CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma.

BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.

Guideline conformity to the Stupp regimen in patients with newly diagnosed glioblastoma multiforme in China.

Aims: To determine how consistently Chinese glioblastoma multiforme (GBM) patients were treated according to the Stupp regimen. Patients and methods: The proportion of treatments conforming to the Stupp regimen and reasons for nonconformity were evaluated in 202 newly diagnosed GBM patients. Results: Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations were temozolomide dosages >75 mg/m2 (58/120; 48.3%) and treatment durations <42 days (84/120; 70.0%) in the concomitant phase and temozolomide dosages <150 mg/m2 (89/101; 88.1%) in the maintenance phase. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments. Conclusion: Increased conformity to the Stupp regimen is needed for GBM patients in China.

Lay abstract In 2005 the European Organization for Research and Treatment of Cancer 26981 study led to US FDA approval for the use of temozolomide in combination with radiotherapy to treat glioblastoma multiforme (GBM). The Stupp regimen consists of fractionated focal irradiation in daily fractions of 2 Gy given 5 days/week for 6 weeks (a total of 60 Gy), plus concomitant daily temozolomide (75 mg/m²/day, 7 days/week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150­200 mg/m²/day for 5 days during each 28-day cycle). In 2012 the Chinese guidelines for the diagnosis and treatment of glioma of the CNS recommended the Stupp regimen as first-line therapy for newly diagnosed GBM. In the present study, compliance of GBM treatments with the Stupp regimen in 28 Chinese centers from 2012­2016 was evaluated. Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations related to temozolomide dosages and treatment durations in the concomitant and maintenance phases. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments.

The role of XBP1s in the metastasis and prognosis of hepatocellular carcinoma.

Tumor metastasis and recurrence are the primary contributors to poor prognosis in patients with hepatocellular carcinoma (HCC). The epithelial-mesenchymal transition (EMT) of tumor cells is the predominant mechanism of HCC progression. XBP1s is a newly discovered molecule involved in the endoplasmic reticulum (ER) stressresponse, which is an adaptive response and defense mechanism in cells that enablessurvival under adverse conditions. Abnormally high XBP1sexpression has been found in tumor cells, but the role of XBP1sin HCC progression remains unclear. We found that the expression of XBP1s in HCC cell lines and tissuesamples was higher than that in control cells and tissuesamples. Clinicopathological analysis showed that the expression of XBP1s was closely correlated with distant metastasis and poor prognosis in HCC. In vivo and invitro experiments confirmed that the overexpression of XBP1s promoted EMT and metastasis in HCC cells. XBP1ssilencing attenuated cellular migration and development of the EMT phenotypein vitro. Through further study to elucidate the molecular mechanism underlying the promotion ofEMT by XBP1s in HCC cells, we confirmed that XBP1s could mediate the expression of Twist. In HCC cells, XBP1s enhanced the expression of Twist and Snail, resulting in a subsequent reduction in the expression of E-cadherin, a contributor to cell-cell adhesion. Overall, this study reveals a novel XBP1s/Twist/Snail axis that mediates EMT in HCC cells and the invasion and metastasis of HCC.

Comparative proteomic analysis of anti-cancer mechanism by periplocin treatment in lung cancer cells.

BACKGROUND: Periplocin is used for treatment of rheumatoid arthritis, reinforcement of bones and tendons, palpitations or shortness of breath and lower extremity edema in traditional medicine. Our previous findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo. But the biological processes and molecular pathways by which periplocin induces these beneficial effects remain largely undefined. METHODS: To explore the molecular mechanisms of periplocin involved in anti-cancer activity, in the present study the protein profile changes of human lung cancer cell lines A549 in response to periplocin treatment were investigated using the proteomics approaches (2-DE combined with MS/MS). Western blot was employed to verify the changed proteins. Interactions between changed proteins were analyzed by STRING. RESULTS: 29 down-regulated protein species named GTP-binding nuclear protein Ran (RAN), Rho GDP-dissociation inhibitor 1 (ARHGDIA), eukaryotic translation initiation factor 5A-1 (EIF5A) and Profilin-1(PFN1), and 10 up-regulated protein species named Heat shock cognate 71 kDa protein (HSPA8),10 kDa heat shock protein (HSPE1), and Cofilin-1(CFL-1) were identified. Among them, GTP-binding nuclear protein Ran (RAN) and Rho GDP-dissociation inhibitor 1 (ARHGDIA) were the most significantly changed (over tenfold). The proteasome subunit beta type-6 (PSMB6), ATP synthase ecto-α-subunit (ATP5A1), Aldehyde dehydrogenase 1 (ALDH1) and EIF5A were verified by immunoblot assays to be dramatically down-regulated. By STRING bioinformatics analysis revealing interactions and signaling networks it became apparent that the proteins changed they are primarily involved in transcription and proteolysis. CONCLUSION: Periplocin inhibited growth of lung cancer by down-regulating proteins, such as ATP5A1, EIF5A, ALDH1 and PSMB6. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of periplocin on lung cancer cells.

