tbuckley/cabot-search huggingface dataset:
Role of IL27 and IL35 as biomarkers and potential targets in acute myeloid leukemia.
Authors: Heba A. Ahmed, Ahmed M. Maklad, Ashraf Elyamany
Journal: Journal of Clinical Oncology (2019)

e18516 Background: Acute myeloid leukemia (AML) is one of the most common leukemia affecting adult. Regulatory T cells (Tregs) are a subset of CD4 (+) T cells that plays a central role immune tolerance. Objective: We aimed to explore the role of interleukin- 27 (IL27) &amp; interleukin- 35 (IL35) produced by T regs and its associations with clinical characteristics and prognostic markers of AML patients. Methods: The study included 70 patients with acute myeloid leukemia (AML) and 30 healthy controls. We used flowcytometry immunophenotyping to confirm the diagnosis of AML. Serum level of interleukin- 27 (IL 27) &amp; interleukin- 35 (IL 35) were measured at diagnosis by enzyme-linked immunosorbentassay (ELISA). Results: Higher levels of IL27 and IL35 were detected in AML patients than the control group (p ≤ 0.001). We used Receiver operating characteristic (ROC) analysis for detection of optimum IL27 &amp; IL35 cut off level needed for predicting AML. ROC curve analysis demonstrated IL27 optimum cutoff is &gt; 43, AUC 0.926 with a sensitivity 74% and Specificity 96.6% (P-value &lt;0.00). IL35 optimum cutoff was &gt; 27.8 AUC 0.972 with 88% and 98% sensitivity and specificity respectively (P-value &lt;0.001). Serum IL27 &amp; IL35 could well identify AML patients from healthy individuals. More importantly IL27 &amp; IL35 correlated with clinical variable, and could be served as an independent prognostic factor. Conclusions: IL27 &amp; IL 35 might have an application as a diagnostic and prognostic indicator for AML patients and could be served as an independent prognostic factor.
Revised European Scleroderma Trials and Research Group Activity Index is the best predictor of short-term severity accrual
Authors: Serena Fasano, Antonella Riccardi, Valentina Messiniti, Paola Caramaschi, Edoardo Rosato, Britta Maurer, Vanessa Smith, Elise Siegert, Ellen De Langhe, Valeria Riccieri, Paolo Airó, Carina Mihai, Jerome Avouac, Elisabetta Zanatta, Ulrich A Walker, Florenzo Iannone, Paloma García De la Peña Lefebvre, Jörg H W Distler, Alessandra Vacca, Oliver Distler, Otylia Kowal-Bielecka, Yannick Allanore, Gabriele Valentini
Journal: Annals of the Rheumatic Diseases (2019)

Background The European Scleroderma Trials and Research Group (EUSTAR) recently developed a preliminarily revised activity index (AI) that performed better than the European Scleroderma Study Group Activity Index (EScSG-AI) in systemic sclerosis (SSc). Objective To assess the predictive value for short-term disease severity accrual of the EUSTAR-AI, as compared with those of the EScSG-AI and of known adverse prognostic factors. Methods Patients with SSc from the EUSTAR database with a disease duration from the onset of the first non-Raynaud sign/symptom ≤5 years and a baseline visit between 2003 and 2014 were first extracted. To capture the disease activity variations over time, EUSTAR-AI and EScSG-AI adjusted means were calculated. The primary outcome was disease progression defined as a Δ≥1 in the Medsger’s severity score and in distinct items at the 2-year follow-up visit. Logistic regression analysis was carried out to identify predictive factors. Results 549 patients were enrolled. At multivariate analysis, the EUSTAR-AI adjusted mean was the only predictor of any severity accrual and of that of lung and heart, skin and peripheral vascular disease over 2 years. Conclusion The adjusted mean EUSTAR-AI has the best predictive value for disease progression and development of severe organ involvement over time in SSc.
Abstract 2692: Elucidation of the pre-B-cell receptor signaling network in acute lymphocytic leukemia cells
Authors: Roland Walter, Khouloud Kouidri, Jessica Peter, Martine Pape, Laura Merschen, Bjoern Haeupl, Carmen Doebele, Hubert Serve, Yanlong Yi, Henning Urlaub, Thomas Oellerich
Journal: Cancer Research (2018)

