Biomarkers of lipid metabolism in gastric cancer: a case control study.

BACKGROUND: The aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer. METHODS: 1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected. RESULTS: Serum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage. CONCLUSIONS: The serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

Proteomic analysis of exosomal proteins associated with bone healing speed in a rat tibial fracture model.

This study investigates the impact of exosomes on bone fracture healing in a rat tibial model, distinguishing between fast and slow healing processes. Bone healing and protein expression were assessed through X-ray examinations, hematoxylin and eosin staining, and immunohistochemical staining. Exosomes were isolated, characterized and subjected to liquid chromatography-mass spectrometry for protein analysis. Molecular differences were explored using differentially expressed protein analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment and protein-protein interaction networks. Differential bone healing patterns and protein expressions were observed between the control and model groups. Exosomes were successfully isolated and characterized, revealing 2004 identified proteins, including distinct expression profiles. Notably, ribosomal proteins, ferritin and beta-actin emerged as pivotal players in bone fracture healing. This study unveils dynamic changes in bone healing and underscores the role of exosomes in the process. Identified proteins and pathways offer valuable insights for developing innovative therapeutic strategies for bone healing.

LncRNA DGUOK-AS1 Promotes Cell Progression in Lung Squamous Cell Carcinoma by Regulation of miR-653-5p/SLC6A15 Axis.

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p.

Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer.

BACKGROUND: Structural variations (SVs) are common genetic alterations in the human genome. However, the profile and clinical relevance of SVs in patients with hereditary breast and ovarian cancer (HBOC) syndrome (germline BRCA1/2 mutations) remains to be fully elucidated. METHODS: Twenty HBOC-related cancer samples (5 breast and 15 ovarian cancers) were studied by optical genome mapping (OGM) and next-generation sequencing (NGS) assays. RESULTS: The SV landscape in the 5 HBOC-related breast cancer samples was comprehensively investigated to determine the impact of intratumor SV heterogeneity on clinicopathological features and on the pattern of genetic alteration. SVs and copy number variations (CNVs) were common genetic events in HBOC-related breast cancer, with a median of 212 SVs and 107 CNVs per sample. The most frequently detected type of SV was insertion, followed by deletion. The 5 HBOC-related breast cancer samples were divided into SVhigh and SVlow groups according to the intratumor heterogeneity of SVs. SVhigh tumors were associated with higher Ki-67 expression, higher homologous recombination deficiency (HRD) scores, more mutated genes, and altered signaling pathways. Moreover, 60% of the HBOC-related breast cancer samples displayed chromothripsis, and 8 novel gene fusion events were identified by OGM and validated by transcriptome data. CONCLUSIONS: These findings suggest that OGM is a promising tool for the detection of SVs and CNVs in HBOC-related breast cancer. Furthermore, OGM can efficiently characterize chromothripsis events and novel gene fusions. SVhigh HBOC-related breast cancers were associated with unfavorable clinicopathological features. SVs may therefore have predictive and therapeutic significance for HBOC-related breast cancers in the clinic.

[Development of needle-thread integrative embedding needle].

The needle-thread integrative embedding needle consists of needle handle, needle core, thread, locker and needle guard. The thread is fixed in the core by the locker. With the needle inserted into acupoint, the locker is separated from the thread, while the thread is embedded directly into acupoint, to achieve one acupoint with one needle. This type of thread embedding needle is operated simply and safely without cross infection occurrence, easy to carry.

Heterogeneity and potential therapeutic insights for triple-negative breast cancer based on metabolic-associated molecular subtypes and genomic mutations.

Objective: Due to a lack of effective therapy, triple-negative breast cancer (TNBC) is extremely poor prognosis. Metabolic reprogramming is an important hallmark in tumorigenesis, cancer diagnosis, prognosis, and treatment. Categorizing metabolic patterns in TNBC is critical to combat heterogeneity and targeted therapeutics. Methods: 115 TNBC patients from TCGA were combined into a virtual cohort and verified by other verification sets, discovering differentially expressed genes (DEGs). To identify reliable metabolic features, we applied the same procedures to five independent datasets to verify the identified TNBC subtypes, which differed in terms of prognosis, metabolic characteristics, immune infiltration, clinical features, somatic mutation, and drug sensitivity. Results: In general, TNBC could be classified into two metabolically distinct subtypes. C1 had high immune checkpoint genes expression and immune and stromal scores, demonstrating sensitivity to the treatment of PD-1 inhibitors. On the other hand, C2 displayed a high variation in metabolism pathways involved in carbohydrate, lipid, and amino acid metabolism. More importantly, C2 was a lack of immune signatures, with late pathological stage, low immune infiltration and poor prognosis. Interestingly, C2 had a high mutation frequency in PIK3CA, KMT2D, and KMT2C and displayed significant activation of the PI3K and angiogenesis pathways. As a final output, we created a 100-gene classifier to reliably differentiate the TNBC subtypes and AKR1B10 was a potential biomarker for C2 subtypes. Conclusion: In conclusion, we identified two subtypes with distinct metabolic phenotypes, provided novel insights into TNBC heterogeneity, and provided a theoretical foundation for therapeutic strategies.

Development of an Active Surveillance or Surgery Model to Predict Lymph Node Metastasis in cN0 Papillary Thyroid Microcarcinoma.

Objective: Involvement of multiple lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) may indicate a progressive disease. To assist treatment decision, we conducted a clinical study to develop and validate a prediction model for the preoperative evaluation of LN metastasis involving more than five lymph nodes in patients with clinical N0 (cN0) PTMC. Material and Methods: Using data from 6,337 patients with cN0 PTMCs at Tianjin Medical University Cancer Institute and Hospital from 2013 to 2017, we identified and integrated risk factors for the prediction of multiple LN metastasis to build a nomogram. The predictive accuracy and discriminative ability of the nomogram were evaluated by the concordance index (C-index) and calibration curve. The model was validated using bootstrap resampling of the training cohort and an independent temporal validation cohort at the same institution. Results: In the training cohort (n = 3,209 patients), six independent risk factors were identified and included the prediction model (PTMC Active Surveillance or Surgery (ASOS) Model), including age, gender, multifocality, tumor size, calcification, and aspect ratio. The PTMC ASOS model was validated both internally and through the temporal validation cohort (n = 3,128 patients) from the same institute. The C-indexes of the prediction model in the training cohort were 0.768 (95% CI, 0.698-0.838), 0.768 and 0.771 in the internal validation and external validation cohorts, respectively. The area under the receiver operating characteristic curve (AUC) was 0.7068 and 0.6799. The calibration curve for probability of large-LN metastasis showed good agreement between prediction by nomogram and actual observation. DCA curves were used for comparison with another model, and IDI and NRI were also calculated. The cutoff value of our model was obtained by the ROC curve. Based on this model and cut point, a web-based dynamic nomogram was developed (https://tjmuch-thyroid.shinyapps.io/PTMCASOSM/). Conclusion: We established a novel nomogram that can help to distinguish preoperatively cN0 PTMC patients with or without metastasis of multiple lymph nodes. This clinical prediction model may be used in decision making for both active surveillance and surgery.

Short-term effect of 0.01% atropine sulphate eye gel on myopia progression in children.

AIM: To investigate the effect of 0.01% atropine sulphate eye gel on myopia progression and axial elongation in a 6-month treatment in children. METHODS: Totally 185 children aged 6-12y with binocular myopia of 3.0 D or less in both eyes were enrolled in this prospective cohort study. The atropine group (n=125) received one drop of 0.01% atropine sulphate eye gel in each eye before bedtime daily. The control group included 60 matched children without drug intervention during the same period. The spherical equivalent and axial length was recorded at baseline and the sixth month of treatment. The efficacy was evaluated by the change of the spherical equivalent and axial length. Adverse events were also recorded. RESULTS: The average spherical equivalent and axial length at baseline were not statistically significant between the atropine group (-1.64±0.80 D, 24.13±0.76 mm) and the control group (-1.59±0.94 D, 24.06±0.77 mm, P>0.05). After 6mo, there was significantly difference in the spherical equivalent progression between the atropine and the control group (-0.27±0.33 vs -0.60±0.35 D, P<0.001), with a relative reduction of 55.0% in myopia progression. The increase in axial elongation in the atropine group was significantly less than control group (0.19±0.14 vs 0.26±0.14 mm, P<0.001), with a relative reduction of 26.9% in axial length. The 84.4% and 38.4% of the eyes progressed by less than 0.50 D and remained stable in the atropine group, compared with 51.7% and 4.2% in the control group. No adverse events were observed. CONCLUSION: Atropine sulphate eye gel 0.01% can slow down myopia progression and axial elongation in children with a 6-month treatment.

