tbuckley/cabot-search huggingface dataset:
Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model
Authors: Amanda Contreras, Megan V. Beems, Andrew J. Tatar, Siddhartha Sen, Prakrithi Srinand, M. Suresh, Tahra K. Luther, Clifford S. Cho
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Adoptive cell transfer (ACT) is a promising cancer immunotherapeutic strategy that remains ineffective for a large subset of patients. ACT with memory CD8+ T cells (T<sub>mem</sub>) has been shown to have superior efficacy compared to traditional ACT with effector CD8+ T cells (T<sub>eff</sub>). T<sub>eff</sub> and T<sub>mem</sub> have complementary physiological advantages for immunotherapy, but previous publications have not examined ACT using a combination of T<sub>eff</sub> and T<sub>mem</sub>. <h3>Methods</h3> Splenocytes harvested from Ly5.1+/C57BL/6 mice during and after infection with lymphocytic choriomeningitis virus (LCMV) were used to generate bona fide effector and memory CD8+ T cells specific for the LCMV epitope peptide GP33. Congenic Ly5.2+/C57BL/6 mice were inoculated with B16F10 melanoma cells transfected to express very low levels of GP33, then treated with ACT 7&nbsp;days later with GP33-specific T<sub>eff</sub>, T<sub>mem</sub>, or a combination of T<sub>eff</sub> + T<sub>mem</sub>. <h3>Results</h3> Inhibition of melanoma growth was strongest in mice receiving combinatorial ACT. Although combinatorial ACT and memory ACT resulted in maximal intratumoral infiltration of CD8+ T cells, combinatorial ACT induced stronger infiltration of endogenous CD8+ T cells than T<sub>mem</sub> ACT and a stronger systemic T cell responsiveness to tumor antigen. In vitro assays revealed rapid but transient melanoma inhibition with T<sub>eff</sub> and gradual but prolonged melanoma inhibition with T<sub>mem</sub>; the addition of T<sub>mem</sub> enhanced the ability of T<sub>eff</sub> to inhibit melanoma in a manner that could be reproduced using conditioned media from activated T<sub>mem</sub> and blocked by the addition of anti-IL-2 blocking antibody. <h3>Conclusions</h3> These findings suggest that a novel combinatorial approach that takes advantage of the unique and complementary strengths of tumor-specific T<sub>eff</sub> and T<sub>mem</sub> may be a way to optimize the efficacy of adoptive immunotherapy.
Breast cancer in Sub-Saharan Africa: 1,000 patients with primary breast cancer in Addis Ababa followed for up to 5 years.
Authors: Eva Johanna Kantelhardt, Peter Zerche, Pietro Trocchi, Assefa Mathios, Anne Reeler, Gemechu Tufa, Bekuretsion Yonas, Andreas Stang, Christoph Thomssen, Solomon Desalegne Bogale
Journal: Journal of Clinical Oncology (2012)

580 Background: There is little information on breast cancer (BC) patients (pts) receiving standardized treatment in Sub-Saharan Africa. This study evaluates pts presenting 2005-10 at the University Radiotherapy Center in Addis Ababa, the only institution in the country offering standardized radiotherapy, systemic therapy and free endocrine treatment (ET) during that time. Methods: All pts with histologically verified BC were included. Ethical approval was obtained. Axios/AstraZenaca provided free ET. Therefore, the majority of pts underwent regular follow-up (FUP). We analyzed survival at 18 months by means of Kaplan-Meier survival analysis. We assumed right-censoring to be unrelated to the risk of metastasis. In a worst case sensitivity analysis, we considered all censored pts developing metastasis. Results: Pts with primary diagnosis between July 1st, 2005 and December 31st, 2010 were included (n=1303). The majority of pts were female (95.2%), most (52.3%) postmenopausal. Mean age was 44.1yrs (20-88yrs). Stages 1-4 presented in 3/19/53/25% respectively (36% unknown). Grade 2 tumors were seen in 434 out of 574 pts (58%). Estrogen receptor was pos. in 251 out of 381 pts (66%). Most M0-pts (n=942) underwent surgery (84%), received chemotherapy (59%), and received ET (63%). Median FUP was 18.4 months, 186 events (metastases) occurred. Metastasis-free survival (MFS) was 86%. Worst case analysis on censored observations revealed that MFS declined down to 52%. Pts with early stage 1/2 showed a better MFS than pts with stage 3 disease (93 to 77%). Surgery (no surgery 78% vs surgery 87%) and ET (79% vs 89%) improved MFS. The 5-year MFS for stage 1/2 was 78% and stage 3 was 38%. Conclusions: To our knowledge this is the first presentation of clinical features in 1300 pts with BC in Sub-Saharan Africa. Most pts in Addis Ababa (AA) are &lt;45yrs and present at stage 3/4. Differences to 5-year MFS from Europe stage 1/2 around 90% (AA 78%) and stage 3 around 70% (AA 38%) are smaller in pts treated with surgery and ET. This data is consistent with overall survival in a treated pt cohort from Uganda stage 1/2: 74% and stage 3/4: 39% (n=285) (Gakwaya Brit J Cancer 2008). Policies should focus on earlier presentation and access to care.
Publisher Correction: TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD
Authors: Matthew A. White, Eosu Kim, Amanda Duffy, Robert Adalbert, Benjamin U. Phillips, Owen M. Peters, Jodie Stephenson, Sujeong Yang, Francesca Massenzio, Ziqiang Lin, Simon Andrews, Anne Segonds-Pichon, Jake Metterville, Lisa M. Saksida, Richard Mead, Richard R. Ribchester, Youssef Barhomi, Thomas Serre, Michael P. Coleman, Justin R. Fallon, Timothy J. Bussey, Robert H. Brown, Jemeen Sreedharan
Journal: Nature Neuroscience (2018)
Abstract 19806: Age-Dependent Prognostic Value of Low Body Mass Index for Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Yasushi Matsuzawa, Chika Kawashima, Ryousuke Sato, Nobuhiko Maejima, Katsutaka Hashiba, Noriaki Iwahashi, Kiyoshi Hibi, Toshiaki Ebbing, Masami Kosuge, Kazuo Kimura
Journal: Circulation (2016)

