tbuckley/cabot-search huggingface dataset:
Ruxolitinib Significantly Prolongs Survival in Both a Primary Mediastinal B-Cell Lymphoma (PMBL) and Hodgkin Lymphoma (HL) Xenograft NSG Mouse Model: Ruxolitinib May be a Potential Adjuvant Agent in the Treatment of PMBL and of HL
Authors: Sanghoon Lee, Changhong Yin, Janet Ayello, Erin Morris, Carmella van de Ven, Mitchell S. Cairo
Journal: Blood (2015)
Frequent cannabis slows nerve signal transmission in the eye, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Frequent cannabis use is associated with significantly slower transmission of nerve signals by retinal ganglion cells in the eye that could explain the drug’s neurotoxic effects on vision, a small study has found.1

Cannabis is widely used and has been legalised in several countries, and others are considering legalising its use. But information on cannabis related toxicity and its effects on activities such as driving is limited, compared with alcohol.

To investigate how cannabis …
Clinical Epidemiology and First-Line Treatment in Immune Thrombocytopenia Adults. Results of the Carmen Prospective Cohort
Authors: Guillaume Moulis, Thibault Comont, Johanne Germain, Natacha Brun, Claire Dingremont, Brice Castel, Sophie Arista, Serge Madaule, Philippe Montané de la Roque, Laurent Prudhomme, Laurent Sailler, Laurent Balardy, Cecile Borel, Stéphane Sire, Guillaume Martin-Blondel, Laurent Alric, Miguel Carreiro, Francis Gaches, Patrick Giraud, Maryse Lapeyre-Mestre, Bertrand Godeau, Odile Beyne-Rauzy, Daniel Adoue
Journal: Blood (2015)
Risk Factors for Pulmonary Hypertension In Patients with Thalassemia Intermedia
Authors: Mehran Karimi, Khaled M Musallam, Maria Domenica Cappellini, Amal El-Beshlawy, Khawla Belhoul, Shahina Daar, Mohamed-SalahEldin Saned, Sally Temraz, Ali T Taher
Journal: Blood (2010)
The impact of pathologic review by central pathologist on selection for treatment modality of localized prostate cancer in candidate for brachytherapy.
Authors: R. Kishimoto, T. Saika, K. Bekku, H. Nose, F. Abarzua, Y. Kobayashi, H. Yanai, Y. Nasu, H. Kumon
Journal: Journal of Clinical Oncology (2011)

213 Background: To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed migration of Gleason grade (GG), and final treatment decision in a cohort of patients who were candidate of permanent prostate brachytherapy (PPB). Methods: From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospital were referred to our hospital for PPB, and all pathological slides of the prostate biopsy were reviewed by single PGU. The patient finally selected their treatment modality based on our recommendation made by reference to the pathological review. Our indication of PPB, basically, is a patient classified good or intermediate risk by NCCN classification. In addition, a patient with primary GS 4 was regarded as unadapted case. Results: Six cases were reinterpreted as no cancer (2.4%), and GG change occurred in 95 cases (38.4%). GG was upgraded in 77 cases (31.2%), and downgraded in 18 cases (7.3%). As a result, a total of 86 patients changed their therapies, and 25 of 86 patients (29%) were changed their therapy based on the pathological review. Conclusions: Approximately 10% of patients were changed to proper therapies by PPB's pathological review. This study shows pathological review for biopsy specimen is mandatory for determination of treatment modality, especially in candidate for PPB. No significant financial relationships to disclose.
Peptide Receptor Radionuclide Therapy for Sarcoidosis
Authors: Constantin Lapa, Götz Ulrich Grigoleit, Heribert Hänscheid, Erdwine Klinker, Pius Jung, Ken Herrmann, Andreas Schirbel, Markus Böck, Andreas K. Buck, Theo Pelzer
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Preclinical Evaluation of Adjuvant Therapy with AMD3100 for Drug Resistant Philadelphia Chromosome Positive and Negative ALL
Authors: Enzi Jiang, Min Yu, Yao-Te Hsieh, Brian DeLaTorre, Asha Kadavallore, Carlton Scharman, Eugene Park, Allen S. Yang, Markus Muschen, John Groffen, Nora Heisterkamp, Yong-Mi Kim
Journal: Blood (2008)
The Immunoregulatory Enzyme Indoleamine 2,3-Dioxygenase (IDO1) Is Expressed by Natural Killer (NK) Cells During Cytokine-Mediated Activation
Authors: Cecilia Evangelisti, Antonio Curti, Sara Trabanelli, Darina Ocadlikova, Michele Baccarani, Roberto massimo Lemoli
Journal: Blood (2010)
Frequency of cisplatin administration in patients presenting with advanced urothelial carcinoma in the community.
Authors: Guru Sonpavde, Deidre Watson, Marcia Tourtellott, Erica Higgins, Charles Lance Cowey, Beth A. Hellerstedt, Thomas E. Hutson, Feng Zhan, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2012)

