tbuckley/cabot-search huggingface dataset:
Differential expression profile of miRNAs and piRNAs in asthmatic and non-asthmatic bronchial smooth muscle cells reveals new possible biomarkers for complex lung diseases
Authors: N. Miglino, E. Alexandrova, A. Hashim, M. Ravo, M. Tamm, F. Baty, M. Brutsche, A. Weisz, P. Borger
Journal: European Respiratory Journal (2014)

Bronchial smooth muscle (BSM) cells are the effector cells of bronchoconstriction and a potent source of inflammatory mediators and angiogenic factors. Small non-coding (snc)RNAs, such as microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) are transcriptional and post-transcriptional regulators of gene expression. Abbarently expressed, they may play a role in airway diseases and/or provide novel biomarkers to characterize lung pathologies.

To assess the miRNAs and piRNAs expression profiles of primary human BSM cells of asthmatic (n=8) and non-asthmatic (n=6) individuals. Library preparation was performed with Illumina TruSeq small RNA sample preparation protocol. Sized smallRNA libraries were gel purified and sequenced on Illumina HiSeq 1500. iMir [BMC Bioinformatics, Dec 2013, 13; 14:362) was used to identify sncRNAs and perform differential expression analysis.

BSM cells of both asthmatics and non-asthmatics expressed 892 and 122 known miRNAs and piRNAs, respectively. 33 miRNAs were differentially expressed in asthmatic vs non-asthmatic BSM cells (p≤0.05, fold-change cut-off≥1.5) and among them 27 were up-regulated and 6 down-regulated. Furthermore, 1 piRNA was found significantly down regulated in BSM cells from asthmatic patients.

We conclude that BSM cells from both asthmatics and non-asthmatics are characterized by distinctly different pools of miRNAs and piRNAs. Differential expression of miRNAs and piRNAs may contribute to, and/or explain, the development of airway diseases and provide novel biomarkers to characterize and discriminate between lung pathologies at an early stage of the diseases.
Cardiac cormorbidities in women with metastatic breast cancer treated with doxorubicin-based and non-doxorubicin-based chemotherapy
Authors: G. J. Watson, M. R. Kugel, H. Shih, C. Tak Piech, R. S. McKenzie
Journal: Journal of Clinical Oncology (2009)

1052 Background: Observational data are sparse regarding cardiac comorbidities in patients with metastatic breast cancer (MBC) newly initiated on chemotherapy. As some MBC treatments are associated with cardiac toxicity, such information would be useful in guiding treatment decisions. The objective of this analysis was to understand the frequency of cardiac comorbidities in MBC patients prior to chemotherapy initiation based on the Medicare 5% standard analytical file (SAF). Methods: The Medicare 5% SAF was used to investigate claims for women with breast neoplasm and &gt; 1 distant metastatic site (based on ICD-9 diagnosis codes) that subsequently received chemotherapy (based on claims with a chemotherapy J code). Cardiac comorbidities [hypertension (HTN), coronary artery disease (CAD), myocardial function (MI), and congestive heart failure (CHF)] prior to initial chemotherapy were reported as non-mutually exclusive categories. The index quarter was based on chemotherapy initiation that occurred between 7/2001 and 12/2006. Patients were categorized based on receipt of non doxorubicin-based chemotherapy (non-DOX) vs DOX-based chemotherapy. Results: The study included 2,587 women with MBC that received cytotoxic chemotherapy subsequent to the diagnosis of MBC. The mean age was higher in the non-DOX group. Both groups reported a significant proportion of patients with cardiac comorbidities prior to chemotherapy, with greater proportions reported in the non-DOX group (table). Conclusions: Cardiac comorbidities were commonly reported in women with MBC prior to chemotherapy. Such information is useful to health care professionals when considering potential interventions for patients with MBC. [Table: see text] [Table: see text]
A Woman With Right Hand and Leg Discoordination
Authors: Robert Jason Perry, Gilbert R. Upchurch
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Pointed Progress in Second-Line Advanced Non–Small-Cell Lung Cancer: The Rapidly Evolving Field of Checkpoint Inhibition
Authors: Barbara Melosky, Quincy Chu, Rosalyn Juergens, Natasha Leighl, Deanna McLeod, Vera Hirsh
Journal: Journal of Clinical Oncology (2016)