Abstract Antigen receptors transduce complex signals and thereby control important cell fate decisions of the B-lineage including differentiation, proliferation and B-cell survival. The initial steps of B-cell development take place in the bone marrow, and the first dependency of a developing B-cell on antigen receptor signaling occurs at the pre-B-cell stage where expression of the pre-BCR is essential for cell survival. In contrast to B-cell-receptor (BCR) signaling, the nature of pre-BCR signals is far less characterized. It is believed that pre-BCRs transduce a constitutive baseline signal that is essential for survival and differentiation of pre-B-cells into immature B-cells. Since pre-BCRs are crucial regulators of pre-B-cell survival and differentiation, it is not surprising that dysregulation of pre-BCR signaling is observed in acute lymphocytic leukemia (ALL) cells where it contributes to survival of the malignant cell clones. To identify drug targets in the pre-BCR signaling network, we have systematically characterized pre-BCR signaling in two pre-BCR-dependent ALL cell lines by quantitative phosphoproteomics. Because pre-BCRs transduce a constitutive baseline signal, we interfered with pre-BCR signaling by either Syk inhibitor treatment or by an inducible shRNA-mediated knock-down of the pre-BCR component Ig-α to monitor pre-BCR-dependent signals. We identified and quantified more than 15,000 phospho-sites. Among these sites, more than 500 were regulated upon interference with pre-BCR signaling. Although the upstream components are shared between pre-BCRs and BCRs, the wiring of their downstream signals occurred to be different which is reflected by our finding that the majority of the identified pre-BCR signaling effectors have not been described in the context of BCR signaling in mature B-cells or lymphomas. Finally, we have identified vulnerabilities in the pre-BCR signaling network by intersecting our phosphoproteomic data with data from loss-of-function CRISPR-Cas9 screens for essential genes in ALL cell lines. Taken together, this study provides a comprehensive dataset for pre-BCR signaling and identifies effector proteins that are relevant for the regulation of ALL cell survival and proliferation. Citation Format: Roland Walter, Khouloud Kouidri, Jessica Peter, Martine Pape, Laura Merschen, Bjoern Haeupl, Carmen Doebele, Hubert Serve, Yanlong Yi, Henning Urlaub, Thomas Oellerich. Elucidation of the pre-B-cell receptor signaling network in acute lymphocytic leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2692.
Early phase II study of weekly paclitaxel as a one hour infusion in patients (pts) with recurrent or metastatic head and neck cancer (HNC)
Authors: Makoto Tahara, Hironubu Minami, Yasuhisa Hasegawa, Akihito Watanabe, Mamoru Tsukuda, Kenichi Nibu, Kichinobu Tomita, Taku Seriu
Journal: Cancer Research (2007)

