Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA.

BACKGROUND: BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. METHODS: Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. RESULTS: The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. CONCLUSION: Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells.

BACKGROUND: Our previous works have demonstrated that 8-bromo-7-methoxychrysin suppressed stemness of human hepatocellular carcinoma (HCC) cell line SMMC-7721 induced by condition medium from hepatic stellate cell line LX-2 that was activated by liver cancer stem-like cells (LCSCs). However, whether and whereby BrMC inhibits the stemness induced by co-culture of LCSCs and LX-2 cells remains to be investigated. METHODS: The second-generation spheres by sphere culture were identified and used as SMMC-7721-and MHCC97H-derived LCSLCs. SMMC-7721-and MHCC97-derived LCSCs/LX-2 cells transwell co-culture system was treated with BrMC and its lead compound chrysin. The concentrations of IL-6, IL-8, HGF and PDGF in condition medium from co-culture were measured by enzyme-linked immunosorbent assay (ELISA). The stemness of SMMC-7721 cells was evaluated by sphere formation assay and western blot analysis for expression levels of cancer stem cell markers (CD133 and CD44).The expression levels of cancer-associated fibroblast markers (FAP-α and α-SMA) were employed to evaluate pathologic activation of LX-2 cells. Addition of IL-6 and/or HGF or deletion of IL-6 and/or HGF was conducted to investigate the mechanisms for BrMC and chrysin treatment in SMMC-7721-derived LCSLCs co-cultured with LX-2cells. RESULTS: The co-culture of LCSLCs with LX-2 cells increased sphere formation capability as well as expression of CD133 and CD44 in SMMC-7721 cells, meanwhile, upregulated expression of FAP-α in LX-2 cells. ELISA indicated that the concentrations of IL-6 and HGF were significantly elevated in Co-CM than that of condition media from co-cultured SMMC-7721 cells/LX-2 cells. Treatment of BrMC and chrysin with co-cultures of SMMC-7721- and MHCC97H-derived LCSLCs and LX-2 cells effectively inhibited the above responses. Moreover, addition of IL-6 and/or HGF induced stemness of SMMC-7721 cells and activation of LX-2 cells, conversely, deletion of IL-6 and/or HGF suppressed those. Furthermore, the inhibitory effects of BrMC and chrysin on stemness of SMMC-7721 cells and activation of LX-2 cells were attenuated by addition of IL-6 or HGF, and enhanced by deletion of IL-6 or HGF. CONCLUSIONS: Our results suggest IL-6 and HGF may be the key communication molecules for the interaction between LCSLCs and HSCs, and BrMC and chrysin could block these effects and be the novel therapeutic candidates for HCC management.

Survival Comparisons between Breast Conservation Surgery and Mastectomy Followed by Postoperative Radiotherapy in Stage I-III Breast Cancer Patients: Analysis of the Surveillance, Epidemiology, and End Results (Seer) Program Database.

Background: This study aims to evaluate the overall and breast cancer-specific survival (BCSS) after breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy plus RT in resectable breast cancer. Moreover, the aim is to also identify the subgroups who benefit from BCS plus RT and establish a predictive nomogram for stage II patients. Methods: Stage I−III breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1990 and 2016. Patients with available clinical information were split into two groups: BCS plus RT and mastectomy plus RT. Kaplan−Meier survival analysis, univariate and multivariate regression analysis, and propensity score matching were used in the study. Hazard ratio (HR) was calculated based on stratified Cox univariate regression analyses. A prognostic nomogram by multivariable Cox regression model was developed for stage II patients, and consistency index (C-index) and calibration curve were used to evaluate the accuracy of the nomogram in the training and validation set. Results: A total of 24,590 eligible patients were enrolled. The difference in overall survival (OS) and BCSS remained significant in stage II patients both before and after PSM (after PSM: OS: HR = 0.8536, p = 0.0115; BCSS: HR = 0.7803, p = 0.0013). In stage II patients, the survival advantage effect of BCS plus RT on OS and BCSS was observed in the following subgroups: any age, smaller tumor size (<1 cm), stage IIA (T2N0, T0−1N1), ER (+), and any PR status. Secondly, the C-indexes for BCSS prediction was 0.714 (95% CI 0.694−0.734). The calibration curves showed perfect agreement in both the training and validation sets. Conclusions: BCS plus RT significantly improved the survival rates for patients of stage IIA (T2N0, T0−1N1), ER (+). For stage II patients, the nomogram was a good predictor of 5-, 10-, and 15-year BCSS. Our study may help guide treatment decisions and prolong the survival of stage II breast cancer patients.

