Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Prognostic performance of pre-treatment NLR and PLR in patients suffering from osteosarcoma.

BACKGROUND: Inflammatory response markers have been proposed to predict the clinical outcomes in various cancers. The aim of this study was to explore the influence of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of osteosarcoma. METHODS: Three hundred fifty-nine patients who underwent curative surgery for osteosarcoma were enrolled from 2005 to 2010. NLR and PLR were calculated from peripheral blood cell counts taken at pre-treatment. Optimal cutoff values of NLR and PLR were determined on the basis of receiver operating characteristic curve analysis. A predictive model was established to predict the clinical outcome for overall survival, and the predictive accuracy of this model was determined by concordance index (c-index). RESULTS: Our results showed that advanced stage and metastasis at diagnosis were significantly associated with the high NLR and PLR groups. NLR was an independent prognostic indicator for overall survival (HR = 1.80, 95% CI = 1.35-2.41, P < 0.001) and progression-free survival (HR = 1.65, 95% CI = 1.26-2.15, P < 0.001), except for PLR. The nomogram could perform well in the prediction of overall survival in patients with osteosarcoma (c-index 0.829). CONCLUSIONS: Our results suggest that both NLR and PLR can reflect clinical prognosis. NLR is more predictive of overall survival and progression-free survival than PLR.

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer.

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

Meat consumption is associated with esophageal cancer risk in a meat- and cancer-histological-type dependent manner.

BACKGROUND: We conducted a systematic review and meta-analysis of meat intake and esophageal cancer risk, with subgroup analyses based on meat type and histological type of cancer. AIMS: The purpose of this study was to investigate the association between meat intake and risk of esophageal cancer. METHODS: We searched MEDLINE, EMBASE and Cochrane Library (April 2013) for cohort and case-control studies that assessed meat intake and esophageal cancer risk. Random-effect or fixed-effect models were used to pool relative risks (RRs) from individual studies with heterogeneity and publication bias analyses carried out. Seven cohort and 28 case-control studies were included. RESULTS: The summary RRs for esophageal cancer for the highest versus lowest consumption categories were 1.19 (95 % confidence interval [CI] 0.98-1.46) for total meat, 1.55 (95 % CI 1.22-1.96) for red meat, 1.33 (95 % CI 1.04-1.69) for processed meat, 0.72 (95 % CI 0.60-0.86) for white meat, 0.83 (95 % CI 0.72-0.96) for poultry, and 0.95 (95 % CI 0.76-1.19) for fish. When striated by histological subtype, positive associations were seen among esophageal squamous cell carcinoma and red meat, white meat and poultry, and esophageal adenocarcinoma with total meat and processed meat. CONCLUSIONS: Meat consumption is associated with esophageal cancer risk, which depends on meat type and histological type of esophageal cancer. High intake of red meat and low intake of poultry are associated with an increased risk of esophageal squamous cell carcinoma. High meat intake, especially processed meat, is likely to increase esophageal adenocarcinoma risk. And fish consumption may not be associated with incidence of esophageal cancer.

[Efficacy and safety of rh-endostatin combined with docetaxel in second-line or intolerant toxicity for first-line treatment in patients with advanced non-small cell lung cancer].

