Development and Optimization of A Human Hepatocellular Carcinoma Patient-Derived Organoid Model for Potential Target Identification and Drug Discovery.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal tumor worldwide and its late discovery and lack of effective specific therapeutic agents necessitate further research into its pathogenesis and treatment. Organoids, a novel model that closely resembles native tumor tissue and can be cultured in vitro, have garnered significant interest in recent years, with numerous reports on the development of organoid models for liver cancer. In this study, we have successfully optimized the procedure and established a culture protocol that enables the formation of larger-sized HCC organoids with stable passaging and culture conditions.

Single-cell transcriptome sequencing reveals potential novel combination of biomarkers for antibody-based cancer therapeutics in hepatocellular carcinoma.

Antibody-based cancer therapeutics is developing rapidly in recent years for its advantages in precisely targeting the tumor cells. However, tumor-specific cell surface antigens are still lacking, and the heterogeneity of tumor mass greatly impeded the development of effective drugs. In the present study, single-cell RNA sequencing was used to dissect tumor heterogeneity in human hepatocellular carcinoma (HCC).

Should people with chronic liver diseases be vaccinated against COVID-19?

Hepatic impairment in coronavirus disease 2019 (COVID-19) may derive from cholangiocyte damage in the beginning, but not from direct infection of hepatocytes. Chronic liver disease patients co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited overexpression of angiotensin-converting enzyme 2 receptors and overwhelming cytokine storm. Consensus has been reached that we should encourage as many people as possible to be vaccinated in order to achieve herd immunity.

Knockdown of lncRNA ZNRD1-AS1 suppresses gastric cancer cell proliferation and metastasis by targeting the miR-9-5p/HSP90AA1 axis.

LncRNAs play an important role in a variety of biological processes, such as cancer pathogenesis. The lncRNA zinc ribbon domain containing 1 antisense RNA 1 (ZNRD1-AS1) is a natural antisense transcript of ZNRD1. In this study, we found that ZNRD1-AS1 levels were significantly upregulated in gastric cancer tissues compared to those in adjacent healthy gastric tissues.

Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management.

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application.

Identification of prognostic claudins signature in hepatocellular carcinoma from a hepatocyte differentiation model.

Background: Loss of terminal differentiation markers and gain of stem cell-like properties are a major hallmark of cancer malignant progression. Identification of novel biomarkers representing tumor developmental progeny and predictive of patients' prognosis would greatly benefit clinical cancer management.

Methods: Human embryonic stem cells were induced to differentiate into hepatocytes along hepatic lineages.

A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets.

Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro.

Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients With Malignant Ascites Secondary to Unresectable Gastric Cancer.

Background: To compare the efficacy of 3 chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC).

Materials And Methods: From January 2010 to December 2013, 38 GC patients were randomly divided into 3 groups and treated by laparoscopic HIPPC with 1 of the 3 following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin (L-OHP), Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the 3 groups.

LncRNA AC093818.1 accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression.

Gastric cancer (GC) is a highly prevalent type of metastatic tumor. The mechanisms underlying GC metastasis are poorly understood. Some long noncoding RNAs (lncRNAs) reportedly play key roles in regulating metastasis of GC.

Thermo-chemotherapy inhibits the proliferation and metastasis of gastric cancer cells via suppression of EIF5A2 expression.

Purpose: Thermo-chemotherapy (TCT) is a new approach for the treatment of cancer that combines chemotherapy with thermotherapy. In the present study, we investigated the relationship between eukaryotic translation initiation factor 5A2 (EIF5A2) and TCT sensitivity in gastric cancer (GC) to further illuminate the molecular mechanism underlying the effect of TCT on GC.

Methods: A TCT cell model was constructed, and EIF5A2 was silenced or overexpressed by infection with a lentivirus expressing either EIF5A2 or EIF5A2 shRNA.

Development of an oncogenic dedifferentiation SOX signature with prognostic significance in hepatocellular carcinoma.