3526  Background: Weekly paclitaxel in pts with a variety of cancers has demonstrated similar efficacy andbetter tolerability than standard 3-weekly paclitaxel. A prior phase II study (Brotherton TW, Proc. ASCO 921, 2001) performed with paclitaxel at 80mg/m2/week in 48 pts with chemotherapy-pretreated HNC reported a response rate of 9.3 %. We conducted an early phase II study to evaluate the efficacy and toxicity of weekly paclitaxel in pts with recurrent or metastatic HNC. Methods: Theeligibility required: histologically proven HNC with recurrent or metastatic lesion, measurable disease, PS 0-2, adequate organ function, and no more than one prior chemotherapy regimen. Pts were administered a weekly 1-hour infusion of paclitaxel 100 mg/m2, for 6 of 7 weeks until disease progression or unacceptable toxicities occurred. Results: Between Feb and Nov, 2004, 37 pts were enrolled and 36 pts (30 male, 6 female) were assessable for response and toxicity; median age 61 (range 44-74); PS 0-1 of 35 pts; 32 pts had previously received chemotherapy. 20 pts underwent surgery, and 30 pts received radiotherapy. In total, 105 cycles of weekly paclitaxel were administered (median 2 cycles; range 1-10). The median dose intensity was 82.1 mg/m2 per week. Most common non-hematological toxicities were neuropathy, alopecia and fatigue. The incidence of neuropathy of grade 3 or greater was 2.8%. Most common hematological toxicities were leucopenia and neutropenia. The incidence of neutropenia of grade 3 or greater was 36.1%. The overall response rate was 33.3 % (2 CR, 10 PR, 95% CI 18.6-51.0%) according to WHO criteria and 25.7% (2CR, 7 PR, 95%CI 12.5-43.3%) according to RECIST criteria. After a median follow up time of 196 days, median duration of response was 259 days (range 102-538) and time to progression was 96 days (95%CI 69-140days). Conclusion: Weekly paclitaxel demonstrated a promising activity with acceptable toxicity in recurrent or metastatic HNC pts.
Immunological effects after an adoptive cellular immunotherapy with reactivated autologous memory T-Cells from bone marrow
Authors: F. Schuetz, J. Rom, K. Ehlert, V. Schirrmacher, A. Schneeweiss, C. Sohn, P. Beckhove
Journal: Journal of Clinical Oncology (2006)

12502 Tumor-reactive CD4 and CD8 memory T cells (MTC) can be found in bone marrow (BM) of the majority of primary and metastatic breast cancer patients. In xenotransplant mouse models these cells, upon specific re-activation ex vivo, mediated efficient rejection of autologous breast tumors suggesting that the polyclonal natural MTC repertoire possesses therapeutic potential. In order to clinically exploit these anti-tumor capacities we treated 11 advanced metastasized breast cancer patients with autologous, tumor-reactive, reactivated MTC of BM in a phase-1 trial. Activation of T cells was done by MCF-7 lysate pulsed dendritic cells (DC). After reactivation both, T cells and pulsed DC were injected once intravenously. Peripheral blood was drawn on day 0, 1, 7, 14, 28. BM-re-aspiration was done on day 28 and 84. While TAA-reactive memory T cells were absent in the peripheral blood (PB) before therapy, 5 from 11 patients (=responders) showed TAA-specific PB T cell reactivity 7 days after therapeutic cell application suggesting a massive proliferation and mobilization into the blood of TAA-reactive T cells in these patients. A comparison of responders to adoptive cellular immunotherapy with non-responders revealed differences in the numbers of therapeutic cells that could be generated ex vivo and in the decreased frequency of tumor-reactive MTC in responders’ BM on days 28 and 84 which could be expained by a mobilization due to in situ activation by co-transferred DCs or due to local or systemic cytokine signals by transferred, activated T lymphocytes. Such effect might have contributed to the high numbers of circulating TAA-reactive T cells observed 7 days after the transfer. Furthermore we observed different concentrations of IL-4, IL-10, TNF-α, and INF-γ in PB and BM between the two groups leading to the hypothesis of a polarization in T cell responses (T1 type in responders vs T2 type in non-responders). No significant financial relationships to disclose.
Activation of Cdc2 contributes to apoptosis in HPV E6 expressing human keratinocytes in response to therapeutic agents
Authors: Zhiguo Liu, Tingting Li, Lina Zhao, Yingwang Liu, Daiming Fan, Jason Chen
Journal: Cancer Research (2007)