OBJECTIVE: To analyze the efficacy and safety of combination of rh-endostatin (Endostar) with docetaxel treatment on patients of non-small cell lung cancer (NSCLC) who presented PD or intolerable toxicity in/after first-line chemotherapy. METHODS: A randomized, double-blind, placebo-controlled and multi-center clinical trial was conducted. Patients with stage IIIB/IV of NSCLC experienced previous chemotherapy of one-regimen were screened for this trial. A total of 68 cases were included in this study. Single docetaxel and that combined with endostar were conducted in two arms. The response, time to progression (TTP) and adverse effects were observed in both arms. RESULTS: The objective response rate (ORR) and clinical benefit rate (CBR) were 0 and 62.5% in the combined arm, along with 0 and 53.3% in the single docetaxel arm, with a non-significant difference between the two groups (all P > 0.05), respectively. The median TTPs in the combined and single docetaxel arms were 2.63 and 2.07 months, respectively (P = 0.079). The median TTPs of the participants with progressive disease (PD) after first-line chemotherapy were 1.33 and 1.67 months in the combined and single docetaxel arms, respectively (P = 0.946). The median TTPs of the participants with intolerant adverse effects in first-line chemotherapy were 4.70 months and 3.17 months in the combined and single docetaxel arms, respectively (P = 0.070). The median TTPs of the patients with SD after 2 therapeutic cycles in the combined and single docetaxel arms were 6.23 months and 3.27 months, respectively (P = 0.040). The differences between two arms were non-significant in adverse, serious adverse and cardiovascular adverse effects (all P > 0.05). CONCLUSIONS: Endostar may prolong TTP in patients with advanced NSCLC benefited from docetaxel treatment without increased toxicities.

[Ulinastatin's early effects on kidney's expression of HSP70 and IL-6 after mechanical injury of kidney].

OBJECTIVE: To investigate the significance of ulinastatin's effects on kidney's expression of IL-6, HSP70 after mechanical injury. METHODS: Sixity-six adult female Wistar rats were randomly divided into three groups: 6 in the group of control, 30 in the group of trauma, 30 in the group injected ulinastatin after trauma. The model of trauma rats was made with free-fall bio-impactor striking the spinal column and ribs of rats. To detect the IL-6 and HSP70 expression of each group's renal tissue at 1 h, 6 h, 12 h, 24 h and 36 h after trauma with tissue chip and immunohistochemical stain. RESULTS: IL-6 and HSP70 expression of renal tissue was low with group of control. Compared with group of control, the expression of IL-6 strengthened at 1 h, 6 h, 12 h, 24 h after trauma (P < 0.05),the expression of HSP70 with group of trauma strengthened at 6 h after trauma (P < 0. 05). The expression of IL-6 with group injected ulinastatin after trauma were more lower than group of trauma, the expression of HSP70 at 1 h, 24 h, 36 h after trauma was higher than group of trauma especially at 1 h (P< 0.05). CONCLUSION: Ulinastatin can reduce the risk of renal injury in early times after trauma especially at 1 h. The protective effects of ulinastatin may be associated with the restrict the expression of IL-6, up-regulation of HSP70 expression, and change the proportion between IL-6 and HSP70 expression.

The anxiolytic-like effects of ginsenoside Rg3 on chronic unpredictable stress in rats.

The present study is to evaluate the anxiolytic-like activities underlying ginsenoside Rg3 (GRg3). The anxiolytic-like activities were induced by GRg3 (20 and 40 mg/kg, i.g), evidenced by blocking the decreased time and entries in the open arms in elevated plus maze test and by reversing the increased latency to feed in novelty-suppressed feeding test. In addition, the decreased levels on progesterone, allopregnanolone, serotonin (5-HT) in the prefrontal cortex and hippocampus of chronic unpredictable stress (CUS) were blocked by GRg3 (20 and 40 mg/kg, i.g). Furthermore, the increased corticotropin releasing hormone, corticosterone and adrenocorticotropic hormone were blocked by GRg3 (20 and 40 mg/kg, i.g). Collectively, the anxiolytic-like effects produced by GRg3 were associated with the normalization of neurosteroids biosynthesis, serotonergic system as well as HPA axis dysfunction.

