tbuckley/cabot-search huggingface dataset:
Sirolimus and cyclophosphamyde in advanced inoperable mixoid chondrosarcoma.
Authors: A. Longhi, G. Bianchi, M. C. Salone, S. Ferrari
Journal: Journal of Clinical Oncology (2011)

e20512 Background: Mixoid chondrosarcoma (CS) is a chemoresistant tumor. Merimsky O reported a case report of a patient with multiple lung metastases from mixoid CS of ribs treated succeffully with Sirolimus and Cyclophosphamyde. We wanted to assess the feasibility and effectiveness of this combination in patients with inoperabile metastatic mixoid CS in a exploratory pilot study. Methods: Eligible criteria were: patients with inoperabile advanced metastatic mixoid G2 or G3 (FNCLCC) chondrosarcoma and patients who refused demolitive surgery All patients had progressive measurable disease, good bone marrow, renal and hepatic functions, ECOG PS >/= 2. Treatment schedule was as reported by Merimsky: Cyclophosphamyde 200 mg/d po days 1-7 and 15-21; Sirolimus 1 mg x3/d day 1-21 d every 28 days. Blood count, chemistry, Sirolimus levels were tested every 2 wks. Evaluation of response was done according to RECIST criteria. Ethical Commetee approval was obtained Chondrosarcoma has slow growth, it was reported (Maky R) the best physician assessed response to chemotherapy was Stable Disease of at least 6 mos reached in not more then 25% in pts with metastatic CS. Our end point was a PFS >/=6 months in at least 40% of patients. Results: From 1 January 2010 to 31 January 2011 we enrolled 8 consecutive patients. 7 patients had lung metastases, one patient had a pelvic inoperable metastases. Male:female=6:2. Median age 61 (47-72). 3 patients received other lines of chemotherapy for metastatic disease. Tolerability to treatment was good: 2 patient reported an increase of total cholesterol (G3,G1), 4 pts of tryglycerids (G1,G2) that recovered with statine. Nausea and vomiting (G2G3) was reported in 2 patients and required a reduction of Cyclophosphamyde dose. Sirolimus avarage level was 9,1 (safe range 4-12). At 31 January 2011. Median PFS is 6 months (3-12) 3 patients with lung metastases are on treatment with stable disease. 5 patients stop tretment for Progression after a median of 3 ms. Conclusions: The combination of the mTor inhibitor sirolimus and cyclophosphamyde is safe, well tolerated in advanced mixoid CS patients, preliminary results are encouraging.
VAD-doxil vs.VAD-doxil Plus Thalidomide as Initial Treatment in Patients with Multiple Myeloma: A Multicenter Randomized Trial of the Greek Myeloma Study Group.
Authors: Konstantinos Zervas, Dimitra Mihou, Irini Katodritou, Anastasia Pouli, Chrisanthi H. Mitsouli, Athanasios Anagnostopoulos, Souzana Delimbasi, Marie-Christine Kyrtsonis, Nikolaos Anagnostopoulos, Evangelos Terpos, Panagiotis Zikos, Meletios A. Dimopoulos
Journal: Blood (2006)
ZAP-70 Intron-1 DNA Methylation Status: A Simplified Method of Determination by Pyrosequencing in B Chronic Lymphocytic Leukemia.
Authors: Sylvain Chantepie, Dominique Vaur, Christophe Grunau, Veronique Salaun, Melanie Briand, Stéphane Cheze, Pascal Gauduchon, Michel Leporrier, Sophie Krieger
Journal: Blood (2008)
The science of consciousness must include its more advanced forms
Authors: Andrew Vonasch, E J Masicampo, Roy F Baumeister
Journal: Behavioral and Brain Sciences (2016)