Evaluation of response to stereotactic body radiation therapy for nonsmall cell lung cancer: PET response criteria in solid tumors versus response evaluation criteria in solid tumors.

OBJECTIVE: Recommendations for surveillance after stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung cancer (NSCLC) are not well defined. Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess radiotherapeutic response both quantitatively and metabolically. The aim of this study was to evaluate therapeutic response following SBRT in early-stage NSCLC patients by comparing PERCIST with the currently widely used RECIST. MATERIALS AND METHODS: Forty-nine patients with early-stage NSCLC who had been prescribed SBRT were studied. Responses of lesion were evaluated using CT and 18F-FDG PET according to the RECIST and PERCIST methods. PET-CT scans were obtained before SBRT and 3-6 months after SBRT. Associations between overall survival (OS) and clinicopathologic results (histology, tumor location, tumor size, lymphatic invasion, clinical stage, and radiotherapeutic responses in RECIST and PERCIST) were statistically analyzed. The median patient follow-up was 30 months. RESULTS: Thirteen patients had stage IA, 9 stage IB, 10 stage IIA, and 17 stage IIB biopsy-proven NSCLC. Three-year OS was 79.6%. CT scans indicated three regional recurrences. PET-CT/chest indicated three regional recurrences and distant metastasis. Significant differences were observed in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P = 0.0041). Univariate analysis showed that clinical stage, RECIST, and PERCIST were significant factors associated with OS, whereas by multivariate analysis PERCIST was the only predictor of OS. SMD, PMD/PMR, and CMR in PERCIST criteria were indicative of a 9.900-fold increase in the risk of OS in early NSCLC patients [risk ratio, 9.900 (95% CI, 1.040-21.591); P = 0.001]. CONCLUSION: RECIST based on the anatomic size reduction rate did not demonstrate the correlation between radiotherapeutic response and prognosis in patients with early-stage NSCLC receiving SBRT. However, PERCIST was shown as the strongest independent predictor of outcomes. PERCIST might be considered more suitable for the evaluation of NSCLC tumor response to SBRT than RECIST.

[Safety and efficacy of three-dimensional conformal radiotherapy combined with temozolomide in treatment of diffuse brainstem gliomas].

OBJECTIVE: To study the safety and efficacy of three-dimensional conformal radiotherapy in combination with temozolomide in treatment of patients with diffuse brainstem glioma. METHODS: Twelve patients with MRI-confirmed diffuse brainstem glioma received 54 Gy three-dimensional conformal radiotherapy for 6 weeks with 1.8 Gy per fraction, 5 times per week. All of the patients were given daily oral temozolomide 75 mg/m(2) during radiotherapy. Four weeks after radiotherapy, all of the patients received 6 cycles of temozolomide, each cycle lasted 5 days with 28 days interval between each two cycles. 150 mg/m(2) of temozolomide was given for the first cycle for five days, followed by 200 mg/m(2) of the drug for the rest of the cycles if no significant drug-related toxicities were observed. Magnetic resonance imaging and laboratory tests were performed to evaluate the efficacy and adverse reactions. RESULTS: In the 12 patients, CR was 1 case (8.3%), PR 6 cases (50.0%), SD 2 cases (16.7%), and PD 3 cases (25.0%). The overall clinical benefit rate was 75.0%. Progression-free survival rate was 75.0% (9/12) at 6 months and 50.0% (6/12) at 1 year. The one-year overall survival rate was 75.0%. There were no severe temozolomide-related toxicities. CONCLUSIONS: Concurrent temozolomide with three-dimensional conformal radiotherapy and followed by 6 cycles of temozolomide chemotherapy for diffuse brainstem gliomas have a better clinical efficacy, good tolerance and with no severe toxicities.