The anxiolytic-like effects of estazolam on a PTSD animal model.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder. Estazolam has been shown to produce anxiolytic-, hypnotic-, amnestic-, and sedative-like effects. However, few studies are concerned about its anti-PTSD-like effects. The anti-PTSD-like effects of estazolam were evaluated by single prolonged stress animal model. After exposure to single prolonged stress, rats (Sprague-Dawley, male, 8 weeks) were administered by estazolam (0.5, 1 and 2 mg/kg, i.p.) from day 2 to 13 once daily. The behavioral assessments were performed during treatment with drugs. After the behavioral evaluation, the role of allopregnanolone in the anti-PTSD-like effects of estazolam was also evaluated via astrocyte cells and brain tissues (e.g. prefrontal cortex, hippocampus, and amygdala). The PTSD-like behavioral deficits were significantly blocked by estazolam (1 and 2 mg/kg, i.p.) without affecting locomotor activity. Consistently, the levels on allopregnanolone were increased by estazolam (1 and 2 mg/kg, i.p.) in prefrontal cortex, hippocampus, and amygdala. The levels of allopregnanolone were increased by sertraline (1 µmoL/L) and estazolam (4 µmoL/L), while the effects were antagonized by trilostane (1 µmoL/L) and finasteride (1 µmoL/L) in astrocyte cells, respectively. Collectively, the anxiety-like behavior deficits were ameliorated by estazolam in the single prolonged stress animal model that was associated with biosynthesis of allopregnanolone.

Long noncoding RNA LINC00961 inhibits cell invasion and metastasis in human non-small cell lung cancer.

Long noncoding RNAs (LncRNAs) expression has been found to be misregulated in multiple human cancers, and a growing number of studies have revealed that lncRNAs can function as important oncogenes or tumor suppressors. In this study, we identified a lncRNA-LINC00961, which was significantly down-regulated in human non-small cell lung cancer tissues. Decreased LINC00961 was associated with NSCLC patients advanced clinical stage, lymph node metastasis, and shorter survival time. Further experiments demonstrated that LSD1 could directly bind to LINC00961 promoter regions and epigenetically repress its transcription in NSCLC cells. Moreover, MTT assays showed that LINC00961 had no influence on NSCLC cell proliferation. Ectopic overexpression of LINC00961 inhibits NSCLC cell migration, invasion in vitro and metastasis in vivo. Finally, qRT-PCR and western blot assays revealed that LINC00961 could act as a tumor suppressor partially via affecting ß-catenin expression. Collectively, decreased LINC00961 might play a key role in NSCLC progression, and may serve as a novel prognostic marker in human NSCLC.

Prognostic significance of lymphocyte-to-monocyte ratio in diffuse large B-cell lymphoma: a systematic review and meta-analysis.

Published evidence on the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in diffuse large B-cell lymphoma (DLBCL) is controversial. We performed an updated meta-analysis from 12 reports with 5021 patients to more accurately evaluate the prognostic value of LMR in DLBCL. Herein, we confirmed that patients with low LMR had shorter overall survival and progression-free survival than those with high LMR in DLBCL. Subgroup analyses indicated that patient source, cut-off values of LMR, treatment methods, and sample size showed similar prognostic performance in DLBCL patients. No significant heterogeneity was observed for progression-free survival (PFS, P (het) = 0.192) among the enrolled studies. The meta-analysis suggests that the LMR may be a potential biomarker in the prediction of clinical outcomes for DLBCL patients.

Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients.

Long noncoding RNAs have been documented as having widespread roles in carcinogenesis and cancer progression. However, roles of long noncoding RNAs in osteosarcoma remain unclear. This study is to investigate the clinical relevance and biological functions of long noncoding RNA 91H in osteosarcoma. Herein, we confirmed that 91H expression was notably increased in osteosarcoma patients and cell lines compared to healthy controls and normal human bone cell lines. High expression of 91H was significantly correlated with advanced clinical stage, chemotherapy after surgery, and tumor size >5 cm. Furthermore, 91H was an independent prognostic factor for overall survival in osteosarcoma patients after treatments. Additionally, the knockdown of 91H expression inhibited osteosarcoma cells' proliferation and promoted their apoptosis in vitro. In summary, these findings indicate that 91H may be a novel biomarker for risk prognostication and also provide a clue to the molecular etiology of osteosarcoma.

