tbuckley/cabot-search huggingface dataset:
A phase I study of vorinostat (suberoylanilide hydroxamic acid, SAHA) in Japanese patients with gastrointestinal (GI) cancer
Authors: K. Chin, K. Hatake, T. Hamaguchi, K. Shirao, T. Doi, K. Noguchi, J. E. Garcia-Vargas, A. Ohtsu
Journal: Journal of Clinical Oncology (2008)

15656 Background: Vorinostat is an inhibitor of histone deacetylases with clinical activity in patients (pts) with various types of cancer including cutaneous T-cell lymphoma. However, the safety, clinical activity and PK profile in Japanese pts with GI cancer had not been evaluated until now. Methods: Japanese pts with GI cancers who failed standard therapy were enrolled into 2 dose levels that were recommended doses used outside Japan. For a course of 21 days, vorinostat was to be administered 300 mg BID for 3 consecutive days followed by a 4 day-rest (Level 1) and to be escalated to 400 mg QD continuous (Level 2) to evaluate its safety. PK and response were also assessed. Results: All 16 enrolled pts had GI cancer: 10 gastric cancer, 3 rectal cancer, and 3 colon cancer. Median age was 58 yrs [32–73] and no. of prior regimens was 4 [2–6]. All were assessed for safety and 1 pt was excluded from PK assessment due to incomplete dose received on the first day. At level 1, none of the 10 pts experienced DLT. In cycle 1 at level 2, 2/6 pts developed Grade 4 thrombocytopenia as DLT, and 1 pt developed a non-DLT Grade 3 thrombocytopenia. Although the PK profiles were generally consistent with the results in the previous phase I study (ASCO2007 Abs#14015), the above 3 pts in level 2 showed higher exposure, which was clinically and pharmacologically meaningful, compared with the previous data on 400 mg QD in the Japanese solid tumor pts. All ≥Grade 3 drug-related adverse events which were thrombocytopenia (31.3%) and anemia (6.3%) resolved with supportive therapy. Of all 16 pts, 8 pts achieved SD as best response. Median duration of SD was 3.4 m. Of the 8 pts with gastric cancer who received 300 mg BID, 3 achieved SD for >4.0 m, including 1 who maintained SD for 8.1 m. This study is complete as of Oct 2007. Conclusions: This study demonstrates that 300 mg BID for 3 consecutive days followed by a 4 day-rest every week was a tolerable dose regimen for Japanese GI cancer based on safety and PK results. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck
Activity and Safety of Trabectedin in patients with Sarcomatoid / Biphasic Malignant Pleural Mesothelioma (MPM)
Authors: D. Cortinovis, L. Hollander, I. Floriani, F. Grosso, A. Marinello, G.L. Ceresoli, I. Pacchetti, P.A. Zucali, M. Tiseo, M. D'Incalci, S. Canova, F. Ugo, S. Vukcaj, M.I. Abbate, S. Zai, P. Bidoli
Journal: Annals of Oncology (2015)
Differential Expression of Tumor-Associated Antigens in Human Colon Carcinomas Xenografted Into Nude Mice&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: D V Gold, D Shochat, F J Primus, D L Dexter, P Calabresi, D M Goldenberg
Journal: JNCI Journal of the National Cancer Institute (1983)

The tumor-associated antigen profile of a number of different human colon carcinomas xenografted into inbred Swiss nude mice was examined to determine whether the tumors could serve as useful models for antigen purification, radioimmunodetection, and immunotherapy. Extreme heterogeneity was observed both by radioimmunoassay and immunohistochemical procedures for the expression of carcinoembryonic antigen (CEA), colon-specific antigens (CSAp), and colonic mucin antigen (CMA) within the tumors. Four of 10 tumors (DLD-2, DLD-3, DLD-5, and HCT-10) were high producers of CEA (greater than 75 micrograms/g wet tissue wt). Two of these (DLD-2 and HCT-10) correlated with a high production of CSAp and CMA, whereas the other 2 produced low quantities of these antigens. Another tumor, HCT-14-OM1, produced large amounts of CMA yet produced moderate amounts of CEA and low quantities of CSAp. Immunohistochemical analyses of CEA gave a mostly diffuse cellular and cell surface staining for all of the tumors. Staining for CSAp was very focal, as in DLD-5 where only a few of the tumor cells were stained. Staining of CMA was limited; however, DLD-2, HCT-10, and HCT-14-OM1 showed intense cystoplasmic and intraluminal staining. A determination of the tumor antigen profile may be useful in characterization and classification of the tumor as well as enabling the selection of the proper antibody or antibodies for immunodetection and immunotherapy.
Prospective randomised phase II study of gemcitabine and vinorelbine versus gemcitabine and docetaxel combination in patients with previously untreated advanced non-small cell lung cancer
Authors: Y. Fernández, E. Esteban, N. Villanueva, J. Fra, I. Muñiz, P. Jimenez, M. Luque, J. Vieitez, E. Estrada, A. Lacave, J. M. Buesa
Journal: Journal of Clinical Oncology (2006)