Abstract Morsella et al. argue that science should not focus on high forms of consciousness. We disagree. An understanding of high forms of consciousness is invaluable to the scientific study of consciousness. Moreover, it poses challenges to the passive frame theory. Specifically, it challenges the notions that conscious thoughts are not connected and that consciousness serves skeletomotor conflict only.
Individual care plans reduce falls and broken hips in New Zealand hospitals
Authors: Jacqui Wise
Journal: BMJ (2016)

New Zealand is believed to be the first country in the world to achieve a national reduction in the number of in-hospital falls that result in a broken hip, a paper published in the New Zealand Medical Journal shows.1

A nationwide initiative by the Health Quality and Safety Commission reduced the number of in-hospital falls that resulted in a fractured neck of femur by 40% from December 2014 to June 2016. In that time the number of broken or fractured hips resulting from in-hospital falls decreased …
Establishment of a Novel CNS Infiltrated Xenograft Model through Engraftment of Patient-Derived Acute Lymphoblastic Leukemic Cells Into NOD/SCID/γc Null Mouse
Authors: Itaru Kato, Akira Niwa, Megumu Saito, Hisanori Fujino, Satoshi Saida, Hidefumi Hiramatsu, Koichi Oshima, Mamoru Ito, Souichi Adachi, Toshio Heike, Tatsutoshi Nakahata
Journal: Blood (2010)
Transarterial infusion chemotherapy with cisplatin plus S-1 for treating hepatocellular carcinoma: Results of a phase I trial.
Authors: Tetsuji Terazawa, Shunsuke Kondo, Chigusa Morizane, Tomohiro Yamaguchi, Satoshi Shimizu, Shuichi Mitsunaga, Masafumi Ikeda, Hideki Ueno, Takuji Okusaka
Journal: Journal of Clinical Oncology (2012)

357 Background: In Japan, transarterial infusion chemotherapy (TAI) with cisplatin (CDDP) is used for advanced hepatocellular carcinoma (HCC) patients (pts), and the response rate (RR) was 33.8% in previous phase (P) II study. S-1, oral systematic chemotherapy, is also promised for advanced HCC pts, and achieved 23.1% RR in previous P-II study. The clinical feasibility and efficacy of CDDP for TAI plus S-1 in pts with advanced HCC has not yet been investigated. Thus, we performed this trial to determine the recommended dose (RD). Methods: Although 13 Child–Pugh class A or B pts with advanced HCC entered themselves for this P-I trial, 1 pts of them was excluded from this trial due to the breach of criteria. The pts received TAI with CDDP (infusion on day 1 of the courses) plus S-1 (daily oral administration on days 1–21 of the courses), every 5 weeks until disease progression. The dose-escalation scheme is provided in the table below. Results: Three dose levels were used for the 12 pts. Dose-limiting toxicity was not observed in 3 pts at level 1, 3 pts at level 2, and 7 pts at level 3; therefore, the RDs for CDDP and S-1 were considered to be 65 mg/m 2 and 80–120 mg/day, respectively (level 3). Grade 3 adverse events were reported for 10 pts and were considered to be related to the study drugs for 6 pts: 2 pts, increased alanine aminotransferase level; 2 pts, increased aspartate aminotransferase level; 1 pt, anemia; and 1 pt, decreased platelet count. The total number of treatment courses was 25, with a mean of 1.5 courses per pt (range, 1–6 courses). The median progression-free survivaltime was 73 days. The disease control rate was 58% (7/12) ; 2 pts (16%) achieved partial response and 5 (42%) had stable disease. Conclusions: TAI with CDDP plus S-1 can be used safely with promising tumor control for treating advanced HCC. The RD to be used for a P-II study of this regimen was determined to be level 3. [Table: see text]
Incorporation of laparoscopic D2 dissection into the management of gastric adenocarcinoma (GCa) in a community-based setting.
Authors: Danielle Anna Bischof, Carol Jane Swallow, Peter Kenneth Stotland, John Anstruther Hagen, Lazar Victor Klein
Journal: Journal of Clinical Oncology (2012)

117 Background: A recent meta-analysis suggests that lymph node (LN) retrieval may be inferior when gastrectomy for GCa is performed laparoscopically rather than open. The purpose of this study was to examine the pathologic evaluation, postoperative morbidity and receipt of adjuvant treatment associated with adoption of D2 lymphadenectomy in a community setting. Methods: Routine D2 LN dissection was instituted as part of laparoscopic GCa resection at two community hospitals in Toronto in July 2008. Sequential cases up to Feb 2011 were identified and charts reviewed retrospectively. LN retrieval, margin status, morbidity, mortality and receipt of adjuvant treatment were examined. Results: Twenty-nine patients were identified; 69% were male and the median age was 69 (28-84). All patients underwent D2 lymphadenectomy, 10 with total gastrectomy (TG) and 19 with subtotal (STG). Pathologic evaluation showed that all patients underwent an R0 resection. Median number of LNs retrieved was 32 (15-62) and 93% of patients had adequate LN assessment according to AJCC 7 staging criteria. Sixty-five percent of patients had nodal metastases. There were 8 major complications in 7 patients including 3 post-operative deaths (10% mortality): one patient died in hospital from anastomotic leak and two after discharge from PE (1) and evisceration through the specimen extraction site (1). Four patients commenced neoadjuvant chemotherapy, but only 2 completed the planned pre-operative regimen. Ten additional patients started post-operative adjuvant chemo-radiotherapy, but only 5 completed it. Fifteen patients received no adjuvant treatment. Reasons for lack of adjuvant treatment were: early stage (n=4), medically unfit (2), post-operative death (2), patient declined (5) and early post-operative distant metastatic disease (2). Conclusions: Laparoscopic gastrectomy with D2 lymphadenectomy can be performed in a community setting with excellent margin status and LN retrieval results and complication rates comparable to those previously reported in prospective trials of open resection. Barriers to receipt/completion of adjuvant therapy in this setting should be explored.
Phase II trial of gemcitabine, carboplatin, and bevacizumab in chemotherapy-naive patients (Pts) with advanced/metastatic urothelial carcinoma (UC).
Authors: A. V. Balar, M. I. Milowsky, A. B. Apolo, I. Ostrovnaya, A. Iasonos, A. Trout, A. M. Regazzi, I. R. Garcia-Grossman, D. J. Gallagher, D. F. Bajorin
Journal: Journal of Clinical Oncology (2011)

248 Background: Effective treatment for pts with advanced UC unfit to receive cisplatin-based therapy remains an unmet need. A recent phase III study showed limited benefit of gemcitabine-carboplatin (GC) alone (median OS 9.3 months) (DeSantis ASCO 2010). We recently identified the VEGF-axis as a viable pathway for UC treatment (JCO 2010;Mar 10). We propose that bevacizumab, a monoclonal antibody against VEGFR, may be safely added to GC and improve time to progression (TTP) in pts with advanced UC. Methods: Primary endpoints (N=47 planned enrollment) were median TTP, to test an improvement of 50% over a 4.8 months median TTP seen with GC alone (Urology 2004;64:479), and safety. Secondary endpoints were response rate (RR) and overall survival (OS). Pts first received a single dose of bevacizumab 10 mg/kg. 2 weeks later they received 6 cycles of gemcitabine 1,000 mg/m 2 on day(D) 1 and D 8, and both carboplatin AUC 4.5 and bevacizumab 15 mg/kg on D1 every 21 days. Pts who achieved at least stable disease were eligible to receive maintenance bevacizumab at 15 mg/kg q21 days for 18 additional doses. Restaging evaluations were performed after every 3 cycles of therapy. Results: 51 pts (37 M, 14 F; median age 67 (Range 42-83)) were enrolled from 6/06 to 6/10. Primary tumor sites include bladder (31), renal pelvis (17) and ureter (2). 38 pts (74.5%) had visceral disease including lung (22), liver (13), bone (9) and adrenal (2). 13 pts had LN only disease. 46 of 51 pts were evaluable for response rate (RR) and TTP, 51 for toxicity. RR by RECIST was 46% (21 pts; PR 18, CR 3). 12 achieved stable disease; 1 too early to assess. Responses by MSKCC Risk Scores of 0, 1 and 2 were seen in 8/11(73%), 10/29 (35%), and 3/6 (50%) pts, respectively. 39% of pts had grade 3/4 toxicity, notably vascular thromboembolic events (VTE) in 18%. Conclusions: Bevacizumab can be safely added to GC in the treatment of advanced UC. The 16% VTE rate is similar to the 17% rate seen at MSKCC with GC alone. (JCO 2009;27:15s). Addition of bevacizumab does not improve the RR seen with GC alone in phase II and III studies (Bellmunt Eur J Cancer 2001; DeSantis ASCO 2010). Analysis of bevacizumab's impact on TTP and OS is ongoing and will be updated. [Table: see text]
Effect of the novel anti-androgen ARN-509 on response and seizure in castration-resistant prostate cancer models.
Authors: J. H. Hager, N. D. Smith, E. Bischoff, M. E. Jung, C. L. Sawyers, R. A. Heyman, P. J. Rix
Journal: Journal of Clinical Oncology (2011)

