Real-world status, efficacy and prognosis analysis of first-line treatment for unresectable hepatocellular carcinoma in patients treated at multiple centres.

OBJECTIVE: To present the real-world status and explore the predictors of the efficacy and prognosis of first-line treatment for unresectable hepatocellular carcinoma (uHCC). METHODS: Real-world data of uHCC patients who underwent first-line treatment at 4 hospitals in Northern Anhui, China, from July 2019 to December 2022 were retrospectively collected. The clinicopathological features, haematological indicators, including superoxide dismutase (SOD) and vascular endothelial growth factor-A (VEGF-A), efficacy and safety data were analysed. RESULTS: A total of 153 patients were enrolled and most of them treated with targeted therapy combined with immunotherapy (TI). Compared to patients treated with TI, patients who were administrated with TI plus locoregional therapy (TIL) showed longer median progression-free survival (mPFS) and median overall survival (mOS) times (both p < 0.05), with manageable safety profiles. Moreover, compared to patients with low baseline serum levels of SOD, patients with high baseline serum SOD levels had a better treatment efficacy and had longer mPFS and mOS times (all p < 0.05). Subgroup analyses indicated that patients with low SOD levels had longer mPFS times when receiving TIL than when receiving TI (p = 0.005), but, among patients with high SOD levels, their prognoses were not substantially different between TIL and TI (p > 0.05). Additionally, patients in the low-VEGF-A group had a longer mOS time than patients in the high-VEGF-A group (p = 0.004). In comparison with TI, TIL can improve the survival time among patients with high VEGF-A levels but not among patients with low VEGF-A levels. CONCLUSIONS: TI was the most commonly first-line systemic therapy for uHCC patients, with better efficacy and outcomes when combined with locoregional therapy in a certain population. Baseline serum SOD and VEGF-A were found to be potential predictive biomarkers for decision-making, treatment response, and outcome in patients with uHCC in the primary care setting.

TI was the most commonly used first-line systemic therapy regimen for uHCC patients in Northern Anhui, China.TIL might conferred better therapeutic efficacy and outcome than TI in specific uHCC populations.The baseline serum SOD level was found to be positively correlated with first-line treatment efficacy and patients' prognosis in uHCC, and low-SOD patients with a dismal prognosis was identified to have potential to benefit from TIL.High baseline serum VEGF-A levels were associated with poor efficacy and short OS times in uHCC patients. For patients with a high baseline VEGF-A, TIL is recommended as the first-line treatment.

Proteomic Analysis of the Supernatant from Bone Marrow Mesenchymal Stem Cells under High Glucose Conditions.

Diabetes mellitus hinders the process of bone regeneration by inhibiting the function of mesenchymal stem cells (MSCs) through elevated glucose levels, thereby impeding osteointegration. The stem cell niche (SCN) plays a crucial role in determining the fate of stem cells by integrating various signals. However, the precise mechanism by which high glucose levels affect the SCN and subsequently influence the function of MSCs remains unclear. In this study, we employed proteomic analysis to identify proteins with altered expression in the extracellular matrix (ECM), aiming to elucidate the underlying mechanism. Three cell supernatants were collected from bone marrow mesenchymal stem cells (BMSCs) or BMSCs stimulated with high glucose (BMSCs+Hg). A total of 590 differentially expressed proteins were identified, which were found to be associated with the ECM, including aging, autophagy, and osteogenic differentiation. The findings of our study indicate that elevated glucose levels exert an influence on the molecular aspects of the SCN, potentially contributing to a better comprehension of the underlying mechanism.

Development and validation of novel immune-inflammation-based clinical predictive nomograms in HER2-negative advanced gastric cancer.