THE INFLUENCE OF LOW-DOSE OCCUPATIONAL RADIATION EXPOSURE ON PERIPHERAL BLOOD CELLS IN A COHORT OF CHINESE MEDICAL RADIATION WORKERS.

OBJECTIVES: The study aims to assess the change of peripheral blood cell numbers following protracted low-dose radiation exposure among medical radiation workers. METHODS: A cohort of 375 Chinese medical workers were followed for 5 years (2015-19) and recorded the changes in blood cells and cumulative doses. T-test, least significant difference-T test, variance analysis and correlation analysis were utilized in this study. RESULTS: Compared with the control group, the white blood cells, hemoglobin counts and the ratio of eosinophils in the study group showed a downward trend. The differences in blood cells between groups were mainly found in the number of red blood cells. In a short cumulative time, such as 1 or 3 years, a correlation between the cumulative dose and the quantity of blood cells was detected, but not at 5 years. CONCLUSIONS: There is no significant difference in the blood cell counts between different types of work, and the long-term cumulative dose has not been statistically correlated with the number of blood cells. So that the number of peripheral blood cells can no longer be used as a good indicator of radiation damage.

Perspectives on the role of breast cancer susceptibility gene in breast cancer.

PURPOSE: Breast cancer susceptibility gene 1/2 can repair damaged DNA through homologous recombination. Besides, the local immune microenvironment of breast cancer is closely linked to the prognosis of patients. But the relationship of breast cancer susceptibility gene 1/2 expression and local immunosuppressive microenvironment in breast cancer is not clear. The aim of this study was to discuss the correlation between them. METHODS: The fresh primary breast tumors and paired normal tissues of 156 cases of breast cancer patients as well as peripheral blood of 156 cases among them in Tianjin Medical University Cancer Institute and Hospital from January 2014 to October 2018 were collected. The association between breast cancer susceptibility gene 1/2 germline mutation and immune status of microenvironment in situ was analyzed. RESULTS: The results indicated that the germline mutation of breast cancer susceptibility gene 1/2 was inconsistent with the breast cancer susceptibility gene 1/2 protein expression, and the proportion of immune cells in patients with negative expression of breast cancer susceptibility gene 1/2 protein was higher than patients with positive expression of breast cancer susceptibility gene 1/2 protein (p < 0.05). And the expression of programmed cell death protein 1, cytotoxic T-Lymphocyte Antigen 4, programmed death ligand-1 of CD3+ T cells in patients with negative expression of breast cancer susceptibility gene 1/2 protein was higher than patients with positive expression of breast cancer susceptibility gene 1/2 protein (p < 0.05). The breast cancer susceptibility gene 1 protein expression was significantly correlated with family history of breast cancer patients (p = 0.006), local lymph node metastases (p = 0.001), and TNM staging (p ≤ 0.001). The breast cancer susceptibility gene 2 protein expression was significantly related to local lymph node metastases (p ≤ 0.001), III stage rate(p = 0.003) and molecular subtyping (p ≤ 0.001). Besides, the 5 years disease free survival was worse for G1 group and pathological III stage patients than other groups and other TNM stage patients. CONCLUSION: In short, the immune therapy may be a potential therapy method for breast cancer patients with negative expression of breast cancer susceptibility gene 1/2 protein.

Identification of Three Circulating MicroRNAs in Plasma as Clinical Biomarkers for Breast Cancer Detection.

The diagnostic value of microRNAs (miRNAs) for breast cancer (BC) is largely unknown. Here, our research aim was to explore new circulating miRNAs for BC diagnosis. First, we identified 14 common differentially expressed miRNAs in tissues by TCGA_BRCA and GSE97811 datasets and preliminarily validated them in serum by the GSE73002 dataset. Furthermore, we examined three plasma miRNAs in BC patients (n = 108) and healthy subjects (n = 103) by RT−PCR, namely, hsa-miR-100-5p, hsa-miR-191-5p and hsa-miR-342-3p. The levels of these three miRNAs in BC patients were higher than those in healthy controls (p < 0.05). The ROC curve analysis revealed that these three miRNAs had high diagnostic efficacy for BC and early-stage BC. The combination of hsa-miR-100-5p and hsa-miR-191-5p was the optimal combination for the diagnosis of BC and early-stage BC. Additionally, hsa-miR-100-5p was correlated with stage I−II, T1 stage, N0 stage and Luminal A subtype (p < 0.05). Hsa-miR-191-5p and hsa-miR-342-3p were irrelevant to TNM stage, T stage, N stage and molecular subtypes. Meanwhile, the biological function analysis indicated that these three miRNAs are mainly involved in the calcium signaling pathway, MAPK signaling pathway and microRNAs in cancer. In conclusion, these three miRNAs demonstrate a positive effect on detection and discovery in BC.

The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families.

OBJECTIVE: Approximately 5%-10% of breast cancer (BC) patients display familial traits that are genetically inherited among the members of a family. The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families. METHODS: Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families. RESULTS: Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8% (96/116) of the cases. Among these, 80.8% of the mutated genes were related to DNA damage repair. Fourteen possible disease-causing variants were identified in 13 of 27 BC families. Only 25.9% (7/27) of the BC families exhibited hereditary deficiency in BRCA1/2 genes, while 22.2% of the BC families exhibited defects in non-BRCA genes. In all, 41.7% (40/96) of the mutation carriers had BRCA mutations, 88.5% (85/96) had non-BRCA mutations, and 30.2% (29/96) had both BRCA and non-BRCA mutations. The BC patients with BRCA mutations had a higher risk of axillary lymph node metastases than those without mutations (P < 0.05). However, the BC patients with non-BRCA mutations frequently had a higher occurrence of benign breast diseases than those without mutations (P < 0.05). CONCLUSIONS: In addition to BRCA1/2, genetic variants in non-BRCA DNA repair genes might play significant roles in the development of familial/hereditary BC. Therefore, profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.

[International standard ISO 22236 Traditional Chinese medicine-Thread-embedding acupuncture needle for single use: experience and recommendation].

The ISO 22236 Traditional Chinese medicine-Thread-embedding acupuncture needle for single use, as the first international standard (IS) in acupoint thread-embedding field, has been officially published by International Organization for Standardization (ISO) in 2020. The background of its development, difficulties and countermeasures in the process of development were reviewed, and the experience of standard development was summarized, aiming to provide methods and references for future IS development of acupuncture and moxibustion instruments. It is suggested that strengthening the discourse power in the process of IS development, increasing the compound talents cultivation for IS, valuing the importance of enterprises in the development of IS, and creating an advantageous environment for the development of IS are the keys to improve the level of standardization of acupuncture and moxibustion instruments and play a more important role in the IS development.

High Risk Thyroid Nodule Discrimination and Management by Modified TI-RADS.

OBJECTIVE: Thyroid cancer is the most common primary malignant disorder of the thyroid. We aimed to illustrate the modified TI-RADS report system for differentiating malignant thyroid nodules from benign ones, and especially its role in the management of high risk nodules. METHODS: In this retrospective study, 5,162 healthy individuals who underwent thyroid ultrasound according to modified TI-RADS from January 2014 to December 2014 were enrolled and followed up during the whole 5 years, and the medical data were investigated and reviewed. RESULTS: The total detection rate of thyroid nodules was 39.40%. The total detection rate of thyroid cancer was 0.66%. Most thyroid cancers were single-shot, located at unilateral, at early clinical stages, without lymph node metastases, and with low recurrence risk. All patients had thyroid papillary carcinoma, except one thyroid medullary carcinoma. Based on modified TI-RADS classification, at the end of 5 years follow-up, more changes of thyroid nodules grade status were observed in grades 4a and above. The higher the grade status, the more malignant advances were occurred. The modified TI-RADS report system played an instructional role in adding medical treatment choice and decision for clinicians. CONCLUSION: The modified TI-RADS report system plays an important role in thyroid benign and malignant nodule identification and management.

