[Expression and clinical significance of MTDH and VEGF in triple-negative breast cancer].

OBJECTIVE: To study the expression and clinical significance of MTDH and VEGF in triple-negative breast cancer (TNBC). METHODS: Tissue samples of 168 breast cancers (including 112 TNBC tissue and 56 non-TNBC tissue), 10 breast fibroadenomas and 15 normal breast tissues were collected. Postoperative specimens were examined by immunohistochemistry for MTDH and VEGF expression. The correlation between the expression of MTDH and VEGF and clinicopathological features was analyzed. RESULTS: MTDH and VEGF were expressed in 57.1% and 49.4% of breast cancer patients, 64.3% and 56.3% in TNBC patients, respectively, significantly higher than that in the non-TNBC tissues, breast fibroadenomas and normal breast tissues (P<0.05 for all). Statistically significant correlation was found between the MTDH and VEGF expressions (r=0.356, P<0.001). Moreover, MTDH expression was correlated with tumor size, BMI index, lymph node metastasis, pathological stage, recurrence and metastasis, and the expression of p53 and Ki-67 proteins (P<0.05 for all). The VEGF protein expression was correlated with lymph node metastasis, pathological staging, recurrence and metastasis, and the expression of Ki-67 protein (P<0.05 for all). The patients with high expression of MTDH and VEGF showed a lower DFS and OS (P<0.05 for both). CONCLUSIONS: MTDH and VEGF expression may be correlated with tumor angiogenesis and progression and has the potential to be valuable prognostic factors in patients with TNBC.

MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway.

BACKGROUND: Trastuzumab resistance is almost inevitable in the management of human epidermal growth factor receptor (HER) 2 positive breast cancer, in which phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss is implicated. Since metadherin (MTDH) promotes malignant phenotype of breast cancer, we sought to define whether MTDH promotes trastuzumab resistance by decreasing PTEN expression through an NFκB-dependent pathway. METHODS: The correlations between MTDH and PTEN expressions were analyzed both in HER2 positive breast cancer tissues and trastuzumab resistant SK-BR-3 (SK-BR-3/R) cells. Gene manipulations of MTDH and PTEN levels by knockdown or overexpression were utilized to elucidate molecular mechanisms of MTDH and PTEN implication in trastuzumab resistance. For in vivo studies, SK-BR-3 and SK-BR-3/R cells and modified derivatives were inoculated into nude mice alone or under trastuzumab exposure. Tumor volumes, histological examinations as well as Ki67 and PTEN expressions were revealed. RESULTS: Elevated MTDH expression indicated poor clinical benefit, shortened progression free survival time, and was negatively correlated with PTEN level both in HER2 positive breast cancer patients and SK-BR-3/R cells. MTDH knockdown restored PTEN expression and trastuzumab sensitivity in SK-BR-3/R cells, while MTDH overexpression prevented SK-BR-3 cell death under trastuzumab exposure, probably through IκBα inhibition and nuclear translocation of p65 which subsequently decreased PTEN expression. Synergized effect of PTEN regulation were observed upon MTDH and p65 co-transfection. Forced PTEN expression in SK-BR-3/R cells restored trastuzumab sensitivity. Furthermore, decreased tumor volume and Ki67 level as well as increased PTEN expression were observed after MTDH knockdown in subcutaneous breast cancer xenografts from SK-BR-3/R cells, while the opposite effect were found in grafts from MTDH overexpressing SK-BR-3 cells. CONCLUSIONS: MTDH overexpression confers trastuzumab resistance in HER2 positive breast cancer. MTDH mediates trastuzumab resistance, at least in part, by PTEN inhibition through an NFκB-dependent pathway, which may be utilized as a promising therapeutic target for HER2 positive breast cancer.

Integrated analysis of disulfidoptosis-related genes identifies NRP1 as a novel biomarker promoting proliferation of gastric cancer via glutamine mediated energy metabolism.

