Does the primary tumor site in stage I extranodal natural killer/T-cell lymphoma matter?

The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value. Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study. All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy. In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved. A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group). We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups. In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS. Multivariate analyses showed that the primary site (p=0.011) and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS. In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor. So, we think PCNI for stage I ENKTCL patients is not necessary. Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis. And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.

The prognostic significance of human ovarian aging-related signature in breast cancer after surgery: A multicohort study.

Background: Recent studies have shown that ovarian aging is strongly associated with the risk of breast cancer, however, its prognostic impact on breast cancer is not yet fully understood. In this study, we performed a multicohort genetic analysis to explore its prognostic value and biological features in breast cancer. Methods: The gene expression and clinicopathological data of 3366 patients from the The Cancer Genome Atlas (TCGA) cohort, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort and the GSE86166 cohort were analyzed. A total of 290 ovarian aging-related genes (OARGs) were included in the establishment of the prognostic model. Furthermore, functional mechanisms analysis, drug sensitivity, and immune cell infiltration were investigated using bioinformatic methods. Results: An eight OARG-based signature was established and validated using independent cohorts. Two risk subgroups of patients with distinct survival outcomes were identified by the OARG-based signature. A nomogram with good predictive performance was developed by integrating the OARG risk score with clinicopathological factors. Moreover, the OARG-based signature was correlated with DNA damage repair, immune cell signaling pathways, and immunomodulatory functions. The patients in the low-risk subgroup were found to be sensitive to traditional chemotherapeutic, endocrine, and targeted agents (doxorubicin, tamoxifen, lapatinib, etc.) and some novel targeted drugs (sunitinib, pazopanib, etc.). Moreover, patients in the low-risk subgroup may be more susceptible to immune escape and therefore respond less effectively to immunotherapy. Conclusions: In this study, we proposed a comprehensive analytical method for breast cancer assessment based on OARG expression patterns, which could precisely predict clinical outcomes and drug sensitivity of breast cancer patients.

[Effects of pioglitazone on mitochondrial membrane potential of neonate rat's myocardial cells after hypoxia/reoxygenation].

OBJECTIVE: To explore the effectiveness and mechanism of pioglitazone on mitochondrial membrane potential of neonate rat's myocardial cells after hypoxia/reoxygenation. METHODS: Primary cultured myocardial cells of neonate Sprague-Dawley rats were pretreated with different concentrations of pioglitazone, pioglitazone's inhibitor and Chelerythrine, an inhibitor of protein kinase C (PKC). Hypoxia/reoxygenation model was established after 24 h of pretreatment. Subsequently, the mitochondrial membrane potential was detected with JC-1 staining under laser confocal microscopy during reoxygenation phase. RESULTS: Compared with the control group, red/green fluorescent ratio of myocardial cells in the H-r model group decreased significantly after hypoxia/reoxygenation (red/green fluorescent ratio reduced from 1.20 +/- 0.05 to 1.13 +/- 0.02, P<0.01 ), and also decreased in 0.1 micromol/ L, 1 micromol/L and 2 micromol/L pioglitazone group (1.11 +/- 0.01, 1.10 +/- 0.01, 1.16 +/- 0.03, P<0.01, respectively). The red/green fluorescent ratio in pioglitazone + GW9662 group (1.12 +/- 0.02) and pioglitazone + Chelerythrine group (1.07 +/- 0.01) were both significantly lower than those in 2 micromol/L pioglitazone group (P<0.01). CONCLUSION: The mitochondrial membrane potential of neonate rat's myocardial cells was descend after hypoxia/ reoxygenation, while pioglitazone can interrupt the process, indicating that the activation may be relevant to peroxisome proliferator-activated receptor gamma (PPARgamma) ligand and PKC pathway.

[Comparison of genetic diversity among five mating types of Liriodendron revealed by SSR markers].

The exploration of relationships between mating patterns and genetic diversity of progenies has theoretical and practical significance for both interspecies hybridization breeding and seed orchard management in tree species. Sixteen plants of Liriodendron chinense, L. tulipifera, and hybrid Liriodendron were chosen as the mating parents. Fourteen combinations were obtained from 5 types of mating types including inter-species mating, intra-species mating, multi-male parent pollination, backcross and self-cross in Liriodendron. Thirty progenies from each combination together with 16 mating parents were sampled to appraise their genetic diversity and inter-parent genetic distance using 16 SSR loci. Overall, a rela-tively high level of genetic diversity was found in the progenies of the 14 mating combinations in Liriodendron. The order of genetic diversity levels among the progenies of 5 types of mating systems from high to low was multi-male parent polli-nation, inter-species, backcross, intra-species, and self-cross, respectively. A significant positive correlation was found be-tween genetic distance of the mating parents and genetic diversity of corresponding progeny, indicating that the bigger the genetic distance of mating parents, the higher the progeny genetic diversity. The level of genetic diversity of the progenies of reciprocal crosses with the same parents was almost identical.

[Mesenchymal Stem Cells Stimulated by Growth Factors Release Exosomes with Potent Proangiogenic Activity].

