tbuckley/cabot-search huggingface dataset:
Gemcitabine and oxaliplatin combination: A multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer
Authors: A. Font, E. Esteban, J. Carles, M. A. Climent, J. L. Gonzalez-Larriba, A. Berrocal, J. Bellmunt, I. Garcia-Ribas, X. Marfa, X. Fabregat
Journal: Journal of Clinical Oncology (2004)

4544 Background: Although cisplatin is considered the cornerstone for the treatment of advanced bladder cancer, up to 50% of the patients (pts) cannot receive it because they are considered unfit mainly due to poor renal function. New non nephrotoxic regimens are needed. Gemcitabine and oxaliplatin are active, non-nephrotoxic and with non-overlapping toxicity and therefore being attractive to be studied in combination for unfit bladder cancer patients. Methods: Thirty-six pts unfit (mainly due to renal function,creatinine clearance < 60 mL/min) to receive standard cisplatin-based treatment were included in this multicentric phase II. We describe here the first 27 patients and give response data from the first 12 evaluable pts. Median age was 69 years (range 60–81), 24 male and 3 female, median ECOG was 1 (range 0–2). Three pts had received previous adjuvant chemotherapy and 2 were previously treated with radiotherapy. Fifteen pts had one or two metastatic sites and 12 pts had more than two metastatic sites. Calculated median creatinine clearance was 48 mL/min (range 30–76). Patients were treated with gemcitabine 1200 mg/m2 d 1 and 8 and oxaliplatin 100 mg/m2 on day 8 every 21 days. Results: Median number of cycles was 3 (range 1–6). A total of 74 cycles are evaluable for toxicity. Grade 3–4 hematological toxicity was mild. Grade 3 anemia was reported in 19% of the cycles Grade 3 thrombopenia in 11.5% and Grade 3–4 neutropenia in 4.6% of the cycles. Hospitalization due to neutropenia and fever was required for 2 pts. So far 12 pts are evaluable for efficacy for an overall response rate of 50% (6 partial responses, 5 stabilizations and 1 progression).Conclusion: Gemcitabine-oxaliplatin is an active and tolerable combination in unfit patients with locally advanced or metastatic urothelial cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co.; Sanofi-Synthelabo
Improved event free survival (EFS) with the novel retinoid, bexarotene (BEX) and gemcitabine/carboplatin (G/C) in non-small cell lung cancer (NSCLC)
Authors: M. J. Edelman, J. Kendall, R. Smith, P. F. Hausner, K. Kalra, L. A. Doyle, L. Thomas
Journal: Journal of Clinical Oncology (2004)

7104 Background: BEX (Targretin) is a novel retinoid targeting the RXR receptor. RXR expression has been correlated with survival in NSCLC. Phase I/II data have indicated prolonged survival in NSCL...
Abstract 2321: A hematopoietic stem cell factor drives brain tumor initiating cell genesis through Notch signaling
Authors: Sunghak Kim, Eun-Jung Kim, Park Cheol Gyu, Se-Yeong Oh, Minata Mutsuko, Hyunggee Kim, Ichiro Nakano
Journal: Cancer Research (2015)

