Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy.

The aim of this study is to assess the effectiveness and safety of anlotinib in conjunction with concurrent radiochemotherapy for the treatment of locally advanced head and neck malignant tumors, including cases exhibiting local or neck recurrence and metastasis. Between June 2020 and June 2023, 42 patients diagnosed with locally advanced head and neck malignant tumors or presenting with local or neck recurrence and metastasis were recruited. These individuals received treatment that combined anlotinib with concurrent radiochemotherapy, followed by a minimum of two cycles of oral anlotinib upon completion of the initial treatment regimen. Among the 19 patients diagnosed with nasopharyngeal carcinoma, 14 patients attained a complete response, while four patients achieved partial response, resulting in an overall response rate of 94.74% (18/19). Conversely, among the 23 patients with non-nasopharyngeal carcinoma, two patients achieved complete response and 16 attained partial response, yielding a response rate of 78.26% (18/23). The 6-month progression-free survival rate was 95.24%. After treatment, serum vascular endothelial growth factor receptor levels exhibited a significant decrease compared with pretreatment levels. Notably, no instances of treatment-related serious adverse reactions were recorded. The combination of anlotinib with concurrent radiochemotherapy demonstrates favorable efficacy in managing locally advanced head and neck malignant tumors, including instances of local or neck recurrence and metastasis. Furthermore, the treatment regimen is characterized by an acceptable safety profile and tolerability.

Pyruvate Kinase M2 Knockdown Suppresses Migration, Invasion, and Epithelial-Mesenchymal Transition of Gastric Carcinoma via Hypoxia-Inducible Factor Alpha/B-Cell Lymphoma 6 Pathway.

Gastric carcinoma is a common malignant cancer. Pyruvate kinase M2 (PKM2) is highly expressed in cancers, including gastric carcinoma. However, its function and molecular mechanism in gastric carcinoma remains unclear. Here, we aimed to explore the function and the underlying mechanism of PKM2 on malignant phenotypes in gastric carcinoma. In this study, the mRNA levels and protein levels of PKM2 in gastric carcinoma cell lines and normal gastric mucosa epithelial cell lines were detected using quantitative real-time PCR and western blot, respectively. PKM2 was downregulated by siRNA transfection. HIF-1α or BCL-6 was upregulated by corresponding overexpression plasmid. Cell viability was detected using CCK-8 assay. Cell invasion and migration were determined using transwell assay. Higher expression of PKM2 was observed in human gastric carcinoma cell lines MKN-45 and SGC-7901 than in the normal gastric mucosa epithelial cell line GES-1. PKM2 knockdown suppressed cancer cell invasion and migration and inhibited the epithelial-mesenchymal transition (EMT) phenotype by inhibiting E-cadherin and promoting vimentin and N-cadherin expression. Also, we observed that PKM2 knockdown suppressed the hypoxia-inducible factor alpha (HIF-1α) and B-cell lymphoma 6 (BCL-6) signaling pathway. HIF-1α overexpression reversed the function of PKM2 silencing on cell invasion, migration, EMT, and BCL-6 expression. BCL-6 overexpression also reversed the function of PKM2 silencing on cell invasion, migration, and EMT but did not affect HIF-1α expression. Taken together, data from our study suggest that PKM2 knockdown impeded cell migration, invasion, and EMT of gastric carcinoma cells via the HIF-1α/BCL-6 pathway.

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR-149-5p/IL-6/STAT3 pathway.

Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed-loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real-time PCR (RT-PCR) was employed to detect circ_0000654 and miR-149-5p expression in ESCC tissues. Circ_0000654 and miR-149-5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT-PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual-luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR-149-5p, miR-149-5p and IL-6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR-149-5p and facilitated ESCC progression by indirectly activating the IL-6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR-149-5p and activating the IL-6/STAT3 signaling pathway.

CircRNA_001569 promotes cell proliferation through absorbing miR-145 in gastric cancer.

Gastric cancer severely threatens human life, while its pathogenesis is still unclear. The present study was to explore the potential pathogenic mechanism underlying gastric cancer. Real-time PCR was performed to detect the expression of circRNA_001569 and miR-145; western blot was performed to detect the expression of NR4A2. Cell cycle and apoptosis was determined using flow cytometry, and cell viability was determined using Cell counting kit-8 (CCK-8) assay. Luciferase reporter assay was carried out to validate the relationship between miR-145 and NR4A2. Both circRNA_001569 and NR4A2 were overexpressed in tissues and cells of gastric cancer, while miR-145 was down-regulated. Overexpressed circRNA_001569 significantly increased cell viability, and decreased cell apoptosis, while down-regulated circRNA_001569 dramatically decreased cell viability and promoted cell apoptosis. CircRNA_001569 regulated the expression of miR-145, the effect of pcDNA-circRNA_001569 was abolished by miR-145 mimic and the effect of si-circRNA_001569 was abolished by miR-145 inhibitor. MiR-145 targets NR4A2 to regulate its expression. Overexpressed miR-145 suppressed cell viability and promoted cell apoptosis. Taken together, the present study indicated that overexpressed circRNA_001569 promoted cell viability of gastric cancer through suppressing the expression of miR-145, which was mediated by NR4A2. The research will provide great theoretical basis for further clinical diagnosis and therapy.

Overexpression of HOTAIR leads to radioresistance of human cervical cancer via promoting HIF-1α expression.

BACKGROUND: HOTAIR was known to enhance radioresistance in several cancers. However, the function of HOTAIR on radioresistance involving the regulation of HIF-1α in cervical cancer has not been reported. METHODS: BALB/c nude mice were injected subcutaneously with HeLa cells and irradiated by X-ray. The tumor volume was measured and the expression of HOTAIR in tumors was detected by quantitative real-time PCR. Western blot was performed to detect the protein level of HIF-1α. MTT (3-(4,5-Dimethylthiazol-2-yl) 22,5-diphenyltetrazolium bromide) assay and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to examine the cell viability and cell apoptosis of HeLa cells and C33A cells exposed to radiation. RESULTS: Radiotherapy inhibited the tumor growth in mice bearing HeLa cells. Radiotherapy reduced the expression of HOTAIR and HIF-1α in tumor tissues and HeLa cells or C33A cells. HOTAIR overexpression abrogated the effect of radiation on the cell viability and cell apoptosis of HeLa and C33A cells. HOTAIR also upregulated the expression of HIF-1α in HeLa and C33A cell exposed to radiation. HIF-1α knockdown reversed increasing cell viability and reducing apoptosis of HeLa and C33A cell induced by HOTAIR overexpression. HOTAIR overexpression promoted tumor growth in mice bearing HeLa and exposed to radiation. CONCLUSION: Radiotherapy might inhibit cervical cancer cell growth through HOTAIR/HIF-1α pathway.

Combination radiotherapy and cantharidin inhibits lung cancer growth through altering tumor infiltrating lymphocytes.

This study aimed to detect the effect of combination radiotherapy and cantharidin on lung cancer growth. We found that combination therapy with radiotherapy and cantharidin was more effective in inhibiting the tumor growth than radiotherapy or cantharidin alone. It decreased the percentage of CD4+ Tregs and enhanced the percentage of CD8+ T cells, CD4+ Teff cells when comparing to that of single treatment. Combination therapy promoted a great increase in double producing CD8+ T cells and CD4+ Teff cells in tumor infiltrating lymphocytes. Overexpression of CTLA4 reversed the inhibitory action of combination treatment on cancer growth. Our data suggest that combining radiotherapy and cantharidin may have synergistic effects in driving tumor rejection by increasing T-cell infiltration, proliferation and cytokine production.