tbuckley/cabot-search huggingface dataset:
Multicenter phase II trial of temozolomide (TMZ) and rituximab (RIT) for recurrent primary CNS lymphoma (PCNSL): North American Brain Tumor Consortium (NABTC) study 05-01.
Authors: L. Nayak, L. E. Abrey, J. Drappatz, M. R. Gilbert, D. A. Reardon, K. Lamborn, P. Y. Wen, M. Prados, L. M. DeAngelis, A. M. P. Omuro
Journal: Journal of Clinical Oncology (2011)

2039 Background: Salvage chemotherapy for PCNSL has been poorly characterized, with few, mostly retrospective studies reporting objective response rates (RR) of 26-53% and 1y overall survival (OS) of 35-57%. Based on single-agent activity, two small retrospective studies investigated the combination of TMZ and RIT, reporting ORR 53-100% and 1y OS of 50-55%. To confirm these results, a multicenter phase II trial was initiated through the former NABTC, now Adult Brain Tumor Consortium. Methods: Immunocompetent pts with recurrent PCNSL, KPS≥60 and adequate organ/ bone marrow function were eligible. Treatment started with an induction phase with RIT (750mg/m2) on days 1, 8, 15, 22 and TMZ (150mg/m2) days 1-7 and 15-21. If MRI on day 28 showed response or stable disease, six cycles of consolidation TMZ were given (150-200mg/m2 X5/28 days). Following consolidation, maintenance methylprednisolone (1g IV monthly) was given until progression. Primary endpoint was RR (N=40 planned). Results: Due to slow accrual and preliminary analysis suggesting futility, the study was closed prematurely (N=16 pts enrolled). The median age was 63 (47-79), median KPS was 90 (60-100); 12 were women. Number of previous chemotherapies was one in 11 pts, two in 2 pts and three in 3 pts. Grades 1-2 toxicities included hemoglobin (3 pts), platelets (3), skin rash (1); no grade 3-5 toxicity was seen. Although first MRI showed response in 5/14 evaluable pts, subsequent MRI confirmed the response in only 2, both of which were complete (RR: 14%; 95% CI 17-43). The median PFS was 7 weeks (CI 4-13); 1y OS was 71% (CI 40-88); median OS was not reached (median followup: 37m). Conclusions: The favorable results from retrospective studies were not reproduced in this prospective study. Efficacy was modest, with short-lived responses likely reflecting the low efficacy of the single agent TMZ consolidation phase. OS results were favorable, suggesting subsequent treatments were effective. Given the favorable toxicity profile, this regimen could be an option for pts who are not candidates for more effective therapies such as radiotherapy, high-dose chemotherapy/ stem-cell rescue or MTX re-challenge.
Immune Reactions Following Reduced-Intensity Allogeneic Stem Cell Transplantation (Allo-CST): Role of Plasma IL-7 and IL-15 Levels, and Their Receptors
Authors: Thiant Stephanie, Jacques Trauet, Eva De Berranger, Laurent B Pascal, Jean Paul Dessaint, Myriam Labalette, Ibrahim Yakoub-Agha
Journal: Blood (2010)
A retrospective review of squamous cell carcinoma of the anal canal in HIV-positive and HIV-negative patients
Authors: N. Hammad, P. A. Philip, A. F. Shields, L. K. Heilbrun, R. Venkatramanamoorthy, B. F. El-Rayes
Journal: Journal of Clinical Oncology (2009)

