Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis.

BACKGROUND: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. METHODS: UBE2T expression in HNSC patient samples and the correlation between its expression and patients' survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. RESULTS: The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC. CONCLUSION: Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.

Galectin-1 overexpression induces normal fibroblasts translate into cancer-associated fibroblasts and attenuates the sensitivity of anlotinib in lung cancer.

We aimed to investigate galectin-1 overexpression induces normal fibroblasts (NFs) translates into cancer-associated fibroblasts (CAFs). Galectin-1 overexpression was conducted in Human embryonic lung fibroblasts (HFL1) cell. The motilities of H1299 and A549 cells were measured. Human umbilical vein endothelial cell (HUVEC) proliferation and tube formation ability were assessed. Tumor volume and tumor weight was recorded. Cells motilities were increased, while apoptosis rates were decreased after CMs co-cultured. B-cell lymphoma-2 (Bcl-2) expression level was increased, while Bcl2-associatedX (Bax) and cleaved-caspase3 decreased. CMs treatment enhanced HUVEC proliferation and tube formation. Tumor volume and weight in CMs treated mice were increased, and the sensitivity of anlotinib in co-cultured cells was decreased. Our results revealed that galectin-1 overexpression induced NFs translated into CAFs.

Apatinib combined with concurrent chemoradiotherapy in patients with subglottic small cell carcinoma: a case report.

Subglottic small cell carcinoma (SSMCC) is a rare type of neoplasm, meaning that laryngeal cancer guidelines in several countries, including the National Comprehensive Cancer Network (NCCN) guidelines, do not include treatment principles for SSMCC. Angiogenesis is an established factor in tumor initiation, growth, and dissemination. Apatinib mesylate, an orally administered drug, is a novel inhibitor of vascular endothelial growth factor receptor-2, a key mediator of angiogenesis, and has been shown to be safe and efficacious in the treatment of certain types of malignant tumors. To the best of our knowledge, there are few reports on the treatment of SSMCC with apatinib combined with concurrent chemoradiotherapy. In the present report of SSMCC in a 64-year-old woman, oral apatinib was given daily at a dose of 250 mg in combination with concurrent chemoradiotherapy; the only toxicities reported were mild leukopenia and finger numbness. Clear and rapid efficacy was observed with the disappearance of the tumor mass. Our findings indicate that apatinib combined with concurrent chemoradiotherapy may be effective in patients with SSMCC, with adverse reactions within the manageable range, thus representing an additional treatment option for this type of malignancy.

Ce-Based Nanoparticles Loaded with Cisplatin for Tumour Radiotherapy.

The combination of radiotherapy and chemotherapy is a common and useful treatment mode for tumours. But traditional methods inevitably lead to a variety of side effects. A drug delivery system (DDS), which has good biocompatibility and strong anti-tumour ability, is expected to solve this problem. Studies have shown that Ce-based nanoparticles (NPs) have good radiosensitization effect through the photoelectric effect. Hence, cisplatin-loaded LiLuF4 :Ce3+scintillation NPs (NP + Cis) were first constructed in this study, which was synthesized by the crystal precipitation method and characterized by transmission electron microscopy (TEM). Subsequently, its toxicity was verified, and the radiosensitization effect and basic radiosensitization mechanism on tumour cells and tumour-bearing mice were researched. Results showed that NP + Cis triggered massive DNA damage and effectively inhibited cell viability in vitro under the exposure of X-ray irradiation (IR). Moreover, the experiments in vivo showed that the NP + Cis had higher biosafety, which could absorb enough irradiation and produce a synergistic inhibitory effect on tumours through the releasing of Cis. NP + Cis can improve the performance of DDS in chemoradiotherapy.

Radiotherapy for recurrent central Giant cell granuloma: a case report.

BACKGROUND: Central giant cell granuloma (CGCG) is a rare, non-neoplastic, benign lesion that exhibits expansive and osteolytic biological behavior. CGCG treatment and management is challenging for clinicians. CASE PRESENTATION: This report presents the treatment and management of recurrent, aggressive CGCG after surgical resection. After informed consent was obtained, the patient underwent radiotherapy. The lesion size was reduced significantly, with no evidence of recurrence or malignant transformation. CONCLUSIONS: This treatment experience indicates that radiotherapy can be used as a rescue treatment for complicated CGCG involving vital neurovascular structures of the cranial base.

