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Radiotherapy has become an increasingly widespread modality for treating hepatocellular cancer (HCC); however, the development of radioresistance significantly limits its effectiveness and invariably leads to tumor recurrence. Cancer stem cell (CSC) theory offers a potential explanation for tumor relapse and radioresistance, but the underlying mechanism remains unknown. Herein we investigate the role of miRNA in molecular regulation of stemness and radioresistance in HCC. Two HCC radiation-resistant cell lines (Huh7-RR and SMMC-7721-RR) were established by selecting the radioresistant subpopulation from HCC cells via clonogenic survival assays. MiRNA Sequencing was used to identify potential radiosensitivity involved miRNA in HCC-RR cells. Xenograft tumor mouse model was established for in vivo study. CSC properties were assessed using sphere formation assay and side population (SP) cells analysis. We found that miR-34a-5p was significantly downregulated in HCC-RR cells. Overexpression of miR-34a-5p counteracts CSC properties and enhances radiosensitivity in HCC. Mechanistic investigation revealed that c-MYC is the direct target of miR-34a-5p. Overexpression of miR-34a-5p reversed c-MYC-induced radioresistance. Moreover, we found that the specific molecular mechanism was that c-MYC activated CHK1 and CHK2, which are two key DNA damage checkpoint kinases, and facilitated the DNA damage response to radiation. Repression of the miR-34a-5p-cMYC-CHK1/CHK2 axis contributes to the acquisition of radioresistance in HCC cells. In summary, the miR-34a-5p-c-MYC-CHK1/CHK2 axis counteracts cancer stem cell-like properties and enhances radiosensitivity in hepatocellular cancer through repression of the DNA damage response. [ABSTRACT FROM AUTHOR]

Scavenger receptor class B type I (SR-BI), a well-documented high-density lipoprotein receptor, has been implicated in the development and progression of human cancer. However, little is known regarding the expression profile and clinical value of SR-BI in gastric adenocarcinoma. In the present study immunohistochemistry analysis was performed on a well-annotated gastric adenocarcinoma tissue microarray to investigate the association between SR-BI expression and clinicopathological parameters or patient outcome. The results revealed that SR-BI expression was detected in 69% of the 84 gastric adenocarcinomas. Moreover, a significant association was observed between low SR-BI expression and poor histological grade, higher Tumor-Node-Metastasis T stage, higher N stage and diffuse type carcinoma. Low SR-BI expression was also significantly associated with a shorter overall survival time in patients with gastric adenocarcinoma, although it was not an independent prognostic factor. Overall, the results of the present study demonstrated that SR-BI was possibly involved in gastric carcinogenesis and could be used as a biomarker to predict malignancy of gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Scavenger receptor class B type I (SR-BI) has been linked to the development and progression of breast cancer. However, its clinical significance in breast cancer remains unclear. Here, we evaluated SR-BI expression in a well-characterized breast cancer tissue microarray by immunohistochemistry. High SR-BI expression was observed in 54 % of all breast cancer cases and was significantly associated with advanced pTNM stage ( P = 0.002), larger tumor size ( P = 0.023), lymph node metastasis ( P = 0.012), and the absence of ER ( P = 0.014). The Kaplan-Meier survival analysis revealed that patients with high SR-BI expression had significantly shorter overall survival (OS) ( P = 0.004). Moreover, multivariate analysis with adjustment for other prognostic factors confirmed that SR-BI was an independent prognostic factor for patient outcome ( P = 0.017). Overall, our study demonstrated that high SR-BI expression was related to conventional parameters indicative of more aggressive tumor type and may serve as a new prognostic marker for poor clinical outcome in human breast cancer. [ABSTRACT FROM AUTHOR]

Scavenger receptor class B type I (SR-BI) has been linked to the development and progression of breast cancer. However, its clinical significance in breast cancer remains unclear. Here, we evaluated SR-BI expression in a well-characterized breast cancer tissue microarray by immunohistochemistry. High SR-BI expression was observed in 54 % of all breast cancer cases and was significantly associated with advanced pTNM stage (P = 0.002), larger tumor size (P = 0.023), lymph node metastasis (P = 0.012), and the absence of ER (P = 0.014). The Kaplan-Meier survival analysis revealed that patients with high SR-BI expression had significantly shorter overall survival (OS) (P = 0.004). Moreover, multivariate analysis with adjustment for other prognostic factors confirmed that SR-BI was an independent prognostic factor for patient outcome (P = 0.017). Overall, our study demonstrated that high SR-BI expression was related to conventional parameters indicative of more aggressive tumor type and may serve as a new prognostic marker for poor clinical outcome in human breast cancer.

Alveolar soft-part sarcoma (ASPS) is an uncommon soft-tissue neoplasm, which is commonly found in the deep soft tissues of the extremities, with a propensity for recurrence and metastasis. However, the metastasis of ASPS to the heart is exceedingly rare. The present study reports such a rare case with cardiac metastasis. Using computed tomography, a 37-year-old man was diagnosed with brain, lung and spleen metastases from a previously treated ASPS in the left forearm. Cardiac metastasis was then diagnosed 1 month later. Despite chemotherapy and palliative whole-brain radiotherapy, the patient succumbed to the disease shortly after. This case suggests that the widespread metastases and cardiac involvement of ASPS may result in a poor outcome.