tbuckley/cabot-search huggingface dataset:
Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple-Negative Breast Cancer
Authors: Yasmine Assadipour, Nikolaos Zacharakis, Jessica S. Crystal, Todd D. Prickett, Jared J. Gartner, Robert P.T. Somerville, Hui Xu, Mary A. Black, Li Jia, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John R. Wunderlich, Zhili Zheng, Yong-Chen Lu, Paul F. Robbins, Steven A. Rosenberg, Stephanie L. Goff, Steven A. Feldman
Journal: Clinical Cancer Research (2017)

Purpose: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer.Experimental Design: A TNBC metastasis was resected for TIL generation and whole-exome sequencing. Tandem minigenes or long 25-mer peptides encoding selected mutations were electroporated or pulsed onto autologous antigen-presenting cells, and reactivity of TIL was screened by upregulation of CD137 and IFNγ ELISPOT. The nature of the T-cell response against a unique nonsynonymous mutation was characterized.Results: We identified 72 nonsynonymous mutations from the tumor of a patient with TNBC. CD4+ and HLA-DRB1*1501-restricted TILs isolated from this tumor recognized a single mutation in RBPJ (recombination signal binding protein for immunoglobulin kappa J region). Analysis of 16 metastatic sites revealed that the mutation was ubiquitously present in all samples.Conclusions: Breast cancers can express naturally processed and presented unique nonsynonymous mutations that are recognized by a patient's immune system. TILs recognizing these immunogenic mutations can be isolated from a patient's tumor, suggesting that adoptive cell transfer of mutation-reactive TILs could be a viable treatment option for patients with breast cancer. Clin Cancer Res; 23(15); 4347-53. ©2017 AACR.
Retransplantation From Haploidentical Donors After Graft Failure in Pediatric Patients Results in Low Transplant Related Mortality and Favourable Long Term Survival
Authors: Heiko-Manuel M Teltschik, Frank Heinzelmann, Tobias F. Feuchtinger, Matthias Pfeiffer, Ingo Müller, Rupert Handgretinger, Peter Lang
Journal: Blood (2011)
DC subset–specific induction of T cell responses upon antigen uptake via Fcγ receptors in vivo
Authors: Christian H.K. Lehmann, Anna Baranska, Gordon F. Heidkamp, Lukas Heger, Kirsten Neubert, Jennifer J. Lühr, Alana Hoffmann, Katharina C. Reimer, Christin Brückner, Simone Beck, Michaela Seeling, Melissa Kießling, Didier Soulat, Anne B. Krug, Jeffrey V. Ravetch, Jeanette H.W. Leusen, Falk Nimmerjahn, Diana Dudziak
Journal: The Journal of Experimental Medicine (2017)

Dendritic cells (DCs) are efficient antigen-presenting cells equipped with various cell surface receptors for the direct or indirect recognition of pathogenic microorganisms. Interestingly, not much is known about the specific expression pattern and function of the individual activating and inhibitory Fcγ receptors (FcγRs) on splenic DC subsets in vivo and how they contribute to the initiation of T cell responses. By targeting antigens to select activating and the inhibitory FcγR in vivo, we show that antigen uptake under steady-state conditions results in a short-term expansion of antigen-specific T cells, whereas under inflammatory conditions especially, the activating FcγRIV is able to induce superior CD4+ and CD8+ T cell responses. Of note, this effect was independent of FcγR intrinsic activating signaling pathways. Moreover, despite the expression of FcγRIV on both conventional splenic DC subsets, the induction of CD8+ T cell responses was largely dependent on CD11c+CD8+ DCs, whereas CD11c+CD8− DCs were critical for priming CD4+ T cell responses.
Implementation of surgeon-initiated Oncotype DX ordering among patients with breast cancer to reduce chemotherapy wait times.
Authors: Katya Losk, Rachel A. Freedman, Nancy U. Lin, Mehra Golshan, Susan Lester, Stephen Pochebit, Kelsey Natsuhara, Kristen Camuso, Tari A. King, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2017)

