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Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.

Most of the patients with oral and maxillofacial malignancy are in the middle and advanced stages at diagnosis and the incidence rate is increasing in recent years. Chemotherapy alone is difficult to benefit the survival of patients with advanced oral and maxillofacial malignancy. Ultrasound hyperthermia is a new and effective treatment for malignant tumor, which is developing rapidly in addition to conventional treatment. However, at present, ultrasound hyperthermia has not been widely used in the treatment of oral and maxillofacial malignancy. Therefore, formation of a guideline on ultrasound hyperthermia for oral and maxillofacial malignancy is mandatory, in order to promote and standardize the clinical practice of ultrasound hyperthermia in this field, and improve the long-term survival rate and quality of life of patients.

Tumor hyperthermia is to heat tumor tissue with biological thermal effect that can kill cancer cells when achieved effective treatment temperature. However, the temperature distribution of hyperthermia is uneven and it can not be accurately oriented to the tumor region. In this paper, an array antenna which can realize large-scale heating was designed for tumor microwave hyperthermia. ZrMOF-Cys nanoparticles (ZMC NPs) were prepared as the sensitizer of microwave hyperthermia. In the experiment of hyperthermia, array antenna and ZMC NPs are combined to achieve the goal of conformal hyperthermia and enhance the effect of hyperthermia. ZMC NPs have excellent heating effect, biodegradability and low cytotoxicity. ZMC NPs were injected into tumorbearing BALB/c mice by tail vein. Due to enhanced permeability and retention effect (EPR), ZMC NPs can enrich tumor sites to the greatest extent at 6 h. After 6 h of injection, the mice were treated with array antenna. The experimental results indicate that the combination of array antenna and ZMC NPs makes the temperature of tumor site higher than that of surrounding normal tissue, which has an excellent therapeutic effect, and the tumor inhibition rate reaches 87.52%. Phantom models experiments are also proved that the combination of array antenna and ZMC NPs can achieve the effect of conformal thermotherapy. This work provides a new direction for the development of conformal hyperthermia.

Peroxisome proliferator-activated receptors (PPARs) are members of nuclear transcription factors. The functions of the PPAR family (PPARA, PPARD, and PPARG) and their coactivators (PPARGC1A and PPARGC1B) in maintenance of lipid and glucose homeostasis have been unveiled. However, the roles of PPARs in cancer development remain elusive. In this work, we made use of 11,057 samples across 33 TCGA tumor types to analyze the relationship between PPAR transcriptional expression and tumorigenesis as well as drug sensitivity. We performed multidimensional analyses on PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B, including differential expression analysis in pan-cancer, immune subtype analysis, clinical analysis, tumor purity analysis, stemness correlation analysis, and drug responses. PPARs and their coactivators expressed differently in different types of cancers, in different immune subtypes. This analysis reveals various expression patterns of the PPAR family at a level of pan-cancer and provides new clues for the therapeutic strategies of cancer.

MicroRNA-155 is over-expressed in many human cancers, but researches on its association with malignant oesophageal squamous cell carcinoma (ESCC) are limited. The aim of the present study was to evaluate the potential value of

In recent decades, a large number of research studies have been conducted to improve the treatment strategy against epithelial ovarian cancer, but women in advanced stage still have poor outcomes. The development of advanced treatments must be continued to overcome the limitation. Docetaxel, a semi-synthetic product derived from the Pacific Taxus extract, has been studied for many years for its potent anticancer applications. Aiming to solve the problems of its highly lipophilicity, insolubility and adverse side effects, nanocarriers were applied. Relying on the integration of nanoparticles which had optimized sizes, shapes, and surface properties, the effect of docetaxel was enhanced. In this study, we designed a novel drug loaded gel-forming nanoparticle system (Doc-NMs-hydrogel composites), which acted as a sustained drug depot for docetaxel. Docetaxel was encapsulated into MPEG-PCL and then into blank thermosensitive hydrogel Pluronic F-127. Characterization showed that the prepared Doc-NMs had high drug loading (7%), minor particle size (37 nm), relatively good water solubility. Moreover, the cytotoxicity, apoptosis induction and the antitumor effects of Doc-NMs-hydrogel composites on mice abdominal SKOV-3 ovarian cancer model were investigated in vivo. Compared with other groups, at the same dosage, Doc-NMs-hydrogel composites show better apoptosis induction and cell growth inhibition. In conclusion, the prepared Doc-NMs-hydrogel composites enhanced anti-tumor activity by increasing local docetaxel concentration, maintaining stable and sustained drug release, prolonging drug retention time in tumors, and reducing toxicity to normal tissues. Doc-NMs-hydrogel composites might have great potential clinical application in anti-ovarian cancer activity.