285 Background: Renal dysfunction, poor performance status, advanced age, and comorbidities may preclude standard frontline cisplatin-based chemotherapy in patients with advanced urothelial carcinoma (UC). We hypothesized that cisplatin-based regimens are not administered to the majority of patients in the community. A study was conducted to identify chemotherapy regimens administered by medical oncologists in community-based cancer centers. Methods: A retrospective study was conducted on patients with AJCC stage 4 UC presenting from 2001 to 2010 to Texas Oncology Cancer Centers. The frontline chemotherapy regimen was classified as cisplatin-based, carboplatin-based, non-platinum based and no chemotherapy administered. The association of age with administration of cisplatin was studied. Results: A total of 298 patients with stage 4 disease were eligible for this analysis out of 3574 patients with UC in this database. Of the 298 patients, 197 (66.1%) were male, the median age was 70 years (range 28-97), and the primary sites of disease were bladder (243, 81.5%), renal pelvis (41, 13.8%) and ureter (14, 4.7%). The regimens administered were cisplatin-based in 107 patients (35.9%), carboplatin-based in 81 (27.2%), non-platinum in 25 (8.4%), no chemotherapy was administered in 71 (23.8%) and data were not available in 14 patients (4.7%). Cisplatin administration appeared more common in patients aged ≤70 years (62 of 150, 41.3%) as opposed to &gt;70 years (45 of 148, 30.4%), p=0.05. Non-cisplatin regimens or no chemotherapy were trending to be more commonly administered to patients &gt;70 years (64.2 vs. 54.7%, p=0.10). Limitations of a retrospective database study apply and the reasons for not administering cisplatin are unclear. Conclusions: Cisplatin-based chemotherapy was administered to 35.9% of patients presenting with AJCC stage 4 UC to community cancer centers. Given that the majority of patients may not be cisplatin-eligible or candidates for chemotherapy, this population has a significant unmet need. Drug development focused on single agent therapy with tolerable, convenient and efficacious agents or combination regimens without a cisplatin backbone should be a priority.
The TOR Kinase Inhibitor INK128 Is Effective in Pre-B Acute Lymphoblastic Leukemia Models
Authors: David A Fruman, Matthew Robert Janes, Sharmila Mallya, Collin C Vu, Marie P. Shieh, Michael B. Lilly, Leonard S Sender, Michael B Martin, Pingda Ren, Yi Liu, Christian Rommel
Journal: Blood (2011)
MicroRNAs as emerging biomarkers for micrometastasis detection in genitourinary tumors.
Authors: V. Medina Villaamil, I. Santamarina Caínzos, G. Aparicio Gallego, M. Quindós Varela, D. Dopico Vázquez, S. Antolín Novoa, R. García Campelo, M. Reboredo, M. Valladares Ayerbes, L. M. Antón Aparicio
Journal: Journal of Clinical Oncology (2011)

