NCAPH serves as a prognostic factor and promotes the tumor progression in glioma through PI3K/AKT signaling pathway.

Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.

TCAF2 drives glioma cellular migratory/invasion properties through STAT3 signaling.

Glioma is an intracranial tumor characterized by high mortality and recurrence rates. In the present study, the association of TRPM8 channel-associated factor 2 (TCAF2) in glioma was investigated using bioinformatics, showing significant relationships with age, WHO grade, IDH, and 1p/19q status, as well as being an independent predictor of prognosis. Immunohistochemistry of a glioma sample microarray showed markedly increased TCAF2 expression in glioblastoma relative to lower-grade glioma, with elevated expression predominating in the tumor center. Raised TCAF2 levels promote glioma cell migratory/invasion properties through the epithelial-to-mesenchymal transition-like (EMT-like) process, shown by Transwell and scratch assays and western blotting. It was further found that the effects of TCAF2 were mediated by the activation of STAT3. These results suggest that TCAF2 promotes glioma cell migration and invasion, rendering it a potential drug target in glioma therapy.

PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma.

The tumor immunosuppressive microenvironment (IME) significantly affects tumor occurrence, progression, and prognosis, but the underlying molecular mechanisms remain to make known. We investigated the prognostic significance of PDPN and its role in IME in glioma. Weighted gene co-expression network analysis (WGCNA) found PDPN closely related to IDH wildtype status and higher immune score. Correlation analysis suggested PDPN was highly positively relevant to immune checkpoints expression and immune checkpoints block responding status. Correlation analysis together with verification in vitro suggested PDPN highly positively relevant tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs). Least absolute shrinkage and selection operator (LASSO) regression employed to develop the prediction model with TANs and TAMs markers showed that high risk scores predicted worse prognosis. We highlight that PDPN overexpression is an independent prognostic indicator, and promotes macrophage M2 polarization and neutrophil degranulation, ultimately devotes to the formation of an immunosuppressive tumor microenvironment. Our findings contribute to re-recognizing the role of PDPN in IDH wildtype gliomas and implicate promising target therapy combined with immunotherapy for this highly malignant tumor.

A Novel Prognostic Signature Based on Glioma Essential Ferroptosis-Related Genes Predicts Clinical Outcomes and Indicates Treatment in Glioma.

Background: Ferroptosis is a form of programmed cell death (PCD) that has been implicated in cancer progression, although the specific mechanism is not known. Here, we used the latest DepMap release CRISPR data to identify the essential ferroptosis-related genes (FRGs) in glioma and their role in patient outcomes. Methods: RNA-seq and clinical information on glioma cases were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). FRGs were obtained from the FerrDb database. CRISPR-screened essential genes (CSEGs) in glioma cell lines were downloaded from the DepMap portal. A series of bioinformatic and machine learning approaches were combined to establish FRG signatures to predict overall survival (OS) in glioma patients. In addition, pathways analysis was used to identify the functional roles of FRGs. Somatic mutation, immune cell infiltration, and immune checkpoint gene expression were analyzed within the risk subgroups. Finally, compounds for reversing high-risk gene signatures were predicted using the GDSC and L1000 datasets. Results: Seven FRGs (ISCU, NFS1, MTOR, EIF2S1, HSPA5, AURKA, RPL8) were included in the model and the model was found to have good prognostic value (p < 0.001) in both training and validation groups. The risk score was found to be an independent prognostic factor and the model had good efficacy. Subgroup analysis using clinical parameters demonstrated the general applicability of the model. The nomogram indicated that the model could effectively predict 12-, 36-, and 60-months OS and progression-free interval (PFI). The results showed the presence of more aggressive phenotypes (lower numbers of IDH mutations, higher numbers of EGFR and PTEN mutations, greater infiltration of immune suppressive cells, and higher expression of immune checkpoint inhibitors) in the high-risk group. The signaling pathways enriched closely related to the cell cycle and DNA damage repair. Drug predictions showed that patients with higher risk scores may benefit from treatment with RTK pathway inhibitors, including compounds that inhibit RTKs directly or indirectly by targeting downstream PI3K or MAPK pathways. Conclusion: In summary, the proposed cancer essential FRG signature predicts survival and treatment response in glioma.

[Total trans-oral endoscopic thyroidectomy and cervical lymphadenectomy: a human cadavers surgery study].

