tbuckley/cabot-search huggingface dataset:
A multi-functional nanoplatform for efficacy tumor theranostic applications
Authors: Jinjin Shi, Hongling Zhang, Zhaoyang Chen, Lihua Xu, Zhenzhong Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem (MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy (PTT) and X-ray imaging. Doxorubicin (DOX) was loaded onto MoS2-PEG with a high drug loading efficiency (~69%) and obtained a multifunctional drug delivery system (MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property, demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.
Hematopoietic Stem Cell Transplantation (HSCT) from Alternative Donors for Acute Leukemia at High-Risk of Relapse. The Haploidentical Option.
Authors: Franco Aversa, Antonio Tabilio, Adelmo Terenzi, Stelvio Ballanti, Alessandra Carotti, Franca Falzetti, Andrea Velardi, Teresa Aloisi, Leonardo Flenghi, Jean Pierre Saab, Yair M. Reisner, Massimo F. Martelli
Journal: Blood (2005)
Abstract 4301: Endothelial angiopoietin-2 expression correlates with tumor angiogenesis and response to sunitinib in metastatic renal cell carcinoma
Authors: Anita Lampinen, Juhana Rautiola, Tuomas Mirtti, Ari Ristimäki, Heikki Joensuu, Petri Bono, Pipsa Saharinen
Journal: Cancer Research (2015)

Abstract Background: Angiopoietin-2 (Ang2) is an endothelial cell derived growth factor, which promotes tumor angiogenesis, tumor growth and metastasis. Ang2 is a promising target for anti-angiogenic therapies, but its potential as a biomarker for anti-angiogenic therapies remains unknown. The purpose of this study was to evaluate expression of the Ang2-Tie2 signalling pathway components in metastatic RCC (mRCC) patients treated with sunitinib, a modern multitarget TKI. Materials and methods: We evaluated Ang2, CD31 and Ki67 expression in tumors of 136 patients with metastatic RCC (mRCC) treated with first-line sunitinib from formalin-fixed paraffin-embedded tumor samples using immunohistochemistry. Results: Ang2 was exclusively expressed in the endothelial cells of tumor blood vessels. Using a cutoff of ≥50 Ang2+ vessels/microscopic field, 38% of the samples had high Ang2 expression. High Ang2 expression correlated with high CD31+ vessel density (p = 0.002). 91% of patients with high Ang2 expression had partial response (PR) or stable disease (SD) as best response to sunitinib as compared with 76% of those with low Ang2 expression (P = 0.033). High CD31+ vessel density correlated with a high clinical benefit rate (P = 0.015), and with low levels of Ki-67+ tumor cells (P = 0.018). Combined high expression of both Ang2 and CD31 predicted even better clinical benefit rate with 100% of the patients with high Ang2 and CD31 expression (n = 25) achieving PR/SD as compared with 77% among the rest of the patients (n = 101; P = 0.007). Only one patient (8%, n = 12) with papillary RCC, but 49 (41%) patients with clear cell RCC had high Ang2 expression (P = 0.03). Conclusions: In this first study to investigate Ang2 expression and outcome in mRCC patients treated with sunitinib, high Ang2 expression in the tumor vasculature was predictive for sunitinib efficacy. Citation Format: Anita Lampinen, Juhana Rautiola, Tuomas Mirtti, Ari Ristimäki, Heikki Joensuu, Petri Bono, Pipsa Saharinen. Endothelial angiopoietin-2 expression correlates with tumor angiogenesis and response to sunitinib in metastatic renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4301. doi:10.1158/1538-7445.AM2015-4301
OP55BIOCHEMICAL ANALYSIS COMBINED WITH 3D STRUCTURAL PROTEIN MODELLING IDENTIFIES THE ROLE OF SPECIFIC MITOCHONDRIAL MUTATIONS IN GBM
Authors: Kathleen Keatley, Stavros Polyzoidis, Keyoumars Ashkan, Simon J. Heales, Helen L. Fillmore, Iain P. Hargreaves, John E. McGeehan, Rhiannon E. Lloyd, Geoffrey J. Pilkington
Journal: Neuro-Oncology (2015)

INTRODUCTION: Altered mitochondrial metabolism is a hallmark of glioblastoma (GBM). Previous work in our group using next generation sequencing of GBM cell line mitochondrial DNAs (mtDNAs), combined with 3D structural protein analysis, identified 42 non-synonymous mutations, including 8 within the MT-CYB subunit of complex III (CIII) of the mitochondrial respiratory chain (MRC). Four MT-CYB mutations were predicted to impact on function and concomitant measurement of the MRC enzyme activities in a cohort of GBM cell lines revealed their potential structure-function relationships. METHOD: A cohort of 5 adult GBM cell lines were grown at 37°C and 5% CO2 and 25% O2 until 80% confluent. The cells were treated to allow access of ligands to the inner mitochondrial membrane so that relative activities of complex I, II, linked II/III and IV could be determined spectrophotometrically. RESULTS: Although diverse MRC activity profiles were seen between GBM cell lines, a relationship between CII/CIII activity and the MT-CYB mutation F18L was observed which correlated with structural predictions. GBM cell lines containing F18L, exhibited statistically elevated CII/CIII activity (p > 0.0001) relative to a non-neoplastic control cell line. CONCLUSION: We show a link between a single mtDNA mutation and altered mitochondrial metabolism in GBM which highlights the predictive power of our combined approach. F18L is a germ-line mutation occurring in ∼30% of GBM-patients, raising the possibility that some patients are predisposed to alterations in mitochondrial function. F18L thus provides a target for diagnostic/prognostic research and the development of patient-specific therapeutics.
Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes
Authors: T.H. Ho, D.J. Serie, M. Parasramka, J.C. Cheville, B.M. Bot, W. Tan, L. Wang, R.W. Joseph, T. Hilton, B.C. Leibovich, A.S. Parker, J.E. Eckel-Passow
Journal: Annals of Oncology (2016)
Direct Activation of STAT5 by TEL-Lyn Fusion Protein Promotes Induction of Myeloproliferative Neoplasms with Myelofibrosis
Authors: Yusuke Takeda, Chiaki Nakaseko, Hiroaki Tanaka, Masahiro Takeuchi, Makiko Yui, Atsunori Saraya, Satoru Miyagi, Chikako Ohwada, Emiko Sakaida, Koutaro Yokote, Atsushi Iwama
Journal: Blood (2010)
Should Intensive Chemotherapy Be Required for All Mantle Cell Lymphoma Patients
Authors: Zhen Tang Lao, Kathleen Khoo, Jasmine Koh, Whee Sze Ong, Tiffany Tang, Richard Quek, Leonard Tan, Daryl Tan, Miriam Tao, Soo Yong Tan, Soon Thye Lim, Kevin Tay
Journal: Blood (2011)
Evidence of MicroRNA-29b and Sp1/NFκB-HDAC Regulatory Network for KIT Expression in KIT-Driven Acute Myeloid Leukemia (AML): Biologic and Therapeutic Implications.
Authors: Shujun Liu, Lai Chu Wu, Jiuxia Pang, Ramasamy Santhanam, Sebastian Schwind, Yue-Zhong Wu, Christopher Hickey, Jianhua Yu, Anjali Mishra, Heiko Becker, Chenglong Li, Roger Briesewitz, Robert A. Baiocchi, Kenneth K. Chan, Michael A. Caligiuri, John C. Byrd, Danilo Perrotti, Ramiro Garzon, Guido Marcucci
Journal: Blood (2009)
Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double‐Blind, Randomized, Parallel‐Group Trial
Authors: N. Yokogawa, H. Eto, A. Tanikawa, T. Ikeda, K. Yamamoto, T. Takahashi, H. Mizukami, T. Sato, N. Yokota, F. Furukawa
Journal: Arthritis & Rheumatology (2016)

Objective To assess the efficacy and tolerability of hydroxychloroquine (HCQ) in patients with cutaneous lupus erythematosus (CLE), in a phase III clinical trial conducted in Japan. Methods We conducted a double‐blind, randomized, parallel‐group clinical trial. This was a baseline‐controlled study, and the group differences were evaluated in an exploratory analysis. A total of 103 patients with active CLE (according to a Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI] activity score of ≥4) were included. Patients were randomized 3:1 to receive HCQ or placebo during the 16‐week double‐blind period, and all patients were given HCQ during the following 36‐week single‐blind period. The primary efficacy end point was a reduction in the CLASI activity score at week 16. The secondary end points included the central photo evaluation (5‐point scale), patient's global assessment (7‐point scale), the Skindex‐29 score, and investigator's global assessment (7‐point scale, based on the other 3 secondary end points). In patients with systemic lupus erythematosus, fatigue and musculoskeletal pain were assessed. Safety was assessed up to week 55. Results The mean CLASI score at week 16 was significantly improved from baseline in both the HCQ group and the placebo group: mean change −4.6 (95% confidence interval [95% CI] −6.1, −3.1) ( P &lt; 0.0001), and mean change −3.2 (95% CI −5.1, −1.3) ( P = 0.002), respectively, without between‐group difference ( P = 0.197). The investigator's global assessment demonstrated a greater proportion of “improved” and “remarkably improved” patients in the HCQ group (51.4% versus 8.7% in the placebo group [ P = 0.0002 between groups]). The other secondary end points supported the efficacy of HCQ. Cellulitis, drug eruption, hepatic dysfunction, and Stevens‐Johnson syndrome were shown to be serious adverse events related to HCQ use. Conclusion The results of this randomized clinical trial support the efficacy and tolerability of HCQ in patients with CLE.
Combined KIT and CTLA-4 Blockade in Patients with Refractory GIST and Other Advanced Sarcomas: A Phase Ib Study of Dasatinib plus Ipilimumab
Authors: Sandra P. D'Angelo, Alexander N. Shoushtari, Mary Louise Keohan, Mark A. Dickson, Mrinal M. Gounder, Ping Chi, Jennifer K. Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph Patrick Erinjeri, Mark J. Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina Antonescu, Ronald P. DeMatteo, Richard D. Carvajal, William D. Tap
Journal: Clinical Cancer Research (2016)

A phase Ib study of dasatinib plus ipilimumab in patients with gastrointestinal stromal tumor (GIST) and other sarcomas was performed on the basis of preclinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic.
Lenalidomide IS Able to Restore Immune SYSTEM IN MULTIPLE MYELOMA PATIENTS.
Authors: Annalisa Chiarenza, Nunziatina Parrinello, Piera La Cava, Eleonora Spina, Daniele Tibullo, Cesarina Giallongo, Maide Cavalli, Alessandra Romano, Paolo Fiumara, Giuseppe A Palumbo, Francesco Di Raimondo
Journal: Blood (2009)
489. Localized, siRNA-Mediated Silencing of PHD2 to Promote Wound Vascularization
Authors: John R. Martin, Christopher E. Nelson, Mukesh K. Gupta, Fang Yu, Scott A. Guelcher, Jeffrey M. Davidson, Craig L. Duvall
Journal: Molecular Therapy (2015)

We have recently developed a platform for sustained, local release of siRNA loaded endosomolytic nanoparticles (siNPs) from biodegradable poly(ester urethane) (PEUR) tissue engineering scaffolds [1]; this platform was designed to achieve local, gene-specific silencing to promote healing of tissue defects. We are developing this platform to promote local angiogenesis through sustained silencing of prolyl hydroxylase domain protein 2 (PHD2) [2], a negative regulator of the hypoxia induced factor 1α (HIF1α).
Abstract 5148: NR5A2 is essential for pancreas development and affects pancreas carcinogenesis
Authors: Sahar Nissim, Olivia Weeks, John Hedgepeth, Julia Wucherpfennig, Xiao-Xu Wang, Alec Kimmelman, Wolfram Goessling
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers today. A genome-wide association study (GWAS) has implicated the nuclear receptor NR5A2 in modulating risk for pancreatic cancer. While a role for this gene in pancreatic cancer has not been previously recognized, it plays an important role in stem cell pluripotency and metabolism. Using the zebrafish model, we demonstrate that genetic or pharmacologic inhibition of nr5a2 activity results in absence of exocrine pancreas, while leaving endocrine pancreas unaffected, indicating an essential role in pancreas organ formation. Further, we localize nr5a2 expression to the endodermal bud that gives rise to the exocrine pancreas, consistent with a role for nr5a2 in regulating differentiation of pancreas progenitors. In resected human PDAC specimens and in vitro cell lines, we find that NR5A2 expression is altered compared to normal ductal epithelium. Moreover, shRNA knockdown of NR5A2 dramatically alters proliferation of PDAC cell lines, supporting the hypothesis that NR5A2 is involved in pancreatic carcinogenesis. These data support a model that NR5A2 regulates the proliferation and differentiation of exocrine pancreas progenitor cells during development. We postulate that loss-of-function of NR5A2 results in dysregulation of these processes in the adult pancreas by driving acinar cells to acquire properties of progenitor cells, and therefore is an important step in pancreas oncogenesis. Note: This abstract was not presented at the meeting. Citation Format: Sahar Nissim, Olivia Weeks, John Hedgepeth, Julia Wucherpfennig, Xiao-Xu Wang, Alec Kimmelman, Wolfram Goessling. NR5A2 is essential for pancreas development and affects pancreas carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5148. doi:10.1158/1538-7445.AM2015-5148
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may overcome adverse prognosis in patients with diffuse large B-cell lymphoma (DLBCL) with an activated B-cell (ABC) molecular profile.
Authors: U. Borate, M. Steciuk, K. Alexander, J. Lynch, L. Nabell, V. Reddy, J. M. Foran
Journal: Journal of Clinical Oncology (2011)

e18522 Background: The genomic expression profiling of DLBCL into ABC and germinal center B cell (GCB) has divided patients into two groups with dramatically different prognoses. We explored the effect of ASCT on patients with relapsed DLBCL and unknown molecular subtype. Methods: We performed a 10 year retrospective review of patients with relapsed/refractory DLBCL that underwent ASCT. We analyzed diagnostic biopsies with TMAs using the Hans algorithm. We excluded patients with other lymphomas,insufficient tissue or incomplete data. The Chi squared test and the Kaplan-Meier method was used for statistical analyses. Results: We identified 37 patients with relapsed/refractory DLBCL. Data from 20 patients was analyzed after excluding 17 patients. 13 (65%) were ABC type and 7 (35%) were the GCB type. There was no statistically significant difference between patient characteristics in both groups. Median age was 52 yrs (44% > 60 yrs in the ABC and 42% in GCB group). 1 patient in each group had a high IPI score. 69% of patients in the ABC group and 57% of the GCB group had a CR to first line chemotherapy. 46% of the ABC and 42% of the GCB group had Relapse-1 sensitive disease at ASCT. Only 2 patients (ABC group) had primary refractory disease. 53% of patients in the ABC and 71% of patients in the GCB groups were greater than 24 months from diagnosis to ASCT. The median follow-up of was 48 months (23–69 months). The median EFS in the GCB group was 48 months, while the median EFS in the ABC group has not been reached (p = 0.84). The median OS in the GCB and ABC groups is 61 months and 48 months respectively (p = 0.98). Conclusions: In our retrospective analysis of patients with relapsed/refractory DLBCL, 65% of patients that proceeded to an ASCT were of the ABC profile compared to 35% with the GCB profile. However the GCB profile did not predict for a difference in the EFS and OS after ASCT and the median EFS for patients with the ABC profile has not been reached. This suggests that high dose chemotherapy may overcome poor prognostic factors of the ABC profile in patients selected for ASCT and a larger multicenter study is planned to confirm these observations.
Surveillance endoscopique des patients présentant de multiples polypes coliques
Authors: N. Musquer
Journal: Endoscopy (2015)

L'HAS a clarifié en 2004 et actualisé en 2014 les modalités de surveillance endoscopique en fonction du niveau de risque de cancer colorectal (CRC). Néanmoins, en dehors des cas particuliers de PAF ou de syndrome de Lynch, le rythme de suivi des patients atteints d'autres types de polyposes adénomateuses ou festonnées est nettement moins bien codifié alors même qu'ils présentent très probablement un risque important de cancer.
PWE-051 Retrospective study examining the consequence of neutropaenia during treatment with pegylated interferon-2-α plus ribavirin for hepatitis C infection
Authors: S McClements, P Quinn, H Lloyd, P Ellul, A Davies, C Brown, J Keating
Journal: Gut (2010)

<h3>Introduction</h3> A common side effect of treatment with PGI2α and Ribavirin is bone marrow suppression and subsequent neutropaenia. This often results in dose adjustment for fear of rendering patients (pts) more susceptible to serious infection. Our experience is that pts tolerate the neutropaenia without adverse effects and we usually only consider dose reductions if other compelling reasons co-existent. This study was designed to identify the rates of neutropaenia in our treatment group and to determine if they were at greater risk of serious infections. <h3>Methods</h3> All pts who started and completed their treatment for Chronic Hepatitis C infection with combination therapy with PGI2α and ribavirin between April 2006 – September 2009 were included in the study. Three pts failed to attend for follow-up and were excluded from the study. As per BSG guidance, pts had their full blood counts monitored weekly for the first month then monthly thereafter while on treatment. The incidence of serious infection was monitored by reviewing clinical notes and hospital admissions. <h3>Results</h3> Total number of pts included in the study was 120 (Female=29, Male=91). The genotypes of our patient group were as follows: genotype 1a, 43 pts; genotype 1B, 10 pts; genotype 2a, 2 pts; genotype 2b, 9pts; genotype 3a, 55 pts. Pts with genotype 1 had 48 weeks of treatment and pts with genotype 2 or 3 had 24-week of treatment. Doses were weight adjusted as recommended by national guidelines. Neutropaenia was classified as a neutrophil count &lt;1.5×10<sup>9</sup>/l and was observed in 52 pts (43%) (Female=17, Male=35). The degree of neutropaenia was further subdivided into; Mild 1.0×10<sup>9</sup>/l–1.5×10<sup>9</sup>/l (35 pts); Moderate 0.5×10<sup>9</sup>/l–1.0×10<sup>9</sup>/l (14 pts) and Severe &lt;0.5×10<sup>9</sup>/l (3 pts). Dose adjustments were only advised in 3 pts (2 with co-existent neutropaenia and thrombocytopaenia and 1 with recurrent mouth ulcers). Serious infection requiring hospital admission or discontinuation of treatment was not identified in any pts. Of the pts who developed neutropaenia, 46 (88%) had negative PCR at the end of treatment and 40 pts (77%) had sustained virological response (SVR) at 1 year follow-up. <h3>Conclusion</h3> Although the incidence of neutropaenia in pts treated with PGI2α plus Ribavirin is relatively common (43% in our series), the risk of resultant serious infection appears remote. Neutropaenia appears to be a more frequent occurrence in treated female pts (59% females cf. 38% males, p&lt;0.05). Dose reduction is such pts developing neutropaenia as suggested by current guidance appears to be unnecessary and may diminish the likelihood of viral eradication and SVR.
Abstract 2276: Oncostatin M promotes breast cancer metastasis to lung by affecting initial stages of metastasis
Authors: Ken Tawara, Celeste Bolin, Jordan Koncinsky, Cheryl L. Jorcyk
Journal: Cancer Research (2015)

Abstract Recent studies suggest that cancer cells destined to establish metastatic lesions may shed early during tumor development, potentially even from carcinoma in situ. Furthermore, these cells may disseminate and lay dormant in a metastatic microenvironment (MME) for years before macrometastases are detectable. While inflammatory cytokines are known to be important in promoting breast cancer metastasis, their effect on tumor cell dissemination needs to be clarified. In this study, we investigate the effect of the interleukin-6-related, inflammatory cytokine oncostatin M (OSM) on early stages of breast cancer metastasis. First, we establish the expression pattern of OSM in human breast tissue using tissue microarrays. OSM is expressed in epithelial cells at higher levels in invasive ductal carcinoma (IDC) than in adjacent normal breast tissue, but is expressed at highest levels in ductal carcinoma in situ (DCIS). This suggests that autocrine-produced OSM may be important in breast tumor invasion and in the promotion of initial steps of metastasis. OSM increases early stage metastatic potential in vitro in aggressive 4T1.2 triple negative breast cancer cells (TNBCs) by inducing tumor cell detachment and migration. These findings are corroborated by in vivo studies using an orthotopic 4T1.2 mouse model of breast cancer. Reduced OSM expression in 4T1.2 (4T1.2-shOSM) cells is sufficient to inhibit the progression and the final number and volume of metastases in the lung, as well as circulating tumor cell (CTC) numbers in Balb/c mice. The number of CTCs is further reduced in a Balb/c OSM knockout background, demonstrating the importance of both paracrine- and autocrine-produced OSM in this process. Furthermore, orthotopic injection of 4T1.2-shOSM cells increases animal survival post-primary tumor resection, while bypassing the early stages of metastasis by injecting cells directly into the systemic circulation does not. As expected, in an orthotopic xenograft MDA-MB-231 human breast cancer mouse model, peri-tumoral injection of recombinant OSM increases the number of CTCs as well as spontaneous metastasis to lung. Taken together, these results suggest that suppression of OSM levels in the tumor microenvironment could be a highly effective therapeutic strategy for halting breast cancer metastasis to lung. Citation Format: Ken Tawara, Celeste Bolin, Jordan Koncinsky, Cheryl L. Jorcyk. Oncostatin M promotes breast cancer metastasis to lung by affecting initial stages of metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2015-2276