Long non-coding RNAs (lncRNAs) have been widely highlighted due to their involvement in various types of cancers, including glioma; however, the exact mechanism and function by which they operate in regard to spinal cord glioma remain poorly understood. LOC101928963 was screened out for its differential expression in spinal cord glioma by microarray analysis. Therefore, this study was conducted to investigate the modulatory effects of LOC101928963 on spinal cord glioma by binding to phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1). The expression of LOC101928963 and LOC101928963 was characterized in spinal cord glioma tissues, and their interaction was examined by dual-luciferase reporter gene assay. Cells with LOC101928963 that exhibited elevated or suppressed levels of PMAIP1 were established to substantiate the mechanism between LOC101928963 and PMAIP1. qRT-PCR and western blot methods were subsequently applied to determine the expression of cell-proliferation- and apoptosis-related genes in response to the alterations of LOC101928963 and PMAIP1. Glioma cell proliferation and apoptosis were assessed by MTT assay and flow cytometry. Decreased cell apoptosis and PMAIP1 expression, as well as overexpressed LOC101928963, were exhibited among spinal cord glioma tissues. LOC101928963 overexpression was observed to promote cell proliferation and cell-cycle entry and inhibit the process of apoptosis. PMAIP1, a target of LOC101928963, displayed a downregulated level following the elevation of LOC101928963. The present results strongly emphasize the neutralization effect of PMAIP1 overexpression on spinal cord glioma progression induced by the overexpression of LOC101928963. The data obtained during the study highlighted the inhibitory role of LOC101928963 silencing in spinal cord glioma through the increase in PMAIP1, which suggests a potential target in the treatment of spinal cord glioma. Keywords: LOC101928963, PMAIP1, spinal cord glioma, proliferation, apoptosis

BackgroundThe oesophageal carcinoma patients show high incidence of malnutrition, which negatively affects their therapy outcome. Moreover, benefits of enteral nutrition remain to be studied in details in these patients. Therefore, we set to assess the effects of enteral nutrition on the nutritional status, treatment toxicities and survival in the oesophageal carcinoma patients treated with concurrent chemoradiotherapy (CCRT).Materials and MethodsEligible patients were randomly assigned to either the experimental or control group. The patients in the experimental group were treated with a whole-course enteral nutrition management, while the control group were provided a unsystematic nutrition without setting intake goals for energy and protein. The primary endpoint was a change in body weight, while the secondary endpoints included nutrition-related haematological indicators, toxicities, completion rate of treatment and survival.ResultsA total of 222 patients were randomised to either the experimental (n=148) or control (n=74) group. Patients in the experimental group showed significantly less decrease in body weight, serum albumin and haemoglobin levels, a lower incidence rates of grade ≥3 myelosuppression and infection, and a higher completion rate of CCRT than those in the control group. While analyses of the 2 and 3 year overall survival (OS) and progression-free survival (PFS) did not reveal differences between these groups, we observed a significantly higher OS at 1 year (83.6% vs. 70.0%). In the subgroup analysis, patients with patient-generated subjective global assessment (PG-SGA)=C were likely to have better OS and PFS with enteral nutrition.ConclusionsIn EC patients treated with CCRT, enteral nutrition conferred positive effects on the nutritional status, treatment toxicities and prognosis, which mandate its inclusion in clinical practice.Clinical Trial RegistrationThis prospective trial has been registered with www.clinicaltrials.gov as NCT02399306.

