High Systemic Immune-Inflammation Index (SII) Represents an Unfavorable Prognostic Factor for Small Cell Lung Cancer Treated with Etoposide and Platinum-Based Chemotherapy.

PURPOSE: Systemic immune-inflammation index (SII) has been demonstrated to be closely associated with prognosis of a series of solid tumors. However, its role in small cell lung cancer (SCLC) remains poorly understood. The present study aims to evaluate the prognostic significance of pretreatment SII in SCLC treated with etoposide and platinum-based chemotherapy. METHODS: Sixty hundred and fifty-three newly diagnosed SCLC patients were enrolled. The optimal cut-off values for SII and LDH (lactate dehydrogenase) were obtained by a receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed by univariate and multivariate analyses. RESULTS: The optimal cut-off values of pretreatment SII and LDH were 748.51 × 109/L and 188.5 U/L, respectively. High pretreatment SII was significantly associated with advanced tumor stage (limited disease, LD vs. extensive disease, ED; 26.3% vs 46.5%; p < 0.001). On univariate analysis, age < 65 years, female, non-smoker, limited disease, SII < 748.51 × 109/L, LDH < 188.5 U/L, distant metastasis numbers < 2, chemotherapy + radiotherapy, and chemotherapy + surgery were closely correlated with a prolonged OS (p < 0.05). The median OS for patients in high SII group was 12.0 months, compared with that of 17.0 months for patients in low SII group. Multivariate analysis showed smoking history (p = 0.014), tumor stage (p < 0.001), pretreatment SII (p < 0.001), LDH (p = 0.002), distant metastasis numbers (p = 0.006), and chemotherapy + radiotherapy (p < 0.001) were independent prognostic factors of OS. Furthermore, SII remained prognostic significance for SCLC stratified by variable subgroups analysis. CONCLUSION: Pretreatment SII represents a powerful prognostic biomarker for SCLC patients treated with etoposide and platinum-based chemotherapy. It is significant for treatment strategy making in clinics.

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line.

BACKGROUND/AIMS: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. METHODS: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. RESULTS: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. CONCLUSION: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.

Advances in malignant peritoneal mesothelioma.

BACKGROUND: Malignant mesothelioma is a rare, insidious, and aggressive tumor arising from the mesothelial surface of pleural and peritoneal cavities, the pericardium, or the tunica vaginalis, with an increasing incidence worldwide, high misdiagnosis rate, and overall negative prognosis. A total of 20% of all cases is peritoneum in origin. METHODS: The present study is a review of literatures focusing on the advances in epidemiology, clinical presentations, radiological features, diagnosis, misdiagnosis, management, and prognostic factors of malignant peritoneal mesothelioma (MPM) occurred in the past decades. RESULTS: Asbestos, SV40, and radiation exposures have been demonstrated to be correlated with the pathogenesis of MPM. The main presentations are abdominal distension and pain. Computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) play an important role in the preoperative imaging and staging. Definitive diagnosis is made on the basis of immunohistochemistry. Prognostic factors have been identified and verified. Negative indicators include advanced age, male gender, poor performance status, non-epithelial histology, and absence of surgery. The management of MPM has evolved from single chemotherapy to multimodality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy, radiotherapy, and immunotherapy. Promising results have been achieved after a combined treatment of CRS and HIPEC, with an elevated median survival time of 29.5-92 months and a 5-year survival rate of 39-63%. CONCLUSIONS: CRS and HIPEC represent the standard treatment strategy for selected patients with MPM, and patients with unresectable tumors can benefit from the combined treatment of chemotherapy, radiotherapy, and immunotherapy.

MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes.

Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3'-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy.

The combination of pretreatment prognostic nutritional index and neuron-specific enolase enhances prognosis predicting value of small cell lung cancer.