The effects of PK11195 on the MCF-7 and T47D were associated with the allopregnanolone biosynthesis, which was mediated by Translocator Protein 18 KDa.

Breast cancer is currently the most common malignancy affecting women worldwide. It had been shown that the allopregnanolone biosynthesis was associated with tumorigenesis and PK11195, the Translocator Protein 18 KDa (TSPO) antagonist, had the effects of the allopregnanolone biosynthesis. However, little is known about the association between the effects of PK11195 on the breast cancer and the allopregnanolone biosynthesis. To evaluate this, the breast cancer cell lines MCF-7 and T47D were cultured. Cell viability and proliferation were determined by CCK-8 assay. The IC50 of PK11195 on the MCF-7 and T47D were 5.4 nM and 6 nM. The cell viability and proliferation of AC-5216 (TSPO selective ligand, 3 and 6 nM) was blocked by PK11195 (5.4 nM and 6 nM). Moreover, we evaluated the role of allopregnanolone biosynthesis in the effects of TSPO on breast cancer. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the allopregnanolone level. We found that the allopregnanolone level was increased by AC-5216 (3 and 6 nM) and the increase was reversed by PK11195 (5.4 nM and 6 nM, resepectively) in MCF-7 and T47D. The TSPO mRNA level was determined by real time polymerase chain reaction (PCR). The TSPO mRNA level were increased by AC-5216 (6 nM), which the increases were reversed by PK11195 (5.4 nM and 6 nM, resepectively) in MCF-7 and T47D. Collectedly, it firstly indicated that the effects of PK11195 on MCF-7 and T47D were associated with the decrease of allopregnanolone biosynthesis, which was mediated by TSPO.

Efficacy of adoptive cellular therapy in patients with gastric cancer: a meta-analysis.

AIM: To systemically evaluate the efficacy and safety of adoptive cellular therapy for the treatment of gastric cancer (GC). MATERIALS & METHODS: We performed a systemic review and meta-analysis of nine eligible trials with GC and evaluated the effect of adoptive cellular therapy on the overall survival (OS) rate, T-cell subsets and adverse events. RESULTS: Overall, 829 patients were involved in the analysis. Adoptive cellular therapy significantly improved the OS rate compared with the control group. Meanwhile, we observed greatly increased percentages of CD3(+), CD4(+) and CD4(+)/CD8(+) in cellular therapy groups. CONCLUSION: Adoptive cellular therapy combined with adjuvant therapy resulted in significantly better OS rates, progression-free survival and T-lymphocyte responses in patients with GC.

The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha.

The aim of this article was to investigate the effect of ambroxol on radiation lung injury and the expression of transforming growth factor beta(1) (TGF-beta(1)), as well as tumor necrosis factor alpha (TNF-alpha) in plasma. Totally, 120 patients with locally advanced lung cancer in radiotherapy were randomized into treatment and control groups. Patients in the treatment group took ambroxol orally at a dosage of 90 mg, three times per day for 3 months from the beginning of radiotherapy. The expression of TGF-beta(1) and TNF-alpha in plasma was analyzed. The clinical symptoms and lung diffusing capacity were monitored using high resolving power computed tomography. The level of TGF-beta(1) in the control group was increased (11.8 +/- 5.5 ng/ml), whereas in ambroxol-treated patients, the increase was not significant (5.6 +/- 2.6 ng/ml, P < 0.001). Radiotherapy-induced elevation of TNF-alpha levels, seen in control patients, was also abolished after treatment with ambroxol (5.1 +/- 1.0 vs. 2.4 +/- 0.8 ng/ml, P < 0.001). In the treatment group, carbon monoxide diffusion capacity was not significantly decreased at 6, 12, and 18 months post-radiotherapy, compared with the control group (P < 0.05). Ambroxol decreased the expression of TGF-beta(1) and TNF-alpha, and minimized the diminishment of lung diffusion capacity after radiotherapy.