Purpose: To explore the predictive value of multiple immune-inflammatory biomarkers including serum VEGFA and systemic immune-inflammation index (SII) in HER2-negative advanced gastric cancer (AGC) and establish nomograms for predicting the first-line chemotherapeutic efficacy, progression-free survival (PFS) and overall survival (OS) of patients with this fatal disease. Methods: From November 2017 to April 2022, 102 and 34 patients with a diagnosis of HER2-negative AGC at the First Affiliated Hospital of Bengbu Medical College were enrolled as development and validation cohorts, respectively. Univariate and multivariate analyses were performed to evaluate the clinical value of the candidate indicators. The variables were screened using LASSO regression analysis. Predictive models were developed using significant predictors and are displayed as nomograms. Results: Baseline VEGFA expression was significantly higher in HER2-negative AGC patients than in nonneoplastic patients and was associated with malignant serous effusion and therapeutic efficacy (all p<0.001). Multivariate analysis indicated that VEGFA was an independent predictor for first-line therapeutic efficacy and PFS (both p<0.01) and SII was an independent predictor for first-line PFS and OS (both p<0.05) in HER2-negative AGC patients. The therapeutic efficacy model had an R2 of 0.37, a Brier score of 0.15, and a Harrell's C-index of 0.82 in the development cohort and 0.90 in the validation cohort. The decision curve analysis indicated that the model added more net benefits than VEGFA assessment alone. The PFS/OS models had Harrell's C-indexes of 0.71/0.69 in the development cohort and 0.71/0.62 in the validation cohort. Conclusion: The established nomograms integrating serum VEGFA/SII and commonly available baseline characteristics provided satisfactory performance in predicting the therapeutic efficacy and prognosis of HER2-negative AGC patients.

A Comparative Study of Seminars Combined with Case-Based Learning versus Lecture-Based Learning for Cancer Pain Teaching in Medical Oncology Internship.

PURPOSE: To determine whether the teaching method of seminars combined with case-based learning (CBL) is superior to the traditional lecture-based learning (LBL) for teaching cancer pain in medical oncology internship. METHODS: Sixty medical and nursing interns in the medical oncology department of our hospital were selected between January 2019 and December 2020. Thirty students received traditional LBL instruction as the control group, and 30 students received combined seminars and CBL instruction as the observation group. The teaching evaluation and assessment was performed by theoretical and practical examinations and questionnaires. RESULTS: In the after-class examination, case analysis, clinical practice and overall scores of the observation group were higher than those of the control group (all p < 0.001). Theoretical knowledge scores did not differ significantly between the two groups (p = 0.470). In the questionnaire regarding attitudes towards opioid use, the observation group had better perceptions of using opioids than the control group (all p < 0.01). In the meantime, students in the observation group outperformed the control group in four aspects: self-learning (p < 0.001), analytical and problem-solving (p < 0.001), clinical thinking (p = 0.001), and clinical practice (p = 0.002) abilities all improved, while stimulating learning interest (p = 0.184) and enhancing theoretical knowledge mastery (p = 0.221) were not significantly different from those of the control group. Overall, students in the observation group were more satisfied with the teaching, teaching methods and teacher performances than the control group (all p < 0.001). CONCLUSION: Compared to the LBL, the combination of seminars and CBL is a more effective teaching method for cancer pain management, which is worth further study.

miR­337­3p inhibits gastric tumor metastasis by targeting ARHGAP10.

Several microRNAs (miRNAs) are known as regulatory molecules involved in gastric tumor metastasis. The expression of miR­337­3p was revealed to be downregulated in metastatic gastric tumor cells. Overexpression of miR­337­3p in gastric cancer cells resulted in the reduction of their invasive abilities. To characterize the functions of miR­337­3p, miR­337­3p was expressed in a metastatic lymph node­derived gastric tumor cell line, SGC­7901. Overexpression of miR­337­3p reduced the viability of cells but had no effects on the cell cycle. Wound healing and Transwell migration assays revealed that miR­337­3p inhibited the migration capacity of cells. miR­337­3p was capable of binding to the 3'­untranslated region of a cytoskeleton­associated molecule, ARHGAP10. Overexpression of miR­337­3p reduced the mRNA and protein levels of ARHGAP10 and the co­expression of ARHGAP10 and miR­337­3p resulted in the recovery of cell migration capacity. Furthermore, the injection of miR­337­3p­overexpressing SGC­7901 cells into an immunodeficient mouse model resulted in a decrease in tumor metastasis in the liver and lungs. The present results indicated that miR­337­3p regulates gastric tumor metastasis by targeting the cytoskeleton­associated protein ARHGAP10.

Factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy.