INTRODUCTION: Tumor and immune-inflammatory biomarkers have been demonstrated to be closely associated with cancer prognosis. OBJECTIVE: The present study aims to assess the prognostic value of pretreatment prognostic nutritional index (PNI), carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) in small cell lung cancer (SCLC). METHODS: A retrospective analysis of 301 SCLC patients treated with platinum-based chemotherapy was performed. Overall survival (OS) was assessed by Kaplan-Meier and multivariate Cox hazard analyses. RESULTS: The median OS for total cases was 15.0 months. On univariate analysis, tumor stage (P < 0.001), pretreatment PNI (P < 0.001), CEA (P = 0.039), NSE (P = 0.010), distant metastasis numbers (P < 0.001), and thoracic radiotherapy (P < 0.001) were found to be the predictors of OS. Multivariate analysis showed limited stage, high PNI, NSE < 15 µg/L, and chemoradiotherapy were positive independent prognostic factors (P < 0.05). Low PNI and NSE ≥ 15 µg/L were closely correlated with a high tumor burden status. Three cohorts of SCLC with significant different survival outcomes were divided based on variable PNI and NSE levels. Patients with high PNI and NSE < 15 µg/L showed the best OS of 24.5 months, while patients with low PNI and NSE ≥ 15 µg/L had the worst survival outcome of 10.0 months. Patients with low PNI and NSE < 15 µg/L or high PNI and NSE ≥ 15 µg/L had the similar outcome of 16.5 and 17.0 months, respectively. CONCLUSIONS: Pretreatment PNI and NSE were independent prognostic factors of SCLC. The combination of PNI and NSE enhanced the OS predicting ability, and patients with high PNI and NSE < 15 µg/L had the best survival outcome.

High systemic immune-inflammation index is a predictor of poor prognosis in patients with nonsmall cell lung cancer and bone metastasis.

Aim: This study aimed to evaluate whether systemic immune inflammation (SII) is correlated with overall survival (OS) in patients with nonsmall cell lung cancer (NSCLC) and bone metastasis. Settings and Design: This was a retrospective analysis of the value of pretreatment SII in patients with NSCLC and bone metastasis. Subjects and Methods: Two hundred and thirty-four patients with pathologically confirmed NSCLC and bone metastasis treated at Harbin between January 2008 and May 2010 were included. Baseline clinical characteristics and pretreatment SII were collected for further analysis. Statistical Analysis Used: Receiver operating characteristic curve analysis was used to calculate the optimal cutoff value for SII. Survival analysis was performed using the Kaplan-Meier method. Factors associated with OS were identified by univariate and multivariate analyses. Results: The optimal cutoff value for pretreatment SII was 618.3 × 109/L. Pretreatment SII ≥618.3 × 109/L was more commonly seen in patients with a greater number of distant metastases (<2 vs. ≥2, 56.4% vs. 70.0%, P = 0.033). Univariate analysis showed that sex, tumor histology, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score, pretreatment SII, and systemic chemotherapy were associated with OS (P < 0.05). Multivariate analysis showed that sex (hazard ratio [HR] = 1.349, 95% confidence interval [CI] = 1.029-1.708, P = 0.030), ECOG-PS (HR = 1.674, 95% CI = 1.256-2.232, P < 0.001), SII (HR = 1.456, 95% CI = 1.100-1.927, P = 0.009), and systemic chemotherapy (HR = 0.596, 95% CI = 0.437-0.813, P = 0.001) were independent prognostic factors. Subgroup analyses found that SII was prognostic for patients with the following characteristics: age <65 years (P = 0.002), female (P = 0.021), nonsmoker (P = 0.010), histology of adenocarcinoma (P = 0.022), ECOG-PS <2 (P = 0.013), two or more distant metastases (P = 0.004), and two or more bone metastases (P = 0.009). Conclusions: Pretreatment SII may be a prognostic biomarker for NSCLC and bone metastasis.

Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome.

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis. Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression. Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p < 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p < 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p < 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5-2.7, p < 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9-1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4-2.7, p < 0.001). Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.

High prognostic nutritional index (PNI) as a positive prognostic indicator for non-small cell lung cancer patients with bone metastasis.

