tbuckley/cabot-search huggingface dataset:
A Rab20-Dependent Membrane Trafficking Pathway Controls M. tuberculosis Replication by Regulating Phagosome Spaciousness and Integrity
Authors: Laura Schnettger, Angela Rodgers, Urska Repnik, Rachel P. Lai, Gang Pei, Martijn Verdoes, Robert J. Wilkinson, Douglas B. Young, Maximiliano G. Gutierrez
Journal: Cell Host & Microbe (2017)

The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication. Rab20 is specifically and significantly upregulated in the sputum of human patients with active tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of defense that promotes maintenance of Mtb within intact membrane-bound compartments for efficient elimination.
Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
Authors: James D McKay, Rayjean J Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil E Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A Pooley, David C Qian, Xuemei Ji, Geoffrey Liu, Maria N Timofeeva, Stig E Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher A Haiman, Lynne R Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F M van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer A Doherty, Matt P Barnett, Chu Chen, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H-Erich Wichmann, Judith Manz, Thomas R Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard S Houlston, John McLaughlin, Victoria L Stevens, Philippe Joubert, Maxime Lamontagne, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D Tobin, Louise V Wain, Thorunn Rafnar, Thorgeir E Thorgeirsson, Gunnar W Reginsson, Kari Stefansson, Dana B Hancock, Laura J Bierut, Margaret R Spitz, Nathan C Gaddis, Sharon M Lutz, Fangyi Gu, Eric O Johnson, Ahsan Kamal, Claudio Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Christopher I Amos
Journal: Nature Genetics (2017)
Afatinib (A) plus cetuximab (C) in the treatment of patients (pts) with NSCLC: The story so far
Authors: E. Smit, J.-C. Soria, Y.Y. Janjigian, H.J.M. Groen, W. Pao, E. Calvo, A. Gazzah, J. Fan, M. Ould-Kaci, L. Horn
Journal: Annals of Oncology (2017)
Nab-paclitaxel and gemcitabine for the treatment of pancreatic adenocarcinoma at an academic center.
Authors: Zhubin Gahvari, Noelle K. LoConte, Sam Joseph Lubner, Daniel Mulkerin, Clifford Suhyun Cho, Emily Winslow, Sharon M. Weber, Dustin A. Deming
Journal: Journal of Clinical Oncology (2015)

e15261 Background: The combination of nab-paclitaxel (nab-P) and gemcitabine (G) is a standard of care for patients (pts) with metastatic pancreatic ductal adenocarcinoma (PDA). This regimen was shown to improve PFS and OS for pts with PDA and was well-tolerated in the first-line setting. Limited data are available describing the use of this regimen in a general population and in the second-line setting. Methods: A single-institution retrospective chart review of pts who received the combination of nab-P and G for PDA from 2011-2014 was performed after Institutional Review Board approval. Results: A total of 27 pts were treated with this regimen. The median age was 59 years old (33-81) and the ECOG PS was 0 (22%), 1 (74%), and 2 (4%). 9/27 pts were treated in the first-line setting and a PFS of 5.5 months (mos) and an OS of 7.6 mos was observed. The benefit from nab-P and G in the second-line setting depended on the prior therapy. Nab-P and G were given following adjuvant G in 10 pts with a PFS of 2.3 mos. Nab-P and G were given following FOLFIRINOX without prior G in 6 pts with a PFS of 8.2 mos. No difference in PFS was noted based on age or baseline PS. Dose modifications were required frequently in this population. In 20/27 pts nab-P and G were initiated at standard dosing of nab-P (100-125 mg/m2) and G (1000 mg/m2) on days 1, 8, and 15 every 4 weeks. Cycle 1 dose modifications occurred in 50% due to neutropenia, thrombocytopenia, or fatigue. In 7 pts nab-P and G were initiated at reduced doses due to baseline symptoms or prior therapy. Cycle 1 dose reductions were required in 29% of these pts. The PFS for pts with a reduction in nab-P and G either initially or during cycle 1 was 5.5 mos. 78% of pts required a dose modification at some point during their course of nab-P and G. Grade 3 hematologic events were observed in 70% of pts. Conclusions: In this population of pts treated with nab-P and G for PDA, a similar PFS and OS was observed compared to previous reports. This regimen, however, required a greater number of dose reductions most commonly due to hematologic toxicities. The PFS advantage for nab-P and G was maintained in the second-line setting following FOLFIRINOX. A trend towards decreased PFS was seen in pts who received prior G.
Urinary metabotypes in patients with chronic hepatitis C virus infection as revealed by nuclear magnetic resonance-based metabolomics
Authors: E. Biliotti, A. Tomassini, D. Palazzo, G. Capuani, F. Sciubba, R. Esvan, M. De Angelis, C. Franchi, G. Iaiani, P. Maida, M. Spaziante, P. Rucci, A. Miccheli, G. Taliani
Journal: Journal of Hepatology (2017)
Early biomarkers of response to carfilzomib in multiple myeloma (MM): Modulation of CXCR4 and induction of autophagy.
Authors: Manisha Bhutani, Min-Jung Lee, Yusuke Tomita, Sunmin Lee, Ari Frosch, Mattias Carlsten, Seth M. Steinberg, Neha Korde, Ola Landgren, Jane B. Trepel
Journal: Journal of Clinical Oncology (2014)

e19572 Background: Carfilzomib (cfz), a selective and irreversible proteasome inhibitor is a critical component of the highly effective cfz + lenalidomide (len) + dexamethasone (dex) [CRd] anti-MM regimen. Little is known about early biomarkers of response to cfz. Here we measure CXCR4 and autophagy, which have been implicated in myeloma cell survival, in bone marrow samples from MM patients at baseline and after one day of cfz treatment and analyze the correlation of these biomarkers with clinical response. Methods: Newly diagnosed MM patients received 8 cycles of CRd, followed by 24 cycles of len maintenance on a phase II clinical trial. Cycle one day one comprised cfz only, len and dex were added on day two; for remaining cycles CRd started on day one. Thirty-one paired bone marrow aspirates before and one day after single agent cfz were collected, viably frozen and analyzed for autophagy and CXCR4 expression in plasma cells and lymphoid cells using multiparametric flow cytometry. Malignant plasma cells and non-myelomatous lymphoid cells were identified using phenotypic markers including CD138, CD38, CD45 and CD20. CXCR4 expression was quantified with PE-conjugated anti-CXCR4 antibody and autophagy was quantified with the Cyto-ID Autophagy Detection Kit. Clinical responses were evaluated using standard International Myeloma Working Group criteria. Results: Patients who responded to cfz at 24 hours with a decrease or no change in CXCR4 expression in plasma cells showed early clinical response [stringent complete response (CR) + CR + near CR] in cycles 1-3 compared with those who had an increase in CXCR4 expression (p=0.0069). Autophagy in plasma cells was significantly induced after one day of cfz treatment (p=0.0053). Cfz treatment did not induce autophagy in lymphoid cells. Unlike CXCR4 expression, induction of autophagy in plasma cells was not associated with clinical response. Conclusions: CXCR4 modulation and autophagy induction were observed in MM patients' bone marrow plasma cells after one day of cfz monotherapy. CXCR4 modulation after one day of cfz monotherapy was predictive of early clinical response to CRd regimen. Clinical trial information: NCT01402284.
End restrictions on prescribing Viagra, urges coalition
Authors: G. Yamey
Journal: BMJ (2001)

Two competing manufacturers of the top selling prescription “superaspirins” in the United States, vying for a marketing edge, went before a panel of the US Food and Drug Administration (FDA) last week to ask the government to relax ulcer warnings on their labels but failed to win the expanded wording that they sought.

Traditional non-steroidal anti-inflammatory drugs block both the related enzymes (cyclo-oxygenase-1 (COX 1) and cyclo-oxygenase-2 (COX 2)), which cause inflammation and pain. But COX 1 also protects the stomach lining. Researchers found that they …
Mass spectrometric determination of the rate of depurination of 7-methylguanine, 3-methyladenine and 7-methyladenine after reaction of methyl methanesulfonate with DNA
Authors: Muhammad Zahid, Kevin Olson, Sandra Gunselman, Dhrubajyoti Chakravarti, Eleanor Rogan, Ercole L. Cavalieri
Journal: Cancer Research (2004)

1554  Extensive studies on polycyclic aromatic hydrocarbons (PAH), and endogenous and synthetic estrogens have demonstrated that covalent binding of carcinogens to the N-7 of guanine (Gua) and N-3 and N-7 of adenine (Ade) causes cleavage of the glycosyl bond between the purine base and deoxyribose, leading to depurination of these adducts. The resulting apurinic sites represent a critical intermediate in the production of mutations by error-prone repair (Chakravarti, et. al. Oncogene 20: 7945, 2001). Studies with estradiol-3,4-quinone (E2-3,4-Q) and E2-2,3-Q indicated that depurination of the N3Ade adduct is instantaneous, whereas the N7Gua depurinates slowly with a half life of 3 h. At the same time we observed that treatment of E2-3,4-Q on SENCAR mouse skin generated specifically A to G mutations in the H-ras oncogene. These findings suggest that the apurinic (AP) sites generated by rapid depurination of the N3Ade adduct induce mutations by error-prone repair, whereas the apurinic sites generated by slow depurination can be repaired without mutation. To substantiate this hypothesis, we studied the rate of depurination of 7-CH3guanine (7-CH3Gua), 3-CH3adenine (3-CH3Ade) and 7-CH3Ade after treatment of DNA with methyl methanesulfonate (MMS). MMS is an alkylating agent, which predominantly methylates nitrogen atoms in purine bases. The removal of these lesions leads to the formation of AP sites and could generate AT→TA or GC→TA transversions, if depurination is rapid. Reaction mixtures containing 0.87 mM MMS, 3 mM calf thymus DNA in 0.067 M sodium-potassium phosphate buffer (pH 7.0) in a total volume of 10 ml were incubated at 37°C for 0.5 to 200 h. At each time-point, the DNA was precipitated with two volumes of ethanol and the supernatant was analyzed for methylated adducts by LC-MS. The half lives of 7-CH3Gua, 3-CH3Ade and 7-CH3Ade were found to be approximately 70, 50 and 50 h, respectively. The slow rate of depurination of these adducts will allow further study on the role of fast and slow depurination in mutagenesis. (Supported by grant PO1 CA49210 and RO1 CA49917)
A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma
Authors: Thomas Martin, Rachid Baz, Don M. Benson, Nikoletta Lendvai, Jeffrey Wolf, Pamela Munster, Alexander M. Lesokhin, Claudine Wack, Eric Charpentier, Frank Campana, Ravi Vij
Journal: Blood (2017)
A novel population of immunosuppressive CD8 T cells is expanded in patients with decompensated liver disease
Authors: F. Lebosse, N. Kumar, O. Pop, R. Nathwani, A. Singanayagam, S. Mukherjee, T.Z. Hou, A. Quaglia, F. Zoulim, J. Wendon, M. Thursz, A. Dhar, W. Khamri, C.G. Antoniades
Journal: Journal of Hepatology (2017)
Burden of disease and change in practice in critically ill infants with bronchiolitis
Authors: Luregn J. Schlapbach, Lahn Straney, Ben Gelbart, Janet Alexander, Donna Franklin, John Beca, Jennifer A. Whitty, Subodh Ganu, Barry Wilkins, Anthony Slater, Elizabeth Croston, Simon Erickson, Andreas Schibler
Journal: European Respiratory Journal (2017)

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs).We assessed changes in admission rate, respiratory support, and outcomes of infants <24 months with bronchiolitis admitted to ICU between 2002 and 2014 in Australia and New Zealand.During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11-15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27-0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (p<0.001). We observed considerable variability in practice between units, with six-fold differences in risk-adjusted intubation rates that were not explained by ICU type, size, or major patient factors. Annual direct hospitalisation costs due to severe bronchiolitis increased to over USD30 million in 2014.We observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs.
Developmental transitions: integrating environmental cues with hormonal signaling in the chromatin landscape in plants
Authors: Jun Xiao, Run Jin, Doris Wagner
Journal: Genome biology (2017)

Plant development is predominantly postembryonic and tuned in to respond to environmental cues. All living plant cells can be triggered to de-differentiate, assume different cell identities, or form a new organism. This developmental plasticity is thought to be an adaptation to the sessile lifestyle of plants. Recent discoveries have advanced our understanding of the orchestration of plant developmental switches by transcriptional master regulators, chromatin state changes, and hormone response pathways. Here, we review these recent advances with emphasis on the earliest stages of plant development and on the switch from pluripotency to differentiation in different plant organ systems.
Strong decrease of patients with advanced liver disease and more adherence problems to HCV therapy as DAA regimen enter third year of existence in Germany
Authors: J. Petersen, K. Wursthorn, K. Olah, T. Lorenzen, A. Plettenberg, S. Unger, C. Czaja-Harder, A. Burchard, K. Matschenz, A. Stoehr, P. Buggisch
Journal: Journal of Hepatology (2017)
Self-reactive VH4-34–expressing IgG B cells recognize commensal bacteria
Authors: Jean-Nicolas Schickel, Salomé Glauzy, Yen-Shing Ng, Nicolas Chamberlain, Christopher Massad, Isabelle Isnardi, Nathan Katz, Gulbu Uzel, Steven M. Holland, Capucine Picard, Anne Puel, Jean-Laurent Casanova, Eric Meffre
Journal: The Journal of Experimental Medicine (2017)

The germline immunoglobulin (Ig) variable heavy chain 4–34 (VH4-34) gene segment encodes in humans intrinsically self-reactive antibodies that recognize I/i carbohydrates expressed by erythrocytes with a specific motif in their framework region 1 (FWR1). VH4-34–expressing clones are common in the naive B cell repertoire but are rarely found in IgG memory B cells from healthy individuals. In contrast, CD27+IgG+ B cells from patients genetically deficient for IRAK4 or MYD88, which mediate the function of Toll-like receptors (TLRs) except TLR3, contained VH4-34–expressing clones and showed decreased somatic hypermutation frequencies. In addition, VH4-34–encoded IgGs from IRAK4- and MYD88-deficient patients often displayed an unmutated FWR1 motif, revealing that these antibodies still recognize I/i antigens, whereas their healthy donor counterparts harbored FWR1 mutations abolishing self-reactivity. However, this paradoxical self-reactivity correlated with these VH4-34–encoded IgG clones binding commensal bacteria antigens. Hence, B cells expressing germline-encoded self-reactive VH4-34 antibodies may represent an innate-like B cell population specialized in the containment of commensal bacteria when gut barriers are breached.
Whole transcriptome analysis of ductular reaction from patients with alcoholic hepatitis. Similarities to ductular reaction in DDC mouse model
Authors: B. Aguilar-Bravo, D. Rodrigo-Torres, M. Coll, L. Revilla, D. Blaya, L. Perea, J. Vallverdú, I. Graupera, L. Dubuquoy, P. Mathurin, J. Caballeria, P. Gines, P. Sancho-Bru
Journal: Journal of Hepatology (2017)
Long-term prognosis following acute-on-chronic liver failure
Authors: E.L. Yoon, T.Y. Kim, D.S. Song, H.Y. Kim, C.W. Kim, Y.K. Jung, D.H. Sinn, J.Y. Jang, M.Y. Kim, S.W. Jeong, S.G. Kim, E. Choi, K.T. Suk, D.J. Kim
Journal: Journal of Hepatology (2017)
A phase I/II study of the MEK inhibitor BAY 86-9766 (BAY) in combination with gemcitabine (GEM) in patients with nonresectable, locally advanced or metastatic pancreatic cancer (PC): Phase I dose-escalation results.
Authors: Jean-Luc Van Laethem, Volker Heinemann, Uwe Marc Martens, Jacek Jassem, Patrick Michl, Marc Peeters, Colin D. Weekes, Raphael Maréchal, Jens Stieler, Marius Giurescu, Prabhu Rajagopalan, Vittorio Luigi Garosi, Hanno Riess
Journal: Journal of Clinical Oncology (2012)

4050 Background: Targeting the RAS–RAF–MEK–ERK pathway may be useful in the treatment of PC, as 75–90% of PCs have KRAS mutation. BAY is an orally bioavailable, potent, allosteric MEK 1/2 inhibitor that showed single-agent activity, and synergistic activity with GEM, in ectopic, orthotopic, syngenic and patient-derived xenograft PC models. Methods: The phase I part aimed to determine the maximum tolerated dose (MTD) of BAY in combination with GEM, and the pharmacokinetics of BAY and GEM. 3+3 study design was used. After informed consent, eligible patients with advanced PC received GEM 1000 mg/m 2 (30-min, once-weekly IV infusion for 7 out of 8 weeks in cycle 1 [C1], and 3 out of 4 weeks in subsequent cycles) and oral BAY 30 mg BID (dose level 1 [DL1]) or 50 mg BID (DL2). No escalation beyond DL2 was planned. MTD was the highest dose at which maximum 1 out of 6 evaluable patients displayed dose-limiting toxicities (DLT) during C1. Results: As of 6 Jan 2012, 17 patients were enrolled and treated (10 at DL1, 7 at DL2). DL1 cohort has completed; DL2 evaluation is ongoing. At DL1, DLTs occurred in 1/6 evaluable patients: a patient with extensive liver metastasis developed chemotherapy-associated steatohepatitis (CASH) and died of hepatic failure. Rare CASH cases have been reported to be associated with GEM alone, but co-involvement of BAY currently cannot be ruled out. To date, 3 patients have completed C1 at DL2 without DLTs. DL2 completion is expected in March 2012. BAY+GEM showed a manageable tolerability profile. The most frequent treatment-related grade 3–4 adverse event (AE) at any DL was neutropenia (n=6). The most frequent clinically relevant BAY-related AE was acneiform rash (n=11), which was mostly grade 1–2 (one case grade 3) and manageable. BAY+GEM showed evidence of clinical efficacy: partial responses were seen in 4/10 patients at DL1 and 1/3 patients at DL2. No pharmacokinetic interaction between BAY and GEM was seen at DL1. Conclusions: In patients with advanced PC, BAY 30 mg BID in combination with GEM had a manageable safety profile, with acneiform rash as the clinically most relevant toxicity attributable to BAY.
Comparative Evaluation of Prognostic Factors That Assess the Natural History of Chronic Lymphocytic Leukemia
Authors: Brian Giacopelli, Amy S. Ruppert, Yue-Zhong Wu, Laura Z. Rassenti, William G. Wierda, Kanti R Rai, Neil E. Kay, Jennifer R. Brown, Thomas J. Kipps, John C. Byrd, Christopher C Oakes
Journal: Blood (2016)
Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer
Authors: Amanda E D Van Swearingen, Maria J Sambade, Marni B Siegel, Shivani Sud, Robert S McNeill, Samantha M Bevill, Xin Chen, Ryan E Bash, Louisa Mounsey, Brian T Golitz, Charlene Santos, Allison Deal, Joel S Parker, Naim Rashid, C Ryan Miller, Gary L Johnson, Carey K Anders
Journal: Neuro-Oncology (2017)

Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases. Using human-derived TNBC cell lines, synthetic lethal small interfering RNA kinase screens were evaluated with brain-penetrant inhibitors against MEK1/2 (selumetinib, AZD6244) or phosphatidylinositol-3 kinase (PI3K; buparlisib, BKM120). Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination. Tumors were analyzed by western blot and multiplexed kinase inhibitor beads/mass spectrometry to assess treatment effects. Screens identified MEK+PI3K and MEK+PDGFR inhibitors as tractable, rational combinations. Dual treatment of selumetinib with buparlisib or pazopanib was synergistic in TNBC cells in vitro. Both combinations improved survival in intracranial SUM149 and MDA-MB-231Br, but not MDA-MB-468 or MDA-MB-436. Treatments decreased mitogen-activated protein kinase (MAPK) and PI3K (Akt) signaling in sensitive (SUM149 and 231Br) but not resistant models (MDA-MB-468). Exploratory analysis of kinome reprogramming in SUM149 intracranial tumors after MEK ± PI3K inhibition demonstrates extensive kinome changes with treatment, especially in MAPK pathway members. Results demonstrate that rational combinations of the clinically available inhibitors selumetinib with buparlisib or pazopanib may prove to be promising therapeutic strategies for the treatment of some TNBC brain metastases. Additionally, effective combination treatments cause widespread alterations in kinase pathways, including targetable potential resistance drivers.
Free fatty acids enhance CD36 knockdown in primary human hepatocytes and abrogate PTEN expression – recapitulation of NASH-associated HCC
Authors: Ö. Kücükoglu, C. Labenz, S. Sydor, M. Schlattjan, J. Best, G. Gerken, A. Canbay, J.-P. Sowa
Journal: Journal of Hepatology (2017)