tbuckley/cabot-search huggingface dataset:
Photomutagenicity and phototoxicity of the breast cancer therapy agent tamoxifen
Authors: Lei Wang, Zheng Wang, Shuguang Wang, William Hardy, Peter P. Fu, Hongtao Yu
Journal: Cancer Research (2005)

4771  Tamoxifen, an anti-estrogen therapy agent for patients with breast cancer, has been widely used. More then 500,000 women in the US are being treated with this drug. It is known that long-term treatment of this drug significantly increase women endometrial cancer. Tamoxifen-DNA adducts have been found in rat liver and in the endometrial tissue of certain women treated with this drug. There is no research into on the possible toxic effects initiated by light irradiation since tamoxifen absorbs UV component of the sunlight. Therefore, a photo-Ames test with Salmonella TA 102 is performed by irradiating the bacteria in plate mixed with various amounts of tamoxifen. It shows that tamoxifen is strongly photomutagenic in Salmonella typhimurium TA102 at concentrations as low as 0.08 μM and reaches maximum photomutagenicity at 0.4 μM under 4.6 J/cm2 of UVA and 8.4 J/cm2 of visible light. Tamoxifen with concentrations of greater than 0.4 μM is the phototoxic, leading to bacteria death. At concentrations of greater than 25 μM, severe bacteria death is observed. Furthermore, tamoxifen showed photocytotoxicity and photogenotoxicity in human HaCaT keratinocytes and supercoiled ΦΧ174 phage DNA. This suggests that the photomutagenicity shown in TA102 might be due to DNA fragmentation caused by the concurrent exposure to tamoxifen and light. Acknowledgement: This research was in part supported by the National Institutes of Health: NIH SCORE S06 GM08047 and the US Army Research Office DAAD 1901-1-0733.
Mismatch repair (MMR) detection in urothelial carcinoma (UC) and correlation with immune checkpoint blockade (ICB) response.
Authors: Gopa Iyer, Francois Audenet, Sumit Middha, Maria Isabel Carlo, Ashley Marie Regazzi, Samuel Funt, Hikmat Al-Ahmadie, David B. Solit, Jonathan E. Rosenberg, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2017)

4511 Background: High mutation burden correlates with response to ICB in UC. Loss of function alterations or epigenetic silencing of MMR genes results in MMR deficient (MMR-D) UC, leading to a microsatellite instability (MSI) mutation signature. We used a CLIA-certified pipeline (MSISensor) to interrogate Next Generation sequencing (NGS) data from UC tumors to identify MMR-D patients (pts). We correlated MMR-D with mutation load and response to ICB. Methods: 447 tumors from 424 UC pts underwent prospective NGS using the MSK-IMPACT exon capture assay and genomic interrogation of microsatellite (MS) sites using MSIsensor, which assesses the number/length of MS within the targeted regions of tumor-normal sample pairs. Loci are considered unstable (somatic) if k-mer distributions are significantly different between tumor and matched normal using a standard multiple testing correction of χ2 p-values. The fraction of unstable sites is reported as an MSIsensor score. MSI high tumors have scores &gt;10 while &lt;3 are denoted MS stable. Scores from 3-10 were categorized as MS intermediate. Results: Thirteen pts (3%) had an MSI score &gt;10 and a median mutation count of 52 (36.5-73.5) vs 8 (5-13) in 410 non-MMR-D pts (p&lt;0.01). Ten pts (71%) had upper tract UC. Of 9 pts with germline sequencing performed, 8 (89%) had heritable loss of function mutations in MMR proteins (Lynch syndrome, LS). One pt had a somatic MSH2 mutation. Fifteen pts had MS scores from 3-10: 3 had LS, one a BRCA1 germline alteration, and 9 did not have germline testing available. Two pts with MSI scores &lt;3 had extremely high mutation loads (213 and 414) and both had POLE mutations. Five pts received ICB therapy for metastatic and all achieved near-complete or complete responses. No MMR-D pt has died at 27 months follow-up vs 125 non-MMR-D pts (p=0.014). Conclusions: The MSI Sensor assay can discriminate MSI high from MMR proficient UC. While rare, MMR-D UC is characterized by a high mutation load, strong association with Lynch syndrome, and durable responses to ICB, similar to data in colon cancer. An MMR-D signature should trigger genetic testing for Lynch syndrome. ICB should be considered early in the treatment course of patients with MMR-D metastatic UC.
Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial
Authors: John H Beigel, Yajing Bao, Joy Beeler, Weerawat Manosuthi, Alex Slandzicki, Sadia M Dar, John Panuto, Richard L Beasley, Santiago Perez-Patrigeon, Gompol Suwanpimolkul, Marcelo H Losso, Natalie McClure, Dawn R Bozzolo, Christopher Myers, H Preston Holley, Justin Hoopes, H Clifford Lane, Michael D Hughes, Richard T Davey, Michael Winnie, Dinh V Dinh, Raghu Seethala, Hiram Garcia, Joe Pouzar, Michael Seep, Ernie Riffer, Belinda Bart, Sadia Dar, Melanie Hoppers, John Panuto, Heather Rowe, Alex Slandzicki, Cameron Wolfe, Donna Desantis, Barr Baynton, Richard L Beasley, Norman Markowitz, Zebediah A Stearns, Josalyn Cho, Marcy Goisse, Thomas A Wolf, Jennifer Kay, Nila Dharan, William Fitzgibbons, Mark Woodruff, Todd Bell, Thomas Lenzmeier, Robert Schooley, Marie-Carmelle Elie, Patricia Winokur, Robert Finberg, Christopher Hurt, Pablo Tebas, Fred R Sattler, Madhavi Ampajwala, Donald Batts, Mark Bloch, Richard Moore, Dominic Dwyer, Javier Romo-Garcia, Santiago Perez Patrigeon, Ana Patricia Rodríguez Zulueta, Weerawat Manosuthi, Ploenchan Chetchotisakd, Kiat Ruxrungtham, Anchalee Avihingsanon, Gompol Suwanpimolkul, Winai Ratanasuwan, Sergio Lupo, Liliana Trape, Marcelo H Losso, Laura M Macias, Gustavo Lopardo, Laura Barcelona, Analia Mykietuk, Maria F Alzogaray
Journal: The Lancet Infectious Diseases (2017)
miR-130a Deregulates PTEN and Stimulates Tumor Growth
Authors: Huijun Wei, Ri Cui, Julian Bahr, Nicola Zanesi, Zhenghua Luo, Wei Meng, Guang Liang, Carlo M. Croce
Journal: Cancer Research (2017)

Abstract H-RasV12 oncogene has been shown to promote autophagic cell death. Here, we provide evidence of a contextual role for H-RasV12 in cell death that is varied by its effects on miR-130a. In E1A-immortalized murine embryo fibroblasts, acute expression of H-RasV12 promoted apoptosis, but not autophagic cell death. miRNA screens in this system showed that miR-130a was strongly downregulated by H-RasV12 in this model system. Enforced expression of miR-130a increased cell proliferation in part via repression of PTEN. Consistent with this effect, miR-130a overexpression in human breast cancer cells promoted Akt phosphorylation, cell survival, and tumor growth. In clinical specimens of multiple human cancers, expression of miR-130 family members correlated inversely with PTEN expression. Overall, our results defined miR-130a as an oncogenic miRNA that targets PTEN to drive malignant cell survival and tumor growth. Cancer Res; 77(22); 6168–78. ©2017 AACR.
Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair
Authors: Kunwoo Lee, Michael Conboy, Hyo Min Park, Fuguo Jiang, Hyun Jin Kim, Mark A. Dewitt, Vanessa A. Mackley, Kevin Chang, Anirudh Rao, Colin Skinner, Tamanna Shobha, Melod Mehdipour, Hui Liu, Wen-chin Huang, Freeman Lan, Nicolas L. Bray, Song Li, Jacob E. Corn, Kazunori Kataoka, Jennifer A. Doudna, Irina Conboy, Niren Murthy
Journal: Nature Biomedical Engineering (2017)
Results of Australasian Gastrointestinal Trials Group (AGITG) Arctic study: An international audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines (FP).
