tbuckley/cabot-search huggingface dataset:
First analysis of EORTC trial 26951, a randomized phase III study of adjuvant PCV chemotherapy in patients with highly anaplastic oligodendroglioma
Authors: M. J. van den Bent, J.-Y. Delattre, A. A. Brandes, M. J. B. Taphoorn, K. Hoang Xuan, H. Bernsen, M. Frenay, W. Grisold, T. Gorlia, D. Lacombe
Journal: Journal of Clinical Oncology (2005)

1503 Background. Anaplastic oligodendroglioma are sensitive to chemotherapy. EORTC 26951 was initiated to investigate whether the addition of 6 cycles PCV chemotherapy after radiotherapy (RT) improves overall survival (OS) and progression free survival (PFS). Methods. Eligibility criteria: histologically confirmed newly diagnosed anaplastic oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) with ≥ 25% oligodendral elements; age between 18–70 years; ECOG Performance Status (PS) 0–2; written informed consent. After stratification for age, institution, extent of resection, ECOG PS, and prior surgery for a low grade oligodendroglioma patients were randomized to either 33 x 1.8 Gy radiotherapy (control arm) or to the same radiotherapy followed by 6 cycles of standard PCV chemotherapy (PCV arm). Primary endpoint was overall survival, with PFS as a secondary endpoint. Results. 368 patients were randomised, 185 to the PCV arm and 183 patients to the control arm. Median follow-up is 4.1 years, 204 patients (55.4%) have died. Treatment groups were well balanced with respect to known prognostic factors. The median number of administered PCV cycles was 3; 35% of patients completed at least 5 cycles. At recurrence, PCV chemotherapy was given to 64% of patients in the control arm vs to 11% in the PCV arm. In addition, 51% of the patients in the PCV arm and 48% of patients in the control arm received other chemotherapy (mostly temozolomide) at recurrence. PFS was significantly increased after adjuvant PCV chemotherapy (table; hazard ratio (HR) 0.69; 95% confidence interval (CI) [0.53;0.88], p = 0.0035). However, no difference in OS was observed (HR 0.88; 95% CI [0.67;1.16]. Conclusion. Adjuvant PCV chemotherapy prolongs PFS from 13 months to 24 months in AOD/AOA, without a statistically significant improvement of OS. Analysis of 1p/19q status is in progress. No significant financial relationships to disclose.
Phase II study of carboplatin, irinotecan, and thalidomide in patients with advanced non-small cell lung cancer (NSCLC)
Authors: A. A. Miller, D. Case, J. Atkins, J. Giguere
Journal: Journal of Clinical Oncology (2004)

7132 Background: We hypothesized that thalidomide improves the response and toxicity profile of chemotherapy with carboplatin and irinotecan because of its novel mechanism of action (anti-angiogenic, anti-neoplastic, anti-inflammatory) which is different from classic chemotherapy and because it causes constipation which may counteract diarrhea of irinotecan. Methods: Treatment consists of carboplatin AUC = 5 iv over 30 min day 1 and irinotecan 50 mg/m2 iv over 90 min day 1 and 8 q 21 days. Thalidomide is given continuously po qhs starting on day 1 until progressive disease; the starting dose is 200 mg/d which is escalated by 100 mg per week if tolerated (max. 1,000 mg/d). The objectives are to determine the response rate, time to progression, overall survival, and toxicity profile. Key eligibility criteria: NSCLC stage IIIB (malignant pleural effusion) and IV; measurable disease; no prior chemotherapy; prior radiation only allowed for brain metastasis, neurologically stable; performance status (PS) 0–1; adequate hematologic, hepatic and renal function. Results: So far, 36 patients have been entered, but 2 never received protocol treatment; characteristics of 34 treated patients: median age 65 (47–79); female/male 8/26; black/white 2/32; PS 0/1 in 10/24; stage 3/4 in 6/28. 23 patients are evaluable for response: partial 5 (22%), stable 12 (52%). The median time to progression is 3.6 months (95% CI, 2.3–4.9). 19 of 34 patients have died. The median survival time is 7.3 months (95% CI, 3.4–14.2). Frequent toxicities are neutropenia (grade 3/4 in 20%/8%), fatigue/malaise (grade 3/4 in 16%/4%), and nausea/vomiting (grade 3/4 in 20%/0%). Diarrhea grade 3/4 occurred in 4%/4%. No patient had lethal toxicity. Conclusions: Treatment with carboplatin, irinotecan, and thalidomide on this regimen is tolerable with reversible neutropenia as the major toxicity. Accrual to this study continues to more firmly establish the objective response rate and survival time. *Supported by NCI grant U10CA81851–04 Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene; Pharmacia
The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling
Authors: Maria Maiarù, Keri K. Tochiki, Marc B. Cox, Leonette V. Annan, Christopher G. Bell, Xixi Feng, Felix Hausch, Sandrine M. Géranton
Journal: Science Translational Medicine (2016)