Drug resistance gene expression and chemotherapy sensitivity detection in Chinese women with different molecular subtypes of breast cancer.

Objective: The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women, by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers. Methods: The expression of drug resistance genes including Topo II, GST-π, P-gp, LRP, and CD133 were detected with immunohistochemistry in a tissue microarray. Drug sensitivity tests included those for paclitaxel, epirubicin, carboplatin, vinorelbine, and fluorouracil and were conducted on primary cancer tissue cells and cell lines, including the T47D, BT-474, and MDA-MB-231 cells and human breast cancer xenografts in nude mice. Results: The different drug resistant genes Topo II, GST-π, P-gp, and LRP were differentially expressed among different molecular subtypes of breast cancers (P < 0.05). Positive expression of CD133 was highest in basal-like breast cancer (P < 0.05). Kaplan-Meier survival analysis showed that positive expressions of Topo II and CD133 both correlated with shorter disease-free survival (DFS) (P < 0.05) and overall survival (P < 0.05), and positive expression of LRP correlated only with shorter DFS (P < 0.05). BT-474 showed chemosensitivity to paclitaxel and epirubicin, while MDA-MB-231 showed chemosensitivities to paclitaxel, epirubicin, carboplatin, and fluorouracil (T/C ≤ 50%). The basal-like and HER2+ breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells (P < 0.05). Conclusions: The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.

A Urinary Metabolomics Analysis Based on UPLC-MS and Effects of Moxibustion in APP/PS1 Mice.

OBJECTIVE: Alzheimer's disease (AD) is a common neurodegenerative disorder with the symptoms of cognitive impairment and decreased learning and memory abilities. Metabolomics can reflect the related functional status and physiological and pathological changes in the process of AD. Moxibustion is a unique method in traditional Chinese medicine, which has been used in the treatment and prevention of diseases for thousands of years. METHODS: A total of 32 APP/PS1 mice were randomly divided into the model group, moxibustion group, moxa smoke group and smoke-free moxibustion group (n=8/group), using the random number table method, while eight C57BL/6 mice were used as the control group. The five groups were measured for 20 min/day, 6 days/week, for 4 weeks. After 4 weeks' experiment, all the mice were placed in metabolic cages to collect urine continuously for 24 hours, for UPLC-MS analysis. RESULTS: Principal component analysis (PCA) was used to identify the different metabolites among the five groups, and partial least squares discriminant analysis (PLS-DA) was performed to reveal the effects on the metabolic variance. Sixteen potential biomarkers were identified among the five groups, primarily related to amino acid metabolism, starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, and aminoacyl biosynthesis. There were 17 differences in the potential metabolites between the control and model groups, involving the metabolism of amino acid, purine, pyrimidine, nicotinic acid and nicotinamide, and biosynthesis of pantothenate and coenzyme A. Fifteen potential biomarkers were identified between the model and moxibustion groups, related to starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, glyoxylate, dicarboxylate anions and some amino acid metabolism. CONCLUSION: Moxibustion can regulate the metabolism of substance and energy by improving the synthesis and decomposition of carbohydrates and amino acids in APP/PS1 transgenic AD model mice.

Active surveillance as a management strategy for papillary thyroid microcarcinoma.

Active surveillance (AS) can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma (PTMC), with the absence of clinically apparent lymph nodes, extrathyroidal extensions, and distant metastasis. After reviewing the reports on AS of low risk PTMCs worldwide, we introduced AS, and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up schedules. Moreover, the requirement of cytological diagnosis, progression evaluation methods, necessity of thyrotropin suppression, and medical costs were issues that both clinicians and patients considered. The usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient risk. Clinicians may adopt measures like dynamic monitoring, risk stratification, and making personal follow-up schedules to minimize these potential risks. By appropriately selecting PTMC patients, AS can be an effective alternative treatment to immediate surgery.