Introduction: Underweight individuals have increased risk of death. The age-dependent relationship between body mass index (BMI) and subsequent cardiovascular events in patients with ST-segment Ele...
Dosimetric Predictors of Symptomatic Cardiac Events After Conventional-Dose Chemoradiation Therapy for Inoperable NSCLC
Authors: Nikhil Yegya-Raman, Kyle Wang, Sinae Kim, Meral Reyhan, Matthew P. Deek, Mutlay Sayan, Diana Li, Malini Patel, Jyoti Malhotra, Joseph Aisner, Lawrence B. Marks, Salma K. Jabbour
Journal: Journal of Thoracic Oncology (2018)
Ethics and the Legalization of Physician-Assisted Suicide
Authors: Allen H. Roberts
Journal: Annals of Internal Medicine (2018)

Letters5 June 2018Ethics and the Legalization of Physician-Assisted SuicideAllen H. Roberts II, MD, MDiv, MA (Bioethics)Allen H. Roberts II, MD, MDiv, MA (Bioethics)Georgetown University Medical Center, Washington, DC (A.H.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0082 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I applaud the ACP's reaffirmation of opposition to PAS in Sulmasy and colleagues' position paper (1). In an era where ethical discourse and dialogue have been reduced to assertions of “autonomy” that are inattentive to the weight of both community and moral order, the ACP's reaffirmation should serve as a watershed moment, a tripwire and stumbling block to the unbridled advance of a practice that has been regarded as anathema by civilized society and by majority scholarly opinion of all major religions for 2 millennia.Assisted suicide today will inevitably lead to active euthanasia tomorrow. The embrace ...Reference1. Snyder L, Mueller PS; Ethics, Professionalism and Human Rights Committee of the American College of Physicians. Ethics and the legalization of physician-assisted suicide: an American College of Physicians position paper. Ann Intern Med. 2017;167:576-8. [PMID: 28975242]. doi:10.7326/M17-0938 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Georgetown University Medical Center, Washington, DC (A.H.R.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0082. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEthics and the Legalization of Physician-Assisted Suicide: An American College of Physicians Position Paper Lois Snyder Sulmasy , Paul S. Mueller , and Ethics and the Legalization of Physician-Assisted Suicide Lois Snyder Sulmasy and Paul S. Mueller Ethics and the Legalization of Physician-Assisted Suicide E. Wesley Ely Ethics and the Legalization of Physician-Assisted Suicide Banu E. Symington Ethics and the Legalization of Physician-Assisted Suicide Timothy L. Gieseke Ethics and the Legalization of Physician-Assisted Suicide Christie Reimer Metrics 5 June 2018Volume 168, Issue 11Page: 834KeywordsConflicts of interestDisclosureEuthanasiaPeriodic acid SchiffSuicide ePublished: 5 June 2018 Issue Published: 5 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7.
Authors: François Quenet, Dominique Elias, Lise Roca, Diane Goere, Laurent Ghouti, Marc Pocard, Olivier Facy, Catherine Arvieux, Gerard Lorimier, Denis Pezet, Frederic Marchal, Valeria Loi, Pierre Meeus, Hélène De Forges, Trevor Stanbury, Jacques Paineau, Olivier Glehen
Journal: Journal of Clinical Oncology (2018)

