Pneumonectomy combined with SU5416 or monocrotaline pyrrole does not cause severe pulmonary hypertension in mice.

In the field of pulmonary hypertension (PH), a well-established protocol to induce severe angioproliferation in rats (SuHx) involves combining the VEGF-R inhibitor Sugen 5416 (SU5416) with 3 wk of hypoxia (Hx). In addition, injecting monocrotaline (MCT) into rats can induce inflammation and shear stress in the pulmonary vasculature, leading to neointima-like remodeling. However, the SuHx protocol in mice is still controversial, with some studies suggesting it yields higher and reversible PH than Hx alone, possibly due to species-dependent hypoxic responses. To establish an alternative rodent model of PH, we hypothesized mice would be more sensitive to hemodynamic changes secondary to shear stress compared with Hx. We attempted to induce severe and irreversible PH in mice by combining SU5416 or monocrotaline pyrrole (MCTP) injection with pneumonectomy (PNx). However, our experiments showed SU5416 administered to mice at various time points after PNx did not result in severe PH. Similarly, mice injected with MCTP after PNx (MPNx) showed no difference in right ventricular systolic pressure or exacerbated pulmonary vascular remodeling compared with PNx alone. These findings collectively demonstrate that C57/B6 mice do not develop severe and persistent PH when PNx is combined with either SU5416 or MCTP.NEW & NOTEWORTHY We attempted to establish a mouse model of severe and irreversible pulmonary hypertension by substituting hypoxia with pulmonary overcirculation. To do so, we treated mice with either SU5416 or monocrotaline pyrrole after pneumonectomy and performed hemodynamic evaluations for PH. Despite this "two-hit" protocol, mice did not exhibit signs of severe pulmonary hypertension or exacerbated pulmonary vascular remodeling compared with PNx alone.

DNA Methylation and Chromatin Accessibility Impact Subgenome Expression Dominance in the Common Carp (Cyprinus carpio).

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.

Primary treatment and recent survival trends in patients with primary diffuse large B-cell lymphoma of central nervous system, 1995-2016: A population-based SEER analysis.

This retrospective cohort study aimed to evaluate primary treatment and recent survival trends in patients with primary diffuse large B-cell lymphoma of central nervous system (CNS) from 1995 to 2016. Using the SEER data, patients diagnosed with non-HIV-associated primary central nervous system lymphoma (PCNSL)-diffuse large B-cell lymphoma (DLBCL) aged ⩾18 years between 1995 and 2016 were identified. The year of diagnosis was divided into the time period-1 (1995-2002), the time period-2 (2003-2012), and the time period-3 (2013-2016). Chi-square tests, the Kaplan-Meier method, log-rank test, and Cox regression model were used in the analysis. Overall, 3760 patients were included. Both the use of radiotherapy alone and the application of combined chemoradiotherapy decreased significantly, following the wider use of chemotherapy alone during 1995-2016. There was a significant improvement in PCNSL cause-specific survival (CSS) (period-1: 13 months vs. period-2: 19 months vs. period-3: 41 months, p < 0.001). Survival of patients aged above 70 years did not change from the time period-1 to the time period-2 (p = 0.101). However, there was an increase in CSS from the time period-2 to the time period-3 in the elderly patients (period-2: 5 months vs. period-3: 9 months, p < 0.001). On multivariable analyses, diagnosed in the time period-3 was significantly and independently associated with better CSS (hazard ratio 0.577, 95% confidence interval 0.506-0.659, p < 0.001). Our analysis shows the use of radiotherapy in the treatment of PCNSL has waned over the study span. There was a significant improvement in CSS during 1995-2016, which reflected developments in treatment over time. The elderly patient population also gained a significant CSS benefit in the most recent period.

Dominant Elongase Activity of Elovl5a but Higher Expression of Elovl5b in Common Carp (Cyprinus carpio).

