Biological Procedures Online最新文献

Lung cancer remains the leading cause of cancer related deaths worldwide. Immunotherapy and combination therapies, involving chemotherapy, radiotherapy, and tumor anti-angiogenesis therapy, have shown promising clinical results and are expected to become a key approach in the future management of lung cancer. However, due to immune resistance, immunotherapy remains highly effective in only a subset of patients, while many others either do not respond initially or develop resistance over time. Moreover, immune-related adverse events induced by immunotherapy, further complicate treatment outcomes and prognosis. Immune-related biomarkers and ImmuneScores have driven the development of personalized immunotherapy strategies for lung cancer, and they can aid in predicting immune resistance, and forecasting immune-related adverse events (irAEs). This review summarizes the prognosis value of immune-related biomarkers and ImmuneScores in immunotherapy and combination therapies for lung cancer. The aim is to provide a foundation for personalized treatment and management of lung cancer, while offering guidance for future research directions in immunotherapy.

Tumor recurrence driven by mitochondrial hypermetabolism remains a critical challenge in cancer therapy, as aberrant energy metabolism fuels therapeutic resistance and disease progression. We aimed to develop a multifunctional nanoplatform combining mitochondrial metabolism inhibition, photothermal therapy, and controlled chemotherapy to overcome tumor recurrence mechanisms. Biodegradable polydopamine nanoparticles (PDA-DOX-CO NPs) were engineered via molecular self-assembly, co-loading doxorubicin (DOX) and a carbon monoxide (CO) prodrug. The PDA-DOX-CO NPs demonstrated three synergistic therapeutic effects: (1) Photothermal ablation (48.38 °C tumor hyperthermia), (2) CO-mediated mitochondrial suppression, and (3) Spatiotemporally controlled DOX release. In HCT-116 tumor models, PDA-DOX-CO NPs with NIR irradiation induced 60% tumor complete ablation. Histopathological analysis confirmed significant apoptosis induction and mitochondrial morphology alterations in treated tumors. This "metabolic blockade + energy depletion + precision delivery" paradigm provides a synergistic solution to tumor recurrence, demonstrating enhanced therapeutic efficacy and biosafety through mitochondrial-targeted multimodal action.

Hepatocellular carcinoma (HCC) ranks as the third most common malignant tumor globally. Although hyperthermia has shown promise as a non-invasive treatment for tumors, its specific mechanisms and impact on HCC remain underexplored. This study aims to investigate the effects of hyperthermia on HCC proliferation and apoptosis and to elucidate the role of the Hippo signaling pathway in these processes. Huh7 and HepG2 HCC cells were cultured at various temperatures (37 °C, 40 °C, 43 °C, and 46 °C), with 37 °C as the control. Cell proliferation, apoptosis, and cell cycle distribution were assessed via CCK-8 assays and flow cytometry. A subcutaneous xenograft model in nude mice, treated with indocyanine green (ICG) and near-infrared (NIR) irradiation to achieve local hyperthermia, was used to evaluate in vivo tumor growth. RNA-seq and KEGG pathway analyses identified differentially expressed genes, and Western blotting and immunofluorescence were used to confirm the involvement of the Hippo signaling pathway. Hyperthermia at 43 °C significantly inhibited Huh7 and HepG2 cell proliferation and induced apoptosis, accompanied by cell cycle arrest. In vivo, local hyperthermia reduced tumor volume and weight in the ICG + NIR-treated group. RNA-seq and KEGG analyses revealed that the Hippo signaling pathway was activated under hyperthermic conditions, with YAP expression and nuclear translocation markedly downregulated. Further experiments showed that YAP overexpression mitigated hyperthermia-induced effects on cell proliferation and apoptosis, underscoring the role of the Hippo pathway. These findings demonstrate that hyperthermia inhibits HCC growth by regulating the Hippo signaling pathway, reducing cell proliferation, and promoting apoptosis. This study highlights the potential of hyperthermia as an effective therapeutic approach for HCC, with implications for developing targeted hyperthermic therapies.

Background: Lung cancer exhibits a high degree of heterogeneity, rendering its treatment one of the most difficult challenges. Current laboratory lung cancer models cannot fully preserve the diversity of the disease and predict drug responses. Owing to the rarity of human-derived samples, transgenic mouse models can be extensively used in fundamental research.