Background: Gradual loss of terminal differentiation markers and gain of stem cell-like properties is a major hall mark of cancer malignant progression. The stem cell pluripotent transcriptional factor SOX family play critical roles in governing tumor plasticity and lineage specification. This study aims to establish a novel SOX signature to monitor the extent of tumor dedifferentiation and predict prognostic significance in hepatocellular carcinoma (HCC).

Long noncoding RNA LINC00673 epigenetically suppresses KLF4 by interacting with EZH2 and DNMT1 in gastric cancer.

Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients.

Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death.

Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group.

Optimized construction of MUC1-VNTR DNA vaccine and its anti-pancreatic cancer efficacy.

Considering mucin 1-variable number tandem repeat (MUC1-VNTR) as a novel target for pancreatic cancer immunotherapy, the present study aimed to screen and identify the pVAX1-MUC1-VNTR DNA vaccine with the strongest immunogenicity. Following construction of a pVAX1-MUC1-VNTR plasmid, immature dendritic cells (DCs) were subjected to transfection, and mature DCs were then co-cultured with autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting interferon (IFN)-γ were determined using an enzyme-linked immunospot assay, and CytoTox was also used to examine the MUC1-VNTR-specific Lethal effect of CTLs on Capan2 cells.

Port-Site Metastases and Chimney Effect of B-Ultrasound-Guided and Laparoscopically-Assisted Hyperthermic Intraperitoneal Perfusion Chemotherapy.

Purpose: CO₂ leakage along the trocar (chimney effect) has been proposed to be an important factor underlying port-site metastasis after laparoscopic surgery. This study aimed to test this hypothesis by comparing the incidence of port-site metastasis between B-ultrasound-guided and laparoscopically-assisted hyperthermic intraperitoneal perfusion chemotherapy (HIPPC).

Materials And Methods: Sixty-two patients with malignant ascites induced by gastrointestinal or ovarian cancer were divided into two groups to receive either B-ultrasound-guided or laparoscopically-assisted HIPPC.

Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer.

Background: To compare the efficacy of three chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC).

Materials And Methods: From January 2010 to December 2013, 38 GC patients were randomly divided into three groups and treated by laparoscopic HIPPC with one of the three following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin [trans-(±)-diaminocyclohexane oxalatoplatinum (l-OHP)], Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the three groups.

The complete mitochondrial genome of Japanese macaque, Macaca fuscata fuscata (Macaca, Cercopithecinae).

In this study, the complete mitochondrial genome sequence of Japanese macaque, Macaca fuscata fuscata, with the total length of 16,565 bp, is determined for the first time. This mitogenome harbors 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). The overall base composition is A (31.

The complete mitochondrial genome of malbrouck monkey, Chlorocebus cynosuros (Chlorocebus, Cercopithecinae).

In this study, the complete mitochondrial genome sequence of malbrouck monkey, Chlorocebus cynosuros, with the total length of 16,334 bp, is reported for the first time. Similar to other monkeys, it contains a typically conserved structure including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). The base composition was A (32.

Hypoxia augments the calcium-activated chloride current carried by anoctamin-1 in cardiac vascular endothelial cells of neonatal mice.

Background And Purpose: The molecular identity of calcium-activated chloride channels (CaCCs) in vascular endothelial cells remains unknown. This study sought to identify whether anoctamin-1 (Ano1, also known as TMEM16A) functions as a CaCC and whether hypoxia alters the biophysical properties of Ano1 in mouse cardiac vascular endothelial cells (CVECs).

Experimental Approach: Western blot, quantitative real-time PCR, confocal imaging analysis and patch-clamp analysis combined with pharmacological approaches were used to determine whether Ano1 was expressed and functioned as CaCC in CVECs.

Endothelial progenitor cells in cardiovascular diseases: from biomarker to therapeutic agent.

Regenerative medicine techniques to recover cardiac and vascular function are being increasingly investigated as management strategies for cardiovascular diseases. Circulating endothelial progenitor cells (EPCs) derived from bone marrow are immature cells capable of differentiating into mature endothelial cells and play a role in vascular reparative processes and neoangiogenesis. The potency of EPCs for cardiovascular regeneration has been demonstrated in many preclinical studies and therapeutic utility of EPCs has been evaluated in early-phase clinical trials.