tbuckley/cabot-search huggingface dataset:
Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia
Authors: Amélie Trinquand, Nuno R. dos Santos, Christine Tran Quang, Francesca Rocchetti, Benedetta Zaniboni, Mohamed Belhocine, Cindy Da Costa de Jesus, Ludovic Lhermitte, Melania Tesio, Michael Dussiot, François-Loïc Cosset, Els Verhoeyen, Françoise Pflumio, Norbert Ifrah, Hervé Dombret, Salvatore Spicuglia, Lucienne Chatenoud, David-Alexandre Gross, Olivier Hermine, Elizabeth Macintyre, Jacques Ghysdael, Vahid Asnafi
Journal: Cancer Discovery (2016)

Cancer onset and progression involves the accumulation of multiple oncogenic hits, which are thought to dominate or bypass the physiologic regulatory mechanisms in tissue development and homeostasis. We demonstrate in T-cell acute lymphoblastic leukemia (T-ALL) that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent T-cell receptor (TCR) signaling has antileukemic properties and enforces a molecular program resembling thymic negative selection, a major developmental event in normal T-cell development. Using mouse models of T-ALL, we show that induction of TCR signaling by high-affinity self-peptide/MHC or treatment with monoclonal antibodies to the CD3ε chain (anti-CD3) causes massive leukemic cell death. Importantly, anti-CD3 treatment hampered leukemogenesis in mice transplanted with either mouse- or patient-derived T-ALLs. These data provide a strong rationale for targeted therapy based on anti-CD3 treatment of patients with TCR-expressing T-ALL and demonstrate that endogenous developmental checkpoint pathways are amenable to therapeutic intervention in cancer cells.T-ALLs are aggressive malignant lymphoid proliferations of T-cell precursors characterized by high relapse rates and poor prognosis, calling for the search for novel therapeutic options. Here, we report that the lineage-specific TCR/CD3 developmental checkpoint controlling cell death in normal T-cell progenitors remains switchable to induce massive tumor cell apoptosis in T-ALL and is amenable to preclinical therapeutic intervention. Cancer Discov; 6(9); 972-85. ©2016 AACR.See related commentary by Lemonnier and Mak, p. 946This article is highlighted in the In This Issue feature, p. 932.
The Effect of Vascular Occlusion on Transplanted Tumors
Authors: J. S. Youngner, G. H. Algire
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article The Effect of Vascular Occlusion on Transplanted Tumors Get access J. S. Youngner, J. S. Youngner Search for other works by this author on: Oxford Academic PubMed Google Scholar G. H. Algire G. H. Algire National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 3, December 1949, Pages 565–579, https://doi.org/10.1093/jnci/10.3.565 Published: 01 December 1949 Article history Received: 05 April 1949 Published: 01 December 1949
Out-of-pocket cost trends for Medicare patients with newly diagnosed cancer.
Authors: Amol Narang, Lauren Nicholas
Journal: Journal of Clinical Oncology (2015)

6623 Background: While rising cancer care costs have been well-documented, the extent to which these costs have translated into increased patient financial burden is unclear. To address this question, we used a nationally, representative panel survey to characterize trends over time in the out-of-pocket (OOP) costs of newly diagnosed cancer patients. Methods: Medicare-eligible, community-dwelling participants in the biennial Health and Retirement Study who reported a new cancer diagnosis between 2002-2012 were identified (N = 1409). Respondent-reported OOP costs included the following categories: hospital stays, doctor visits, outpatient surgery, prescription drugs, home health, dental care, and special facilities. A multivariate generalized linear model and quantile regression were used to assess the mean, median, and 90thpercentile of OOP costs. Adjusted levels of OOP costs were compared over time using a contrast test. Results: Mean annual OOP costs decreased from $7868 (95% CI: $6477 - $9259) for patients with a new cancer diagnosis at the 2002 survey to $4242 (95% CI: $2642 - $5841) for patients with a new cancer diagnosis at the 2012 survey, a decline of $3626 (95% CI: $1508 - $5745, p = 0.001). Median annual OOP costs declined by $580 (95% CI: $66 - $1095, p = 0.03). The steepest decline in OOP costs occurred between 2004 and 2008 (mean: $5070, 95% CI: $2944 - $7195, p < 0.001; median: $1031, 95% CI: $515 - $1547, p < 0.001), while OOP costs did not significantly change between 2008 and 2012 (mean: $779, 95% CI: -1411 – 2969, p = 0.486; median: $17, 95% CI: -515 – 549, p = 0.949). The 90th percentile of annual OOP costs similarly declined over the study period from $13,203 (95% CI: $11,403 - $15,002) to $8063 (95% CI: $5,995 - $10,131), a decline of $5,140 (95% CI: $2,340 - $7,880, p < 0.001). Conclusions: Despite the growing costs of cancer care,Medicare patients with newly diagnosed cancer were increasingly shielded from high OOP costs over the study period, with a sharp decline between 2004 and 2008 which may be attributable to the introduction of Medicare part D. Given the more recent plateau in OOP costs and proposals to increase cost-sharing in this population, close monitoring of OOP cost trends will be important for avoiding excessive financial burden.
Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review
Authors: Rokas Navickas, Diane Gal, Aleksandras Laucevičius, Agnė Taparauskaitė, Monika Zdanytė, Paul Holvoet
Journal: Cardiovascular Research (2016)