17052 Background: Previous comparative studies have shown similar efficacy and less toxicity with either the Gemcitabine(G)/Vinorelbine(V) or Gemcitabine/Docetaxel(D) combination with respect to platinum-based chemotherapies in patients with advanced NSCLC. This trial was designed to test the efficacy and safety of both GV and GD combination in non-selected patients with advanced NSCLC. Methods: Patients (n = 39) with ≤75 years of age, KPS ≥ 60% and adequate haematological, renal and hepatic function were randomly assigned to: G 1250 mg/m 2 i.v. d1 and d8 plus either V 25 mg/m 2 i.v. d1 and d8 or D 35 mg/m 2 i.v. d1 and d8 every 3 weeks. Prophylactic i.v. ranitidine (50 mg), diphenhydramine (25 mg) and dexamethasone (8 mg) were prescribed just prior to the administration of taxane that was given over 30 minutes immediately before gemcitabine. Results: Baseline characteristics were comparable in GV (n = 20) and GD (n = 19) arms: median age (67 years) and KPS (70%), most patients were male (79%), had metastatic disease (85%) and adenocarcinoma histology (55%). Treatment indicated objective response of 7 (35%) versus 6 (31%) patients, median time-to-treatment failure of 120 versus 90 days, and overall survival of 209 versus 177 days in GV and GD arms respectively. The most common non-haematological toxicities were (GV versus GD; No. of patients): grade 2–4 pulmonary toxicity in 1 versus 7 (37%); grade 2–3 diarrhoea in 0 versus 4 (21%) and oedemas 1 versus 3. Grade 2–4 haematological toxicities in 5 versus 2 patients. All side effects were reversible phenomena since resolution was achieved by suspending the treatment and in the case of the pulmonary toxicity, by the prescription of additional corticoids. Conclusion: The combination of Gemcitabine/Docetaxel does not have a favourable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity. Further patients’ enrolment was stopped and the study has been terminated. This kind of toxicity and alternative schedules of GD combination warrant further investigation. No significant financial relationships to disclose.
Evaluation of FDG PET in early axillary lymph node response to neoadjuvant chemotherapy in locally advanced breast cancer patients
Authors: C. Rousseau, C. Bodet-Milin, J. Bennouna, L. Ferrer, L. Campion, B. Bridji, C. Sagan, M. Ricaud, I. Resche, F. Kraeber-Bodere, M. Campone
Journal: Journal of Clinical Oncology (2006)

10500 Background: Regional axillary lymph node status has remained the single most independent variable to predict prognosis both in terms of disease recurrence and survival. This study aimed to prospectively assess sequential FDG PET findings as early predictors of axillary lymph node response to neoadjuvant chemotherapy in locally advanced breast cancer patients. Methods: A total of 255 attenuation-corrected scans were obtained from 51 patients. Images were acquired with a PET/CT scanner (GE Discovery LS) following administration of FDG (5 MBq/kg) at baseline, and after the first, second, third, and sixth course of chemotherapy. Clinical examination and US were used to assess the size of axillary lymph nodes. PET data were interpreted using standardized uptake values (SUV) corrected or not for partial volume effects. Changes in the SUV were considered as surgical/histopathological responses. Results: This study focused on axillary lymph node staging, therefore, primary breast tumor data were not considered in the analysis. The sensitivity, specificity, and accuracy of axillary node staging was higher with PET (75%, 87%, 80%) than with clinical examination and US (50%, 78%, 63%, and 50%, 83%, and 65%, respectively), and even the more so when PET images were corrected for partial volume effects (86%, 83%, 84%). Significant differences between absolute FDG uptake values in responders and non-responders were observed at baseline (p &lt; 0.05). While FDG uptake did not vary much in non-reponders, as confirmed by histopathology, it markedly decreased to baseline levels in responders (p &lt; 10 −5 ). Fifty percent of baseline SUV was considered the best cut-off value to distinguish responders from non-responders. The sensitivity, specificity, negative predictive value, and accuracy of FDG PET after one course of chemotherapy were respectively, 96%, 75%, 95%, and 84%. Tumor response assessment by clinical examination or US was never statistically significant whatever the cut-off. Conclusions: The pathological status of regional axillary lymph nodes in locally advanced breast cancer patients can be accurately predicted after one course of neoadjuvant chemotherapy based on FDG PET images. No significant financial relationships to disclose.
Red blood cell distribution with in patients With chronic obstructive pulmonary disease
Authors: Akif Özgül, Ekrem Seyhan, İmran Ömur
Journal: European Respiratory Journal (2013)