High Expression of Nuclear Transcription Factor-κB is Associated with Cisplatin Resistance and Prognosis for Ovarian Cancer.

BACKGROUND: Abnormal activation of the nuclear transcription factor-κB (NF-κB) signaling pathway plays a crucial role in the chemoresistance of tumor cells. This study aimed to explore the significance of NF-κB in the chemoresistance of ovarian cancer. MATERIALS: We performed immunohistochemical staining for evaluating the expression of NF-κB in cancer tissues. The MTT assay was performed for analyzing cell proliferation, Western blotting was performed to quantify NF-κB p65, and flow cytometry was used to determine the apoptosis rate. RESULTS: Nuclear NF-κB p65 over-expression was closely associated with ovarian cancer with advanced FIGO stage, residual disease ≥1 cm, low histologic grade, platinum resistance and refractory, chemotherapy resistance (P< 0.05). FIGO stage I-II and residual disease <1 cm were associated with complete response (CR) to chemotherapy, while FIGO stage I-II, residual disease <1cm and absence of lymph node (LN) metastasis were associated with platinum sensitivity. In multivariate logistic regression, residual disease ≥1 cm was a risk factor for response to chemotherapy, while the over-expression of nuclear NF-κB p65 was a risk factor for sensitivity to chemotherapy. In the ROC curves, nuclear NF-κB p65 expression had the discriminative ability for sensitivity to chemotherapy (AUC = 0.637, P = 0.021). Furthermore, nuclear NF-κB p65 expression was an independent prognostic factor. Western blotting showed that NF-κB p65 level in cisplatin-resistant cells (C13* and A2780cp) was significantly higher than that in cisplatin-sensitive cells (OV2008 and A2780s) (P < 0.05), and this increased expression could be suppressed by NF-κB inhibitor-PDTC treatment. The proliferation inhibitory rates of cisplatin in C13* and A2780cp cells increased after PDTC treatment in a concentration-dependent manner. PDTC treatment could also enhance cisplatin-induced apoptosis. CONCLUSION: NF-κB was associated with the clinicopathological features, chemoresistance, and prognosis of ovarian cancer. The NF-κB inhibitor PDTC can enhance cisplatin sensitivity of platinum-resistant C13* and A2780cp ovarian cancer cells.

ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer.

The aim of the present study was to analyze the expression levels of angiopoietin-like 4 (ANGPTL4) in breast cancer to investigate the association between ANGPTL4 and breast cancer. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues, including 205 invasive ductal carcinoma (IDC) of no special type, 40 normal breast, 40 atypical ductal hyperplasia (ADH) and 40 ductal carcinomas in situ (DCIS) tissues. The non-parametric Kruskal-Wallis test was used to evaluate the differential expression of ANGPTL4 and clinicopathological parameters in breast cancer. Kaplan-Meier analysis and Cox regression analysis were used to evaluate the association between the expression levels of ANGPTL4 and the prognosis of breast cancer. The results revealed that ANGPTL4 expression was higher in IDC (63.4%; 130/205) compared with in normal breast tissues (17.5%; 7/40), ADH (30%; 12/40) and DCIS (37.5%; 15/40). The clinical significance of ANGPTL4 expression was analyzed in a total of 205 IDC tissues, and high expression levels of ANGPTL4 were positively associated with pathological stage (P<0.001), tumor size (P<0.001), histological grade (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P<0.001) and local recurrence (P<0.001). Kaplan-Meier analysis revealed that patients with high ANGPTL4 expression had a shorter overall survival (OS; P<0.001) and disease-free survival (DFS; P<0.001) compared with patients with low ANGPTL4 expression. Multivariate Cox regression analysis revealed that ANGPTL4 was an independent prognostic factor for breast cancer OS (P=0.034) and DFS (P=0.011). The results of the present study demonstrated that ANGPLT4 was associated with malignant progression and poor prognosis of breast cancer, suggesting that ANGPLT4 may be a novel therapeutic target for breast cancer.