OBJECTIVE: To find an approach for trans-oral endoscopic thyroidectomy (TOET) and cervical lymphadenectomy using conventional endoscopic surgical instruments on frozen fresh cadavers. METHODS: Six frozen fresh cadavers were used in three groups of trans-oral trocar installation experiments: oral vestibule installation, sublingual region installation, and combined bi-vestibular and sublingual installation. TOET (with pretrachealis method to thyroid fixation removal) and cervical lymphadenectomy were performed experiments on another 6 frozen fresh cadavers using the best access approach found in the aforementioned experiments. RESULTS: In oral vestibule trocar installations, the trocars caused large lacerated wound and damaged air tightness. In sublingual installations, only one trocar could be installed in the sublingual area because the space in sublingual area was limited. In combined bi-vestibular and sublingual installations, no gland, vessel or nerve was damaged. Combined bi-vestibular and sublingual access were selected as the surgical approach on the basic of analysis the merits of each approach. TOET and cervical lymphadenectomy in area III, IV, VI, VII were performed without making any accessory damage through combined bi-vestibular and sublingual access approach. CONCLUSIONS: TOET is feasible. Combined bi-vestibular and sublingual approach is available for TOET. Part of the cervical lymph nodes could be resected. Pretrachealis approach to thyroid fixation removal can still be used.

The treatment of intrahepatic calculosis by applying helix hydro-jet lithotripsy under video choledochoscope: a report of 30 cases.

BACKGROUND AND AIMS: Intrahepatic lithiasis is a common disease in southeast Asia [Sheen-Chen and Chou, Acta Chir Scand 156:387-390, 1990], and a difficult problem of biliary surgery. There is no established method of treating patients with intrahepatic stones [Uchiyama et al., Arch Surg 137:149-533, 2002]. In recent years, resection of the affected liver lobe or segment is the best therapeutic option to completely remove the source of recurrent infection. The need for endoscopic treatment modalities is evident because hepatic resections are combined with a high morbidity and mortality rate [Andersson et al., HPB Surg 2:145-147, 1990; Adamek et al., Scand J Gastroenterol 34:1157-1161, 1999]. Hepatic resection only fit the cases in which the stones localized in one lobe or segment, while it doesn't fit the cases which have polystones in left and right biliary tract. Duodenoscope can only get the stones in the common bile duct and cannot deal with the intrahepatic lithiasis. The management of intrahepatic lithiasis can only be treated by intraoperative or postoperative choledochoscope. For big stones or compact stones, lithotripsy should be applied. But the laser lithotripsy and the electrohydraulic lithotripsy can cause serious complications such as perforation of bile duct. It needs a safer and more reliable treatment for intrahepatic lithiasis. The aim of our work is to study the lithotrity treatment of intrahepatic lithiasis by using helix hydro-jet under Video Choledochoscope. MATERIALS AND METHODS: From March 31, 2003 to October 20, 2004, 30 intrahepatic stone patients were treated. Eighteen of them were women and 12 were men, with ages ranging from 35 to 80 years (mean, 58 years). According to B ultrasound and computed tomography (CT) scan report, there were five cases of intrahepatic lithiasis and common bile duct stones, 25 cases of left and right hepatic duct stones, and one case with giant intrahepatic stone (1.5 x 1.5 x 1.2 cm). Intraoperative or postoperative choledochoscopic helix hydro-jet lithotripsy was applied through a video choledochoscope. For the patients to have the intraoperative choledochoscopic helix hydro-jet lithotripsy, they should be diagnosed correctly by B ultrasound or CT scan. The biliary tract reconstruction by spiral CT scan is as helpful as MRCP or ERCP for clinical diagnosis. For the patients to have the postoperative choledochoscopic helix hydro-jet lithotripsy, they should be diagnosed correctly by T-tube cholangiography and BUS and CT scan. All patients should be verified without stones remaining in the bile duct after lithotripsy by choledochoscopic examination and T-tube cholangiography, and should be examined by BUS again after 6 months to 1 year. We decide whether complications occurred by observation of symptoms and signs after choledochoscopy and lithotripsy. RESULTS: Seventy-five intrahepatic stones with diameter ranging from 0.6 to 1.5 cm were successfully fragmentized in 30 patients using of helix hydro-jet lithotripsy. These fragmentized stones mainly are bilirubin stones. The lithotripsy was carried for 45 times and the procedure needs 1-1.5 h. Helix hydro-jet lithotripsy are used in 16 cases during operation and 12 cases after operation; two cases during operation and after operation. Intrahepatic calculosis was cleaned out completely and verified by postoperative choledochoscope examination and postoperative T-tube cholangiography examination. No complications were observed. CONCLUSION: Helix hydro-jet lithotripsy under video choledochoscope is a safe and effective method for the removal of intrahepatic stone. No bile duct damnified and perforation was observed. The procedure is without pain and heat, and the pressure can be adjusted easily. The research provides a new way of using the helix hydro-jet, and a new way of curing the intrahepatic lithiasis.