Abstract Glioblastomas (GBMs) maintain their cellular heterogeneity with glioma stem cells (GSCs) producing a variety of tumor cell types. Here, we interrogated the oncogenic roles of Lim domain only 2 (LMO2) in GBM and GSCs in mice and human. High expression of LMO2 was found in human patient-derived GSCs compared to the differentiated progeny cells. LMO2 is required for GSC growth both in vitro and in vivo, as shRNA-mediated LMO2 silencing attenuated tumor growth derived from human GSCs. Further, LMO2 is sufficient to induce stem cell characteristics (stemness) in mouse pre-malignant astrocytes, as forced LMO2 expression facilitated in vitro and in vivo growth of astrocytes derived from Ink4a/Arf null mice and acquisition of GSC phenotypes. A subset of mouse and human GSCs converted into vascular endothelial-like tumor cells both in vitro and in vivo, which phenotype was attenuated by LMO2 silencing and promoted by LMO2 overexpression. Mechanistically, the action of LMO2 for induction of glioma stemness is mediated by transcriptional regulation of Jagged1 resulting in activation of the Notch pathway, whereas LMO2 directly occupies the promoter regions of the VE-cadherin gene for a gain of endothelial cellular phenotype. Subsequently, selective ablation of human GSC-derived VE-cadherin-expressing cells attenuated vascular formation in mouse intracranial tumors, thereby significantly prolonging mouse survival. Clinically, LMO2 expression was elevated in GBM tissues and inversely correlated with prognosis of GBM patients. Taken together, our findings describe novel dual roles of LMO2 to induce tumorigenesis and angiogenesis, and provide potential therapeutic targets in MGs. Citation Format: Sunghak Kim, Eun-Jung Kim, Park Cheol Gyu, Se-Yeong Oh, Minata Mutsuko, Hyunggee Kim, Ichiro Nakano. A hematopoietic stem cell factor drives brain tumor initiating cell genesis through Notch signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2321. doi:10.1158/1538-7445.AM2015-2321
The effect of different sequencing regimens of taxanes and anthracyclines in the primary systemic treatment (PST) of breast cancer (BC) patients (pts): M. D. Anderson Cancer Center retrospective analysis.
Authors: R. H. Alvarez, G. Bianchini, L. Hsu, M. Cristofanilli, F. J. Esteva, L. Pusztai, A. Buzdar, G. N. Hortobagyi, V. Valero
Journal: Journal of Clinical Oncology (2010)

548 Background: Taxane (T) and anthracycline (A) based regimens are commonly used sequentially in the PST setting in BC. It is unknown whether the efficacy of such combinations is affected by their sequence of administration. The purpose of this analysis was to assess the clinical relevance of different sequences of T and A in pts receiving PST. Methods: 1,414 pts with stage I-III BC were treated at MDACC between 1994-2009 with sequential PST T→A (84%) or A→T (16%). T-based and A-based regimens included only paclitaxel, and FAC/FEC regimens, respectively. Pts treated with trastuzumab or docetaxel were excluded. Results: The median follow up was 48.5 months and median age 50.2 years (range 23-83). 530 pts (37.4%) had stage I-IIA, 541 (38.2%) stage IIB-IIIA, and 343 (24.2%) stage IIIB-IIIC BC. 958 pts (67.7%) had hormone-receptor (HR) positive BC and 161 (11.3%), HER-2 positive. Because the two groups of patients were not identical in the distribution of prognostic factors at baseline, multivariate regression analysis (MVRA) were used to adjust for imbalances. pCR was observed in 12.4% and 20.9% patients treated with A→T and T→A respectively (OR 0.53, 95% CI 0.35-0.81; p = 0.003). In MVRA after adjustment for age, clinical stage, grade, LVI, HR and HER2 status, the sequence A→T was associated with a marginally significant lower likelihood of pCR (OR 0.63, CI 0.39-1.02; p = 0.059). In Cox univariate analysis A→T sequence was associated with higher risk of relapse (HR 1.95; CI 1.48-2.58 p < 0.0001) and death (HR 2.00; CI 1.46-2.75; p < 0.0001). In multivariate analysis, after stratification for period at diagnosis and adjustment for age, clinical stage, hormonal-receptor status, grade and LVI, AT sequence was associated with higher risk of relapse (HR 1.49 CI 1.10-2.03; p = 0.01) but not significantly associated with survival (HR 1.28; CI 0.90-1.84, p = 0.17). Conclusions: In this retrospective analysis, sequential T→A compared to A→T regimens in the PST setting was associated with higher likelihood of pCR and lower risk of relapse. These results are hypothesis-generating and should lead to prospective comparisions of the two sequences. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis Novartis
A Comparison of Antiarrhythmic-Drug Therapy with Implantable Defibrillators in Patients Resuscitated from Near-Fatal Ventricular Arrhythmias
Authors: The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators
Journal: New England Journal of Medicine (1997)

Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias. They can be treated with either an implantable cardioverter–defibrillator or antiarrhythmic drugs, but the relative efficacy of these two treatment strategies is unknown.
Histocompatibility Variations in Mouse Tumor Cells and Embryonic Tissue With the Use of C57BL/10Sn Strain and Its Isogenic Resistant Strains&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S. S. Dhaliwal
Journal: JNCI Journal of the National Cancer Institute (1964)