Inhibition of KiSS-1 on metastasis of nasopharyngeal carcinoma implant tumor in nude mice.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant neoplasm originated from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. KiSS-1 is an inhibitor of tumor metastasis in a range of cancers. METHODS: We establish a cell substrain of SUNE-1-5-8F (NPC cell line from humans) that trsnfected with lentiviral vectors carried with KiSS-1 gene and were selected by puromycin. A transplantation tumor animal model in BALB/c-nu mice was successfully established with a substrain that stably overexpressed KiSS-1. RESULTS: Our result showed that the size of transplantation tumor in the nude mice with KiSS-1 overexpression in transplantation tumor was not difference from the size of transplantation tumor in the controlled transplantation tumor mice. We detected metastatic tumor in lung but not in liver. Moreover, we also found that in the nude mice with KiSS-1 overexpression in transplantation tumor showed extremely fewer metastatic tumor in lung compared with the controlled transplantation tumor mice model. In conclusion, KiSS-1 may be beneficial for the inhibition of metastasis of human NPC. CONCLUSION: This study may throw light on the treatment of NPC and may help improve the prognosis of patients with NPC.

Distribution of metastasis in the brain in relation to the hippocampus: a retrospective single-center analysis of 565 metastases in 116 patients.

OBJECTIVE: To examine the distribution of brain metastases (BM) in relation to the hippocampus, so as to determine the risk of metastasis in the hippocampus, and thus provide experimental evidence for the hippocampal avoidance (HA) in patients with BM during radiotherapy. METHODS: (1) For the retrospective analysis of 116 patients diagnosed with malignancies, confirmed as BM, from December 2014 to December 2016 at the First Affiliated Hospital of Bengbu Medical College. We obtained the T1-weighted, postcontrast axial, sagittal, and coronal Magnetic Resonance imaging (MRI) images f the patients, in supine position, using the head restraints and head thermoplastic masks to adjust the positioning, with computed tomography (CT) positioning scan ranging from the head to the mandible (layer thickness: 3 mm). CT and MRI images were fused on a Philips Pinnacle v9.8 treatment planning system;(2) Every metastasis of the 565 metastases was contoured;(3) hippocampus were contoured, and hippocampus with 5 mm expansion envelopes were analyzed;(4) Using the SPSS 16.0 software, we analyzed the relation between the distribution and age, sex, Karnofsky performance status (KPS), primary site, aggregate volume of intracranial metastases and the whole brain. The data were analyzed using a binary logistic regression analysis method, with two-sided P < 0.05 for statistical significance. RESULTS: In this study, we recruited 116 patients with 565 metastases. Among them, 1.7% (n = 2) had metastases in the hippocampus, and 11.2% (n = 13) had metastases within 5 mm of the hippocampus, of which more than half were patients with non-small cell lung cancer (n = 7). Using a binary logistic regression to analyze the relation between the metastases located within 5 mm of the hippocampus and age (P = 0.395), sex (P = 0.139), KPS (P = 0.724), primary site (P = 0.894), aggregate volume of intracranial metastases (p = 0.093) and the whole brain (p = 0.998), and none of them showed statistically significant difference between them and the metastases location (P>0.05). CONCLUSION: This study showed a low risk for the perihippocampal metastases (PHM) and no significant correlation between PHM and age, sex, KPS, primary site, aggregate volume of intracranial metastases and the whole brain. Accordingly, it is may be acceptable to avoid the perihippocampal region during whole brain radiotherapy.

G­protein­coupled receptor 120 regulates the development and progression of human esophageal cancer.

