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.

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.

Surgical treatment of acute calculous cholecystitis complicated with hepatic dysfunction.

To evaluate the timing, feasibility, and necessity of early laparoscopic cholecystectomy (LC) in the management of patients with acute calculous cholecystitis complicated with hepatic dysfunction.The clinical data of 60 patients with acute calculous cholecystitis complicated with hepatic dysfunction treated from January 2016 to January 2018 were analyzed retrospectively. A total of 32 patients underwent LC within 72 hours of the cholecystitis attack, 28 patients after 72 hours. The results were compared with those from 28 patients with delayed LC.All the patients were operated by experienced surgeons, and no LC transfer to open operation. No significant differences were detected in the operation time, postoperative complications, intraoperative blood loss, white TBIL, ALT, GGT before and after the operation between the 2 groups (P > .05). Patients who underwent early LC had a short hospital stay and fewer hospital costs (P < .05). All the patients were cured.It is safe, feasible, and necessary to perform LC within 72 hours in patients with acute calculous cholecystitis complicated with hepatic dysfunction. Such patients show a high positive correlation between the inflammation of acute calculous cholecystitis and the damage of hepatic function.

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.

Humeral brown tumor as first presentation of primary hyperparathyroidism caused by ectopic parathyroid adenomas: report of two cases and review of literature.

Two cases of brown tumor of the humerus caused by ectopic parathyroid adenomas were presented, which to our knowledge has not been previously documented in the international literature. There are two highlights in these two cases. First, brown tumors of the long bones may commonly involve femur and tibia, rarely involve humerus in association with primary hyperparathyroidism. Second, ectopic parathyroid adenomas of our patient had an unusual location of this disorder. We explored the role of ultrasound, MIBI scintigraphy as well as FNAB (fine needle aspiration biopsy) in diagnosis of brown tumor especially simultaneously occurrence of ectopic parathyroid adenomas and the importance of a thorough diagnostic work-up. The contemporary diagnosis and treatment options will be emphasized.