Most diploid freshwater and marine fish encode one elovl5 elongase, having substrate specificity and activities towards C18, C20 and C22 polyunsaturated fatty acids (PUFAs). The allo-tetraploid common carp is hypothesized to encode two duplicated elovl5 genes. How these two elovl5 genes adapt to coordinate the PUFA biosynthesis through elongase function and expression divergence requires elucidation. In this study, we obtained the full-length cDNA sequences of two elovl5 genes in common carp, named as elovl5a and elovl5b. Functional characterization showed that both enzymes had elongase activity towards C18, C20 and C22 PUFAs. Especially, the activities of these two enzymes towards C22 PUFAs ranged from 3.87% to 8.24%, higher than those in most freshwater and marine fish. The Elovl5a had higher elongase activities than Elovl5b towards seven substrates. The spatial-temporal expression showed that both genes co-transcribed in all tissues and development stages. However, the expression levels of elovl5b were significantly higher than those of elovl5a in all examined conditions, suggesting that elovl5b would be the dominantly expressed gene. These two genes had different potential transcriptional binding sites. These results revealed the complicated roles of elovl5 on PUFA synthesis in common carp. The data also increased the knowledge of co-ordination between two homoeologs of the polyploid fish through function and expression divergence.

Combination of Anti-PD-1 Antibody, Anlotinib and Pegaspargase "Sandwich" With Radiotherapy in Localized Natural Killer/T Cell Lymphoma.

Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase "sandwich" with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m2 were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn't report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance.

Novel Insights into the Therapeutic Potential of Lung-Targeted Gene Transfer in the Most Common Respiratory Diseases.

Over the past decades, a better understanding of the genetic and molecular alterations underlying several respiratory diseases has encouraged the development of new therapeutic strategies. Gene therapy offers new therapeutic alternatives for inherited and acquired diseases by delivering exogenous genetic materials into cells or tissues to restore physiological protein expression and/or activity. In this review, we review (1) different types of viral and non-viral vectors as well as gene-editing techniques; and (2) the application of gene therapy for the treatment of respiratory diseases and disorders, including pulmonary arterial hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, non-small-cell lung cancer, and COVID-19. Further, we also provide specific examples of lung-targeted therapies and discuss the major limitations of gene therapy.

Geriatric nutritional risk index as an independent prognostic factor in locally advanced nasopharyngeal carcinoma treated using radical concurrent chemoradiotherapy: a retrospective cohort study.

BACKGROUND: Nutritional status is a key factor influencing the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) has been used to predict mortality risk and long-term outcomes. In this study, we aimed to evaluate the predictive value of pretreatment GNRI in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1,065 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma were included. Based on a cutoff value of pretreatment GNRI, patients were divided into two groups (low ≤107.7 and high >107.7). Combining GNRI and baseline Epstein-Barr virus (EBV) DNA, all patients were further stratified into three risk groups, namely, high-risk (high EBV DNA and low GNRI), low-risk (low EBV DNA and high GNRI), and medium-risk (except the above) groups. Multivariate analyses were performed using the Cox proportional hazards model to assess the predictive value of the GNRI. RESULTS: Among the 1,065 patients, 527 (49.5%) and 538 (50.5%) were divided into low and high GNRI groups, respectively. Within a median follow-up of 83 months, patients with a high GNRI score exhibited significantly higher overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) compared to those with low GNRI scores (P<0.05). Multivariate analyses revealed that high GNRI is an independent prognostic factor for OS and PFS (hazard ratio, HR, 0.471, 95% CI, 0.270-0.822, P=0.008; HR 0.638, 95% CI, 0.433-0.941, P=0.023, respectively). Using a combination of baseline GNRI and EBV DNA, a satisfying separation of survival curves between different risk groups for OS, PFS, DMFS was observed. The survival rates of patients in the high-risk group were significantly lower than those in the low- and medium-risk groups (all P<0.001). The combined classification was demonstrated to be an independent prognostic factor for OS and PFS after adjustment using multivariate analysis. CONCLUSIONS: Pretreatment GNRI is an independent prognostic factor for NPC patients. The combination of baseline GNRI score and EBV DNA level improved the prognostic stratification of NPC patients.

R-split-EPOCH plus high dose methotrexate in untreated diffuse large B cell lymphoma with MYC rearrangement or double expression of MYC and BCL-2.