[Effects on structure and secretion of pituitary gland in rats after electromagnetic pulse exposure].

OBJECTIVE: To investigate the exposure effect of electromagnetic pulse (EMP) on the structure and secretion of pituitary gland in rats. METHODS: Forty-eight male SD rats were randomly divided into eight groups. Four groups were subject to the EMP exposure of 200 kV/m and the others received a sham exposure. At different time points (12, 24, 48 & 96 h) post-exposure, the pathological changes of pituitary gland were observed by light and transmission electron microscope. And the serum levels of prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) and luteinizing hormone (LH) were measured dynamically by radioimmunoassay. RESULTS: At 12 h post-exposure, swollen mitochondria with cristae loss, dilatation of Golgi complex and diffusive lysosomes were found in endocrine cells of pituitary gland. The above changes became gradually worse. Mitochondrial vacuolization, the formation of myelin figures, distinct dilatation of endoplasmic reticulum, the occurrence of numerous secondary lysosomes and the clustering of heterochromatin under the nuclear membranes could be observed at 48 h. These lesions were alleviated to some degree at 96 h. The serum levels of PRL and ACTH both increased significantly at 12 h (P < 0.01, P < 0.05) and returned to normal at 24 h. The level of GH decreased significantly at 12 h and then returned gradually to normal at 48 h. The level of TSH decreased at 12 h and reached the lowest point at 24 h, then returned to normal at 96 h. LH increased significantly from 24 h to 96 h. CONCLUSION: The EMP exposure of 200 kV/m may induce the changes of the structure and secretion of pituitary gland in rats.

Abscopal effect of radiation on lymph node metastasis in esophageal carcinoma: A case report and literature review.

The Abscopal effect is a rare phenomenon observed in the treatment of metastatic cancer, where localized irradiation causes a response in non-irradiated tumor sites. Due to the recent success of immunotherapies, the Abscopal effect of radiation therapy has received renewed clinical interest. However, there is limited knowledge regarding the Abscopal effect and radiotherapy treatment of patients with esophageal carcinoma. The present study reports the case of a 65-year-old male patient, who presented with esophageal carcinoma and lymph node metastasis. A transthoracic esophagectomy with left cervical, mediastinal and abdominal lymphadenectomies was performed. A total of 4 cycles of chemotherapy and maintenance therapy with Pembrolizumab was performed until September 2016. Metastases in the left retroperitoneal lymph node in addition to extensive metastases to the pelvic lymph node were observed. The patient received Cyberknife radiotherapy with a dose of 42 Gy in 6 daily fractions targeted at the left retroperitoneal lymph node. Two months after radiation therapy, a positron emission tomography-computed tomography scan revealed complete regression of all lymph node metastases. There is increasing clinical evidence supporting the efficacy of the Abscopal effect, which may be initiated by high-dose radiation. Further research is required to make the Abscopal effect clinically relevant, however it may have potential as a treatment option.

Oncolytic Viruses for Tumor Precision Imaging and Radiotherapy.

In 2003 in China, Peng et al. invented the recombinant adenovirus expressing p53 (Gendicine) for clinical tumor virotherapy. This was the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement. Oncolytic viruses carrying reporter genes can replicate and express genes of interest selectively in tumor cells, thus improving in vivo noninvasive precision molecular imaging and radiotherapy. Here, the latest developments and molecular mechanisms of tumor imaging and radiotherapy using oncolytic viruses are reviewed, and perspectives are given for further research. Various types of tumors are discussed, and special attention is paid to gastrointestinal tumors.

Metabolism-related enzyme alterations identified by proteomic analysis in human renal cell carcinoma.

The renal cell carcinoma (RCC) is one of the most common types of kidney neoplasia in Western countries; it is relatively resistant to conventional chemotherapy and radiotherapy. Metabolic disorders have a profound effect on the degree of malignancy and treatment resistance of the tumor. However, the molecular characteristics related to impaired metabolism leading to the initiation of RCC are still not very clear. In this study, two-dimensional electrophoresis (2-DE) and mass spectra (MS) technologies were utilized to identify the proteins involved in energy metabolism of RCC. A total of 73 proteins that were differentially expressed in conventional RCC, in comparison with the corresponding normal kidney tissues, were identified. Bioinformatics analysis has shown that these proteins are involved in glycolysis, urea cycle, and the metabolic pathways of pyruvate, propanoate, and arginine/proline. In addition, some were also involved in the signaling network of p53 and FAS. These results provide some clues for new therapeutic targets and treatment strategies of RCC.

