m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis.

Radiotherapy is a valid treatment for nasopharyngeal carcinoma (NPC), and radioresistance is the main cause of local NPC treatment failure. However, the underlying mechanisms and valuable markers of radioresistance for NPC remain have not been established. In this study, we observed that the m6A mRNA demethylase fat mass and obesity-associated protein (FTO) was significantly upregulated in radioresistant NPC tissues and cells relative to parental radiosensitive NPC tissues and cells. FTO enhances radioresistance by repressing radiation-induced ferroptosis in NPC. Mechanistically, FTO acts as an m6A demethylase to erase the m6A modification of the OTUB1 transcript and promote the expression of OTUB1, thereby inhibiting the ferroptosis of cells induced by radiation and finally triggering the radiotherapy resistance of NPC. Furthermore, our in vivo experiment results showed that the FTO inhibitor, FB23-2, and the ferroptosis activator, erastin, altered tumor responsiveness to radiotherapy in NPC cell lines and patient-derived xenografts. Our findings reveal, for the first time, that FTO enhances NPC radiotherapy resistance by withstanding radiation-induced ferroptosis, suggesting that FTO may serve as a potential therapeutic target and valuable prognostic biomarker in patients with NPC.

Rare case of an abdominal mass: Reactive nodular fibrous pseudotumor of the stomach encroaching on multiple abdominal organs.

Reactive nodular fibrous pseudotumor (RNFP), which presents abdominal clinical manifestations and malignant radiographic results, usually requires radical resection as the treatment. However, RNFP has been recently described as an extremely rare benign post-inflammatory lesion of a reactive nature, which typically arises from the sub-serosal layer of the digestive tract or within the surrounding mesentery in association with local injury or inflammation. In addition, a postoperative diagnosis is necessary to differentiate it from the other reactive processes of the abdomen. Furthermore, RNFP shows a good prognosis without signs of recurrence or metastasis. A 16-year-old girl presented with a 3-mo history of epigastric discomfort, and auxiliary examinations suggested a malignant tumor originating from the stomach; postoperative pathology confirmed RNFP, and after a 2-year follow-up period, the patient did not display any signs of recurrence. This case highlights the importance of preoperative pathology for surgeons who may encounter similar cases.

Clinical analysis of management of pediatric testicular germ cell tumors.

OBJECTIVE: To analyze our experiences of pediatric testicular tumors and investigate the management of pediatric testicular germ cell tumors. Pediatric testicular tumors are rare and the treatment of them has not been well defined. METHODS: Children treated for primary testicular tumors between January 1998 and July 2010 were retrospectively analyzed. For yolk sac tumor, the difference of survival rates between patients with and without retroperitoneal lymph node dissection (RPLND) was calculated. RESULTS: Eighty-seven cases met our criteria and 78 were germ cell tumors, including 40 cases with yolk sac tumor. Patients were 3-128 months old (median 19), and 53 patients were diagnosed at younger than 2 years of age. For germ cell tumors, serum α-fetoprotein and ß-human chorionic gonadotropin were elevated in 48 and 7 patients, respectively, including 38 and 2 in those with yolk sac tumor. RPLND and chemotherapy were performed in 13 and 19 patients, respectively, and surveillance was performed in 50 patients. With median follow-up of 50 months, 6 patients had recurrence, 4 patients died, and the others achieved complete remission. For stage I yolk sac tumor, the difference of survival rates between patients with and without RPLND was not significant (P = .808). CONCLUSION: Yolk sac tumor is the most common type of pediatric testicular tumor. For stage I yolk sac tumor, radical inguinal orchiectomy is effective, salvage chemotherapy is promising, and RPLND may not be necessary.

Primary mucinous adenocarcinoma of the renal pelvis with elevated CEA and CA19-9.

Primary adenocarcinoma of the renal pelvis is rarely reported in the literature. Here we present a case of primary mucinous adenocarcinoma of the renal pelvis with elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. A 56-year-old woman was referred to our center with intermittent fever and left-sided back pain for 1 month. Computed tomography showed bilateral nephrolithiasis, mild right hydronephrosis and left pyonephrosis accompanied with ambiguous soft tissues. A radionucleorenogram showed that the glomerular filtration rate of the left and right kidney was 0 and 79 ml/min, respectively. Left nephrectomy was performed without lymph node dissection. Histopathology revealed mucinous adenocarcinoma and elevated serum CEA and CA19-9 levels were found. She died of multiorgan metastasis after 5 months. A review of the literature is also reported.

Altered expression of E-cadherin by hepatocyte growth factor and effect on the prognosis of nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF)-related E-cadherin expression and prognosis of patients with nasopharyngeal carcinoma (NPC) are not fully understood. This study investigated HGF-induced altered expression of E-cadherin and the relationship between prognosis and modulation of E-cadherin by HGF in NPC. METHODS: 135 cases of NPC were collected, and expression of HGF, c-Met, and E-cadherin in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association and alteration of E-cadherin by HGF treatment in NPC cell lines were evaluated by immunocytochemical staining, Western blot, and invasion assay. RESULTS: Both high HGF expression in tumor cells (62.9%, 85/135 cases) and nonmembranous E-cadherin expression (61.5%, 83/135 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. However, only abnormal E-cadherin expression (P = 0.001) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, exogenous HGF decreased and internalized E-cadherin expression from cell membrane to cytoplasm, with obvious cellular morphological change. HGF-treated NPC cells exhibited significantly enhanced invasive ability in Matrigel matrix-coated Transwell chamber assay. CONCLUSION: HGF may contribute to cell invasion in NPC by modulating E-cadherin-mediated cell-cell adhesion through downregulation and internalization of E-cadherin. Altered expression of E-cadherin by HGF is a valuable predictor for prognostic evaluation of NPC patients.

[Clinicopathological significance of expression and amplification of P21-activated kinase 1 gene in colorectal carcinoma].

OBJECTIVE: To investigate the clinicopathological value of the expression and amplification of P21-activated kinase 1 gene (PAK1) in colorectal carcinoma(CRC). METHODS: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) methods were used to examine the protein expression, amplification of PAK1 and cell apoptosis in 80 cases of CRC and 30 cases of colorectal adenoma by tissue microarray. RESULTS: IHC showed an overexpression of PAK1 protein in 26% of colorectal adenomas and 62% of CRCs. Significant association was found between expression of PAK1 and tumor histological grade as well as tumor clinical stage(P<0.05). In poor-differentiated(G(3)) CRCs, PAK1 expression in 90% carcinoma was up-regulated, which was significantly higher than that in tumors of G(1/2)(51%). Overexpression of PAK1 was detected in 78% of CRCs in later clinical stages (Dukes C, D), which was significantly higher than that in early clinical stages (Dukes A,B, 53%). In addition, negative correlation between PAK1 overexpression and cell apoptosis was observed in these CRC cohorts(P<0.05). FISH revealed that amplification of PAK1 gene was examined in only 3% CRCs. CONCLUSIONS: Overexpression of PAK1 protein may play an important role in development and progression of colorectal neoplasms and it is closely associated with the malignant histological and invasive phenotype of CRCs. The expression of PAK1 in CRC may be used as one of the new molecular markers in predicting tumors malignant potential and progression.