OBJECTIVE: To explore the proangiogenic activity of exsomes released by human umbilical cord mesenchymal stem cells (MSCs) stimulated by erythropoietin and platelet-derived growth factor BB (PDGF-BB). METHODS: Human umbilical cord-derived MSCs were seeded and maintained in culture overnight. The media were then replaced by alpha-MEM containing EPO (1 U/ml) and/or PDGF-BB (50 ng/ml), and the culture was maintained for 72 hours. The exosomes from the culture supernatants were isolated with a routine ultra-catrifagation method. Flow cytometric analysis was performed to identify the origin of the exosomes, and their morphological features were observed by using a transmission electron microscopy. The exosomes were added at a concentration of 10 µg/ml into the culture system of human umbilical cord vein endothelial cells. MTT assay was used to evaluate the proliferative status. The Matrigel assay was used to observe the formation of net-work structures which were calculated after culture for 12 hours. RESULTS: Flow cytometric analysis showed that microparticles released by human umbilical cord MSCs expressed CD9, CD63 and CD81, which was in accordance with the surface molecular features of exosomes. Under an electron microscope, the exosomes took the featured cystic shape. The protein contents of exosomes released by untreated, EPO-stimulated, PDGF-BB-stimulated and EPO plus PDGF-BB stimulated MSCs (108 cells) were 256±124 µg, 1021±392 µg, 830±265 µg and 2207±733 µg, respectively. The results revealed that MSCs treated by EPO and PDGF-BB released significantly higher amounts of exosomes (P<0.01). MTT assay proved that the exosomes from EPO and PDGF-BB treated MSCs had more potent proliferation-promoting activity on human umbilical cord vein endothelial cells than those from untreated MSCs. The Matrigel assay showed that the numbers of capillary-like structures in untreated, EPO-, PDGF-BB and EPO plus PDGF-BB-treated groups were 2.6±0.84, 4.6±1.57, 4.2±0.78 and 6.3±1.34 per high power objective. Treatment with EPO or PDGF-BB dramatically enhanced the numbers of capillary liue structure, compared with that of untreated group (P<0.01) and those in EPO and PDGF-BB combination group was significantly greater than those of EPO or PDGF-BB group (P<0.01). CONCLUSION: EPO and PDGF-BB can stimulate MSCs to release exosomes with more potent proangiogenic activity.

Cancer risk in older people receiving statin therapy: a meta-analysis of randomized controlled trials.

BACKGROUND: Although statins are well tolerated by most aged people, their potential carcinogenicity is considered as one of the biggest factors limiting the use of statins. The aim of the present study was to determine the risk of cancer in people aged over 60 years receiving statin therapy. METHODS: A comprehensive search for articles published up to December 2015 was performed, reviews of each randomized controlled trials (RCTs) that compared the effects of statin mono-therapy with placebo on the risk of cancer in people aged > 60 years were conducted and data abstracted. All the included studies were evaluated for publication bias and heterogeneity. Pooled odds ratios (OR) estimates and 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: A total of 12 RCTs, involving 62,927 patients (31,517 in statin therapy group and 31,410 in control group), with a follow-up duration of 1.9-5.4 years, contributed to the analysis. The statin therapy did not affect the overall incidence of cancer (OR = 1.03, 95% CI: 0.94-1.14, P = 0.52); subgroup analyses showed that neither the variety nor the chemical properties of the statins accounted for the incidence of cancer in older people. CONCLUSIONS: Our meta-analysis findings do not support a potential cancer risk of statin treatment in people over 60 years old. Further targeted researches with a longer follow-up duration are warranted to confirm this issue.

[Effect of pioglitazone on hypoxia/reoxygenation injury and protein kinase C expression in neonatal rat cardiomyocytes].

OBJECTIVE: To observe the effect of pioglitazone on hypoxia/reoxygenation injury and the expression of protein kinase C (PKC) in neonatal rat cardiomyocytes. METHODS: Neonatal Sprague-Dawley rat cardiomyocytes in primary culture were treated with pioglitazone or GW9662 for 24 h prior to hypoxia/reoxygenation injury. Cardiomyocyte apoptosis was evaluated with Hoechst33258 staining and the expression of PKC was detected using Western blotting. RESULTS: In the early stage of hypoxia/reoxygenation injury, the apoptosis rates of the cardiomyocytes increased significantly from (0.20∓0.03)% of the control level to (12.22∓1.45)% (P<0.05). Pretreatment with pioglitazone significantly lowered the apoptosis rate of the cardiomyocytes with hypoxia/reoxygenation injury to (8.32∓0.89)%, and this effect was antagonized by GW9662, a specific blocker of peroxisome proliferators activated receptors γ (PPARγ). Pioglitazone did not cause increased expression of PKC in the cardiomyocytes. CONCLUSION: Pioglitazone can ameliorate neonatal rat cardiomyocyte injury induced by hypoxia/reoxygenation partially by activating PPARγ and does not increase the expression of PKC in the cells.