Application of serum NY-ESO-1 antibody assay for early SCLC diagnosis.

BACKGROUND: NY-ESO-1 antibody is one of the cancer-related antibodies. The purpose of this study was to investigate the diagnostic role of the NY-ESO-1 humoral immune response in small cell lung cancer (SCLC). METHODS: We recombined the recombinant protein of NY-ESO-1 antibody and NSE, analyzed them by Enzyme-linked immunosorbent assay, and then established the Receiver Operating Characteristic (ROC) curve to estimate the diagnostic value of NY-ESO-1 antibody, NSE and their combinations. RESULTS: According to detection, the positive rate of NY-ESO-1 humoral immune response (26.3%), NSE (43.8%) and their combinations (10.5%) were all lower than the negative rate which indicated that the NY-ESO-1 antibody might be down-regulated in SCLC. And the positive rate wasn't related to clinicopathologic characteristics. The ROC curve demonstrated that with a 37.17% sensitivity and a 91.7% specificity along with a AUC of 0.619 for NY-ESO-1ab as well as with a 48.3% sensitivity and a 90.87% specificity along with a AUC value of 0.773 for NSE, their diagnostic value were both high. Besides, the diagnostic value of their combinations was also good for a AUC of 0.83 and a 69.12% sensitivity and a 91.8% specificity. There were significant difference of diagnostic value among three types above (NY-ESO-1 vs. NSE, P < 0.01; The Combinations vs. NY-ESO-1, P < 0.0001; and the Combinations vs. NSE, P < 0.04). CONCLUSION: In conclusion, NY-ESO-1ab, NSE and their combinations all were important diagnostic markers for SCLC. Moreover, the diagnostic value of their combinations was higher than any single of them. And NY-ESO-1 humoral immune to NSE might be a potential diagnostic indicator in SCLC.

Clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in evaluating relapsed and refractory nasopharyngeal carcinoma: A case report.

For patients with locoregionally advanced nasopharyngeal carcinoma (NPC), radiotherapy, chemotherapy and even targeted therapy are widely accepted treatments. These treatments, although they mostly achieve locoregional tumor control, they may also be associated with complex post-treatment changes, such as edema, loss of tissue planes, fibrosis, mucositis and scarring, which may interfere with the detection of local recurrence and the response to therapy. However, timely detection is crucial for deciding whether treatment modification or discontinuation is required. This is the case report of A 51-year-old nasopharyngeal carcinoma patient with cervical nodal metastases (CNM). Following radiotherapy, chemotherapy and targeted therapy, multislice spiral enhanced computed tomography (CT), enhanced magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT of the neck were performed to compare the extent of the CNM. The enhanced CT and MRI images were unremarkable, whereas the 18F-FDG PET/CT images revealed the exact recurrence or remission. Therefore, 18F-FDG PET/CT exhibits a better sensitivity and specificity for evaluating the response to combined treatment compared to CT and/or MRI.

Growth inhibitory effect of adenovirus-mediated tissue-targeted expression of ribosomal protein L23 on human colorectal carcinoma cells.

A large body of evidence has established murine double minute 2 (MDM2) as a crucial negative regulator of p53 and the major suppressor of p53 function in tumors with wild-type (wt)-p53. Therefore, by inhibiting MDM2 one may reactivate p53 in tumor cells, leading to their demise. Previous studies revealed that ribosomal protein L23 (RPL23) inhibited MDM2-mediated p53 ubiquitination through direct binding to MDM2, and subsequently induced the p53 level as well as its activity, suggesting that it may be a candidate for use in tumor gene therapy. In the present study, we developed a recombinant adenoviral vector expressing the RPL23 gene under control of the carcinoembryonic antigen (CEA) promoter (rAd/CEA-RPL23), and using an in vitro system with cultured human colorectal carcinoma LoVo cells harboring the wt-p53 gene, we proved that rAd/CEA-RPL23 infection could induce the accumulation of endogenous wt-p53 protein and thus lead to the inhibition of tumor cell growth via inducing cell cycle arrest and apoptosis. In vivo treatment of rAd/CEA-RPL23 also exhibited a significant inhibitory effect on tumor growth in nude mice bearing LoVo xenografts. Furthermore, we showed that rAd/CEA-RPL23 synergized with classic chemotherapeutic agent 5-fluorouracil (5-FU) and enhanced its activity against LoVo cells in vivo and in vitro. Taken together, the data presented here suggest that CEA promoter-targeted exogenous RPL23 expression could be of therapeutic value against human colorectal carcinoma that retains wt-p53.