28 Background: ARN-509 is a second-generation anti-androgen discovered in a screen to identify full androgen receptor (AR) antagonists in the context of AR over-expressing prostate cancer cells, a model for castration resistant prostate cancer (CRPC). It has been reported that other second-generation anti-androgens, MDV3100 and BMS-641988, can induce seizures at high dose in pre-clinical species and man and that this is mediated through antagonism of the CNS-based GABA A receptor. To define the clinical potential of ARN-509, we carried out a comprehensive assessment of its in vitro and in vivo activity in validated models of CRPC and assessed its seizure inducing potential. Methods: ARN-509 and MDV3100 were profiled in a series of assays to monitor both on- and off-target activity. Comparative in vivo efficacy in the LNCaP/AR mouse xenograft model of CRPC and pharmacokinetics were determined. Seizure inducing potential was assessed in an acute pentylenetetrazol (PTZ) infusion model. Results: In vivo, in the LNCaP/AR model of CRPC, an ARN-509 dose of 10 mg/kg/day exhibited tumors regressions equivalent in frequency and magnitude to a 30 mg/kg/day dose of MDV3100. Tumor re-growth following once daily dosing (30 mg/kg) for 28 days revealed that ARN-509 treated tumors exhibited a more durable response than MDV3100 treated tumors as evidenced by a significantly longer time to re-growth. At doses that yielded equivalent degree of tumor regression, the steady state plasma and brain levels were significantly lower for ARN-509 (10 mg/kg) than MDV3100 (30 mg/kg). ARN-509 and MDV3100 exhibit similar binding affinity to the GABA A receptor; IC 50 3.0 and 2.7 mM, respectively. In vivo seizure potential of ARN-509 and MDV3100 was assessed in an acute PTZ infusion model in mice. MDV3100 was found to produce a dose dependant lowering of seizure threshold, while ARN-509 had no effect at any dose tested. Conclusions: ARN-509 is a second-generation anti-androgen with significant efficacy and an appropriate safety profile that supports its clinical development in both CRPC and earlier stages of prostate cancer. ARN-509 is currently in a phase I/II study in CRPC patients. [Table: see text]
The impact of neoadjuvant hormone therapy on the permanent <sup>125</sup>I-seed brachytherapy for low- or intermediate-risk prostate cancer.
Authors: Ryuta Tanimoto, Kensuke Bekku, Shin Ebara, Motoo Araki, Hiroyuki Yanai, Norihisa Katayama, Yasutomo Nasu, Hiromi Kumon
Journal: Journal of Clinical Oncology (2012)

