Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model

Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril would further attenuate cancer cachexia in vivo. After injection with colon-26 adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following four treatment groups for 7 days (n?=?8 per group): (1) placebo, (2) RGZ, (3) imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose mass, serum metabolic markers and cytokines, and the expression of nuclear factor-κB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From days 14 to 16, all treatments significantly reduced tumor volume (P?<?0.05). From days 10 to 16, improvements in the tumor-free body weight were observed in the RGZ and RGZ+imidapril groups. In addition, significant improvements in both gastrocnemius muscle and epididymal adipose mass were observed in all treatment groups (all, P?<?0.05). Furthermore, all treatments significantly increased tumor necrosis factor alpha levels as compared to those observed in the healthy control animals (P?<?0.001). Insulin levels significantly increased in the placebo group as compared to those in the healthy control group (P?<?0.05), which were reduced in all the treatment groups (P?<?0.05). Finally, whereas all treatments significantly reduced atrogin-1 levels as compared to the placebo group (all, P?<?0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and RGZ+imidapril groups (both, P?<?0.05). Thus, all three treatments reduce tumor growth and alleviate cancer cachexia; however, synergistic effects of RGZ+imidapril combination therapy were not observed.     

Effect of bone marrow mesenchymal stem cells on hepatocellular carcinoma in microcirculation

This study aims t explore the effect and application of bone marrow mesenchymal stem cells (BMSCs) on hepatocellular carcinoma in microcirculation by observing the angiogenesis of hepatocellular carcinoma in transplanted area. BMSCs were isolated and cultured primarily using the method of whole bone marrow culture and identifying surface antigens of third-generation bone marrow-derived mesenchymal stem cells using flow cytometry. Hepatoma cells cultured with BMSCs-conditioned medium (BMSCs-CM) were assayed using the cell proliferation rate of the MTT method. Nude mice were divided into control group (group A), BMSCs cell transplantation group (group B), HepG-2 cell group (group C), and combined BMSCs and HepG-2 cell cotransplanted group (group D). The result showed that the microvascular density was not significantly different in groups A and B. However, the microvascular density at 14 days was higher than 0 day in group C (P?<?0.05). In group D, the microvascular density at 14 days was higher than that of 7 and 0 days (P?<?0.05) and 7 days was higher than 0 days (P?<?0.05). It was showed that the microvascular density did not get significant difference at 0 and 7 days in the four groups (P?>?0.05). But the microvascular density of group C was higher than groups A and B at 14 days (P?<?0.05), group D was higher than groups A and B at 14 days (P?<?0.05) and group D was higher than group C at 14 days (P?<?0.05). BMSCs could promote the growth of microvascular in hepatoma cells in a transplanted area.     

Effects of aerobic exercise on cancer-related fatigue in breast cancer patients receiving chemotherapy: a meta-analysis

Increasing scientific evidences suggest that aerobic exercise may improve cancer-related fatigue in breast cancer patients, but many existing studies have yielded inconclusive results. This meta-analysis aimed to derive a more precise estimation of the effects of aerobic exercise on cancer-related fatigue in breast cancer patients receiving chemotherapy. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through July 1, 2013 without language restrictions. Crude standardized mean difference (SMD) with 95 % confidence interval (CI) was calculated. Twelve comparative studies were assessed with a total of 1,014 breast cancer patients receiving chemotherapy, including 522 patients in the aerobic exercise group (intervention group) and 492 patients in the usual care group (control group). The meta-analysis results revealed that the Revised Piper Fatigue Scale (RPFS) scores of breast cancer patients in the intervention group were significantly lower than those in the control group (SMD?=??0.82, 95% CI?=??1.04?～??0.60, P?<?0.001). However, there was no significant difference in the Functional Assessment of Chronic Illness Treatment-Fatigue scale (FACIT-F) scores between the intervention and control groups (SMD?=?0.09, 95% CI?=??0.07?～?0.25, P?=?0.224). Subgroup analysis by ethnicity indicated that there were significant differences in RPFS and FACIT-F scores between the intervention and control groups among Asian populations (RPFS: SMD?=??1.08, 95% CI?=??1.35?～??0.82, P?<?0.001; FACIT-F: SMD?=?1.20, 95 % CI?=?0.70?～?1.71, P?<?0.001), but not among Caucasian populations (all P?>?0.05). The current meta-analysis indicates that aerobic exercise may improve cancer-related fatigue in breast cancer patients receiving chemotherapy, especially among Asian populations.     

Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit

Summary Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enchanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low- protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8–12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1,n=15; group 2,n=14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high-performance liquid chromatography (HPLC) with fluorometric detection. The low-protein diet significantly decreased doxorubicin clearance (48±3 vs 59±4 ml min^–1 kg^–1;P<0.05), prolonged the terminal climination half-life (28±2 vs 22±2 h;P<0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722±122 vs 1405±71 ng h ml^–1;P<0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-portein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52±5 vs 40±2 h;P<0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy.Supported by the Department of Veterans Affairs and the American Heart Foundation     

Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model

Purpose: To investigate the effect of heat shock protein (HSP) modulation on tumour coagulation by combining radiofrequency (RF) ablation with adjuvant liposomal quercetin and/or doxorubicin in a rat tumour model.

Methods: Sixty R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved study. Initially, 60 tumours (n?=?6, each subgroup) were randomised into five groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1?mg/kg), (3) IV liposomal quercetin followed 24?h later with RF, (4) RF followed 15?min later by IV liposomal doxorubicin (8?mg/kg), (5) IV liposomal quercetin 24?h before RF followed by IV liposomal doxorubicin 15?min post-ablation. Animals were sacrificed 4 or 24?h post-treatment and gross coagulation diameters were compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved caspase-3 expression. Comparisons were performed by using Student t-tests or ANOVA.

Results: Combination RF-quercetin significantly increased coagulation size compared with either RF or liposomal quercetin alone (13.1?±?0.7?mm vs. 8.8?±?1.2?mm or 2.3?±?1.3?mm, respectively, P?<?0.001 for all comparisons). Triple therapy (quercetin-RF-doxorubicin) showed larger coagulation diameter (14.5?±?1.0?mm) at 24?h than quercetin-RF (P?=?0.016) or RF-doxorubicin (13.2?±?1.3?mm, P?=?0.042). Combination quercetin-RF decreased Hsp70 expression compared with RF alone at both 4?h (percentage of stained cells/hpf 22.4?±?13.9% vs. 38.8?±?16.1%, P?<?0.03) and 24?h (45.2?±?10.5% vs. 81.1?±?3.6%, P?<?0.001). Quercetin-RF increased cleaved caspase-3 expression at both 4?h (percentage of stained cells/hpf 50.7?±?13.4% vs. 41.9?±?15.1%, P?<?0.03) and 24?h (37.4?±?7.8% vs. 33.2?±?6.5%, P?=?0.045); with, triple therapy (quercetin-RF-doxorubicin) resulting in the highest levels of apoptosis (45.1?±?10.7%) at 24?h. Similar trends were observed for rim thickness.

Conclusions: Suppression of HSP production using adjuvant liposomal quercetin can increase apoptosis and improve RF ablation-induced tumour destruction. Further increases in tumour coagulation can be seen including an additional anti-tumour adjuvant agent such as liposomal doxorubicin.     

High expression of APAF-1 elevates erythroid apoptosis in iron overload myelodysplastic syndrome