e15586 Background: Human immunodeficiency virus (HIV) infected patients (pts) are at increased risk for squamous cell carcinoma of the anal canal (SCCAC) and the incidence of SCCAC has increased in the era of HAART (highly active antiretroviral therapy). The outcome of SCCAC in HIV (+) pts has not been evaluated in prospective trials and the published literature is limited to small retrospective case series. The aim of this study is to describe the outcome, tolerability, and overall survival (OS) in pts with and without HIV infection treated at Karmanos Cancer Institute, at Wayne State University from 1991 to 2007. Methods: We performed a retrospective chart review. We collected data regarding HIV status, demographics (age, gender, race), stage at diagnosis, treatment, response to treatment, toxicity, and survival. Results: Fifty pts with SCCAC were identified, of whom 18 were HIV (+) and 32 were HIV (−), 26% Caucasians, 68% African American, 56% males and 44% females. HIV (+) pts had significantly better stage (p = 0.011) and less frequent reduced chemotherapy dose (p = 0.001). There were no significant differences by HIV status in type of chemotherapy received, frequency of reduced radiotherapy dosage, use of diverting colostomy, or frequency of relapse. Diverting colostomy was required in 29% of HIV (+) pts and 18% of HIV (−) pts. The major toxicities observed in HIV (+) and (−) pts were diarrhea (36% vs. 64%), neutropenia (27% vs. 21%), and skin toxicity secondary to radiotherapy (XRT: 82% vs. 100%; p = 0.034). Median (OS) was 62.6 months for HIV (+) pts and 71.8 months for HIV (−) pts (p = 0.787). Conclusions: HIV (+) pts had better stage, received standard chemotherapy dose more often, and had more frequent XRT dermatitis than HIV (−) pts. Otherwise, there was no major difference in treatment toxicities. A higher proportion of HIV (+) pts required diverting colostomy. Survival is somewhat shorter among HIV (+) patients. No significant financial relationships to disclose.
Randomized phase III trial of gefitinib or pemetrexed as second-line treatment in patients with non-small cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01).
Authors: M. Ahn, J. Sun, J. S. Ahn, S. Kim, K. H. Lee, Y. J. Min, H. J. Yun, H. Kim, H. Song, Y. H. Kim, B. Kim, I. G. Hwang, K. Lee, I. S. Woo, H. Ryoo, K. H. Lee, H. G. Yi, J. Jang, J. H. Kwon, K. Park
Journal: Journal of Clinical Oncology (2011)

7603 Background: To compare the efficacy of gefitinib versus pemetrexed as second-line therapy in never-smokers with advanced pulmonary adenocarcinoma previously treated with platinum-based chemotherapy. Methods: Eligible patients had a performance status 0 to 2, previous treatment with one prior platinum-based regimen, pulmonary adenocarcinoma, and never-smoking state. Epidermal growth factor receptor (EGFR) mutation status was not considered for the enrollment. Randomized patients received either gefitinib 250 mg per oral every day or pemetrexed 500 mg/m2 iv day 1 with vitamin B12 and folic acid supplement every 21 days. The primary end point was progress-free survival (PFS). Results: One hundred thirty-five patients were randomly assigned with being stratified with performance status (0-1 vs. 2) and gender. Overall response rates were 30.1% and 14.9% (P < 0.001) for gefitinib and pemetrexed, respectively. The primary endpoint of PFS was met with 9.4 months for gefitinib versus 2.9 months for pemetrexed, which was significantly different (P = 0.010). The median overall survival has not been reached yet in both groups. The 1-year survival rate for gefitinib and pemetrexed arm was 73.6% and 70.5% (P = 0.89), respectively. The further analyses of EGFR mutation status, post-study treatment and adverse events will be presented on the ground. Conclusions: Gefitinib showed superior efficacy to pemetrexed as second-line therapy in clinically selected NSCLC patients in Korea. Considering sequence of salvage therapy, gefitinib would be preferable to pemetrexed in enriched NSCLC patients.
Abstract 4358: Targeting connexin 43 with α-connexin carboxyl-terminal (ACT1) peptide in breast cancer
Authors: Christina Grek, Joshua Matthew Rhett, Melissa Abt, Jaclynn Bruce, Gautam Ghatnekar, Elizabeth S. Yeh
Journal: Cancer Research (2015)