BACKGROUND: The aim of this study was to evaluate the clinical factors relevant to the prognosis of patients with esophageal cancer who received intensity-modulated radiotherapy (IMRT). METHODS: The data of 60 patients admitted to our hospital from January 2014 to December 2015 with pathologically confirmed esophageal cancer were retrospectively reviewed. All patients received IMRT. Patients were divided into groups according to two-year survival: those who survived > 2 years after treatment, and those who died within 2 years of treatment. The potential clinical factors relevant to prognosis were evaluated by logistic regression analysis. RESULTS: Single factor analysis showed that lesion length (P < 0.05), tumor diameter (P < 0.05), T stage (P < 0.05), N stage (P < 0.05), and combined chemotherapy (P < 0.05) were associated with the prognosis of esophageal cancer patients who received IMRT. Logistic regression analysis demonstrated that T stage (odds ratio = 3.62; P < 0.05) and N stage (odds ratio = 2.98; P < 0.05) were independent factors relevant to prognosis. CONCLUSION: T stage and N stage influence the long-term curative effects of IMRT for esophageal cancer. The higher the stage, the lower the two-year survival rate.

Efficacy and Safety of Vinorelbine Plus Cisplatin vs. Gemcitabine Plus Cisplatin for Treatment of Metastatic Triple-Negative Breast Cancer After Failure with Anthracyclines and Taxanes.

BACKGROUND This study aimed to compare the efficacy and safety of vinorelbine plus cisplatin (NP regimen) vs. gemcitabine plus cisplatin (GP regimen) for treatment of metastatic TNBC after failure with anthracyclines and taxanes. MATERIAL AND METHODS A total of 48 patients with metastatic TNBC that failed in anthracyclines and taxanes treatment were enrolled and randomly grouped. Patients in the NP group (n=22) were given 25 mg/m² vinorelbine on days 1 and 8 and 25 mg/m² cisplatin on days 2-4 of each 21-day cycle, while subjects in the GP group (n=26) were administered 1000 mg/m² gemcitabine on days 1 and 8 and 25 mg/m² cisplatin on days 2-4 of each 21-day cycle. The treatment response and adverse events were compared between the 2 groups every 2 cycles. RESULTS The ORR, DCR, and median TTP were 45.5%, 77.3%, and 5 months in the NP group, and 46.2%, 80.8%, and 5.2 months in the GP group, and no significant differences were observed in ORR, DCR, and median TTP between the 2 groups (P>0.05). The major adverse events included grade I-II bone marrow inhibition, gastrointestinal reactions, and phlebitis, and a lower incidence of thrombocytopenia and rash and a higher incidence of phlebitis was found in the NP group than in the GP group (P<0.05). CONCLUSIONS Either NP or GP regimen is active and tolerated in treatment of metastatic TNBC with anthracyclines and/or taxanes resistance, which may be used as a salvage treatment for metastatic TNBC.

TCF21 genetic polymorphisms and breast cancer risk in Chinese women.

Transcription factor 21 (TCF21) functions as a tumor suppressor and is inactivated in several types of cancer. The purpose of this study is to investigate whether TCF21 genetic polymorphisms(rs2327429 T>C, rs2327430 T>C, rs2327433 A>G, rs12190287 C>G, rs7766238 G>A, rs4896011 T>A) are associated with the risk of breast cancer in Chinese women. Logistic regression analyses showed that TCF21 rs12190287 polymorphism was significantly associated with the reduced risk of breast cancer. Stratified analyses based on pathological type indicated that TCF21 rs12190287 polymorphism was only associated with the reduced risk of infiltrative ductal carcinoma. Real-time quantitative PCR analyses revealed that compared with those carrying rs12190287 CC genotype, subjects with GG genotype had higher expression levels of TCF21 mRNA in normal breast tissues. Furthermore, luciferase activity assay showed that the rs12190287 G allele weakened the binding affinity of hsa-miR-224 to TCF21 3' UTR. These findings suggest that TCF21 rs12190287 polymorphism can regulate TCF21 expression and may serve as a potential marker for genetic susceptibility to breast cancer.

Complete mitochondrial genome sequence and mutations of the Glioma model inbred C57BL/6 mice strain.

In the present work we undertook the complete mitochondrial genome sequencing of an important glioma model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.

Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis.

