclusions: Combination therapy with gemcitabine and epitope peptides derived from VEGFR was well tolerated and the optimal dose for further clinical trials might be 3 mg/body. No significant financial relationships to disclose.
Phase II study of combination cisplatin, docetaxel and erlotinib in patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC)
Authors: E. S. Kim, M. S. Kies, B. S. Glisson, L. E. Ginsberg, F. C. Holsinger, B. J. Burke, M. Truong, A. S. Tsao, W. K. Hong, S. M. Lippman
Journal: Journal of Clinical Oncology (2006)

5521 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for advanced or recurrent HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received one regimen of induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75mg/m 2 and cisplatin 75mg/m 2 , intravenously every 3 weeks and erlotinib 150 mg by mouth daily. Patients were treated with growth factor support. Results: 37 pts have been enrolled thus far. Median age is 56 years (range 39–72). Median ECOG PS is 1 (range 0–2). 32 pts are evaluable for confirmed response using RECIST criteria. Complete responses have been in observed in 3 pts, partial responses in 18 pts and 8 pts have stable disease for an overall response rate of 66% and disease control rate of 91%. Only 2 pts progressed after 2 cycles of treatment. 5 pts had grade 3/4 neutropenia (2 febrile),1 pt had grade 4 diarrhea, and 2 pts had grade 3 rash. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusion: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in advanced HNSCC. Data collection for response rate, duration of response and survival is ongoing. Trial accrual continues up to 50 patients and biopsies are being collected for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). The full data set will be presented at the annual meeting. [Table: see text]
Oncology studies funded by the FDA Office of Women's Health: 1994-2009.
Authors: E. O. Fadiran, T. Nguyen, A. Parekh
Journal: Journal of Clinical Oncology (2010)

e13659 Background: The FDA Office of Women's Health (OWH) funds studies to assess women's participation in clinical trials submitted to FDA and to understand sex differences in disease development, detection, prevention, and outcomes. This project assesses the impact of OWH funded oncology studies. Methods: The final reports were reviewed and grouped as 1. Molecular Mechanism of Treatment Associated Toxicities (MMTAT), 2. Molecular Mechanism of Tumor Development and Suppression (MMTDS), 3. Demographics (DEM), 4. Detection/Prevention (D/P), and 5. Data Analysis (DA). Results: Of 29 oncology studies 19 were completed. MMTAT (9): Five studies investigated tamoxifen toxicities and supported the black box warning of ,serious and life- threatening uterine malignancies- in labeling that was added in 2002. Others studied 1) sex differences in transporter genes linked to tolerability and toxicity, 2) co-administration of anti-HER2 antibody with doxorubicin to show that cardiotoxicity in rats did not intensify, 3) genotoxic and carcinogenic activities of soy isoflavones, and 4) myelosuppression of progenitor stem cells to alkylating agents. MMTDS (4):Two studies identified possible mediators in tumor necrosis and their effects on lymphoma tumor growth in mice, one study assessed carcinogenicity of breast implants and one study utilized photo-carcinogenicity testing in mice to determine threshold level of solar similar light. DEM (2): One study developed a food consumption frequency questionnaire to identify modifiable risk factors in consumption of culture-specific food by African-American women. The other study established a link between low mammography rates and low household income levels. D/P (2): Two studies explored how to improve detection of breast cancer tumors and tumor progression, the economic benefits of mammography regulation and procedures to monitor chemotherapy treatment response. DA (2): These studies provided alternative statistical analysis methods and survival models to improve the outcomes of research studies, data collection and analytical methods. Conclusions: The funded oncology studies contributed to the understanding of treatment toxicities, tumor development, and detection/prevention of cancer in women. No significant financial relationships to disclose.