tbuckley/cabot-search huggingface dataset:
Cyclin-A1 expression in acute myeloid leukemia stem cells and its representation as an immunogenic antigen that can be targeted by cytotoxic T cells.
Authors: Sebastian Ochsenreither, Ravindra Majeti, Keith Loeb, Derek L. Stirewalt, Ulrich Keilholz, Irving L Weissman, Philip D Greenberg
Journal: Journal of Clinical Oncology (2012)

2523 Background: Targeted T-cell therapy represents a more specific and less toxic alternative to allogeneic stem cell transplantation for providing a cytotoxic anti-leukemic response to eliminate the leukemic stem cell (LSC) compartment in acute myeloid leukemia (AML). The aim of this study was to identify a leukemia-associated antigen that is both immunogenic and exhibits selective high expression in AML LSCs. Methods: Expression microarrays of leukemic and normal cells were used to identify suitable candidate genes. Cyclin-A1 appeared to be differentially expressed, and was further analyzed by quantitative RT-PCR, intracellular FACS staining, and immunofluorescence microscopy. T-cell clones specific for cyclin-A1 were generated by stimulation in vitro with an overlapping peptide library, followed by cloning of responding cells. Specificity of the clones was documented by intracellular IFNg and tetramer staining. Cytotoxicity was determined by chromium release and caspase-3 cleavage assays. Results: To identify target candidates with a suitable expression pattern, microarray data from LSCs, hematopoietic cells and healthy tissues were compared. Cyclin-A1 was found to be selectively expressed in LSCs of &gt;50% of AML patients, but minimally expressed in normal tissues with exception of testis. Using dendritic cells and monocytes pulsed with a cyclin-A1 peptide library, T-cells were generated against eight cyclin-A1 oligopeptides. Two HLA A2-restricted epitopes were further characterized, and specific T-cell clones recognized both peptide-pulsed target cells and the HLA A2-positive AML line THP-1. Furthermore, cyclin-A1-specific CD8 T-cells lysed primary AML cells. Conclusions: Cyclin-A1, known to be important in meiosis, is expressed in AML LSCs and testis and can be targeted by T-cells. Thus, cyclin-A1 is the first prototypic LSC-associated leukemia-testis-antigen. Cyclin-A1 already has been shown to be leukemogenic in mice and to promote proliferation and survival in AML blasts. This pro-oncogenic activity, together with high expression levels and a multitude of immunogenic epitopes, make it a promising target for T-cell based therapy approaches.
A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes
Authors: Edda María Elvarsdóttir, Teresa Mortera-Blanco, Marios Dimitriou, Thibault Bouderlique, Monika Jansson, Isabel Juliana F. Hofman, Simona Conte, Mohsen Karimi, Birgitta Sander, Iyadh Douagi, Petter S. Woll, Eva Hellström-Lindberg
Journal: Leukemia (2019)

Established cell culture systems have failed to accurately recapitulate key features of terminal erythroid maturation, hampering our ability to in vitro model and treat diseases with impaired erythropoiesis such as myelodysplastic syndromes with ring sideroblasts (MDS-RS). We developed an efficient and robust three-dimensional (3D) scaffold culture model supporting terminal erythroid differentiation from both mononuclear (MNC) or CD34+-enriched primary bone marrow cells from healthy donors and MDS-RS patients. While CD34+ cells did not proliferate beyond two weeks in 2D suspension cultures, the 3D scaffolds supported CD34+ and MNC erythroid proliferation over four weeks demonstrating the importance of the 3D environment. CD34+ cells cultured in 3D facilitated the highest expansion and maturation of erythroid cells, including generation of erythroblastic islands and enucleated erythrocytes, while MNCs supported multi-lineage hemopoietic differentiation and cytokine secretion relevant for MDS-RS. Importantly, MDS-RS 3D-cultures supported de novo generation of ring sideroblasts and maintenance of the mutated clone. The 3D cultures effectively model a clonal disease characterized by terminal erythroid failure and can be used to assess therapeutic compounds.
Clonal replacement of tumor-specific T cells following PD-1 blockade
Authors: Kathryn E. Yost, Ansuman T. Satpathy, Daniel K. Wells, Yanyan Qi, Chunlin Wang, Robin Kageyama, Katherine L. McNamara, Jeffrey M. Granja, Kavita Y. Sarin, Ryanne A. Brown, Rohit K. Gupta, Christina Curtis, Samantha L. Bucktrout, Mark M. Davis, Anne Lynn S. Chang, Howard Y. Chang
Journal: Nature Medicine (2019)
Among Women Seeking Abortion, Continuing Pregnancy Linked to Worse Physical Health
Authors: Rita Rubin
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Evaluation of neoadjuvant chemotherapy for esophageal cancer.
Authors: Hitoshi Kawasaki, Kenichi Hakamada
Journal: Journal of Clinical Oncology (2012)