Authors: David Ransom, Kate Wilson, Sarwan K. Bishnoi, John Simes, Desmond Yip, Christos Stelios Karapetis, Val Gebski, Stephen Gordon, Marion Fournier, David Raymond Ferry, Haider Abbas, Rachel A Midgley, Timothy Jay Price
Journal: Journal of Clinical Oncology (2012)

e13007 Background: Cardiac toxicity (CT) is an uncommon but potentially fatal side effect of FP. The incidence of further CT if the same chemotherapy is continued is reported to be 20% (Jensen SA et al. Risk factors and prevention of cardiac toxicity induced by 5-fluorouracil or capecitabine. Cancer Chemotherapy &amp; Pharm. 58:487-93, 2006). Management of these patients remains poorly defined. Treatment options include continuing same dose and schedule of FP, adding a nitrate and calcium antagonist; switching to bolus FP; or substituting with raltitrexed. Previous publications of patients experiencing CT and switching FP to raltitrexed are limited to case reports. Methods: AGITG &amp; OCTO (Oncology Clinical Trials Office – Oxford) members identified patients who had CT from FP, and were subsequently switched to raltitrexed. CT included angina, myocardial infarct (MI) or arrhythmia. A coronary angiogram was not mandatory. Results: 38 patients were included in clinical audit. Cancer diagnoses included colorectal (35pts), cervix (1), oesophageal (1) and ampullary carcinoma (1). Median age - 61 years (range 36-81). 24 patients (63%) were male. Median number of cycles prior to switching to raltitrexed was 2 (range 1-11). FP regimens included FOLFOX, CAPOX, continuous infusion 5FU, capecitabine alone. 35 patients had angina, 6 MI, and 1 arrhythmia with some patients experiencing &gt;1 event at that time. 7 patients experienced two separate CT events, and 2 had three events prior to switching to raltitrexed. Following CT 8 patients received raltitrexed alone, 29 received raltitrexed in combination with other agents or radiotherapy and one received raltitrexed alone followed by combination. Median number of raltitrexed cycles was 5 (range 1-21). After switching to raltitrexed 2 patients experienced another cardiac event (5.3%, 95% CI:1.5-17.3), significantly different from 20% (p=0.023), the reported rate of cardiac toxicity due to continuing FP. Conclusions: For patients who experience CT from FP switching to raltitrexed is an option with the rate of additional cardiac events lower than previously reported for continuing same FP.
Consider Quality of Life to Improve Quality of Cancer Guidelines
Authors: Larissa Nekhlyudov, Catherine M. Alfano, David Weller
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
<i>Notes from the Field:</i> Increase in Reported Hepatitis A Infections Among Men Who Have Sex with Men — New York City, January–August 2017
Authors: Julia Latash, Marie Dorsinville, Paula Del Rosso, Mike Antwi, Vasudha Reddy, HaeNa Waechter, Jacqueline Lawler, Heather Boss, Philip Kurpiel, P. Bryon Backenson, Charles Gonzalez, Shannon Rowe, Tasha Poissant, Yulin Lin, Guo-Liang Xia, Sharon Balter
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Since 2011, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has typically been notified of three or fewer cases of hepatitis A virus (HAV) infection each year among men who have sex with men (MSM) who reported no travel to countries where HAV is endemic. This year, DOHMH noted an increase in HAV infections among MSM with onsets in January-March 2017, and notified other public health jurisdictions via Epi-X, CDC's communication exchange network. As a result, 51 patients with HAV infection involving MSM were linked to the increase in NYC.
Combining amino amide salts in mucoadhesive films enhances needle-free buccal anesthesia in adults
Authors: Renê Oliveira do Couto, Camila Cubayachi, Paulo Linares Calefi, Renata Fonseca Vianna Lopez, Vinícius Pedrazzi, Cristiane Masetto De Gaitani, Osvaldo de Freitas
Journal: Journal of Controlled Release (2017)
COSMOS: MOR208 plus idelalisib or venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a Bruton's tyrosine kinase inhibitor (BTKi)—A two-cohort phase II study.