INTRODUCTION: Increasing evidence shows the close association between prognostic nutritional index (PNI) and overall survival (OS) of solid cancers including lung cancer. However, the role of PNI in non-small cell lung cancer patients (NSCLC) with bone metastasis remains unclear. OBJECTIVE: To explore the prognostic role of PNI in NSCLC patients with bone metastasis. METHODS: A retrospective analysis of 259 initially diagnosed NSCLC with bone metastasis was conducted. Univariate and multivariate analysis were used to assess the potential prognostic roles of parameters. RESULTS: The most common symptoms initially presented were cough and chest pain. Two hundred patients (77.2%) received the treatment of bisphosphonates. Patients with low PNI were found in 154 (59.5%) patients. Median survival time for all cases was 286 days. The median OS for patients with low and high PNI was 227 and 389 days, respectively. The 6-month, 1-year and 2-year survival rates for patients with low PNI were 66.2%, 29.9% and 10.4% compared to 79.0%, 52.4% and 26.7% in patients with high PNI level. On univariate analysis, female patients, non-smokers, high PNI and systematic chemotherapy (P < 0.05) were shown to be closely correlated with a better prognosis of NSCLC patients with bone metastasis. Only PNI (P = 0.002), systematic chemotherapy (P = 0.026) and distant metastasis number (P = 0.044) held statistical significance on multivariate analysis. CONCLUSIONS: PNI represents a non-invasive, efficiency and convenient biomarker of NSCLC patients with bone metastasis. High PNI, systematic chemotherapy and distant metastasis number <2 are independent positive prognostic factors of NSCLC patients with bone metastasis.

Author Correction: Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical impact of pretreatment prognostic nutritional index (PNI) in small cell lung cancer patients treated with platinum-based chemotherapy.

INTRODUCTION: Numbers of prognostic factors of small cell lung cancer (SCLC) have been demonstrated in previous studies. However, the identification of biomarkers with easy access, convenience, and low consumption is of great value in clinics. OBJECTIVES: In order to find such a biomarker, a single institution study with 1156 SCLC patients was retrospectively conducted to assess the prognostic value of prognostic nutritional index (PNI) on SCLC patients treated with platinum-based chemotherapy. METHODS: The optimal cut-off values were determined by a receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to assess their prognostic values for overall survival (OS). RESULTS: On univariate analysis, age, smoking history, tumor stage, PNI, radiotherapy, and surgery were significantly associated with OS. Age, stage, PNI, radiotherapy, and surgery held statistical significance on multivariate analysis. High PNI was closely associated with younger age, limited disease, and radiotherapy. PNI was also demonstrated to be an independent prognostic factor in subgroups analysis, especially in patients with age ≤ 60, no smoking history, no family history of tumor, and no radiotherapy. CONCLUSIONS: Age ≤ 60 years, limited disease, high PNI, radiotherapy, and surgery were independent positive prognostic factors of SCLC patients treated with chemotherapy. PNI was a good biomarker for the assessment of SCLC prognosis for its easy access, convenience to be calculated, and low consumption. Pretreatment PNI can better predict the prognosis of SCLC, especially in patients with age ≤ 60, no smoking history, no family history of tumor, and no radiotherapy.

IL-17 induces macrophages to M2-like phenotype via NF-κB.

BACKGROUND: Tumor-associated macrophage (TAM) is emerging as one of the important complications in cancer promotion. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, plays an active role in promoting M2 macrophage differentiation (TAMs are M2-like phenotypes). In this study, we aimed to evaluate that IL-17 stimulates key phenotypic and functional signatures of M2 macrophages associated with cancer progression in non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: The markers and cytokines of M2 macrophages were detected in THP-1-derived macrophages and mouse peritoneal macrophages treated with IL-17. The activation of nuclear factor kappa B (NF-κB) and nuclear localization of p65 in IL-17-treated cells were investigated. The BAY11-7082 inhibitor and the siRNA of p65 were used to block the NF-κB activation. A total of 85 patients who underwent surgery for histologically verified NSCLC were enrolled in this study. The expression of IL-17 and M2 macrophage markers were assessed by immunostaining. Survivals were estimated using the Kaplan-Meier method. RESULTS: The CD163 and CD206 cell surface markers and transforming growth factor beta (TGF-ß), vascular endothelial growth factor (VEGF) and IL-10 of M2 macrophages were significantly increased in IL-17-treated THP-1-derived macrophages in a dose-dependent manner. IL-17 increased the mRNA levels of Arginase I and Fizz1, the phosphorylation of IkBα and nuclear localization of p65 (a subunit of NF-κB). The BAY11-7082 abrogated IL-17-induced CD206 and CD163 expression, TGF-ß, VEGF, IL-10, Arginase I and Fizz1 expression and p65 nuclear translocation. Further experiments showed that IL-17 induced the expression of CD206, CD163, Arginase I, Fizz1 and Ym1 in mouse peritoneal macrophages that were inhibited by siRNA of p65. The immunostaining experiments on human NSCLC tissues indicated that high IL-17 expression was significantly correlated with CD163 and c-Maf. The intratumoral IL-17+ CD163+ c-Maf+ cells were associated with NSCLC progression. CONCLUSION: IL-17 stimulated macrophages to M2-like phenotypes via NF-κB activation. IL-17 may be a potential therapeutic target for NSCLC.