Bacgraund: Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease (CVD). Red blood cell distribution width (RDW) is a newly recognized risk marker in patients with established CVD. It is unknown whether RDW is associated with in COPD patients.

Aims: To study value of RDW in patients with COPD and to compare the value of this measurement with cardiac, respiratory, and hemotological status.

Method: Two hundred five patients patients with stable COPD and 110 healthy controls cases were enrolled in the study. Demographic, clinical, echocardiographic, and laboratory characteristics were registered in COPD patient.

Results: In the overall patients, the RDW level had a mean value of 15.1± 2.1. The RDW values were higher in the COPD group than in the controls (p< 0.001). RDW was positively correlated with C-reactive protein (CRP) (p= 0.008), right ventricular dysfunction (RVD) (P< 0.001), presence of CVD (p<0.01) and pulmonary arterial hypertension (PAH) (P= 0.03). In multivariable logistic regression, the presence of high RDW was the only parameter independently predicting RVD in patients with COPD (odds ratio, 2.098; P = .017).

Conclusion: RDW may be used to identify COPD patients with RV failure. RDW is independently associated with cardiovascular disease in patients with COPD.
Repeated mannitol or NaCl hyperosmolar exposure of bronchial epithelial cells to mimic exercise-induced airways damage
Authors: Laura Chimenti, Roberta Santagata, Vincenzo Bellia, Ramon Farrè, Maria R. Bonsignore
Journal: European Respiratory Journal (2011)

Hyperosmolarity of the airway surface lining fluid might be involved in exercise-induced airway epithelial damage. Hyperosmolarity causes release of interleukin 8 (IL-8) by bronchial epithelial cells (BEC) in vitro, but the effects of repeated hyperosmolar exposure on BEC are unknown. 16HBE cells were exposed to NaCl or Mannitol (Mann) (320, 640, 960, 1280 mOsm/kg H2O) in culture medium for 10 or 40 min for 3 consecutive days; at 24 h after each exposure, supernatants were collected and stored at -80 C for subsequent IL-8 measurements (RD however, IL-8 release decreased at days 2-3 compared to day 1 (p<0.05). Repeated NaCl or Mann treatment for 10 min decreased cell viability by 10-20% (p<0.0001), while hyperosmolar exposure for 40 min decreased cell viability in an dose-dependent manner at day 1 and dramatically at days 2-3 (-60% for NaCl, -40% for Mann at highest concentrations, p<0.0001). NaCl was cytotoxic compared to Mann (p<0.05). PJNK expresssion increased dose-dependently with hyperosmolarity at days 1-2 but decreased at day 3; IL-8 release was blocked by a specific JNK inhibitor (SP600125). Therefore, hyperosmolar exposure acutely activates BEC through JNK activation, whereas prolonged hyperosmolar exposures repeated for 3 days decrease IL-8 release likely due to major epithelial damage.
Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood
Authors: Valerie Tutwiler, Rustem I. Litvinov, Andrey P. Lozhkin, Alina D. Peshkova, Tatiana Lebedeva, Fazoil I. Ataullakhanov, Kara L. Spiller, Douglas B. Cines, John W. Weisel
Journal: Blood (2015)
The O-Linked N-Acetylglucosamine Transferase Modifies HOXA9 and Inhibits HOXA9-Driven Immortalization
Authors: Jean-Francois M Rual, Jay L. Hess, Tao Xu, Cailin Collins, Honglai Zhang, Kimberly Ha, Sung Soo Park, Joel Bronstein, Jingya Wang
Journal: Blood (2013)
Response to Letter Regarding Article, “Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism”
Authors: Teruo Noguchi, Satoshi Yasuda, Tatsuhiro Shibata, Shoji Kawakami, Tomotaka Tanaka, Yasuhide Asaumi, Tomoaki Kanaya, Toshiyuki Nagai, Kazuhiro Nakao, Masashi Fujino, Kazuyuki Nagatsuka, Hatsue Ishibashi-Ueda, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Hisao Ogawa
Journal: Circulation (2016)
Bringing healthcare to the UK’s abused domestic workers
Authors: Richard Hurley
Journal: BMJ (2016)

