tbuckley/cabot-search huggingface dataset:
P2.04-10 Biomarkers of Pathological Response on Neo-Adjuvant Chemo-Immunotherapy Treatment for Resectable Stage IIIA NSCLC Patients
Authors: R. Laza-Briviesca, A. Cruz-Bermudez, M. Casarrubios, E. Nadal, A. Insa, R. Garcia Campelo, N. De Dios Alvarez, M. Domine, M. Majem, D. Rodriguez-Abreu, V. Calvo De Juan, A. Martinez-Marti, J. De Castro Carpeno, M. Cobo, G. López-Vivanco, E. Del Barco, R. Bernabe, N. Viñolas, I. Barneto, S. Viteri, B. Massuti, M. Provencio
Journal: Journal of Thoracic Oncology (2019)
Colony-Stimulating Factor 1 Receptor (CSF1R) Activates AKT/mTOR Signaling and Promotes T-Cell Lymphoma Viability
Authors: Carlos Murga-Zamalloa, Delphine C.M. Rolland, Avery Polk, Ashley Wolfe, Hiran Dewar, Pinki Chowdhury, Ozlem Onder, Rajan Dewar, Noah A. Brown, Nathanael G. Bailey, Kedar Inamdar, Megan S. Lim, Kojo S.J. Elenitoba-Johnson, Ryan A. Wilcox
Journal: Clinical Cancer Research (2019)

Peripheral T-cell lymphomas are clinically aggressive and usually fatal, as few complete or durable remissions are achieved with currently available therapies. Recent evidence supports a critical role for lymphoma-associated macrophages during T-cell lymphoma progression, but the specific signals involved in the cross-talk between malignant T cells and their microenvironment are poorly understood. Colony-stimulator factor 1 receptor (CSF1R, CD115) is required for the homeostatic survival of tissue-resident macrophages. Interestingly, its aberrant expression has been reported in a subset of tumors. In this article, we evaluated its expression and oncogenic role in T-cell lymphomas.Loss-of-function studies, including pharmacologic inhibition with a clinically available tyrosine kinase inhibitor, pexidartinib, were performed in multiple in vitro and in vivo models. In addition, proteomic and genomic screenings were performed to discover signaling pathways that are activated downstream of CSF1R signaling.We observed that CSF1R is aberrantly expressed in many T-cell lymphomas, including a significant number of peripheral and cutaneous T-cell lymphomas. Colony-stimulating factor 1 (CSF1), in an autocrine or paracrine-dependent manner, leads to CSF1R autophosphorylation and activation in malignant T cells. Furthermore, CSF1R signaling was associated with significant changes in gene expression and in the phosphoproteome, implicating PI3K/AKT/mTOR in CSF1R-mediated T-cell lymphoma growth. We also demonstrated that inhibition of CSF1R in vivo and in vitro models is associated with decreased T-cell lymphoma growth.Collectively, these findings implicate CSF1R in T-cell lymphomagenesis and have significant therapeutic implications.
EP1.16-13 Characteristics and Clinical Outcomes in Patients with Non-Small Cell Lung Carcinoma in Fundacion Santa Fe De Bogota: 42 Months Experience
Authors: A.V. Ospina Serrano, L.E. Pino Villareal, J.M. Segovia Gomez, I.C. Triana Avellaneda
Journal: Journal of Thoracic Oncology (2019)
P1.01-88 PS 2 Patients with Advanced EGFR Mutant NSCLC: Subset Analysis of a Phase III Randomized Trial Comparing Gefitinib to Gefitinib with Chemotherapy
Authors: K. Prabhash, V. Noronha, V. Patil, A. Joshi, A. Chougule
Journal: Journal of Thoracic Oncology (2019)
MA21.05 Phase II Trial of the Combination of Alectinib with Bevacizumab in ALK-Positive Nonsquamous Non-Small Cell Lung Cancer
Authors: S. Watanabe, N. Matsumoto, J. Koshio, A. Ishida, T. Tanaka, T. Abe, D. Ishikawa, S. Shoji, K. Nozaki, K. Ichikawa, R. Kondo, A. Otsubo, A. Aoki, T. Kajiwara, K. Koyama, S. Miura, H. Yoshizawa, T. Kikuchi
Journal: Journal of Thoracic Oncology (2019)
EP1.03-07 Prevalence and Clinicopathological Characteristics of EIF1AX Mutations in Chinese Patients with Non-Small Cell Lung Cancer
Authors: W. Wang, C. Xu, Q. Zhang, W. Zhuang, Y. Zhu, Y. Huang, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2019)
Recent advances in the development of nanoparticles for multimodality imaging and therapy of cancer
Authors: Mei Liu, Redmond‐Craig Anderson, Xiaoli Lan, Peter S. Conti, Kai Chen
Journal: Medicinal Research Reviews (2019)

This review explores recent work directed toward the development of nanoparticles (NPs) for multimodality cancer imaging and targeted cancer therapy. In the growing era of precision medicine, theranostics, or the combined use of targeted molecular probes in diagnosing and treating diseases is playing a particularly powerful role. There is a growing interest, particularly over the past few decades, in the use of NPs as theranostic tools due to their excellent performance in receptor target specificity and reduction in off-target effects when used as therapeutic agents. This review discusses recent advances, as well as the advantages and challenges of the application of NPs in cancer imaging and therapy.
EP1.04-41 Efficacy of Immunotherapy in Elderly Patients with Non-Small Cell Lung Cancer: A Multicentric Experience from Argentina
Authors: M. Rizzi, N. Minatta, M. Rizzo, G. Recondo, M. Naveira, L. Lupinacci, A. Kuzminin, M. Faura, A. Perfetti, S. Sena, M. Bluthgen
Journal: Journal of Thoracic Oncology (2019)
Central metal-derived co-assembly of biomimetic GdTPP/ZnTPP porphyrin nanocomposites for enhanced dual-modal imaging-guided photodynamic therapy
Authors: Jiefei Wang, Zhongjie Wang, Yong Zhong, Yan Zou, Chong Wang, Haigang Wu, Albert Lee, Weitao Yang, Xiao Wang, Yanjie Liu, Dongya Zhang, Jiliang Yan, Mingcong Hao, Meng Zheng, Roger Chung, Feng Bai, Bingyang Shi
Journal: Biomaterials (2019)
Response to ‘Application of MS score in macrophage activation syndrome patients associated with adult onset Still’s disease’ by Wang <i>et al</i>
Authors: Francesca Minoia, Angelo Ravelli
Journal: Annals of the Rheumatic Diseases (2019)

We are grateful to Wang et al 1 for testing our diagnostic score for macrophage activation syndrome (MAS)2 in their patients with adult onset Still disease (AOSD). Because it is increasingly recognised that systemic juvenile idiopathic arthritis (sJIA) and AOSD represent the same disease occurring at different ages3 4 and considering that the two illnesses share a similar risk for MAS, it is important to investigate whether the current diagnostic tools are applicable to both conditions.

Wang and colleagues evaluated retrospectively the capacity of the MAS/sJIA (MS) score to detect MAS in AOSD by comparing 60 patients with MAS, whose diagnosis was made by HLH-2004 criteria and confirmed by the caring rheumatologists, with 390 patients without MAS. They found that the application of the MS score with the cut-off of ≥ –2.1 obtained in our study yielded a maximum …
P2.01-72 Safety of Palliative Radiotherapy and Immune Checkpoint Inhibitors in Patients with Metastatic Non-Small Cell Lung Cancer
Authors: M. Tjong, M. Ragulojan, I. Poon, S. Cheng, M. Doherty, Y. Ung, P. Cheung, P. Cheema
Journal: Journal of Thoracic Oncology (2019)
Expression of angiogenic mediators in head and neck cancer
Authors: M. Usó, R. Sirera, E. Jantus Lewintre, N. Mosquera, E. Zapater, A. Cabrera, E. Sanmartín, A. Berrocal, J. Basterra, C. Camps
Journal: Journal of Clinical Oncology (2009)

e17032 Background: In cancer, systematic analysis of mRNA expression levels can contribute to define a molecular network of lung carcinogenesis and establish predictive and prognostic molecular markers. Altered mRNA expression in certain angiogenic and anti-angiogenic genes such as vascular endothelial growth factor family of ligands and their receptors together with other molecules implicated in angiogenesis could predict disease outcome and add prognostic information at diagnosis. Methods: We performed RT-qPCR in frozen head and neck cancer specimens from untreated patients who had undergone surgical resection (n = 23). Samples were processed for mRNA extraction following standard procedures and quantification of gene expression was expressed as relative concentration normalized by an endogenous gene. The following angiogenic genes were quantified: PDGF-A, PlGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D, COX-2, bFGF, HGF, IL-8; and anti-angiogenic genes: Angiomotin and endostatin. Results: Median age was 56.5 years, range (31–79), 17 patients presented squamous carcinoma of the larynx; 8 patients were stage III and the other 15 stage IV. None of the patients received pre-surgery chemo or radiotherapy and 10 patients reveived post-surgery treatment. Our results show that tumor samples had significant higher expression of PDGF, PlGF, COX-2, and IL-8 and a deep down-regulation of angiomotin. However, those data show no correlation between the levels of expression and stage of the disease. Conclusions: Our results reveal that there is an increase in the expression of the pro-angiogenic mediators PDGF, PlGF, COX-2, and IL-8 and a downregulation of angiomotin that may mediate the inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels in the tumoral area. This data suggest that more research are needed in other angiogenic mediators that VEGF, that PlGF and angiomotin have some role in cancer progression and could be a promising new biomarker in head and neck cancer. No significant financial relationships to disclose.
Global patterns of opioid use and dependence: harms to populations, interventions, and future action
Authors: Louisa Degenhardt, Jason Grebely, Jack Stone, Matthew Hickman, Peter Vickerman, Brandon D L Marshall, Julie Bruneau, Frederick L Altice, Graeme Henderson, Afarin Rahimi-Movaghar, Sarah Larney
Journal: The Lancet (2019)
Counseling Reduces Physician Burnout
Authors: Anita Slomski
Journal: JAMA (2019)

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
P1.11-12 Genetic Landscape and Immune Microenvironment Features in Recurrence in Stage IA of Lung Adenocarcinoma
Authors: L. Yang, J. Zhang, H. Xu, G. Yang, F. Xu, Y. Song, X. Shi, L. Wu, H. Zhang, J. Ying, Y. Wang
Journal: Journal of Thoracic Oncology (2019)
P1.01-31 Evaluating Engineered Heme-Sequestering Peptides for Treating Non-Small Cell Lung Cancer Orthotopic Tumor Model Using Multi-Modality Imaging
Authors: S. Zhong, J. Chen, J. Campbell, J. Gerberich, G. Hao, L. Zhang, L. Liu
Journal: Journal of Thoracic Oncology (2019)
P1.04-44 Radiomics for Predicting Response to First-Line Anti-PD1 Therapy in Advanced NSCLC
Authors: C. Ackermann, I. Fornacon-Wood, R. Tay, P. Manoharan, G. Price, C. Lindsay, C. Faivre-Finn, F. Blackhall, D. Cobben
Journal: Journal of Thoracic Oncology (2019)
MA07.02 Early Change of dNLR Is Correlated with Outcomes in Advanced NSCLC Patients Treated with Immunotherapy
Authors: L. Mezquita, I. Preeshagul, E. Auclin, D. Saravia, L. Hendriks, H. Rizvi, D. Planchard, W. Park, E. Nadal, J.C. Ruffinelli, S. Ponce, C. Audigier-Valette, S. Carnio, S. Novello, G. Zalcman, M. Majem, A. Mariniello, A.M. Dingemans, G. Lopes, C. Rossoni, J. Pignon, N. Chaput, M. Hellmann, K. Arbour, B. Besse
Journal: Journal of Thoracic Oncology (2019)
Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade
Authors: Imran G. House, Peter Savas, Junyun Lai, Amanda X.Y. Chen, Amanda J. Oliver, Zhi L. Teo, Kirsten L. Todd, Melissa A. Henderson, Lauren Giuffrida, Emma V. Petley, Kevin Sek, Sherly Mardiana, Tuba N. Gide, Camelia Quek, Richard A. Scolyer, Georgina V. Long, James S. Wilmott, Sherene Loi, Phillip K. Darcy, Paul A. Beavis
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Response rates to immune checkpoint blockade (ICB; anti-PD-1/anti-CTLA-4) correlate with the extent of tumor immune infiltrate, but the mechanisms underlying the recruitment of T cells following therapy are poorly characterized. A greater understanding of these processes may see the development of therapeutic interventions that enhance T-cell recruitment and, consequently, improved patient outcomes. We therefore investigated the chemokines essential for immune cell recruitment and subsequent therapeutic efficacy of these immunotherapies. Experimental Design: The chemokines upregulated by dual PD-1/CTLA-4 blockade were assessed using NanoString-based analysis with results confirmed at the protein level by flow cytometry and cytometric bead array. Blocking/neutralizing antibodies confirmed the requirement for key chemokines/cytokines and immune effector cells. Results were confirmed in patients treated with immune checkpoint inhibitors using single-cell RNA-sequencing (RNA-seq) and paired survival analyses. Results: The CXCR3 ligands, CXCL9 and CXCL10, were significantly upregulated following dual PD-1/CTLA-4 blockade and both CD8+ T-cell infiltration and therapeutic efficacy were CXCR3 dependent. In both murine models and patients undergoing immunotherapy, macrophages were the predominant source of CXCL9 and their depletion abrogated CD8+ T-cell infiltration and the therapeutic efficacy of dual ICB. Single-cell RNA-seq analysis of patient tumor-infiltrating lymphocytes (TIL) revealed that CXCL9/10/11 was predominantly expressed by macrophages following ICB and we identified a distinct macrophage signature that was associated with positive responses to ICB. Conclusions: These data underline the fundamental importance of macrophage-derived CXCR3 ligands for the therapeutic efficacy of ICB and highlight the potential of manipulating this axis to enhance patient responses.
P2.14-25 Lorlatinib Induced Protective Autophagy via the AKT–mTOR Pathway in ALK- Rearrangement Lung Cancer Cells
Authors: C. Lu, L. Li, H. Rui, C. Lin, S. Hao, C. Hu, Y. Wang, H. Chen, H. Yong
Journal: Journal of Thoracic Oncology (2019)
Uncovering the mechanisms of exertional dyspnoea in combined pulmonary fibrosis and emphysema
Authors: Camila M. Costa, J. Alberto Neder, Carlos G. Verrastro, Marcelle Paula-Ribeiro, Roberta Ramos, Eloara M. Ferreira, Luiz E. Nery, Denis E. O'Donnell, Carlos A.C. Pereira, Jaquelina Ota-Arakaki
Journal: European Respiratory Journal (2019)

The prevailing view is that exertional dyspnoea in patients with combined idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) can be largely explained by severe hypoxaemia. However, there is little evidence to support these assumptions. We prospectively contrasted the sensory and physiological responses to exercise in 42 CPFE and 16 IPF patients matched by the severity of exertional hypoxaemia. Emphysema and pulmonary fibrosis were quantified using computed tomography. Inspiratory constraints were assessed in a constant work rate test: capillary blood gases were obtained in a subset of patients. CPFE patients had lower exercise capacity despite less extensive fibrosis compared to IPF (p=0.004 and 0.02, respectively). Exertional dyspnoea was the key limiting symptom in 24 CPFE patients who showed significantly lower transfer factor, arterial carbon dioxide tension and ventilatory efficiency (higher minute ventilation ( V ′ E )/carbon dioxide output ( V ′ CO 2 ) ratio) compared to those with less dyspnoea. However, there were no between-group differences in the likelihood of pulmonary hypertension by echocardiography (p=0.44). High dead space/tidal volume ratio, low capillary carbon dioxide tension emphysema severity (including admixed emphysema) and traction bronchiectasis were related to a high V ′ E / V ′ CO 2 ratio in the more dyspnoeic group. V ′ E / V ′ CO 2 nadir &gt;50 (OR 9.43, 95% CI 5.28–13.6; p=0.0001) and total emphysema extent &gt;15% (2.25, 1.28–3.54; p=0.01) predicted a high dyspnoea burden associated with severely reduced exercise capacity in CPFE Contrary to current understanding, hypoxaemia per se is not the main determinant of exertional dyspnoea in CPFE. Poor ventilatory efficiency due to increased “wasted” ventilation in emphysematous areas and hyperventilation holds a key mechanistic role that deserves therapeutic attention.
MA14.05 A Randomized Phase III Trial of Fruquintinib Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (FALUCA)
Authors: S. Lu, G. Chen, Y. Sun, S. Sun, J. Chang, Y. Yao, Z. Chen, F. Ye, J. Lu, J. Shi, J. He, X. Liu, Y. Zhang, Z. Liu, J. Fang, Y. Cheng, C. Hu, W. Mao, Y. Hu, Y. Gong, L. Shan, Z. Yang, Y. Song, W. Li, C. Bai, B. Wang, R. Ma, Z. Zheng, M. Liu, Z. Jie, L. Cao, W. Liao, H. Pan, D. Huang, Y. Chen, J. Yang, S. Qin, S. Ma, L. Liang, Z. Liu, J. Zhou, M. Tao, Y. Huang, F. Qiu, Y. Huang, Y. Hua, Y. Chen, W. Su
Journal: Journal of Thoracic Oncology (2019)
P1.01-97 Modified RANO-LM Criteria to Evaluate the Radiological Response of Osimertinib in EGFR T790M Positive NSCLC with Leptomeningeal Metastases
Authors: M. Seong, S. Park, H.A. Jung, J. Sun, S. Lee, J.S. Ahn, K. Park, S.T. Kim, M. Ahn
Journal: Journal of Thoracic Oncology (2019)
Novel property of Se-methyl-L-selenocysteine as a histone deacetylase inhibitor in human prostate cancer cells.
Authors: Jeong-In Lee, Arthur Cooper, Raghu Sinha, John Pinto
Journal: Cancer Research (2008)

3048  Studies show that histone deacetylase (HDAC) inhibitors disrupt the cell cycle and/or induce apoptosis and that cancer cells appear to be more sensitive than non-transformed cells. With the knowledge that epidemiological studies support a protective role of organoselenium against development of prostate cancer, we hypothesize that Se-methyl-L-selenocysteine (MSC), a component of selenium-enriched yeast, is metabolized to an HDAC inhibitor and regulates proliferative and/or apoptotic responses in human prostate cancer cells. An aminotransferase (glutamine transaminase K) and L-amino acid oxidase convert MSC to the corresponding α-keto acid (β-methylselenopyruvate, BMS) in a cell-free system. Both enzymes also catalyze a β-elimination side reaction yielding pyruvate, ammonium and methylselenol. BMS structurally resembles the HDAC inhibitor, butyrate, but with the potential redox action of selenium targeting a zinc-thiolate ligand in the active site. To test our hypothesis, both androgen responsive (LNCaP) and androgen independent (C4-2, PC-3 and DU145) prostate cancer cells were cultured for various time intervals in medium supplemented with MSC. Acetylated histones (as evidence of HDAC inhibition) and HDAC activity were measured in nuclear and cytosolic fractions. Results show that nuclear expression of acetylated histone 3 was significantly increased by 24-h in all MSC-treated cell lines, demonstrating the attenuation of HDAC activity. By contrast, MSC itself had no direct HDAC inhibitory activity in nuclear extracts (LNCaP, C4-2, PC-3 and DU145), suggesting that a metabolite(s) of MSC, rather than MSC itself, inhibits HDAC activity in prostate cancer cells. HPLC analysis of cytosolic extracts incubated with MSC in a transamination reaction mixture with α-keto-γ-methiolbutyrate showed metabolism of MSC with concomitant formation of a transaminase product, tentatively identified as BMS. In addition to a transamination product, a β-elimination product (methylselenol) may also contribute to control of prostate cancer progression. MSC and/or its metabolite(s) down-regulate the levels of Redox Factor-1 and NF-κB, redox sensitive proteins that affect cellular proliferative and apoptotic responses. This study demonstrates a previously unrecognized effect of MSC as an HDAC inhibitor in addition to targeting redox-sensitive signaling proteins and transcription factors and adds a new understanding to mechanisms by which naturally-occurring organoselenium prevents progression of human prostate cancer. Supported by NCI RO1 CA11184 and NIH R01 ES08421.
P2.01-98 Neutrophil-Platelet Score (NPS), a Predictive Systemic Inflammation Score for Pembrolizumab in First Line of Advanced NSCLC Patients
Authors: X. Mielgo Rubio, P. Cruz, M. Sereno, L.E. Chara, L. Cabezon-Gutierrez, A. Velastegui, A. López, R. Lopez Castro, M. Sotelo, J. Rubio, J.A. Núñez, E. Pérez Fernández, C. Olier, J. De Castro Carpeno, M. Antoñanzas, S. Falagan, I. Nalda Ariza, S. Custodio, P. Dhimes, C. Aguado
Journal: Journal of Thoracic Oncology (2019)
Endoscopic ultrasound-guided gallbladder drainage, transpapillary drainage, or percutaneous drainage in high risk acute cholecystitis patients: a systematic review and comparative meta-analysis
Authors: Babu P. Mohan, Shahab R. Khan, Sushruth Trakroo, Suresh Ponnada, Mahendran Jayaraj, Ravishankar Asokkumar, Douglas G. Adler
Journal: Endoscopy (2019)

Endoscopic transpapillary gallbladder drainage (ETGBD) and endoscopic ultrasound-guided gallbladder drainage (EUSGBD) are alternatives to percutaneous gallbladder drainage (PCGBD) for patients with acute cholecystitis who are unfit for surgery. Data comparing these modalities are limited and have reported conflicting results.We searched multiple databases from inception to May 2019 to identify studies that reported on ETGBD, EUSGBD, and PCGBD in the management of acute cholecystitis in patients with a high surgical risk. Aims were to compare the pooled rates of technical success, clinical success, adverse events, and disease recurrence.1223 patients (22 studies), 557 patients (14 studies), and 13 351 patients (46 studies) were treated by ETGBD, EUSGBD, and PCGBD, respectively. The pooled technical and clinical successes were: ETGBD 83 % (95 % confidence interval [CI] 80.1 - 85.5, I2 = 29) and 88.1 % (95 %CI 83.6 - 91.4, I2 = 50), respectively; EUSGBD 95.3 % (95 %CI 92.8 - 96.9, I2 = 0) and 96.7 % (95 %CI 94.0 - 98.2, I2 = 0), respectively; and PCGBD 98.7 % (95 %CI 98.0 - 99.1, I2 = 0) and 89.3 % (95 %CI 86.6 - 91.5, I2 = 84), respectively. Clinical success with EUSGBD was significantly superior to the other approaches. All complications were comparable between the groups. Pancreatitis occurred with ETGBD in 5.1 % (95 %CI 3.5 - 7.3), whereas bleeding and perforation occurred with EUSGBD in 4.3 % (95 %CI 2.7 - 6.8) and 3.7 % (95 %CI 2.3 - 6.0), respectively. Stent migration occurred with PCGBD in 7.4 % (95 %CI 5.5 - 10.0).EUSGBD demonstrated better clinical success than ETGBD and PCGBD in the management of acute cholecystitis patients at high surgical risk.
Comprehensive Analysis of ERK1/2 Substrates for Potential Combination Immunotherapies
Authors: Lei Yang, Liangzhen Zheng, Wee Joo Chng, Jeak Ling Ding
Journal: Trends in Pharmacological Sciences (2019)

Recent clinical and therapeutic success with RAF and MEK1/2 inhibitors has revolutionized the existing treatment schemes for previously incurable cancers like melanomas. However, the overall therapeutic efficacies are still largely compromised by the dose-limiting side effects and emerging drug resistance mechanisms. Accumulating evidence has revealed the intricate nature of the RAS-RAF-MEK1/2-ERK1/2 pathway, such as activation mechanisms, kinase-substrate relationships, crosstalk with parallel signaling pathways, feedback regulations, and intimate interplay with immune responses. Limited strategies are currently available to exploit the benefits of combining RAF-MEK1/2-ERK1/2 pathway inhibitors with other targeted therapies or immunotherapies. Here, we compiled the kinase-substrate relationships and analyzed the intricate signaling networks of the renowned pathway, providing an integrated and simplified visualization, to reveal the potentials of RAS-RAF-MEK1/2-ERK1/2-based combination therapies.