tbuckley/cabot-search huggingface dataset:
Hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil, and oxaliplatin plus intravenous cetuximab (Cet) (Optiliv) after failure on one versus two or three chemotherapy protocols in patients (pts) with unresectable liver metastases from wt KRAS colorectal cancer (LM-CRC) (European phase II clinical trial NCT00852228).
Authors: Michel Ducreux, Pasquale F. Innominato, Mohamed Hebbar, Denis Michel Smith, Céline Lepère, C. N. J. Focan, Rosine Guimbaud, Carlos Carvalho, Salvatore Tumolo, Sameh Awad, Stephanie Truant, Denis Castaing, Abdoulaye Karaboué, Thierry De Baere, Francis Kunstlinger, Mohamed Bouchahda, Valerie Boige, Philippe Rougier, Rene Adam, Francis Levi
Journal: Journal of Clinical Oncology (2013)

3599 Background: Optiliv allowed complete macroscopic resection (R0-R1) of previously unresectable LM-CRC in 28% of the pts, despite failure of 1-3 prior chemotherapy protocols (Lévi et al. Proc ASCO GI 2013). Purpose: To assess tolerability and efficacy of Optiliv according to previous chemotherapy exposure. Methods: Pts received iv Cet (500 mg/m²) and chronomodulated or conventional HAI of Irinotecan (180 mg/m²), 5-Fluorouracil (2800 mg/m²), and Oxaliplatin (85 mg/m²) q2 wks. Liver surgery was performed according to q6wks multidisciplinary reviews. Pts were categorized according to Optiliv as 2 nd (N=29 pts) vs 3 rd -4 th chemotherapy line (N=35 pts). Results: Pt characteristics were similar in both groups. Overall, there were 22F and 42 M, aged 33-76 years, with good PS (0/1/2: 40/22/2) and predominantly liver lesions. LM-CRC were bilateral in 51 pts (79.7%), with a median of 10 metastases (1-50), 6 segments involved (1-8), and largest diameter of 52 mm (15-172). 61 pts (2 nd line, 27; 3 rd -4 th line, 34) received a median of 6 courses (1-15). Grade 3-4 toxicities per pt were similar in both groups except for abdominal pain (2 nd line, 15% vs 3 rd -4 th line, 35%, p=0.07), diarrhea (7% vs 24%, p=0.09), thrombocytopenia and febrile neutropenia (0 vs 9%, p=0.25). Four CR were achieved in 2 nd line (15%) vs none in 3 rd -4 th line. Respective objective response rates were 63% and 38% (p=0.05). R0-R1 resections were performed in 11/27 pts (41%) on 2 nd line vs 6/34 pts (18%) on 3 rd -4 th line (p=0.06), resulting in respective median progression-free survival (PFS) of 14.2 months [7.8 - 20.7] vs 7.3 [5.5 - 9.1] (p=0.002). Median overall survival (OS) was not reached at 3 years in the pts on Optiliv as 2 nd line vs 15.2 months in the more heavily pretreated pts (p&lt;0.001). Conclusions: Intravenous Cet and triplet hepatic artery infusion resulted in the doubling of secondary surgical resection rate of LM-CRC, PFS and OS in 2 nd lineas compared to 3 rd -4 th line. Optiliv now deserves upfront testing. Clinical trial information: NCT00852228.
Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study
Authors: Tsutomu Takeuchi, Mark C Genovese, Boulos Haraoui, Zhanguo Li, Li Xie, Rena Klar, Ana Pinto-Correia, Susan Otawa, Pedro Lopez-Romero, Inmaculada de la Torre, William Macias, Terence P Rooney, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2018)

Objectives This study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day. Methods Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks. Results Patients in both groups maintained LDA (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups. Conclusions In a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.