LBA3503 Background: Promising results have been obtained during the last decade using cytoreductive surgery (CRS) plus HIPEC for selected patients with colorectal PC who are amenable to complete macroscopic resection. This is the first trial to evaluate the specific role of HIPEC, after CRS, for the treatment of PC of colorectal origin. Methods: Prodige 7 is a randomized phase III, multicenter trial. Patients with histologically proven and isolated PC, peritoneal cancer index (PCI) ≤25 were eligible. Randomization (1:1) was stratified by center, complete macroscopic resection (R0/1 vs R2), and neoadjuvant systemic chemotherapy. Patients were treated with CRS plus HIPEC with oxaliplatin or CRS alone, in association with systemic chemotherapy. The primary endpoint was the overall survival (OS). Secondary endpoints were relapse-free survival (RFS) and toxicity. 264 patients were required to show a gain in median OS from 30 to 48 months (HR = 0.625) with a two-sided α = 0,046 and 80% power. Results: 265 patients from 17 centers were included between February 2008 and January 2014: 132 in Arm without HIPEC and 133 in Arm with HIPEC. The median age was 60 years (range: 30-74). Baseline characteristics were well balanced. The overall post-operative mortality rate was 1.5% and was not different between the two arms. The morbidity rates did not differ statistically at 30 days. At 60 days, the grade 3-5 morbidity rate was significantly higher with HIPEC (24.1% vs. 13.6%, p= 0.030). After a median follow up of 63.8 months (95% CI: 58.9-69.8), the median OS was 41.2 months (95% CI 35.1-49.7) in the non-HIPEC Arm and 41.7 months (95% CI: 36.2-52.8) in the HIPEC Arm, HR = 1.00 (95% CI: 0.73-1.37) p = 0.995. The median RFS was 11.1 months (95% CI: 9-12.7) in non-HIPEC Arm and 13.1 months (95% CI: 12.1-15.7) in HIPEC Arm, HR = 0.90 (95% CI: 0.69-1.90) (p = 0.486), whilst the 1-year RFS rates were 46.1% in non-HIPEC Arm and 59 % in the HIPEC Arm. Conclusions: The therapeutic curative management of PC from colorectal cancer by CRS shows satisfactory survival results. While the addition of HIPEC with oxaliplatin does not influence the OS. Clinical trial information: NCT00769405.
Avoiding Unnecessary Antibiotic Exposure in Premature Infants
Authors: Matthew J. Bizzarro
Journal: JAMA Network Open (2018)

Dustin D. Flannery, DO; Rachael K. Ross, MPH; Sagori Mukhopadhyay, MD, MMSc; Alison C. Tribble, MD; Karen M. Puopolo, MD, PhD; Jeffrey S. Gerber, MD, PhD
Efficacy of annexin A3 blockade in sensitizing hepatocellular carcinoma to sorafenib and regorafenib
Authors: Man Tong, Noélia Che, Lei Zhou, Steve T. Luk, Phillis W. Kau, Stella Chai, Elly S. Ngan, Chung-Mau Lo, Kwan Man, Jin Ding, Terence K. Lee, Stephanie Ma
Journal: Journal of Hepatology (2018)
Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia
Authors: Bianca D. Santomasso, Jae H. Park, Darin Salloum, Isabelle Riviere, Jessica Flynn, Elena Mead, Elizabeth Halton, Xiuyan Wang, Brigitte Senechal, Terence Purdon, Justin R. Cross, Hui Liu, Behroze Vachha, Xi Chen, Lisa M. DeAngelis, Daniel Li, Yvette Bernal, Mithat Gonen, Hans-Guido Wendel, Michel Sadelain, Renier J. Brentjens
Journal: Cancer Discovery (2018)

Abstract CD19-specific chimeric antigen receptor (CAR) T-cell therapy is highly effective against relapsed or refractory acute lymphoblastic leukemia (ALL), but is hindered by neurotoxicity. In 53 adult patients with ALL, we found a significant association of severe neurotoxicity with high pretreatment disease burden, higher peak CAR T-cell expansion, and early and higher elevations of proinflammatory cytokines in blood. Patients with severe neurotoxicity had evidence of blood–cerebrospinal fluid (CSF) barrier disruption correlating with neurotoxicity grade without association with CSF white blood cell count or CAR T-cell quantity in CSF. Proinflammatory cytokines were enriched in CSF during severe neurotoxicity with disproportionately high levels of IL6, IL8, MCP1, and IP10, suggesting central nervous system–specific production. Seizures, seizure-like activity, myoclonus, and neuroimaging characteristics suggested excitatory neurotoxicity, and we found elevated levels of endogenous excitatory agonists in CSF during neurotoxicity. Significance: We detail the neurologic symptoms and blood, CSF, and neuroimaging correlates of neurotoxicity associated with CD19 CAR T cells and identify neurotoxicity risk factors. Our findings implicate cellular components other than T cells and suggest novel links between systemic inflammation and characteristic neurotoxicity symptoms. Cancer Discov; 8(8); 958–71. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 899
Safety and efficacy of obinutuzumab in Chinese patients with B‐cell lymphomas: a secondary analysis of the GERSHWIN trial
Authors: Yan Qin, Yuqin Song, Zhixiang Shen, Xin Du, Wei Ji, Wanling Hsu, Jun Zhu, Yuankai Shi
Journal: Cancer Communications (2018)

Abstract Background Patients with relapsed/refractory B‐cell lymphomas have limited treatment options. GERSHWIN is an open‐label, single‐arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20 + relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B‐cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e.g., safety, and efficacy and pharmacodynamics). Methods Patients received 1000 mg obinutuzumab intravenously on days 1, 8, and 15 of cycle 1 (CLL patients; first dose split over 2 days), and on day 1 of cycles 2–8. Each cycle lasted for 21 days; the treatment period was 24 weeks. All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety, efficacy, as well as pharmacodynamics. Results A total of 48 patients (&gt; 18 years of age) were enrolled (CLL: 12; DLBCL: 23; FL: 13). The subjects received a median of two lines of anticancer treatment prior to the enrollment. Thirty‐five patients (72.9%) had at least one adverse event (AE). The most frequent AE was infusion‐related reactions (15 patients; 31.3%), followed by pyrexia (11 patients; 22.9%). Treatment‐related AEs were reported in 28 patients (58.3%), and included one death (interstitial lung disease). End‐of‐treatment (EoT) response rate was 33.3%. Best overall response rate was 47.9%. Most CLL patients achieved a partial response at EoT (58.3%). CD19 + depletion occurred in 75.0% of the patients with CLL, and all patients with FL and DLBCL. Conclusions The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B‐cell lymphomas were similar to that observed in previous studies in non‐Chinese patients; no new safety signals were observed. Clinical trial registration ID NCT01680991
SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells
Authors: Yang Liang, Toma Tebaldi, Kai Rejeski, Poorval Joshi, Giovanni Stefani, Ashley Taylor, Yuanbin Song, Radovan Vasic, Jamie Maziarz, Kunthavai Balasubramanian, Anastasia Ardasheva, Alicia Ding, Alessandro Quattrone, Stephanie Halene
Journal: Leukemia (2018)
Financial Hardship and the Economic Effect of Childhood Cancer Survivorship
Authors: Paul C. Nathan, Tara O. Henderson, Anne C. Kirchhoff, Elyse R. Park, K. Robin Yabroff
Journal: Journal of Clinical Oncology (2018)

In addition to the long-term physical and psychological sequelae of cancer therapy, adult survivors of childhood cancer are at an elevated risk for financial hardship. Financial hardship can have material, psychological, and behavioral effects, including high out-of-pocket medical costs, asset depletion and debt, limitations in or inability to work, job lock, elevated stress and worry, and a delaying or forgoing of medical care because of cost. Most financial hardship research has been conducted in survivors of adult cancers. The few studies focused on childhood cancer survivors have shown that these individuals are at elevated risk for having difficulties with affording needed health care and report high out-of-pocket medical expenses, difficulty with paying medical bills, or consideration of filing for bankruptcy. Childhood cancer survivors are more likely to be unable to work or to have missed work because of poor health. They are more likely to report difficulties with obtaining insurance coverage and rely more frequently on government-sponsored insurance. Globally, countries able to provide curative cancer therapies have witnessed a growing population of survivors, which places a burden on their health care systems because survivors are more likely to require hospitalization and experience a higher burden of chronic illness than the general population. Guidelines for surveillance for late effects are intended to reduce the burden of morbidity, but research is needed to determine whether such surveillance is cost effective. Of note, risk-based survivor care should include routine surveillance for financial hardship. Improved measures of financial hardship, enhanced data infrastructure, and research studies to identify survivors and families most vulnerable to financial hardship and adverse health outcomes will inform the development of targeted programs to serve as a safety net for those at greatest risk.
Evaluation of androgen receptor expression in pretreatment, posttreatment and recurrent breast cancer patients.
Authors: Reiki Nishimura, Tomofumi Osako, Yasuyuki Nishiyama, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue, Nobuyuki Arima
Journal: Journal of Clinical Oncology (2018)