The incidence and mortality of gastric cancer rank fifth and fourth worldwide among all malignancies, respectively. Additionally, disulfidoptosis, a recently identified form of cellular demise, is closely linked to the initiation and advancement of malignancies. This study aims to create a novel signature of disulfidptosis-related genes (DRGs) and to further explore its association with the tumor immune microenvironment. Based on our comprehensive study, a prognostic signature consisting of 31 DRGs in stomach adenocarcinoma (STAD) was identified and characterized. Through the integrative analyses involving gene expression profiling, machine learning algorithms, and Cox regression models, the prognostic significance of these DRGs was demonstrated. Our findings highlight their strong predictive power in assessing overall survival across diverse patient datasets, and their better performance than traditional clinicopathological factors. Moreover, the DRGs signature showed association with the characteristics of the tumor microenvironment, which has implications for the immune modulation and therapeutic strategies in STAD. Specifically, NRP1 emerged as a key DRG with elevated expression in STAD, showing correlation with the advanced stages of diseases and poorer outcomes. Functional studies further revealed the role of NRP1 in promoting STAD cell proliferation through the modulation of glutamine metabolism. Overall, our study underscores the clinical relevance of DRGs as biomarker and potential therapeutic targets in STAD management, providing insights into disease biology and personalized treatments.

SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression.

BACKGROUND: The multiple tyrosine kinase inhibitors SU6668 have a promising therapeutic effect on the progression of hematological malignancies and some solid tumors. Here, we determined its effect on triple negative breast cancer (TNBC) cells and explored the potential molecular mechanism. METHODS: In this study, MDA-MB-231 cells were treated with SU6668 (15 µM, 30 µM) for 72 h and the change of proliferation was examined by MTT and tablet cloning. DNA ploidy was detected by flow cytometric analysis with PI staining. Double-label immunofluorescence method was used to detect the expression and distribution of MTDH proteins. VEGFR2, HIF-1α, MTDH, E-cadhrein, and SMA expressions were detected by Western bolt assay. RESULTS: This study showed that SU6668 inhibited the proliferation and induced polyploidization of MDA-MB-231 cells in a dose dependent form. SU6668 exposure increased the distribution of MTDH in cytoplasm and decreased its distribution in nuclei. After the treatment of SU6668, VEGFR2, HIF-1α, MTDH and SMA proteins were down-regulated, while E-cadhrein was up-regulated in MDA-MB-231 cells. CONCLUSIONS: In conclusion, SU6668 exposure maybe induces polyploidization, inhibit EMT and influence the expression of MTDH, which suppresses the proliferation in TNBC cells. MTDH is a key signal protein in downstream of VEGF/HIF-1αpathway in MDA-MB-231 cells, which may be used as the potential target in the treatment of TNBC.

[Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer].

OBJECTIVE: To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer. METHODS: Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days. RESULTS: LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05). CONCLUSIONS: The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

[Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: a prospective study].

OBJECTIVE: To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy. METHODS: One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study, and they were randomized into 2 groups, i.e., treatment group, which received the therapy of CIK cells transfusion, and control group, which was given regular follow-up. Meanwhile, patients with positive hormone receptor in the two groups were given endocrine therapy, and the patients with positive axillary lymph nodes were given radiotherapy to the chest wall and regional lymph nodes. The difference of quality of life between the two groups was analyzed according to the EORTC QLQ-BR53 quality of life questionnaire, and the adverse reactions were monitored. RESULTS: As regarding the functional evaluation, the physical function scores of patients of the treatment group were (83.43 ± 14.87) and (88.55 ± 11.62) at 3 and 6 months after the CIK cell therapy, respectively, significantly higher than the baseline value [(74.83 ± 13.82), P < 0.05)]. Global health status/QOL scores were (83.30 ± 19.09) and (89.68 ± 10.81), significantly higher than the baseline value [(77.72 ± 21.05), P < 0.05]. As regarding symptoms, the scores of fatigue, nausea, vomiting and loss of appetite of patients in the treatment group were higher than the baseline value, with significant differences (P < 0.05). The nausea and vomiting scores in the control group at 3 and 6 months of followed-up were (26.67 ± 22.56) and (21.47 ± 21.06), significantly lower than the baseline values [(33.31 ± 27.07), P < 0.05]. The scores of worrying about the future in the patients of treatment group were (47.56 ± 30.84) and (42.33 ± 26.95) after 3 and 6 months, significantly better than the baseline value [(57.41 ± 30.63), P < 0.05]. The systematic therapy side effects scores were (31.95 ± 27.52) and (23.72 ± 22.87), significantly better than the baseline value [(40.56 ± 26.28), P < 0.05]. The scores of arm edema were (45.26 ± 25.42) and (36.61 ± 20.51), significantly milder than the baseline value [(55.11 ± 22.82), P < 0.05]. In the control group, the scores of arm edema were (44.85 ± 28.94) and (38.64 ± 23.68), significantly lower than the baseline values [(53.26 ± 23.84) points, P < 0.05]. Alopecia scores were (29.93 ± 24.72) and (24.18 ± 22.66), significantly lower than the baseline values [(35.92 ± 22.08), P < 0.05]. In the treatment group, the patients' physical function, social function and global health status/QOL, fatigue, insomnia, and worrying about the future rates were significantly higher than that of the control group (P < 0.05 for all). Three patients after CIK reinfusion had transient fever, and 6 cases felt pain in the lower limb, but the symptoms were relieved after symptomatic treatment. CONCLUSIONS: Therapy of autologous CIK cells transfusion can significantly improve the quality of life of breast cancer patients, and the adverse reactions during the treatment can be alleviated by symptomatic treatment.