Notch1 Signaling in NOTCH1-Mutated Mantle Cell Lymphoma Depends on DLL4 and Is a Potential Target for Specific Antibody Therapy
Authors: Elisabeth Höring, Berta Colom Sanmarti, Silvia Xargay-Torrent, Walter E Aulitzky, Heiko van der Kuip, Elias Campo, Mónica López-Guerra, Dolors Colomer
Journal: Blood (2016)
Racial and Geographic Differences in Breastfeeding — United States, 2011–2015
Authors: Erica H. Anstey, Jian Chen, Laurie D. Elam-Evans, Cria G. Perrine
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Breastfeeding provides numerous health benefits for infants and mothers alike. The American Academy of Pediatrics recommends exclusive breastfeeding for approximately the first 6 months of life and continued breastfeeding with complementary foods through at least the first year (1). National estimates indicate substantial differences between non-Hispanic black (black) and non-Hispanic white (white) infants across breastfeeding indicators in the United States (2). CDC analyzed 2011-2015 National Immunization Survey (NIS) data for children born during 2010-2013 to describe breastfeeding initiation, exclusivity through 6 months and duration at 12 months among black and white infants. Among the 34 states (including the District of Columbia [DC]) with sufficient sample size (≥50 per group), initiation rates were significantly (p<0.05) lower among black infants than white infants in 23 states; in 14 of these states (primarily in the South and Midwest), the difference was at least 15 percentage points. A significant difference of at least 10 percentage points was identified in exclusive breastfeeding through 6 months in 12 states and in breastfeeding at 12 months in 22 states. Despite overall increases in breastfeeding rates for black and white infants over the last decade, racial disparities persist. Interventions specifically addressing barriers to breastfeeding for black women are needed.
Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells
Authors: Robin M Meyers, Jordan G Bryan, James M McFarland, Barbara A Weir, Ann E Sizemore, Han Xu, Neekesh V Dharia, Phillip G Montgomery, Glenn S Cowley, Sasha Pantel, Amy Goodale, Yenarae Lee, Levi D Ali, Guozhi Jiang, Rakela Lubonja, William F Harrington, Matthew Strickland, Ting Wu, Derek C Hawes, Victor A Zhivich, Meghan R Wyatt, Zohra Kalani, Jaime J Chang, Michael Okamoto, Kimberly Stegmaier, Todd R Golub, Jesse S Boehm, Francisca Vazquez, David E Root, William C Hahn, Aviad Tsherniak
Journal: Nature Genetics (2017)
Re: Philipp Mandel, Felix Preisser, Markus Graefen, et al. High Chance of Late Recovery of Urinary and Erectile Function Beyond 12 Months After Radical Prostatectomy. Eur Urol 2017;71:848–50
Authors: Paolo Capogrosso, Francesco Montorsi, Andrea Salonia
Journal: European Urology (2017)
Abstract 106: Pluripotent Stem Cell Microrna-294 Induces Cardiomyocyte Proliferation and Augments Cardiac Function After Myocardial Infarction
Authors: Mohsin Khan, Emily Nickoloff, Jennifer Johnson, Suresh Verma, Jessica Ibetti, Venkata N Garikipati, Jibin Zhou, Cynthia Benedict, Walter J Koch, Raj Kishore
Journal: Circulation Research (2015)

Rationale: Embryonic heart is characteristic of rapidly dividing cardiomyocytes that give rise to sufficient numbers required to build a working myocardium. In contrast, cardiomyocytes retain some proliferative capacity in the neonates but lose most of it in adulthood. Embryonic stem cell cycle (ESCC) miRs are a class of microRNAs regulating the unique cell cycle of ESCs and their characteristic pluripotency. Nevertheless, expression of miR-294, a member of the ESCC miRs is lost during developmental transitions from the ESCs to mature cells. Effect of miR-294 to induce cardiac proliferation and heart function has not been previously studied. Objective: To determine whether miR-294 drives cardiomyocyte cell cycle reentry leading to augmentation of cardiac function after myocardial infarction. Methods and Results: miR expression analysis in the heart during development revealed elevated levels of miR-294 in the prenatal stages while the expression was lost in the neonates and adults as confirmed by qRT-PCR. Neonatal ventricular cardiomyocytes (NRVMs) were treated with miR-294 mimic to determine the effect on proliferation and cell cycle. Elevated mRNA levels of cyclins A2, E1, CDK2 together with c-myc, E2F1 and E2F3 was observed in NRVMs treated with 25nM mimic for miR-294. Additionally, miR-294 treated NRVMs showed in AKT phosphorylation along with enhanced protein levels of cyclin D1 and E2F1. Increased expression of p-histone 3, Ki67 and Aurora B kinase (G2/M) was confirmed by immunocytochemistry in NRVMs after miR-294 treatment compared to control cells. Administration of miR-294 in mice subjected to myocardial infarction demonstrated augmentation of cardiac function in mice receiving miR-294 8 weeks after injury. Increase myocyte proliferation was observed in the heart after miR-294 treatment as analyzed by BrdU uptake, p-Histone 3 and Aurora B expression by immunostaining. Concurrently, a decrease in infarct size along with decreased apoptosis was observed in the miR-294 hearts compared to the control. Conclusion: Ectopic expression of miR-294 recapitulates embryonic signaling and enhances cardiomyocyte ability to proliferate and reenter the cell cycle leading to augmented cardiac function in mice after myocardial infarction.
Versatile synthetic alternatives to Matrigel for vascular toxicity screening and stem cell expansion
Authors: Eric H. Nguyen, William T. Daly, Ngoc Nhi T. Le, Mitra Farnoodian, David G. Belair, Michael P. Schwartz, Connie S. Lebakken, Gene E. Ananiev, Mohammad Ali Saghiri, Thomas B. Knudsen, Nader Sheibani, William L. Murphy
Journal: Nature Biomedical Engineering (2017)
Abstract P008: Fibronectin Enhances Survival and Proliferation via Pim-1 and β1 Integrin in Cardiac Progenitor Cells
Authors: Mathias Konstandin, Mirko Völkers, Grady Gastelum, Natalie Gude, Mark A Sussman
Journal: Circulation Research (2011)

Background: Cardiac Progenitor Cells (CPC) are pivotally involved in cardiac repair. Extracellular matrix (ECM) components also contribute decisively in cardiac remodeling after myocardial infarction (MI). However, impact of ECM on CPC function and the involved signaling pathways have not been clearly elucidated. This study examines the relationship of ECM to cardioprotective signaling mediated by Pim-1, a serine/threonine kinase downstream of Akt, in CPC. Methods: Isolated mouse CPCs were plated on fibronectin (FN) or albumin coated dishes. FACS analysis and fluorescence based cell quantification have been used to determine viability and proliferation under stress and growth conditions. Signaling pathways were analyzed by immunoblotting, qRT-PCR and siRNA. Immunhistochemistry (IHC) has been used for in vivo studies after MI in mice. Results: FN inhibits starvation and staurosporine induced cell death in CPCs and promotes proliferation in conjunction with induction of Pim-1 expression. Protective and pro-proliferative effects of FN are abrogated by inhibition of Pim-1. Fibronectin signaling operates through the β1 integrin receptor that is crucial for FN-mediated signaling. Ongoing studies correlate these observations with in vivo responses to cardiomyopathic injury such as infarction challenge. Conclusion: FN provides pro-survival and pro-proliferative effects in CPCs in a Pim-1 kinase and β1 integrin dependent manner. Involved molecules colocalize in vivo in an infarction injury model. The causal contribution of FN in regeneration and wound healing after MI is to be confirmed by studies of a conditional FN knock-out mouse that is under construction.
MicroRNA‐206 prevents the pathogenesis of hepatocellular carcinoma by modulating expression of met proto‐oncogene and cyclin‐dependent kinase 6 in mice
Authors: Heng Wu, Junyan Tao, Xiaolei Li, Tianpeng Zhang, Lei Zhao, Yao Wang, Lei Zhang, Jun Xiong, Zhi Zeng, Na Zhan, Clifford J. Steer, Li Che, Mingjie Dong, Xiaomei Wang, Junqi Niu, Zhuoyu Li, Guiqing Yan, Xin Chen, Guisheng Song
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and therapeutic agents for this malignancy are lacking. MicroRNAs play critical roles in carcinogenesis and present tremendous therapeutic potential. Here, we report that microRNA‐206 is a robust tumor suppressor that plays important roles in the development of HCC by regulating cell‐cycle progression and the cMet signaling pathway. MicroRNA‐206 was underexpressed in livers of two HCC mouse models, human individuals bearing HCC, and human HCC cell lines. Combining bioinformatic prediction and molecular and cellular approaches, we identified cMET (Met proto‐oncogene), cyclin D1 ( CCND1 ), and cyclin‐dependent kinase 6 ( CDK6 ) as functional targets of microRNA‐206. By inhibiting expression of cMET , CCND1 , and CDK6 , microRNA‐206 delayed cell‐cycle progression, induced apoptosis, and impaired proliferation of three distinct human HCC cell lines. Systemic administration of microRNA‐206 completely prevented HCC development in both cMyc and V‐Akt murine thymoma viral oncogene homolog 1/neuroblastoma RAS viral oncogene homolog (AKT/Ras) HCC mice, whereas 100% of control mice died from lethal tumor burdens. Conversely, reintroduction of cMet or Cdk6 into livers of cMyc and AKT/Ras HCC mice recovered growth of HCC inhibited by microRNA‐206. These results strongly suggested that cMet and Cdk6 were two functional targets that mediated the inhibitory effect of microRNA‐206 on the development of HCC. MicroRNA‐206 overexpression demonstrated a profound therapeutic effect on HCC in xenograft and cMyc HCC mice. Conclusion: In summary, this study defines a potentially critical role of microRNA‐206 in preventing the growth of HCC and suggests its use as a potential therapeutic strategy for this malignancy. (H epatology 2017;66:1952–1967)
Outcomes for Allogeneic Hematopoietic Cell Transplantation for AML and High-Grade MDS in Older Adults in the Era of T-Replete Haploidentical Donor Grafts. a Single Center Multivariate Analysis
Authors: Zain Bashey, Scott R. Solomon, Lawrence E. Morris, H. Kent Holland, Xu Zhang, Melhem Solh
Journal: Blood (2016)
Mechanical Circulatory Support Devices for Acute Right Ventricular Failure
Authors: Navin K. Kapur, Michele L. Esposito, Yousef Bader, Kevin J. Morine, Michael S. Kiernan, Duc Thinh Pham, Daniel Burkhoff
Journal: Circulation (2017)

Right ventricular (RV) failure remains a major cause of global morbidity and mortality for patients with advanced heart failure, pulmonary hypertension, or acute myocardial infarction and after major cardiac surgery. Over the past 2 decades, percutaneously delivered acute mechanical circulatory support pumps specifically designed to support RV failure have been introduced into clinical practice. RV acute mechanical circulatory support now represents an important step in the management of RV failure and provides an opportunity to rapidly stabilize patients with cardiogenic shock involving the RV. As experience with RV devices grows, their role as mechanical therapies for RV failure will depend less on the technical ability to place the device and more on improved algorithms for identifying RV failure, patient monitoring, and weaning protocols for both isolated RV failure and biventricular failure. In this review, we discuss the pathophysiology of acute RV failure and both the mechanism of action and clinical data exploring the utility of existing RV acute mechanical circulatory support devices.
Use of Neoadjuvant Platinum—The Ongoing Conundrum
Authors: Hope S. Rugo, Karen Gelmon
Journal: JAMA Oncology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract #3392: Transient pAkt increase after chemo exposure predicts strength of synergy for combinations of the PI3K inhibitor GDC-0941 and chemotherapeutics
Authors: Jeffrey Wallin, Kyle Edgar, Jane Guan, Lori Friedman, Marcia Belvin
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The PI3K/PTEN pathway is frequently disrupted in cancer cells and is implicated in multiple aspects of tumor growth and survival. Inhibition of this pathway therefore represents a rational target for therapeutic intervention. Resistance to many anticancer agents has been attributed to a failure to decrease PI3K/PTEN pathway signaling resulting in cell survival. Hence, inhibitors of the pathway have potential utility both as single agents and in combination with other targeted and cytotoxic therapies. In these studies we have explored the use of a Class I PI3K inhibitor, GDC-0941, in combination with chemotherapeutics. We have found in many cases that inhibition of PI3K significantly enhances the effects of chemo in vitro. Analysis of combinations using viability assays in multiple cell lines indicated that pathway mutational status was not strongly associated with synergy. Instead, we discovered that increased nuclear pAkt in response to the chemotherapeutic as a single agent was often predictive of the strength of synergy with GDC-0941. This correlation did not depend on endogenous levels of pAkt. We also found that pAkt levels were decreased upon GDC-0941 dosing regardless of the presence or absence of the chemo and regardless of whether the combinations were synergistic or not. Overall, these results suggest that chemo combinations involving PI3K inhibitors should be efficacious in vivo.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3392.
Induction of apoptosis by extracelluar organic metabolite isolated from actinomycete Streptomyces sp. BIT-64 in human leukemia cells
Authors: Yung Hyun Choi, Min Ho Han, Cheng-Yun Park, Gi-Young Kim, Byung Tae Choi, Won Ho Lee, Seong-Yun Jeong
Journal: Clinical Cancer Research (2007)

A11  Marine organisms have produced a wide variety of structurally unique and biologically active natural products. As a part of a research program aimed at the discovery of active compounds from marine organisms, we isolated an extracelluar organic metabolite (EOM) from marine actinomycete Streptomyces sp. BIT-64 from Jinhae Bay (southern coast of Korea) and investigated the antiproliferative mechanism of EOM in cultured human leukemic cell lines (U937, HL-60, K562 and THP-1). The exposure of leukemic cells to EOM resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner, as measured by the MTT assay, trypan blue exclusion method, fluorescent microscopy, agarose gel electrophoresis and flow cytometry assay. The EOM treatment induced the proteolytic activation of caspase-3, which was associated with the down-regulation modulation of anti-apoptotic Bcl-2 protein and a concomitant degradation of poly(ADP ribose) polymerase. However, EOM-induced caspase-3 activation and apoptosis were significantly attenuated in Bcl-2 overexpressing U937 cells. z-DEVD-fmk, a caspase-3 specific inhibitor, blocked caspase-3 activation and increased the survival rate of EOM-treated U937 cells. Moreover the activity of Akt was inhibited in EOM-treated cells, and PI3K/Akt inhibitor, LY294002, sensitized the cells to EOM-induced apoptosis. Our data collectively imply that the down-regulation Akt signaling pathway may play a key role in EOM-induced apoptosis in U937 cells. Thus, our findings imply that some of the biological functions of Bcl-2 may be attributed to their ability to inhibit EOM-induced apoptosis and it is suggested that this compound can be a promising anti-cancer agent for leukemia cells.
Mutational Shift in FLT3 and NPM1-Positive Acute Myeloid Leukemia (AML) Relative to Therapy and Disease Progression
Authors: Priya D Velu, Chris C.S. Hsiung, Kiarash Salafian, Adam Bagg, Jennifer J.D. Morrissette, Selina Luger
Journal: Blood (2016)
Posing Causal Questions When Analyzing Observational Data—Reply
Authors: Steven N. Goodman, Sebastian Schneeweiss
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal