The correlation between CT features and insulin resistance levels in patients with T2DM complicated with primary pulmonary tuberculosis.

The aim is to investigate the correlation between computed tomography (CT) features and insulin resistance levels in patients with type 2 diabetes mellitus (T2DM) complicated with primary pulmonary tuberculosis (PTB). Nearly, 268 untreated PTB patients complicated with T2DM were divided into two groups according to the optimal cutoff value of HOMA-IR score for the Chinese population: HOMA-IR ≤ 2.69 (Group I: 74 patients), >2.69 (Group II: 194 patients). The basic characteristics and changes of CT manifestations were analyzed. In the two groups, the detection rate of large segmented leafy shadow was 39.2% and 78.9%; the air bronchogram sign detection rate was 40.5% and 80.9%; the discovery rate of mouth-eaten cavity was 33.8% and 73.7%; the thin-walled cavity detection rate was 2.7% and 16.0%; the rate of multiple cavities was 35.1% and 69.6%; and bronchial tuberculosis was found in 4.1% and 35.6%, respectively. The detection rates of lesions in Group II were significantly higher than in Group I (p < .05). HOMA-IR was found independently associated with large segmented leafy shadow, air bronchial sign, thin-walled cavity, and bronchial tuberculosis. The level of insulin resistance can effectively reflect the severity of PTB patients with T2DM. CT scan can directly provide image information in clinics. These two examinations can guide clinicians to accurately formulate subsequent treatment plans.

Correction to: Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.

An amendment to this paper has been published and can be accessed via the original article.

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.

BACKGROUND: Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. METHODS: Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. RESULTS: Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvß3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvß3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. CONCLUSIONS: Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC. Video Abstract.

FGFR4 Links Glucose Metabolism and Chemotherapy Resistance in Breast Cancer.

BACKGROUND/AIMS: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. METHODS: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR). Protein expression was detected by Western blotting analysis and mRNA expression was detected using q-PCR. Cell survival ratio was determined by the cell counting kit 8 assay. The role of fibroblast growth factor receptor 4 (FGFR4) in glycolysis, chemoresistance, and the underlying mechanisms were studied by using gene expression microarray and short hairpin RNA-mediated gene knockdown. RESULTS: We found that glycolytic flux are increased in two doxorubicin (ADR)-resistant breast cancer cell lines compared with their parental wild type cells, as demonstrated by increased glucose uptake, lactate release, and extracellular acidification rate (ECAR). By gene expression microarray, we identified FGFR4 as a critical modulator of ADR resistance and enhanced glucose metabolism. Genetic silencing of FGFR4 increased the chemosensitivity and suppressed the enhanced glycolytic flux in ADR-resistant cells. Mechanistically, activation of FGFR4 signaling in ADR-resistant cells led to the phosphorylation of FGF receptor substrate 2 (FRS2) and further activated the downstream MAPK/ERK signaling. Pharmacological inhibition of FGFR4-FRS2-ERK signaling pathway significantly blocked the chemoresistant and glycolytic phenotypes of ADR-resistant cells. CONCLUSION: Our findings suggest that high levels of FGFR4 can increase glucose metabolism and lead to chemoresistance in breast cancer and reveal the mechanistic basis for targeting FGFR4 as a therapeutic opportunity for chemoresistant tumors.

Multiple primary malignancies - hepatocellular carcinoma combined with splenic lymphoma: A case report.

BACKGROUND: Primary liver cancer is one of the most common malignant tumours, while primary splenic lymphoma is a rare malignancy. Thus, cases of hepatocellular carcinoma (HCC) combined with splenic lymphoma are extremely rare. CASE SUMMARY: We present a 62-year-old woman who was admitted to the Interventional Radiology Department with a lump in the spleen and liver as well as multiple enlarged lymph nodes visible by ultrasound. Contrast-enhanced computed of the abdomen revealed a circular, low-density, shallow mass (approximately 2.6 cm in diameter) in the left intrahepatic lobe and multiple round, low-density shadows in the spleen with clear boundaries (maximum diameter 7.6 cm). Based on the characteristic clinical symptoms and explicit radiological findings, the clinical diagnosis was HCC with metastasis to the liver portal, retroperitoneal lymph nodes, and spleen. After transcatheter arterial chemoembolization and sequential radiofrequency ablation, the -fetoprotein level returned to the normal range, and the hepatitis B cirrhosis improved. In addition, splenic tumour biopsy confirmed the diagnosis of primary malignant lymphoma, which went into remission after chemotherapy. CONCLUSION: HCC with primary splenic non-Hodgkin lymphoma is extremely rare and easily misdiagnosed. Better understanding would facilitate early diagnosis, treatment and prognosis.

Percutaneous biliary stent combined with brachytherapy using 125I seeds for treatment of unresectable malignant obstructive jaundice: A meta-analysis.

BACKGROUND: Malignant obstructive jaundice (MOJ) is a common pathologic manifestation of malignant biliary obstruction. Recently, several clinical trials have explored the clinical effectiveness of intraluminal 125I seed-based brachytherapy for MOJ patients, and various outcomes have been reported. AIM: To assess the efficacy and safety of percutaneous biliary stents with 125I seeds compared to conventional metal stents in patients with unresectable MOJ. METHODS: A systematic search of English-language databases (PubMed, Embase, Cochrane Library, and Web of Science) was performed to identify studies published prior to June 2020 that compared stents with or without 125I seeds in the treatment of unresectable MOJ. The outcomes analyzed included primary outcomes (stent patency and overall survival) and secondary outcomes (complications and liver function parameters). RESULTS: Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis. Of the 875 included patients, 404 were treated with 125I seed stents, while 471 were treated with conventional stents. Unadjusted pooled analysis demonstrated that compared to conventional stents, 125I seed stents extended the stent patency time [hazard ratio (HR) = 0.36, 95% confidence interval (CI) = 0.28-0.45, P < 0.0001] and overall survival period (HR = 0.52, 95%CI = 0.42-0.64, P < 0.00001). Subgroup analyses based on the type of 125I seed stent and type of study design showed consistent results. However, there were no significant differences in the occurrence of total complications [odds ratio (OR) = 1.12, 95%CI = 0.75-1.67, P = 0.57], hemobilia (OR = 1.02, 95%CI = 0.45-2.3, P = 0.96), pancreatitis (OR = 1.79, 95%CI = 0.42-7.53, P = 0.43), cholangitis (OR = 1.13, 95%CI = 0.60-2.13, P = 0.71), or pain (OR = 0.67, 95%CI = 0.22-2, P = 0.47). In addition, there were no reductions in the levels of serum indices, including total bilirubin [mean difference (MD) = 10.96, 95%CI = -3.56-25.49, P = 0.14], direct bilirubin (MD = 7.37, 95%CI = -9.76-24.5, P = 0.4), alanine aminotransferase (MD = 7.52, 95%CI = -0.71-15.74, P = 0.07), and aspartate aminotransferase (MD = -4.77, 95%CI = -19.98-10.44, P = 0.54), after treatment. Publication bias was detected regarding the outcome overall survival; however, the conclusions were not changed after the adjustment. CONCLUSION: Placement of stents combined with brachytherapy using 125I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage. Thus, it can be considered an effective and safe treatment for unresectable MOJ.

Drug-eluting beads-transcatheter arterial chemoembolization with or without iodine-125 treatment is effective and tolerable in treating advanced non-small cell lung cancer patients: a pilot study.