Hsa-miR-330-5p Aggravates Thyroid Carcinoma via Targeting FOXE1.

BACKGROUND: Thyroid carcinoma (TC) is one of the frequent endocrine malignancies, and growing evidence suggests that aberrant microRNA (miRNA) expression contributes to TC development and progression. Nevertheless, the function of miR-330-5p in the progression of TC remains unknown. METHODS: The expression levels of miR-330-5 in patients with thyroid carcinoma and healthy controls were detected, and their potential diagnostic and prognostic values were analyzed. RESULTS: In this study, we firstly found that miR-330-5p expression was markedly upregulated in TC tissue and cell lines. Functionally, the downregulation of miR-330-5p suppressed TC cell proliferation, migration, and invasion. Further studies revealed that miR-330-5p negatively regulated the expression of forkhead box E1 (FOXE1). More importantly, the results of rescue experiments suggested that FOXE1 overexpression reduced the positive effects of miR-330-5p overexpression in TPC-1 and K-1 cells. CONCLUSIONS: This work revealed that miR-330-5p facilitated the TC progression through targeting FOXE1, which may offer novel therapeutic options for TC.

Efficacy and safety of tenofovir disoproxil fumarate and tenofovir alafenamide fumarate in preventing HBV vertical transmission of high maternal viral load.

BACKGROUND: Hepatitis B virus (HBV) infection is a significant global health problem and > 42-52% of patients are infected during perinatal period. Tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) have been widely recognized as the main compounds used for antiviral treatment of hepatitis B. The present study evaluated the efficacy and safety of TAF in reducing HBV vertical transmission. METHODS: A total of 72 pregnant women, who met the inclusion criteria, were randomly divided into the TDF (300 mg/day, n = 36) and TAF (25 mg/day, n = 36) groups. Clinical and laboratory data were analyzed and compared between the two groups. RESULTS: No significant differences in alanine aminotransferase, total bilirubin, blood creatinine and blood urea nitrogen levels were noted between the two groups after treatment. The serum HBV DNA viral load and hepatitis B e antigen (HBeAg) levels of the two groups were significantly decreased following treatment, whereas the difference between the two groups was not statistically significant. The levels of urine retinol-binding protein and ß2-microglobulin had no significant change after TAF treatment (p > 0.05), but increased significantly after TDF treatment (p < 0.05). All drug concentrations were undetectable in umbilical cord blood (UCB) and breast milk samples of the TAF group, while the drug concentration of UCB and breast milk samples in the TDF group was 2.98 ± 1.44 and 19.16 ± 15.26 ng/ml, respectively. All infants were tested negative for serum hepatitis B surface antigen, HBV DNA, and HBeAg. CONCLUSIONS: Both TAF and TDF effectively block the mother-to-child transmission of hepatitis B. TAF was superior to TDF with regard to renal safety and breastfeeding.

Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial­to­mesenchymal transition.