1067  Infection with human papillomaviruses (HPV) is strongly associated with the development of cervical cancer. The HPV E6 induces cell proliferation and apoptosis in cervical cancer precursor lesions. Although inactivation of the tumor suppressor p53 plays an important role for E6 to promote cell growth, the molecular basis of E6-induced apoptosis is poorly understood. While it is expected that inactivation of p53 by E6 should lead to a reduction in apoptosis, numerous studies demonstrated that E6 could in fact sensitize cells to apoptosis. In the present study, we demonstrated that expression of E6 in human keratinocytes rendered sensitization to chemotherapeutic agents. The cell death was shown to be apoptosis involving caspase activation and the mitochondria pathway. To explore mechanisms involved in sensitization of E6 expressing cells to apoptosis, we used a proteomic approach to identify proteins differentially expressed in E6 expressing and control keratinocytes. Among nearly a thousand proteins examined, Cdc2 was demonstrated to be the most dramatically up-regulated protein in E6 expressing cells and was therefore further characterized. Using genetic, pharmacologic, and siRNA strategy, a role of Cdc2 in E6 expression-conferred apoptosis was demonstrated. Thus these results have important therapeutic implications in enhancing the efficacy of chemotherapy.
Hepatic Bile Formation
Authors: Norman B. Javitt
Journal: New England Journal of Medicine (1976)

Bile-Acid-Independent Bile FlowSodium transport is under investigation as a physiologic mechanism for the generation of the bile-acid-independent fraction of canalicular bile flow. The electrolyte content of bile at low bile acid output consists mostly of inorganic sodium salts. Since it is known that sodium transport provides an osmotic gradient for bulk water flow across other membranes, interest has centered on its role in hepatic bile formation.Studies of the sodium-potassium gradient across erythrocyte membranes have led to the recognition of a membrane carrier.37 A specific macromolecule in the membrane continually transfers sodium outwardly and potassium inwardly. Energy for the . . .
Quantitative Analysis of Multiplexed Immunofluorescence in T-Cell Lymphoma
Authors: Sanjay de Mel, Shou Nian Choo, Shuangyi Fan, Hoang Mai Phuong, Michal Hoppe, Wee Joo Chng, Anand Jeyasekharan, Siok Bian Ng
Journal: Blood (2017)
Heterogeneity of Treatment Effects From an Intensive Lifestyle Weight Loss Intervention on Cardiovascular Events in Patients With Type 2 Diabetes: Data From the Look AHEAD Trial
Authors: Tamar I. de Vries, Jannick A.N. Dorresteijn, Yolanda van der Graaf, Frank L.J. Visseren, Jan Westerink
Journal: Diabetes Care (2019)

To explore the presence of heterogeneity of treatment effect (HTE) of an intensive lifestyle intervention on the occurrence of major cardiovascular events (MACE) in overweight or obese patients with type 2 diabetes, and to identify patient characteristics associated with individual treatment effect.In 4,901 participants from the Action for Health in Diabetes (Look AHEAD) trial, a penalized Cox regression model to predict treatment effect of intensive lifestyle intervention for the risk of MACE was derived, including all possible treatment-by-covariate interaction terms. The ability of the model to predict HTE was confirmed by calculating hazard ratios (HRs) and absolute risk change in quartiles of predicted treatment effect, and baseline patient characteristics were compared between quartiles.In quartile 1 of predicted treatment effect, with the highest predicted risk reduction, there was a significant treatment benefit of intensive lifestyle intervention (HR 0.64 [95% CI 0.49-0.83]), whereas there was no effect from treatment in quartiles 2 and 3 (HR 0.81 [95% CI 0.58-1.14] and 1.13 [95% CI 0.80-1.60], respectively) and a detrimental effect in quartile 4 (HR 1.37 [95% CI 1.09-1.73]). Several patient characteristics in demographics, medical history, physical examination, and laboratory values were associated with the level of treatment effect.This post hoc analysis of the Look AHEAD trial showed that an intensive lifestyle intervention aimed at weight loss may reduce cardiovascular events in selected patients but may have a detrimental treatment effect in others.
Antimicrobial Surfaces: Stereochemical Strategy Advances Microbially Antiadhesive Cotton Textile in Safeguarding Skin Flora (Adv. Healthcare Mater. 15/2019)
Authors: Jiangqi Xu, Hongjuan Zhao, Zixu Xie, Scott Ruppel, Xiaqing Zhou, Shuang Chen, Jun F. Liang, Xing Wang
Journal: Advanced Healthcare Materials (2019)