Polymorphisms in FKBP51 are associated with stress-related psychiatric disorders and influence the severity of pain symptoms experienced after trauma. We report that FKBP51 (FK506 binding protein 51) is crucial for the full development and maintenance of long-term pain states. Indeed, FKBP51 knockout mice, as well as mice in which silencing of FKBP51 is restricted to the spinal cord, showed reduced hypersensitivity in several persistent pain models in rodents. FKBP51 deletion did not compromise the detection of acute painful stimuli, a critical protective mechanism. Moreover, the intrathecal administration of the specific FKBP51 inhibitor SAFit2 reduced the severity of an established pain state, confirming the crucial role of spinal FKBP51 in nociceptive processing. Finally, glucocorticoid signaling, which is known to modulate persistent pain states in rodents, was impaired in FKBP51 knockout mice. This finding suggested that FKBP51 regulates chronic pain by modulation of glucocorticoid signaling. Thus, FKBP51 is a central mediator of chronic pain, likely in humans as well as rodents, and is a new pharmacologically tractable target for the treatment of long-term pain states.
Quantitative determination of predictive cancer biomarkers in formalin-fixed, paraffin-embedded tissue using a new, fully automated method for RNA isolation
Authors: B. M. Müller, R. Kronenwett, G. Hennig, K. Weber, K. Bohmann, K. J. Winzer, G. Kristiansen, C. Petry, M. Dietel, C. Denkert
Journal: Journal of Clinical Oncology (2009)

11032 Background: Personalized cancer therapy depends on the evaluation of tissue-based biomarkers in routine tumor samples. As many new biomarkers are measured on the mRNA level, standardized procedures for mRNA analysis in formalin-fixed, paraffin-embedded (FFPE) tissue are needed. In this study, we present a novel, standardized, and fully automated method for fast isolation of total RNA from FFPE tissue sections. Methods: Tissue samples (n = 501) from 167 breast carcinomas which had been stored between 2 months and 21 years were investigated. Total RNA was extracted from tissue sections using a new method based on silica-coated iron oxide beads in combination with a specific liquid-handling robot. Novel and unique features of the method are an automated extraction-integrated deparaffinization step and a bead-based negative selection step to eliminate any undigested tissue. Yield of RNA was assessed using the Ribogreen assay. mRNA fragment lengths were estimated by reverse transcription PCR (RT-PCR) for G6PDH. Expression of the breast cancer biomarkers ESR1, PGR and HER2 was measured by kinetic RT-PCR (kPCR) and compared with immunohistochemistry (IHC). Results: RNA was successfully isolated from all samples, with a mean yield of 1.4 μg/sample (range: 0.1–7.8 μg) and fragment lengths of at least 150 bp in 99% of samples. PCR analyses could be performed in all samples. Investigating three sections of each tumor, we observed a low section-to-section variability of kPCR results (root of mean squared errors of relative ESR1, PGR or HER2 expression in three sections: 0.2–0.5 Ct values). Comparing kPCR results with IHC, we detected a good concordance between both methods, with agreements of 98.4% (standard error [SE]: 2.7%) for ESR1, 84.4% (SE: 5.3%) for PGR and 89.9% (SE: 8.9%) for HER2. Conclusions: This novel RNA extraction method is a major technical improvement for implementation of reproducible, high-throughput and cost-efficient testing of cancer biomarkers in the clinical routine and in gene-expression research studies using archived FFPE material in molecular labs. [Table: see text]
Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions
Authors: Mauro Giacomelli, Rajesh Kumar, Annarosa Soresina, Nicola Tamassia, Tiziana Lorenzini, Daniele Moratto, Sara Gasperini, Marco Cassatella, Alessandro Plebani, Vassilios Lougaris, Raffaele Badolato
Journal: Journal of Allergy and Clinical Immunology (2016)
Phase II study of gemcitabine, capecitabine and bevacizumab for advanced pancreatic cancer (APC) with ECOG PS 0–1
Authors: M. M. Javle, R. V. Iyer, J. Yu, D. Q. Wilkinson, H. R. Nava, J. T. Phelan, A. M. Litwin, J. M. Haney, J. F. Gibbs, B. W. Kuvshinoff
Journal: Journal of Clinical Oncology (2006)