Tumors induced in hybrid mice between C57BL/10Sn and its isogenic resistant (IR) strains (shown to be coisogenic) were used for the study of histocompatibility variants in mouse tumor cells. In previous studies A/Sn and its IR strains have been used. These were later shown to be not coisogenic or homozygous. Both hybrid sarcomas and lymphomas were used. Unlike A/Sn and its IR strains, all sarcomas and lymphomas tested produced variants when transplanted in the parental strains. Again, for any hybrid combination, no parental strain was favored for variant production. The number of variants produced deviated from generation to generation. Different sublines of the same tumor also gave different numbers of variants. The number of variants decreased with reduction in inoculum. This indicates that the pre-existence of certain cell clones in the initial inoculum is important in variant production. The variants were highly specific and stable. Homozygous tumors, however, failed to produce true variants. Cytological studies showed that the variants had larger numbers of cells at hyperdiploidy and triploidy than the original tumor. In view of the cytological instability and the difference in transplantation behavior of hybrid tumors, it is concluded that tumors are not good material for the study of somatic mutations. Embryonic tissue was also investigated for histocompatibility changes. As large numbers of cells were required to establish a growth in adult mice, it was found that embryonic tissue could not be used for this purpose.
Retinoids as anticancer agents.
Authors: F L Meyskens
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.3.588 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8445437 Retinoids as anticancer agents. F L Meyskens JrxF L Meyskens JrSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.3.588 PDF "Retinoids as anticancer agents.." Journal of Clinical Oncology, 11(3), pp. 588–589© 1993 by American Society of Clinical Oncology
Randomized phase II trial of budesonide versus placebo in high-risk population with screening-detected lung nodules: Update on secondary endpoints
Authors: B. Bonanni, A. Guerrieri-Gonzaga, D. Radice, D. Serrano, C. Varricchio, S. Ferretti, H. Johansson, E. Szabo, A. Decensi, G. Veronesi
Journal: Journal of Clinical Oncology (2009)

1518 Background: Lung cancer phase II chemoprevention trials have not focused so far on the peripheral lung. CT discovers small, undetermined peripheral nodules, which may be preinvasive lesions. In a recent phase II trial the glucocorticoid Budesonide reduced peripheral nodules at spiral CT. Methods: We performed a randomized, double-blind, placebo-controlled, phase IIb clinical trial of inhaled budesonide in current (CS) or former smokers (FS) with CT-detected peripheral nodules. Primary endpoint: shrinkage effect on nodules. Secondary endpoints: decrease in size/number of the target lesions, modulation of tumor markers in sputum and plasma, toxicity, effect on pulmonary function. Two hundred and two subjects received 800μg budesonide (B) twice daily or placebo (P) for 1 year. CT scans at 0 and 12 months (mts), and clinical evaluation + serum/plasma collection at 0, 3, 6, and 12 months were performed. Subjects were stratified according to gender, smoking habits (CS vs. FS), and nodule characteristics (solid vs. non-solid). Results: Preliminary data had shown no shrinkage of the nodules in the B treated arm in a per subject analysis (primary objective). We present now results on serum markers (ultrasensitive C-reactive protein, CRP), emphysema and pulmonary function. As compared to baseline, CRP median levels show at 12 months a nonsignificant (p = 0.85) reduction: -0.25 ± 0.63 (B) vs. -1.16 ± 0.97 (P). 12-month values are significantly (p = 0.01) associated with baseline values and smoking status, with higher mean values at 12 months in FS (B 2.1 ± 2.0 vs. P 3.4 ± 1.9). Emphysema values at 12 months are significantly higher (p = 0.0022) in the B (+ 0.29 ± 0.06) versus P arm (+ 0.12 ± 0.07). This difference is not correlated to sex (p = 0.7062) and smoking status (p = 0.8044). As regards spirometry, no significant difference on FEV 1% and DLC/VA appears between arms at 12 months: median FEV 1% values 3.7 ± 1.0 for B versus 2.9 ± 1.0 for P (p = 0.6221); median DLC/VA increase of 0.3 ± 1.9 (B) versus decrease of -3.8 ± 1.6 (P) (p = 0.4191). Conclusions: A significant effect of B on ultrasensitive-CRP and pulmonary function has not been shown. CRP results may indicate the lack of systemic absorption of B. Emphysema appears slightly worse in the B arm, particularly in FS; this is worth further investigation. No significant financial relationships to disclose.
Phase 1 first-in-human trial of oral CUDC-907, a dual inhibitor of PI3K and HDAC, in patients with refractory/relapsed lymphoma or multiple myeloma.
Authors: Jesus G. Berdeja, Yasuhiro Oki, Manish R. Patel, Amanda Copeland, Ian Flinn, Sattva Swarup Neelapu, Jaye Viner, Jing Wang, John F. Gerecitano, Anas Younes
Journal: Journal of Clinical Oncology (2015)