Kallistatin, which protects organs and cells against inflammation, fibrosis and oxidative stress, is mainly synthesized and secreted in liver. However, its relationship to human liver disease remains unclear. The purpose of this study was to explore the relationship between serum kallistatin and clinical evidence of both cirrhosis and hepatocellular carcinoma (HCC), and to determine if serum kallistatin levels could be used as a diagnostic indicator of hepatic health status, especially human liver cirrhosis (LC). Our cohort consisted of 115 patients with clinically proven liver fibrosis (LF), LC, or HCC by liver biopsies, and 31 healthy controls (CON). Serum kallistatin levels were quantified by ELISA. Results of the present study demonstrated that irrespective of the underlying etiology, serum kallistatin levels were significantly lower in the LF/LC group when compared with the CON group. A decrease in serum kallistatin levels appeared to reflect the extent of cirrhosis, with the lowest levels associated with higher grades of cirrhosis. Patients with LC had a noticeable correlation between serum kallistatin levels and other serum biochemical indicators. The area under the curve (AUC) for LC, viral liver cirrhosis (VLC) and alcoholic liver cirrhosis (ALC) was 0.845, 0.757 and 0.931, respectively. In conclusion, our findings demonstrated that kallistatin, a plasma protein produced by the liver, can be a useful and reliable diagnostic indicator of hepatic health status, especially for LC.

Pri-miR-124 rs531564 polymorphism and colorectal cancer risk.

MiR-124 functions as a tumor suppressor and plays an important role in tumorigenesis. A common polymorphism (rs531564, C>G) in the pri-miR-124 has been recently studied in connection with cancer risk. The aim of the present study was to investigate the association between pri-miR-124 rs531564 polymorphism and the risk and clinicopathological characteristics of colorectal cancer (CRC). Two case-control studies involving 900 CRC patients and 1110 cancer-free controls showed that pri-miR-124 rs531564 polymorphism was significantly associated with the decreased risk of CRC in Xuzhou population [GG vs. CC: OR = 0.25, 95%CI = 0.09-0.67, P = 0.003; (CG+GG) vs. CC: OR = 0.73, 95%CI = 0.56-0.94, P = 0.01; GG vs. (CC+CG): OR = 0.27, 95%CI = 0.10-0.70, P = 0.004; G vs. C: OR = 0.70, 95%CI = 0.56-0.89, P = 0.003], Bengbu population [GG vs. CC: OR = 0.20, 95%CI = 0.04-0.90, P = 0.02; GG vs. (CC+CG): OR = 0.21, 95%CI = 0.05-0.95, P = 0.03; G vs. C: OR = 0.72, 95%CI = 0.54-0.98, P = 0.03] and pooled population [GG vs. CC: OR = 0.26, 95%CI = 0.11-0.59, P<0.001; (CG+GG) vs. CC: OR = 0.76, 95%CI = 0.62-0.93, P = 0.008; GG vs. (CC+CG): OR = 0.27, 95%CI = 0.12-0.62, P < 0.001; G vs. C: OR = 0.71, 95%CI = 0.59-0.85, P<0.001]. Additionally, pri-miR-124 rs531564 polymorphism was significantly associated with the decreased risk of poor differentiation and lymph node metastasis of CRC. Our results suggest that pri-miR-124 rs531564 polymorphism may be a genetic modifier for developing CRC. However, further studies are needed to validate our findings.

MicroRNA-498 is downregulated in non-small cell lung cancer and correlates with tumor progression.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancer, with highly aggressive, lethal malignancy and microRNAs have already been proven to be associated with NSCLC tumorigenesis. In this study, we sought to determine the expression, the clinical value and its role in NSCLC tumor progression. METHODS: Clinical NSCLC tissues and common cell lines were collected. Real-time PCR was performed to quantify the miR-498 expression. In addition, the association of miR-498 expression with clinical pathological factors and prognosis was statistically analyzed. Furthermore, cell proliferation was measured after miR-498 was overexpressed transiently in cells. RESULTS: We found that miR-498 was significantly decreased in NSCLC tumors as well as cell lines, when compared with their separated controls. Decreased miR-498 expression was associated with sex, tumor type and tumor size. Functionally, ectopic expression of miR-498 in A549 and H661 cells inhibited cell proliferation. CONCLUSION: Our data indicated that miR-498 is downregulated and correlated with tumor progression, which might be a putitive therapeutic target in NSCLC treatment.

eNOS Genetic Polymorphisms and Cancer Risk: A Meta-Analysis and a Case-Control Study of Breast Cancer.

The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case-control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility.Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case-control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV.In conclusion, our meta-analysis and case-control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer.

Clinicopathological significance and biological role of TCF21 mRNA in breast cancer.