52 Background: MicroRNAs regulate numerous aspects of normal and pathological cellular processes, including cancer. Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in genitourinary (GU) tumors. miRNAs may also be considered as potential therapeutic targets when overexpression is associated to pathogenic effect. miRNAs may constitute a promising new class of cancer biomarkers for CTC detection. The aim of this work is identify miRNAs potentially useful for CTC detection in blood samples from patients with GU tumors: bladder, prostate and renal tumors. Methods: miRGator, miRBase, smiRNAdb, GeneHUB-GEPIS, microRNA.org and miRNAMap free databases were used in order to identify miRNAs as biomarkers for CTC detection. In silico data were used to identify miRNAs highly expressed in GU tumors, but absent in hematopoietic-derived sources. RNA enriched in miRNAs was isolated from: GU tumors (bladder: HT1376, HT1197; prostate: VCaP, LNCaP and renal: ACHN, A704) and hematopoietic cell lines, GU tumor tissues (N= 6) and healthy blood samples (N= 19). mirVana miRNA and RiboPure Blood isolation kits were used. Using qRT-PCR miRNAs tumor-related were amplified. Results: Bioinformatic analysis included tissue-specific and oncogenic miRNAs and showed that mir-31, mir-136, mir-133a, mir-145, mir-187, mir-200a, mir-200b, mir-200c, mir-368 and hsa-let-7c levels were up-regulated in tumor tissues from patients with advanced GU tumors. For instance, relative expression of mir-31 was 6-timeshigher in bladder cell lines than in normal peripheral blood, mir-200c was 10 4 -times higher in renal tumor tissue than in normal peripheral blood and finally hsa-let-7c was 3-times higher in prostate tumor tissue than in healthy blood samples. Conclusions: These results suggest that this bioinformatic approach is an useful high-throughout method to identified GU tumors-associated miRNAs. The selected miRNAs should be further evaluated for their potential as markers for CTC detection, prognosis and therapeutic outcome. This work was supported by Grants PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III. No significant financial relationships to disclose.
A Phase I Study of IMGN529, an Antibody-Drug Conjugate (ADC) Targeting CD37, in Adult Patients with Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma (NHL)
Authors: Anastasios Stathis, Arnold S. Freedman, Ian W. Flinn, Kami J. Maddocks, Steven Weitman, Jesus G. Berdeja, Alex V. Mejia, Emanuele Zucca, Rebecca Green, Angela Romanelli, Sybil H Zildjian, Rodrigo Ruiz-Soto, Lia Palomba
Journal: Blood (2014)
RASSF8 Overexpression Expands KLS Cells in Vitro and Blocks Murine Hematopoietic Stem Cells in a Primitive Phenotype.
Authors: Helene M. Schoemans, Rikkert Snoeckx, Shannon Buckley, Elda Mimiola, Sarah Schouteden, Catherine M. Verfaillie
Journal: Blood (2008)
Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung
Authors: Ismé M. de Kleer, Mirjam Kool, Marjolein J.W. de Bruijn, Monique Willart, Justine van Moorleghem, Martijn J. Schuijs, Maud Plantinga, Rudi Beyaert, Emily Hams, Padraic G. Fallon, Hamida Hammad, Rudi W. Hendriks, Bart N. Lambrecht
Journal: Immunity (2016)
Guided growth of auditory neurons: Bioactive particles towards gapless neural – electrode interface
Authors: Hao Li, Fredrik Edin, Hisamitsu Hayashi, Olafur Gudjonsson, Niklas Danckwardt-Lillieström, Håkan Engqvist, Helge Rask-Andersen, Wei Xia
Journal: Biomaterials (2016)

Cochlear implant (CI) is a successful device to restore hearing. Despite continuous development, frequency discrimination is poor in CI users due to an anatomical gap between the auditory neurons and CI electrode causing current spread and unspecific neural stimulation. One strategy to close this anatomical gap is guiding the growth of neuron dendrites closer to CI electrodes through targeted slow release of neurotrophins. Biodegradable calcium phosphate hollow nanospheres (CPHSs) were produced and their capacity for uptake and release of neurotrophins investigated using 125I-conjugated glia cell line-derived neurotrophic factor (GDNF). The CPHSs were coated onto CI electrodes and loaded with neurotrophins. Axon guidance effect of slow-released neurotrophins from the CPHSs was studied in an in vitro 3D culture model. CPHS coating bound and released GDNF with an association rate constant 6.3 × 103 M-1s-1 and dissociation rate 2.6 × 10-5 s-1, respectively. Neurites from human vestibulocochlear ganglion explants found and established physical contact with the GDNF-loaded CPHS coating on the CI electrodes placed 0.7 mm away. Our results suggest that neurotrophin delivery through CPHS coating is a plausible way to close the anatomical gap between auditory neurons and electrodes. By overcoming this gap, selective neural activation and the fine hearing for CI users become possible.
Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Gut Acute Graft-Versus-Host-Disease (GVHD)
Authors: Florent Malard, Céline Bossard, Jessy Arbez, Patrice Chevallier, Thierry Guillaume, Jacques Delaunay, Jean-François Mosnier, Philippe Saas, Mohamad Mohty, Béatrice Gaugler
Journal: Blood (2011)
Bcl2 as a surrogate prognostic and predictive marker in triple-negative breast cancer.
Authors: T. M. A. Abdel-Fatah, P. D. Dickinson, P. Moseley, J. S. Reis-Filho, A. R. Green, I. O. Ellis, S. Chan
Journal: Journal of Clinical Oncology (2011)

