Advancements in neoadjuvant immune checkpoint inhibitor therapy for locally advanced head and neck squamous Carcinoma: A narrative review.

The prevalent treatment paradigm for locally advanced head and neck squamous carcinoma (HNSCC) typically entails surgery followed by adjuvant radiotherapy and chemotherapy. Despite this, a significant proportion of patients experience recurrence and metastasis. Immune checkpoint inhibitors (ICIs), notably pembrolizumab and nivolumab, have been established as the first and second lines of treatment for recurrent and metastatic HNSCC (R/M HNSCC). The application of ICIs as neoadjuvant immunotherapy in this context is currently under rigorous investigation. This review synthesizes data from clinical trials focusing on neoadjuvant ICIs, highlighting that the pathological responses elicited by these treatments are promising. Furthermore, it is noted that the safety profiles of both monotherapy and combination therapies with ICIs are manageable, with no new safety signals identified. The review concludes by contemplating the future direction and challenges associated with neoadjuvant ICI therapy, encompassing aspects such as the refinement of imaging and pathological response criteria, selection criteria for adjuvant therapies, evaluation of the efficacy and safety of various combination treatment modalities, and the identification of responsive patient cohorts.

A-Kinase Interacting Protein 1 Promotes Cell Invasion and Stemness via Activating HIF-1α and ß-Catenin Signaling Pathways in Gastric Cancer Under Hypoxia Condition.

Background: A-Kinase interacting protein 1 (AKIP1) relates to gastric cancer growth, metastasis, and prognosis, while its regulation on gastric cancer invasion and stemness under hypoxia microenvironment is not reported. Therefore, this study aimed to explore this topic to uncover AKIP1's role in gastric cancer under hypoxia. Methods: Gastric cancer cell lines AGS and MKN45 were cultured under hypoxia condition, then transfected with AKIP1 or negative control (NC) overexpression plasmid or AKIP1 or NC knockdown plasmid. Furthermore, rescue experiments were conducted by transfecting HIF-1α or ß-catenin overexpression plasmid, combined with AKIP1 or NC knockdown plasmid. Afterward, cell invasion, CD133+ cell proportion, sphere number/1,000 cells, and HIF-1α and ß-catenin pathways were measured. Results: The invasive cell count, CD133+ cell proportion, and sphere number/1,000 cells were enhanced in both AGS cells and MKN45 cells under hypoxia, and AKIP1 expression was also elevated. AKIP1 knockdown inhibited cell invasion, CD133+ cell proportion, sphere number/1,000 cells, HIF-1α, vascular endothelial growth factor (VEGF), ß-catenin, and calcium-binding protein (CBP) expressions in AGS cells and MKN45 cells under hypoxia, while AKIP1 overexpression presented with the opposite effect. Then, in rescue experiments, HIF-1α overexpression and ß-catenin overexpression both promoted cell invasion, CD133+ cell proportion, and sphere number/1,000 cells, which also attenuated the effect of AKIP1 knockdown on these functions in AGS cells and MKN45 cells. Conclusion: AKIP1 promotes cell invasion and stemness via activating HIF-1α and ß-catenin signaling pathways in gastric cancer under hypoxia condition.

Long noncoding RNA PVT1 promotes hepatoblastoma cell proliferation through activating STAT3.

BACKGROUND: Hepatoblastoma is the most common liver malignancy in children. The long noncoding RNA (IncRNA) PVT1 plays oncogenic roles in human cancers; however, its regulation and function in hepatoblastoma remain poorly understood. PURPOSE: This study was designed to investigate the regulation and function of PVT1 in hepatoblastoma. METHODS: PVT1 expression was compared between human hepatoblastoma tissues and adjacent non-tumor tissues, and then analyzed using Kaplan-Meier method. The proliferation of hepatoblastoma cells was determined by BrdU incorporation assay. The tumor xenograft model was used to assess tumor proliferation in vivo. The gene expression level was measured by qRT-pCR, Western blot and immunohistochemistry analyses. RESULTS: Compared with normal counterparts, PVT1 is upregulated in human hepatoblastoma tissues as well as in hepatoblastoma cell lines. Additionally, PVT1 promotes the proliferation of hepatoblastoma cells in vitro and accelerates tumor growth in xenograft model in vivo. Mechanistically, PVT1 promotes the activation of the signal transducer and activator of transcription 3 (STAT3), which leads to the transcriptional activation of downstream targets involved in cell cycle progression, and moreover,STAT3 inhibition with the selective inhibitor stattic abolishes PVT1 pro-proliferative role in hepatoblastoma cells. CONCLUSION: PVT1 promotes hepatoblastoma cell proliferation through activating STAT3-induced cell cycle progression, which may implicate PVT1 as a potential therapeutic target for hepatoblastoma treatment.

Anti-bacterial activity of mutant chensinin-1 peptide against multidrug-resistant Pseudomonas aeruginosa and its effects on biofilm-associated gene expression.

Nosocomial infections with Pseudomonas aeruginosa (PA) are difficult to treat due to the low outer membrane permeability of the bacterium and the development of resistance. In the present study, the anti-microbial peptide (AMP) mutant chensinin-1 (MC1) was revealed to exhibit anti-bacterial activity against a multidrug-resistant PA (MRPA) strain in vitro, and the minimum inhibitory concentration was 25 µM, which was 4-fold higher than that of the native strain. MC1 was able to disrupt the integrity of the cytoplasmic membrane in the native PA strain and MRPA and had a similar membrane depolarization ability in these strains, but the outer membrane permeability of MRPA cells was lower than that of native PA cells, as determined by a 1-N-phenylnaphthylamine assay. In addition, the abundance of the gene Psl encoding for biofilm-associated polysaccharides was detected using Congo red, and a high concentration of MC1 inhibited the formation of MRPA biofilms. Furthermore, the expression levels of biofilm-associated genes affected by the AMP, MC1, were quantified by polymerase chain reaction analysis. The results indicated that MC1 induced biofilm inhibition by downregulating the relative expression of specific biofilm polysaccharide-associated genes, including pelA, algD and pslA. The present results indicated that the AMP MC1 may be an effective antibiotic against MRPA strains.