Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

Sorafenib may provide survival benefits for patients with advanced hepatocellular carcinoma. However, tumor cells can display primary or secondary resistance to Sorafenib. To identify genes capable of conveying Sorafenib resistance, we performed a genome-wide CRISPR transcriptional activation library (SAM) in human Huh7 cells. We identified that a group of sgRNAs were significantly enriched in Sorafenib resistant Huh7 cells, which indicated that these sgRNAs up-regulated their target genes and induced resistance. We finally identified LRP8 as a key gene that can drive HCC cell to acquire sorafenib resistance. All three sgRNAs targeting LRP8 were identified in Sorafenib resistant Huh7 cells with high copy. We also showed that sorafenib-acquired resistant Huh7 cells have much higher LRP8 expression level than parental Huh7 cells. We proved that overexpression of LRP8 in HCC cell lines activated ß-catenin and significantly promoted its resistance to Sorafenib. We further showed that overexpression of LRP8 reduced the apoptosis level of HCC cell lines. To summary, genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.

Wandering spleen torsion with portal vein thrombosis: A case report.

BACKGROUND: Wandering spleen is rare clinically. It is characterized by displacement of the spleen in the abdominal and pelvic cavities and can have congenital or acquired causes. Wandering spleen involves serious complications, such as spleen torsion. The clinical symptoms range from asymptomatic abdominal mass to acute abdominal pain. Surgery is required after diagnosis. Cases of wandering spleen torsion with portal vein thrombosis (PVT) are rare. There is no report on how to eliminate PVT in such cases. CASE SUMMARY: Ultrasound and computed tomography revealed a diagnosis of wandering spleen torsion with PVT in a 31-year-old woman with a history of childbirth 16 mo previously who received emergency treatment for upper abdominal pain. She recovered well after splenectomy and portal vein thrombectomy combined with continuous anticoagulation, and the PVT disappeared. CONCLUSION: Rare and nonspecific conditions, such as wandering splenic torsion with PVT, must be diagnosed and treated early. Patients with complete splenic infarction require splenectomy. Anticoagulation therapy and individualized management for PVT is feasible.

The prognostic ability of radiotherapy of different colorectal cancer histological subtypes and tumor sites.

The prognostic significance of radiotherapy (RT) for colorectal cancer (CRC) has shown conflicting results, particularly among different pathological subtypes, including adenocarcinoma (AC), mucinous adenocarcinoma (MC), and signet-ring cell carcinoma (SR). This study analyzed the prognosis of three pathological CRC types and focused on the prognostic significance of RT on three CRC histological subtypes. Patients diagnosed with AC (n = 54,174), MC (n = 3813), and SR (n = 664) in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (2010-2017) were evaluated. Cox regression models and competitive risk models were built to assess the effect of RT on the risk of CRC-associated death. Potential interactions between RT and stratified variables including age, sex, and tumor location were examined by multiplicative models. Compared with AC patients, SR patients had the worst overall survival (OS) among 3 subtypes of CRC (log-rank test, p < 0.001). Compared with patients who did not receive radiotherapy, RT was associated with a 1.09-fold (HR = 1.09, 95%[CI]: 1.03, 1.15) elevated risk of death among AC patients. In the SR group, RT significantly reduced the risk of death by 39% (HR = 0.61, 95%[CI]: 0.39-0.95). However, RT did not appear to independently influence survival in the MC group (HR = 0.96, 95%[CI]: 0.77, 1.21). In the subgroup analysis, tumor location (colon and rectum) significantly modified the association between RT and the risk of death among the AC and SR patients (p for interaction < 0.05). SR patients exhibited a worse OS (overall survival) than AC patients, and the effect of RT varied according to CRC histological subtypes. This can ultimately lead to more personalized and effective treatment strategies for CRC patients.

Clinicopathologic characteristics and prognosis for male breast cancer compared to female breast cancer.

Male breast cancer (MBC) is rare. Due to limited information, MBC has always been understudied. We conducted a retrospective population-based cohort study using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The clinical and biological features of female breast cancer (FBC) patients were compared with MBC patients. Cox regression models and competing risks analyses were used to identify risk factors associated with cancer-related survival in MBC and FBC groups. Results showed that MBC patients suffered from higher TNM stages, tumor grades, and a higher percentage of hormone receptor-positive tumors, compared with FBC patients (all p < 0.05). In addition, the breast tumor locations varied a lot between males and females (p < 0.05). FBC patients were associated with superior overall survival than MBC patients. Results from multivariate cox regression and competing risks analyses showed age, race, T, N, M-stages, tumor grades, estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) overexpression were independent prognosis factors in FBC patients (all p < 0.05). MBC patients had similar risk factors to FBC patients, but PR and HER-2 status did not independently influence survival (all p > 0.05). Tumor location was an independent prognostic factor for both gender groups.

MTF2 Induces Epithelial-Mesenchymal Transition and Progression of Hepatocellular Carcinoma by Transcriptionally Activating Snail.

BACKGROUND: Metal regulatory transcription factor 2 (MTF2) has been previously reported as a protein binding to the metal response element of the mouse metallothionein promoter, which is involved in chromosome inactivation and pluripotency. However, the function of MTF2 in tumor formation and progression has not yet been completely elucidated. METHODS: The expression of MTF2 and clinicopathological characteristics were evaluated by hepatocellular carcinoma (HCC) tissue microarray of 240 specimens. The role of MTF2 on HCC progression was determined using MTT, crystal violet, and transwell assays. Tumor growth was monitored in a xenograft model, and intrahepatic metastasis models were established. RESULTS: The expression of MTF2 was increased in HCC and strongly associated with the clinical characteristics and prognosis. Forced expression of MTF2 in HCC cells significantly promoted cell growth, migration, and invasion in vitro. In contrast, downregulation of MTF2 inhibited cell growth, migration, and invasion in vitro. Moreover, knock down of MTF2 suppressed tumorigenesis and intrahepatic metastasis of HCC cells in vivo. Mechanistically, MTF2 overexpression may promote growth and epithelial-mesenchymal transition processes of HCC cells by facilitating Snail transcription. CONCLUSION: MTF2 promotes the proliferation, migration, and invasion of HCC cells by regulating Snail transcription, providing a potential therapeutic candidate for patients with HCC.