1024 Background: TNBC patients have a relatively poor prognosis and the optimal choice of chemotherapy for this subgroup has not yet been defined. Studies have shown TNBC is a heterogeneous group of tumours and certain subgroups of TNBC could benefit from neoadjuvant therapy. In this study, we hypothesized that Bcl2 immunohistochemical expression could accurately stratified TNBC into low- and high risk patients and predict their response to chemotherapy. Methods: Three independent series of BC were immunohistochemically profiled for Bcl2; a) 296 and 153 of primary TNBC and non TNBC respectively, in which adjuvant CMF chemotherapy was given, b) 63 TNBC and 160 non-TNBC locally advanced primary BC treated with anthracycline-based chemotherapy c) 31 TNBC and 209 non-TNBC in which all patients were primarily treated with surgery followed by anthracycline-based chemotherapy. Results: In patients with TNBC who received CMF chemotherapy, multivariate Cox regression models demonstrated that Bcl2 was significantly associated with patient outcome; TNBC/ low Bcl2 tumours were associated with a three-fold increased risk of death ((p=0.000039) and recurrence ( p =0.0001) compared to TNBC/high Bcl2 tumours. In patients with BC treated with neoadjuvant anthracycline based chemotherapy, 18/63 (28%) TNBC achieved a pathological complete response (pCR) vs. 17/144 (12%) of non-TNBC (p=0.006). 42% of TNBC with low level of Bcl2 achieved pCR compared with 11% of TNBC with high Bcl2 expression (p=0.02). After neoadjuvant treatment, patients with TNBC with low and high Bcl2 expression had similar clinical outcome. Conclusions: In patients with TNBC who received CMF chemotherapy, Bcl2 expression reclassified patients into two groups: low risk (Bcl2+) versus high risk (Bcl2-) of BC mortality and recurrence. Anthracycline based neoadjuvant therapy is an effective treatment for TNBC with low levels of Bcl2 expression and is associated with a higher pCR rate. Adding Bcl2 to the panel of TNBC phenotype markers could help guide treatment decisions in this group of patients and ultimately lead to better patient outcome.
MC0553: A phase II safety and efficacy study with the VEGF receptor tyrosine kinase inhibitor pazopanib in patients with metastatic urothelial cancer.
Authors: R. Pili, R. Qin, P. J. Flynn, J. Picus, M. Millward, W. M. Ho, H. C. Pitot, W. Tan, C. Erlichman, U. N. Vaishampayan
Journal: Journal of Clinical Oncology (2011)