Non-small-cell lung cancer (NSCLC) is globally prevalent and associated with high rates of mortality. Immune checkpoint pathways are often exploited by tumors to evade immunity-mediated destruction, and checkpoint inhibitors can reactivate tumor-related immune responses. This review considers available clinical evidence for the use of checkpoint inhibitors in the treatment of second-line advanced NSCLC.Our systematic search revealed 20 clinical trials evaluating checkpoint inhibitors in the second-line setting, three of which were randomized trials comparing programmed cell death protein 1 and programmed death ligand 1 (PD-L1) inhibitors to docetaxel, the current standard of care in this setting.A randomized phase II trial comparing the PD-L1 inhibitor atezolizumab to docetaxel did not demonstrate improved survival for atezolizumab in patients overall, although a trend toward improved survival with increased PD-L1 expression was apparent. Twin phase III trials showed significantly improved survival for the programmed cell death protein 1 inhibitor nivolumab compared with docetaxel in patients with both squamous and nonsquamous disease. PD-L1 expression correlated with improved survival in patients with nonsquamous disease, and patients with low levels of PD-L1 expression (< 10%) and those with EGFR mutations are unlikely to benefit. Checkpoint inhibitor therapy is generally well tolerated and associated with low rates of grade 3 or 4 adverse events compared with standard care.Level 1 evidence exists to support the use of nivolumab as second-line treatment of patients with squamous advanced NSCLC, as well as in select patients with nonsquamous disease. Benefits remain unknown in patients with targetable driver mutations, and use of PD-L1 expression to guide therapy remains controversial. Results from ongoing randomized trials evaluating biomarkers and other checkpoint inhibitors will further our understanding of this rapidly evolving area of oncology.
Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer
Authors: Hikmat A Al-Ahmadie, Gopa Iyer, Byron H Lee, Sasinya N Scott, Rohit Mehra, Aditya Bagrodia, Emmet J Jordan, Sizhi Paul Gao, Ricardo Ramirez, Eugene K Cha, Neil B Desai, Emily C Zabor, Irina Ostrovnaya, Anuradha Gopalan, Ying-Bei Chen, Samson W Fine, Satish K Tickoo, Anupama Gandhi, Joseph Hreiki, Agnès Viale, Maria E Arcila, Guido Dalbagni, Jonathan E Rosenberg, Bernard H Bochner, Dean F Bajorin, Michael F Berger, Victor E Reuter, Barry S Taylor, David B Solit
Journal: Nature Genetics (2016)
Specificities in Human Cell-Mediated Cytotoxicity 2
Authors: Mitsuo Takasugi, Donna Akira, Julie Takasugi, Max R. Mickey
Journal: JNCI Journal of the National Cancer Institute (1977)

Specificity of natural cell-mediated cytotoxicity was investigated through selective reactions detected by direct cell-mediated cytotoxicity and by inhibition of cytotoxicity through competition. Assuming that target cells reacting alike in direct cytotoxicity shared common antigens, we classified 10 target cells into three groups by target antigens: TA (target antigen) 1, 2, and 3. Partial confirmation of the three groups was achieved in the cross-competition assay. The distinction of TA 1 as a group was clear but some cross-reactivity existed between TA 2 and TA 3 cells.
Effects of diagnosis and context on dangerousness
Authors: R L Binder, D E McNiel
Journal: American Journal of Psychiatry (1988)

The authors extensively reviewed the medical records of 253 patients hospitalized on a locked, university-based psychiatric unit. They found that schizophrenic and manic patients were more likely than patients with other diagnoses to be assaultive before admission. In the hospital, however, manic patients were the most likely to be assaultive. The results of this study show that the risk of violence among different diagnostic groups of patients varies according to context and is moderated by situational variables. These findings have implications for the assessment of dangerousness before and during hospitalization.
Role of echocardiography in assessment of pulmonary hypertension secondary to COPD
Authors: Talaat Arafa, Ezzat Rizk, Abdelmonem Elshabrawi, Khaled Naguib, Kamel Hassan, Mohammed Elsheikh
Journal: European Respiratory Journal (2014)