Results: We established a mouse lung cancer organoid (LCO) model derived from a genetically engineered mouse model that can spontaneously develop lung cancer. Morphological and molecular assays demonstrated that the lung cancer organoids retained the histological architecture and stem-like characteristics of their parental tumors. Successfully constructed lung cancer organoids were amenable for high-throughput drug screening in vitro.

Conclusions: This method can be used for the construction and identification of mouse-derived lung cancer organoids, which can be used to further comprehend the pathophysiology of lung cancer and evaluate drug responses in personalized medicine.

Viral hepatitis is a significant danger to global public health as it is the primary cause of mortality worldwide. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are well-established infectious agents that significantly contribute to the development and transmission of hepatocellular carcinoma (HCC). Hepatitis E virus (HEV) is the pathogen responsible for acute viral hepatitis. 80% of liver malignancies are HCC, with HBV and HCV infections being the primary cause of seventy to eighty% of HCC cases. HEV may exacerbate liver inflammation and make other infections more severe. New vaccinations against the hepatitis virus are being developed to reduce the required doses for inducing an effective immune response and to help establish long-term protection in populations hyporesponsive to the vaccine. RNA-based vaccinations have emerged as a viable alternative. mRNA vaccines can help bridge the gap between the availability of effective vaccines and the rise of pandemic infectious diseases. Both human and animal studies have demonstrated that these vaccinations induce long-lasting and safe immunological responses. This review highlights the challenges faced in developing vaccines for the hepatitis virus, explicitly focusing on different vaccine candidates aimed at preventing or mitigating the illness. Here, we review the progress and comprehensive assessments of an mRNA-based vaccine designed to combat HAV, HBV, HCV, HDC, and HEV.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, associated with high morbidity and mortality worldwide. Despite advancements in diagnostic methods and systemic treatments, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), the development of drug resistance remains a significant challenge in HCC management. Traditional treatments such as surgical resection and transarterial chemoembolization offer limited efficacy, especially in advanced stages. Although novel therapies like lenvatinib, sorafenib, regorafenib, and ICIs have shown promise, their effectiveness is often hindered by primary and acquired resistance, leading to poor long-term survival outcomes. This review focuses on the molecular mechanisms underlying resistance to targeted therapies and immunotherapies in HCC. Key factors contributing to resistance include alterations in the tumor microenvironment (TME), immune evasion, hypoxia, changes in cellular metabolism, and genetic mutations. Additionally, molecular players such as ferroptosis, autophagy, apoptosis, endoplasmic reticulum stress, ABC transporters, and non-coding RNAs(ncRNAs) are discussed as contributors to drug resistance. Understanding these mechanisms is critical for the development of novel therapeutic strategies aimed at overcoming resistance, improving patient outcomes, and ultimately enhancing survival rates in HCC patients.

Lung cancer is the leading cause of cancer-related deaths globally. Prolonged targeted therapy use can lead to drug resistance and target mismatches, necessitating more effective and safer treatment strategies. Recent research has focused on the tumor microenvironment, which includes immune and stromal cells that play roles in tumor proliferation, metastasis, and neovascularization. Tumor-associated macrophages (TAMs) are key immune cells in the tumor microenvironment, promoting tumor invasion, metastasis, and immune escape. Their infiltration density in lung cancer tissue is a poor prognostic factor. Piperlongumine (PL), extracted from Piper longum, possesses antitumor and anti-inflammatory properties, inducing apoptosis and inhibiting invasion and metastasis in lung cancer cells. This study aims to elucidate the correlation between endoplasmic reticulum stress (ERS) in lung cancer cells and M2-type TAM polarization and the role of PL in regulating lung cancer progression. The network pharmacologic analysis revealed that Piperlongumine inhibits lung cancer progression by inducing endoplasmic reticulum stress. In vivo experiments demonstrated that Piperlongumine significantly reduced tumor volume and decreased the proportion of M2-type macrophages. Within the co-culture system, lung cancer cells were shown to promote macrophage M2-type polarization and enhance cancer cell migration. Piperlongumine effectively inhibited these effects by inducing endoplasmic reticulum stress in cancer cells, thereby reducing M2 polarization and cell migration. The addition of endoplasmic reticulum stress inhibitor 4-PBA counteracted Piperlongumine's effects, further underscoring the crucial role of ERS in the treatment mechanism. Piperlongumine suppresses lung cancer growth by inducing endoplasmic reticulum stress, which inhibits macrophage M2-type polarization and reduces cell migration. These findings support Piperlongumine's potential as a therapeutic agent and offer a foundation for targeting endoplasmic reticulum stress to modulate TAM function in lung cancer treatment.