Purpose: Diffuse large B cell lymphoma (DLBCL) with MYC rearrangement or double expression of MYC and BCL-2 (DE DLBCL) has a relatively poor prognosis and does not respond well to standard R-CHOP. In the current study, we aimed to investigate the efficacy and safety of R-split-EPOCH plus high dose methotrexate (HD-MTX) in the particular patient population. Methods: A total of 28 patients diagnosed with DE DLBCL or DLBCL with MYC rearrangement between January 2015 and December 2018 were included and retrospectively analyzed. All the participants underwent R-split-EPOCH plus HD-MTX as introduction therapy, with split infusion of etoposide, doxorubicin, and vincristine for 48 hours on D1-2 and D10-11, respectively. Results: The overall objective response (ORR) rate was 100%, with 24 (85.7%) complete response (CR) and 4 (14.3%) partial response (PR). The CR rate was 76.9% and 93.3% for DLBCL patients with MYC rearrangement and DE DLBCL patients, respectively. The 1- and 3-year PFS rate was 100% and 74.9%, respectively. The 1- and 3-year OS rate was 100% and 92.9%, respectively. Grade 3/4 non-hematological toxicity and grade 3/4 hematological toxicity occurred in 50% and 85.7% of patients, respectively. No treatment-related death was reported. Conclusions: R-split-EPOCH plus HD-MTX regimen is an effective and feasible treatment option for DE DLBCL and DLBCL with MYC rearrangement.

[Paclitaxel liposome for the treatment of castration-resistant prostate cancer].

OBJECTIVE: To investigate the effect and safety of the 3-week paclitaxel liposome protocol in the treatment of castration-resistant prostate cancer (CRPC). METHODS: This retrospective study included 40 cases of CRPC treated by the 3-week paclitaxel liposome protocol from February 2014 to February 2019, which involved intravenous injection of 10 mg dexamethasone in 100 ml normal saline on the first day and that of metoclopramide and panxi tora azole on the second day, followed by about 3 hours of intravenous drip of paclitaxel liposome at 135 mg/m2 for a course of 3 weeks. During the follow-up period, the patients received detection of the serum PSA level before treatment and chest x-ray and whole-body bone scan every six months. After two courses of treatment, the patients were observed for the changes in the serum PSA level, relief of bone pain, quality of survival, overall survival rate, overall survival time and toxic reactions. The protocol was continued unless the patient underwent progression, refused for unacceptable toxicity, or died. RESULTS: The patients were aged 59 to 79 (mean 68.80±5.67) years old, with the serum PSA level of (28.05 ± 3.22) µg/L at the baseline and (4.12 ± 0.23) µg/L after treatment. Thirty-eight of the patients were followed up for 3 to 33 (mean 12.2) months. PSA-based evaluation showed therapeutic effectiveness in 14 cases (35%), stable condition in 21 (52.5 %) and progression in 5 (12.5 %). Of the 18 patients with bone metastasis and pain, 16 (88.9 %) experienced relief of the symptoms and reduced the use of painkillers, with the bone pain scores of 5.20 ± 1.22 vs 2.79 ± 0.57 before and after treatment. By the end of the follow-up, the overall survival rate was 55.0% (22/40) and the median survival time was 17 months (95% CI: 13.4－24.6). During the treatment, no obvious adverse reactions were observed except for anemia in 1 case and hair loss in another. CONCLUSIONS: For the treatment of CRPC in China, the 3-week paclitaxel liposome protocol has the advantages of desirable safety, low toxicity, acceptable drug tolerance and improved quality of survival, but its curative effect needs to be verified with more randomized clinical trials with larger samples and longer follow-ups.

Effects of 6-mercaptopurine in pressure overload induced right heart failure.

BACKGROUND: Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB). METHODS: Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses. RESULTS: PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats. CONCLUSION: Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.

Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non-Hodgkin lymphoma.

Patients with Non-Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP-16) alone and that of MCC using both VP-16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI-LY-10 and SU-DHL-6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low-dose VP-16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP-16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy-related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP-16 48 hours + RAD001 24 hours is the optimal method for treating NHL.

Identification of two microRNA signatures in whole blood as novel biomarkers for diagnosis of nasopharyngeal carcinoma.

BACKGROUND: Early diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). MicroRNAs (miRNAs) are dysregulated and play important roles in carcinogenesis. Therefore, this study aimed to identify diagnostically relevant circulating miRNA signatures in patients with NPC. METHODS: Total RNA was extracted from whole blood samples obtained from 120 patients with NPC, 30 patients with head-neck tumors (HNT), and 30 healthy subjects (HSs), and examined by using a custom microarray. The expression levels of four miRNAs identified by using the microarray were validated with quantitative real-time reverse transcription polymerase chain reaction. The 120 patients with NPC and 30 HSs were randomly assigned to training group-1 and validation group-1, respectively. By using significance analysis of microarray (SAM), the specific miRNA expression profiles in whole blood from patients with NPC are obtained. By using lasso regression and adaptive boosting, a diagnostic signature was identified in training group-1, and its accuracy was verified in validation group-1. By using the same methods, another signature to distinguish patients with NPC from those with HNT and HSs was identified in training group-2 and confirmed in validation group-2. RESULTS: There were 117 differentially expressed miRNAs (upregulated and downregulated fold change ≥ 1.5) between the patients with NPC and HSs, among which an 8-miRNA signature was identified with 96.43% sensitivity and 100% specificity [area under the curve (AUC) = 0.995] to diagnose NPC in training group-1 and 86.11% sensitivity and 88.89% specificity (AUC = 0.941) in validation group-1. Compared with traditional Epstein-Barr virus (EBV) seromarkers, this signature was more specific for NPC. Furthermore, a 16-miRNA signature to differentiate NPC from HNT and HS (HNT-HS) was established from 164 differentially expressed miRNAs, which diagnosed NPC and HNT-HS with 100% accuracy (AUC = 1.000) in training group-2 and 87.04% (AUC = 0.924) in validation group-2. CONCLUSIONS: The present study identified two miRNA signatures for the highly accurate diagnosis and differential diagnosis of patients with NPC from HSs and patients with HNT. The identified miRNAs might represent novel serological biomarkers and potential therapeutic targets for NPC.

Efficacy of controlled-release oxycodone for reducing pain due to oral mucositis in nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy: a prospective clinical trial.

BACKGROUND: Pain due to oral mucositis (OM) is a major problem during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients. METHODS: We enrolled 56 NPC patients receiving CCRT and allocated them into two groups: moderate pain group (n = 27) and a severe pain group (n = 29) according to the degree of pain reported (moderate = numerical rating scale (NRS) score 4-6 or severe = NRS score 7-10) at initiation of controlled-release oxycodone (CRO) treatment. RESULTS: Total dose of CRO was significantly higher in severe pain patients than in moderate pain patients (791.60 ± 332.449 mg vs. 587.27 ± 194.940 mg; P = 0.015). Moderate pain patients had significantly better quality of life (P = 0.037), lower weight loss (P = 0.030) and more active CCRT response (90.9% vs. 64.0%; P = 0.041). Although 24-h pain control rate was comparable in the two groups (85.2% vs. 86.2%; P = 0.508), the moderate pain group score eventually stabilized at ~ 2 vs. 3 in the severe pain group (P < 0.001); the titration time to reach bearable pain (NRS ≤ 3) was also significantly shorter in moderate pain patients (2.45 ± 0.60 days vs. 3.60 ± 1.98 days; P = 0.012). Incidence of adverse events was comparable in both groups. CONCLUSIONS: The study findings suggest that early introduction of low-dose CRO at the moderate pain stage could help reduce the total dose required, provide better pain control, improve quality of life, and enhance CCRT response.

Inhibition of prostate cancer DU145 cell growth with small interfering RNA targeting the SATB1 gene.