The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.
Pathogenesis and Pathology of Mastocytosis
Authors: Dean D. Metcalfe, Yoseph A. Mekori
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

Systemic mastocytosis is a clonal disorder of mast cells that may variably present with characteristic skin lesions, episodes of mast cell mediator release, and disturbances of hematopoiesis. No curative therapy presently exists. Conventional management has relied on agents that antagonize mediators released by mast cells, inhibit mediator secretion, or modulate mast cell proliferation. Recent advances in the molecular understanding of the pathophysiology of systemic mastocytosis have provided new therapeutic considerations, including new and novel tyrosine kinase inhibitors.
Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort
Authors: Yannick Allanore, Christopher P Denton, Thomas Krieg, Peter Cornelisse, Daniel Rosenberg, Barbara Schwierin, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2016)

Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort Digital vasculopathy in systemic sclerosis (SSc) consists of a spectrum of Raynaud's phenomenon (RP), digital ulcers (DUs), critical digital ischaemia and escalation to gangrene.2][3] Although gangrene is not infrequent in the clinic, data on the prevalence and 1736
Adrenal Metastasis of a Poorly Differentiated Adenocarcinoma Mimicking a Pheochromocytoma on 18F-FDOPA PET/CT
Authors: Céline Heimburger, Gerlinde Averous, Emmanuelle Charlin, Hervé Lang, Jean-Emmanuel Kurtz, Alessio Imperiale
Journal: Clinical Nuclear Medicine (2016)

We report the surprising intense uptake of F-FDOPA in a right adrenal metastasis of a poorly differentiated metastatic adenocarcinoma of unknown primary mimicking a pheochromocytoma in a hemodialyzed patient with the typical Menard's triad and increased serum catecholamines. Our observation emphasizes that F-FDOPA is not a specific radiotracer for pheochromocytoma and paraganglioma investigation, although it is currently and successfully used in this clinical setting. Moreover, we underline that kidney failure may be responsible for abnormally high serum catecholamines values even in subjects without pheochromocytoma, leading to erroneous diagnostic conclusions particularly in patients with adrenal masses.
MAGE-A3 cancer immunotherapeutic in resected stage IB-III NSCLC patients with or without sequential or concurrent chemotherapy.
Authors: Jean-Louis Pujol, Johan F. Vansteenkiste, Tommaso Martino De Pas, Djordje Atanackovic, Martin Reck, Michiel Thomeer, Jean-Yves Douillard, Gianpiero Fasola, Vanessa Potter, Paul Taylor, Lionel Bosquee, Muriel Debois, Pedro de Sousa Alves, Jamila Louahed, Frederic Lehmann, Vincent G. Brichard
Journal: Journal of Clinical Oncology (2012)