TCF21 is known to function as a tumor suppressor and deregulated in several types of cancers; however, its role in breast cancer remains poorly understood. The aim of this study was to examine the expression of TCF21 messenger RNA (mRNA) in breast cancer and evaluate its clinical significance and biological role in tumor progression. TCF21 mRNA expression was analyzed in breast cancer cell lines and tissues by qRT-PCR. Overexpression approach was used to investigate the biological functions of TCF21 mRNA in breast cancer cell line (MDA-MB-231). A notably lower level of TCF21 mRNA expression was found in breast cancer cell lines and tissues. Furthermore, the low expression of TCF21 mRNA was associated with large tumor size and positive lymph node metastasis. Functional analysis showed that overexpression of TCF21 mRNA inhibited cell proliferation and epithelial-mesenchymal transition (EMT) of MDA-MB-231. In conclusion, our data provided the first evidence that TCF21 mRNA is significantly downregulated in breast cancer cell lines and tissues and regulates breast cancer cell proliferation and EMT. Thus, TCF21 may act as a potential therapeutic target for breast cancer intervention.

Scalable downstream strategies for purification of recombinant adeno- associated virus vectors in light of the properties.

Recombinant adeno-associated virus (rAAV) vector is one of the promising delivery tools for gene therapy. Currently, hundreds of clinical trials are performed but the major barrier for clinical application is the absence of any ideal large scale production technique to obtain sufficient and highly pure rAAV vector. The large scale production technique includes upstream and downstream processing. The upstream processing is a vector package step and the downstream processing is a vector purification step. For large scale downstream processing, the scientists need to recover rAAV from dozens of liters of cell lysate or medium, and a variety of purification strategies have been developed but not comprehensively compared till now. Consequently, this review will evaluate the scalable downstream purification strategies systematically, especially those based on the physicochemical properties of AAV virus, and attempt to find better scalable downstream strategies for rAAV vectors.

Calcium-ion-modulated ceramic hydroxyapatite resin for the scalable purification of recombinant Adeno-Associated Virus serotype 9.

Column chromatography has been widely used as a scalable purification strategy for recombinant adeno-associated virus (rAAV) vectors. The rAAV1, 2, 4, 5, 6, 8 and 9 serotypes could be separated using affinity resins, ion exchange resins or other types of resins. Apatite resin has displayed outstanding performance in protein purification in the past 10 years, and ceramic hydroxyapatite (CHT) chromatography resin with a polyethylene glycol (PEG) modulation has recently been used for rAAV1 and rAAV9 vectors. This study reports the use of CHT chromatography modulated by calcium ions instead of PEG for rAAV9 purification. Calcium-ion-containing buffers effectively improve the inclusion of CHT as a capture resin, the resin-binding capacity and the yield. The optimum calcium ion concentration is 30ppm, and the optimum pH is 7.0. A frontal analysis indicated that the binding capacity of CHT at 2ml/min reaches 65.1mg total protein per ml of resin. A previously developed purification strategy consists of CHT followed by ANX anion exchange chromatography. The vector yield of this approach is approximately 70%, and a software analysis indicated a vector purity exceeding 98%. The residual host cell (HEK293) protein contents are 24.75±2.32ng and 67.21±2.10ng, and the Benzonase residue contents are 1.55±0.10pg and 1.95±0.16ng per 10(13) vector genome copies (G.C.) separated by CHT/ANX and CsCl. In addition, CHT/ANX yields 798.44±50.10pg of plasmid DNA and 2.17±0.11ng of HEK293 DNA, while CsCl purification yields 840.27±76.14pg of plasmid DNA and 2.43±0.19 of HEK293 DNA. The two methods produce vectors with similar in vitro and in vivo potencies. The results indicated that the CHT/ANX method is suitable for the scalable purification of the rAAV9 vector.

Specific Recognition of Breast Cancer Cells In Vitro Using Near Infrared-Emitting Long-Persistence Luminescent Zn3Ga2Ge2O10:Cr3+ Nanoprobes.

In this paper, near-infrared emitting long-persistence luminescent Zn3Ga2Ge2O10:Cr3+ (ZGG) nanoparticles with diameters of 30-100 nm and bright luminescence were prepared by a sol-gel synthesis method. After the surface amination, the nanoparticles were further bioconjugated with breast cancer-specific monoclonal antibody (anti-EpCAM) to form ZGG-EpCAM nanoprobes which can specifically target breast cancer cell lines (MCF7) in vitro. The results of in vitro images show that the luminescence signals from the cells treated with ZGG-EpCAM nanoprobes are stronger than those from cells treated with ZGG-unconjugated antibody, indicating that the prepared ZGG-EpCAM nanoprobes possessed excellent specific recognition capability. Furthermore, due to their long afterglow properties, the imaging could persist more than 1 h. Therefore, these nanoprobes could not only provide a high specificity detection method for cancer cells but also realize the long-time monitoring. Developed near-infrared emitting long-persistence luminescent nanoprobes will be expected to find new perspectives for cell therapy research and diagnosis applications.