Prostate cancer is a common visceral cancer of men worldwide. It is important to develop a more effective treatment for prostate cancer to overcome the treatment resistance that occurs with recurrence. RNA interference has been demonstrated to be a powerful tool for gene knockdown and has potential as a cancer treatment. It has been previously demonstrated that staining of special AT-rich sequence-binding protein 1 (SATB1) was stronger in prostatic carcinoma with metastasis compared with prostatic carcinoma without metastasis. In the present study, SATB1 small interfering (si)RNA was transfected into prostate cancer DU145 cells and normal human lung fibroblast cells, and cell proliferation was investigated using a Cell Counting kit-8. Three siRNA were transfected into cells using siPORT Lipid Transfection agent, and blank control and negative control groups were established. The cells were harvested and SATB1 mRNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. DU145 cell adhesion, migration and invasion capabilities were determined using cell adhesion, Transwell and Transwell with Matrigel assays, respectively. Silencing SATB1 significantly inhibited DU145 cell growth, adhesion, migration and invasive capability in vitro, indicating that a SATB1-targeting siRNA was successfully engineered. The results of the present study suggest that SATB1 siRNA may be a potential agent for treating human prostate cancer.

Inhibition of prostate cancer cell growth in vivo with short hairpin RNA targeting SATB1.

Despite previous advances, the treatment options for prostate cancer remain limited. For the purposes of gene knockdown, the utility of RNA interference has been demonstrated and is considered to have therapeutic potential. In the present study, a short hairpin RNA (shRNA) was used to assess the effect of special AT-rich sequence binding protein (SATB1) downregulation on the growth and metastatic potential of prostate cancer in xenograft nude mice. A plasmid carrying shRNA targeting SATB1, pSilencer-SATB1-shRNA, was successfully engineered. Using this plasmid, significant downregulation of SATB1 mRNA and protein expression in the DU145 prostate cancer cells was observed. pSilencer-SATB1-shRNA was demonstrated to be markedly efficacious against prostate cancer xenografts in nude mice. These results may lead to a novel method of improving gene therapy efficacy against prostate cancer via regulating the function of SATB1.

Detection rate of prostate cancer following biopsy among the northern Han Chinese population: a single-center retrospective study of 1022 cases.

BACKGROUND: Prostate cancer is known to have ethnic and regional differences. The study aimed to clinically evaluate the detection rate of prostate cancer on transrectal ultrasonography (TRUS)-guided prostate biopsy and analyze its characteristics among the northern Han Chinese population at a single center. METHODS: Between October 2009 and September 2016, a total of 1027 Chinese men, who had undergone TRUS-guided prostate biopsy at Qingdao Municipal Hospital, were retrospectively analyzed. Prostate biopsies were performed in the case of an abnormally elevated serum PSA level, and/or abnormal digital rectal examination (DRE) findings, and/or suspicious prostatic imaging findings. RESULTS: Of the 1022 men enrolled in the analysis, 438 patients (42.8%) were diagnosed with prostate adenocarcinoma histologically. When serum PSA levels were divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to 100.0, and ≥ 100.0 ng/ml), the detection rates of prostate cancer were 12.4, 15.9, 34.1, 66.2, and 93.8%, respectively. With serum PSA levels of 4.0 to 10.0 ng/ml, the cancer detection rates for a normal DRE and a suspect DRE finding were 13.5 and 58.2%, respectively. Accordingly, the cancer detection rates for a normal imaging and a suspect imaging finding were 13.5 and 58.2%, respectively. Besides, a large proportion of the patients were in the clinically advanced stage. CONCLUSIONS: The present study data reported a relatively higher prostate cancer detection rate of 42.8% and that the majority of the patients presented with clinically advanced prostate cancers within a local clinical urologic practice. An early detection and screening program for prostate cancer is of great need to reduce the burden from this disease among the northern Han Chinese population.

TIMELESS confers cisplatin resistance in nasopharyngeal carcinoma by activating the Wnt/ß-catenin signaling pathway and promoting the epithelial mesenchymal transition.

