tbuckley/cabot-search huggingface dataset:
Phase II study of low dose (LD) and high dose (HD) premarin in androgen independent prostate cancer (AIPC)
Authors: M. Pomerantz, J. Manola, M. Taplin, G. Bubley, M. Inman, J. Lowell, P. Kantoff, W. K. Oh
Journal: Journal of Clinical Oncology (2006)

4560 Background: Estrogens, including DES, transdermal estradiol, estramustine and PC-SPES, have shown antitumor activity in AIPC. We tested two doses of Premarin to determine efficacy and safety of this commonly available estrogen. Methods: Patients with progressive AIPC were eligible. Prior estrogen use, significant cardiac or thromboembolic disease, and concurrent steroids were not allowed. Patients were randomized to Premarin 1.25 mg once (LD) or 3 times (HD) daily. Prophylactic breast irradiation was encouraged and warfarin 1 mg daily was required, unless contraindicated. After the first stage of accrual, the LD arm was closed because of limited activity, while the HD arm continued to the 2nd stage. Results: 46 patients were enrolled; 17 patients were randomized to LD Premarin, 29 patients assigned to HD Premarin by randomization or direct assignment. One patient withdrew consent prior to therapy. Median follow up is 5.3 months. Median age was 69 years (range 52–86) and median PSA 84.6 ng/ml (range 2.5–794.1). 19 patients (41%) had measurable disease. PSA declines ≥ 50% were seen in 0% (95% C.I., 0–19.5) and 32.1% (95% C.I., 15.9–52.4) of patients treated with LD and HD premarin. 1 patient treated with HD Premarin had a partial measurable response (8.3%; 95% C.I., 0.2–38.5). Median time to progression was 3.3 and 3.2 months in the LD and HD arms, respectively. Premarin was well tolerated in 45 evaluable patients. One grade 4 toxicity was noted, a stroke in the LD arm. Grade 3 toxicity was rare with 1 allergic reaction, 2 DVTs and 3 episodes of GI toxicity in one patient. Two patients experienced grade 3 elevations in PT requiring modification of warfarin dose. No significant gynecomastia was reported. Analysis of serially drawn hormone levels and molecular correlates of treatment response is pending. Conclusions: HD Premarin is associated with a 32.1% PSA response rate, while no responses were seen with LD Premarin. A measurable response was noted in 1 of 12 patients treated with HD Premarin. Toxicity was modest, though thromboembolism was seen even with prophylactic warfarin. Ongoing studies are evaluating molecular and clinical predictors of response. No significant financial relationships to disclose.
CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39
Authors: Xiao Zhang, Xia Ouyang, Zhenjian Xu, Junzhe Chen, Qiuyan Huang, Ya Liu, Tongtong Xu, Julie Wang, Nancy Olsen, Anping Xu, Song Guo Zheng
Journal: Molecular Therapy (2019)

Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor β (TGF-β) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo. CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39− partner cells in vivo. Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.
ITCC phase I study of erlotinib as single agent in children with refractory and relapsed malignant brain tumors and in combination with irradiation in newly diagnosed brain stem glioma
Authors: B. Geoerger, D. Hargrave, A. Ndiaye, D. Frappaz, F. Doz, P. Leblond, J. Gentet, R. Riccardi, X. Paoletti, M. Le Deley, G. Vassal
Journal: Journal of Clinical Oncology (2007)