8537 Background: CUDC-907 is an oral inhibitor of class I PI3K as well as class I and II HDAC enzymes. Anti-tumor effects of CUDC-907 have been demonstrated in B-cell lymphoma and multiple myeloma xenografts via inhibition of PI3K, MAPK, and STAT pathways. Methods: In a 3+3 dose escalation and expansion trial, CUDC-907 was administered on 3 dosing schedules: once daily (QD), intermittent (ie, twice [BIW] or thrice [TIW] weekly), or five days on/two days off (5/2) in 21 day cycles. Re-staging was performed every 2 cycles. Results: 45 subjects received CUDC-907 at doses up to 60 mg on the QD or 5/2 schedules, and up to 150 mg on the BIW or TIW schedules. Dose limiting toxicities occurred in 3 subjects: 1 at 60 mg QD (hyperglycemia and diarrhea); 1 at 150 mg BIW (hyperglycemia); and 1 at 150 mg TIW (diarrhea). No DLT occurred on the 5/2 schedule. The most common treatment-related adverse events (AEs) included diarrhea (44%), fatigue (29%), nausea (16%) and thrombocytopenia (11%). 38 subjects are evaluable for response. 4/8 subjects with DLBCL or t-FL/DLBCL (median of 4 prior therapies) achieved objective responses including 1 CR (DLBCL) and 3 PRs (1 with DLBCL; 2 with t-FL/DLBCL); with 3/8 achieving stable disease (SD). SD lasting a median of 101 days (40 – 717) has been observed in 21/38 (55%) subjects including: HL (8/10) and MM (3/4). PK plasma levels have revealed a dose-dependent increase in CUDC-907 exposure on the BIW and TIW schedules. Accumulation of active metabolite was only observed on the QD schedule. Conclusions: The safety profile of CUDC-907 for gastrointestinal, hematologic, and hyperglycemic AEs was predictable based on experience with other HDAC and PI3K inhibitors. AEs have been reversible and managed with standard interventions or dose interruption, and fatigue and thrombocytopenia have not been dose limiting. CUDC-907 has achieved objective responses and long-term SD across multiple tumor types and dosing schedules, with objective response achieved in a heavily pretreated DLBCL patient population. Though MTD was not reached in the intermittent or 5/2 schedules, expansion is being studied at 120 mg TIW and 60 mg 5/2 dose levels based upon their efficacy and toxicity profiles. Clinical trial information: NCT01742988.
THE EPIDEMIOLOGY OF FOWL CHOLERA
Authors: Thomas P. Hughes
Journal: The Journal of Experimental Medicine (1930)

1. A bacteriological study has been made of 210 fresh strains of Pasteurella obtained from typical cases of fowl cholera on seven widely separated poultry farms. 2. The strains have proved identical in consisting of small, pleomorphic, bipolar staining, Gram-negative, non-motile bacilli. They grew rapidly in infusion broth plus a trace of hemolgobin. They formed acid but no gas in media containing dextrose, saccharose, and mannite; indol was produced. 3. The strains fall into three distinct groups, according to their colony formation on hemoglobin agar. The "fluorescent" colony was large, whitish, opaque, exhibiting, under suitable conditions marked fluorescence. The "blue" colony was smaller, clear slate-blue, and non-fluorescent. The "intermediate" colony was moderately fluorescent at 15-18 hours growth, and "blue" thereafter. It was "blue" at all times when crowded and occasionally of "ring" form. "Fluorescent" colony cultures developed "blue" colony forms under certain conditions; otherwise all forms were stable. 4. Strains from "fluorescent" colonies were resistant to precipitation by acids, to sedimentation by centrifuging, and although they combined with specific antiserum, did not agglutinate. They were relatively highly virulent and occurred in flocks where fowl cholera was epidemic. 5. Strains from "blue" colonies were precipitated by acids over a wide range of concentration and agglutinated strongly in antisera. They were relatively of low virulence and occurred in flocks where fowl cholera was endemic. 6. Strains from "intermediate" colonies varied in behavior betweee the "fluorescent" and "blue" strains. They came from a flock where fowl cholera was epidemic.
Home rehabilitation to improve respiratory muscles in patients recovering from a prolonged ICU stay and in-hospital rehabilitation
Authors: Michele Vitacca, Luca Barbano, Fabio Vanoglio, Alberto Luisa, Amerigo Giordano, Enrica Bertella, Mara Paneroni
Journal: European Respiratory Journal (2014)