Authors: Clemens-Martin Wendtner, John C. Byrd, Robin Foà, Richard Greil, Peter Hillmen, Ulrich Jäger, Wojciech Jurczak, Peter Kelemen, Kamel Laribi, Talha Munir, Johannes Schetelig, Philipp B. Staber, Stephan Stilgenbauer, Jennifer Ann Woyach
Journal: Journal of Clinical Oncology (2017)

TPS7567 Background: Patients (pts) with R/R CLL who discontinue treatment with the BTKi ibrutinib due to progression have a particularly dismal prognosis. A phase I study showed that the Fc-enhanced, humanized, CD19 antibody MOR208 was well tolerated with encouraging single-agent activity in pts with R/R CLL/SLL. In preclinical models, MOR208 showed synergy with idelalisib (an inhibitor of PI3K delta) and venetoclax (an inhibitor of BCL-2), both approved for the treatment of CLL. Methods: This two-cohort, phase II study will investigate MOR208 combined with idelalisib (cohort A) or venetoclax (cohort B) in pts with R/R CLL or R/R SLL and includes a safety run-in phase for each cohort, to be evaluated by an Independent Data Monitoring Committee. Key inclusion criteria: aged ≥18 years, R/R CLL/SLL while receiving a BTKi therapy or intolerance of such therapy, BTKi administered as a single-agent or in combination for at least 1 month as the most recent prior anticancer therapy, ECOG performance status of 0–2, and adequate organ function. Key exclusion criteria: transformed CLL/SLL or Richter’s syndrome, BTKi treatment within 5 days prior to study drug dosing, prior treatment with a CD19-targeted therapy, a PI3K inhibitor (cohort A) or a BCL-2 inhibitor (cohort B). Pts will be treated for a maximum of 24 (28-day) cycles or until disease progression. Treatment will be MOR208 12 mg/kg IV (weekly for the first 3 months, every second week for the next 3 months, and monthly thereafter) in combination with oral idelalisib 150 mg twice-daily or venetoclax administered on a weekly ramp-up dosing schedule to the recommended daily dose of 400 mg. Primary endpoint: overall response rate based on independent review; secondary and exploratory endpoints include: progression-free and overall survival, duration of response, safety, pharmacokinetics, MOR208 immunogenicity, quality of life and minimal residual disease negativity. 120 pts per cohort are planned. Clinical trial information: 2015-002915-14.
Contralateral Prophylactic Mastectomy
Authors: Ramya Ramaswami, Monica Morrow, Reshma Jagsi
Journal: New England Journal of Medicine (2017)

This interactive feature about women with triple-negative breast cancer and family history of breast cancer, but no BRCA1 or BRCA2 mutation, offers a case vignette accompanied by essays that support either recommending or not recommending contralateral prophylactic mastectomy.
Reply to Suissa and Ariel: The FULFIL Trial
Authors: David A. Lipson, Helen Barnacle, Ruby Birk, Noushin Brealey, Nicholas Locantore, David A. Lomas, Andrea Ludwig-Sengpiel, Rajat Mohindra, Maggie Tabberer, Chang-Qing Zhu, Steven J. Pascoe
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Treatment Intensity After Traumatic Brain Injury
Authors: Alexis Colley, Emily Finlayson
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell–Derived Endothelial Cells Encapsulated in a Nanomatrix Gel
Authors: Shin-Jeong Lee, Young-Doug Sohn, Adinarayana Andukuri, Sangsung Kim, Jaemin Byun, Ji Woong Han, In-Hyun Park, Ho-Wook Jun, Young-sup Yoon
Journal: Circulation (2017)

Human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) have limited clinical utility because of undefined components in the differentiation system and poor cell survival in vivo. Here, we aimed to develop a fully defined and clinically compatible system to differentiate hPSCs into ECs. Furthermore, we aimed to enhance cell survival, vessel formation, and therapeutic potential by encapsulating hPSC-ECs with a peptide amphiphile (PA) nanomatrix gel.We induced differentiation of hPSCs into the mesodermal lineage by culturing on collagen-coated plates with a glycogen synthase kinase 3β inhibitor. Next, vascular endothelial growth factor, endothelial growth factor, and basic fibroblast growth factor were added for endothelial lineage differentiation, followed by sorting for CDH5 (VE-cadherin). We constructed an extracellular matrix-mimicking PA nanomatrix gel (PA-RGDS) by incorporating the cell adhesive ligand Arg-Gly-Asp-Ser (RGDS) and a matrix metalloproteinase-2-degradable sequence. We then evaluated whether the encapsulation of hPSC-CDH5+ cells in PA-RGDS could enhance long-term cell survival and vascular regenerative effects in a hind-limb ischemia model with