Yongqiang Yang, Xiaole Li, Pengcheng Zhou, Xiaoyu Deng, Yingyi Wang, Qianqian Dang, Yingjuan Zheng, Daoke Yang Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yingjuan Zheng; Daoke YangDepartment of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, People’s Republic of ChinaTel +86-15738872856; +86-15903650068Email zdyfyzlyy@163.com; 15903650068@163.comPurpose: To analyze the effects of radiotherapy and its timing on the survival and safety of patients with newly diagnosed distant metastatic NPC in non-high-incidence areas.Patients and Methods: We retrospectively analyzed 94 newly diagnosed NPC patients with distant metastatic admitted to our hospital from January 2011 to June 2018. They were divided into three groups: no radiotherapy group received chemotherapy alone, early radiotherapy group was combined with radiotherapy during 1 to 3 cycles of chemotherapy, and late radiotherapy group was combined with radiotherapy after 4– 6 cycles of chemotherapy were effective. The efficacy and side effects of the three groups were compared, and the prognostic factors were analyzed.Results: The 6-month, 1-year and 2-year PFS were 53.6%, 14.3% and 3.6% in no radiotherapy group, 71.0%, 38.7% and 19.4% in early radiotherapy group, 88.6%, 48.6% and 22.9% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the difference was statistically significant (P < 0.017). The 1-year, 2-year and 3-year OS were 75.0%, 32.1% and 0 in no radiotherapy group, 77.4%, 54.8% and 12.9% in early radiotherapy group, 85.7%, 71.4% and 31.4% in late radiotherapy group; the radiotherapy groups were better than the no radiotherapy group, and the differences were statistically significant (P < 0.017). There was no significant difference in OS and PFS between the two radiotherapy groups. Univariate and multivariate analysis showed that HBV (P = 0.031), number of metastases (P = 0.002), liver metastases (P = 0.038), radiotherapy (P < 0.001) and treatment response (P = 0.011) were related to OS. There was no significant difference in the incidence of adverse events (P > 0.017).Conclusion: Early and late combined radiotherapy had similar clinical efficacy and both prolonged PFS and OS for patients with newly diagnosed distant metastatic NPC in non-high-risk areas. If chemotherapy response is expected to be poor, radiotherapy can be received early.Keywords: radiotherapy, nasopharyngeal carcinoma, metastasis, non-high-incidence area, prognosis

The matrix protein (MP) is the core structure of the oncolytic vesicular stomatitis virus (VSV) and it played a vital role during the process of VSV infection and corresponding cytopathic effects in cancer treatment. In this study, a novel delivery synthesized by PEG-PCL-PEG and DOTAP (PPPD) was applied to encapsulate MP plasmids to derive the advantage and overcome the drawback of VSV platform in the treatment of colon cancer. The MP/DPPP micelles were stable in physiological solution, with an average diameter of 102 nm and zeta potential of 5.4 mV. This delivery system has a high encapsulation rate of 96% and transfection efficiency of 36%. A prominent anti-cancer activity of MP/DPPP was found both in Ct26 cells and animal models. The mechanisms of antitumor were further explored in this research. Our results indicated that MP/DPPP micelles were promising agents for future clinical application in the treatment of colon cancer.

Esophageal cancer (EC) patients receiving radiotherapy are at a high risk of malnutrition, which can increase the side effects of radiotherapy, reduce the accuracy and sensitivity of radiotherapy and decrease treatment effect. Therefore, timely and correct nutritional treatment is crucial. To date, however, neither consensus nor guidelines on enteral nutrition (EN) specifically for EC patients receiving radiotherapy exist. Accordingly, an expert consensus conference was held to establish consensus on the use of EN in EC patients receiving radiotherapy. It reflected the opinions of a multidisciplinary group of experts and a review of the current literature, and established common guidelines for nutritional screening and assessment, nutrition counseling, indication for EN, access and formulas of EN, effect evaluation, nutrition plan adjustment, and home enteral nutrition.

Purpose Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers. To evaluate the safety and efficacy of atezolizumab in treating cancers, we conducted this meta-analysis. Methods Embase, PubMed, MEDLINE, the Central Register of Controlled Trials of the Cochrane Library, and the American Society of Clinical Oncology database were searched for relevant studies. The primary outcomes were any grade adverse events (AEs) and grade ≥3 AEs. The secondary outcomes were overall objective response rate, pooled 6-month progression-free survival (PFS) rate, 1-year overall survival (OS) rate, median PFS, and median OS. Results Our meta-analysis was based on 14 clinical trials with 3,266 patients. The total risk of any grade AEs reached 69%, while grade ≥3 AEs happened in only 13% of participants. The overall atezolizumab-related death rate was 0.17%. Major common AEs involved fatigue (24.5%), decreased appetite (13.2%), nausea (12.3%), diarrhea (10.8%), pyrexia (10.7%), pruritus (9.6%), cough (9.5%), edema peripheral (8.6%), and rash (8.4%). The most common severe AEs were fatigue (2.2%), anemia (1.9%), and dyspnea (1.9%). Meanwhile, we found that 6% patients reached complete response and 16% partial response. The pooled 6-month PFS rate and 1-year OS rate were 0.36 (95% CI: 0.31-0.41) and 0.55 (95% CI: 0.49-0.61), respectively. The median PFS varied from 1.5 to 6.1 months, and the median OS ranged from 5.9 to 28.9 months. Conclusion Atezolizumab has a considerable potential in treating cancers with an acceptable risk profile.

Aim: To analyze the role of prophylactic cranial irradiation (PCI) on the survival for patients with limited-stage small-cell lung cancer (LS-SCLC). Patients & methods: We screened patients from SEER database. Kaplan–Meier analysis and Cox proportional hazard model were used to evaluate factors influencing survival. Results: LS-SCLC patients who receiving PCI were associated with better overall survival (OS; p 0.05). Conclusion: PCI remains an effective method for most LS-SCLC patients. However, caution should be taken in recommending PCI for black patients and patients with a tumor size

Colorectal cancer is one of the most common and malignant cancer in the world wide. Recently, combination of target therapy and chemotherapy has generated new promise for colorectal cancer. Apatinib mesylate is a novel and highly selective VEGFR-2 inhibitor, presented with an outstanding activity of anti-angiogensis, which has the potential for treating various tumors. As a traditional chemotherapeutic drug, docetaxel (Taxotere) is a widely used semisynthetic taxoid in solid tumors. In this study, Liposome and Methoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) were constructed as drug delivery system for the delivery of apatinib (Lipo-Apa) and docetaxel (DOC/M), respectively. Co-administration of Lipo-Apa and DOC/M showed synergistically effects on inhibiting cell proliferation and inducing cell apoptosis of CT26 cells in vitro. Moreover, fibrin glue, as a biocompatible adherent hemostat, was used as a kind of vehicle for locally delivery of DOC/M in animal models, for achieving locally high concentration and prolonging releasing time. Combination of Lipo-Apa by gavage and locally delivery of DOC/M showed significantly improved anti-tumor activity in a subcutaneous xenograft model as well as in the abdominal metastasis model of colorectal cancer. In addition, promoted tumor apoptosis, inhibited proliferation and decreased tumor angiogenesis were presented by the co-administration. Finally, our study suggested that combination of oral administration of Lipo-Apa and locally delivery of DOC/M by fibrin glue, has the potential to be applied clinically in colorectal cancer therapy.

BackgroundInvasion and metastasis of cervical cancer are the main factors affecting the prognosis of patients with cervical squamous cell carcinoma (CESC). Therefore, it is of vital importance to find novel biomarkers that are associated with CESC invasion and metastasis, which will aid in the amelioration of individualized therapeutic methods for advanced patients.MethodsThe gene expression profiles of 10 metastatic and 116 non-metastatic samples were downloaded from The Cancer Genome Atlas (TCGA), where differentially expressed genes (DEGs) were defined. Weighted gene correlation network analysis (WGCNA) was employed to identify the stemness-related genes (SRGs). Univariate and multivariate regression analyses were used to identify the most significant prognostic key genes. Differential expression analysis of transcription factor (TF) and Gene Set Variation Analysis (GSVA) were utilized to explore the potential upstream regulation of TFs and downstream signaling pathways, respectively. Co-expression analysis was performed among significantly enriched TFs, key SRGs, and signaling pathways to construct a metastasis-specific regulation network in CESC. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for the network. Additionally, direct regulatory patterns of key genes were validated by ChIP-seq and ATAC-seq data.ResultsDEGs in yellow module acquired via WGCNA were defined as key genes which were most significantly related to mRNAsi. A multivariate Cox regression model was constructed and then utilized to explore the prognostic value of key SRGs by risk score. Area under curve (AUC) of the receiver operating characteristic (ROC) curve was 0.842. There was an obvious co expression pattern between the TF NR5A2 and the key gene VIM (R = 0.843, p < 0.001), while VIM was also significantly co-expressed with hallmark epithelial mesenchymal transition (EMT) signaling pathway (R = 0.318, p < 0.001). Naringenin was selected as the potential bioactive small molecule inhibitor for metastatic CESC based on CMap analysis.ConclusionsVIM positively regulated by NR5A2 affected EMT signaling pathways in metastatic CESC, and naringenin was the inhibitor for the treatment of metastatic CESC via suppressing cancer stemness. This hypothetical signaling axis and potential inhibitors provide biomarkers and novel therapeutic targets for metastatic CESC.

// Xiaoxiao Zuo 1, * , Miao Li 2, * , Ya Yang 1 , Tiansong Liang 1 , Hongyao Yang 1 , Xinhan Zhao 2 and Daoke Yang 1 1 Department of Radiation Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450000, People's Republic of China 2 Department of Internal Medicine Oncology, The Fifth People’s Hospital of Qinghai Province, Xining, Qinghai 810007, China * These authors contribute equally to this work Correspondence to: Daoke Yang, email: ydk8666@126.com Xinhan Zhao, email: zhaoxinhan@mail.xjtu.edu.cn Keywords: cytokines; IL1; breast cancer; case-control; polymorphisms Received: September 06, 2017 Accepted: November 15, 2017 Epub: December 11, 2017 Published: April 06, 2018 ABSTRACT Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12–7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41–0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45–0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer.

// Qianqian Zhu 1, * , Yanan Sun 1, * , Yingying Cui 1 , Ke Ye 1 , Chengliang Yang 1 , Daoke Yang 2 , Jie Ma 1 , Xiao Liu 1 , Jinming Yu 3 , Hong Ge 1 1 Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China 2 Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China 3 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, 250117, Shandong Province, China * These authors contributed equally to this work Correspondence to: Hong Ge, email: gehong616@126.com Keywords: non-small cell lung cancer, brain metastases, epidermal growth factor receptor, tyrosine kinase inhibitors, radiotherapy Received: August 31, 2016 Accepted: December 27, 2016 Published: January 05, 2017 ABSTRACT This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models. Median cranial PFS and OS were longer for the TKI + RT group ( n = 67) than TKI alone group ( n = 66). Intracranial metastasis correlated with a better median OS than extracranial metastasis. For patients with exon 21 mutations, TKI + RT yielded a better median OS and cranial PFS than TKI alone. However, there were no significant differences in median OS and cranial PFS between the two treatment groups for patients with exon 19 deletions. Thus EGFR-mutant NSCLC patients with BM could benefit more from TKI + RT than from TKI monotherapy, especially when they suffer from exon 21 mutations. However, TKI + RT confers no advantage over TKI treatment alone for patients with exon 19 deletions. These results underscore the urgent need to develop individualized disease management strategies in clinical practice.

Metastatic colorectal cancer is a stumbling block in colorectal cancer management due to limited treatment approaches and unfavorable prognosis. Angiogenesis is essential in tumor development and metastasis. Vascular endothelial growth factor receptor (VEGFR) targeted anti-angiogenesis drugs have gain inspiring achievements in cancer treatment. Apatinib is a novel small molecular VEGFR-2 tyrosine kinase targeted drug with poor water-solubility, showing anti-tumor ability in some solid tumors. In this study, PEG modified liposomal Apatinib (Apatinib-Lipo/PEG) was synthesized and applied for colorectal cancer treatment. Results showed that Apatinib-Lipo/PEG could attenuate proliferation and induce apoptosis of CT26 cells. Moreover, Apatinib-Lipo/PEG significantly reduced tumor growth in colorectal peritoneal model as well as subcutaneous model without obvious toxicity. The anti-tumor mechanisms included inhibiting tumor proliferation, promoting tumor apoptosis and suppressing tumor angiogenesis. Thereafter, the application of Apatinib-Lipo/PEG would be very promising in colorectal cancer treatment.

Background Breast cancer (BC) is the most common cancer in women and the second leading cause of cancer‐related deaths among women worldwide. Single nucleotide polymorphisms (SNPs) in cytokine genes have been shown to alter their expressions or functions in patients with BC. In recent years, the molecular structure and function of IL‐1 have been studied. Its genetic polymorphism could affect the transcription and expression of the IL‐1 gene. Moreover, it is closely related to several diseases. This fact and plethora of gene polymorphism data prompted us to investigate the relationship between IL‐1 polymorphisms and IL‐1 protein expression in Chinese Han BC patients. Method In total, 298 patients with BC and 287 healthy control women were studied. The genetic polymorphisms for IL‐1 were analyzed by the MassARRAY sequencing method. Tumor markers and IL‐1β levels were measured by electrochemiluminescence and ELISA, respectively. All gene selection GRCh38 version. Results The rs1143623 (NC_000002.12:g.112838252C>G) (GC), rs16944 (NC_000002.12:g.112837290A>G)(AG), and rs10490571 (NC_000002.12:g.102100877C>T) (CC) SNPs were found to be significantly lower in the BC group than in the controls. The variant G/C genotype of rs1143623 was associated with a significantly increased risk for BC (OR = 2.34, p

Background: Intensity-modulated radiation therapy (IMRT) has been more widely used in extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) because it can maximally improve the local control rate of tumor and reduce the radiation dose received by surrounding normal tissues. However, there has been no consensus on whether IMRT can help to lower the toxic and adverse reactions caused by radiation therapy. The aim of this study is to compare skin toxicity caused by IMRT and conventional radiotherapy in Stage I–II NKTCL. Methods: A total of 93 patients with Stage I–II NKTCL, nasal-type arising in the nasal cavity were consecutively treated using curative radiotherapy between April 2005 and August 2014. These patients received radiotherapy without chemotherapy. Definitive radiotherapy was conducted using conventional radiotherapy in 33 patients and IMRT in the other sixty patients with a regional field and a total dose of 50 Gy. Dosimetric parameters of radiation treatment plans and skin toxicity were analyzed and compared between conventional radiotherapy and IMRT. Results: From the dosimetric analysis, IMRT demonstrated significantly improved dose coverage and homogeneity than conventional radiotherapy. Meanwhile, the Grade 1, 2, and 3 skin toxicity incidences in conventional radiotherapy group were 42.4%, 39.4%, and 18.2%, and in IMRT group were 25.0%, 31.7%, and 43.3%, respectively. Our data suggested that the severity of skin toxicity in IMRT group was statistically higher than that in conventional radiotherapy group. Conclusions: IMRT provided improved dose coverage than conventional radiotherapy. However, IMRT failed to lower patients' risks for skin toxicity and may have the potential to increase skin toxicity.

