tbuckley/cabot-search huggingface dataset:
Microfluidic Encapsulation of Prickly Zinc‐Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy
Authors: Hongbo Zhang, Dongfei Liu, Liang Wang, Zehua Liu, Runrun Wu, Agne Janoniene, Ming Ma, Guoqing Pan, Lina Baranauskiene, Linlin Zhang, Wenguo Cui, Vilma Petrikaite, Daumantas Matulis, Hongxia Zhao, Jianming Pan, Hélder A. Santos
Journal: Advanced Healthcare Materials (2017)

Structural features of nanoparticles have recently been explored for different types of applications. To explore specific particles as nanomedicine and physically destroy cancer is interesting, which might avoid many obstacles in cancer treatment, for example, drug resistance. However, one key element and technical challenge of those systems is to selectively target them to cancer cells. As a proof‐of‐concept, Prickly zinc‐doped copper oxide (Zn–CuO) nanoparticles (Prickly NPs) have been synthesized, and subsequently encapsulated in a pH‐responsive polymer; and the surface has been modified with a novel synthesized ligand, 3‐(cyclooctylamino)‐2,5,6‐trifluoro‐4‐[(2‐hydroxyethyl)sulfonyl] benzenesulfonamide (VD1142). The Prickly NPs exhibit very effective cancer cell antiproliferative capability. Moreover, the polymer encapsulation shields the Prickly NPs from unspecific nanopiercing and, most importantly, VD1142 endows the engineered NPs to specifically target to the carbonic anhydrase IX, a transmembrane protein overexpressed in a wide variety of cancer tumors. Intracellularly, the Prickly NPs disintegrate into small pieces that upon endosomal escape cause severe damage to the endoplasmic reticulum and mitochondria of the cells. The engineered Prickly NP is promising in efficient and targeted cancer treatment and it opens new avenue in nanomedication.
Screening for Depression Through a Glass Darkly
Authors: Alain Braillon
Journal: JAMA Internal Medicine (2017)

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Critical assessment of phase 0 (Ph0) and window of opportunity (WOO) trials: Definitions and reporting.
Authors: Sunil Parimi, Hatim Karachiwala, Yongtao Lin, Jose Gerard Monzon, Vincent Channing Tam, Eric Xueyu Chen, Janet Dancey, Patricia A. Tang
Journal: Journal of Clinical Oncology (2015)

e17710 Background: BothWOO and Ph0 trials are proposed to accelerate investigational new drug (IND) development. There is a lack of consensus on definition, design and value. Our objective was to evaluate clinician views and evaluate quality of reporting for WOO and Ph0 trials. Methods: New drug development experts at major North American institutions were surveyed to determine defining characteristics of Ph0 and WOO trials. The FDA definition of Ph0 (exploratory IND) trial was used. WOO and Ph0 oncology trials in published or abstract form were identified by Medline/EMBASE (1974- 2014). They were evaluated for quality of reporting and concordance with trial definitions. Results: The survey response rate was 27% (30/113); 22% of respondents felt these modalities accelerated drug development. Consensus definitions were developed by the survey results and were based on dose, length of exposure, and primary endpoint (See table). Only 25% (4/16) Ph0 and 61% (22/36) WOO trials satisfied the consensus definitions. The following key elements were inadequately reported (WOO/Ph0): primary endpoint (64%/75%), prior therapies (56%/44%), and description of > grade 3 toxicities (26%) in WOO trials or any toxicity in Ph0 (59%). The following were adequately reported (WOO/Ph0): type of trial (97%/94%), study rationale (92%/94%), number of patients on study (97%/ 100%), drug dosing/administration (97%/88%), and duration of treatment (97%/100%). Conclusions: Our survey helps to clarify distinguishing features between WOO and Ph0 trials. The number of published WOO and Ph0 trials was low compared to other types of trials. Improved quality of reporting is imperative. Characteristics WOO (%) Phase 0 (%) Dose RP2D from phase I (93%) Microdose (85%) Dose escalation (85%) Length of exposure * Weeks (77%) Until progression (50%) Days (72%) Timing * Delay standard therapy (54%) Concurrent with Ph I, II, III (48%, 76%, 32%) Preclinical (30%) Between preclinical/Ph I (74%) Ph I (17%) Primary Endpoint Clinical (37%) Pharmacodynamic (63%) Pharmacodynamic (50%) Pharmacokinetic (50%) * More than one answer was permitted
Short-Term Fasting Induces Cell Cycle Arrest of Immature Hematopoietic Cells and Increases the Number of Naive T Cells in the Bone Marrow of Mice
Authors: Teruhito Takakuwa, Yasuhiro Nakashima, Hideo Koh, Takahiko Nakane, Hirohisa Nakamae, Masayuki Hino
Journal: Blood (2016)
Impact of Infused Peripheral Blood Stem Cell Parameters (Total Nucleated Cells, CD34+ Cells, CD3+ Cells and CFU-GM) on Transplant Outcome after Reduced Intensity Allogeneic HSCT.
Authors: Mauricette Michallet, Quoc-Hung Le, Anne Thiebaut, Sophie Ducastelle, Nicole Raus, Daniela Revesz, Jacques Troncy, Youcef Chelgoum, Jean-Paul Bourgeot, Philippe Dubost, Olivier Hequet, Franck E. Nicolini
Journal: Blood (2007)
The use of drugs acting on the renin-angiotensin system and the incidence of pancreatic cancer.
Authors: Victoria Mandilaras, Nathaniel Bouganim, Jamil Asselah, Hui Yin, Laurent Azoulay
Journal: Journal of Clinical Oncology (2015)

e15244 Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensives. Recently, these drugs have been associated with a protective effect against pancreatic cancer, but data on this putative association remain limited. Objective: To determine whether the use of ACEIs and/or ARBs is associated with a decreased risk of pancreatic cancer. Methods: We conducted a population-based cohort study, using a nested case-control analysis within the UK Clinical Practice Research Datalink population. The cohort consisted of all patients newly-treated with antihypertensive drugs between January 1, 1995 and December 31, 2009, with follow-up until December 31, 2010. Cases were patients newly-diagnosed pancreatic cancer which were matched with up to 10 controls on age, sex, calendar year of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of pancreatic cancer incidence associated with ever use of ACEIs and ARBs. A secondary analysis was conducted to assess whether there the incidence of pancreatic cancer varied with cumulative duration of use of these drugs. Results: A cohort of 547,566 was assembled. During 3,040,332 person years of follow-up, a total of 866 patients were newly-diagnosed with pancreatic cancer (rate: 3/10,000 per year) and matched 8636 controls. Overall, when compared to other antihypertensive drugs, the use of ACEIs was not associated with a decreased risk of pancreatic cancer overall (OR: 1.01, 95% CI: 0.86-1.18) or according to cumulative duration of use. The use of ARBs was not associated with a decreased risk of pancreatic cancer overall (OR: 0.93, 95% CI: 0.75-1.15), while a cumulative duration of use of 1 to 3 years was associated with a 38% decreased 95% CI 0.41-0.95), which returned to the null after more than 3 years of use (OR: 1.05, 95% CI: 0.75-1.46). Conclusions: The use of ARBs and ACEIs was not associated with an overall decreased risk of pancreatic cancer. Additional research is needed to determine whether ARBs may confer a short-term protective effect.
Shedding of Procoagulant Microparticles from Platelets through Integrin Outside-In Signaling Involving WASP and the Actin Cytoskeleton.
Authors: Sandra Cauwenberghs, Marion A.H. Feijge, Alan G.H. Harper, Stewart O. Sage, Elisabeth van Pampus, Joyce Curvers, Johan W.M. Heemskerk
Journal: Blood (2006)
Integration of Receptor Tyrosine Kinases Determines Sensitivity to PI3Kα-selective Inhibitors in Breast Cancer
Authors: Yi-chao Xu, Xiang Wang, Yi Chen, Si-meng Chen, Xin-ying Yang, Yi-ming Sun, Mei-yu Geng, Jian Ding, Ling-hua Meng
Journal: Theranostics (2017)

PI3Kα-selective inhibitor BYL719 is currently in phase II/III clinical trial for the treatment of breast cancer, but highly variable response has been observed among patients.We sought to discover predictive biomarker for the efficacy of BYL719 by dissecting the proliferative signaling pathway mediated by PI3K in breast cancer.BYL719 concurrently inhibited the phosphorylation of AKT and ERK in PIK3CA-mutated human breast cancer cells.PI3K-regulated ERK phosphorylation was independent of canonical PDK1/AKT/mTOR pathway, while it was associated with RAF/MEK.Hyper-activation of EGFR or RAS abrogated inhibition of ERK phosphorylation by BYL719.Furthermore, hyper-activation of receptor tyrosine kinases (RTKs) including EGFR, c-MET, FGFR and HER3 but not IGF-1R restored ERK phosphorylation and cell viability suppressed by BYL719, suggesting the discriminative functions of RTKs in cell signaling and proliferation.By profiling 22 breast cancer cell lines, we found that BYL719 was more potent in cell lines where phosphorylation of both AKT and ERK was attenuated than those where only AKT phosphorylation was inhibited.The potency of BYL719 was further found to be significantly correlated with the expression profile of RTKs in breast cancer cells.Specifically, overexpression of EGFR, c-MET and/or FGFR1 forecasted resistance, while overexpression of IGF-1R and/or HER2 predicted sensitivity to BYL719 in breast cancer cells.Similar correlation between BYL719 efficacy and expression profile of RTKs was found in patient-derived xenograft models of breast cancer.Thus, inhibition of ERK phosphorylation by PI3Kα inhibitor BYL719 contributes to its antitumor efficacy and is determined by the converged signaling from RTKs.The expression profile of RTKs in breast cancer tissue could be potentially developed as a predictive biomarker for the efficacy of PI3Kα inhibitors.
The Role of the Cytoplasmic Domain of the FcγRI α Chain in FcγRI Signaling.
Authors: Sharon Hunter, Zhen-Yu Huang, Paul Chien, Moo-Kyung Kim, Randall G. Worth, Anthony B. Daniels, Tai-Hee Kim-Han, Zena K. Indik, Alan D. Schreiber
Journal: Blood (2004)
Abstract P4-02-08: Opto-acoustic imaging of the breast: Downclassification and upclassification of suspicious breast masses
Authors: GLG Menezes, RM Pijnappel, C Meeuwis, B Bisschops, J Veltman, PT Lavin, RM Mann
Journal: Cancer Research (2017)

Abstract Background Imagio® is an opto-acoustic (OA) breast imaging system designed to concomitantly collect OA images together with diagnostic ultrasound (CDU). The device is intended to improve distinction between benign and malignant masses. In this interim analysis of the post-market surveillance MAESTRO study we report the results of 75 patients who had breast masses classified as BI-RADS 4a and 4b by CDU. Aim We assessed OA's sensitivity, specificity, and its ability to downgrade benign masses and upgrade malignant masses based on the probability of malignancy (POM) and BI-RADS category. Methods Seventy-five patients with 78 breast masses were evaluated with OA prior to biopsy. For each mass, the radiologist scored 5 OA features, assigned a POM and BI-RADS category. OA sensitivity, specificity, and BI-RADS downgrade and upgrade percentages were assessed with and without contribution from a previously derived nomogram. Results The mean POM difference between malignant and benign masses was higher for OA (37%) than for CDU (27%). OA specificity was 43% without the nomogram and 68% with the nomogram. OA sensitivity was 97% with and without the nomogram. With OA 43% of benign masses could be downgraded and 47% of malignant masses could be upgraded in BIRADS category. Conclusion These results appear to confirm the previously reported ability of OA to improve the differentiation between benign and malignant masses compared to CDU alone, to potentially decrease negative biopsies, and to upgrade BI-RADS category in malignant masses. The MAESTRO study (n=200) may further confirm these results. Citation Format: Menezes GLG, Pijnappel RM, Meeuwis C, Bisschops B, Veltman J, Lavin PT, Mann RM. Opto-acoustic imaging of the breast: Downclassification and upclassification of suspicious breast masses [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-02-08.
R-HCVAD/R-MTX-Arac (R-HCVAD) Overcomes Risk Features Associated with Inferior Outcomes In the Treatment of Newly Diagnosed, High-Risk Diffuse Large B-Cell Lymphoma (DLBCL).
Authors: Anthony R Mato, Tatyana Feldman, Tania Zielonka, Pritish K. Bhattacharyya, Alexandria Campaiola, Rina P Shah, Maria Rosario, Coleen Bejot, Susan Stives, Mary Curtin, Rosalba Vicioso, Stuart L Goldberg, Andrew L Pecora, Andre Goy
Journal: Blood (2010)
Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial
Authors: David C Lye, Sophia Archuleta, Sharifah F Syed-Omar, Jenny G Low, Helen M Oh, Yuan Wei, Dale Fisher, Sasheela S L Ponnampalavanar, Limin Wijaya, Linda K Lee, Eng-Eong Ooi, Adeeba Kamarulzaman, Lucy C Lum, Paul A Tambyah, Yee-Sin Leo
Journal: The Lancet (2017)
Association Between Acute Leukoencephalopathy and Long-Term Neurobehavioral and Brain Imaging Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated with Chemotherapy Only
Authors: Yin Ting Cheung, Noah D. Sabin, Wilburn E. Reddick, Deepa Bhojwani, Wei Liu, Tara M. Brinkman, John O. Glass, DeoKumar Srivastava, Leslie L. Robison, Ching-Hon Pui, Melissa M. Hudson, Kevin R. Krull
Journal: Blood (2015)
Abstract B57: RNAi Nanotechnology for Cancer Target Validation and Therapy
Authors: Jinjun Shi
Journal: Cancer Research (2017)

Abstract RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets, and for treatment of a myriad of important human diseases including cancer. The ubiquitous application of RNAi in cancer research and therapy is nevertheless hindered by the challenge of effective systemic in vivo delivery of RNAi agents (e.g., siRNA) to solid tumors, which requires overcoming of multiple physiological barriers, such as enzymatic degradation, rapid elimination by renal excretion or by the mononuclear phagocyte system (MPS), poor tumor penetration, and insufficient cellular uptake and endosomal escape. Here we will describe the rational design and development of unique nanoparticle platforms to address these obstacles. These siRNA nanoparticles have been successfully applied to evaluate the therapeutic role of different targets (e.g., prohibitin1) in treating solid tumors, and have demonstrated significant potential for the clinical development of novel cancer therapies. Note: This abstract was not presented at the conference. Citation Format: Jinjun Shi. RNAi Nanotechnology for Cancer Target Validation and Therapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B57.
Bortezomib (Velcade)-Melphalan-Prednisone (VMP) Versus Velcade- Thalidomide-Prednisone (VTP) in Elderly Untreated Multiple Myeloma Patients: Which Is the Best Partner for Velcade: An Alkylating or An Immunomodulator Agent?
Authors: Maria-Victoria Mateos, Albert Oriol, Joaquín Martínez, Ma Teresa Cibeira, Raquel de Paz, Ma José Terol, José García-Laraña, Enrique Bengoechea, Rafael Martínez, Alejandro Martin, Felipe de Arriba, Luis Palomera, José Hernández, Jose-Luis Bello, María-Luisa Martín, Yolanda González, Joan Blade, Juan José Lahuerta, J.F San Miguel
Journal: Blood (2008)
Chronic Graft Versus Host Disease (GVHD) Does Not Impact Cardiovascular Risk Factors in Survivors of Allogeneic Hematopoietic Stem Cell Transplantation (SCT) up to the Second Decade Post-Transplant,
Authors: Priyanka A Pophali, Kamna Chawla, Eleftheria K. Koklanaris, Avan Antia, Simar Chawla, Sawa Ito, Jeffrey K. Klotz, Robert Q. Le, A. John Barrett, Minoo Battiwalla
Journal: Blood (2011)
PP86. CAN FRUIT JUICE PHYTOCHEMICALS HAVE A CHEMOTHERAPEUTIC EFFECT IN THE TREATMENT OF GLIOMA?
Authors: Ms Shofiya Salim, Dr Tim Snape, Dr Philip Welsby, Dr Gail Welsby
Journal: Neuro-Oncology (2017)

INTRODUCTION: Glioblastoma multiforme (GBM), is the most common and malignant primary brain tumour in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Epidemiological studies have shown a positive correlation between consumption of fruits and vegetables in the reduced risk and prevention of cancers, resulting in improved mortality rates. Phytochemicals are bioactive non-nutrient plant compounds which have particular roles within plants including contributing to reproduction and growth, defence mechanisms against pathogens and parasites, as well as providing colour and fragrance to the plant. Various fruits encompass differing antioxidant abilities which are derived from their phytochemical components. Research has emphasised the importance of antioxidants and their ability to neutralise reactive oxygen species (ROS) which cause oxidative damage to lipids, proteins and nucleic acids. Phytochemicals can be classified into five main categories; phenolics, carotenoids, nitrogen-containing compounds, organosulfur compounds and alkaloids, of which phenolics (polyphenols) are the most common and widely distributed. With their ability to combat reactive oxygen species and cross the blood brain barrier, polyphenols have the potential to improve current treatment options and outcomes of GBM. METHODS: Gold standard end-point assays were used to determine the total phenolic, total flavonoid and total antioxidant capacity of five freeze-dried fruit samples (acai berry, maqui berry, goji berry, strawberry and cranberry). Using the most common polyphenol reference standards, high performance liquid chromatography (HPLC) was then undertaken to identify and measure individual polyphenols present in each fruit sample. RESULTS: Strawberry was found to have the highest flavonoid content (2.45 ± 0.292 mg/ml catechin) and antioxidant capacity (7.30 ± 0.01mM TROLOX equivalence) of the fruit samples tested. Subsequent HPLC analysis indicated high levels of punicalagin in comparison to the other fruits (which ranged from 4.44mM to 0.03mM TROLOX equivalence). CONCLUSIONS: This data suggests that the high flavonoid levels, and in particular punicalagin, found in strawberry, contributes to the antioxidant capacity of this fruit juice. Current studies are underway to test this compound in vitro using the established cell lines of U87 MG (Grade IV human glioblastoma) and SVG-p12 (human foetal astroglia) in conditions of normoxia (95% air/5% CO2) and hypoxia (1% O2 / 5% CO2) to mimic the tumour environment.
Low pathologic complete response (pCR) rate to neoadjuvant chemotherapy in invasive lobular carcinoma of breast: Analysis of subgroup of four phase II trials
Authors: P. Khosravi-Shahi, Y. Izarzugaza Peron, G. Perez-Manga
Journal: Journal of Clinical Oncology (2009)

601 Background: Pathologic complete response (pCR) after preoperative chemotherapy (PCT) is associated with better outcome in locally advanced breast cancer (LABC). However, the pCR rate according to histology usually is not considered in trials. Methods: Patients (p) with histologically confirmed lobular carcinoma (LC), including in four phase II trials (AT, ATX, TXH, and BTX) conducted in our center, were eligible. Radiotherapy (RT) and hormone therapy (Ht) were allowed after surgery. Expression of markers was determined by IHC before CT. Primary objective of the study was to evaluate pCR rate in this subgroup of ps. Secondary endpoints were: clinical response rate (CRR), breast conservative surgery rate (BCSR), pathologic tumoral size (pTS), disease-free survival (DFS), and overall survival (OS). Results: A total of 185 ps including in the four trials were evaluated. Sixteen ps had LC (16/185 = 8.65%): median age = 50 y (38–66); premenopausal = 56.2%; left breast = 56.2%; median clinical (c) tumor size = 5 cm (3–6); stage:IIA = 6.7%; IIB = 26.7%; IIIA = 33.3%; IIIB = 33.3%; T:cT3 = 50%; cT4 = 28.6%; cN+ = 71.4% (median pN = 2 [0–32]); grade: G2 = 60%, G3 = 40%; ER+ = 78.6%; PgR+ = 64.3%; HER-2+ = 6.25%; phenotype by IHC: Luminal (HR+/HER-2-) = 75% (12/16); Luminal/HER-2+ (HR+/HER-2+) = 6.25%; triple negative (3/16) = 18.75%; p53+ = 25%; EGFR negative = 90%; median Ki-67 = 20% (5–70); adjuvant trastuzumab (H) = 6.25%; RT = 60%, median dose = 50Gy; Ht = 78.6% (tamoxifen = 55%; AI = 45%); type of PCT: docetaxel (T), capecitabine (X), and H (TXH) = 1p (6.2%); doxorubicin (A), T, and X (ATX) = 5 ps (31.2%); bevacizumab, T, and X (BTX) = 5 ps (31.2%); AT = 5 ps (31.2%); median of 5 cycles (2–6). Primary End-Point: Only 1 p (6.25%) had pCR in breast and nodes, and another p had a pCR only in breast, but not in nodes (pCR in breast = 2/16). Second End-Points: 1) CRR = 56.25% (complete = 12.5%; partial = 43.75%; no response = 37.5%; progression = 6.25%); 2) BCSR = 12.5%; 3) Median pTS = 2 cm(0 cm-6 cm); 4) Survival data are not mature. Only four events had occurred. With a median follow-up of 31 months, median DSF and OS has not been reached. Four-years DFS = 57%; and 3-y OS = 81%. Survival data will be updated in the meeting. Conclusions: PCT in LC is associated with very low pCR. No significant financial relationships to disclose.
NCCN Guidelines Insights: Bone Cancer, Version 2.2017
Authors: J. Sybil Biermann, Warren Chow, Damon R. Reed, David Lucas, Douglas R. Adkins, Mark Agulnik, Robert S. Benjamin, Brian Brigman, G. Thomas Budd, William T. Curry, Aarati Didwania, Nicola Fabbri, Francis J. Hornicek, Joseph B. Kuechle, Dieter Lindskog, Joel Mayerson, Sean V. McGarry, Lynn Million, Carol D. Morris, Sujana Movva, Richard J. O'Donnell, R. Lor Randall, Peter Rose, Victor M. Santana, Robert L. Satcher, Herbert Schwartz, Herrick J. Siegel, Katherine Thornton, Victor Villalobos, Mary Anne Bergman, Jillian L. Scavone
Journal: Journal of the National Comprehensive Cancer Network (2017)

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.
Combination of Epigenetic Agents Synergistically Reverse the Malignant Phenotype in Models of T-Cell Lymphoma
Authors: Enrica Marchi, Matko Kalac, Danielle C Bongero, Christine M McIntosh, Laura K Fogli, Luigi Scotto, Maura Rossi, Pier Luigi Zinzani, Stefano Pileri, Pier Paolo Piccaluga, Owen A. O'Connor
Journal: Blood (2011)