Background  Mild to moderate pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) and is associated with increased risk of exacerbation and decreased survival Echocardiography is an important modality in non invasive assessment of PH and has been used to screen for the disease, determine right and left heart structure and function, and assess response to therapy in persons with PH THE AIM OF WORK  The aim of this study was to evaluate the rule of echocardiography indiagnosis and assessment of PH in COPD patients in different stages of severity   Subjects & Methods  This study included 80 patients with chronic obstructive pulmonary disease admitted in chest department of Al-Azhar University Hospital in (Damietta) in years 2011-2013The patients were divided into four groups :-   Group A:  included (20) patients with stable COPD. Group B:  included (20) patients with COPD in exacerbation.   Group C:  included (20) healthy cigarette smokers without manifestations of COPD.  Group D:  included (20) healthy non-smokers normal persons.Classification of the severity of pulmonary hypertension was done based on the (American Society of Echocardiography) guidelines Results PH was ranged from 18 to 82 mmHg with a mean of 30.63±14.01 ; the highest values were observed in COPD exacerbation groupB (44.40 ±18.79, followed by stable COPD group A (33.40±9.01) , PAP values was increased in COPD patients ( 26 patients 65%) Conclusion The results of the present study showed an association of pulmonary hypertension in 65% of COPD cases, and this reflects impact of clinical , physiologic and pathologic changes of the disease on PAP.
A phase II study of preoperative docetaxel, cisplatin, and capecitabine in patients with gastric carcinoma.
Authors: Pei-Jye Voon, Mu-Yar Soe, Ying Kiat Zee, Benjamin Chuah, Robert S. C. Lim, Asim Shabbir, Jimmy So, Wei-Peng Yong
Journal: Journal of Clinical Oncology (2012)

89 Background: Perioperative chemotherapy has been shown to improve outcomes among patients with locally advanced gastric adenocarcinoma. As docetaxel (D), cisplatin (C), and capecitabine (X) are active agents in gastric adenocarcinoma, we conducted a phase II trial to assess the efficacy and tolerability of preoperative DCX in patients with gastric adenocarcinoma. Methods: We enrolled patients with locally advanced gastric adenocarcinoma (clinical T3/4 or N positive) to preoperative DCX repeated every 21 days for three cycles, followed by surgery. The first cohort of 10 patients received docetaxel 35 mg/m 2 , cisplatin 35mg/m 2 on days 1 and 8, with capecitabine 750 mg/m 2 twice daily from day 1 to day 14. A subsequent cohort of another 11 patients had dose modifications for docetaxel and cisplatin, both to 30mg/ m 2 on days 1 and 8. Results: Twenty-one patients were recruited. Median age was 61 years. Seventy-one percent of patients completed a total of 3 cycles of planned chemotherapy. Fourteen patients have successfully undergone surgery. R0 resection rate was 88%. Pathological complete response (pCR) and near complete response (pnCR) were both 17%. Preoperative radiological assessment showed a partial response rate of 65% after 2 cycles of treatment. Good pathological response (pCR and pnCR) was associated with better event-free survival (26 months vs 12 months, p=0.031). Common grade 3/4 toxicities were diarrhea (38%), neutropenia (30%), stomatitis (14%) and hypokalemia (14%). However, the diarrhea rate was reduced to 15% with dose modifications as mentioned above after 50% of the first cohort of 10 patients developed grade 3/4 diarrhea during the first cycle of chemotherapy. Febrile neutropenia rate was 14%. There was one treatment related death before surgery but no postoperative mortality. Conclusions: Preoperative DCX is highly active with modest toxicity in locally advanced gastric adenocarcinoma. DCX represents an attractive alternative regimen without the need for protracted infusional drug in perioperative chemotherapy for patients with locally advanced gastric adenocarcinoma. Good pathological response is associated with better outcome.
Prevalence, predictors and risk factors of anxiety and depression in cancer patients. A nation-wide survey
Authors: C. Caminiti, F. Campione, C. Sivelli, F. Diodati, R. Passalacqua
Journal: Journal of Clinical Oncology (2004)