Advances in the study of serum tumor markers of lung cancer.

Lung cancer is among the most prevalently occurring carcinomas worldwide, and reducing lung cancer mortality depends on early detection, diagnosis, and treatment. Given the rapid development of molecular biology and modern techniques for diagnosis and treatment, the study of serum tumor markers has gained extensive application in early diagnosis, treatment effect monitoring, and prognosis evaluation. Serum tumor markers possess the advantages of easy detection, noninvasive operation, and cost-effectiveness. This article reviews the progress in the study of serum tumor markers of lung cancer.

Stereotactic body radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis.

The purpose of this study was to evaluate the clinical efficacy, toxicity and adverse effects of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). A total of 101 patients diagnosed with primary HCC with PVTT were enrolled in this study and were randomly divided into three groups as follows: group A, 34 patients treated with γ-SBRT followed by TACE; group B, 37 patients treated with TACE followed by γ-SBRT; and group C, 30 patients treated with γ-SBRT alone. The effective response rate for the entire patient sample was 87.1% (88/101) following a 3-month treatment. The differences in the response rate, survival rate, α-fetoprotein level restoration rate and rate of improvement of abdominal distention and discomfort between groups A and B were not statistically significant (P>0.05). However, the rates of groups A and B were higher compared to those of group C (P<0.05). The exacerbation rate of liver function in group A was lower compared to that in group B (P<0.05), although it exhibited no statistically significant difference from that in group C (P>0.05). No severe radiation-related complications were reported during the follow-up period. The combination of γ-SBRT and TACE was shown to be a relatively effective local treatment for primary HCC patients with PVTT. Compared to γ-SBRT followed by TACE and γ-SBRT alone, TACE followed by γ-SBRT may exert a negative effect on liver function. These results suggested that the combination of TACE and γ-SBRT may be considered a relatively effective, safe and feasible treatment method for primary HCC patients with PVTT, although TACE followed by γ-SBRT may negatively affect liver function.

Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.

AIMS: Brachyury overexpression has been reported in various human malignant neoplasms, but its expression and function in hepatocellular carcinoma progression and metastasis remains unknown. The present study aimed to evaluate the critical role of Brachyury in HCC metastasis. METHODS: The expression of Brachyury in human HCC (SMMC7721, HepG2, FHCC98, and Hep3B) and control cell lines was analyzed using quantitative reverse-transcriptase polymerase chain reaction and immunoflourence methods. Cancerous tissues collected from patients with HCC (n = 112) were analyzed using immunohistochemical method; a microarray analysis of HCC tissues was performed to explore the clinicopathological variables of HCC. The migratory and invasive capacities of Brachyury-SMMC7721 and Brachyury-HepG2 transfected cells were evaluated using in vitro scratch wound healing and Matrigel invasion assays, respectively. Further, six-week-old male BALB/c nude mice (n = 10) model was used in vivo assay. RESULTS: Elevated expression of Brachyury was detected in HCCs (62.5%) compared with that in adjacent nontumorous tissues. Clinicopathological analysis revealed a close correlation of Brachyury expression with distant metastasis and poor prognosis of HCC. Overexpression of Brachyury promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells in vitro and in vivo. Brachyury overexpression enhanced Akt activation by inhibiting phosphatase and tensin homolog (PTEN), which led to subsequent stabilization of Snail, a critical EMT mediator. CONCLUSION: The study findings suggest that elevated Brachyury facilitates HCC metastasis by promoting EMT via PTEN/Akt/Snail-dependent pathway. Brachyury plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.

Bioinformatic analysis of the membrane cofactor protein CD46 and microRNA expression in hepatocellular carcinoma.