To be, or not to be, that is the microbe's question when they meet a borneol modified surface. In this case, a borneol-decorated cotton textile (BDCT) is presented in article number 1900232 by Xing Wang and co-workers. The unique stereochemical strategy will lead to new opportunities for managing and controlling microbes.
In vivo imaging of fluorescently labeled human uveal melanoma cells in nude mice
Authors: Patrick Logan, Jean-Claude Marshall, Bruno Fernandes, Sebastian Di Cesare, Shawn Maloney, Miguel Burnier
Journal: Cancer Research (2007)

496  Purpose: Uveal melanoma is the most common primary intraocular tumor in adults which metastasizes predominantly to the liver and usually results in death within a year. Due to the lack of a lymphatic system, uveal melanoma cells can only exit the eye through the bloodstream effectively reducing the number of variables involved in the metastatic cascade. Therefore, uveal melanoma is an ideal candidate for hematogenous metastasis research. The objective of this study was to establish an animal model for liver metastasis utilizing fluorescent-labeled human uveal melanoma cells injected into the bloodstream of nude mice.  Methods: The human uveal melanoma cell line 92.1 was transfected with Green Fluorescent Protein (GFP) and infused with a transient fluorescent marker. Three nude mice were sedated and 5 x 105 fluorescently labeled uveal melanoma cells in a volume of 100 micro-liters were injected into the tail vein. Immediately following injection, a skin flap was made in the abdomen of the mice to allow for imaging using an inverted epifluorescence microscope. Following imaging, the mice were sacrificed and all organs were harvested for histopathological examination.  Results: Immediately following injection, fluorescing cells were visible in vivo. The cells were visualized in the liver parenchyma and sinusoids of each mouse. In the first five minutes small clusters of cells and isolated individual melanoma cells were detected. Between five and ten minutes, increased numbers of melanoma cells were detected in both the liver parenchyma and sinusoids. At 15 minutes, a further increase in the number of melanoma cells were noted in the liver parenchyma. The signal to noise ratio was low, allowing for clear distinction between the human uveal melanoma cells and native liver tissue. Conclusion: This study demonstrates the feasibility of visualizing tail-vein injected, fluorescent-labeled human uveal melanoma cells in nude mice. Uveal melanoma cells could be clearly distinguished from mouse liver cells. These positive results have initiated the establishment of a haematogenous dissemination model of metastasis in nude mice. This information will allow us to develop a time line of metastatic growth in order to test any future systemic treatments.
Safety and quality assurance of MR-guided focused ultrasound (MRgFUS) in palliation of painful bone metastases.
Authors: Joshua E. Meyer, Lili Chen, Pejman Ghanouni, Suzanne LeBlang, Mark Hurwitz
Journal: Journal of Clinical Oncology (2013)

9565 Background: Palliation of bone metastases is typically performed with radiation therapy (RT). However, a significant minority of patients cannot obtain durable relief from RT. MRgFUS combines non-invasive focused ultrasound with MR guidance. Preliminary phase III results comparing MRgFUS to sham treatment have demonstrated efficacy. This study examines the safety of this procedure in a large prospective, multi-center study. Methods: Patients with a painful bone metastasis were randomized (3:1) to either MRgFUS or sham treatment for the single most painful lesion. Sham patients were given the opportunity to cross over after 2 weeks. Each adverse event (AE) was recorded prospectively and scored for severity and relation to treatment. Results: Thirty-seven patients were enrolled to receive sham treatment and 115 to receive MRgFUS. Sites of treatment were: 102 pelvis, 28 thorax, 7 lower extremity and 2 upper extremity. Seventy-seven target lesions were osteolytic, 29 were osteoblastic and 33 were mixed. Treatment was discontinued prior to completion in 8 treatments. Of these, 7 were pelvic targets and 6 lesions were osteolytic. The most common reasons for discontinuation were pain (4) and patient movement (2). Forty-seven percent of treatment patients and 2.7% of sham patients reported at least one AE. Of 76 AEs, 67 were considered non-significant and anticipated, 57 being intra-procedure pain. Four significant events included 2 possibly related fractures at treated lytic lesion sites, 1 grade 3 skin burn and 1 patient with neuropathy. Four patients experienced events unrelated to study treatment and 1 patient experienced temporary apnea from anesthesia described as incidental. Conclusions: MRgFUS is a safe treatment for palliation of painful bone metastases. Ninety-three percent of MRgFUS treatments were carried out to completion. Three percent of patients experienced significant AEs, including 2 fractures of treated lytic tumors. These safety data reinforce and confirm previous experience with this technology and encourage its use for patients not suitable for RT. Clinical trial information: NCT00656305.
Site of metastases does not influence the clinical outcome of children with metastatic Germ Cell Tumors (GCT). A report from the Childrens Oncology Group (COG)
Authors: M. H. Malogolowkin, W. B. London, B. Cushing, R. Giller, M. Davis, J. Cullen, T. A. Olson
Journal: Journal of Clinical Oncology (2006)

9002 Background: To describe the clinical outcome of children with metastatic GCT (stage IV) at diagnosis according to the primary metastatic site(s). Methods: From March 1990 to February 1996, 299 children and adolescents with stage III/IV gonadal and stage I-IV extragonadal GCT were eligible for a Pediatric Intergroup high-risk (HR) GCT trial. Patients were randomized to receive 4–6 courses of cisplatin (P) standard dose [ 20 mg/m 2 /day (d) × 5] or high-dose (HDP) [40 mg/m 2 /d × 5] with etoposide (E) 100 mg/m 2 /d × 5 and bleomycin (B) 15 mg/m 2 on d1. We retrospectively investigated the outcome of patients with stage IV and compared their outcome according to metastatic site(s). Results: There were 133 patients with stage IV disease. The median age was 2.6 years (y) [range, 3 d-19.3 y], 70 were female. Primary sites included: 43 testicular, 14 ovarian, 76 extragonadal (45 sacroccocygeal, 28 mediastinal, 3 other). Histologies included: 66 pure yolk sac tumors, 21 immature teratomas and yolk sac tumors, 26 mixed germ cell tumors, 7 pure germinoma/seminoma/dysgerminomas, 1 immature teratoma with a non-classic germ cell tumor, 2 mixed germ cell tumor admixed with a nonclassic germ cell tumor, 5 pure choriocarcinomas, and 5 patients with unknown histology. There were no statistically significant differences in the 5-year EFS or OS rates by site of metastases. Of the 19 patients with either bone or brain involvement, 17 patients had bone and 3 had brain metastases. Conclusion: The outcome for patients with metastatic GCT is excellent with contemporary cisplatin-based regimes and is independent of the site of metastatic disease. [Table: see text] No significant financial relationships to disclose.
Measles cases at highest point since 2006 as outbreaks continue to spread
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Global measles cases are the highest they have been since 2006, with almost three times as many cases reported to date in 2019 as there were at the same time last year, the latest preliminary report from the World Health Organization has found.1

From January 1 to July 31 this year, 182 countries reported 364 808 measles cases, up from 129 239 cases reported by 181 countries over the same period in 2018.

WHO has warned that ongoing outbreaks are straining healthcare systems and leading to serious illness, disability, and deaths in many parts of the world.

The largest outbreaks have been seen in countries with low …