As we wrap up this year’s winter appeal, <b>Richard Hurley</b> reports on some of Doctors of the World’s work in London. The charity is well versed in bringing care to the most vulnerable people in developing and developed countries. You’ve raised more than £25 000 so far, and there’s still time to donate
Abstract 118: Epigenetic Regulation of Ventricular Development
Authors: Youngsook Lee, Eunjin Cho, Matthew Mysliwiec
Journal: Circulation Research (2014)

Perturbations of the epigenetic machinery can lead to the deregulation of cardiac gene expression, resulting in defective cardiac development and cardiac hypertrophy. Due to a groundbreaking discovery of histone demethylases such as Jumonji (Jmj) family factors, histone methylation is now considered as a reversible epigenetic mark. Jarid2/Jumonji is the founding member of the JMJ family. Jarid2 is enzymatically inactive, but functions as a transcriptional regulator. Jarid2 critically regulates cardiovascular development as well as ES cell differentiation and generation of iPS cells. Jarid2 knockout (KO) mice exhibit cardiac defects including hyper-trabeculation with noncompaction of the ventricular wall. Although Jarid2 interacts with Polycomb Repressor Complex in ES cells, the precise function of Jarid2 in cardiac development remains to be determined. Therefore, we set out to determine molecular mechanisms of Jarid2 critical for cardiac development. To identify cardiac-specific roles of Jarid2, we generated deletion of Jarid2 in early cardiac progenitors using Nkx2.5-Cre Knock-in mice (Jarid2Nkx-KI). Jarid2Nkx-KI mice recapitulate partial phenotypic defects observed in Jarid2 KO including hyper-trabeculation, thin myocardium and ventricular septal defects. By overlapping ChIP-chip and microarray analyses, we have identified potential transcriptional targets of Jarid2, which are occupied by Jarid2, SETDB1, H3K9me3 or H3K27me3, and upregulated in Jarid2 mutant hearts. 174 genes including Isl1 were identified as dysregulated genes that showed accumulation of Jarid2 and H3K27me3. 172 genes including Bmp10 were identified as dysregulated genes and were occupied by Jarid2, SETDB1 and H3K9me3. Isl1, Bmp10/p-Smad1/5/8, and Ifgbp2 were upregulated in Jarid2Nkx-KI hearts by qRT-PCR and Western blotting. Islet1 plays crucial roles in early cardiac development and a marker for cardiac progenitors. Jarid2 occupancy was observed at the Isl1 promoter region by ChIP assays in WT hearts, which was reduced in Jarid2Nkx-KI. All together, our data indicate that Jarid2 regulates target gene expression by interacting with different histone modifiers depending on the cell/promoter context, which is critical for ventricular wall maturation.
Erratum. Small Fiber Neuropathy in Patients With Latent Autoimmune Diabetes in Adults. Diabetes Care 2015;38:e102–e103
Authors: Uazman Alam, Omar Asghar, Ioannis N. Petropoulos, Maria Jeziorska, Hassan Fadavi, Georgios Ponirakis, Andrew Marshall, Mitra Tavakoli, Andrew J.M. Boulton, Nathan Efron, Rayaz A. Malik
Journal: Diabetes Care (2015)
High Dose Cyclophosphamide (HDCy) Post Stem Cell Transplant (SCT) Following High Dose Melphalan (HDMel) Based Conditioning As a Dual Strategy For Chemotherapy Dose Intensity and Graft Versus Host Disease (gvhd) Prophylaxis In Matched and Mismatched allogeneic (allo) SCT
Authors: Rajneesh Nath, Jan Cerny, Muthalagu Ramanathan, Glen D Raffel, Jayde Bednarik, Neng Yu, Zankar Desai, Lindsey Shanahan, Natasha Fortier, Mridula George, Aimee Kroll-Desrosiers
Journal: Blood (2013)
Impact of skeletal complications on total medical care costs in prostate cancer patients with bone metastases
Authors: J. M. McKiernan, T. E. Delea, M. Liss, J. S. Edelsberg, J. Brandman, J. C. Sung, M. K. Raut, G. Oster
Journal: Journal of Clinical Oncology (2004)