259 Background: Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are produced by bladder cancer cell lines in vitro and expressed in human tumor tissues. Preclinical studies have also shown that bladder cancer cell lines express VEGF receptor 1 and 2 on their surface membrane. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and antitumor activity in several preclinical models. A two-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib administered to patients with metastatic, urothelial carcinoma. Methods: Patients with one prior systemic therapy for recurrent, metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally daily for 4 week cycle. Results: Nineteen patients were enrolled. Median age was 66 years, with &gt; 89% of patients presenting poorly differentiated bladder cancer. Adverse event data is available on 18 patients. No grade 4 or 5 events have been experienced. Nine patients have experienced 11 grade 3 adverse events of which 7 were deemed at least possibly related to treatment. Most common toxicities were anemia, thrombocytopenia, leucopenia and fatigue. For stage 1, none of the first 16 evaluable patients were deemed success (CR or PR) by the RECIST criteria during the first four 4-week cycles of treatment. Median progression- free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore, the trial was recommended to be permanently closed. Correlative studies including measurement of VEGF levels in archived tissues and blood are pending. Conclusions: Pazopanib did not show activity in urothelial carcinoma patients. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies. [Table: see text]
Menopause Is Associated with Accelerated Lung Function Decline
Authors: Kai Triebner, Bobette Matulonga, Ane Johannessen, Sandra Suske, Bryndís Benediktsdóttir, Pascal Demoly, Shyamali C. Dharmage, Karl A. Franklin, Judith Garcia-Aymerich, José Antonio Gullón Blanco, Joachim Heinrich, Mathias Holm, Debbie Jarvis, Rain Jõgi, Eva Lindberg, Jesús Martínez Moratalla Rovira, Nerea Muniozguren Agirre, Isabelle Pin, Nicole Probst-Hensch, Luca Puggini, Chantal Raherison, José Luis Sánchez-Ramos, Vivi Schlünssen, Jordi Sunyer, Cecilie Svanes, Steinar Hustad, Bénédicte Leynaert, Francisco Gómez Real
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause.Objectives: To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause.Methods: The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect.Measurements and Main Results: Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by −10.2 ml/yr (95% confidence interval [CI], −13.1 to −7.2) in transitional women and −12.5 ml/yr (95% CI, −16.2 to −8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by −3.8 ml/yr (95% CI, −6.3 to −2.9) in transitional women and −5.2 ml/yr (95% CI, −8.3 to −2.0) in post-menopausal women.Conclusions: Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.
Rituximab Monotherapy Is an Effective Treatment for Splenic Marginal Zone B-Cell Lymphomas (SMZL).
Authors: Maria N. Dimopoulou, Christina Kalpadakis, Evangelia M. Dimitriadou, Marie-Christine Kyrtsonis, Styliani I. Kokoris, Panagiotis Tsaftaridis, Flora N. Kontopidou, Marina P. Siakantaris, Eleni Plata, Theodoros P. Vassilakopoulos, Maria K. Angelopoulou, Gerassimos A. Pangalis
Journal: Blood (2005)
Phase IB trial redesign to test role of IL2 with anti-PSMA designer T cells to yield responses in advanced prostate cancer.
Authors: Richard P. Junghans
Journal: Journal of Clinical Oncology (2012)

70 Background: We created a chimeric antigen receptor (CAR) for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” specifically kill prostate cancer cells in vitro and in vivo in animal models (Ma et al. Prostate 2004:61:12-25). FDA approved a Phase I clinical trial. Methods: Patient T cells are retrovirally transduced and expanded. Patients undergo non-myeloablative (NMA) conditioning to create “hematologic space” into which designer T cells are infused for engraftment and improved in vivo efficacy. Patients are co-administered continuous infusion IL2. Patients are monitored for safety and response. Results: Five patients were treated, three at 10^9 and two at 10^10 cell dose levels with safety. Partial responses (PR) were seen in 2/5 patients (40%), with PSA suppressions of 50 and 70% over 1-2 months and PSA progression delay of 70 and 150 days. Yet these responses were observed only at the lowest T cell dose (10^9 cells) and not the higher tested dose (10^10 cells). Response correlated with plasma IL2 that was as much as 10-fold lower in non-responders vs responders. This low IL2 correlated in turn with high engrafted fractions of infused activated T cells. This prompted a hypothesis that infused activated T cells at high engrafted cell numbers absorbed out IL2 to a level too low to sustain dTc activation for effective tumor killing. A study redesign will test high dose IL2 (HDI) versus moderate dose IL2 (MDI) in Phase Ib/Pilot at 10^10 cell dose, then advancing to the maximum practical dose (MPD, 10^11 cells) of dTc under the optimal IL2 plan. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised with encouraging early results. We postulate that adequate higher IL2 in vivo will allow the greater potency of higher dTc doses to be revealed, thereby potentially inducing PSA reductions of 100%, with durable remissions of metastatic prostate cancer that is refractory to all other treatments. Patients are being recruited. This clinical trial received funding from US Army/DOD and from Prostate Cancer Foundation for preclinical work.