Apoptotic protease-activating factor 1 (APAF-1) is a central component of the intrinsic pathway of apoptosis. Our study aims at searching the role of APAF-1 in iron overload myelodysplastic syndrome (MDS). Erythroid apoptosis rate, mRNA expression levels of APAF-1, and caspase-9 activity were determined by flow cytometry, quantitative real-time PCR, and colorimetric assay in MDS patients, respectively. In addition, K562 and MDS-L cell lines were incubated with different concentrations of ferric ammonium citrate (FAC) or ferric ammonium citrate?+?desferrioxamine (FAC?+?DFO) in vitro to observe the alteration in erythrocyte apoptosis rate, APAF-1 mRNA, and protein expression levels. Moreover, as control, erythroid apoptosis rate and APAF-1 mRNA expression were detected after silencing APAF-1 expression by endoribonuclease-prepared small interfering RNAs (esiRNAs) in K562 and MDS-L cell lines. Both erythroid apoptosis rate and APAF-1 mRNA expression of the iron overload (IO) group were significantly higher than those of the non-IO group (P?<?0.001 and P?<?0.001). There is a significant difference of caspase-9 activity between the IO group and the non-IO group (P?<?0.001). Erythroid apoptosis rate and APAF-1 mRNA expression of K562 and MDS-L cell lines significantly elevated after FAC incubation in different concentrations (P?<?0.001 and P?<?0.001 for K562; P?<?0.001 and P?<?0.001 for MDS-L), while erythroid apoptosis rate and APAF-1 mRNA expression in the FAC?+?DFO group declined (P?<?0.001 and P?<?0.001 for K562; P?<?0.001 and P?<?0.001 for MDS-L). After silencing of APAF-1 expression with specific esiRNAs, erythroid apoptosis rate and APAF-1 mRNA expression of K562 and MDS-L cell lines markedly decreased (P?<?0.001 and P?<?0.001 for K562; P?<?0.001 and P?<?0.001 for MDS-L). APAF-1 plays an important role in iron-induced erythroid apoptosis increase in MDS.     

Lentivirus-mediated CD/TK fusion gene transfection neural stem cell therapy for C6 glioblastoma

A suicide gene can convert nontoxic prodrugs into toxic products to kill tumor cells. In this study, our aim was to transfect lentivirus-mediated CD/TK fusion gene into Wistar rat’s neural stem cells (NSC) and then implant the NSC into a C6 glioma model to observe a C6 glioma growth inhibition effect. Primary NSC and stable transfection CD/TK fusion gene cell lines were established. To observe the tumor size and rat survival period in different groups, C6 glioma cell apoptosis and cell viability rate were applied to analyze the tumor inhibition effect of the neural stem cells’ transfected CD/TK fusion gene. C6 cell viability showed that CDglyTK-NSC + GCV/5-Fc (group 1) was lower than CDglyTK-NSC (group 2), NSC + GCV/5-Fc (group 3), and control (group 4) from day 2 (p?<?0.05), and the apoptosis rate was higher in group 1 compared with that of other groups (50.6 %, p?<?0.05) either in vitro or in vivo (35.47 %, p?<?0.05); both cell viability and apoptosis had no significance in the other three groups. In vivo, tumor size in group 1 was 7.76?±?1.37 mm³, which is smaller than the others (group2 27.28?±?4.11 mm³, group3 27.94?±?2.08 and 28.61?±?2.97 mm³; p?<?0.05). The other groups’ tumor size was not significant (p?>?0.05). Survival time of rats treated with CDglyTK-NSC + GCV/5-Fc (group 1) was significantly longer than that of the other groups (p?<?0.05; group 1 48.86?±?1.97, group 2 28.67?±?3.75, group 3 31.5?±?1.27, group 4 29.3?±?1.33). We also showed that the transfected C6 cells had a migratory capacity toward gliomas in vivo. Transfected CD/TK fusion gene neural stem cells combined with propyl–guanosine and 5-flucytosine double prodrug significantly inhibit the development of glioma.     

Impairment of breast cancer cell invasion by COX-2-specific inhibitor NS398: roles of CXCR4 and of uPA system

Inhibition of cyclooxygenase-2 (COX-2) is known to impair cancer cell metastatic behaviour, but the mechanisms involved largely remain elusive. We aimed to analyse whether the antimetastatic effect of COX-2 inhibition in breast cancer cells could be explained by variations in the expression levels of chemokine receptor CXCR4, vascular endothelium growth factor (VEGF) and UPA/UPAR components of the urokinase plasminogen activator system (uPAR). Breast cancer cell line MDA-MB-231 was exposed to COX-2-specific inhibitor NS398. Experimental data were assessed using Matrigel invasion tests, qRT-PCR, ELISA, flow cytometry and MTT test. Exposure to NS398 had no major effect on cell viability, apoptosis or VEGF production. Cell invasion was significantly decreased with reductions ranging from of 3.6% with 10???M NS398 to 81.04% with 100???M NS398. CXCR4 membrane expression was significantly reduced by 18% (P?<?0.05) when cells were treated with 100???M of NS398 for 72?h. UPA mRNA levels were significantly reduced to 78 and 63% after treatment with 10???M NS398 for 48 and 72?h, respectively (P?<?0.05). UPAR mRNA levels also decreased with mild NS398 concentrations, reaching the lowest level of 56% with 50???M of NS398 for 48?h (P?<?0.05). With NS398 higher concentrations, UPAR and UPA expression levels increased. According to our results, impairment of expression of CXCR4, UPA and UPAR differentially contribute to the antimetastatic effect of COX-2 inhibitors depending on drug concentration.     

Promoter methylation of DAPK gene may contribute to the pathogenesis of nonsmall cell lung cancer: a meta-analysis

We performed a meta-analysis of cohort studies to determine whether promoter methylation of the death-associated protein kinase (DAPK) gene contributes to the pathogenesis of nonsmall cell lung cancer (NSCLC). A range of electronic databases were searched: MEDLINE (1966?～?2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980?～?2013), CINAHL (1982?～?2013), Web of Science (1945?～?2013), and the Chinese Biomedical Database (CBM; 1982?～?2013) without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Our meta-analysis integrated results from 12 clinical cohort studies that met all inclusion criteria with a total of 1,027 NSCLC patients. We observed that the frequency of DAPK gene methylation in cancer tissues were significantly higher than that in the adjacent normal and benign tissues (cancer tissues vs. benign tissues: OR?=?8.50, 95 % CI?=?5.88?～?12.28, P?<?0.001; cancer tissues vs. adjacent tissues: OR?=?5.95, 95 % CI?=?4.11?～?8.60, P?<?0.001; cancer tissues vs. normal tissues: OR?=?4.75, 95 % CI?=?3.28?～?6.87, P?<?0.001; respectively). Subgroup analysis by ethnicity demonstrated that DAPK gene methylation was closely associated with the development and progression of NSCLC among both Asians and Caucasians (all P?<?0.05). Furthermore, we conducted a subgroup analysis based on sample source and discovered that DAPK gene methylation was implicated in the pathogenesis of NSCLC in both blood and tissue subgroups (all P?<?0.05). Our results suggest that DAPK promoter methylation may be involved in NSCLC carcinogenesis. Thus, the detection of aberrant DAPK methylation may be helpful in the diagnosis and prognosis of NSCLC.     

Improved survival after pancreatic re-resection of positive neck margin in pancreatic cancer patients. A systematic review and network meta-analysis

The oncological benefit of achieving a negative pancreatic neck margin through re-resection after a positive frozen section (FS) is debated. Aim of this network meta-analysis is to evaluate the survival benefit of re-resection after intraoperative FS neck margin examination following pancreatectomy for ductal adenocarcinoma.A systematic search of studies comparing different strategies for the management of positive FS was performed. Patients were classified in three groups based on FS and permanent section (PS): Group A (FS-, PS-R0), Group B (FS+, PS-R0), Group C (FS±, PS-R1). A frequent random-effects network-meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). Primary endpoint was overall survival (OS). Secondary endpoints were pathological outcomes.Seven retrospectives studies with 4205 patients were included and 99.1% of the pancreatic resections were pancreatoduodenectomies. Group A had the highest probability of better OS (SUCRA = 90%), compared to Group B (SUCRA = 48.7%) and Group C, which was the worst prognostic scenario (SUCRA = 11.3%). Group B had still a probability of longer OS compared to Group C (SUCRA = 48.7% vs 11.3%). Pathological features were more favourable in Group A, with the highest SUCRA for T1-T2 tumors (92.6%), N0 status (89.4%), absence of perineural invasion (92.3%). Heterogeneity was low (τ-value <0.1) for OS, and moderate (τ-values: 0.1–0.6) for pT, pN, and perineural invasion.In conclusion, negative neck margin after primary resection (FS negative) or re-resection of a positive FS was associated with improved survival compared with PS-R1. However, any intraoperative positive FS can be considered as a prognostic factor associated with a more aggressive disease.     