Abstract Expression and functional studies have identified connexins (Cxs), a family of gap junction proteins, as potential tumor suppressors. Studies suggest that connexin 43 (Cx43) has a role in breast cancer cell proliferation, differentiation, and migration. Although pan-gap junction drugs are available, the lack of specificity of these agents increases the opportunity for off target effects. Consequently, a therapeutic agent that specifically modulates Cx43 would be beneficial and has not been tested in breast cancer. In this study, we now test a Cx43 specific agent, called α-connexin carboxyl-terminal (ACT1), in breast cancer. Our studies demonstrate that modulation of Cx43 activity in breast cancer can be effectively achieved with the agent ACT1 to sustain Cx43-mediated gap junctional activity resulting in impaired malignant progression. Furthermore, using ER+ and HER2+ breast cancer cell models, we show that ACT1 treatment enhances the activity of lapatinib and tamoxifen. Citation Format: Christina Grek, Joshua Matthew Rhett, Melissa Abt, Jaclynn Bruce, Gautam Ghatnekar, Elizabeth S. Yeh. Targeting connexin 43 with α-connexin carboxyl-terminal (ACT1) peptide in breast cancer. [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 4358. doi:10.1158/1538-7445.AM2015-4358
BCL6 Rearrangement Detected by FISH Analysis Is a Poor Prognostic Factor in the “Non-Germinal Center Phenotype” of Diffuse Large B-Cell Lymphoma.
Authors: Jun Takizawa, Sadao Aoki, Akihito Momoi, Toshiki Kitajima, Masutaka Higashimura, Naoya Nakamura, Yoshifusa Aizawa
Journal: Blood (2006)
Abstract 4443: PB-42: Design and characterization of a glutathione pro-drug selectively delivered to normal tissue and not tumor tissue
Authors: James P. Thomas, Peter G. Geiger
Journal: Cancer Research (2015)

Abstract The vast majority of cancer treatment regimens involve cytotoxic chemotherapy or radiation with a narrow therapeutic index. More than ½ of all approved anticancer drugs are associated with generation of reactive oxygen species. We have developed a molecule that selectively increases glutathione in normal tissues while not protecting cancer cells. Our compound has a backbone of the glutathione (GSH) precursor γ-glutamyl cysteine, with each acid group protected by ethyl ester moieties. The PB-42 molecule then leverages the dramatic differences in endothelial alkaline phosphatase between normal and cancerous tissues, similar to amifostine. Selectivity is based on a phosphorothioate moiety that requires activation by alkaline phosphatase. We have developed a robust, scalable synthetic pathway for PB-42. Cultured cells incubated with PB-42 dramatically increase intracellular GSH and total nonprotein sulfhydral (NPSH) levels several fold over controls. This process is totally dependent on activation with alkaline phosphatase. Increased GSH and NPSH levels translate into dramatic resistance to the cytotoxic effects of common chemotherapeutic agents such as cisplatin or melphalan. GSH increases are not inhibited by prior incubation with the γ-glutamyl cysteine synthase inhibitor buthionine sulfoximine (BSO), demonstrating that PB-42 enters into the GSH synthetic pathway beyond the allosterically controlled step and is not simply providing intracellular cysteine. Cells initially depleted of endogenous GSH with BSO demonstrated dramatic increases in GSH after co-incubation with PB-42 and alkaline phosphatase. PB-42 was well tolerated in vivo and was able to abrogate cisplatin-induced nephrotoxicity. PB-42 could offer several advantages in selective protection against the toxic effects of chemotherapy and radiation therapy as compared to amifostine, in that it generates the natural sulfhydral GSH, that in addition to acting as a bulk thiol, also participates in a number of enzyme based protective systems. Note: This abstract was not presented at the meeting. Citation Format: James P. Thomas, Peter G. Geiger. PB-42: Design and characterization of a glutathione pro-drug selectively delivered to normal tissue and not tumor tissue. [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 4443. doi:10.1158/1538-7445.AM2015-4443
Management and evaluation of non-supervised home exercise program in a convalescent phase of acute myocardial infarction.
Authors: Kenji Ueshima, Muneyasu Saito, Atsushi Simohara, Sadahiko Uchimoto, Masao Kawaguchi, Kenichi Fukami, Tetsuya Sumiyoshi, Kazuo Haze, Katsuhiro Hiramori
Journal: Circulation (1990)