Background: Immunotherapy has been recognized as a significant advancement in cancer treatment by promoting the body's immune system to identify and eliminate cancer cells more effectively. Unlike conventional therapies, immunotherapy can enhance the natural capabilities of human immune system. Chimeric Antigen Receptor T-cell (CAR-T) therapy involves genetical-modified T-cells from patients to better catch and attack cancer cells. Up to date, CAR-T therapy has shown particular promise in treating certain types of leukemia and lymphoma, highlighting the transformative potential of immunotherapy.

Results: Literature data search using PubMed, CNKI, and Wanfang were searched to collect eligible studies up to January 2025. The primary outcomes of complete response rate (CRR), objective response rate (ORR), dead rate (DR), and other adverse reactions were evaluated. Secondary outcomes (CRR, ORR, and DR) of subgroup analysis from different cancer types, origins, and outcomes for survival rate were analyzed for our final results. A total of 649 studies were initially identified through database searching. After removing duplicates and non-clinical cancer studies, 32 eligible studies were included in this work. The pooled data included 819 patients for objective response rate (ORR), 843 patients for complete response rate (CRR), and 868 patients for dead event. In the included studies, 24 reported ORR data, revealing an objective response rate of 84.86% (695/819) with little heterogeneity (OR: 0.87, 95% CI 0.80-0.91, P = < 0.01, I² = 61%); 24 studies showed a CRR of 65.30% (491/843) with significant heterogeneity (OR: 0.58, 95% CI: 0.43-0.72, P < 0.01, I² = 84%); 27 studies showed a mortality rate of 23.73% (206/868) with significant heterogeneity (OR: 0.19, 95% CI: 0.11-0.32, P < 0.01, I² = 77%). Subgroup analysis based on cancer type revealed that ORR was higher in multiple myeloma (86.77%, 400/461) compared with leukemia (84.92%, 259/305) and lymphoma (67.92%, 36/53). In parallel, heterogeneity observed based on case origins suggested that Chinese cases showed significantly higher ORR, CRR, and survival rates compared with American ones.

Conclusions: This meta-analysis provides valuable insights into the potential of immunotherapy, particularly CAR-T, in cancer treatment. Findings showed the different efficacy and safety of immunotherapy in treating multiple cancers, with various objective response rates. Continued studies from more trials with different populations are needed to optimize their efficacy in further cancer treatment and precision medicine.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized primarily by social deficits and repetitive behaviors. The mechanisms of ASD are complex and are not yet fully understood, although many ASD risk genes and mouse models have been reported. It has been suggested that deletion of PRRG4 (proline-rich and Gla domain 4) deletion may contribute to autism symptoms in patients with WAGR (Wilms' tumor, aniridia, gonadoblastoma, mental retardation) syndrome. The mouse model with PRRG4 gene deletion has not been reported so far. This study investigated whether brain-specific conditional knockout of PRRG4 induces ASD-like symptoms in mice by crossing the PRRG4^fl/fl mice with Emx1-Cre mice, which express Cre in the cerebral cortex and hippocampus.

Results: The PRRG4 brain-specific knockout (PRRG4^fl/^fl-Cre⁺, PRRG4-CKO) mice exhibited social deficits, repetitive behaviors, and anxiety-like symptoms compared to PRRG4^fl/fl control mice according to the results of various behavioral tests. PRRG4 knockout led to the increase in total dendritic length, branching, and dendritic spine density in the pyramidal neurons of the cerebral cortex and hippocampus, as well as enhanced levels of synaptic proteins including SYP and PSD95. Immunoprecipitation experiment with PRRG4 antibodies showed dramatic decreased interaction of PRRG4 and MAGI2 proteins in brain tissues from PRRG4-CKO mice compared to PRRG4^fl/fl control mice. GST-RBD pull-down assay showed a significant decrease in RhoA-GTP levels in the cerebral cortex and hippocampus of PRRG4-CKO mice.

Conclusions: Brain-specific conditional knockout of the PRRG4 in mice leads to ASD-like symptoms. PRRG4 protein may regulate dendritic and synaptic development in mice by activating RhoA through interaction with MAGI2. These findings provide evidence for a comprehensive understanding of PRRG4 function in vivo and support the association between PRRG4 loss and ASD phenotypes observed in WAGR syndrome.