The aim of the present study was to investigate the role of G­protein coupled receptor 120 (GPR120) in esophageal cancer and explore the related mechanisms. The expression of GPR120 in esophageal cancer tissues was examined by immunohistochemistry. Correlation analysis was performed to investigate the association between the level of GPR120 and clinical parameters. The expression of GPR120 was evaluated in esophageal cancer cell lines and the effects of GPR120 on cell proliferation, clone formation, migration and invasion were evaluated in an in vitro cell model and an in vivo ectopic tumor nude mice model. In addition, the effect of GPR120 on epithelial­mesenchymal transition (EMT), PI3K and I­κB pathway, as well as angiogenesis and inflammation­related cytokines was explored in order to elucidate the underlying mechanisms. Significantly increased expression of GPR120 was observed in esophageal cancer tissues compared to normal tissues. The expression of GPR120 was significantly related with histological grade, TNM stage and lymph node metastasis. GPR120 knockdown significantly decreased cell proliferation, clone formation, migration and invasion in vitro and decreased tumor growth in vivo. Furthermore significantly increased levels of E­cadherin and decreased levels of N­cadherin and vimentin, decreased level of Akt phosphorylation and I­κB phosphorylation, as well as decreased levels of vascular endothelial growth factor (VEGF), interleukin­8 (IL­8) and cyclooxygenase­2 (Cox­2) and its corresponding protein PGE2 were observed as the underlying mechanisms. In conclusion, we observed an increased level of GPR120 in esophageal cancer tissues, which served as a positive regulator of the development and progression of esophageal cancer. Multiple mechanisms including EMT, PI3K and I­κB pathway, as well as angiogenesis and inflammation­related cytokines were involved.

KAI1/CD82 Genetically Engineered Endothelial Progenitor Cells Inhibit Metastasis of Human Nasopharyngeal Carcinoma in a Mouse Model.

BACKGROUND Endothelial progenitor cells (EPCs) are regarded as promising targeted vectors for delivering therapeutic genes or agents in cancer therapy. The purpose of this study was to investigate the role of intravenously administered KAI1/CD82 genetically transduced EPCs in the tumorigenesis and metastasis of nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS EPCs were isolated from human umbilical cord blood, expanded in culture, and stably transduced with lentiviral vectors expressing KAI1/CD82. The KAI1/CD82 EPCs were injected intravenously into nude mice bearing human NPC xenografts. Tumor growth and the incidence of liver and lung metastases were observed. Expression of KAI1/CD82 was determined by immunofluorescent staining. RESULTS The NPC model was successfully established. Tumor growth was not suppressed when mice were injected with KAI1/CD82 EPCs (KAI1/CD82 EPCs group) compared with when non-transduced EPCs was present (EPCs group) or the control (1.485±0.234, 1.388±0.204, and 1.487±0.223g, respectively; P>0.05). However, the incidence of lung metastasis was significantly reduced in the KAI1/CD82+ EPCs group compared with the EPCs group and the control group (10%, 55% and 45%, respectively; P=0.005), and there was a significant decrease in the number of metastatic foci on the lung surface (17.50±3.54, 34.27±5.35, and 38.44±9.63 respectively; P=0.007). Moreover, KAI1/CD82 was expressed in lung metastatic foci of the KAI1/CD82 EPCs group, but not in the EPCs group and control group. CONCLUSIONS EPCs can be used as a delivery vehicle for suppressor genes KAI1/CD82 to NPC, and the migration of KAI1/CD82 genetically engineered EPCs can inhibit NPC lung metastasis in a mouse model.

Extracranial metastases of high-grade glioma: the clinical characteristics and mechanism.

BACKGROUND: This presentation of two cases and literature review discusses the epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment, and prognosis of high-grade glioma with extracranial metastases. METHODS: A retrospective analysis of the clinical features of two cases of malignant glioma, including metastatic sites, pathological data, and treatment methods, and a literature review was performed. RESULTS: Two patients developed extracranial metastases within 1 year after surgery for primary glioma. One patient developed cervical lymph node and bone metastases while the other developed bone metastases, and both patients died within 2 months after the diagnosis of the extracranial metastasis. CONCLUSION: Extracranial metastases may develop from malignant gliomas. According to the literature, the most common extracranial site is intraspinal (along the neural axis), followed by the vertebrae, lungs, liver, and lymph nodes. The complex metastatic mechanism remains unclear, and the prognosis is very poor, with a survival duration of less than 6 months.