4117 Background: Gemcitabine and capecitabine chemotherapy may result in improved survival for patients (pts) with APC and good performance status. Preclinical synergy between these agents and bevacizumab (BV) and encouraging results of angiogenic inhibition in PC formed the rationale for this study. Endpoints: Primary: progression-free survival (PFS), Secondary: response rates, overall survival, toxicity assessment and quality of life (QOL). Methods: Pts with APC (inoperable stage III or IV), ECOG PS 0–1, normal organ and marrow function were eligible. Schema: Avastin 15 mg/kg, q 21 days; capecitabine 650 mg/m 2 bid x 14 days, both starting day 1; gemcitabine 1000 mg/m 2 days 1 &amp; 8; cycles repeated q 21 days. The study has a power of 0.8 at 0.05 significance level to determine if PFS is ≥ 4.1 months with study regimen (2.5 months with gemcitabine). Results: Twenty-six (of planned 34) pts have been enrolled; 22 pts were evaluable for response (4 too early). Median age 64 years (range 38–79), 12 are male, one stage III, 25 stage IV. Median of 3 cycles/pt (range 1–16) with a total 105 cycles. Responses (RECIST): 7 partial responses (32%; 95% CI: 14%-55%), 12 stable disease, 3 progressive disease. The median PFS is 8.2 months (C.I. 4.7–11.3). Estimated median overall survival is 9.1 months (C.I. 8.3-undetermined). Five% improvement in QOL occurred in 7/15 pts (95% C.I: 21–73%). Grade 3 toxicities: proteinuria (n=1), neutropenia (n=2), thrombocytopenia (n=1), pulmonary embolism (n=2), nausea (n=2), emesis (n=2), diarrhea (n=1), infection (n=1), anemia (n=1) and hemorrhage (n=1). Grade 4 toxicities: neutropenia, cerebrovascular accident and diarrhea (n=1, each). One treatment related death occurred (hemorrhage). Conclusion: In this interim analysis, encouraging response rates, PFS and QOL improvement occurred with the addition of BV to gemcitabine and capecitabine. Toxicity profile is acceptable. Accrual is ongoing. Acknowledgement: Study is supported by a grant from NCCN and by Genentech. [Table: see text]
Bronchiolitis: A 9 years epidemic seasons analysis
Authors: Marianna Ferrara, Giulia Cangiano, Stefano Papasso, Ambra Nicolai, Melania Evangelisti, Raffaella Nenna, Federico Gentile, Chiara Di Mario, Marco Mariani, Carolina Scagnolari, Alessandra Pierangeli, Fabio Midulla
Journal: European Respiratory Journal (2014)