[Identification of metabolites of antitumor lead compound T-OA in rat urine by HPLC-HRMS].

OBJECTIVE: To study the major metabolites of antitumor lead compound T-OA (oleanolic acyl-3, 5, 6-trimethyl pyrazine-2-methyl ester) in rat urine, in order to preliminarily infer its metabolic mode in rats. METHOD: Rat urines of the blank group, the raw material group (ligustrazine TMP and oleanolic acid OA Moore equivalent) and the T-OA group were collected and freeze-dried; Solids were extracted by ethyl acetate; And then the extracts were re-dissolved with acetonitrile. HPLC-HRMS coupling technique was adopted to find the potential mass spectrum peak under ESI(+) (see symbol) ESI(-) modes. Metabolite-related information was obtained by comparing the three groups of spectra. RESULT: One metabolite of OA and two metabolites of TMP were identified in the raw material group; none metabolite of T-OA but one phase II metabolite was detected in the T-OA group. CONCLUSION: It is the first time to identify one phase II metabolite of T-OA and one phase II metabolite of OA were identified in rat urine. On that basis, the researchers preliminarily inferred that T-OA does not show the efficacy in the form of raw material. The HPLC-HRMS method established could be used to identify metabolites of related derivative structures. This paper could also provide certain reference for designing pro-drugs based on oleanolic acid.

IL-27 -964A>G polymorphism and the risk of breast cancer: a case-control study.

Interleukin-27 (IL-27) is a new member of the IL-12 family which plays a key role in antitumor immunity. The aim of the present study was to investigate the association between a potentially functional polymorphism (rs153109, -964A>G) at the promoter of IL-27 and the risk of breast cancer in a Chinese population. We determined the genotypes of 326 breast cancer cases and 460 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression was used to analyze the association between -964A>G polymorphism and breast cancer susceptibility. There was no significant association between IL-27 -964A>G polymorphism and the risk of breast cancer. However, in the stratified analysis by menopausal history, IL-27 -964A>G polymorphism was associated with a decreased risk of breast cancer in premenopausal women (GG vs. AA: OR = 0.48, 95 % CI = 0.26-0.89; G vs. A: OR = 0.75, 95 % CI = 0.59-0.97). Taken together, our study suggested that IL-27 -964A>G polymorphism may be a protective factor for breast cancer in premenopausal women.

Expression of ALDH1 and TGFß2 in benign and malignant breast tumors and their prognostic implications.

The specific mechanism underlying the role of putative stem cell marker aldehyde dehydrogenase 1 (ALDH1) playing in development and progression of breast cancer is currently unclear. Transforming growth factor ß (TGFß) signaling pathway is reported to be activated in most cancers. Thus a study was initiated to explore possible differences and correlation of ALDH1 and TGFß2 expression in the most common malignant and benign tumors of the breast in Chinese women. Samples of 75 breast cancer tissues, 30 paracancerous normal tissues, and 39 fibroadenoma breast tissues were investigated for the expression of ALDH1 and TGFß2 using immunohistochemistry. The positive rates of ALDH1 and TGFß2 protein were 62.67% and 66.67%, respectively, in breast cancer tissues, which were significantly higher than that in normal fibroadenoma breast (P<0.05) and paracancerous tissues (P<0.01). ALDH1 and TGFß2 status were significantly associated with tumor histological grade and receptor status (P<0.05). Expression of ALDH1 was found to be positively correlative to TGFß2 in breast cancer (r = 0.33, P<0.01). Expression of both proteins remained significantly associated with reduced overall survival (OS) by univariate analysis (P<0.05). Multivariate Cox regression analysis showed that ALDH1 expression, tumor stage, and lymph node status are independent prognostic factors in invasive breast cancer patients. Thus ALDH1 and TGFß2 play important roles in the development of breast cancer. The ALDH1 phenotype is an independent predictor of poor prognosis, and TGFß2 signaling pathway activation might be involved in the pathological regulation of ALDH1 in breast cancer.