Cancer/testis antigens (CTAs) expression in resected lung cancer.

BACKGROUND: Increasing evidence shows cancer/testis antigens (CTAs) play a key role in oncogenesis. Our pre-study finds that MAGEA1, MAGEA10, MAGEB2, KK-LC-1, and CTAG1A/B have high expression frequencies at the protein level. We aim to explore their prognostic role and correlations with clinical characteristics in resected lung cancer at the mRNA level. METHODS: Thirty-eight surgical lung cancer samples were included. Validation study was performed based on The Cancer Genome Atlas database. The prognostic roles of CTAs were evaluated by Kaplan-Meier and multivariate analysis. RESULTS: High expression of MAGEA1 (16.7% vs 65.0%, P=0.004), MAGEA10 (61.1% vs 95.0%, P=0.016), MAGEB2 (55.6% vs 95.0%, P=0.007), and KK-LC-1 (16.7% vs 55.0%, P=0.020) was closely correlated with lymph node metastasis at diagnosis. Patients with TNM stage II or III had a higher expression of MAGEA10 (57.1% vs 91.7%, P=0.034) and KK-LC-1 (14.3% vs 50.0%, P=0.039) compared with patients in TNM stage I. High CTAG1A/B expression showed unfavorable prognosis in all cases (P<0.05). Subgroup analysis showed high CTAG1A/B expression was a negative prognostic factor of survival (P=0.031) in patients with TNM stage II or III. Although no statistical significance was reached, high CTAG1A/B also showed a similar prognostic trend in lung adenocarcinoma (ADC) and squamous cell carcinoma. The Cancer Genome Atlas database showed the negative prognostic role of CTAG1A/B was mainly induced by CTAG1B (NY-ESO-1, P=0.047) and high CTAG1B expression (hazard ratio =2.733, 95% CI: 1.348-5.541, P=0.005) was an independent negative prognostic factor of lung ADC. CONCLUSION: CTAs represent potential candidate targets for immunotherapy and their expression was closely correlated with tumor stage. High CTAG1B expression was an independent negative prognostic factor of lung ADC.

Establishment of cancer/testis antigen profiling based on clinicopathological characteristics in resected pathological stage III non-small cell lung cancer.

BACKGROUND: Cancer/testis antigen (CTA) expression was found to be highly heterogeneous in previous studies. We aimed to establish a precision CTA profiling in resected stage III non-small cell lung cancer (NSCLC) and demonstrate the best CTA combination covering the widest range of NSCLC cases. MATERIALS AND METHODS: The expression of 10 CTAs was evaluated in 200 resected stage III NSCLC tissue specimens at protein level. Hierarchical clustering and python programming language analyses was used to demonstrate CTA expression and coverage. RESULTS: The most commonly expressed CTAs for total cases were MAGEA1 (60.0%), MAGEA10 (50.0%), and KK-LC-1 (47.5%). CTA expression was histology dependent, and concurrent expression was common. The best 2, 3, and 4 CTA combination covered 72.0%, 76.5%, and 79.5% of total cases, respectively. Stratified analysis based on variable clinicopathological characteristics achieved the maximum coverage of 92.3% with only 2 CTA combination in patients with features of male sex, positive smoking history, and adenocarcinoma, compared with a 85.0% coverage when 10 CTAs were assessed. Selected CTA expression was correlated with prognosis based on subgroup analysis. No significant difference was found between CTA expression and epidermal growth factor receptor mutant status. CONCLUSION: We established an individualized CTA profiling in resected stage III NSCLC based on 10 CTA expression. With the help of computer programming language, the goal of the maximum CTA expression coverage was reached by using the least CTA combination based on sex, smoking history, and histology. These results were significant for the further study of CTA-specific T-cell immunotherapy.

Selected patients can benefit more from the management of etoposide and platinum-based chemotherapy and thoracic irradiation-a retrospective analysis of 707 small cell lung cancer patients.