The aim of the present study was to observe the influence of the small breast epithelial mucin (MUCL1) (also known as SBEM) gene on migration and invasion ability of breast cancer cells and to explore the potentially involved mechanism. SBEM­interference plasmid and SBEM­overexpressing plasmid were constructed. SBEM­knockdown or SBEM­â€‹overexpressing MCF­7 and MDA­MB­231 breast cancer cells were established by lentivirus­mediated stable transfection method. The scratch wound­healing assay and Transwell chamber experiment were used to detect the influence of the SBEM gene on the migration and invasion abilities of MCF­7 and MDA­MB­231 cells. Real­time PCR (polymerase chain reaction) and western blotting were used to detect the expression of epithelial­to­mesenchymal transition (EMT)­related markers and regulators. The cell morphology was observed after transfection. The SBEM­knockdown or SBEM­overexpressing MCF­7 and MDA­MB­231 cells were established successfully. The migration and invasion abilities were decreased after SBEM was downregulated, and were increased after SBEM was overexpressed both in MCF­7 and MDA­MB­231 cell lines. The mRNA and protein expressions of N­cadherin, Twist and vimentin were elevated following SBEM overexpression, while the expression of E­cadherin and claudin­1 were found to be decreased following SBEM overexpression. In conclusion, SBEM has the potential to promote migration and invasion ability of breast cancer cells via promoting epithelial­to­mesenchymal transition.

Demethylation of the HACE1 gene promoter inhibits the proliferation of human liver cancer cells.

HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) is frequently downregulated or lost in numerous types of cancer, including liver cancer. The aim of the present study was to examine whether demethylation of the HACE1 gene could inhibit tumour progression. The expression of HACE1 was detected in liver cancer cell lines. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas)-based demethylation single guide RNAs for the HACE1 gene promoter were designed and transfected into liver cancer cells. Subsequently, proliferation was detected by MTT and colony formation assays, and optineurin (OPTN) ubiquitination and microtubule-associated proteins 1A/1B light chain 3B protein levels were detected by immunoblotting. The levels of HACE1 were significantly reduced in liver cancer cell lines compared with in a normal liver cell line. Demethylation of the HACE1 gene promoter increased HACE1 expression, inhibited the proliferation of liver cancer cells, and promoted OPTN ubiquitination and autophagy activity in liver cancer cells. In conclusion, activation of HACE1 expression by promoter demethylation may provide a suitable approach for anticancer therapy.

Anti-tumor effect of chitin oligosaccharide plus cisplatin in vitro and in vivo.

BACKGROUND: Lung cancer is one of the most common malignant tumors in human beings, and cisplatin is a widely used chemotherapy drug, but its clinical application is limited because of its dose-dependent toxicity and drug resistance. Chitin is known to have various biological activities including anti-tumor, but the insoluble feature in common solvents greatly restricts its application. Chitin oligosaccharide is a small water-soluble molecule degraded from chitin without any toxic effect. METHODS: Chitin oligosaccharide was adopted to investigate the effects on lung adenocarcinoma A549 cells and tumor xenografts of nude mice. The experiments were divided into control group, chitin oligosaccharide group, cisplatin group and combination group. MTS assay, cell scratch test and migration assay were used to observe the proliferation and migration of A549 cells, and Western blot was used to detect the expression levels of caspase8, caspase3 and BAK. Ki67 and P53 expressions of tumor xenografts were detected to explore the effects of drugs on tumor prognosis. RESULTS: The results in vitro showed that chitin oligosaccharides could inhibit the proliferation and migration of A549 cells, and the effect was superior to chitin oligosaccharide or cisplatin when combined with cisplatin. Chitin oligosaccharide plus cisplatin up-regulated the expression level of caspase8 and caspase3, while had minor influence on the expression level of BAK. In vivo experiments showed that chitin oligosaccharide plus cisplatin could down-regulate the expression level of Ki67, while had minor influence on the expression level of P53. CONCLUSION: The study demonstrated that chitin oligosaccharide plus cisplatin had positive synergistic effects, and it is possible to improve the prognosis of lung adenocarcinoma patients by up-regulating the expression level of caspase8, caspase3 and down-regulating the expression level of Ki67.

Insights into the effect of nickel (Ni(II)) on the performance, microbial enzymatic activity and extracellular polymeric substances of activated sludge.

The performance, nitrogen removal rate, microbial enzymatic activity and extracellular polymeric substances (EPS) of activated sludge were assessed under nickel (Ni(II)) stress. The organic matter and NH4+-N removal efficiencies were stable at less than 10 mg/L Ni(II) and subsequently decreased with the increment of Ni(II) concentration from 10 to 30 mg/L. The specific oxygen uptake rate and dehydrogenase activity kept stable at less than 5 mg/L Ni(II) and then declined at 5-30 mg/L Ni(II). Both specific ammonia-oxidizing rate (SAOR) and specific nitrite-oxidizing rate (SNOR) decreased with the increment of Ni(II) concentration. The changing trends of ammonia monooxygenase and nitrite oxidoreductase activities were matched those of SAOR and SNOR, respectively. The nitrite-reducing rate and nitrate-reducing rate illustrated a similar variation tendency to the nitrite reductase activity and nitrate reductase activity, respectively. Ni(II) impacted on the production, chemical composition and functional group of EPS. The relation between the sludge volume index and the EPS production exhibited a better linear function with a negative slope, demonstrating that Ni(II) improved the sludge settleability despite of the increase of EPS production.