This study investigated the expression, clinicopathological significance and mechanism of action of TIMELESS, a mammalian homolog of a Drosophila circadian rhythm gene, in nasopharyngeal carcinoma. Quantitative real-time PCR, western blotting and immunohistochemistry revealed TIMELESS was upregulated in NPC cell lines (n = 8 vs. NP69 cells), and freshly-frozen (n = 6) and paraffin-embedded human NPC specimens (n = 108 vs. normal samples/non-tumor cells). TIMELESS expression was associated with T category (P = 0.002), N category (P = 0.001), clinical stage (P < 0.001), metastasis (P = 0.047), vital status (P = 0.013) and serum Epstein-Barr DNA (P = 0.005). High TIMELESS expression was associated with poorer overall survival (80.7% vs. 95.9%; P = 0.004) and progression free survival (68.1% vs. 88.0%; P = 0.005). Univariate and multivariate analysis revealed TIMELESS was an independent prognostic factor for overall survival and progression free survival. Stable ectopic overexpression of TIMELESS in NPC cell lines conferred resistance to cisplatin-induced apoptosis in vitro and in vivo, promoted an epithelial-to-mesenchymal transition phenotype, and activated the Wnt/ß-catenin pathway and downstream gene transcription; knockdown of TIMELESS had the opposite effects. TIMELESS may play a role in the development of NPC and could represent a valuable prognostic factor and potential therapeutic target.

Overexpression of Kinesin Family Member 20A Correlates with Disease Progression and Poor Prognosis in Human Nasopharyngeal Cancer: A Retrospective Analysis of 105 Patients.

BACKGROUND: Numerous studies have shown Kinesin family member 20A (KIF20A) may play a critical role in the development and progression of cancer. However, the clinical value of KIF20A in nasopharyngeal carcinoma (NPC) is unknown. Here, we investigated the expression pattern of KIF20A in NPC and its correlation with clinicopathological features of patients. METHODS: Real-time PCR and Western blotting were used to quantify KIF20A expression in NPC cell lines and clinical specimens compared with normal controls. KIF20A protein expression was also examined in archived paraffin embedded tumor samples from 105 patients with pathologically confirmed NPC by immunohistochemistry (IHC). Statistical analyses were applied to assess the associations between KIF20A expression and the clinicopathological features and survival outcomes. Effects on migration and invasion were assessed by wound healing and transwell invasion assays after KIF20A silencing. RESULTS: KIF20A was significantly overexpressed at both the mRNA and protein levels in NPC cell lines and human tumor tissues. 45/105 (42.9%) of NPC specimens expressed high levels of KIF20A among the KIF20A detectable cases. Statistical analysis revealed that high KIF20A expression was significantly associated with gender (P = 0.046), clinical stage (P<0.001), T category (P = 0.022), N category (P<0.001), distant metastasis (P = 0.001) and vital status (P = 0.001). Moreover, Higher KIF20A expression patients had shorter overall survival (OS) and progression-free survival (PFS) (P = 0.001 and P = 0.001; log-rank test). In multivariate analysis, KIF20A was an independent prognostic factor for OS and PFS in the entire cohort (P = 0.033, P = 0.008). Knock down of KIF20A expression significantly suppressed NPC cell's migration and invasion. CONCLUSIONS: KIF20A is overexpressed and may serve as an independent prognostic biomarker in NPC. Targeting KIF20A reduces migration and invasion of NPC cells.

[Risk factors of prostate cancer in urban Qingdao: a case-control study].

OBJECTIVE: To investigate the risk factors of prostate cancer in urban Qingdao and provide some theoretical evidence for the scientific prevention and treatment of the disease. METHODS: We performed a hospital-based matched case-control study in Qingdao Municipal Hospital. The cases and controls were matched in age, gender, nationality and the place of residence. All the subjects were interviewed face to face in the hospital using a questionnaire, and the data analyzed by the conditional logistic regression method. RESULTS: According to the 258 valid questionnaires collected, the prostate cancer risk was significantly higher in the cases with a family history of cancer than in those without (OR = 2.58), and so was it in the men with the first spermatorrhea at the age of < or = 15 years than in those at the age of > or = 18 years (OR = 2.27). A decreased risk of prostate cancer was found among the men with the first experience of sexual intercourse between 25 to 30 years of age (OR = 0.76). An increased risk was shown in those with sexual intercourses > or = 4 times per week before 35 years old (OR = 2.57), masturbations > or = 3 times per week (OR = 2.30) and a drinking history (alcohol > or = 150 g/d) of > or = 10 years (OR = 2.83). CONCLUSION: Positive family history of cancer, earlier age of the first spermatorrhea, sexual intercourses > or = 4 times per week before 35 years old, frequent masturbations, and heavy drinking for more than 10 years are risk factors for prostate cancer.