Overexpression of Interferon-Inducible Protein 16 Promotes Progression of Human Pancreatic Adenocarcinoma Through Interleukin-1ß-Induced Tumor-Associated Macrophage Infiltration in the Tumor Microenvironment.

Activation of inflammasomes has been reported in human pancreatic adenocarcinoma (PAAD); however, the expression pattern and functional role of inflammasome-related proteins in PAAD have yet to be identified. In this study, we systemically examined the expression and role of different inflammasome proteins by retrieving human expression data. Several genes were found to be differentially expressed; however, only interferon-inducible protein 16 (IFI16) expression was found to be adversely correlated with the overall survival of PAAD patients. Overexpression of IFI16 significantly promoted tumor growth, increased tumor size and weight in the experimental PAAD model of mice, and specifically increased the population of tumor-associated macrophages (TAMs) in the tumor microenvironment. Depletion of TAMs by injection of liposome clodronate attenuated the IFI16 overexpression-induced tumor growth in PAAD. In vitro treatment of conditioned medium from IFI16-overexpressing PAAD cells induced maturation, proliferation, and migration of bone marrow-derived monocytes, suggesting that IFI16 overexpression resulted in cytokine secretion that favored the TAM population. Further analysis suggested that IFI16 overexpression activated inflammasomes, thereby increasing the release of IL-1ß. Neutralization of IL-1ß attenuated TAM maturation, proliferation, and migration induced by the conditioned medium from IFI16-overexpressing PAAD cells. Additionally, knockdown of IFI16 could significantly potentiate gemcitabine treatment in PAAD, which may be associated with the reduced infiltration of TAMs in the tumor microenvironment. The findings of our study shed light on the role of IFI16 as a potential therapeutic target for PAAD.

Development and Validation of a Nomogram for Predicting Survival in Patients with Advanced Pancreatic Ductal Adenocarcinoma.

This study aimed to develop and validate an effective prognostic nomogram for advanced PDAC patients. We conducted a prospective multicenter cohort study involving 1,526 advanced PDAC patients from three participating hospitals in China between January 1, 2004 and December 31, 2013. Two thirds of the patients were randomly assigned to the training set (n = 1,017), and one third were assigned to the validation set (n = 509). Multivariate cox regression analysis was performed to identify significant prognostic factors for overall survival to develop the nomogram. Internal and external validation using C-index and calibration curve were conducted in the training set and validation set respectively. As results, seven independent prognostic factors were identified: age, tumor stage, tumor size, ALT (alanine aminotransferase), ALB (albumin), CA 19-9, HBV infection status, and these factors were entered into the nomogram. The proposed nomogram showed favorable discrimination and calibration both in the training set and validation set. The C-indexes of the training set and validation set were 0.720 and 0.696 respectively, which were both significantly higher than that of the staging system (C-index = 0.613, P < 0.001). In conclusion, the proposed nomogram may be served as an effective tool for prognostic evaluation of advanced PDAC.

Combined application of diclofenac and celecoxib with an opioid yields superior efficacy in metastatic bone cancer pain: a randomized controlled trial.

BACKGROUND: Metastatic bone cancer pain is one of the most common clinical cancer pains and is caused by many factors. This study was conducted to explore the clinical efficacy of using two non-steroidal anti-inflammatory drugs (NSAIDs) along with an opioid in treating metastatic bone cancer pain. MATERIAL AND METHOD: A total of 342 patients with a pain score of 7-10 on the visual analog scale (VAS) were recruited for 4 weeks of treatment and randomly assigned to three different groups-one group received two NSAIDs (diclofenac and celecoxib), one group received diclofenac, and one group received celecoxib. All patients received morphine sulfate 10 mg/12 h with a reduction of 50% or addition of 25% each time until the VAS score was <5. The VAS score, remission rate (RR), breakthrough pain (BTP), morphine sulfate dose and side-effects among the three groups were compared. RESULTS: After 4 weeks of treatment, we found that using two NSAIDs along with an opioid could yield a significantly lower VAS score (p = 0.006), higher RR (p = 0.0002) and fewer incidences of BTP (p = 0.011), compared to the use of only one NSAID. Furthermore, using two NSAIDS could significantly decrease the consumption of morphine sulfate compared to using each NSAID in isolation (p = 0.0031 in week 1; p = 0.020 in week 2; p = 0.0012 in week 4). Additionally, using two NSAIDs could produce fewer incidences of dizziness (p = 0.002), constipation (p < 0.0001) and drowsiness (p < 0.0001). CONCLUSION: Although limited by the relatively small samples, these results indicate that using two NSAIDs along with an opioid in treating metastatic bone cancer pain was more effective and acceptable, which is worthy of further clinical application.

Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efficacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted. OBJECTIVE: This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC. SEARCH STRATEGY: PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013. INCLUSION CRITERIA: We selected randomized controlled trials based on specific criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC. DATA EXTRACTION AND ANALYSIS: The modified Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status (KPS), and severe toxicity. RevMan 5.0 software was used for data syntheses and analyses. Risk ratio (RR) and 95% confidence interval (CI) were calculated; if the hypothesis of homogeneity was not rejected (P>0.1, I(2)<50%), the fixed-effect model was used to calculate the summary RR and the 95% CI. Otherwise, a random-effect model was used. RESULTS: In this review, 19 studies were included based on the selection criteria. Of them, 13 studies were of high quality and 6 studies were of low quality, according to the modified Jadad scale. When the TCMH plus EGFR-TKI treatment groups were compared with the EGFR-TKI control groups the meta-analysis demonstrated a statistically significant higher ORR (RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2), DCR (RR 1.18; 95% CI 1.09 to 1.27; P<0.000 1), one-year survival rate (RR 1.21; 95% CI 1.01 to 1.44; P=0.04), 2-year survival rate (RR 1.91; 95% CI 1.26 to 2.89; P=0.002) and improved or stable KPS (RR 1.38; 95% CI 1.26 to 1.51; P<0.000 01). Severe toxicity for rash was decreased (RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as were nausea and vomiting (RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea (RR 0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that findings of the meta-analysis were robust to study quality. In the funnel plot analysis, asymmetry was observed, and publication bias was indicated by Egger's test (P=0.03). CONCLUSION: TCMH intervention can increase efficacy and reduce toxicity when combined with EGFR-TKI for advanced NSCLC, although this result requires further verification by more well designed studies.

[Xuefu zhuyu oral liquid intervened stress-stimulated depression model rats].

OBJECTIVE: To observe effects of xuefu zhuyu Oral Liquid (XZOL) on the brain behavior and monoamine neurotransmitter 5-HT, and brain derived neurotrophic factor (BDNF) content on depression model rats. METHODS: Male SD rats were randomly divided into the control group, the model group, the XZOL group, and the Deanxit Tablet group, 12 in each group. The depressive rat model was established by chronic unpredictable mild stress method. XZOL was administered to rats in the XZOL group by gastro-gavage, while Deanxit Tablet was given to those in the Deanxit Tablet group by gastrogavage. The intervention lasted for two weeks. The behavioral changes were observed by sucrose water consumption test and open-field test. The 5-HT and BDNF contents were detected using ELISA. RESULTS: After chronic stress stimulus, experimental rats in the model group might have abnormal behavioral changes and lowered 5-HT content, showing statistical difference when compared with the control group (P <0.01). No obvious change in stimulated rats' behavior after intervention of XZOL and Deanxit Tablet. 5-HT content was not obviously reduced (P>0.05). Besides, XZOL was superior to Deanxit Tablet in increasing the 5-HT content (P<0.05). But the brain BDNF level of rats in the model group was not statistically different from that of rats in the model group (P >0.05), while the brain BDNF level of rats in the XZOL group and the Deanxit Tablet group was lower than that of rats in the model group (P <0.01). CONCLUSIONS: Stress can lead to behavioral changes and lowered 5-HT content of rats. The intervention of XZOL could fight against depression-induced behavioral changes and increase 5-HT content. But it did not significantly affect the brain BDNF level. We inferred that it might not effect through the BDNF pathway.

[Effects of qisheng mixture on chemotherapy induced myelosuppression in patients with colorectal cancer].

OBJECTIVE: To observe the intervention of Qisheng Mixture (QM) on the chemotherapy induced myelosuppression in patients with colorectal cancer. METHODS: One hundred and twenty patients with colorectal cancer at Ruijin Hospital, Shanghai Jiaotong University School of Medicine were randomly assigned to the pure chemotherapy group (as the control group) and the QM + chemotherapy group (as the treatment group), 60 in each group. All patients received FOLFOX4 or XELOX regimen for totally 6 cycles. Patients in the treatment group took QM 150 mL at the end of chemotherapy, once in the morning and once in the evening for 7 successive days, totally 6 therapeutic courses. The total and average dosages of using granulocyte colony stimulating factor (G-CSF) were observed in all patients. The changes of white blood cell (WBC) counts were determined before chemotherapy and after the 6th chemotherapy. The hemoglobin (Hb), red blood cell (RBC), and platelet (PLT) counts were observed before chemotherapy, before the 4th chemotheray, and after the 6th chemotherapy. The clinical symptoms integrals (fatigue, liability to catch cold, aphthous stomatitis, pharyngalgia, pale complexion, poor appetite, vomiting, diarrhea, and so on) and the safety indicators (the functions of the liver and kidney, urine routines) were observed. The grading toxic and adverse reactions, KPS scoring, body weight, and the efficacy of the symptoms integrals were compared between the two groups. RESULTS: During the treatment period the total and average dosages of G-CSF used were larger in the control group than in the treatment group (P<0.01). After treatment the WBC count of the two groups were reduced with statistical difference (P<0.01). The WBC counts were higher in the treatment group than in the control group in the whole therapeutic process except the first chemotherapy (P<0.01, P<0.05). Compared with before treatment in the same group, RBC and PLT were reduced in the two groups before the 4th chemotherapy, RBC, Hb, and PLT were reduced after treatment (P<0.05, P<0.01). Better effects on body weight were obtained in the treatment group than in the control group with statistical difference (P<0.01). Compared with the control group, the clinical symptoms integrals such as fatigue, liability to catch cold, pharyngalgia, pale complexion, poor appetite, vomiting, and diarrhea were reduced (P<0.01). Compared with the control group, the toxic and adverse reactions were reduced in the treatment group before the 4th chemotherapy (P<0.01). CONCLUSIONS: QM could effectively intervene chemotherapy induced myelosuppression in patients with colorectal cancer. It was a safe Chinese medicine compound with lower toxicity.