[Apoptosis-inducing effect of alternol on mouse lymphocyte leukemia cells and its mechanism].

Alternol is purified from fermentation productions of microorganisms named as Alternaria alternata var. monosporus. The research is to investigate the apoptosis-inducing effect of alternol on mouse lymphocyte leukemia (L1210) cells and the possible mechanisms. MTT method was used to evaluate the viability of L1210 cells. Apoptosis of L1210 cells was detected by morphological assessment, DNA electrophoresis assay and flow cytometry. Western blotting analysis was carried out to determine the apoptosis-related proteins. Proliferation inhibition of L1210 cells by alternol was found remarkably in a dose-dependent manner. When treated with alternol, apoptotic morphological features of L1210 cells were observed by fluorescent microscopy (AO/EB) and the apoptosis rate was also elevated in a time-dependent manner. After treatments with various concentrations of alternol for 48 h, DNA laddering appeared. The increase of reactive oxygen species (ROS) production was found after cells were exposed to alternol for 6 h, while the decrease of mitochondrial transmembrane potential (delta psi m) was not found until cells were exposed to alternol for 24 h. Furthermore, the level of Bcel-2 and Bcl-2/Bax was down-regulated, while the level of caspase-3 and caspase-9 but not caspase-8 was up-regulated when alternol was added for 72 h. In summary, the results suggested that alternol could inhibit the proliferation of L1210 cells and induce apoptosis of L1210 cells, which was mediated by mitochondria-dependent pathway.

Lambert-Eaton myasthenic syndrome in a patient with small-cell lung cancer: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder characterized by fluctuating proximal limb muscle weakness, decreased deep tendon reflexes and various autonomic symptoms. LEMS is reportedly the most common neurological paraneoplastic syndrome. This is the case report of a patient with small-cell lung cancer (SCLC) who developed LEMS. A 68-year-old male patient presented with a 6-month history of progressive weakness of the proximal limbs and a 2-month history of xerostomia. The patient was admitted to the Department of Neurology of the People's Liberation Army General Hospital of Shenyang Military Region (Shenyang, China). The symptoms of the patient were not relieved with supportive therapy. Further laboratory tests, electrodiagnostic studies, chest computed tomography and immunohistochemical staining confirmed the diagnosis of LEMS in the presence of SCLC. Following administration of two cycles of rescue chemotherapy with a combination of etoposide and cisplatin, the symptoms of the patient were gradually relieved and, after six cycles of therapy, the primary malignancy completely regressed. In conclusion, a diagnosis of LEMS may lead to the timely detection of SCLC, significantly improving patient prognosis and survival.

High expression of UBD correlates with epirubicin resistance and indicates poor prognosis in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is prone to recurrence and metastasis with worse prognosis. Epirubicin-based chemotherapy is of great importance for patients with TNBC, but resistance to epirubicin severely limits the application of this drug and this has emerged as a major problem in the treatment of TNBC. The ubiquitin protein D (UBD) molecule has often been considered a tumor oncogene, and has been shown to promote the recurrence and metastasis of malignant tumor cells. Since the role of UBD in epirubicin resistance and its prognostic value in TNBC have not been reported, the study reported here was designed to identify the epirubicin-resistance molecule and clarify the related biomarker for TNBC prognosis. METHODS: UBD plasmid was transfected into MDA-MB-231 cells, and the cells were exposed to epirubicin to observe the ability of UBD in epirubicin resistance. UBD expression was also detected in 78 breast cancer tissues by immunohistochemistry. Statistical methods were used to study the relationship between UBD expression and epirubicin resistance in TNBC treatment. Kaplan-Meier survival analysis was used to determine the correlation between UBD expression and TNBC patients' prognostic parameters. RESULTS: UBD expression was found increased in breast cancer tissues. Forced UBD expression was found to have a relationship with TNBC epirubicin resistance in vitro. High expression of UBD was found in TNBC, compared with in non-TNBC, and this played a positive role in epirubicin resistance and indicated the poor prognosis of TNBC treatment. CONCLUSION: UBD may play an important role in epirubicin resistance in TNBC. UBD has the potential to be a novel biomarker in TNBC chemoresistance and may be a promising therapeutic target for TNBC patients.

Prognostic analysis of Chinese patients with metastasis renal cell cancer receiving sorafenib: results from a multicenter long-term follow-up retrospective study.

The effects of sorafenib for Chinese patients with metastatic renal cell cancer (mRCC) were evaluated to figure out the relationship between clinical variables and prognosis. The data were analyzed retrospectively from six comprehensive cancer centers in Northeast China. All cases were diagnosed as mRCC histopathologically without exception. Patients were taken 400 mg sorafenib orally twice daily until progression of disease or intolerable toxic reaction occurred. Overall survival (OS), progression-free survival (PFS), and the influence of clinical variables on survival were appointed as main outcome measures. Clinical data were analyzed using SPSS statistical software. P<0.05 was considered as statistically significant. A total of 131 patients were available for survival analysis. The median follow-up periods were 16.9 months, and the median OS and PFS were 16.1 months and 10.5 months, respectively. Univariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, and previous therapy were significantly associated with OS, whereas PFS was merely associated with ECOG PS and previous therapy. The multivariate analysis suggested that ECOG PS, metastatic sites, and previous therapy were the independent prognostic factors for OS, and ECOG PS and previous therapy as the independent prognostic factors for PFS. In the subgroup analysis for patients with visceral metastasis, the prognosis of patients with lung metastasis alone was better than those cases with liver metastasis alone or multiple organs metastasis. In our study, sorafenib shows a higher curative activity for patients with mRCC in Northeast China. ECOG PS, metastatic lesions, and previous therapy may be important parameters for OS and PFS prediction. Lung metastases alone may be a more sensitive indicator for sorafenib than other organ metastases.

Rosiglitazone amplifies the sensitivity of docetaxel and reduces the expression of CD44v6.

Breast cancer seriously impairs physical and mental health in females. Currently, with further investigation into drugs, a number of new pharmacological effects have been found that offer new methods for clinical application in the treatment of breast cancer. As a widely used antidiabetic drug, rosiglitazone (Ros) has become well known for its anticancer effects, mediated by the activation of peroxisome proliferator-activated receptor γ and downregulated expression of the associated invasion gene. The objective of the present study was to investigate the combination of Ros and docetaxel (DOC) and whether DOC has any effect on breast cancer cell lines. The results showed that the combination of Ros and DOC may cooperate to increase anti-growth efficacy. The additive inhibitory effects on cell proliferation were sequence-dependent and are not likely to be associated with cell cycle arrest. This suggested that the target activation of associated factors of the signaling pathway by Ros may be a compelling ally in cancer treatment. In addition, evidence was provided for a convergence of Ros and DOC to induce the reduced expression of CD44v6. Future studies are required to confirm which associated gene of Ros is significant in blocking the signaling pathway.

Prognostic function of Ki-67 for pathological complete response rate of neoadjuvant chemotherapy in triple-negative breast cancer.

AIMS AND BACKGROUND: Triple-negative breast cancer (TNBC) has fluctuating pathological complete response (pCR) rates to neoadjuvant chemotherapy (NAC) according to published reports. Biomarkers predicting pCR rates of NAC would improve TNBC patients' outcomes. We conducted a meta-analysis to estimate the prognostic function of Ki-67 in relation to pCR rates of NAC in TNBC. METHODS AND STUDY DESIGN: Relevant publications in the literature from January 2006 to March 2013 were selected by searching PubMed, SpringerLink, Web of Science, Scopus and the Cochrane Library. The quality of prognostic studies was evaluated according to the standard reported by Hayden et al. Relative risk (RR) and 95% confidence interval (CI) were used to estimate the prognostic function of Ki-67 for pCR rates in TNBC. The fail-safe number was used to detect possible publication bias. Review Manager and MIX software was used to merge extracted data. RESULTS: The pCR rate of TNBC with high Ki-67 expression was 3.36 times that of low Ki-67 expression TNBC. The merged RR was 3.36 (95% CI: 1.61-7.02) and the fail-safe number was 34. No obvious publication bias but heterogeneity of the case series was detected. CONCLUSIONS: Ki-67 was a predictor of pCR rates to NAC in TNBC.