Forty-eight miscellaneous patients (66±12 years) with recent acute respiratory failure necessitating a prolonged ICU stay and an in-hospital rehabilitation were randomized in two groups: treatment (T) and control (C).  T underwent a 6-month home-based rehabilitation program (2 sessions/day, 7 days/week of mobilization, cardiorespiratory training, walking, limb strength exercises supervised by caregiver, periodic home-visits/phone reinforcements) while C underwent standard care.  Maximum inspiratory and expiratory pressures (MIP, MEP), dynamic volumes (FEV1, FVC), arterial blood gases, dyspnea, basal activities daily life, peripheral force measurements, Takahashi and 6 min walking distance tests, quality of life, safety, adherence, patient satisfaction, survival, readmissions and costs were evaluated.  After 6 months, T showed more improvement than C in MIP (14±17 vs. -0.2±14 cmH20) and MEP (27±27 vs. 6±21 cmH20) (all p  In prolonged ICU-stay survivors discharged after rehabilitation, a 6-month, home-based, relatively low-cost, safe, caregiver-guided physiotherapy intervention had positive effects only on respiratory muscles.
Evaluation of pharmacokinetics (PK) and pharmacodynamics (PD) of patupilone and warfarin in patients (pts) with advanced solid tumors: An open-label, phase I study
Authors: C. H. Takimoto, S. Fu, N. Dhillon, M. M. Mita, A. C. Mita, W. Cheung, Y. Xu, A. Ali, A. Johri, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

2548 Background: Warfarin is an effective anticoagulant frequently prescribed to cancer pts who are at increased risk of thrombotic events. Clinical data show patupilone, a novel epothilone, inhibits growth of a variety of solid tumors. In vitro studies show patupilone to be a weak inhibitor of CYP2C9 enzymes, the main enzyme in (S)-warfarin metabolism. This ongoing drug-drug interaction study evaluates patupilone’s effects on the PK/PD of (S)-warfarin in pts with advanced malignancies. Methods: This open-label, single- arm, multicenter, phase I study evaluates pts who completed 2 warfarin doses (20 mg oral) and 2 cycles of patupilone (single 10 mg/m2 20 min IV infusion every 3 weeks). On cycle 1 Day 1, pts received warfarin; on Day 8, patupilone was administered. On cycle 2 Day 1, warfarin was given prior to the patupilone infusion. PK/PD samples (predose to 168 hrs) were drawn during cycles 1 and 2. Results: Twelve of the 17 enrolled pts who completed 2 cycles of patupilone with PK/PD samples were evaluable. Median age was 63 yrs (range 20–79). The most common adverse events (AEs) suspected to be study drug related were diarrhea 77%, nausea 35%, and fatigue 41%. Seven G3 AEs were suspected to be related to study drug: diarrhea (3), increased INR (3), and dehydration. There were no G4 AEs. Preliminary PD data show the mean AUCINR with and without patupilone was 252 (39% CV) and 247 (45% CV), and the mean AUCFactor-VII was 9,684 (41% CV) and 10,938 (72% CV), respectively. There is no statistical difference in either mean AUCINR or AUCFactor-VII between patients with or without patupilone. PK data will be presented. Conclusions: Based on the current preliminary PD data there is no evidence of drug-drug interaction between patupilone and (S)-warfarin. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis, Pharmion Novartis Novartis, Pharmion Novartis, Pharmiion