9556 Background: Erlotinib hydrochloride (OSI-774), a selective inhibitor of the EGFR tyrosine kinase, may be active in childhood brain tumors, particularly in combination with irradiation. Methods: Multicenter, non-randomized phase I study with separate dose findings for erlotinib as single agent in children with refractory or relapsing brain tumors (group 1), and combined to irradiation in newly diagnosed brain stem glioma (group 2). Erlotinib was administered orally daily at 75, 100, 125 or 150 mg/m 2 . Dose escalation was performed in a classical 3+3 methodology for group 1 and according to the continuous reassessment method for group 2; dose-limiting toxicity (DLT) was evaluated at 3 and 6 weeks, respectively. Results: In total, 31 patients have been entered to date, 30 received treatment, 17 in group 1 (3 relapsing brain stem glioma, 4 ependymoma, 4 oligodendroglioma, 6 other) and 13 in group 2 with a median age of 9 and 6 years (range 4–16 and 2–12), respectively. Median treatment duration was 1.5 and &gt;5 months, respectively. In group 1, 3 patients each were treated at 75 mg/m 2 and 100 mg/m 2 , 7 at 125 mg/m 2 , 4 at 150 mg/m 2 . One patient with a glioneuronal tumor treated at 125 mg/m 2 experienced G5 intra-tumoral hemorrhage at day 4 which was considered as DLT; at 150 mg/m 2 , 1 patient with an oligodendroglioma experienced G3 asthenia at day 18 and G3 intratumoral hemorrhage at day 29, and 1 patient with an ependymoma experienced G5 intra-tumoral hemorrhage at day 49. In group 2, 1/6 patients treated with erlotinib 75 mg/m 2 and irradiation experienced seizures and died, no DLT occurred in 6 patients at 100 mg/m 2 . Non-hematological toxicities included G1-G2 erythema, folliculitis, dry skin, trichomegaly, G1 transaminitis, bilirubinemia, G1–3 asthenia, G1–5 intra-tumoral hemorrhage. Minor tumor response was observed in an oligodendroglioma. Pharmacokinetic and biological evaluations are ongoing. Conclusions: Erlotinib was well tolerated in children with cutaneous symptoms being the most frequent treatment toxicity. However, neurological toxicity and intra-tumoral hemorrhage was notable in these children with brain tumors. Inclusion at 125 mg/m 2 is ongoing to confirm the MTD. No significant financial relationships to disclose.
Disease Risk Index (DRI) Score Stratification and Composite End-Point GvHD-Free Relapse-Free Survival (GRFS) May Optimize Transplant Decision-Making Process in Haploidentical Stem Cell Transplantation
Authors: Maria Teresa Lupo-Stanghellini, Gabriele Antonarelli, Francesca Lorentino, Elisa Sala, Mara Morelli, Raffaella Greco, Magda Marcatti, Simona Piemontese, Tommaso Perini, Andrea Angelo Assanelli, Matteo Giovanni Carrabba, Alessandra Forcina, Serena Camilla Dalto, Sara Mastaglio, Sarah Marktel, Francesca Lunghi, Elena Guggiari, Fabio Giglio, Francesca Pavesi, Luca Vago, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Fabio Ciceri
Journal: Blood (2016)
Randomized phase II study of docetaxel with or without DMXAA (AS1404) in hormone-refractory metastatic prostate cancer (HRMPC)
Authors: R. Pili, M. Rosenthal
Journal: Journal of Clinical Oncology (2007)