8121 Background: Prevalence of psychological distress and its determining factors are not well known and need to be studied further to allow adequate interventions. We present the results of a nation-wide survey establishing, for the first time, the prevalence of anxiety and depression in unselected italian cancer patients and the association between psychological distress and clinical and social-demographic variables. Methods: 3293 consecutive cancer patients, waiting for a visit or for a chemotherapy session in 38 oncology clinics nationwide (3 NCI, 25 in large cities and 10 in smaller towns), completed the Hospital Anxiety and Depression Scale (HADS). The questionnaire was anonimous, and was distributed to patients and collected by personnel not employed in the ward. Data were analyzed through logistic regression. Results: 3197 questionnaires (97%) were collected. Mean age was 59 (18–93); 61% were female. Overall 34% of patients exhibited moderate to severe psychological distress (whole score above threshold 10). Results of the stepwise logistic regression analyses are reported below. Factors significantly associated with a higher level of anxiety and/or depression are: female gender, care received in Southern Italy, living alone, and longer time since cancer diagnosis. Protective factors are: higher education, presence of a point where patients can receive cancer information and support (PIS) in the ward, presence of a psychologist in the team, and good prognosis of the tumor. Conclusions: Psychological distress is relevant and is closely associated with the social, cultural, organizational context where patients are cared for, along with personal and clinical factors. Thus it seems urgent both to improve clinicians' capacity to discriminate abnormal anxiety/depression and to equip oncology divisions with psychologists and informative/supportive facilities for patients. No significant financial relationships to disclose.
Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women.
Authors: T Fornander, L E Rutqvist, H E Sjöberg, L Blomqvist, A Mattsson, U Glas
Journal: Journal of Clinical Oncology (1990)

The decrease in sex steroid hormone levels after the onset of menopause is associated with bone loss and subsequent osteoporosis. Tamoxifen has antiestrogenic properties and may thus theoretically decrease bone mineral density, particularly after long-term treatment. Bone mineral density (BMD) was assessed in 75 recurrence-free postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen (40 mg daily) for 2 or 5 years versus no adjuvant endocrine therapy. The measurements were done about 7 years after the initial randomization. BMD was measured with single-photon absorptiometry (SPA) at two levels of the distal forearm representing cortical and trabecular bone. The BMD was found to be similar among tamoxifen patients compared with the controls. For cortical bone, the BMD was 1.03 g/cm2 (95% confidence interval [Cl], 0.97 to 1.09) among tamoxifen patients and 1.03 g/cm2 (95% Cl, 0.96 to 1.11) in controls. For trabecular bone, the values were 0.74 g/cm2 (95% Cl, 0.70 to 0.79) and 0.73 g/cm2 (95% Cl, 0.68 to 0.79), respectively. The results thus did not indicate an accelerated postmenopausal bone loss with long-term adjuvant tamoxifen.
Metronomic chemotherapy (MC) in the neoadjuvant setting: Results of two parallel feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC) (Traq-Me and TAME).
Authors: Vanessa Petry, Alessandro Leal, Roberto J. Arai, Simone Marinho, Marcelo Paiva, Jose R. Piato, Marcio Rosa, Paulo M. Hoff, Max S. Mano
Journal: Journal of Clinical Oncology (2012)