Targeted inhibition of Notch1 gene enhances the killing effects of paclitaxel on triple negative breast cancer cells.

OBJECTIVE: To study the influence of targeted inhibition of Notch1 gene on the killing effects of paclitaxel on triple negative breast cancer cells. METHODS: The triple negative [estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (Her2)] breast cancer cell line MDA-MB-231 and ER/PR/HER-2-positive breast cancer cell line MCF-7 were cultured, transfected with Notch1-siRNA-overexpression plasmid and blank plasmid, and treated with different concentrations of paclitaxel, and then the cell proliferation activity and apoptosis rate as well as the mRNA expression of Caspase-3, Caspase-9 and Bcl-2 were determined. RESULTS: Paclitaxel could decrease the MDA-MB-231 and MCF-7 cell proliferation activity as well as Bcl-2 mRNA expression, and increase MDA-MB-231 and MCF-7 cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression in dose-dependent manners; with the same dose of paclitaxel treatment, the inhibitory effects on MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression as well as the promoting effects on MDA-MB-231 cell apoptosis and mRNA expression of Caspase-3 and Caspase-9 were weaker than those on MCF-7 cell; after 0.5 µM paclitaxel combined with Notch1-siRNA treatment, MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression were significantly lower than those after 0.5 µM paclitaxel combined with control plasmid treatment while cell apoptosis rate and mRNA expression of Caspase-3 and Caspase-9 were higher than those after 0.5 µM paclitaxel combined with control plasmid treatment. CONCLUSIONS: Targeted inhibition of Notch1 gene may enhance the killing effects of paclitaxel on triple negative breast cancer cells by up-regulating the expression of Caspase-3 and Caspase-9 and inhibiting the expression of Bcl-2.

Diagnosis and surgical treatment of mediastinal solitary fibrous tumor.

AIM: The aim of this study was to investigate the clinical features as well as the diagnosis and treatment methods for mediastinal solitary fibrous tumor (MSFT). METHODS: The clinical data of 13 patients treated for pathologically confirmed MSFT were retrospectively analyzed. The clinical symptoms were mainly cough, chest tightness, chest pain and chest discomfort. It was difficult to distinguish MSFT from other types of tumors simply via imaging results, hence, the confirmative diagnosis required pathological and immunohistochemistry analysis. RESULTS: The tumors were completely resected for all patients. All patients were discharged after surgery and followed up for 2-85 months. One patient died of cerebral hemorrhage 2 months after the surgery, and the rest of the patients experienced no recurrence or metastasis during the follow-up period. CONCLUSIONS: MSFT is a rare type of mediastinal tumor, and the diagnosis requires pathological and immunohistochemical analysis. Surgical treatment is preferred, and a complete resection can achieve a good prognosis; however, postoperative adjuvant radiotherapy might be necessary for cases with extensive external invasion.

Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. METHODS: A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. RESULTS: The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. CONCLUSIONS: The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

Reversal of galectin-1 gene silencing on resistance to cisplatin in human lung adenocarcinoma A549 cells.

This study aims to investigate reversal of Galectin-1 gene silencing on resistance to cisplatin in human lung adenocarcinoma A549 (or A549/DDP) in vivo and in vitro. The stably transfected lentivirus vector was used to silence Galectin-1 in human lung adenocarcinoma cell line A549 and A549/DDP cells and the cell lines were cultured and passaged. RT-PCR and western blot assay were used to test A549, A549/DDP cells, silenced Galectin-1A549 (A549/I) cells, Galectin-1 mRNA and protein expression levels, respectively, in A549/DDP (A549/DDP/I) cells. CCK8 assay was used to measure median inhibitory concentration (IC50) in each group and resistant index of A549/DDP cells and A549/DDP/I cells. Tumor model in nude mice was established by armpit injection of A549, A549/DDP, A549/I, A549/DDP/I cells. Cisplatin was injected intraperitoneally in tumor models and growth of tumor was observed in vivo model. Four weeks later, nude mice were killed and tumor weight and diameter was measured. mRNA and protein expression of Galectin-1 in A549/DDP cells was higher than that in A549 cells. mRNA and protein expression of Galectin-1 in A549/DDP/I cells was lower than that in A549/DDP cells. Moreover, IC50 values ​​and resistance index in A549/DDP cells was higher than that in A549 cells group and IC50 values ​​and resistance index A549/DDP/I cell group were lower than that in A549/DDP cells. Additionally, tumor weight and volume in A549/DDP/I cell group were lower than that in A549/DDP. In conclusion, Galectin-1 gene silencing would improve the sensitivity of A549/DDP cells to cisplatin in vivo and in vitro.