BACKGROUND Malignant giant cell tumor of bone (MGCTB) is a rare histological type of malignant tumor that has a high tendency for local relapse and distant metastasis and ultimately leads to a poor prognosis. The purpose of this study was to describe the epidemiological features, identify the prognostic factors, and construct nomograms for patients with MGCTB. MATERIAL AND METHODS Patients with MGCTB that was histologically diagnosed between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. Survival analysis, Lasso regression, and random forests were used to identify the prognostic variables and establish the nomograms for patients with MGCTB, while an external cohort of 37 patients from our own institution and an external cohort of 163 patients from the SEER database in 2016 were used to validate the generalization performance of the nomograms. RESULTS In total, univariate and multivariable analysis indicated that age, International Classification of Diseases for Oncology, historical stage, primary site, surgery information, radiotherapy, and chemotherapy were independent prognostic variables for overall survival or cause-specific survival. Nomograms based on the multivariable models were built to predict survival, and we achieved a higher C-index in subsequent multidimensional validation. CONCLUSIONS Age, historical stage, and chemotherapy were independent prognostic variables for overall survival and cause-specific survival of MGCTB patients, and radiotherapy and primary site were independent prognostic variables for overall survival. Nomograms based on significant clinicopathological features and clinical experience can be effective in predicting the probability of survival for MGCTB patients.

Radiotherapy resistance is the main cause of the the poor prognosis of some nasopharyngeal carcinoma (NPC) patients. Yet, the exact mechanism is still elusive. In the present study, we explored the clinical and biological role of protein arginine methyltransferase 5 (PRMT5) in NPC. Our results revealed that PRMT5 was overexpressed in NPC tissues when compared with that in adjacent non-tumor tissues by quantitative RT-PCR and immunoblotting. High expression of PRMT5 was correlated with adverse outcomes of NPC patients as determined by the scoring of a tissue microarray. Silencing of PRMT5 promoted the radiosensitivity of 5-8F and CNE2 cells as determined by cell proliferation and colony formation assays. Furthermore, fibroblast growth factor receptor 3 (FGFR3) was identified as one of the downstream targets of PRMT5, and the silencing of PRMT5 decreased the mRNA and protein levels of FGFR3 in the 5-8F and CNE2 cells. Silencing of FGFR3 induced similar phenotypes as the inhibition of PRMT5, and re-expression of FGFR3 in 5-8F/shPRMT5 and CNE2/shPRMT5 cells restored the proliferation and colony formation ability induced by irradiation exposure. Our results indicate that PRMT5 is a marker of poor prognosis in NPC patients. PRMT5 promoted the radioresistance of NPC cells via targeting FGFR3, at least partly if not totally. PRMT5 and its downstream effector FGFR3 may be potential targets for anticancer strategy.

Colorectal cancer (CRC) exhibited high incidence rate worldwide and the advanced CRC had a poor prognosis. Thereupon, seeking efficient treatment for CRC is critical. Apatinib is a novel vascular epithelial growth factor receptor (VEGFR) inhibitor with inspiring therapeutic effect in some malignant cancers. In our study, doxorubicin was mixed in fibrin gel and apatinib was encapsulated with self-synthesized liposome. The results showed liposomal apatinib (Lipo-Apatinib) could enhance the intracellular uptake of doxorubicin in vitro. Moreover, compared with doxorubicin loaded fibrin gel (DOX-FG) alone, the combination of DOX-FG and Lipo-Apatinib significantly improved the anti-tumor effect in mice CRC subcutaneous model and abdominal metastasis model Drug combination successfully inhibited tumor angiogenesis and tumor proliferation, and also promoted tumor apoptosis. Our data suggested that combined therapy of DOX-FG and Lipo-Apatinib would be a promising treatment approach for CRC.