166 Background: Oncotype DX testing in breast cancer is associated with delayed chemotherapy initiation, which may adversely impact clinical outcomes and patient satisfaction. We sought to reduce delays between surgery and adjuvant chemotherapy initiation among patients who undergo Oncotype DX testing by developing standard ordering criteria and modifying surgical oncology, medical oncology, and pathology workflows. Methods: We implemented ‘reflex’ Oncotype DX testing for any patient ≤ 65 with the following tumor characteristics: T1cN0 (grade 2-3), T2N0 (grade 1-2), or T1/T2N1 (grade 1-2). A new process was developed whereby once pathology review is complete surgeons communicate the results to medical oncologists in real-time and initiate requests for Oncotype DX when appropriate. Medical oncologists can order Oncotype for cases outside the criteria. A streamlined pathology system for receiving and processing Oncotype DX requests was also developed. We then examined 649 consecutive breast cancer patients who received postoperative Oncotype DX testing and measured time intervals between surgery date, Oncotype DX order date, Oncotype DX result received date, and chemotherapy initiation date (if applicable) before and after intervention implementation. Results: The interventions reduced the turnaround time (TAT) from surgery to Oncotype DX order and time to when the results were available by 7.7 days and 6.3 days, respectively. A 6.5 day decrease in the mean time from surgery to chemotherapy initiation was observed. The decrease in the standard deviation also suggests a reduction in process variation. Conclusions: Developing Oncotype DX testing criteria and implementing streamlined workflows among providers has led to a significant reduction in Oncotype DX ordering TAT and wait times to chemotherapy initiation. [Table: see text]
Incorrect Conclusions Concerning Antibiotics and Asthma Exacerbation—Reply
Authors: Ateev Mehrotra, Jeffrey A. Linder
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
Whooping cough booster in pregnancy is highly protective for newborns, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Maternal pertussis vaccination provides more than 90% protection for babies in the first two months of life, the critical period before they can receive their first childhood jabs, research has shown.1

In 2012 the Department of Health urged pregnant women to be vaccinated against whooping cough because of rising numbers of cases in infants.2 The UK’s Joint Committee on Vaccination and Immunisation recommends that vaccination should be offered from gestational weeks 16 to 32 to help babies …
Risk of venous thromboembolism in cancer patients treated with cisplatin: A systematic review and meta-analysis.
Authors: Sonia Maria Seng, Ziyue Liu, Sophia Chiu, Tracey Proverbs-Singh, Guru Sonpavde, Toni K. Choueiri, Che-Kai Tsao, Menggang Yu, Noah M. Hahn, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2012)

e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose &gt;30 mg/m 2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.
Triple Negative Myeloproliferative Neoplasms (MPNs) Patients Show Low MPN10 Score and Lower Grades of Bone Marrow Fibrosis
Authors: Yasser Elnahass, Hossam K Mahmoud, Mervat Mattar, Omar Fahmy, Mohamed A. Samra, Rafaat MS Abdelfattah, Hala Fahmy, Ahmed Abdelhameed, Fatma Elrefaey, Hend Elleithy, Wafaa Elmetnawy
Journal: Blood (2016)
Pancreatic cancer cost-of-care in inpatient setting.
Authors: Dhruv Bansal, Pranshu Bansal, Vidit Kapoor
Journal: Journal of Clinical Oncology (2017)

28 Background: Pancreatic cancer continues to carry bad prognosis with modest improvement in survival in the last decade. SEER analysis from 2006-2012 shows a 5-year survival of 7.7% for pancreatic cancer and number of new diagnoses were 11.3 per 100,000 U.S. population in 2003 and 12.7 in 2013. The mortality rate was 10.5 and 10.8 per 100,000 during the same time period. In spite of modest improvement in survival, the cancer care costs including pancreatic cancer continue to rise and inpatient costs contribute a major chunk to cancer care which is often ignored. Methods: We used National Inpatient Sample (NIS) to extract data for patients hospitalized with primary diagnosis of pancreatic cancer using clinical classification software code 17, and corresponding ICD9 codes for the years 2004-2013. NIS is a nationally representative survey of hospitalizations conducted by the Healthcare Cost and Utilization Project. It represents 20% of all hospital data in the US. Trend of rate of hospitalization, mean length of stay (LOS), and mean cost of hospitalization were analyzed. Results: The rate of hospitalization for pancreatic cancer were 11.0 +/-0.5 in 2004 and 11.0 +/-0.3 per 100,00 hospitalizations in 2013. Mean LOS declined from 8.978 +/-0.141 to 7.616 +/-0.105 days between 2004-2013. In the same time period the mean cost of hospital stay increased from $39,533 +/-1,514 to $74,216 +/- 2,408. Conclusions: In the years 2004-2013 the rate of hospitalization for pancreatic cancer remained stable (z test p = 1.0), LOS decreased significantly by approximately 15% (z test p &lt; 0.001), but the mean cost of hospitalization showed the most significant increase throughout the decade with a mean increase of approximately 47% (p &lt; 0.001) in hospital costs. National inflation rate was 23.3% during this time. The gains made in decreasing the LOS has not lead to a decrease in inpatient cost of care. Pancreatic cancer treatment lags behind other cancers with dismal survival rates, and combination chemotherapies are increasingly being used which may add to inpatient cost in future as well although results at this time remain modest. Further research efforts to better identify the factors contributing to inpatient cost should be undertaken.
Modeling the response of colorectal cancer (CRC) to common chemotherapy using multivariate gene expression
Authors: S. C. Glasgow, J. Yu, D. C. Linehan, M. A. Watson, H. L. McLeod
Journal: Journal of Clinical Oncology (2004)