Background Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Aim To describe infants hospitalized for bronchiolitis during 9 epidemic seasons Oct-May 2004-2013. Methods We enrolled 654 infants (median age 64d, range 7-359d; 355M; mean weight 5.2±1.4kg) hospitalized at the Pediatric Emergency Unit, “Sapienza” University of Rome. 14 respiratory viruses were detected with RT-PCR from nasal aspirates; data were extracted from clinical charts. Results Among children enrolled, 600 (91.7%) were Caucasian, 488 (74.6%) had siblings, 174 (26.6%) attended nursery, 233 (35.8%) had siblings attending school, and 495 (75.7%) were exclusively breastfed. Family history of atopy was referred in 244 infants (34.3%) and of asthma in 149 (22.8%); 296 infants (45.3%) had smoking cohabitants. 64 infants (9.8%) were admitted to PICU. Respiratory viruses were detected in 323 infants (49.2%): RSV in 206 infants (31.3%), HRV in 45 (7%), HBoV in 14 (4.3%), HMPV in 9 (2.8%), other viruses 9 (2.8%) and co-infections in 34 (10.5%). Among virus positive infants, 237 (73.4%) occurred between December to February with a peak of 111 infants (34.4%) in January. HBoV infants were older than RSV and HRV infants (140.8±106d vs 70.8±49.4d and vs 68.7±58.2d; p≤0.001). Eosinophils' count was higher in HRV infants than in those with RSV (221.8±311/mm3 vs 124.5±136.5/mm3; p=0.008). No significant differences were detected in terms of schooling, breastfeeding, family history of atopy and asthma, and smoking cohabitants. Conclusion The clinical aspects of the disease remain stable in the past nine years. RSV is the main virus involved. HRV infection seems to affect atopic infants.
Abstract 276: Prehospital Advanced Airway Management Without Intravenous Access May Negatively Affect Favorable Neurological Outcome in Children With Out-of-Hospital Cardiac Arrest
Authors: Nobuaki Inoue, Naoki Shimizu, Kunio Ohta, Masahiko Nitta, Naohiro Yonemoto, Hiroshi Nonogi, Ken Nagao, Takeshi Kimura
Journal: Circulation (2013)

Background: Although advanced airway management and intravenous (IV) access for patients with out-of-hospital cardiac arrest (OHCA) are thought to be lifesaving procedures at prehospital settings, recent data suggested that these procedures might lead to poorer neurological outcome for adult population. This association needs to be studied further for pediatric population as well. Methods: Data were collected through a Japanese nationwide, population-based registration form for OHCA from 2005 to 2011 involving 13,159 consecutive children aged less than 18 years old. Data regarding OHCA patients such as age, etiology, bystander CPR, and others were collected. Main outcome measure was favorable neurological outcome at one month from OHCA event, which was defined as cerebral performance category 1 or 2. OHCA patients who did not receive any resuscitative intervention by prehospital personnel were excluded from the analysis. Results: 12,510 OHCA pediatric patients were eligible to the analysis. Among these, 465 (3.7%) patients had both IV access and advanced airway (IV+/AA+), 328 (2.6%) patients had only IV access (IV+/AA-), 1,685 (13.5%) patients had only advanced airway (IV-/AA+), and 10,032 (80.2%) patients had neither of them (IV-/AA-). Devices of advanced airway management were esophageal obturator airway (60%), laryngeal mask (30%), and endotracheal tube (10%). Favorable neurological outcome at one month from OHCA event for IV-/AA- group (4.2% [412/10,032]) was compared with other groups. IV-/AA+ group had the worst outcome (1.9% [32/1685]; OR 0.45, 95% CI; 0.31 - 0.64) followed by IV+/AA+ group (3.4% [16/465]; OR 0.82, 95%CI; 0.49 - 1.37) and IV+/AA- group (3.7% [12/328]; OR 0.88, 95% CI; 0.49 - 1.57). Baseline characteristics for these groups were not significantly different except for age distribution as IV-/AA- group were younger than others. There was no statistical difference in neurological outcome between IV-/AA+ group and IV+/AA+ group. Conclusion: Advanced airway management without IV access seems to negatively affect pediatric OHCA patients. Obtaining IV access and further intervention by prehosital personnel may compensate this effect.
Carcinocythemia as the single extension of breast cancer: Report of a case and review of the literature
Authors: S. Seronie-Vivien, E. Mery, J.P. Delord, G. Fillola, J. Tkaczuk, J.J. Voigt, R. Bugat
Journal: Annals of Oncology (2001)