7013 Background: Previous trials with the MAGE-A3 recombinant (rec) protein formulated with an immunostimulant have shown induction of specific immune responses and signals of clinical activity in different cancer diseases. In this phase I/II study (NCT 00455572), we evaluated the safety profile of the MAGE-A3 cancer immunotherapeutic (CI), formulated with the rec MAGE-A3 protein and the AS15 immunostimulant, and the induction of specific immune response with or without adjuvant chemotherapy (CT). Methods: MAGE-A3 CI was administered i.m. 8q3w in resected MAGE-A3+ stage IB-III NSCLC patients (pts). Three cohorts (C) were evaluated: Immunization with concurrent cisplatin plus vinorelbine (C1), sequentially after the same CT (C2) or with no CT (C3). The anti-MAGE-A3 humoral and cellular immune responses were evaluated by ELISA and intracellular cytokine staining (T cells producing both IFNg and TNF) respectively. Adverse Events (AEs) were graded according to CTCAE v. 3.0. Results: A total of 38/55 treated pts received the 8 doses schedule (15/19 in C1, 14/18 in C2, 9/18 in C3). Almost all pts reported at least one AE, mostly general constitutional disorders and administration site reactions. Six patients reported related grade 3 AEs. No related grade 4-5 AE or related SAE were reported. Immunogenicity results in the total treated population are reported in the table below. Conclusions: In this trial, patients in cohorts 2 and 3 correspond to the two populations enrolled in the Phase III MAGRIT trial evaluating the same MAGE-A3 CI. The phase I/II results suggest that this CI is well tolerated and induces in all treated pts specific antibodies against MAGE-A3 after 4 doses in presence or not of concurrent or sequential adjuvant CT. About 25% of the treated pts are considered as CD4 responders in presence or not of concurrent or sequential adjuvant CT. [Table: see text]
Epstein Barr Virus (EBV) Reactivation After Reduced Intensity Conditioning (RIC) Unrelated Umbilical Cord Blood Transplantation (UCBT)
Authors: Zinaida Peric, Xavier Cahu, Patrice Chevallier, Eolia Brissot, Florent Malard, Thierry Guillaume, Jacques Delaunay, Sameh Ayari, Viviane Dubruille, Steven Le Gouill, Beatrice Mahe, Thomas Gastinne, Nicolas Blin, Beatrice Saulquin, Jean-Luc Harousseau, Philippe Moreau, Noel Milpied, Marianne Coste-Burel, Berthe-Marie Imbert-Marcille, Mohamad Mohty
Journal: Blood (2010)
The effect of BCG intravesical therapy and recurrence on PDL1 expression in non-invasive bladder cancers.
Authors: Michael E. Hurwitz, Adebowale Adeniran, Xiaopan Yao, Navid Hafez, Kurt Alex Schalper, David L. Rimm, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2015)

e15504 Background: Treatment of metastatic bladder cancers that express PDL1 with an anti-PDL1 antibody (MPDL3280) resulted in response rates of 40-50%. Approximately 30% of metastatic bladder cancers express PDL1. The determinants of which bladder cancers express PDL1 are unknown. We examined the expression of PDL1 in non-invasive bladder cancer samples and assessed whether its expression changed upon subsequent biopsies depending on whether patients had intravesical BCG treatment or not. Methods: IHC using an antibody against PDL1 (E1L3N) was performed on paraffin embedded TURB samples from patients treated at the Yale Cancer Center from 2000-2013 who had had pathological specimens from at least two TURBs separated by at least three months. Samples were scored as positive if any staining was seen within tumor cells. Fisher’s Exact Tests were used for comparisons among samples and the paired proportion test was used for paired data analysis. Results: Samples from 39 patients fulfilled the requirements. 23/39 received intravesical therapy with BCG between their first and second biopsies; 16/39 did not. 13 of the patients also had a third biopsy. Treatment with intravesical BCG did not correlate with PDL1 expression. PDL1 staining was positive in 7/39, 12/39 and 7/13 samples from first, second and third biopsies, respectively (p = 0.048 by Fisher’s Exact Test). Conclusions: PDL1 expression appears to increase as disease recurs. In this cohort, BCG expression did not correlate with PDL1 expression.
ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease
Authors: Carole A. Warnes, Roberta G. Williams, Thomas M. Bashore, John S. Child, Heidi M. Connolly, Joseph A. Dearani, Pedro del Nido, James W. Fasules, Thomas P. Graham, Ziyad M. Hijazi, Sharon A. Hunt, Mary Etta King, Michael J. Landzberg, Pamela D. Miner, Martha J. Radford, Edward P. Walsh, Gary D. Webb
Journal: Journal of the American College of Cardiology (2008)
Final results of a FNCLCC French Sarcoma Group multicenter randomized phase II study of gemcitabine (G) versus gemcitabine and docetaxel (G+D) in patients with metastatic or relapsed leiomyosarcoma (LMS)
Authors: P. Pautier, B. Bui Nguyen, N. Penel, S. Piperno-Neumann, C. Delcambre-Lair, E. Bompas, F. Collin, A. Rey, M. Jimenez, F. Duffaud
Journal: Journal of Clinical Oncology (2009)

