Case Report: Durable complete response of metastatic hepatocellular carcinoma with asymptomatic hyperamylasemia to combined immunotherapy of anti-cytotoxic T lymphocyte-associated antigen 4 plus anti-programmed cell death-1 antibodies

BackgroundCombined immunotherapy has shown promising results in the treatment of advanced HCC, whereas the priority population that would respond to the combined immunotherapy is still elusive. In addition, HCC with asymptomatic hyperamylasemia was not reported previously.Case presentationAn aged patient was diagnosed as HCC with BCLC stage C (bone metastasis). Notably, this patient showed asymptomatic hyperamylasemia. The patient was then enrolled in a trial evaluating combined immunotherapy of anti-PD-1 antibody sintilimab (IBI308) plus anti-CTLA-4 antibody (IBI310) in advanced HCC. After being treated with combined immunotherapy, this patient rapidly achieved complete response (CR) according to mRECIST criteria or immune partial response (iPR) according to iRECIST criteria and maintain the CR state for more than 12 months. Interestingly, serum levels of amylase and lipase in this patient were reduced after treatment.ConclusionWe reported, for the first time, a case of metastatic HCC with asymptomatic hyperamylasemia, and suggested that HCC patients with asymptomatic hyperamylasemia may benefit from combined immunotherapy of anti-CTLA-4 and PD-1 antibodies

Alkaline phosphatase combined with γ-glutamyl transferase is an independent predictor of prognosis of hepatocellular carcinoma patients receiving programmed death-1 inhibitors

BackgroundImmunotherapy plays an increasingly critical role in the systemic treatment of HCC. This current study aimed to establish a novel prognostic predictor of Programmed death 1 (PD-1) inhibitor therapy in hepatocellular carcinoma (HCC) independent of Child-Pugh grade.MethodsOur study screened patients with HCC who received PD-1 inhibitors at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2018 to December 2020. ALG grade was determined by the patient’s serum ALP and GGT levels before the initiation of PD-1 inhibitors. The endpoints of our study were overall survival (OS) and progression free survival (PFS). Follow-up ended at May 31, 2022.ResultsEighty- five patients (77 with Child−Pugh grade A, 8 with Child−Pugh grade B at baseline) were enrolled according to the inclusion criteria. Patients with Child−Pugh grade A achieved longer PFS and OS than those with Child−Pugh grade B. Patients with ALG grade 3 at baseline showed worse tumor response and poorer survival, and ALG grade could stratify patients with Child−Pugh grade A into subgroups with significantly different prognosis.ConclusionsALG grade, combining ALP and GGT, is a novel and readily available prognostic marker and the predictive effect of ALG grade on patient prognosis is independent of Child−Pugh grade

Bleeding due to a probable interaction between warfarin and Gouqizi (Lycium Barbarum L.)

Unlike what is widely anticipated by the public, herbal medicines are not always safe despite being natural. We describe a 65-year-old Chinese man taking a prolonged maintenance dose of warfarin who experienced an elevated international normalized ratio (INR) with associated bleeding after drinking Gouqizi (goji berry) wine. This report illustrates that large doses (more than 6–12 g) of Gouqizi can significantly enhance the anticoagulant action of warfarin and may cause similar adverse effects in keeping with three previous reports. Therefore, the use of herbal medicines must adhere to pharmacopoeia-recommended guidelines, including dosage regimes. Doctors should advise patients regarding possible interactions between herbs and warfarin when prescribing and should increase the frequency of INR monitoring for those patients concurrently receiving warfarin and medicinal herbs. Further study is needed to do for the mechanism of interaction between Gouqizi and warfarin

Revisiting the chaperonin T‐complex protein‐1 ring complex in human health and disease: A proteostasis modulator and beyond

Abstract Background Disrupted protein homeostasis (proteostasis) has been demonstrated to facilitate the progression of various diseases. The cytosolic T‐complex protein‐1 ring complex (TRiC/CCT) was discovered to be a critical player in orchestrating proteostasis by folding eukaryotic proteins, guiding intracellular localisation and suppressing protein aggregation. Intensive investigations of TRiC/CCT in different fields have improved the understanding of its role and molecular mechanism in multiple physiological and pathological processes. Main body In this review, we embark on a journey through the dynamic protein folding cycle of TRiC/CCT, unraveling the intricate mechanisms of its substrate selection, recognition, and intriguing folding and assembly processes. In addition to discussing the critical role of TRiC/CCT in maintaining proteostasis, we detail its involvement in cell cycle regulation, apoptosis, autophagy, metabolic control, adaptive immunity and signal transduction processes. Furthermore, we meticulously catalogue a compendium of TRiC‐associated diseases, such as neuropathies, cardiovascular diseases and various malignancies. Specifically, we report the roles and molecular mechanisms of TRiC/CCT in regulating cancer formation and progression. Finally, we discuss unresolved issues in TRiC/CCT research, highlighting the efforts required for translation to clinical applications, such as diagnosis and treatment. Conclusion This review aims to provide a comprehensive view of TRiC/CCT for researchers to inspire further investigations and explorations of potential translational possibilities