5115 Background: DMXAA (AS1404) is a small-molecule agent that disrupts tumor vasculature. Combination of DMXAA with taxanes produces synergistic inhibition of tumor growth in animal models. A randomized phase II study in non-small cell lung cancer reported a substantial survival benefit when DMXAA was added to paclitaxel-based chemotherapy. This randomized phase II study examined the effect of adding DMXAA to docetaxel in HRMPC. Methods: Patients had progressive metastatic, androgen-independent, histologically confirmed prostate adenocarcinoma previously untreated with cytotoxics. Patients were randomized 1:1 to receive docetaxel (75 mg/m 2 ) ± DMXAA (1,200 mg/m 2 ) every 21 days for up to 10 cycles. Efficacy endpoints were prostate-specific antigen (PSA) response rate, objective response rate, time to tumor progression, duration of response and disease stabilization, time to PSA progression, and median and 1-year survival. Results: 74 patients were randomized: 34 to DMXAA plus docetaxel (DMXAA arm) and 40 to docetaxel alone (control arm). Median baseline PSA values were 83 ng/ml (range 6–3574 ng/ml) in the DMXAA arm and 87 ng/ml (range 1–570 ng/ml) in the control arm. PSA response data are available from 64 patients (see table ). Latest safety data show a similar number of serious adverse events reported across the treatment groups with 15 and 19 in the DMXAA and control arms, respectively. Conclusions: Addition of DMXAA to standard-dose docetaxel was well tolerated and the combination produced a substantially higher PSA response rate than docetaxel alone. DMXAA demonstrates promising activity in this patient population. [Table: see text] [Table: see text]
Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial
Authors: Jean-Michel Constantin, Matthieu Jabaudon, Jean-Yves Lefrant, Samir Jaber, Jean-Pierre Quenot, Olivier Langeron, Martine Ferrandière, Fabien Grelon, Philippe Seguin, Carole Ichai, Benoit Veber, Bertrand Souweine, Thomas Uberti, Sigismond Lasocki, François Legay, Marc Leone, Nathanael Eisenmann, Claire Dahyot-Fizelier, Hervé Dupont, Karim Asehnoune, Achille Sossou, Gérald Chanques, Laurent Muller, Jean-Etienne Bazin, Antoine Monsel, Lucile Borao, Jean-Marc Garcier, Jean-Jacques Rouby, Bruno Pereira, Emmanuel Futier, Cayot Sophie, Godet Thomas, Guerin Renaud, Verlac Camille, Chabanne Russel, Cosserant Bernard, Blondonnet Raiko, Lautrette Alexandre, Eisenmann Nathanael, Muller Laurent, Massanet Pablo, Boutin Caroline, Barbar Saber, Roger Claire, Belafia Fouad, Cisse Moussa, Monnin Marion, Conseil Matthieu, Carr Julie, De Jong Audrey, Dargent Auguste, Andreu Pascal, Lebouvrier Thomas, Launey Yoann, Roquilly Antoine, Cinotti Raphael, Boutin Caroline, Tellier Anne-Charlotte, Barbaz Mathilde, Cohen Benjamin, Lemarche Edouard, Bertrand Pierre-Marie, Arberlot Charlotte, Zieleskiewicz Laurent, Hammad Emmanuelle, Duclos Garry, Mathie Calypso, Dupont Herve, Veber Benoit, Orban Jean-Christophe, Quintard Hervé, Rimmele Thomas, Crozon-Clauzel Julien, Le Core Marinne, Grelon Fabien, Assefi Mona, Petitas Frank, Morel Jerome, Molliex Serge, Hadanou Nanadougmar
Journal: The Lancet Respiratory Medicine (2019)
Two phase 1 studies of MPC-6827, a novel vascular disrupting agent (VDA), in patients with advanced solid tumors and CNS metastases
Authors: R. Kurzrock, W. Akerley, D. Hong, C. Ng, T. Warren, K. Zavitz, C. McCage, M. Laughlin, L. Camacho
Journal: Journal of Clinical Oncology (2007)

3604 Background: MPC-6827 is a novel competitive inhibitor of tubulin polymerization via the colchicine binding site and functions as a highly potent (1–10nM) cytotoxic agent and as a VDA. MPC-6827 inhibits tumor cell growth and survival in vitro and in vivo, with activity in xenograft models of mouse melanoma and human cancers of the ovary, breast, prostate, colon and pancreas. The compound is not a substrate for multidrug resistance pumps and reaches high CSF concentrations. Methods: Two 3+3 designed dose-escalating Phase 1 studies were conducted to define the safety, tolerability, maximum tolerated dose (MTD) and PK of weekly IV administrations of MPC-6827 for pts with advanced solid malignancies (trial 1; N=46 pts) and measurable CNS involvement (trial 2; N=17 pts). In trial 2, there was intrasubject dose escalation for the first cycle and subsequent cycles were dosed at the highest dose achieved in Cycle 1. Antitumor activity was evaluated by RECIST guidelines in both studies. Results: Dose escalation proceeded until MTD was determined at 3.3 mg/m 2 . The dose limiting toxicity was acute coronary syndrome. Common mild to moderate toxicities included fatigue, headache, flushing, diarrhea, nausea, vomiting and arthralgias. There were no neurological deficits observed and no evidence of myelosuppression. No objective responses were observed. Radiographic changes consistent with vascular disruption in tumors were documented in a number of subjects at higher doses. Conclusions: MPC-6827 is safe and overall well tolerated. MTD is 3.3 mg/m 2 . Vascular flow modulation analyses are ongoing. MPC-6827 is currently in Phase 2 development. No significant financial relationships to disclose.
Paranasal sinus squamous cell carcinomas (PNSSCC) incidence and survival trends.
Authors: Benjamin Ansa, Michael Goodman, Kevin Ward, Scott A. Kono, Taofeek Kunle Owonikoko, William Grist, Trad Wadsworth, Mark El-Deiry, Amy Y. Chen, Suresh S Ramalingam, Jonathan Jay Beitler, Fadlo Raja Khuri, Dong M Shin, Nabil F. Saba
Journal: Journal of Clinical Oncology (2012)