e14709 Background: Neoadjuvant chemotherapy (CT) followed by surgery has become the standard treatment in patients with clinical stage II/III thoracic esophageal cancer. This study evaluated our experience with this treatment approach. Methods: We evaluated 39 patients that underwent an esophagectomy after neoadjuvant concurrent 5-fluorouracil/cisplatin CT, and investigated the clinical and pathological results of neoadjuvant CT. Results: The 3-year overall survival (OS) rate was 70%. Clinical CR, PR, SD and PD were observed in 0, 22, 14 and 3 patients, respectively, and response rate was 56.4%. The 3-year OS of clinical CR group was significantly better than that of clinical PD group. The OS of clinical CR group was not significantly different from that of clinical SD group. Down-staging was observed in 13 cases (33%), but OS was not significantly different between down-staging group and non-down-staging group. Pathological complete response was observed in 1 case (3%). According to lymph node metastasis, down-grading was observed in 11 cases (28%) (responder). The OS was significantly better in responders compared with those in non-responders (100% vs. 50%, p=0.024). Conclusions: Neoadjuvant chemotherapy can be a good option in treatment of clinical stage II/III thoracic esophageal cancer. Especially in this study, the patients with pathological lymph node response are expected to have better outcome in survival.
The role of intensive care in the changing paradigm of modern cancer care.
Authors: Louise Catherine Connell, Fauzi Othman, John McCaffrey, Desmond Carney, Brian Marsh, Catherine Margaret Kelly
Journal: Journal of Clinical Oncology (2012)

e19632 Background: Many metastatic cancers are now treated like a chronic disease. Expanding treatment options, increasing age; varying co-morbid illness; and improving cancer-specific survival mean that decisions regarding the timeliness and appropriateness of transfer to the Intensive Care Unit (ICU) are complex. We sought to examine the clinical, demographic and outcome characteristics of oncology/haematology patients transferred to ICU at a large academic teaching hospital. Methods: Data was extracted from a prospectively maintained database for all patients with documented malignancy admitted to ICU between September 2009 &amp; December 2011.Clinicopathological variables examined included; cancer type; tumour stage; time from diagnosis; age; co-morbidities; and treatment history. The Sequential Organ Failure Assessment (SOFA), an ICU-specific scoring system, was reviewed for each patient. We report 30 day and 6-month mortality. Results: A total of 52 patients have been analysed to date. The common cancer types were well represented; breast (11.5%), colorectal (11.5%), lung (11.5%) and acute leukaemia (19.2%). Mean age at time of ICU admission was 60 years (range 29-82). The maximum number of prior lines of chemotherapy (CT) was 5 (range 0-5). Approximately 50% of patients had metastatic disease at time of ICU admission. The most frequent reasons for admission were sepsis (n=16, 31%) and respiratory distress (n=15, 29 %). Use of mechanical ventilation, vasopressors and renal dialysis was 51.9%, 61.5% &amp; 21.1% respectively. Four patients (7.7 %) received CT in the ICU setting. ICU-specific mortality was 28.8% (n=15).Thirty-day and 6-month mortality rates were 38.5% &amp; 61.5% respectively. Conclusions: A significant proportion of patients admitted to ICU had advanced disease and had received multiple lines of CT previously. The ICU-specific mortality rate was lower than expected at 28.8% and may reflect stringent selection criteria. Patients transferred tended to have had long periods of disease remission/stabilisation or had a new diagnosis of malignancy with unknown CT sensitivity status. Analysis of patient selection at ward level is on-going and will identify other factors influencing ICU transfer decisions.
Cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer (E-SCLC): Final “common arm”: Comparative outcomes analysis of JCOG 9511 and SWOG 0124
Authors: P. Lara, K. Chansky, T. Shibata, H. Fukuda, T. Tamura, N. Saijo, M. Redman, H. J. Lenz, R. Natale, D. R. Gandara
Journal: Journal of Clinical Oncology (2009)

8027 Background: S0124 was a large North American phase III trial (n=651) that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with E-SCLC, contrary to the results of J9511, a phase III trial exclusively in Japanese patients (n=154). As S0124 and J9511 protocols used identical treatment regimens and similar eligibility criteria, we compared demographics, toxicity, and outcomes using patient-level data and a “common arm” analysis to explore potential reasons for the divergent results. Methods: In both trials, patients with documented E-SCLC and adequate end-organ function were randomized to receive either cisplatin 60 mg/m2 day 1 + irinotecan 60 mg/m2 days 1, 8, &amp; 15 Q 4 weeks or cisplatin 80 mg/m2 day 1 + etoposide 100 mg/m2 days 1–3 Q 3 weeks. Demographics and outcomes data were compared among 805 patients enrolled in J9511 and S0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status. Results: Of 671 patients in S0124, 651 were eligible. Patient characteristics (J9511 &amp; S0124, respectively): Mean age - 61 &amp; 62 years; Male sex - 132 (86%) &amp; 370 (57%), p&lt;0.001; Performance status 0 - 19 (12%) &amp; 211 (32%), p&lt;0.001. Efficacy and toxicity comparisons are summarized below. Conclusions: Significant differences in patient demographics, toxicity, and efficacy exist between J9511 and S0124 populations. These results, relevant in the current era of clinical trials globalization, warrant 1) consideration of differential patient characteristics and outcomes amongst populations receiving identical therapy; 2) utilization of the “common arm” model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected. [Table: see text] [Table: see text]
Indoor tanning prevalence after the International Agency for Research on Cancer statement on carcinogenicity of artificial tanning devices: systematic review and meta‐analysis
Authors: A.J. Rodriguez‐Acevedo, A.C. Green, C. Sinclair, E. Deventer, L.G. Gordon
Journal: British Journal of Dermatology (2019)

Exposure to artificial tanning devices is carcinogenic to humans, and government regulations to restrict or ban indoor tanning appear to be increasing. We evaluated changes in the international prevalence of indoor tanning among adolescents and adults after artificial tanning devices were classified as carcinogenic by the International Agency for Research on Cancer (IARC) in 2009. Systematic searches in PubMed and Web of Science databases were undertaken. Overall, 43 studies reporting 'ever' or 'past‐year' indoor tanning exposure after 2009 were identified. We used metaregression analysis to evaluate the prevalence of indoor tanning over time. Random effects meta‐analysis was used to summarize the prevalence of indoor tanning in adolescents and adults according to sex, region and presence of age prohibitions. Global prevalence of indoor tanning in adolescents for 2013–2018 was 6·5% [95% confidence interval (CI) 3·3–10·6], 70% lower than the 22·0% (95% CI 17·2–26·8) prevalence for 2007–2012. Among adults, the prevalence was 10·4% (95% CI 5·7–16·3) for 2013–2018, a decrease of 35% from 18·2% for 2007–2012. Since 2009, the overall past‐year prevalence among adolescents was 6·7% (95% CI 4·4–9·6) and 12·5% (95% CI 9·5–15·6) among adults. The prevalence of tanning indoors in the past year was similar in North America (adults, 12·5%; adolescents, 7·6%) and Europe (adults, 11·1%; adolescents, 5·1%). In 2009, three countries had regulations restricting indoor tanning, compared with 26 countries today. Prevalence of indoor tanning has declined substantially and significantly in adolescents and adults since the 2009 IARC statement, reflecting the rise in regulations that limit this source of unnecessary exposure to carcinogenic ultraviolet radiation. What is already known about this topic? Indoor tanning is associated with an increased risk of melanoma. A meta‐analysis of worldwide indoor tanning prevalence for 1986–2012 found a past‐year prevalence of 18% in adolescents and 14% in adults, with higher prevalences during the period 2007–2012. Policies to regulate indoor tanning began to be implemented across the globe in 2009. Only one study carried out in the U.S.A. has evaluated the efficacy of such policies in reducing indoor tanning prevalence. What does this study add? For the period 2013–2018, we found indoor tanning prevalences of 6·7% in adolescents and 11·9% in adults. This implies a reduction in indoor tanning use of 70% in adolescents and 35% in adults during the last 10 years. Our study encourages policy makers to strengthen indoor tanning regulations that reduce sunbed use among the general population in order to produce maximum public health benefit.
Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice
Authors: Jing Wen, Di Wu, Meng Qin, Chaoyong Liu, Lan Wang, Duo Xu, Harry V. Vinters, Yang Liu, Emiko Kranz, Xin Guan, Guibo Sun, Xiaobo Sun, YooJin Lee, Otoniel Martinez-Maza, Daniel Widney, Yunfeng Lu, Irvin S. Y. Chen, Masakazu Kamata
Journal: Nature Biomedical Engineering (2019)
Safety Study of Salvage Chemotherapy High-Dose Ara-C/Mitoxantrone (HAM) and Type I FLT3-TKI Crenolanib in First Relapsed/Primary Refractory AML
Authors: Swaminathan P. Iyer, Yogesh Jethava, Chatchada Karanes, John R. Eckardt, Robert Collins
Journal: Blood (2016)
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Authors: Aimée Parker, Sonia Fonseca, Simon R. Carding
Journal: Gut Microbes (2019)

The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.
Cystatin C, an additional marker of ovarian cancer extent: A pilot study
Authors: G. Wcislo, L. Bodnar, K. Szarlej-Wcislo, A. Gasowska-Bodnar, C. Szczylik
Journal: Journal of Clinical Oncology (2007)

16080 Background: Cystatin C is a cysteine protease inhibitor which has been recommended as the marker of glomerular filtration rate (GFR). We investigated significance of cystatin C in relation to ovarian cancer extent and its feasibility in assessment of renal function in patient with ovarian cancer (OC) who underwent chemotherapy. Methods: We prospectively included consecutive patients with OC who underwent chemotherapy : cisplatin 75 mg/m2 plus 24-hour infusion of paclitaxel 135 mg/m2 every three week after surgery. Before chemotherapy serum renal markers were noted as: creatinine (Cr), cystatin C (Cys C), albumin, creatinine clearance (ClCr) calculated by using 24-hour urine collection per 1.73 m2, creatinine clearance estimated with formulas Cocroft- Gault (ClCG) and Modification of Renal Disease (MDRD1), respectively. Results: Between February 2003 and January 2006 37 patients were enrolled onto this study. Median age 54 year (range from 28 to 68). Cystatin C and CrCl weakly correlated (R Spearman= -0.36; p=0,03). There were no correlation between cystatin C and other markers of GFR (serum creatinine, ClCG, MDRD1). We showed correlation between cystatin C and tumor extent revealed by spiral CT- scan (&gt; 1 cm diameter) after surgery (R Spearman= 0.4; p=0.01), and CA 125 (R Spearman= 0.4, p=0.03). Cut-off values were established as medians for both factors, and patients with high and low values had no statistical differences in overall survival (log- rank test, p=0.9). Conclusions: We believe that cystatin C could imply OC extent in patients.This factor weakly was correlated with CrCl, and no correlated with other GFR parameters. No significant financial relationships to disclose.
Metronomic weekly paclitaxel in metastatic or recurrent non-small cell lung cancers.
Authors: Nidhi Tandon, Vanita Noronha, Kumar Prabhash
Journal: Journal of Clinical Oncology (2013)

e19095 Background: Metastatic non small cell lung cancer (NSCLC) has a median survival of 4 months in absence of therapy. We present our experience with metronomic weekly paclitaxel in patients with metastatic or recurrent NSCLC and those with poor performance status. Methods: This is a retrospective analysis of prospectively collected data of patients with metastatic or recurrent NSCLC without significant neuropathy who were heavily pretreated or platinum ineligible from Feb 2010 to Oct 2012 at our centre. Patients were treated with paclitaxel at 80 mg/m 2 over 1 hour weekly and underwent regular follow up. Chemotherapy was discontinued on disease progression or intolerable side -effects or patients choice. Patients who received at least 4 cycles of chemotherapy were included in the analysis. Toxicity was graded according to CTCAEv4.03. Statistics were calculated using SPSSv18.0. The progression-free survival was calculated from date of start of paclitaxel till date of symptomatic deterioration, radiological progression or start of next line of therapy or death due to any cause. Overall survival was calculated from date of start of paclitaxel to the date of death due to any cause. Results: Of the 100 patients studied (median age = 57 y, range 29–77 y), 74% were males, 51% were smokers, 45% had comorbidities, 35% had PS&gt;2 and 74% had adenocarcinoma. About 53% received &gt;2 prior lines of chemotherapy. Patients received a mean of 16.9 cycles of paclitaxel (range 4-72) after which it was withheld in 63% due to PD (53% radiological, 10% clinical) and in 12% due to toxicity. The response rates were 37% (CR-3% and PR-34%) while 35% had SD. 9% required dose reduction while 32% had delay in dose administration. G.3 adverse events observed were 12%-anaemia, 10%-neutropenia, 2%-febrile neutropenia, 15%- sensory neuropathy and 4%-motor neuropathy. The median OS was 12 months while median PFS was 5 months. Conclusions: Weekly paclitaxel is a promising and well tolerated therapy for advanced NSCLC.
Dual inhibition of IGF-IR and ALK as an effective strategy to eradicate NPM-ALK+ T-cell lymphoma
Authors: Bhawana George, Suraj Konnath George, Wenyu Shi, Abedul Haque, Ping Shi, Ghazaleh Eskandari, Magnus Axelson, Olle Larsson, Ahmed O. Kaseb, Hesham M. Amin
Journal: Journal of Hematology & Oncology (2019)

Abstract Background Nucleophosmin-anaplastic lymphoma kinase-expressing (NPM-ALK + ) T cell lymphoma is an aggressive neoplasm. NPM-ALK, an oncogenic tyrosine kinase, plays a critical role in this lymphoma. Recently, selective ALK inhibitors have emerged as a first-line therapy for this neoplasm. Unfortunately, ALK inhibitors were hindered by emergence of resistance and relapse. We have previously demonstrated that type I insulin-like growth factor receptor (IGF-IR) is commonly expressed and activated in this lymphoma. In addition, IGF-IR and NPM-ALK are physically associated and reciprocally enhance their phosphorylation/activation. Herein, we tested the hypothesis that combined inhibition of IGF-IR and NPM-ALK could significantly improve the effects of inhibiting each kinase alone. Methods We used clinically utilized inhibitors of IGF-IR (picropodophyllin; PPP) and ALK (ASP3026) to assess the in vitro cellular effects of combined treatment versus treatment using a single agent. Moreover, we used a systemic NPM-ALK + T cell lymphoma mouse model to analyze the in vivo effects of PPP and ASP3026 alone or in combination. Results Our data show that combined treatment with PPP and ASP3026 decreased the viability, proliferation, and anchorage-independent colony formation, and increased apoptosis of NPM-ALK + T cell lymphoma cells in vitro. The in vitro effects of combined treatment were synergistic and significantly more pronounced than the effects of PPP or ASP3026 alone. Biochemically, simultaneous antagonism of IGF-IR and ALK induced more pronounced decrease in pIGF-IR Y1135/1136 , pNPM-ALK Y646 , and pSTAT3 Y705 levels than antagonizing IGF-IR or ALK alone. Moreover, combined targeting of IGF-IR and NPM-ALK decreased significantly systemic lymphoma tumor growth and improved mice survival in vivo. Consistent with the in vitro results, the in vivo effects of the combined therapy were more pronounced than the effects of targeting IGF-IR or ALK alone. Conclusions Combined targeting of IGF-IR and ALK is more effective than targeting IGF-IR or ALK alone in NPM-ALK + T cell lymphoma. This strategy might also limit emergence of resistance to high doses of ALK inhibitors. Therefore, it could represent a successful therapeutic approach to eradicate this aggressive lymphoma. Importantly, combined inhibition is feasible because of the clinical availability of IGF-IR and ALK inhibitors. Our findings are applicable to other types of cancer where IGF-IR and ALK are simultaneously expressed.
Blood pressure control and clinical outcomes in acute intracerebral haemorrhage: a preplanned pooled analysis of individual participant data
Authors: Tom J Moullaali, Xia Wang, Reneé H Martin, Virginia B Shipes, Thompson G Robinson, John Chalmers, Jose I Suarez, Adnan I Qureshi, Yuko Y Palesch, Craig S Anderson
Journal: The Lancet Neurology (2019)