[Dishen Qufeng Decoction for treating allergic rhinitis: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effects of Dishen Qufeng Decoction (DSQFD), a compound traditional Chinese herbal medicine, in treatment of allergic rhinitis. METHODS: Sixty cases of allergic rhinitis were selected and randomized into DSQFD group (30 cases) and cetirizine group (30 cases), and the patients were orally administered DSQFD and cetirizine respectively. The integrals of patients' symptoms, such as sneezing, nose running, nasal occlusion and nasal itching, signs in the nasal conchae and peripheral blood eosinophil (EOS) count were abserved count before and after treatment. RESULTS: DSQFD obviously improved the symptoms and signs of allergic rhinitis. The total response rate of DSQFD treatment was 83.3%, while that of the cetirizine treatment was 86.7%; the EOS counts in both groups were significantly decreased. These results showed statistical difference between the two groups. CONCLUSION: DSQFD is an effective preparation of traditional Chinese medicine for treating allergic rhinitis.

[Effects of serum containing Yiqi Xiaoji Recipe on cell line NKN-28 of gastric cancer].

OBJECTIVE: To explore the effects of serum containing Yiqi Xiaoji Recipe (YQXJR), a compound traditional Chinese herbal medicine for benefiting qi and removing stagnation, on cell line NKN-28 of gastric cancer. METHODS: The experimental SD rats were taken as the provider of the animal serum, and the serum was inactivated before the experiment. The serum was divided into high-dose, medium-dose, low-dose and blank serum groups based on whether the rats were given YQXJR and administration dosage. The inhibition rate was regarded as the observational index. RESULTS: The four groups of serum all had inhibitory effect on the growth of NKN-28 cells depending on the drug concentration. And there were significant differences among the experimental groups. High-dose, medium-dose and low-dose concentrations of serum all could inhibit the growth of NKN-28 cells with positive relations with the concentration and function time. CONCLUSION: YQXJR serum can inhibit the growth of NKN-28 cells depending on the drug concentration and function time.

[Clinical research of intraperitoneal chemotherapy plus Shenmai Injection in treating advanced colorectal cancer].

OBJECTIVE: To study the effects of intraperitoneal chemotherapy (IPC) plus Shenmai Injection (SMI) in treating advanced colorectal cancer following radical resections. METHODS: Fifty-eight cases of colorectal cancer in stage B2 and C following radical resections were divided into two groups: SMI+IPC group (36 cases) and IPC group (22 cases). In the SMI+IPC group, IPC (5-fluorouracil combined with cisplatin) plus SMI was administered, while in the IPC group, only IPC was administered. Clinical symptoms, quality of life (Karnofsky score), white blood cell counts, natural killer cells and CD4/CD8 were observed, and disease-free survival (DFS) rate was also evaluated. RESULTS: The total short-term response rate was 83.33% in the SMI+IPC group, significantly higher than 63.64% in the IPC group (P<0.05). The data of clinical symptoms, quality of life, white blood cell counts, natural killer cells and CD4/CD8 in the SMI+IPC group were also significantly improved as compared with those in the IPC group (P<0.05 or P<0.01). In the SMI+IPC group, 1-, 3- and 5-year DFS rates were 91.7% (33/36), 77.8% (28/36) and 72.2% (26/36) respectively, and those in the IPC group were 90.9% (20/22), 72.7% (16/22) and 45.5% (10/22) respectively. The 5-year DFS rate was significantly improved in the SMI+IPC group as compared with that in the IPC group (P<0.05), while the 1-year and 3-year DFS rates had no significant difference between these two groups. CONCLUSION: IPC plus SMI is effective in treating post-operative patients with advanced colorectal cancer.

[Effect of Baisuifang Granule on cognitive malfunction after cerebral infarction].

OBJECTIVE: To explore the mechanism of Baisuifang Granule in treating cognitive malfunction after cerebral infarction. METHODS: One hundred and sixty patients with cerebral infarction were divided randomly into two groups. Eighty patients were treated with Baisuifang Granule and 80 with nimodipine for two months. Clinical observation and laboratory examinations were performed for Mini-Mental State Examination (MMSE), clinical symptoms, Chinese Stroke Scale (CSS), hemorrheological indexes and fibrinogen before and after the treatment. RESULTS: Baisuifang Granule could improve MMSE, reduce the scores of clinical symptoms and CSS, and meliorate the blood rheology. The total effective rate for clinical symptoms in the Baisuifang treated group accounted to 76.25%, with statistical difference comparing to 58.75% of nimodipine treated group (P<0.05). There was significant difference in symptom integral, CSS and whole blood viscosity at the high shear rate, respectively (P<0.01). CONCLUSION: Baisuifang Granule is an effective Chinese medicine for treating cognitive malfunction after cerebral infarction.