tbuckley/cabot-search huggingface dataset:
GS-006 Glucagon and GLP-1 receptor dual agonist survodutide improved liver histology in people with MASH and fibrosis: Results from a randomized, double-blind, placebo-controlled phase 2 trial
Authors: Arun J Sanyal, Pierre Bedossa, Mandy Fraessdorf, Guy Neff, Eric Lawitz, Elisabetta Bugianesi, Quentin M. Anstee, Samina Ajaz Hussain, Philip N. Newsome, Vlad Ratziu, Azadeh Hosseini-Tabatabaei, Jörn M Schattenberg, Mazen Noureddin, Naim Alkhouri, Ramy Younes
Journal: Journal of Hepatology (2024)
THU-114 Alkaline phosphatase levels at 6 months as a predictor of response to ursodeoxycholic acid at 1 year in patients with primary biliary cholangitis
Authors: Carmen Sendra, María del Pilar Silva-Ruiz, Carlota Jimeno Mate, Patricia Cordero Ruiz, Domingo Pérez-Palacios, Gema Romero, Isabela Angulo-Mcgrath, Pablo Quiros-Rivero, Jose Miguel Rosales-Zábal, Jose Manuel Sousa-Martin
Journal: Journal of Hepatology (2024)
FRI-485 CHKA, a potential target marker for early-stage metabolic dysfunction associated steatotic liver disease induced hepatocellular carcinoma with low fibrosis level: analysis by metabolomic and transcriptomic
Authors: Jihan Sun, Fatima Dahboul, Estelle Pujos-Guillot, Stephanie Durand, Mélanie Petera, Delphine Centeno, Benoit Colsch, Guillaume Zoulim, Delphine Weil-Verhoeven, Vincent Di Martino, Aicha Demidem, Armand Abergel
Journal: Journal of Hepatology (2024)
Personalized cancer T-cell therapy takes the stage, mirroring vaccine success
Authors: Johanna Chiffelle, Alexandre Harari
Journal: The Journal of Experimental Medicine (2024)

Personalized T-cell therapy is emerging as a pivotal treatment of cancer care by tailoring cellular therapies to individual genetic and antigenic profiles, echoing the exciting success of personalized vaccines. We describe here the parallel evolution and analogies of cancer vaccines and T-cell therapies.
CDK4/6 Alters TBK1 Phosphorylation to Inhibit the STING Signaling Pathway in Prostate Cancer
Authors: Wei Li, Feng Guo, Ruijiang Zeng, Huaiyuan Liang, Yinhuai Wang, Wei Xiong, Heshui Wu, Chunguang Yang, Xin Jin
Journal: Cancer Research (2024)

The efficacy of immunotherapy in patients with prostate cancer is limited due to the "cold" tumor microenvironment and the paucity of neoantigens. The STING-TBK1-IRF3 signaling axis is involved in innate immunity and has been increasingly recognized as a candidate target for cancer immunotherapy. Here, we found that treatment with CDK4/6 inhibitors stimulates the STING pathway and enhances the antitumor effect of STING agonists in prostate cancer. Mechanistically, CDK4/6 phosphorylated TBK1 at S527 to inactivate the STING signaling pathway independent of RB1 in prostate cancer cells. CDK4/6-mediated phosphorylation of RB1 at S249/T252 also induced the interaction of RB1 with TBK1 to diminish the phosphorylation of TBK1 at S172, which suppressed STING pathway activation. Overall, this study showed that CDK4/6 suppresses the STING pathway through RB1-dependent and RB1-independent pathways, indicating that CDK4/6 inhibition could be a potential strategy to overcome immunosuppression in prostate cancer. Significance: Inhibiting CDK4/6 activates STING-TBK1-IRF3 signaling in prostate cancer by regulating TBK1 phosphorylation, suggesting that the combination of CDK4/6 inhibitors and STING agonists could be an effective approach to stimulate innate immunity.
Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease
Authors: Tzu-Lung Lin, Yen-Liang Kuo, Juo-Hsin Lai, Chia-Chen Lu, Chang-Tsu Yuan, Chi-Yu Hsu, Bo-Shiun Yan, Lawrence Shih-Hsin Wu, Ting-Shu Wu, Jann-Yuan Wang, Chong-Jen Yu, Hsin-Chih Lai, Jwu-Ching Shu, Chin-Chung Shu
Journal: Gut Microbes (2024)

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of
How an opioid giant deployed a playbook for moulding doctors’ minds
Authors: Sergio Sismondo, Maud Bernisson
Journal: BMJ (2024)

The opioid giant Mallinckrodt, selling more in the US than Purdue Pharma, was forced by the courts to publish more than 1.3 million internal documents. <b>Sergio Sismondo</b> and <b>Maud Bernisson</b> sift through nearly 900 contracts to reveal the tricks used to shape scientific and medical opinions
Ursolic acid: A promising therapeutic agent for NAFLD via inhibition of SPP1-induced Th17 cell differentiation
Authors: So Jung Kim, Jeongeun Hyun
Journal: Clinical and Molecular Hepatology (2024)

Ursolic acid inhibits pro-inflammatory SPP1 in NAFLD Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, encompassing a spectrum of pathological conditions from simple steatosis to non-alcoholic steatohepatitis (NASH), with or without hepatic fibrosis.The global prevalence and incidence of NAFLD are rising in parallel with the epidemics of obesity and metabolic syndrome. 1If NAFLD worsens, it can lead to life-threatening liver damage, including cirrhosis and liver cancer, necessitating proper clinical management in advance.The first-line treatment for NAFLD is weight loss through lifestyle changes, which can reduce hepatic fat and inflammation. 2However, not all patients succeed in losing weight, and NAFLD can occur in both obese and non-obese populations.Although several medicines for metabolic syndrome, such as those for diabetes, obesity, and hyperlipidemia, have been used for NAFLD treatment, these drugs have shown only partial efficacy. 3Currently, only one medicine, Resmetirom (Rezdiffra), which obtained U.S. Food and Drug Administration's approval in 2024, is available for the treatment of non-cirrhotic NASH with moderate to severe liver fibrosis.The global drug market for NAFLD is actively working to develop new medications and obtain approval for a wide spectrum of NAFLD, addressing the significant clinical unmet needs.Ursolic acid, discovered in apple feels in the early 1920s and found abundantly in various fruits and vegetables, is a natural pentacyclic triterpenoid with multiple beneficial effects against oxidative stress, inflammation, and tumorigenesis in various organs, including the skin, colon, breast, and liver. 4Recent studies have shown that ursolic acid can ameliorate insulin resistance, hepatic steatosis, inflammation, and liver hypoxia, which can induce metabolic dysfunctions, and liver fibrosis in preclinical models. 5
Meeting the challenges of HCC post SVR in the Post-DAA Era: A Path Forward
Authors: Seren M. Gedallovich, Paul Y. Kwo
Journal: Clinical and Molecular Hepatology (2024)

Infection with chronic Hepatitis C virus (HCV) has been a major cause of hepatocellular carcinoma (HCC) worldwide.In patients with active viral cirrhosis , there is a 2-5% annual incidence of HCC 1 .The development of direct-acting antiviral (DAA) therapies has led to cure of HCV with sustained virologic response (SVR) in >95% of those treated.Cohort studies have demonstrated up to 70% reduction in risk of development of HCC compared to those who remain viremic 2 .Nevertheless, the risk of HCC post-SVR persists leading to a growing proportion of HCC cases in the post-DAA era.In this issue of Clinical and Molecular Hepatology, Huang et al. discuss risk factors, pathophysiology, and screening strategies for HCC development following HCV eradication 3 .
Trends in malignant pleural mesothelioma prevalence in the United States from 2000 to 2020.
Authors: Bharath Ganesh, Ida Micaily
Journal: Journal of Clinical Oncology (2024)

e20094 Background: Malignant pleural mesothelioma (MPM) is a rare cancer that is closely associated with prolonged asbestos exposure. Its incidence has steadily declined over time with decreasing prevalence of asbestos-related lung disease. Our study aims to provide an update on recent MPM trends in the United States from 2000 to 2020. Methods: This is a retrospective cohort study design. The primary endpoints of this study are age-adjusted MPM rates and annual percentage change (APC) in rates from 2000-2020. We queried the Surveillance, Epidemiology, and End Results (SEER) 17 database for information about demographics, cause of death, and survival time for patients diagnosed with MPM from 2000-2020. For rate analysis, we used the SEER 22 database which covers 22 national cancer registries and approximately 41.9% of the US population. Age-adjusted rate analysis was performed using the National Cancer Institute (NCI) joinpoint regression program. Results: We identified 13,018 patients diagnosed with MPM from 2000-2020 who were eligible for analysis in the SEER 17 database. Individuals with MPM were primarily male (78.2%) and belonged to Non-Hispanic White (80.7%) ancestry. The mean age at diagnosis overall was 72.4 (SD +/- 10.6) years. The overall age-adjusted rate of MPM for all groups decreased from 0.97 (cases per 100,000 population) in 2000 to 0.55 in 2020. When stratified by sex, the MPM rate in males decreased from 1.91 to 0.93. The rate decrease in females over the same period was more modest, from 0.33 to 0.27. Overall APC for all groups from 2000-2013 was -1.45 (95% CI -2.01 to -0.40, p&lt;.05), and from 2013-2020 it was -5.22 (95% CI -8.92 to -3.76, p&lt;.05). The APC for males from 2000-2013 was -1.88 (95% CI -2.62 to -0.62, p&lt;.05) and -6.46 (95% CI -10.49 to -4.57, p&lt;.05) from 2013-2020. The rate decrease for females demonstrated a consistent APC of -0.87 (95% CI -1.54 to -0.26, p&lt;.05) from 2000-2020. Conclusions: MPM is a disease that is best managed at large academic cancer centers due to its rarity. Our study demonstrates an accelerated decline in overall MPM rates since 2013, mainly driven by a similar fall in rates in males over the same period. MPM rates are lower in females and continue to decline, albeit slowly. The continued and reassuring decrease in rates of MPM likely reflects the effectiveness of regulations targeting widespread industrial and residential asbestos use that have been in place since the 1990s. [Table: see text]
Neoadjuvant immunotherapy in sarcomatoid mesothelioma (Alliance A082101).
Authors: Aaron Scott Mansfield, Xiaofei F. Wang, Dennis A. Wigle, Colleen Watt, Kathryn Kelley, Gregory A. Masters, Stephanie A. Berg, David E. Kozono, Tom Stinchcombe
Journal: Journal of Clinical Oncology (2024)

TPS8125 Background: Sarcomatoid mesothelioma is the most aggressive form of pleural mesothelioma and is associated with the worst prognosis of the histologic variants of this disease. In the Checkmate 743 clinical trial the patients with sarcomatoid mesothelioma who received ipilimumab and nivolumab had survival outcomes that were similar to those of patients with epithelioid mesothelioma. In comparison, the patients with sarcomatoid mesothelioma who received chemotherapy had the worst outcomes in this trial, highlighting the known limited efficacy of chemotherapy against this histologic variant. Checkmate 743 demonstrated that ipilimumab and nivolumab is a new standard of care for non-epithelioid mesothelioma. Surgery typically has not been offered to this group of patients given their historically poor outcomes. With the significant survival gains seen patients with sarcomatoid mesothelioma treated with immunotherapy, we hypothesized that surgery may extend the benefits seen with immunotherapy. Methods: Alliance for Clinical Trials in Oncology A082101 is a prospective, phase 2 nonrandomized clinical trial for patients with sarcomatoid mesothelioma. The co-primary objectives are to determine the percentage of patients with potentially resectable sarcomatoid mesothelioma able to proceed with surgery after neoadjuvant ipilimumab and nivolumab, and the progression-free survival (PFS) at 12 months (12-month PFS) after the initiation of ipilimumab and nivolumab. For sample size determination, we assumed that if the true rate of surgery is 75% or greater, it would indicate that neoadjuvant immunotherapy is feasible to be given prior to surgery. On the other hand, if the true rate of surgery is 50% or less it would indicate that neoadjuvant immunotherapy is not worthy of further investigation. Twenty-six (26) eligible patients will be needed to receive neoadjuvant immunotherapy. If 16 or fewer of the 26 eligible patients proceed to surgery, it will be concluded that the experimental therapy is not worthy of further investigation. Otherwise, it will be concluded that the experimental therapy is worthy of further investigation. Safety monitoring will be done through a 6-week run-in for the first 10 patients to assess for pre-operative and post-operative toxicities and complications. Sequential boundaries will be used to monitor severe toxicity and complication rates. Accrual will be halted if excessive numbers of severe toxicity and complications in pre-operative and post-operative phases are seen. The accrual and safety data will be summarized in reports for semiannual reviews by Alliance Data and Safety Monitoring Board. Tumor and blood-based biomarkers will be included as exploratory biomarkers. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT05647265 .
Treating lung cancer in resource limited setting: Retrospective study from Armenia.
Authors: Mariam Mailyan, Davit Zohrabyan, Liana Safaryan, Lilit Harutyunyan, Armen Avagyan, Martin Harutyunyan, Amalya Sargsyan, Nune Karapetyan, Marine Rushanyan, Gohar Mkrtchyan, Anna Avinyan, Mariam Sargsyan, Arevik Galoyan, Julia Kostanyan, Mariam Khachatryan, Elen Baloyan, Samvel Bardakhchyan
Journal: Journal of Clinical Oncology (2024)

e20055 Background: Lung cancer (LC) is second most common cancer by incidence in Armenia. Every year approximately 800-900 new cases are diagnosed, from all cases 55.5% are in the 4th stage. Methods: We have collected data from three oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. In this retrospective hospital-based study the data of patients with LC who were treated at these three centers during the 01 Oct 2009 - 31 Dec 2023 period was collected․ Results: Four hundred and eighty-nine LC patients were involved in the final analysis. Male to female ratio was 6:1. From the all patients 10.6% were diagnosed at age ≤ 50, 79,6% of patients 50-70, and 9.6% ≥ 70 years. In 71.6% of all cases, LC was diagnosed in current or former smokers. Only 3% of patients were diagnosed in stage I, 9.8% in stage II, 44.8% in stage III, 41.1% in stage IV, and for 1.2% of patients' stage was unknown. From all cases 74% of patients had non small cell lung cancer (NSCLC), 22.7% small cell lung cancer (SCLC) and 3.3% had other histological types of lung cancer. Of all patients 63% are dead. The median overall survival (mOS) for all stages was 21 months for the entire cohort. Median OS was not reached for stage I ( &gt; 100 months), was 61 months for stage II, 23 months for stage III, and 13 months for stage IV (p &lt; 0,001). ALK mutation was checked in 22.7%, EGFR in 22%,ROS in 14.1%, KRAS in 11.2%, BRAF in 9.8% and of all patients. From all checked AKL was positive in 1.8%, EGFR in 19.4%, ROS in 2.8%, KRAS in 21.8%, BRAF in 8,3% and of cases. For patients with stage IV lung cancer (41.1%), we found a significant difference in mOS in those who received first line immunotherapy in combination with chemotherapy (19,4%) compared to those who received only chemotherapy (74.1%) (mOS: 24 months vs 11 months accordingly, p = 0.014). For stage I-III LC patients, those who received systematic therapy with cisplatin showed better overall survival than those who received systemic therapy with carboplatin (mOS 31 vs 25 months, p = 0.01), but for stage IV LC patients survival difference was not found (mOS 15 vs 12 months, p = 0.24). Conclusions: In Armenia, lung cancer is mostly diagnosed in the advanced stage where overall survival is approximately one year. In our study population, those who received immunotherapy in combination with chemotherapy showed doubled mOS, compared with only chemotherapy. In the nonmetastatic group, chemotherapy with cisplatin showed a significant increase in mOS compared with carboplatin.
Induction immune checkpoint inhibitors and chemotherapy for patients with stage III non-small cell lung cancer: A real-world experience.
Authors: Shuohan Zheng, Ciming Sun, Hao Zhang, Huimin Xu, Baiqiang Dong, Zan Hou, Ming Chen, QiWen Li
Journal: Journal of Clinical Oncology (2024)

e20057 Background: Immune checkpoint inhibitors (ICIs) have become the standard consolidation therapy for stage III unresectable non-small cell lung cancer (NSCLC). Whether induction ICIs combined with chemotherapy can further improve efficacy is controversial. In this study, we used real-world data to explore the possibility of ICIs plus chemotherapy before definitive chemoradiation therapy (CRT). Methods: Patients with stage III NSCLC (including postoperative recurrence), who received definitive CRT from 2016 to 2022, was retrospective reviewed. Survival outcomes and the incidence of pneumonia were calculated and compared between patients with induction ICIs plus chemotherapy or not. Results: A total of 156 patients undergoing definitive RCT were analyzed. Among them, 103 patients received induction ICIs plus chemotherapy, and 53 patients received induction chemotherapy before RCT or concurrent chemoradiotherapy. The 5-year overall survival (OS) rates were 75.0% and 44.4%, respectively. The median OS was not reached (NR) and 36.5 months, indicating a significant improvement of survival with the addition of induction ICIs (P = 0.03). However, there were no significant differences between the two groups in median progression-free survival (PFS) (22.4 vs. 13.6 months; P = 0.09), locoregional recurrence-free survival (LRFS) (38.0 vs. 36.9 months; P = 0.73), and distant metastasis-free survival (DMFS) (37.8 vs. 25.5 months; P = 0.14). Multivariate analysis showed that induction ICIs plus chemotherapy was an independent favorable prognostic factor for OS (HR 2.89; 95% CI, 1.24-6.75; P = 0.01). The incidence of grade 2 or higher pneumonia in the two groups was 37.2% and 29.2%, respectively (P = 0.35). Additionally, we found that patients with consolidation ICIs after induction ICIs had a better OS, with a 4-year OS rate of 90.7% and 65.5% (P = 0.03). Patients undergoing 5-6 cycles of induction ICIs seemed to have a better outcome compared to those with 3-4 cycles or 1-2 cycles (93.8% vs. 77.4% vs. 60.5%). Conclusions: For patients with stage III NSCLC receiving definitive CRT, the combination of induction ICIs and chemotherapy improves OS without a significant increase of pneumonia in real-world practice. This treatment strategy warrants further research.
Constructing a machine learning-based non-invasive liquid biopsy model for lung cancer detection via miRNA sequencing.
Authors: Jason Chia-Hsun Hsieh, Tsung-Ting Hsieh, Ko-Han Lee, Yu-Hsuen Tu, Po-Ya Chang, Eva Yi-Hsuan Wu, Yu-Chuan Chang, Yen-Jung Lu
Journal: Journal of Clinical Oncology (2024)

e20014 Background: Lung cancer is a prevalent and fatal disease, ranking second among common cancers globally. Early detection and prompt treatment significantly improve survival rates for most cancers, including lung cancer. Presently, low-dose computed tomography (LDCT) is a widely accepted tool for early lung cancer screening. However, it exhibits a high false-positive rate of up to 95%, resulting in overdiagnosis and causing anxiety among patients awaiting diagnosis results. Therefore, investigating alternative effective interventions would provide physicians with additional tools for evaluating lung cancer and making informed decisions. This study employs the concept of liquid biopsy, utilizing next-generation sequencing (NGS) to gather miRNA profiles, aiming to construct a machine learning-driven model for the detection of lung cancer. Methods: We assembled case-control cohorts, comprising 74 lung cancer cases (stage 0-II: 66; III-IV: 8) and 74 age- and gender-matched healthy control subjects, recruited from Chang Gung Memorial Hospital in Linkuo, Taiwan. Plasma derived from whole blood was collected from each subject before any cancer surgery or treatment. Subsequently, we extracted miRNA from the plasma and constructed libraries using the QIAseq miRNA Library kit for miRNA sequencing conducted on the Illumina NextSeq550 platform. RNA-seq data analysis was performed on miRNA sequencing data using the QIAGEN RNA-seq Analysis Portal 5.0. The count per million base (CPM) derived from the quantification results was utilized for differential analysis and constructing the machine learning model. To assess the model's performance, we reserved 10% of the subjects for isolated testing, while the remaining 90% underwent 10-fold cross-validation (CV). Results: The final model, built using logistic regression with six significant differentially expressed miRNAs (fold change &gt; = 2 and P-value &lt; = 0.01), achieved optimal performance. The 10-fold CV demonstrated accuracy: 97.73%; sensitivity: 98.48%; specificity: 96.97%; positive predictive value: 97.01%; negative predictive value: 98.46%. In isolated testing, all 16 subjects, including 8 cases and 8 controls, were correctly identified. Conclusions: This study with 148 subjects showcases the potential of NGS and machine learning for early-stage lung cancer detection via liquid biopsy. However, the sample size is relatively small, lacking cross-site subjects. Therefore, an additional multi-center clinical trial is underway to gather more subjects, aiming for a deeper investigation and more concrete conclusions in the near future.