Carcinocythemia (carcinoma cell leukemia) has been previously described as a rare, late and dramatic event occurring in widespread tumoral disease. We report a case of carcinocythemia occurring in a patient with a particularly indolent breast cancer. When a large amount of circulating tumor cells (CTC) appeared in the blood smears, neither visceral macrometastases nor massive bone marrow infiltration could be detected. We isolated CTC to perform cell cycle analysis and to study the expression of adhesion molecules. A fraction of the CTC was proliferating in the bloodstream but we detected no relevant anomaly of adhesion properties in the CTC. A post-mortem biopsy disclosed an exclusive sinusoidal infiltration of the liver. We propose that in this case, carcinocythemia resulted from the release of CTC from the visceral microcirculation where the proliferation occurred.
Predicting change in physical activity following a physical activity intervention
Authors: Katy Mitchell, Louise Sewell, Sally Singh
Journal: European Respiratory Journal (2014)

In order to target treatment most effectively, it would be interesting to learn who is most or least likely to improve their physical activity (PA) in response to an intervention aimed at improving PA.

A sample of 39 people with COPD [male n=24; mean (SD) age 66(8) years; FEV1 1.45(0.62) litres; BMI 27.60(5.56)] underwent a six-week home-based self-management programme (SPACE FOR COPD) which aimed to improve PA. A range of measures were taken at baseline and 6 weeks, including age, FEV1, BMI, the Incremental Shuttle Walk Test(ISWT), Endurance Shuttle Walk Test (ESWT), Bristol COPD Knowledge Questionnaire (BCKQ), Hospital Anxiety and Depression Scale(HADS), the Pulmonary Rehabilitation Index of Self-Efficacy (PRAISE), the Chronic Respiratory Questionnaire(CRQ) and Medical Research Council (MRC) dyspnoea grade. The SenseWear Armband (SAB) was worn for 7 days at both time points and time in moderate-vigorous activity (MVPA) in bouts of at least 10 minutes was the primary measure collected.

Time in MVPA in 10 minute bouts increased from median (IQR) 45(10-155) minutes at baseline to 96(28-246) minutes at 6 weeks. Backward stepwise linear regression was performed, entering baseline and change from baseline-6weeks on all measures, to predict change in time spent in MPVA accumulated in bouts. Only baseline MRC dyspnoea grade was significant, and accounted for 10% of the variance.

It was not possible to use baseline or change parameters to adequately predict response in PA levels after a PA intervention. It is likely that PA is influenced by a wider range of factors, including environmental and social, that cannot be accounted for in this kind of modelling.
Relationship of the aldosterone-induced protein, GP70, to the conductive Na+ channel.
Authors: H Szerlip, P Palevsky, M Cox, B Blazer-Yost
Journal: Journal of the American Society of Nephrology (1991)

Although one of the primary effects of aldosterone is to increase apical membrane Na+ conductance, as yet none of the proteins induced by the hormone in renal epithelia have been shown to be related to the conductive Na+ channel. Because the toad urinary bladder aldosterone-induced glycoprotein, GP70, has recently been localized to the apical surface of this Na+ transporting epithelium, whether GP70 is associated with the Na+ channel was examined. The specificities of a monoclonal antibody used to characterize GP70 (mAb 20) and a polyclonal antibody raised against the purified bovine renal papillary Na+ channel (anti-CH) were compared: GP70 was specifically immunoprecipitated by both mAb 20 and anti-CH. Moreover, the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile of mAb 20 purified toad urinary bladder membrane preparations was similar to those reported for bovine and A6 cell Na+ channels. Under nonreducing conditions, a single, very large protein was evident; reduction yielded GP70, a 140-kd polypeptide, and a number of minor bands. Interestingly, only GP70 was induced by aldosterone. Thus, GP70 appears to be associated with the toad urinary bladder conductive Na+ channel; whether GP70 is an integral subunit of the channel or whether it functions as a regulatory moiety remains to be determined. Whatever the case, because GP70 is induced by aldosterone, it likely has a central role in Na+ channel modulation.
Context for Understanding Psychosocial Outcomes and Behavior Among Adolescents and Young Adults With Cancer
Authors: Brad Zebrack, Melissa Butler
Journal: Journal of the National Comprehensive Cancer Network (2012)