Out of 636 patients with acute myocardial infarction (AMI) admitted to our institution, 183 patients enrolled in our non-supervised home exercise program immediately after their discharge from the hospital. The first 40 patients were randomized to control and training group, while the remaining 143 patients were included in the training group. Before and after the trial, all patients underwent cardiopulmonary exercise testing; submaximal graded treadmill exercise test with the application of expiratory gas analysis. In the training group, patients performed 2 km walk-jog exercise everyday for 1 month, keeping their heart rate (HR) at 90-100% of that in the anaerobic threshold. HR during exercise was monitored by patients themselves, using HR-meter. The anaerobic threshold significantly increased in the training group; while control group had no significant changes. VO2 and HR significantly increased at the same Borg's indices. Psychological improvement was also obtained in the training group compared to control group. It is concluded that non-supervised home exercise program is effective and easily applicable in the convalescent phase of AMI.
S29 A randomised controlled trial of over the counter medicine CS1002 for acute cough
Authors: SS Birring, J Brew, T Kilbourn, AH Morice
Journal: Thorax (2016)

<h3>Introduction</h3> CS1002 contains diphenhydramine/ammonium-chloride/levomenthol in a demulcent preparation. We conducted a randomised controlled trial to compare the efficacy of CS1002 with Bell’s Simple Linctus (BSL). <h3>Methods</h3> 163 subjects with acute cough associated with upper respiratory tract infection, URTI (onset ≤7 days and cough severity VAS ≥60 mm), presenting to pharmacists (64%) or general practitioners were randomised to CS1002 or BSL. The subjects (mean age 39 years, 57% female) were instructed to take their medication four times daily (5/5/10/10 ml) for 7 days or until resolution. Investigators were blinded to the treatment allocation. The primary analysis, cough severity VAS (0–100) was ANCOVA in an intention to treat population. <h3>Results</h3> CS1002 (n = 82) compared to BSL (n = 75), after 3 days, was associated with a greater reduction in cough severity (adjusted mean(SE) difference 5.9 (4.3), p = 0.18), cough sleep disruption VAS (mean diff 11.6 (4.5), p = 0.01) and cough frequency VAS (mean diff 8.1 (4.1), p = 0.05, Figure 1). There was a greater improvement in QOL (LCQ-acute) with CS1002 compared to BSL after 5 days; mean diff 1.2 (0.6), p = 0.04. The reduction in cough severity with CS1002 was similar in dry/chesty/tickly categories of cough. Cough resolved after 3 days in 24.4% of CS1002 subjects compared to 10.7% BSL, p = 0.02. CS1002 was well tolerated, similar to BSL. <h3>In conclusion</h3> We have conducted the largest RCT in URTI with validated outcome measures. CS1002 reduced the impact of cough associated with URTI with a greater reduction in cough frequency and sleep disruption and improvement in QOL and cough resolution compared to BSL.
Abstract 3781: Effects of a novel microtubule inhibitor, AK301 on Apc heterozygote colon cells
Authors: Avijeet Chopra, Amy Anderson, Daniel Rosenberg, Charles Giardina
Journal: Cancer Research (2015)

Abstract Over 80% of the sporadic colon cancers harbor somatic mutations of APC, predominantly resulting in APC protein lacking its C-terminal end. The basic region within the C-terminus of APC interacts with microtubules to promote polymerization, a process essential for establishment of cell polarity and faithful segregation of chromosomes during mitosis. Truncation mutations of Apc have been proposed to act in a dominant negative manner to slow microtubule growth and anchoring. We recently identified a novel microtubule inhibitor, 4-(3-chlorophenyl)piperazin-1-yl) (2-ethoxyphenyl)methanone, referred to as AK301. Our in vitro tubulin polymerization assay indicates that AK301 disrupts microtubule polymerization, but does not completely abrogate microtubule growth. In addition, in silico molecular docking predicts a novel and unique binding orientation of AK301 to the colchicine-binding domain of β-tubulin. We examined the effects of AK301 on microtubule dynamics in Apc+/+ and ApcMin/+ cells. Here we show that ApcMin/+ cells normally maintain shorter microtubules under normal growth conditions. Following treatment with AK301, mutant cells show more extensive cytoskeletal and mitotic spindle abnormalities. Moreover, AK301-treated ApcMin/+ cells showed centrosome declustering, evident from multiple Aurora A kinase foci; bipolar assembly was observed in the corresponding untreated ApcMin/+ cells or treated Apc+/+ cells. Overall, AK301 and its derivatives may help illuminate the regulation of microtubule dynamics in Apc mutant cells and provide insight into the consequences of targeting their microtubule assembly defect. Note: This abstract was not presented at the meeting. Citation Format: Avijeet Chopra, Amy Anderson, Daniel Rosenberg, Charles Giardina. Effects of a novel microtubule inhibitor, AK301 on Apc heterozygote colon cells. [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 3781. doi:10.1158/1538-7445.AM2015-3781
Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha–Targeting Antibody–Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study
Authors: Kathleen N. Moore, Lainie P. Martin, David M. O’Malley, Ursula A. Matulonis, Jason A. Konner, Raymond P. Perez, Todd M. Bauer, Rodrigo Ruiz-Soto, Michael J. Birrer
Journal: Journal of Clinical Oncology (2017)