The management of small cell lung cancer (SCLC) has reached a plateau. Etoposide and platinum-based chemotherapy plus thoracic irradiation remain the standard treatment strategy for SCLC. Our study aims to assess the potential prognostic factors of patients treated with etoposide and platinum-based chemotherapy and explore which group of patients can benefit more from standard treatment strategies. On univariate analysis, age>65 years, male patients, KPS (Karnofsky Performance Status)≤80 points, positive smoking history, anemia, lymphocyte counts≤1.65×109/L, neutrophil to lymphocyte ratio (NLR)>3.18, lymphocyte to monocyte ratio (LMR)≤2.615, lactate dehydrogenase (LDH)>216.5 U/L, alkaline phosphatase (ALP)>119.5 U/L, absence of surgery, absence of thoracic irradiation, chemotherapy cycles<4, metastatic sites≥2 and extensive disease were correlated with a poor prognosis. Gender, KPS, chemotherapy cycles, thoracic irradiation, metastatic sites, LDH and tumor stage held statistical significance on multivariate analysis (p<0.05). High LDH was closely correlated with extensive disease, metastatic sites≥2, anemia, low LMR, high NLR and ALP levels. Subgroup analysis showed patients with male gender, KPS≤80 points, LDH≤216.5U/L, extensive disease and metastatic sites<2 could benefit more from ≥4 chemotherapy cycles. Patients with male gender, KPS>80 points, LDH≤216.5U/L, limited disease and metastatic sites<2 could benefit more from thoracic irradiation (p<0.05 on uni- and multivariate analysis). In conclusion, female patients, KPS>80 points, chemotherapy cycles≥4, thoracic irradiation, metastatic sites<2, LDH≤216.5U/L and limited disease were independent positive prognostic factors for SCLC patients treated with etoposide and platinum-based chemotherapy. Selected patients can benefit more from the management of ≥4 cycles of chemotherapy and thoracic irradiation.

Predictive factors analysis for malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an uncommon disease with a dismal prognosis and unclear natural history. The present study aims to assess potential prognostic factors and management of MPM. METHODS: Clinical records of 39 patients with MPM between December 2003 and April 2014 were retrospectively reviewed. Overall survival was identified with Kaplan-Meier curves and Cox regression analysis. RESULTS: Mean age of 39 patients was 55.0 years; asbestos exposure was recorded in two patients. Main presentations were abdominal distension, abdominal pain, and weight loss. Thrombocytosis, low serum albumin level, and anemia were principal laboratory abnormalities. Ascites, peritoneal cavity mass, and peritoneum thickening were the main signs on CT scans. Cytoreductive surgery (CRS) plus adjuvant therapies were performed in 22 patients, single chemotherapy in 13, and best supportive care in 4. Median survival time was 10.0 months after pathological diagnosis, with a 6-, 12-, 18-, and 24-month survival rate of 84.4, 31.6, 18.5, and 15.8 %, respectively. Significant prognostic factors were age, performance status (PS), abdominal pain, serum albumin level, thrombocytosis, and treatment strategy on univariate analysis, while only age, abdominal pain, and treatment strategy hold statistical significance on multivariate analysis. CONCLUSIONS: Age ≤65 years, abdominal pain, and CRS plus adjuvant therapy are independent positive prognostic factors of MPM.

Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer.

The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. However, it remains unclear how IL-17 might contribute to tumor angiogenesis. In our study, IL-17 enhanced the formation of vessel-like tubes in HUVECs both directly (when HUVECs were incubated with IL-17) and indirectly (when HUVECs were incubated in conditioned cell media (CCM) from IL-17-treated cancer cells). Our results from experiments using siRNA-mediated knockdowns of STAT3 and GIV suggest that the effects of IL-17 were mediated by activating STAT3/GIV signaling in NSCLC cells and subsequently up-regulating its downstream target VEGF. Consistent with these findings, immunostaining experiments on human NSCLC tissues indicated that IL-17 and GIV expression were significantly and positively associated with increased tumor vascularity. The clinical significance of IL-17 was authenticated by our finding that the combination of intratumoral IL-17 + cells and GIV expression served as a better prognosticator for survival than either marker alone. Therefore, our finding highlights a novel aspect of STAT3/GIV pathway in the IL-17 promotes tumor angiogenesis of NSCLC.