Clinical significance of KAI1/CD82 protein expression in nasopharyngeal carcinoma.

The aim of this study was to investigate KAI1/CD82 protein expression in human nasopharyngeal carcinoma (NPC) cell lines and human NPC tissues. Immunohistochemistry and western blot analysis were used to detect the localization and expression levels of the KAI1/CD82 protein in five human NPC cell lines. Immunohistochemistry was also conducted to detect the expression of the KAI1/CD82 protein in 70 NPC tissues and 30 non-neoplastic nasopharyngeal tissues. The levels of KAI1/CD82 protein expression were found to decrease as the metastatic potential of cells increased. The expression rate of KAI1/CD82 protein in the NPC tissues (44.3%) was significantly lower than that in the non-neoplastic nasopharyngeal tissues (70.0%) (P<0.05). KAI1/CD82 protein expression in the NPC tissues was not associated with clinical parameters, including gender, age, histological type and T stage, and the positive expression of KAI1/CD82 decreased with increased N staging. The level of KAI1/CD82 protein expression was increased in different human NPC cell lines. The KAI1/CD82 gene was highly expressed in cells with low metastatic potential, while low expression was observed in cells with a high metastatic potential. In addition, the KAI1/CD82 gene was expressed at low levels in nasopharyngeal carcinoma tissues, while high expression was identified in non-neoplastic nasopharyngeal tissues, and was associated with lymph node metastasis. These results indicated that the KAI1/CD82 gene may be involved in the occurrence, development and metastasis of nasopharyngeal carcinoma.

Analysis of the efficacy of intensity-modulated radiotherapy and two-dimensional conventional radiotherapy in nasopharyngeal carcinoma with involvement of the cervical spine.

The aim of the present study was to retrospectively analyze the clinical efficacy and side-effects of two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated radiotherapy (IMRT) in 53 NPC patients with cervical spine involvement, without distant metastases. In total, 53 patients were enrolled in the present study, with 24 being treated with IMRT and 29 being treated with 2D-CRT. All 53 patients received platinum-based concurrent chemotherapy and 4-6 cycles of adjuvant chemotherapy subsequent to radiation. The patients were clinically staged according to the seventh edition of the UICC and AJCC staging systems. Overall survival (OS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) rates were calculated. The 3- and 5-year OS rates were 87.7% and 45.5% in the IMRT-treated group and 65.5% and 9.1% in the 2D-CRT-treated group (P=0.01). The 3- and 5-year LPES rates were 87.4% and 69.9% in the IMRT-treated group compared with 49.4% and 9.4% in the 2D-CRT-treated group, respectively (P=0.00). The 3- and 5-year DMFS rates were 94.4 and 40.8% in the IMRT-treated group and 79.8 and 30.4% in the 2D-CRT-treated group (P=0.13). N stage (P=0.00) and radiotherapy methods (P=0.01) were relevant to the OS and LPFS rates, it also revealed a significant difference when the DMFS rates were analyzed in N stage. The incidence of dry mouth in the IMRT group was significantly lower (P=0.01), but there was no statistically significant difference in acute oropharyngeal mucositis or myelosuppression. IMRT had significant advantages in local control and OS compared with conventional 2D-CRT, but IMRT failed to reduce the incidence of distant metastasis.