201 Background: To determine whether neoadjuvant hormonal therapy improves the biochemical outcome for men with low or intermediate risk prostate cancer and undergoing permanent brachytherapy. Methods: From January 2004 to April 2011, 449 patients with low-risk (221 men) or intermediate-risk (228 men) based on NCCN guideline underwent transperineal ultrasonography-guided permanent 125 I-seed brachytherapy. Of these patients, 186 received neoadjuvant hormonal therapy (NHT). The median patient age was 67 years. The median follow-up (SD) was 48 (20) months (calculated from the day of implantation). Biochemical disease-free (BDF) survival was defined using Phoenix definition. The clinical variables evaluated for BDF survival included presence of NHT, Gleason score, clinical T-stage and pretreatment PSA. Results: For all patients, the 1, 3, 5-year actuarial BDF survival rates were 99.2%, 96.2% and 90% without NHT, 100%, 97.2%, 91.0% with NHT (p=0.954). When stratified by risk group, NHT did not improve the outcome for patients at low risk (P = 0.745) or at intermediate risk (P = 0.888). The duration (&lt;= 5 vs &gt;5 months) or combinations (single vs combined androgen blockade) of hormonal therapy were not statistically significant in predicting biochemical recurrence. In a multivariate analysis (shown below), only the Gleason score was a strong predicting factor, while NHT as well as pretreatment PSA, T stage were insignificant. Conclusions: In patients treated by permanent prostate brachytherapy, NHT did not improve the biochemical outcome for those at low-risk or intermediate-risk features. Furthermore, the duration or combinations of hormonal therapy conferred no additional biochemical advantage. [Table: see text]
A microbiome assessment of medical marijuana
Authors: G.R. Thompson, J.M. Tuscano, M. Dennis, A. Singapuri, S. Libertini, R. Gaudino, A. Torres, J.M.P. Delisle, J.D. Gillece, J.M. Schupp, D.M. Engelthaler
Journal: Clinical Microbiology and Infection (2016)
Role of heat shock protein 90 inhibition with 17-(allylamino)-17 (demethoxygeldenamycin) in muscle-invasive bladder cancer cells.
Authors: H. Williams
Journal: Journal of Clinical Oncology (2011)

273 Background: Muscle invasive bladder cancer portends a poor long term prognosis. Platinum based therapy is the mainstay of treatment but more effective agents are needed for management of this disease. Heat shock protein 90 (Hsp90) is a ubiquitous protein that has been shown to be overexpressed in tumor cells. It functions as a molecular chaperone responsible for the stability and function of a number of proteins critical to the oncogenic process. 17-(allylamino)-17 demethoxygeldanamycin (17 AAG) is a Hsp90 inhibitor that is currently in phase III trials in several tumor models. The purpose of this study was to evaluate the role of 17 AAG treatment for bladder cancer in vitro. Methods: Seven bladder cancer cell lines representing muscle invasive bladder cancer were treated in the presence and absence of 17 AAG. Both short term and long term treatments were evaluated for their effects on growth, motility and invasion of the cancer cells. Expression of proteins involved in cell growth, survival and metastasis were evaluated with Western blotting. Results: Our data demonstrated that 17 AAG treatment resulted in induction of apoptosis, inhibition of cell cycle progression through inhibition of MAP kinase pathway and cyclin D1 expression. Decreased tumor cell motility and invasion was observed with 17 AAG treatment. Several intracellular signaling pathways involved in cell proliferation, invasion and metastasis were inhibited. Conclusions: Hsp90 inhibition in muscle invasive bladder cancer cells impacts growth, motility and invasiveness by inhibiting numerous intracellular signaling pathways. Taken together, these findings suggest a possible role for Hsp90 inhibitors in bladder cancer tumorigenesis. No significant financial relationships to disclose.
Use of comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys to investigate the role of nonmodifiable factors in determining ultimate renal function.
Authors: B. R. Lane, P. Russo, R. Uzzo, A. V. Hernandez, S. A. Boorjian, R. H. Thompson, A. F. Fergany, T. Love, S. Campbell
Journal: Journal of Clinical Oncology (2011)