e12554 Background: Numerous studies have proven the essential regulatory role of ER and PgR in the pathogenesis and growth of breast cancer. The androgen receptor (AR) is frequently expressed in breast cancer, but the exact percentage of AR-positive cases differs significantly and the oncogenic activity in breast cancer is still unclear. The objectives of this study were to assess the AR expression in patients with primary (pre- and posttreatment) and recurrent breast cancer and to determine the correlation between the AR expression and several clinicopathological parameters. Methods: Primary and recurrent breast cancer patients who underwent treatment from March 2017 to January 2018 were enrolled in this study. A total of 395 primary breast cancer cases and 36 recurrent cases were analyzed. Twenty-two primary cases received treatment before surgery. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index value. The AR expression was evaluated using immunohistochemistry (IHC) and the expression was divided into 3 groups; negative, low ( < 10%) and high (≥10%). Breast cancer subtypes were categorized based on the IHC data derived from ER/PgR, HER2 and Ki-67 (cutoff : 20%) in invasive tumors. Results: The AR expression rates were 68.6% (low: 32.9% and high: 35.7%) in primary cases. Patients without pretreatment had a rate of 70.2% and those with pretreatment had a rate of 40.9%. The expression rate of recurrent/metastatic cases was 58.3% (low: 25.0% and high: 33.3%). Higher AR expression significantly correlated with positive ER/PgR, lower Ki-67 values and nuclear grade. However, menopausal status, nodal status, p53 expression did not correlate with AR expression. The AR expression rate was 74.5% in Luminal A, 73.9% in Luminal B, 87.5% in Luminal HER2, 62.5% in HER2 enriched and 38.9% in triple negative cases. Conclusions: The AR expressions were higher in primary breast cancer than in the pretreated and recurrent cases. The expression significantly correlated with ER/PgR positivity, lower Ki-67 values and nuclear grade. However, further studies are needed to determine the predictive and prognostic factors for clinical use.
Ampullary adenocarcinoma: A single center experience.
Authors: Jason Henry, Pritish Iyer, Ross Garberich, Sarah Lindsey Davis, Christopher Hanyoung Lieu, Cheryl Lauren Meguid, Barish H. Edil, Stephen Leong
Journal: Journal of Clinical Oncology (2018)

462 Background: Ampullary adenocarcinoma (AC) is a rare clinical entity representing only 0.2% of gastrointestinal malignancies. While outcomes are superior compared to other hepatobiliary cancers, mortality remains high. There is limited data to guide clinical decisions regarding adjuvant therapy, largely extrapolated from other hepatobiliary cancers. We evaluated treatment strategies and variables associated with survival in patients with AC. Methods: We retrospectively reviewed 54 consecutive patients with pathologically proven AC between January 2012 and August of 2015. Demographic data, adverse prognostic features and adjuvant treatment patterns were examined using a cox univariate hazard model for predictors of overall survival (OS). There were 5 patients who had metastatic disease on presentation who were included for markers of poor prognosis but excluded from treatment analysis. Results: The average age was 64.7 years with 50% male. Treatment strategy included 40.8% surgery alone, 44.9% adjuvant chemotherapy (CT) and surgery, 14.2% chemoradiation (CRT) and surgery while only 1 patient did not have surgery. Open surgical whipple (n = 28) was most frequent followed by laparoscopic whipple (n = 18) and endoscopic resection (n = 2). The two most common chemotherapeutic agents were single agent gemcitabine (74%) and capecitabine plus oxaliplatin. (7%). At time of last follow-up, 20 (37%) patients had died with a median follow-up of 16.8 months (range 1.9 to 47.4). Older age (HR [95% CI]: 1.05 [1.02, 1.09]; p = 0.002), Stage III (6.75 [1.40, 32.53]; p = 0.017), Stage IV (32.44 [32.44, 216.92]; p &lt; 0.001), N stage 1 (8.52 [2.44, 29.67]; p = 0.014), lymphovascular invasion (LVI) (4.80 [1.54, 15.00]; p = 0.007), and peri-neural invasion (PNI) (3.835 [1.197, 12.29]; p = 0.024) were all associated with poor OS. There was no difference in OS between histologic subtype, surgery type, adjuvant CT or CRT. Conclusions: There was no difference in OS between adjuvant CT or CRT, or between surgical modalities. Despite being administered more frequently in patients with adverse prognostic features including LVI, PNI and advanced stage, adjuvant CT or CRT was equivalent to no adjuvant therapy.