MT1X is an oncogene and indicates prognosis in ccRCC.

The metallothionein 1 (MT1) family was previously shown to be involved in metal ion homeostasis, DNA damage, oxidative stress, and carcinogenesis. Our team's previous study showed that MT1X is most closely associated with ccRCC. However, its role in clear cell RCC (ccRCC) remains unclear. The present study aimed to demonstrate MT1X's prognostic value, potential biologic function, impact on the immune system, and influence on cell growth, the cell cycle, apoptosis, and migration in the setting of ccRCC. The relationship between clinical pathologic features and MT1X was analyzed using bioinformatics. We knocked down MT1X in the ccRCC cell line 786O with si-MT1X to verify the results of the bioinformatic analysis at the cytological level. Apoptosis assay, cell cycle assay, wound-healing assay, colony formation assay, and RT-qPCR were performed. MT1X is correlated with the stage (T and M) and grade and is able to be an independent prognostic factor for ccRCC. The TISIDB database analysis showed a significant correlation between MT1X and tumor-infiltrating lymphocytes such as central memory CD8+ T cells and γΔT cells. MT1X was also positively related to immunomodulators such as TGFB1 and CXCR4. We also found that MT1X knockdown inhibits cell growth, induces apoptosis, arrests cells in the S cell cycle, and inhibits the wound healing proportion in ccRCC. Gene set enrichment analysis and quantitative PCR (q-PCR) analysis found that down-regulation of MT1X reduced the accumulation of hypoxia-associated factors. Bioinformatic analysis associated increased MT1X expression with a worse prognosis. Laboratory experiments confirmed bioinformatic findings. MT1X was also found to be an independent prognostic biomarker for ccRCC and is involved in immune system regulation.

A Large Solitary Fibrous Tumor of the Nasal Cavity and Paranasal Sinuses Involving the Anterior Frontal Fossa: A Case Report and Review of the Literature.

The Solitary Fibrous Tumor (SFT) is a rare mesenchymal neoplasm that arises mainly from the pleura. The sinonasal tract is generally not affected by SFT, and less than 100 cases have been reported in the English literature to date. We report an extremely rare SFT of the nasal cavity and paranasal sinuses extending into the anterior frontal fossa through the floor of the anterior skull base. To our knowledge, this case is the fourth SFT of the sinonasal tract involving the anterior frontal fossa in the world. Meanwhile, the tumor, measuring 13 × 6 cm in images, is the largest SFT of the sinonasal tract compared to previously reported cases. Three surgical procedures, including a transcranial one, were performed for the patient to achieve complete removal of the tumor. The diagnosis of SFT was established primarily by immunohistochemical positivity for CD34, STAT6, and negativity for S-100 protein. We emphasize the possibility of recurrence in SFT, and close follow-up is necessary with the help of nasal endoscopy and imaging approaches.

Anti-tumour activity of zinc ionophore pyrithione in human ovarian cancer cells through inhibition of proliferation and migration and promotion of lysosome-mitochondrial apoptosis.

Zinc pyrithione (ZPT) is widely used as an antimicrobial. Zinc is a necessary trace element of the human whose homeostasis associated with several cancers. However, the anticancer effect of increased Zinc in ovarian cancer is still unclear. This study focussed on the anti-tumour effects of ZPT combined with Zinc in SKOV3 and SKOV3/DDP cells. The cell viability, apoptosis, migration, and invasion assays were detected by CCK-8, flow cytometry, wound healing and transwell assay, respectively. The distribution of Zinc in cells was monitored by staining of Zinc fluorescent dye and lysosome tracker. The changes in lysosomal membrane stability were reflected by acridine orange fluorescence and cathepsin D reposition. Expression of the proteins about invasion and apoptosis was evaluated by western blot. The results indicated that ZPT combined with Zinc could notably reduce cell viability, inhibit migration and invasion in SKOV3 and SKOV3/DDP cells. Besides, ZPT performed as a Zinc carrier targeted lysosomes, caused the increase of its membrane permeability and the release of cathepsin D accompanied by mitochondrial apoptosis in SKOV3/DDP cells. In conclusion, our work suggests that ZPT combined with Zinc could inhibit proliferation, migration, invasion, and promote apoptosis by trigger the lysosome-mitochondrial apoptosis pathway in ovarian carcinoma.