321 Background: Factors that determine renal function after partial nephrectomy (PN) are not well defined, including the impact of cold vs. warm ischemia and the relative importance of modifiable and non-modifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing PN. Methods: In 1980–2009, 660 PN were performed at 4 centers for tumor in a solitary-functioning kidney under cold (n=300) or warm (n=360) ischemia. Data were collected in IRB-approved registries; follow- up averaged 4.5 years. Pre- and postoperative glomerular filtration rates (GFR) were estimated via CKD-EPI equation. Results: At 3 months after PN, median GFR decreased by equivalent amounts with cold or warm ischemia (21% vs. 22%, respectively, p=0.7) although median cold ischemic times were much longer (45 vs. 22 min. respectively, p&lt;0.001). In multivariable analyses, increasing age, larger tumor size, lower preoperative GFR, and longer ischemia time were associated with decreased postoperative GFR (p&lt;0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative GFR proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance. Conclusions: This non-randomized comparative study suggests that long-term renal function after PN is determined primarily by the quantity and quality of renal parenchyma that can be preserved. Within the relatively strict parameters of conventional practice, i.e. predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after PN. Nevertheless, type and duration of ischemia remain the most important modifiable factors during PN, and mandate further study. [Table: see text]
HER2 status and histopathologic findings related to tumor regression in gastric carcinomas treated with preoperative chemotherapy.
Authors: Maria D. Begnami, Milton Jose B Silva, Wilson L. Costa, Felipe José Fernandez Coimbra, Marcos Chaves, Heber Salvador de Castro Ribeiro, Patricia Peresi, Celso Mello
Journal: Journal of Clinical Oncology (2012)

145 Background: Neoadjuvant chemotherapy is now the standard of care of patients with resectable gastric carcinomas (GC). Predictive molecular markers and histopathological evidence of tumour response to chemotherapy are not widely available. In this study we evaluated HER2 status and histopathological features associated with tumor regression in 36 GC treated with neoadjuvant chemotherapy followed by surgery. Methods: 36 patients had received ECF, DCF or ECX chemotherapy prior the surgery. The entire tumor beds of the specimens were histologically evaluated. HER2 expression by immunohistochemistry was detected in the biopsy and gastrectomy specimens. Results: 46% of the cases were intestinal type, 40% were diffuse and 14% were unclassified. Nine patients had major clinical and radiological response (CRR) characterized by presence of viable tumor cells less than 50% of the tumor with increased fibrosis (&gt;50%). Three cases had complete CRR showing tumor beds totally replaced by fibrosis. The remaining cases had minimal CRR characterized by viable tumor cells in more than 50% and minimal fibrosis. Necrosis was not found; mucinous metaplasia was observed in three cases of the major CRR. Inflammatory infiltrated was found in all cases. The downstaging of T-stage seems to be greater in the intestinal type than diffuse type (80% vs 44%). HER2+ (score 3) was detected in 16,6% of the biopsy specimen. Only 1 case was HER2+ in the biopsy and in the gastrectomy tissue. All the HER2+ GC showed minimal CRR. Conclusions: The ratio of viable tumor cells and fibrosis is directly associated with tumor response to preoperative chemotherapy. The chemotherapy regimens seem to collaborate to downstaging rates; however the treatment of HER2+ GC group could be improved by the use of Ttrastuzumab.
Phase 1 Dose-Escalation Study of Sotatercept (ACE-011) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma
Authors: Andrew J. Yee, Jacob P. Laubach, Ajay K. Nooka, Elizabeth K. O'Donnell, Edie A. Weller, Nicole R. Couture, Ellen E. Wallace, Jill N. Burke, Cynthia C. Harrington, Marie Puccio-Pick, Abderrahmane Laadem, Matthew L. Sherman, Noopur S. Raje
Journal: Blood (2015)