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.
Mechanisms of Antileukemic Activity of the Multikinase Inhibitors Dasatinib and Ponatinib in Acute Lymphoblastic Leukemia (ALL) Harboring the E2A-PBX1 Fusion Gene
Authors: Tamara Tesanovic, Susanne Badura, Thomas Oellerich, Claudia Doering, Martin Ruthardt, Oliver G. Ottmann
Journal: Blood (2014)
Novel Evidence That Murine and Human Mesenchymal Stromal Cells Express Functional Gonadotropic Hormone Receptors, Demonstrating the Involvement of the Pituitary gonadotropin–bone Marrow Axis in Hematopoiesis
Authors: Malwina Suszynska, Pranesh Gunjal, Agata Poniewierska-Baran, Sylwia Borkowska, Kasia Mierzejewska, Gabriela Schneider, Janina Ratajczak, Magdalena Kucia, Mariusz Z Ratajczak
Journal: Blood (2014)
Outcomes of Patients with Refractory/Relapsed Diffuse Large B-Cell Lymphoma Who Progress After Autologous Stem Cell Transplantation in the Rituximab Era.
Authors: Sarah J. Nagle, Kaitlin Woo, Rosemarie Mick, Stephen J. Schuster, Sunita D. Nasta, Edward A. Stadtmauer, Jakub Svoboda
Journal: Blood (2012)
A single-arm, open-label, multicenter study of complete molecular response (CMR) in patients with newly diagnosed Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) treated with nilotinib.
Authors: Michael R. Savona, Ian W. Flinn, Stuart Goldberg, Robert Leon Robles, David Rizzieri, Jerald P. Radich, Michael J. Mauro, Solveig Ericson, Sandy Yi, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

TPS6636 Background: With more-potent tyrosine kinase inhibitors, increasingly sensitive methods are required to monitor treatment response and quantify minimal residual disease (MRD). Molecular monitoring is recommended by National Comprehensive Cancer Network and European LeukemiaNet guidelines; major molecular response (MMR) correlates with optimal long-term outcomes. CMR, while implying absence of BCR-ABL transcripts, is defined by levels undetectable by current technology (generally ≥4.5 logs reduced below a standardized baseline using quantitative real-time polymerase chain reaction [RT-PCR]). Newer technologies that can detect larger reductions will be important in analyzing correlations between decreased disease burden and long-term outcomes and may assist in selecting patients for “stopping” therapy. Methods: This US study plans to enroll 100 adults with newly diagnosed Ph+ CML-CP within 6 months of diagnosis to receive nilotinib 300 mg twice daily (BID) for up to 2 years. BCR-ABL transcripts are quantified using RT-PCR at a central laboratory. An exploratory molecular assay (digital detection [DiD]) with an additional &gt;1-log sensitivity and mutation detection and quantification will be evaluated. Primary endpoint: the rate of confirmed CMR at 24 months (CMR confirmed by second PCR sample within 3 months; ≥4.5-log reduction of BCR-ABL from standardized baseline on the international scale [IS], equivalent to BCR-ABL ≤0.0032% IS). Dose escalation to 400 mg BID is allowed per protocol. Secondary endpoints: rate of, time to, and duration of complete cytogenetic response (CCyR), MMR, and CMR; rate of and time to loss of CCyR, MMR, and CMR and to progression to accelerated phase/blast crisis; rate of CMR in dose-escalated patients; and event-free, progression-free, and overall survival. Exploratory endpoints: BCR-ABL trends and correlation of mutations with response. The DiD assay data will provide information on BCR-ABL trends below the current CMR threshold and assist in evaluating lower levels of MRD.