6057 Background: Prostate cancer patients with bone metastases often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, or pain requiring surgery, radiotherapy, or opioid analgesics. Previous studies have estimated the costs of SREs by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs have effects on other services. Methods: We used a large US health insurance claims database (7/94 - 6/02) to quantify impact of SREs on total medical care costs in patients with bone metastases of prostate cancer. Subjects included in this analysis had ≥2 encounters with a diagnosis of primary prostate cancer and ≥2 encounters with a diagnosis of metastases to bone. Expected total medical care costs were compared for propensity-matched samples of patients with SREs versus patients without SREs. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≥1 encounter with a diagnosis of pathological fracture or spinal cord compression, or (2) ≥1 bone surgery or radiotherapy procedure, or (3) initiation of opioid analgesic therapy. Results: We identified 542 prostate cancer patients with bone metastases, including 282 (52%) with ≥1 SRE. After matching, there were 181 patients each in the SRE and no-SRE groups with mean follow-up of 13 and 10 months respectively. In the SRE group, expected costs of care directly attributable to SREs were $9,783 per patient. Expected total medical-care costs were $20,484 greater in SRE patients ($59,522 vs $39,038 in the no-SRE group) Conclusions: The costs of SREs in patients with prostate cancer and bone metastases are substantial and potentially greater than previously estimated. Treatments which prevent SREs, such as the intravenous bisphosphonate zoledronic acid, may reduce these costs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Aventis Oncology
Triple Fixation Suture in Operative Gynecology
Authors: A K Mighton
Journal: JAMA (1963)

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The prevalence of obstructive sleep apnoea syndrom in individuals with occupational injuries: A case-control-study
Authors: Stig Solbach, Werner Strobel, Kathrin Uehli, Stefanie Zogg, Selina Duerr, Sabrina Maier, Jörg Leuppi, David Miedinger
Journal: European Respiratory Journal (2014)

Background/Objective:  Some sleep disorders are known risk factors for occupational injuries. The aim of this study was to compare the prevalence of obstructive sleep apnoea syndrome (OSAS) in a population of patients with occupational injuries admitted to the emergency room (ER) to compare with a population of hospital outpatients.   Methods:  Seventy-nine patients with self-afflicted occupational injuries (cases) and 56 outpatients (controls), were recruited at the University Hospital Basel (Switzerland) between 2009 and 2011. All patients had to complete a sleep-related questionnaire and underwent full-night attended polysomnography. We considered an Apnoea- Hypopnea Index (AHI) ≥5 as clinically significant for OSAS.   Results:  Both groups were not different in sex (59.5% men in the patients group versus 48.2%, p=0.22), in age (36.1 years vs 39.3 years, p=0.15) and the BMI (mean 25.9 versus 24.7, p=0.046). None of the cases and controls had a previous diagnosis of OSAS. The median of the AHI was 5 (0 to 55.9) compared to 3.3 (0 to 42.7, p=0.17). Forty cases (50.6%) had an AHI ≥ 5 compared, to 17 (30.4%) controls (p=0.022). Ten cases (12.7%) had an AHI >15 compared to 6 (10.7%) in the control group (p=0.48).   Conclusions:  In our sample individuals with occupational injuries had more often clinically significant an OSAS compared to hospital outpatients treated for other conditions. We suggest that OSAS must be considered as a risk factor for occupational injuries and patients admitted to an ER should be evaluated for this condition.
Unusual Presentations of Malignancy
Authors: Anthony Abner, Matthew Kaufman, Susan Poires, Gregory Gauvin
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.13.3288 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11432897 Unusual Presentations of Malignancy Case 1. Male Inflammatory (?) Breast Cancer Anthony AbnerxAnthony AbnerSearch for articles by this author , Matthew KaufmanxMatthew KaufmanSearch for articles by this author , Susan PoiresxSusan PoiresSearch for articles by this author , Gregory GauvinxGregory GauvinSearch for articles by this author Show More Mt Auburn Hospital, Cambridge, MA https://doi.org/10.1200/JCO.2001.19.13.3288 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology