Combination anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report.

Up to 80% of biliary tract cancer (BTC) patients relapse within 3 years after surgery and the efficacy of second-line treatment remains dismal for patients who progressed on gemcitabine and cisplatin chemotherapy. Median overall survival of patients with palliative chemotherapy is less than 1 year. The feasibility and safety of targeted therapies plus immunotherapies remain scanty currently, and patients with recurrent or advanced BTCs often experience a rapid decline in Eastern Cooperative Oncology Group (ECOG) performance status. This case report is the first report suggesting a 17-month progression-free survival (PFS), partial response, and another 11-month PFS after progressive disease of anlotinib plus toripalimab in advanced BTC with high ECOG performance status. We report a 67-year-old Chinese male with BTC. He was observed with progressive disease after surgical resection, adjuvant chemotherapy, palliative chemotherapy, and diagnosed with American Joint Committee on Cancer clinical stage IV (cT3N0M1) extrahepatic BTC. The patient experienced a rapid decline in performance status, and he received oral anlotinib and toripalimab with informed consent. MRI scans showed partial response on 22 June 2022. PET-CT showed that tumor activity has been inhibited on 8 March 2023. He achieved 17 months of PFS. Although the patient developed solitary lung metastasis, he had a continuous survival benefit from treatment of anlotinib plus toripalimab after lung radiotherapy. Until the writing of the case draft, he had achieved another 11 months of PFS. The present case suggests that anlotinib plus toripalimab might be a potential effective treatment for advanced BTCs patients with high ECOG performance status.

Ligand-Induced Electronic Structure Modulation of Self-Evolved Ni3S2 Nanosheets for the Electrocatalytic Oxygen Evolution Reaction.

Modulating the electronic structure of the electrocatalyst plays a vital role in boosting the electrocatalytic performance of the oxygen evolution reaction (OER). In this work, we introduced a one-step solvothermal method to fabricate 1,1-ferrocene dicarboxylic acid (FcDA)-decorated self-evolved nickel sulfide (Ni3S2) nanosheet arrays on a nickel foam (NF) framework (denoted as FcDA-Ni3S2/NF). Benefiting from the interconnected ultrathin nanosheet architecture, ligand dopants induced and facilitated in situ structural reconstruction, and the FcDA-decorated Ni3S2 (FcDA-Ni3S2/NF) outperformed its singly doped and undoped counterparts in terms of OER activity. The optimized FcDA-Ni3S2/NF self-supported electrode presents a remarkably low overpotential of 268 mV to achieve a current density of 10 mA cm-2 for the OER and demonstrates robust electrochemical stability for 48 h in a 1.0 M KOH electrolyte. More importantly, in situ electrochemical Raman spectroscopy reveals the generation of catalytically active oxyhydroxide species (NiOOH) derived from the surface construction during the OER of pristine FcDA-Ni3S2/NF, contributing significantly to its superior electrocatalytic performance. This study concerns the modulation of electronic structure through ligand engineering and may provide profound insight into the design of cost-efficient OER electrocatalysts.

Targeting Trop-2 in cancer: Recent research progress and clinical application.

The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca2+ signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy. Up to now, the mechanisms and functions associated with Trop-2 have been extensively studied in a variety of solid tumors. According to these findings, Trop-2 plays an important role in cell proliferation, apoptosis, cell adhesion, epithelial-mesenchymal transition, as well as tumorigenesis and tumor progression. In addition, Trop-2 related drugs are also being developed widely. There are a number of Trop-2 related ADC drugs that have demonstrated potent antitumor activity and are currently been studied, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd). In this study, we reviewed the progress of Trop-2 research in solid tumors. We also sorted out the composition and rationale of Trop-2 related drugs and summarized the related clinical trials. Finally, we discussed the current status of Trop-2 research and expanded our perspectives on its future research directions. Importantly, we found that Trop-2 targeted ADCs have great potential for combination with other antitumor therapies. Trop-2 targeted ADCs can reprogramme tumor microenvironment through multiple signaling pathways, ultimately activating antitumor immunity.

A novel immunogenomic prognostic signature in lung squamous carcinoma.

ABSTRACT: Lung squamous carcinoma (LUSC) is a common subtype of lung cancer with limited available therapy and is thus associated with poor survival. Immune infiltrating cells and immune-related genes (IRGs) play a key role in the clinical outcomes of LUSC. In the present study, we aimed to develop a potential immunogenomic prognostic signature for patients with LUSC. The transcriptional profiles of 501 LUSC samples from The Cancer Genome Atlas (TCGA) and 2498 IRGs from the ImmPort database were used to develop the signature by Cox regression analysis. Ten differentially expressed and survival-associated IRGs were used to develop the risk signature, which could serve as an independent prognostic and predictive factor for patients with LUSC. Furthermore, this risk signature correlated with overall survival and clinical features, including age, in patients with LUSC. In addition, we identified 25 transcription factors that may regulate 15 survival-associated IRGs, using a regulatory network. Collectively, this immunogenomic signature could be a robust prognostic tool for patients with LUSC and holds great promise as individualized immunotherapy for LUSC.

Potential Prognostic Biomarkers of Lung Adenocarcinoma Based on Bioinformatic Analysis.

Lung adenocarcinoma (LUAD), which accounts for 60% of non-small-cell lung cancers, is poorly diagnosed and has a low average 5-year survival rate (approximately 20%). It remains the leading cause of cancer-related deaths worldwide. Studies on long noncoding RNAs (lncRNAs) in LUAD-related competing endogenous RNA (ceRNA) networks are limited. We aimed to identify novel prognostic biomarkers for LUAD using bioinformatic tools and data analysis. We systemically integrated differentially expressed genes and clinically significant modules using weighted correlation network analysis. We performed a functional analysis of the collected candidate genes and explored three LUAD-related genes (VWF, PECAM1, and COL1A1) associated with the overall survival rates of patients with LUAD. Based on Cox proportional hazards analysis of candidate mRNAs and lncRNAs together with differentially expressed microRNAs, we constructed ceRNA networks, obtained 12 lncRNAs in the ceRNA networks, and revealed seven novel lncRNAs AC021016.2, AC079630.1, AC116407.1, AC125807.2, AF131215.5, LINC01936, and RHOXF1-AS1. These lncRNAs were found to be associated with overall survival rates and are suitable for the prediction of prognosis by Kaplan-Meier survival and receiver operating characteristic curve analyses. In particular, three lncRNAs-AF131215.5, AC125807.2, and LINC01936-showed an independent prognostic value of overall survival for patients with LUAD. We evaluated the diagnostic capabilities of seven lncRNAs for patients with LUAD using principal component analysis and the Gene Set Variation Analysis index. lncRNAs and crucial genes could be effectively used for distinguishing LUAD tumors from normal tissues in the Gene Expression Omnibus profile. In particular, AC021016.2 showed a significant prognostic value in the validation dataset. Our findings reveal the significance of exploring lncRNAs in cancer-related ceRNAs using bioinformatic strategies.