10527 Background: An objective response rate (RR) of 8% and 17% with G and G+D were respectively reported in metastatic soft tissue sarcomas (Maki, J Clin Oncol. 2007). We previously reported a 5% RR in 41 evaluable patients (pts) with ‘non uterus‘ LMS randomized to each arm of this randomized phase II study (Duffaud, ASCO. 2008). We present here the results of G vs G+D in uterine and all LMS. Methods: Patients had histologically proven metastatic or unresectable LMS, one prior anthracycline- based regimen, age ≥18, measurable disease (RECIST), PS ≤ 2. Treatment was G 1,000 mg/m 2 (over 100 minutes, d1+d8+d15) q28 days (d) or G 900 mg/m 2 (over 90 min, d1+d8) and docetaxel 100 mg/m 2 (over 60 min, d8) q21 days; in the G+D arm, pts received lenograstim d9–15, 25% dose reductions were employed for prior pelvic radiation. The primary endpoint was the objective RR (CR+PR), evaluated every 2 cycles. Stratification was by primary tumor location (uterus vs. non-uterus). The Simon method was used: for “uterus” study, 20 pts per arm for a 74% probability of selecting the arm with a real RR of 50%, expected baseline RR was 40%; for the “non-uterus” study, 20 pts per arm for a 92% probability of selecting the arm with a real RR of 40%, expected baseline RR was 20%. Results: From 02/06 to 12/08, 44 pts were enrolled in the “non-uterus” study, 40 pts in the “uterus” study. Currently 76/82 pts are evaluable for response (41/44 in the “non uterus” and 35/38 in the “uterus” study) and 80/84 for toxicity. In the uterus group the median age is 57 (range 41–80), 24 pts received prior pelvic radiotherapy, the median number of cycles was 5 (range 0–8) and dose received/dose planned (%) were 69% in G arm, 88% of G and 86% of D in G+D arm. No differences in toxicity were observed between both LMS locations: in the G arm, toxicity was moderate except for one pulmonary gr4; in the G+D arm one toxic death was related to gr5 thrombocytopenia and there were 2 non-haemathologic gr4 toxicities; 11 pts stopped for intolerable toxicity (3 in G and 8 in G+D arm) and 1 pt for hypersensitivity (G+D arm). Conclusions: Final tumor response for uterine LMS and updated toxicity and PFS data for all the LMS will be presented during the meeting. [Table: see text]
Mammogenesis and Breast Carcinogenesis in Virgin Female Mice of BALB/c&lt;sub&gt;f&lt;/sub&gt; Substrain With the Milk Agent&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Francesco Squartini, M.D.
Journal: JNCI Journal of the National Cancer Institute (1959)

A morphologic study on the mammary glands of virgin female mice of the BALB/Cf substrain with the milk agent has shown that alveolar development takes place from the end of the 3d month of life until the senile involutional changes affect the end pieces of the glandular tree early in the 2d year. Small clusters of alveoli or small nodules are recognizable by the 4th month and progressively increase in number until they reach a peak at the 10th month. Some of them progress toward large nodules, but the others regress in connection with the senile changes. Large nodules, which appear by the 6th month, show a moderate numerical increase in direct relation to the age of the animal. Some of them progress to cancer, but others do not escape the senile involution. Palpable mammary tumors appear from the 7th month, but no tumors have been observed in females that live longer than 15 months. With the breast development and regression as detectors of the hormonal stimuli, it should be supposed that, in virgin females of the BALB/cf substrain, the mammogenic triad (estrogens + progesterone + prolactin) is effective on the breasts, but only from the 4th month to the end of the 1st year. After this time there is evidence of a lack, or deficiency, of hormonal stimuli, which seems responsible for the senile involutional changes, for the disappearance of nodules, and for the nonoccurrence of mammary tumors in old animals. Results obtained in this substrain cannot be generalized to other strains.
Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas
Authors: Jennifer E. Kim, Mira A. Patel, Antonella Mangraviti, Eileen S. Kim, Debebe Theodros, Esteban Velarde, Ann Liu, Eric W. Sankey, Ada Tam, Haiying Xu, Dimitrios Mathios, Christopher M. Jackson, Sarah Harris-Bookman, Tomas Garzon-Muvdi, Mary Sheu, Allison M. Martin, Betty M. Tyler, Phuoc T. Tran, Xiaobu Ye, Alessandro Olivi, Janis M. Taube, Peter C. Burger, Charles G. Drake, Henry Brem, Drew M. Pardoll, Michael Lim
Journal: Clinical Cancer Research (2016)

Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS.C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed.Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples.This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124-36. ©2016 AACR.
A persisting outbreak of hepatitis A in Puglia, Italy, 1996: epidemiological follow-up
Authors: P L Lopalco, P Malfait, S Salmaso, C A Germinario, M Quarto, S Barbuti, R Cipriani, A Mundo, G Pesole
Journal: Eurosurveillance (1997)

In early 1996, an increase in the notifications of hepatitis A cases was identified in the region of Puglia, in the south east of Italy. An outbreak investigation conducted in May 1996 showed a strong association between illness and consumption of raw sea
Flow Cytometric Characterization of 129 Cases of Peripheral T Cell Lymphoma Not Otherwise Specified (PTCL NOS) and Angioimmunoblastic T Cell Lymphoma (AITL)
Authors: Greg Hapgood, Anja Mottok, Graham W Slack, Randy D. Gascoyne, Christian Steidl, Kerry J. Savage, Andrew P. Weng
Journal: Blood (2015)