2008 Background: Expression of key enzymes in chemotherapy drug pathways correlates with CRC response following treatment. No prior research has simultaneously described the patterns of expression in CRC for 5-fluorouracil, irinotecan and oxaliplatin pathways. Characterizing relative expression levels of these enzymes is a first step towards definitively predicting tumor responsiveness to chemotherapy. Methods: Twelve genes known to influence tumor response to chemotherapy were selected from the pharmacogenetic pathways of 5-fluorouracil, irinotecan and platinum agents. Genes included intracellular targets, DNA repair enzymes, drug transporters and metabolizers. Gene expression was examined in primary colorectal adenocarcinoma and adjacent normal mucosa in 51 patients with stage III or IV disease using TaqMan RT-PCR. Relative expression levels were calculated with β-actin as control using a method to account for differing polymerase amplification efficiencies. Results: TYMS, ERCC1 & 2, GSTP1, TOP1, and UGT1A1 were significantly over-expressed in tumor cells relative to normal mucosa, while CES2, DPYD and ABCG2 were under-expressed (p < 0.05, Wilcoxon matched pairs test). Expression of ABCB1, ECGF and CYP3A4 did not differ significantly between tumor and normal tissues. Expression of enzymes regulating platinum-agent metabolism and DNA repair were co-regulated. Using differential expression relative to normal mucosa as a marker for tumor resistance, predicted tumor response rates were calculated. 19.6% of tumors were predicted responsive to single-agent irinotecan, 7.8% to 5-FU, and 15.7% to oxaliplatin. Two-thirds were predicted resistant to all three drugs. Conclusions: Significant differences in gene expression were found between CRC and normal mucosa. Distinct sensitivity subgroups existed among the 51 patients with pathologically homogenous disease. These preliminary observations allow further research to correlate multivariate gene expression with clinical outcomes in order to develop a model for predicting response to chemotherapy, eventually resulting in patient-specific treatment. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Merck
Cancer testis antigens: Potential new targets for lung cancer.
Authors: Leonardo Mirandola, Jehanzeb Riaz, Rashmi Verma, Saba Radhi, Teresia Pham, Amardeep Aulakh, Venu Konala, Yuefei Yu, Fred Hardwick, Lukman Aderoju Tijani, Nicholas C. D'Cunha, Kayley Trotter, Marjorie Jenkins, Jose A. Figueroa, Diane Duyen Thuy Nguyen, Everardo Cobos, Maurizio Chiriva-Internati, Fabio Grizzi
Journal: Journal of Clinical Oncology (2014)

e19151 Background: Lung cancer patients are usually diagnosed based on their symptoms. Unfortunately, the vast majority of these patients only see a physician when their symptoms have strikingly exacerbated in the advanced stage of lung cancer. Chest X-rays and CT scans have been the primary methods to screen and detect lung cancer, but they may be too costly for patients and may yield a very high false positive results. Therefore, research is heavily invested in finding better screening methods and treatment options. To address these goals, studies have focused on using tumor-associated antigens as markers for screening and targets for therapy, specifically immunotherapy. Methods: We evaluated SP17 RNA and protein expression levels in lung cancer cell lines and primary tumors, and normal cell lines, and determined whether or not CTA SP17, PTTG1, and AKAP-4 were capable of generating CTA-specific cytotoxic T lymphocytes in vitro, capable of killing lung cancer cells. Here, our lab explores the aberrant expression of spermatozoa proteins known collectively as cancer testis antigens (CTAs) that are normally found in the testes. They are usually not recognized as “self” proteins as a consequence of the blood-testis barrier. CTAs have become one of the most significant families of biomarker antigens in the field of oncology and tumor immunology and highly correlative with breast, skin, lung, and ovarian cancers. More specifically, Sp17, PTTG1, and AKAP-4 are CTAs that are hypothesized to be expressed in lung cancer. Results: These findings have been further corroborated through uncovering the interaction of CTA with genes and proteins involved in tumor suppression and homeostasis like p53. Preliminary results from our lab suggest the presence of circulating CTA-specific antibodies in the sera of lung cancer patients, indicating the immunogenicity of SP17, AKAP-4 and PTTG-1. Conclusions: Consequently, antigen detection may be used as a component of a lung cancer-screening program for early detection. Moreover, the immunogenic nature of CTA makes them candidates for immunotherapy in cancer treatment.
Tumor Spread through Air Spaces Affects the Recurrence and Overall Survival in Patients with Lung Adenocarcinoma &gt;2 to 3 cm
Authors: Chenyang Dai, Huikang Xie, Hang Su, Yunlang She, Erjia Zhu, Ziwen Fan, Fangyu Zhou, Yijiu Ren, Dong Xie, Hui Zheng, Xiermaimaiti Kadeer, Donglai Chen, Liping Zhang, Gening Jiang, Chunyan Wu, Chang Chen
Journal: Journal of Thoracic Oncology (2017)
Regulator takes action against four online pharmacies
Authors: Matt Limb
Journal: BMJ (2017)

England’s healthcare regulator has taken enforcement action against four online pharmacy companies for providing prescription medicines that potentially put patients “at risk of harm.”

Inspectors from the Care Quality Commission (CQC) found examples of inappropriate medicines being prescribed, poor recording of medical histories, inadequate identity checks, and lack of communication with the patient’s GP.

One provider, Doctor Matt Ltd, which issued prescriptions after taking as little as 17 seconds to review patient questionnaires, has had its registration suspended until the end of June 2017.

Another, Frosts Pharmacy, has received warning notices after prescribing large quantities of inhalers for asthma without checking whether a patient’s condition was out of control or …
Characterizing 18 Years of the Death With Dignity Act in Oregon
Authors: Charles Blanke, Michael LeBlanc, Dawn Hershman, Lee Ellis, Frank Meyskens
Journal: JAMA Oncology (2017)

<h3>Importance</h3> Numerous states have pending physician-aided dying (PAD) legislation. Little research has been done regarding use of PAD, or ways to improve the process and/or results. <h3>Objectives</h3> To evaluate results of Oregon PAD, the longest running US program; to disseminate results; and to determine promising PAD research areas. <h3>Design, Setting, and Participants</h3> A retrospective observational cohort study of 991 Oregon residents who had prescriptions written as part of the state's Death with Dignity Act. We reviewed publicly available data from Oregon Health Authority reports from 1998 to 2015, and made a supplemental information request to the Oregon Health Authority. <h3>Main Outcomes and Measures</h3> Number of deaths from self-administration of lethal medication versus number of prescriptions written. <h3>Results</h3> A total of 1545 prescriptions were written, and 991 patients died by using legally prescribed lethal medication. Of the 991 patients, 509 (51.4%) were men and 482 (48.6%) were women. The median age was 71 years (range, 25-102 years). The number of prescriptions written increased annually (from 24 in 1998 to 218 in 2015), and the percentage of prescription recipients dying by this method per year averaged 64%. Of the 991 patients using lethal self-medication, 762 (77%) recipients had cancer, 79 (8%) had amyotrophic lateral sclerosis, 44 (4.5%) had lung disease, 26 (2.6%) had heart disease, and 9 (0.9%) had HIV. Of 991 patients, 52 (5.3%) were sent for psychiatric evaluation to assess competence. Most (953; 96.6%) patients were white and 865 (90.5%) were in hospice care. Most (118, 92.2%) patients had insurance and 708 (71.9%) had at least some college education. Most (94%) died at home. The estimated median time between medication intake and coma was 5 minutes (range, 1-38 minutes); to death it was 25 minutes (range, 1-6240 minutes). Thirty-three (3.3%) patients had known complications. The most common reasons cited for desiring PAD were activities of daily living were not enjoyable (89.7%) and losses of autonomy (91.6%) and dignity (78.7%); inadequate pain control contributed in 25.2% of cases. <h3>Conclusions and Relevance</h3> The number of PAD prescriptions written in Oregon has increased annually since legislation enactment. Patients use PAD for reasons related to quality of life, autonomy, and dignity, and rarely for uncontrolled pain. Many questions remain regarding usage and results, making this area suitable for cancer care delivery research.