Across all age groups, cancer affects relationships with family and friends; challenges one's sense of independence; disrupts goals, aspirations, and achievements; alters one's body image and integrity; and poses existential challenges about the world and one's place in it. When diagnosed with cancer, adolescents and young adults (AYAs) in their 20s and 30s face unique challenges compared with younger children and older adults. Understanding how cancer-related challenges manifest needs and desires for psychological and social support services throughout a continuum of care may help clinicians improve cost-effective quality care and patient outcomes. This article provides a context for understanding the experiences of AYAs with cancer and highlights key domains of psychosocial need in this population.
Comparable safety and response rate with bevacizumab in combination with capecitabine/oxaliplatin (CapOx/Bev) versus capecitabine/irinotecan (CapIri/Bev) in advanced CRC (mCRC): A randomized phase II study of the AIO GI tumor study group
Authors: W. H. Schmiegel, A. Reinacher-Schick, W. Freier, G. Dietrich, D. Arnold, S. Kanzler, M. Geissler, U. Graeven, S. Hegewisch-Becker, H. Schmoll
Journal: Journal of Clinical Oncology (2007)

4034 Background: Bevacizumab (Bev) combined with 5-FU/FA and both, irinotecan or oxaliplatin are standard regimens for mCRC. Recently, a phase III trial has demonstrated that infusional 5-FU can be substituted by capecitabine (cape) when combined with oxaliplatin and Bev whereas conflicting data are available for feasibility and efficacy of cape/irinotecan combinations. This randomized phase II trial was to compare safety and efficacy of Bev with either CapOx or CapIri in untreated mCRC. Methods: Eligibility criteria: untreated mCRC pts, ECOG PS &lt;= 2, measurable lesion(s), adequate hematologic and organ function. Primary endpoint was % of pts progression-free after 6 months. Treatment plan: Bev 7.5 mg/kg day (d)1 with either oxaliplatin (130 mg/m 2 d1)/cape (1,000 mg/m 2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200 mg/m 2 d1)/cape (800 mg/m 2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were 20% lower for both, cape and irinotecan, compared to previous trials reporting an unacceptable toxicity profile (Köhne, ASCO 2005). Treatment was continued until progression or unacceptable toxicity. Results: So far, toxicity data are available on 228 (118/110 pts arm A/B) of total 240 pts. Baseline characteristics (arm A/B): median age 64/65 yrs, male 67%/68%. A total of 684/719 cycles (median 6/6 cycles) have been administered. Most common CTC grade 3/4 toxicities (% of pts): Diarrhea 17.0/15.5, hand-foot-syndrome 5.9/2.7, peripheral neuropathy 15.3/0.0. Specific AE′s such as thrombosis, 3° hypertension and GI perforation occurred in 3.4/4.5%, 3.4/0.9% and 0.9/0.9% of pts, respectively. Among 185 evaluable pts (96/89), tumor control rates (CR+PR+SD) in arm A/B were 81.4%/82.8%, overall response rates (CR+PR) were 49.0%/52.7%. Conclusions: Both regimens, CapOx/Bev and CapIri/Bev, are well tolerated without differences in toxicity (except neuropathy). Interestingly, despite the protocol defined dose reduction of CapIri there is seemingly no difference in efficacy as measured by tumor control and response rate. Meanwhile, the trial has finished accrual and data including PFS rate will be presented at the meeting. [Table: see text]