5570 Background: PNSSCC are rare, accounting for 3 percent of all head and neck malignancies. They generally present with local invasion and have a high rate of local recurrence. There has been little information on the trends in incidence and survival of PNSSCC and no randomized trials to guide therapy. We analyzed the incidence rates and survival outcomes for patients diagnosed with PNSSCC in the SEER database. Methods: Data were obtained from the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Newly diagnosed PNSSCC reported to SEER from 1973 through 2008 were categorized according to the patient’s sex, age, year of diagnosis, and stage. The incidence and survival were then examined and compared across different demographic and disease-related categories. Results: A total of2,323 patients were identified. The mean age was 62 years, range: 14-85 yrs; males- accounted for 62.7%. Whites accounted for 75.8%, blacks for 12.2 % and 12.0% were of asian or pacific islanders and other groups. Maxillary sinus primary accounted for 76.3%, ethmoid (10.2%), sphenoid (4.3%). The disease was localized in 9.5%, had regional spread in 72.0% and distant disease in 12.2%, at diagnosis. A statistically significant decrease (Annual Percent Change of -1.6%, 95%CI= [-2.0, -1.1]) in the overall incidence was observed by Joinpoint analysis (p&lt;0.01). The decrease in incidence was significant in patients with maxillary sinus (p&lt;0.01) and was more pronounced in the white population compared to other groups. Both the observed and relative 5-year survival significantly increased over time and this was more notable in the white population compared to other groups. The observed 5-year survival rate increased from 24.9% (95% CI = [20.3-29.6]) during the 1975-1983 time-period to 40.8% (95% CI = [33.4-48.0]) during the most recent period of 2002-2008. Conclusions: There has been a decline in the overall incidence of PNSSCC more notably in the white population and for patients with maxillary sinus tumors. The 5-year observed and relative survival has significantly increased. Our findings should incite more efforts to understand the factors behind the change in incidence and survival.
Immune Biomarkers Identify Sustained Quantitative and Functional Immune Reconstitution in the Setting of Adjunctive Lenalidomide Following T-Depleted RIC-Allo SCT for Multiple Myeloma
Authors: Gordon Cook, Clive R Carter, Kristian Brock, Grant McQuaker, John A Snowden, Charles Crawley, Hannah Hunter, Jamie D. Cavenagh, Mark Lobb, Katherine Cullen, Andrea Hodgkinson, Mirjana Sirovica, Mark Cook
Journal: Blood (2016)
Outcome and evaluation of 1p and 19q deletion by chromogenic in situ hybridization (CISH) in patients with diagnosis of oligodendroglioma (OD) and oligoastrocitoma (OA).
Authors: Santiago Rafael Bella, Jose Roberto Llugdar, Alejo Lingua, Ricardo Alejandro Theaux, Francisco Papalini, Ricardo Olocco, Daniel Lerda
Journal: Journal of Clinical Oncology (2012)