Expression and Significance of RKIP and E-cadherin in Lung Squamous Cell Carcinoma

The purpose of this study was to investigate the expression of Raf kinase inhibitor protein (RKIP) and epithelial cadherin (E-cadherin) in lung squamous cell carcinoma tissue and its correlation with the clinical pathology of lung squamous cell carcinoma. RKIP and E-cadherin mRNA (by RT-PCR) and protein (by western blotting) levels were monitored in carcinoma tissues and surrounding normal tissues from 86 lung squamous cell carcinoma cases, and their positive rates were calculated. The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P?<?0.05). The positive expression rates were significantly lower in those with lymph node metastasis than in those without (P?<?0.05). The lower the degree of tumor differentiation, the lower the E-cadherin mRNA positive expression rate (P?<?0.05). The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in patients at advanced (III, IV) stages than in patients at early (I, II) stages (p?<?0.05); this rate, however, was independent of gender, age, and tumor size (P?>?0.05). The protein levels of RKIP and E-cadherin were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P?<?0.05). The levels were significantly lower in patients with lymph node metastasis than in those without it (P?<?0.05). The lower the degree of tumor differentiation, the lower the protein level of E-cadherin (P?<?0.05). Both RKIP and E-cadherin are tumor suppressors, their low expression levels may be associated with initiation, invasion and/or metastasis, as well as with the inhibition of lung squamous cell carcinoma differentiation.     

Clinicopathological and prognostic significance of chemokine receptor CXCR4 overexpression in patients with esophageal cancer: a meta-analysis

The prognostic significance of CXC chemokine receptor type 4 (CXCR4) for survival of patients with esophageal cancer remains controversial. To investigate its expression impact on clinicopathological features and survival outcome, a meta-analysis was performed. A comprehensive search in the PubMed, Embase, and Web of Science (up to October 8, 2013) was performed for relevant studies using multiple search strategies. Correlation between CXCR4 expression and clinicopathological features and overall survival (OS) was analyzed. A total of 1,055 patients with esophageal cancer from seven studies were included. The pooled odds ratios (ORs) which indicated CXCR4 expression was associated with tumor depth (OR?=?0.35, confidence interval (CI)?=?0.27–0.47, P?<?0.00001), status of lymph node (OR?=?0.36, CI?=?0.21–0.61, P?<?0.0002), TNM (tumor, node, metastasis) stage (OR?=?0.38, CI?=?0.25–0.56, P?<?0.00001), and histological type (OR?=?1.81, CI?=?1.07–3.05, P?=?0.03). Poor overall survival of esophageal cancer was found to be significantly related to CXCR4 overexpression (hazard ratio (HR) 1.49, 95 % CI?=?1.24–1.80, P?<?0.0001), whereas combined ORs exhibited that CXCR4 expression has no correlation with gender or tumor differentiation. Based on the published studies, CXCR4 overexpression in patients with esophageal cancer indicated worse survival outcome and was associated with common clinicopathological poor prognostic factors.     

Implications of Bit1 and AIF overexpressions in esophageal squamous cell carcinoma

Overwhelming evidence has demonstrated that Bit1 and AIF as mitochondrial proteins are implicated in the development and progression of a variety of tumors. However, their expressions and biological functions in esophageal squamous cell carcinoma (ESCC) remain to be delineated. In the present study, we found that Bit1, AIF, and Bcl-2 levels in ESCC tissues were significantly higher than those in normal esophageal epithelial tissues and dysplasia tissues (P?<?0.05). Stepwise investigation demonstrated that Bit1 and Bcl-2 levels were both tightly associated with lymphatic metastasis and TNM staging (P?<?0.05), and the levels of Bit1 mRNA as well as AIF and Bcl-2 proteins were both closely related to tumor differentiation (P?<?0.05), but not related to the patients' age and gender (P?>?0.05). Importantly, Bit1 mRNA and protein levels in ESCC with lymphatic metastasis and TNM staging in III and IV were markedly higher than that without lymphatic metastasis and TMN staging in I and II. Further analysis showed that expression of Bit1 protein was both positively correlated with expressions of AIF and Bcl-2 proteins (r?=?0.408 and 0.405, respectively; P?<?0.05). Correctively, our data cited earlier suggest that Bit1 plays pivotal roles in the development and progression of ESCC, and its biological functions in ESCC may be closely associated with AIF and Bcl-2 levels.     

Recombinant human endostatin combined with radiotherapy inhibits colorectal cancer growth

Background

To examine the effects of recombinant human endostatin combined with radiotherapy on colorectal cancer HCT-116 cell xenografts in nude mice.