197 Background: In a previous randomized trial (SWOG 0012), MC seemed to improve pCR rates compared to standard anthracycline/taxane neoadjuvant chemotherapy (NC). We aimed to evaluate the feasibility of MC with a taxane→anthracycline schedule, which has also been shown potentially superior to the reverse sequence [J Clin Oncol 28:15s, 2010 (suppl; abstr 548)]. We also aimed to establish the feasibility of MC in combination with trastuzumab. Methods: The original accrual goal was 25 HER2+ pts and 40 HER2- pts. HER2- pts received MC consisting of paclitaxel (100mg/m2) x8 weeks followed by doxorubicin (24mg/m2) x9 weeks combined with oral cyclophosphamide (100mg/day), without G-CSF. HER2+ pts also received trastuzumab (4 mg/kg followed by 2mg/kg) concurrently with the entire CT. Objectives: Primary: To evaluate the feasibility of these schedules (defined as a febrile neutropenia [FN] rate no higher than 10%). Secondary: cardiac safety and general tolerability; efficacy as measured by objective clinical, radiological and pathologic complete response (pCR). Results: Almost all pts were staged as III (TraQme 8/9 88% and MeTo 4/11 36%). The HER2+ cohort was prematurely closed after 2 (22%) pts developed G3 pneumonitis (during the metromonic phase). Both responded to medical treatment and recovered. One pt had G2 hand-foot skin reaction (HFS) and another had G2 mucositis. The HER2- cohort was also prematurely closed with only 11 pts because of high rates of mucocutaneous toxicity (G3 HFS in 36%, G3 rash in 9%) and also due to the recent SWOG0221 negative results. There were 2 (18%) cases of FN and 3 (27%) of G4 neutropenia in this cohort, but no cases of pneumonitis. 1/11(9%) HER2- and 5/9HER2+(55%) pts had a pCR. VEGF pathway-related biomarkers were collected and will be presented at a later date. Conclusions: The proposed MC schedules proved too toxic to be considered for further clinical development. In addition, MC resulted in unexpectedly high rates of severe pulmonary toxicity when given in combination with trastuzumab. HER2+ but not HER2- pts had an impressively high pCR rate.
A phase II study of mammalian target of rapamycin (mTOR) inhibitor RAD001 plus imatinib mesylate (IM) in patients with previously treated advanced renal carcinoma (RCC)
Authors: J. S. Chan, J. Vuky, L. A. Besaw, T. M. Beer, C. W. Ryan
Journal: Journal of Clinical Oncology (2007)

15600 Background: The serine-threonine kinase mTOR is a valid target for RCC therapy with temsirolimus treatment resulting in improved overall survival in poor-risk patients (Hudes G et al., ASCO 2006). RAD001 is an oral inhibitor of mTOR which has demonstrated activity in RCC at 10mg/day (Amato R et al., ASCO 2006). IM is a tyrosine kinase inhibitor (TKI) of platelet-derived growth factor receptor (PDGFR), a target that may promote angiogenesis and growth of RCC. Combined mTOR and PDGFR inhibition with RAD001 and IM may achieve vertical blockade through the PI3K/AKT pathway. Methods: Eligibility: metastatic clear cell RCC, performance status (PS) 0–2, adequate organ function, and prior treatment with = 1 systemic therapy. Doses were based on a phase I study of the combination in GIST (Van Oosterom AT et al., ASCO 2005): RAD001 2.5 mg p.o. daily and IM 600 mg p.o. daily. Patients were reimaged every 6 weeks. This is a 2-stage phase II study to determine the 3-month progression-free rate. Results: 14 pts have been enrolled. Median age 66 years (51–79). 6 pts PS 0 and 8 pts PS 1. Median number of prior therapies 1.5 (1–4). 12 of 14 patients had prior TKI therapy. Prior therapies included sorafenib (11 pts), interferon (7), sunitinib (3), bevacizumab (2), erlotinib (1), panitumumab (1), high-dose IL-2 (1). Of 10 pts evaluable for the primary endpoint, 3 are progression-free = 3 months. Best response for 9 pts evaluable by RECIST: PR/CR 0, SD 7, PD 2. Most common adverse events in 11 evaluable patients include nausea (8), edema (7), increased creatinine (7), fatigue (7), transaminase elevation (6), thrombocytopenia (5), leukopenia (5), cough (5), diarrhea (5). Grade 3 adverse events include fatigue (3), LE edema, rash, pleural effusion, increased creatinine, abdominal pain, and thrombocytopenia (1 each). There were no grade 4 toxicities. Unique suspected RAD001 toxicities include grade 3 pneumonitis (1) and angioedema (1). Conclusions: The combination of RAD001 and IM has moderate toxicity. This is one of the first studies in RCC patients predominantly pretreated with a TKI. 3 month progression-free rate appears to be a clinically relevant endpoint in this population. [Table: see text]