e21025 Background: In OD and OA, the 1p and 19q deletion has prognostic value in survival. It is also a predictive factor for response to chemotherapy. Fluorescence in situ hybridization (FISH) is the standard method for its evaluation. CISH could be an alternative that has already been validated in other neoplasias. In OD and OA, this combined deletion is present in about 50% of patients when analyzed with FISH. Methods: Patients resected at Clinica Reina Fabiola from january 2006 to january 2010 and diagnosed of OD and OA were propectivelly included. Paraffin-embebed tumor tissue was analyzed for 1p19q deletions by CISH. The results were correlated to the histology (OD and OA) and grade (II and III) of the tumors. Results: The demographic features of the patients from the present study coincide with literature. The 1p and 19q deletion was found in 3 of the 24 patients analyzed (13%). The combined deletion was only found in those with grade II OD. No combined deletion was found in patients diagnosed of grade III OD and grade II and III OA. In the subgroup of patients with grade II OD, the combined deletion was observed in 3 of 11 patients (27%). The 3 patients in which the deletion in both chromosomes was observed, received treatment with chemotherapy and radiotherapy, all of them with complete response. 5 years DFS was 90%-median follow up 36,8 (CI: 30,5-42,98) Conclusions: The detection of the combined deletion with CISH technique was inferior (13%) than the literature. We cannot demonstrate that CISH is a reliable method for the detection of the 1p and 19q deletion. The possible reasons of this difference could be attributed to the number of patients of the study, to deviations in the procedures of the test or to the fact that the CISH method is not coincident with FISH. This prospectivelly monoinstitutional results are also different to our previous report, and may be due to different pathological evaluation.
Design and characterization of α1-antitrypsin variants for treatment of contact system–driven thromboinflammation
Authors: Steven de Maat, Wariya Sanrattana, Reiner K. Mailer, Naomi M. J. Parr, Martin Hessing, Robert M. Koetsier, Joost C. M. Meijers, Gerard Pasterkamp, Thomas Renné, Coen Maas
Journal: Blood (2019)
Comparison of Multiparametric Magnetic Resonance Imaging and Targeted Biopsy With Systematic Biopsy Alone for the Diagnosis of Prostate Cancer
Authors: Martha M. C. Elwenspoek, Athena L. Sheppard, Matthew D. F. McInnes, Samuel W. D. Merriel, Edward W. J. Rowe, Richard J. Bryant, Jenny L. Donovan, Penny Whiting
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The current diagnostic pathway for patients with suspected prostate cancer (PCa) includes prostate biopsy. A large proportion of individuals who undergo biopsy have either no PCa or low-risk disease that does not require treatment. Unnecessary biopsies may potentially be avoided with prebiopsy imaging. <h3>Objective</h3> To compare the performance of systematic transrectal ultrasonography–guided prostate biopsy vs prebiopsy biparametric or multiparametric magnetic resonance imaging (MRI) followed by targeted biopsy with or without systematic biopsy. <h3>Data Sources</h3> MEDLINE, Embase, Cochrane, Web of Science, clinical trial registries, and reference lists of recent reviews were searched through December 2018 for randomized clinical trials using the terms "prostate cancer" and "MRI." <h3>Study Selection</h3> Randomized clinical trials comparing diagnostic pathways including prebiopsy MRI vs systematic transrectal ultrasonography–guided biopsy in biopsy-naive men with a clinical suspicion of PCa. <h3>Data Extraction and Synthesis</h3> Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the revised Cochrane tool. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. All review stages were conducted by 2 reviewers. <h3>Main Outcomes and Measures</h3> Detection rate of clinically significant and insignificant PCa, number of biopsy procedures, number of biopsy cores taken, and complications. <h3>Results</h3> Seven high-quality trials (2582 patients) were included. Compared with systematic transrectal ultrasonography–guided biopsy alone, MRI with or without targeted biopsy was associated with a 57% (95% CI, 2%-141%) improvement in the detection of clinically significant PCa, a 33% (95% CI, 23%-45%) potential reduction in the number of biopsy procedures, and a 77% (95% CI, 60%-93%) reduction in the number of cores taken per procedure. One trial showed reduced pain and bleeding adverse effects. Systematic sampling of the prostate in addition to the acquisition of targeted cores did not significantly improve the detection of clinically significant PCa compared with systematic biopsy alone. <h3>Conclusions and Relevance</h3> In this meta-analysis, prebiopsy MRI combined with targeted biopsy vs systematic transrectal ultrasonography–guided biopsy alone was associated with improved detection of clinically significant PCa, despite substantial heterogeneity among trials. Prebiopsy MRI was associated with a reduced number of individual biopsy cores taken per procedure and with reduced adverse effects, and it potentially prevented unnecessary biopsies in some individuals. This evidence supports implementation of prebiopsy MRI into diagnostic pathways for suspected PCa.
A Tumor-Localized Approach to Bypass Anti-4-1BB Immuno-Toxicity
Authors: Tina Tianjiao Su, Xiaobin Gao, Jun Wang
Journal: Clinical Cancer Research (2019)

4-1BB (CD137) is an important costimulatory molecule upregulated on antigen-experienced T cells, however, clinical development of 4-1BB agonists has stalled because of significant liver immuno-toxicity. Using rational protein engineering, a next-generation anticalin-antibody-based therapy achieved localized 4-1BB activation triggered by tumor-expressed antigen, helping to revitalize this pathway in immuno-oncology.See related article by Hinner et al., p. 5878.
Correction to: High-affinity peptide ligand LXY30 for targeting α3β1 integrin in non-small cell lung cancer
Authors: Wenwu Xiao, Weijie Ma, Sixi Wei, Qianping Li, Ruiwu Liu, Randy P. Carney, Kevin Yang, Joyce Lee, Alan Nyugen, Ken Y. Yoneda, Kit S. Lam, Tianhong Li
Journal: Journal of Hematology & Oncology (2019)

The original article [1] contains an error in Fig. 2 whereby Fig. 2D has mistakenly been omitted. Fig. 2 can be viewed in its entirety - including Fig. 2D - in this Correction article.