laser Doppler perfusion imaging, bioluminescence imaging, real-time reverse transcription-polymerase chain reaction, and histological analysis.The resultant hPSC-derived CDH5+ cells (hPSC-ECs) showed highly enriched and genuine EC characteristics and proangiogenic activities. When injected into ischemic hind limbs, hPSC-ECs showed better perfusion recovery and higher vessel-forming capacity compared with media-, PA-RGDS-, or human umbilical vein EC-injected groups. However, the group receiving the PA-RGDS-encapsulated hPSC-ECs showed better perfusion recovery, more robust and longer cell survival (> 10 months), and higher and prolonged angiogenic and vascular incorporation capabilities than the bare hPSC-EC-injected group. Surprisingly, the engrafted hPSC-ECs demonstrated previously unknown sustained and dynamic vessel-forming behavior: initial perivascular concentration, a guiding role for new vessel formation, and progressive incorporation into the vessels over 10 months.We generated highly enriched hPSC-ECs via a clinically compatible system. Furthermore, this study demonstrated that a biocompatible PA-RGDS nanomatrix gel substantially improved long-term survival of hPSC-ECs in an ischemic environment and improved neovascularization effects of hPSC-ECs via prolonged and unique angiogenic and vessel-forming properties. This PA-RGDS-mediated transplantation of hPSC-ECs can serve as a novel platform for cell-based therapy and investigation of long-term behavior of hPSC-ECs.
P19.04 Psychosocial counseling in neuro-oncology - analysis of topics and needs of brain tumor patients
Authors: S. Schipmann, E. Suero
Journal: Neuro-Oncology (2017)

Objective: In the field of neuro-oncology an increasing focus is being directed towards the psychosocial needs of patients diagnosed with brain tumors. However, it remains challenging to establish psycho-oncological therapies and interventions that meet the specific needs of these patients. Therefore, the aim of this study was to identify major concerns and burdens of brain tumor patients on the basis of our clinical experience. Methods: This retrospective chart analysis included 53 patients attending supportive psycho-oncological counseling at the Department of Neurosurgery, University of Münster between 2010 and 2014. All patients were counseled by the same therapist, a neurosurgeon with specialization in psycho-oncology. Notes were analyzed based on qualitative content analysis. With regard to physical and psychological symptoms, coping strategies and further concerns mentioned by the patients, thematic categories were established. Notes were then assigned to the categories to analyze their frequency distribution and identify the patients’ main concerns. Results: The cohort had a mean age of 48 years. 30 (56.6%) were female. 23 (43.4%) were diagnosed with high grade glioma, 16 (30.2%) with low grade glioma, 10 (8.9%) with a benign brain tumor and 4 (7.5%) had cerebral metastasis. The median number of consultations per patient was 4 (range 1 - 47). During their first consultation, 36 (67.9%) patients listed their physical symptoms and limitations. 40 (75.5%) suffered psychological symptoms, often accompanied by a depressive disorder. The majority of patients expressed issues related to questions concerning meaning of and priorities in life (71.7%), medical topics and questions (62.3%) and death and mortality (56.6%). Furthermore, the following concerns were primarily mentioned: the shock of being diagnosed with a brain tumor, work and occupation, loss of roles and tasks in daily life, family conflicts, reduced mobility, excessive demand and reduced capacity. Concerning coping modes, more patients showed appropriate strategies (including an active attitude toward the disease; 39.6%) than inappropriate strategies, comprising resignation (20.8%) and rumination (18.9%). Concerning psychological symptoms and topics of conversations, there were no significant differences among patients regardless of the dignity of tumor (p= n.s.). Conclusion: These results provide an insight into major concerns and issues that patients diagnosed with a brain tumor are frequently dealing with. Therefore, they can serve as an important basis for the development of psychosocial intervention concepts. No significant differences between the diagnosis groups were found. This suggests that, regardless of prognosis and tumor natural history, the burdens of patients diagnosed with a brain tumor are similar and all patients, despite of their diagnosis, might benefit from psychosocial support.