The therapeutic potential of membrane complement regulatory protein (mCRP)-neutralizing antibodies is unsatisfactory, which perhaps lies in the complex role of mCRPs in tumor occurrence and development. As a member of the mCRPs, CD46 is a transmembrane protein with a cytoplasmic domain and is implicated more in the control of the alternative complement pathway than of the classical complement pathway. Growing evidence has revealed that both the CD46 signaling pathway and microRNAs (miRNAs) play an important role in the development and progression of hepatocellular carcinoma (HCC). In the present study, we analyzed mCRP expression in different tumor tissues by employing western blotting and qPCR. To address the potential role of miRNAs in CD46 signaling, we set out to profile miRNA expression in CD46-overexpressed and -silenced HepG2 cell lines. Furthermore, bioinformatic analysis was performed to identify downstream targets of CD46 signaling. We found that the levels of CD46 expression in HCC tissues were significantly higher compared to that in the adjacent normal tissues. After complement-related gene expression profiling and unsupervised hierarchical clustering analysis of 10 HCC tissues, a total of 37 miRNAs showed significantly different expression levels before and after CD46 expression change. By bioinformatic analysis, we identified let-7b and miR-17 as downstream targets of CD46 signaling, and that the expression levels of let-7b and miR-17 were negatively correlated with that of CD46 in HepG2 cells. The present study suggests that CD46 plays an important role in HCC carcinogenesis by regulating let-7b and miR-17.

Exploratory study on the correlation between 14 lung cancer-related gene expression and specific clinical characteristics of NSCLC patients.

Personalized medicine has become essential in the treatment of lung cancer. However, the lung cancer-related gene expression profiles in non-small cell lung cancer (NSCLC) patients have not been elucidated. In this study, the correlation between gene expression profiles and clinicopathological characteristics was investigated in NSCLC patients. A total of 95 patients were enrolled in this study. The mRNA expression levels of 14 genes were assessed by multiplex branched DNA liquidchip (MBL) technology and data on 9 clinicopathological characteristics of patients were collected simultaneously. The correlation between gene expression and clinicopathological characteristics was investigated. Out of the 9 clinicopathological parameters, 6 were associated with several of the 14 genes analyzed. Patient gender was associated with TYMS and TOP2A. Clinical stage was associated with VEGFR2, KIT and HER2. There was weak correlation between primary tumor size of ≤3 cm and the expression level of KIT. The mRNA expression levels of VEGFR2 and HER2 correlated with distant metastasis. BRCA1, TYMS, TOP2A and HER2 were associated with histological type. Smoking correlated with higher expression levels of BRCA1, TYMS and TOP2A and lower expression levels of PDGFRß. The results were suggestive of correlation between the clinicopathological parameters of the NSCLC patients and the mRNA expression levels of certain lung cancer-related genes, including BRCA1, TYMS, TOP2A, PDGFRß, VEGFR2, KIT and HER2.

[Efficacy of whole body gamma-knife radiotherapy combined with thermochemotherapy on locally advanced pancreatic cancer].

BACKGROUND & OBJECTIVE: Radiotherapy and chemotherapy are major therapies for locally advanced pancreatic cancer. This study was to evaluate the efficacy of three-dimensional conformal gamma-knife radiotherapy combined with thermochemotherapy on locally advanced pancreatic cancer. METHODS: From December 2001 to January 2006, 75 patients with locally advanced pancreatic cancer were divided into radiotherapy group (37 patients) and combination group (38 patients). All patients received gamma-knife radiotherapy using Stereotactic Radiotherapy Gamma Rays System, with iso-dose curves of 50%-60%, tumor encircling dose of 3.0-4.5 Gy per fraction, 8-11 fractions. The patients in combination group received simultaneous thermotherapy at 41.5-43.5 celsius (1 h/fraction, twice a week for 6 times), and chemotherapy with venous administration of tegafur (0.5-1.0 g) and calcium folinate (CF, 0.2 g) for 4-6 times, or venous administration of gemcitabine (0.6-1.0 g/m2) on Days 1 and 8 and cisplatin (DDP) (20-30 mg/m2) on Days 1-3, repeated every 28 days for 3-6 cycles. RESULTS: At 3 months after treatment, the total response (complete remission and partial remission) rate was 70.7% (53/75); the response rate was 73.7% in combination group and 67.5% in radiotherapy group. The 1-year survival rate was 48.3%, and the 2-year survival rate was 22.1%. The 1-and 2-year survival rates were 51.2% and 26.5% in combination group, and 45.2% and 17.6% in radiotherapy group. No serious complications, such as perforation, bleeding and high fever, were seen during treatment and follow-up. CONCLUSION: 3-D conformal gamma-knife radiotherapy combined with thermochemotherapy is well tolerated and is relatively effective for most patients with locally advanced pancreatic cancer.