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SRY-box transcription factors (SOXs) are effective inducers for the formation of stem-like phenotypes. As a member of SOX family,SOX9(SRY-box transcription factor 9) has been reported to be highly expressed and exert oncogenic functions in multiple human cancers. In this study, we hypothesized thatSOX9could regulate the function of cancer stem/initiating cells (CSCs) to further facilitate the progression of colorectal cancer (CRC). Then, stable transfection of shRNAs was used to silence indicated genes. Loss-of-function experiments were conducted to demonstrate the in vitro function of CRC cells. In vivo study was conducted to determine the changes in tumorigenesis and metastasis in vivo. Bioinformatics analyses and mechanistic experiments were employed to explore the downstream molecules. Presently, GEPIA data indicated thatSOX9was upregulated in 275 COAD (colon adenocarcinoma) samples relative to 349 normal tissues. Besides, we also proved the upregulation ofSOX9in CRC cell lines (HCT15, SW480, SW1116, and HT-29) compared to normal NCM-460 cells. Silencing ofSOX9suppressed cell growth, stemness, migration, and invasion. Mechanistically, SOX9 activated the transcription of lncRNA phenylalanyl-tRNA synthetase subunit alpha antisense RNA 1 (FARSA-AS1), whileFARSA-AS1elevatedSOX9in turn by absorbingmiR-18b-5pand augmentedFARSAvia sequesteringmiR-28-5p. Furthermore, loss ofFARSA-AS1hindered malignant phenotypes in vitro and blocked tumor growth and metastasis in vivo. Notably, we testified thatFARSA-AS1aggravated the malignancy in CRC by enhancingSOX9andFARSA. Our study unveiled a mechanism of SOX9-FARSA-AS1-SOX9/FARSAloop in CRC, which provides some clews of promising targets for CRC.

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Recent studies have shown that abnormal epigenetic regulation plays an important role in the occurrence and development of gastric cancer (5). Polycomb Repressor

Objective We aimed to explore the prognostic value of primary tumor and specific metastases excision on survival among patients with stage IV colorectal cancer (CRC) in the Surveillance, Epidemiology, and End Results (SEER) database. Methods Patients with stage IV CRC were selected using SEER database between 2010 and 2013. Survival rate was calculated according to the Kaplan-Meier method, and differences between curves were tested by the log-rank test. Cox proportional hazards model was used in the multivariable analysis. Results Included in this study were 27 878 patients with distant metastatic CRC. Among the single organ site of metastatic CRC, patients with solitary metastasis of lung showed the highest median overall survival (OS). Both primary and metastatic sites surgical resection for patients with liver, lung, and simultaneous liver and lung metastases had better median OS. Age younger than 65 years, Asian and Pacific Islander, distal colon and rectum, and palliative primary tumor and metastatic lesions resection were associated with better OS after multivariate analysis. Palliative primary tumor and metastatic lesions resection had a significant survival benefit compared with nonsurgical group in selected patients. Conclusion These findings support the use of preemptive surgery in the management of highly selected metastatic CRC patients.

Near‐infrared (NIR) photothermal therapy plays a critical role in the cancer treatment and diagnosis as a promising carcinoma treatment modalities nowadays. However, development of clinical application has been greatly limited due to the inefficient drug release and low tumor accumulation. Herein, we designed a NIR‐light triggered indocyanine green (ICG)‐based PCL core/P(MEO 2 MA‐ b ‐HMAM) shell nanocomposites (PPH@ICG) and evaluated their therapeutic effects in vitro and in vivo. The anticancer drug 5‐fluorouracil (5Fu) and the photothermal agent ICG were loaded into a thermo‐sensitive micelle (PPH@5Fu@ICG) by self‐assembly. The nanoparticles formed were characterized using transmission electron microscopy, dynamic light scattering, and fluorescence spectra. The thermo‐sensitive copolymer (PPH@5Fu@ICG) showed a great temperature‐controlled drug release response with lower critical solution temperature. In vitro cellular uptake and TEM imaging proved that PPH@5Fu@ICG nanoparticles can home into the lysosomal compartments under NIR. Moreover, in gastric tumor‐bearing nude mice, PPH@5Fu@ICG + NIR group exhibited excellent improvement in antitumor efficacy based on the NIR‐triggered thermo‐chemotherapy synergy, both in vitro and in vivo. In summary, the proposed strategy of synergistic photo‐hyperthermia chemotherapy effectively reduced the 5Fu dose, toxic or side effect, which could serve as a secure and efficient approach for cancer theranostics.

We aimed to explore the potential prognostic impact of the metastatic site on the management approach and prognosis of stage IV colorectal cancer patients with synchronous metastases. Synchronous metastatic colorectal cancer patients reported to the Surveillance, Epidemiology, and End Results Program database between 2010 and 2013 were included in this study. Overall survival (OS) was compared between patients with different treatment options using risk-adjusted Cox proportional hazard regression models. Overall, 17,776 patients with stage IV colorectal cancer were identified. Of these patients, 2,052 (11.5%) underwent surgical resection for tumors at both the primary and meta-static sites. Patients who underwent surgical resection of both primary and metastatic sites with liver, lung, and simultaneous liver and lung metastases had a longer median OS ( P < 0.001) than patients who underwent nonsurgical treatments. Cox regression analysis revealed that surgical resection of both primary and metastatic sites was associated with a significantly enhanced OS ( P < 0.001). Colorectal cancer patients with hepatic or pulmonary metastases, who underwent metastasectomy, even in selected patients with both hepatic and pulmonary metastases after multidisciplinary evaluation, could have a better survival benefit than patients who underwent nonsurgical treatments.

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