BACKGROUND: This study aimed to explore the efficacy and safety of drug-eluting beads-transcatheter arterial chemoembolization (DEB-TACE) with or without iodine-125 (125I) seed implantation in treating advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 25 advanced NSCLC patients underwent DEB-TACE were consecutively enrolled, among which 17 cases also received 125I seed implantation post DEB-TACE treatment. Treatment response, overall survival (OS), biochemical indexes and safety profiles were recorded and analyzed. RESULTS: Zero (0.0%), 13 (54.2%), 9 (37.5%) and 2 (8.3%) patients realized complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) respectively, and the objective response rate (ORR) and disease control rate (DCR) were 54.2% and 91.7%. The median OS was 12.6 (95% CI: 7.8-17.5) months. No difference of treatment response or OS was observed between DEB-TACE treatment alone and DEB-TACE plus 125I seed implantation. Predictive factors analysis revealed that tumor size correlated with worse OS. Besides, chest distress grade and dyspnea grade were decreased after DEB-TACE procedure, while clinical symptoms were not changed after 125I seed implantation. The common adverse events (AEs) were fever (32.0%), pain (12.0%) by DEB-TACE treatment, and common AE was pain (26.7%) by 125I seed implantation. CONCLUSIONS: DEB-TACE with or without 125I seed implantation is effective and tolerable in treating advanced NSCLC patients.

CPSF7 regulates liver cancer growth and metastasis by facilitating WWP2-FL and targeting the WWP2/PTEN/AKT signaling pathway.

Alternative splicing within a gene can create different versions of an mRNA, called isoforms. CFIm, composed of a small subunit CFIm25 and two large subunits CFIm68 and CFIm59 (also known as CPSF7), has been proposed as an enhancer-dependent activator of mRNA 3' processing. In this study, we investigated the role of CPSF7 in hepatocellular carcinoma. Experimental evidence suggests that the expression level of CPSF7 is higher in liver cancer cells and tissues than in non-tumor hepatic cells and tissues. Furthermore, knockdown of CPSF7 effectively suppressed cell proliferation, migration and colony formation in liver cancer cells by inhibiting PTEN/AKT signaling. CPSF7 promoted WWP2-FL due to the presence of PTEN ubiquitination sites in this longer transcript. Taken together, we identified that CPSF7 regulates liver cancer growth by targeting WWP2-FL that in turn regulates AKT activation in a PTEN-dependent manner.

CRISPR-Cas9 for cancer therapy: Opportunities and challenges.

Cancer is a genetic disease stemming from cumulative genetic/epigenetic aberrations. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome editing technology has been extensively applied in various cell types and organisms, both in vitro and in vivo, for efficient gene disruption and gene modification. CRISPR-Cas9 has shown great promise for the treatment of cancer. However, despite its advantages and tremendous potential, numerous challenges, such as fitness of edited cells, editing efficiency, delivery methods and potential off-target effects, remain to be solved for completely clinical application. Here, we present the potential applications and recent advances of CRISPR-Cas9 in cancer therapy, and discuss the challenges that might be encountered in clinical applications.

miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression.

BACKGROUND: Resistance to chemotherapeutic treatment is a common phenomenon in cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling pathway has been demonstrated to play a role in tumor initiation, development, and progression. However, little is known about its roles in the HCC chemoresistance. METHODS: In this study, real-time PCR and western blotting were used to identify the expression profile of key components of Hippo signaling pathway between chemoresistant and chemosensitive HCC cell lines. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of microRNA-590-5p/YAP1 axis in the chemoresistant phenotype of HCC cells. FINDINGS: We identified yes-associated protein 1 (YAP1) as the major dysregulated molecules in adriamycin (ADR)-resistant HCC cells. YAP1 was profoundly implicated in the chemoresistant phenotype of HCC cells. Furthermore, microRNA-590-5p was revealed as a functional modulator of YAP1. Importantly, YAP1-mediated chemoresistant phenotype was closely related to increased expression of stemness markers and ATP-binding cassette transporters. HCC patients with poor response to transarterial chemoembolization (TACE) treatment had higher protein level of YAP1 than that in the responsive patients. INTERPRETATION: The microRNA-590-5p/YAP axis plays an important role in the chemotherapeutic resistance of HCC cells, suggesting new adjuvant chemotherapeutic directions in HCC. FUND: National Natural Science Foundation of China, Zhejiang Province Medical and Health Care Key Project, Experimental Animal Science and Technology Projects of Zhejiang Province, Public Welfare Technology Application Research Project of Lishui, Chinese Medicine Science and Technology Projects of Zhejiang Province.