Methods

Forty male BALB/c nude mice were injected with human colorectal cancer HCT-116 cells to form xenografts and then randomized into the following 4 groups (each group comprised ten mice): a control group, an endostatin group (20 mg/kg endostatin once a day for 10 days), a radiotherapy group (a 6-Gy dose was administered via a 6-MV X-ray on day 5 post-inoculation), and a combination therapy group (radiotherapy with endostatin treatment). The tumor growth inhibition rate were detected. CD31, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α) expression and microvascular density (MVD) were evaluated by immunohistochemistry. The expression of VEGF protein was also detected by western blotting.

Results

The tumor growth inhibition rate in the radiotherapy with endostatin treatment group was significantly higher than those in endostatin group or radiotherapy group (77.67% vs 12.31% and 38.59%; n?=?8 per group, P?<?0.05). The results of immunohistochemistry showed that treatment with radiotherapy induced significant increases in CD31, VEGF, and HIF-1α expression and MVD compared with treatment with saline, while treatment with endostatin or radiotherapy with endostatin induced reductions in CD31, VEGF, and HIF-1α expression and MVD compared with treatment with saline (n?=?8 per group, P?<?0.05). The results of western blotting showed that VEGF protein expression in radiotherapy group was significantly increased compared with that in the control group. However, VEGF protein expression in the endostatin or radiotherapy with endostatin groups was significantly decreased compared with that in the control group (n?=?8 per group, P?<?0.05).

Conclusions

Endostatin combined with radiotherapy can significantly inhibit HCT-116 cell xenograft growth, possibly by inhibiting angiogenesis and attenuating tumor cell hypoxia.

     

Polyamidoamine dendrimer liposome-mediated survivin antisense oligonucleotide inhibits hepatic cancer cell proliferation by inducing apoptosis

Polyamidoamine dendrimer (PAMAM) is a new nanometer material, which can transfer the target genes to cells with high efficiency and lower toxicity. This study aims to evaluate antitumor effects of survivin antisense oligonucleotide (survivin-asODN) (carried by polyamidoamine dendrimer liposome) on hepatic cancer in nude mice. Hepatic cancer model was established by injecting SMMC-7721 cells subcutaneously into flanks of nude mice. Polyamidoamine dendrimer and liposome were mixed with survivin-asODN, respectively. The shape and size of complex were observed by transmission electron microscope, and zeta potential was measured by an analytical tool. Encapsulation efficiency and DNA loading level were determined by an ultraviolet spectrophotometer in centrifuging method. Expression of survivin in transplant tumor was measured by Western blotting. No significant difference appeared for diameter and envelopment ratio between PAMAM liposome-survivin-asODN and PAMAM-survivin-asODN (P?>?0.05). Both zeta potential and transfection efficiency in PAMAM liposome-survivin-asODN were higher than that in PAMAM-survivin-asODN complex (P?<?0.05). Expression of survivin protein and weight of tumors in transplanted tumors in PAMAM liposome-survivin-asODN group was less than that in PAMAM-survivin-asODN group (P?<?0.05). Cell apoptosis rate in PAMAM liposome-survivin-asODN group was higher than that of PAMAM-survivin-asODN group (P?<?0.05). In conclusion, polyamidoamine dendrimer liposome can deliver survivin-asODN into hepatic transplanted tumor cells effectively. Ployamidoamine dendrimer liposome-mediated survivin-asODN can inhibit hepatic cell proliferation by inducing apoptosis.     

Changes in T lymphocyte subsets in mice with CT26 colon tumors after treatment with donor lymphocyte infusion

The objective of this study was to detect changes in T lymphocyte subpopulations in mice with CT26 subcutaneous colon cancer after treatment with donor lymphocyte infusion (DLI) and cyclophosphamide (CP) chemotherapy. A colon cancer model was established by subcutaneous injection of CT26 carcinoma cells into BALB/C mice. The mice were randomized into different treatment groups. We recorded survival times, tumor growth inhibition rates, histopathological changes, and T lymphocyte subsets in peripheral blood of the mice. Mice treated with DLI and CP survived 33.5?±?5.02 days, which was significantly longer than the survival time of untreated control mice (16.7?±?2.98 days, P?<?0.01). In addition, the tumor inhibitory rate was higher in mice treated with DLI and CP (89.3 %) than that in mice treated with CP or DLI alone (67.1 and 34.5 %, respectively). There were higher levels of T lymphocytes that were CD3⁺ and CD4⁺ in mice treated with DLI alone or the combination of CP and DLI (P?<?0.05), and the ratio of CD4⁺/CD8⁺ cells was significantly improved in these mice (P?<?0.05). DLI combined with chemotherapy significantly prolonged survival and inhibited tumor growth in mice with CT26 colon cancer. This treatment might also improve immune function in these mice. Donor spleen cells that include high numbers of allogeneic lymphocytes and a few stem cells could induce a graft-versus-tumor effect, leading to elimination of residual cancer cells. This indicates that it is potentially a feasible adoptive cellular immunotherapy strategy for the management of solid tumors.     

Plasma Levels of Phospholipase A2-IIA in Patients with Different Types of Malignancies: Prognosis and Association with Inflammatory and Coagulation Biomarkers

It is well-known that the plasma level of group IIA phospholipase A₂ (sPLA₂-IIA) is increased in patients with malignant diseases, but whether the up-regulated enzyme expression is directly related to tumorigenesis or a consequence of tumor-associated inflammation remains unresolved. In this study we analyzed circulating levels of sPLA₂-IIA, C-reactive protein (CRP), fibrinogen, factor VIII (FVIII), von Willebrand factor (vWF), and antithrombin as biomarkers of inflammation and coagulation in patients with various types of malignancies. Underlying tumor entities were lung, esophageal, gastric, pancreatic, colorectal, head and neck, and hepatocellular carcinomas as well as multiple myeloma and non-Hodgkin’s lymphoma. Plasma levels of sPLA₂-IIA are shown to be markedly increased in all types of analysed malignancies in comparison to the normal range (22.8?±?4.5 μg/L versus <1.9 μg/L). Levels of sPLA₂-IIA correlate positively with CRP (p?<?0.001), fibrinogen (p?<?0.01), FVIII (p?<?0.05), and vWF (p?<?0.05) and negatively with antithrombin levels (p?<?0.05). Kaplan-Meier analyses revealed a statistically prolonged survival time of patients with lower sPLA₂-IIA concentrations (<4 μg/L) in comparison to those with elevated concentrations (>4 μg/L) of this enzyme. In conclusion, the study shows that the measurement of plasma sPLA₂-IIA levels has prognostic values in patients with different types of malignancies. The association of sPLA₂-IIA levels with CRP, fibrinogen, FVIII, and vWF levels supports the importance of inflammatory processes for the up-regulation of sPLA₂-IIA during cancer progression.     

NOB1 in Non-small-cell Lung Cancer: Expression Profile and Clinical Significance

Nin one binding (NOB1) gene has been reported up-regulated in several types of cancer. The aim of this study was to investigate the expression profile of NOB1 in non-small-cell lung cancer (NSCLC) and assess the clinical significance. qRT-PCR was used in the detection of NOB1 mRNA expression both in NSCLC tissue and in adjacent normal lung tissue. Western blot analysis and immunohistochemistry were used in the detection of NOB1 protein expression. The clinicopathological implications of NOB1 were analyzed statistically. It was confirmed by RT-qPCR that expression of NOB1 mRNA in NSCLC cells was higher than in human lung cells (P?<?0.05), and NOB1 mRNA was also over-expressed in NSCLC tissue when compared with adjacent tissue and normal lung tissue (P?<?0.05). Western blot analysis showed that NOB1 protein was significant increased in NSCLC cell lines compared with human lung cell line. Western blot analysis and immunohistochemistry showed that NOB1 protein was significant increased in NSCLC tissue compared with adjacent tissue and normal lung tissue (P?<?0.05). There were significant associations between NOB1 expression and TNM stage, lymph node metastasis, and histopathological grade (P?<?0.05), but not gender, age, smoke, or tumor diameter (P?>?0.05). Our results suggest that enhanced expression of NOB1 gene plays an important role in the occurrence and development of NSCLC. NOB1 may be a potential therapeutic target in NSCLC.