BACKGROUND The interleukins (ILs) are a large family of endogenous cytokines that are crucial in the regulation of inflammation and immunological responses. The IL-1 receptor antagonist (IL-1RN) has been found to be associated with risk breast cancer (BC) in Korean and Indian women. However, little information is found about the polymorphisms of IL-1RN in Chinese Han BC patients. METHODS We investigated the association between single-nucleotide polymorphisms (SNPs) in IL-1RN and BC risk in a case-control study that included 530 BC cases and 628 healthy controls. Six tag SNPs in IL-1RN were selected and genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and sex. RESULTS In the allele model, we found that the frequency of the 'T' allele of rs928940 was significantly lower in BC cases than in controls (OR = 0.776, 95% CI = 0.611-0.985, p = 0.037). In the genetic model analysis, five susceptibility SNPs were found to be associated with BC risk: the minor allele 'G' of rs315919, rs3181052 and rs452204 were associated with a decreased risk of BC under dominant model (p

Background: Promoter methylation is an alternative mechanism of gene silencing in human tumorigenesis. Although a number of methylated genes have been found in non small cell lung cancer (NSCLC), useful methylation markers for early prognostic evaluation of NSCLC remain largely unknown. Methods: Using methylation-specific PCR (MSP), we examined promoter methylation status of PAX6 gene, and explored their association with clinical features in NSCLC via chi-square test. NSCLC patient survival was assessed by Kaplan-Meier analyses and a Cox proportional hazard model was employed for multivariate analyses. Results: The methylation level of PAX6 gene was higher in tumor tissues than that in normal tissues. In addition, PAX6 promoter methylation showed a very significant correlation with differentiation (P = 0.002), distant metastasis (P = 0.024), and TNM stage (P = 0.002). PAX6 gene promoter hyper-methylation was found to be significantly associated with poor overall survival (P = 0.018) and to serve as an independent marker for prognosis using multivariate Cox regression analysis (HR: 2.254, 95% CI: 1.088-4.667, P = 0.029). Conclusion: We found that PAX6 gene was specifically methylated in NSCLC, and demonstrated the effect of promoter methylation of PAX6 gene on clinical outcome in NSCLC, indicating the methylated PAX6 may be useful biomarkers for prognostic evaluation in NSCLC.

4033 Background: Patients with esophageal cancer undergoing CCRT are at high risk of malnutrition. The aim of this study was to investigate the influence of enteral nutrition on nutritional status, treatment tolerance and outcomes in esophageal cancer patients undergoing CCRT. Methods: Patients with inoperable esophageal cancer were randomly assigned (2:1 ratio) to the enteral nutrition group (EN group) or the control group. Patients in the EN group were supported with individual enteral nutrition intervention according to the nutritional status assessment results. The control group was treated with conventional diet guidance. The primary endpoint was the change in body weight from baseline after treatment. Secondary endpoints were nutrition related blood parameter changes, treatment tolerance and outcomes. Results: Between Mar. 2015 and Jan. 2017, 158 patients from ten hospitals were randomised into the EN group (n = 106) and the control group (n = 52). Following CCRT, patients in EN group lost only 0.72±3.27 kg of body weight compared with 2.10±2.89 kg in the control group (P < 0.001). Participants who received EN had less decline than controls in serum albumin (2.66±5.05 g/L and 4.75±4.94 g/L, P < 0.001) and hemoglobin (10.29±15.78 g/L and 18.48±14.66 g/L, P < 0.001). Grade 3/4 leukopenia in the control group was significantly more frequent than the EN group (33.3% vs. 20.0 %, P = 0.011). Patients supported on EN experienced greater chemoradiotherapy completion rates (92.5% vs. 67.3%, P = 0.001) and lower infection rates (18.8% vs 31.7%, P = 0.021). There was significant difference in tumor response between two groups (EN group: 81.1%, control group: 67.3%, P = 0.004). The 1- and 2-year OS rates in the EN group were significantly greater (89.6% and 75.4%, respectively) compared with the control group (78.5% and 57.9%, respectively). Conclusions: Enteral nutrition may be advantageous in patients with esophageal cancer undergoing CCRT by improving nutritional status, treatment tolerance and outcomes. Clinical trial information: NCT 02399306.