Background: Oral squamous cell carcinoma (OSCC) has a high prevalence and predicted global mortality rate of 67.1%, necessitating better therapeutic strategies. Moreover, the recurrence and resistance of OSCC after chemo/radioresistance remains a major bottleneck for its effective treatment. Molecular targeting is one of the new therapeutic approaches to target cancer. Among a plethora of targetable signaling molecules, PDK1 is currently rising as a potential target for cancer therapy. Its aberrant expression in many malignancies is observed associated with glycolytic re-programming and chemo/radioresistance. Methods: Furthermore, to better understand the role of PDK1 in OSCC, we analyzed tissue samples from 62 patients with OSCC for PDK1 expression. Combining in silico and in vitro analysis approaches, we determined the important association between PDK1/CD47/LDHA expression in OSCC. Next, we analyzed the effect of PDK1 expression and its connection with OSCC orosphere generation and maintenance, as well as the effect of the combination of the PDK1 inhibitor BX795, cisplatin and radiotherapy in targeting it. Results: Immunohistochemical analysis revealed that higher PDK1 expression is associated with a poor prognosis in OSCC. The immunoprecipitation assay indicated PDK1/CD47 binding. PDK1 ligation significantly impaired OSCC orosphere formation and downregulated Sox2, Oct4, and CD133 expression. The combination of BX795 and cisplatin markedly reduced in OSCC cell’s epithelial-mesenchymal transition, implying its synergistic effect. p-PDK1, CD47, Akt, PFKP, PDK3 and LDHA protein expression were significantly reduced, with the strongest inhibition in the combination group. Chemo/radiotherapy together with abrogation of PDK1 inhibits the oncogenic (Akt/CD47) and glycolytic (LDHA/PFKP/PDK3) signaling and, enhanced or sensitizes OSCC to the anticancer drug effect through inducing apoptosis and DNA damage together with metabolic reprogramming. Conclusions: Therefore, the results from our current study may serve as a basis for developing new therapeutic strategies against chemo/radioresistant OSCC.

Chemotherapy drugs for oral cancers always cause side effects and adverse effects. Currently natural sources and herbs are being searched for treated human oral squamous carcinoma cells (OSCC) in an effort to alleviate the causations of agents in oral cancers chemotherapy. This study investigates the effect of prodigiosin (PG), an alkaloid and natural red pigment as a secondary metabolite of Serratia marcescens, to inhibit human oral squamous carcinoma cell growth; thereby, developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (OECM1 and SAS cell lines) were used to test the inhibitory growth of PG via cell cytotoxic effects (MTT assay), cell cycle analysis, and Western blotting. PG under various concentrations and time courses were shown to effectively cause cell death and cell-cycle arrest in OECM1 and SAS cells. Additionally, PG induced autophagic cell death in OECM1 and SAS cells by LC3-mediated P62/LC3-I/LC3-II pathway at the in vitro level. These findings elucidate the role of PG, which may target the autophagic cell death pathways as a potential agent in cancer therapeutics.

BACKGROUND:. Stereotactic radiosurgery represents a noninvasive alternative treatment for intracranial metastases.OBJECTIVE:. To investigate the treatme

Locally advanced oral squamous cell carcinoma (OSCC) requires multimodal therapy, including surgery and concurrent chemoradiotherapy (CCRT). CCRT-resistant and recurrent cancer has a poor prognosis. We investigated the effects of Bruton’s tyrosine kinase (BTK) on CCRT-resistant OSCC tissues. The effect of ibrutinib, a first-in-class BTK inhibitor, was tested on stem cell-like OSCC tumorspheres. A tissue array was constructed using tissue samples from 70 patients with OSCC. Human OSCC cell lines, SAS, TW2.6 and HSC-3, were examined. Wound healing, Matrigel invasion, and tumorsphere formation assays, as well as immunofluorescence analysis and flow cytometry, were used to investigate the effects of BTK knockdown (shBTK), ibrutinib, cisplatin, and ibrutinib/cisplatin combination on OSCC cells. We demonstrated that BTK was aberrantly highly expressed in the clinical CCRT-resistant OSCC tissue array, which resulted in poor overall survival in our local Tri-Service General Hospital and freely accessible TCGA OSCC cohorts. shBTK significantly downregulated the stemness markers Nanog, CD133, T cell immunoglobulin-3 (TIM-3), and Krüppel-like factor 4 (KLF4) in SAS tumorspheres and attenuated OSCC cell migration and colony formation. Ibrutinib reduced the number of aldehyde dehydrogenase (ALDH)-rich OSCC cells and reduced tumorsphere formation, migration, and invasion in a dose-dependent manner. Compared with ibrutinib or cisplatin monotherapy, the ibrutinib/cisplatin combination significantly reduced the formation of ALDH + OSCC tumorspheres and enhanced apoptosis. These results demonstrate that ibrutinib effectively inhibits the CSCs-like phenotype of OSCC cells through dysregulation of BTK/CD133 signaling. The ibrutinib/cisplatin combination may be considered for future clinical use.

This study aimed to compare the clinical outcomes of stereotactic ablative radiotherapy (SABR) and conventionally fractionated radiotherapy (CFRT) in hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). HCC patients with PVI treated with radiotherapy from 2007 to 2016 were analysed. CFRT was administered at a median dose of 51.5 Gy (interquartile range, 45–54 Gy) with 1.8–3 Gy per fraction. SABR was administered at a median dose of 45 Gy (interquartile range, 40–48 Gy) with 6–12.5 Gy per fraction. Treatment efficacy, toxicity, and associated predictors were assessed. Among the 104 evaluable patients (45 in the SABR group and 59 in the CFRT group), the overall response rate (ORR, complete and partial response) was significantly higher in the SABR group than the CFRT group (62.2% vs. 33.8%, p = 0.003). The 1-year overall survival (OS) rate (34.9% vs. 15.3%, p = 0.012) and in-field progression-free survival (IFPS) rate (69.6% vs. 32.2%, p = 0.007) were also significantly higher in the SABR vs. CFRT group. All 3 rates remained higher in the SABR group after propensity score matching. Multivariable analysis identified SABR and a biologically effective dose ≥65 Gy as favourable predicators of OS. There was no difference between treatment groups in the incidence of radiation-induced liver disease or increase of Child-Pugh score ≥ 2 within 3 months of radiotherapy. SABR was superior to CFRT in terms of ORR, OS, and IFPS. We suggest that SABR should be the preferred technique for HCC patients with PVI.

Background: Aquaporin 5 (AQP5) is most likely the primary water channel in the human nasal mucosa and acts as a key tight junction protein. The signaling cascades responsible for AQP5 regulation are still works in progress.