Shoubo Cao

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.

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.

Colonic invasion induced by malignant peritoneal mesothelioma.

Novelty: Malignant peritoneal mesothelioma (MPM) is a rare disease confined to peritoneal cavities in most cases, seldom seen in intraand extra-abdominal invasion. In addition, MPM is easy of misdiagnosis and has a poor prognosis. Here, we report a case of colonic invasion induced by MPM in order to help prevent from misdiagnosis and prolong survival time. A 53-year-old male who presented with constipation, weight loss, and occasional abdominal discomfort for 2 months was admitted to the Department of Surgical Oncology, Harbin Medical University Cancer Hospital, November 2013. He was a heavy smoker of 15 packs/month with a history of asbestos exposure in childhood and diabetes mellitus. On physical examination, he had a fixed mass in the right lower quadrant. Routine blood tests and evaluation for tumor markers CEA, CA724, CA19-9, and CA-125 were all in normal range except for a thrombocytosis of 397×10/L. A 3D-enhanced CT of the abdomen showed an irregular thickening wall of hepatic flexure of colon, and the thickener area can be reached 16.8 mm, closely adjacent to intestine. At the same time, an infiltrating mass of 67.7 mm in size, multiple small peritoneal nodules, and abdominal swelling lymph nodes can also be seen in abdominal CT. There were no remarkable findings on the endoscopic examination, and the colonoscopy suggested an infiltrating lesion located in the hepatic flexure of colon, ruptured in the surface, and easily bled when touched. Laparotomy was performed, peritoneal nodules were intraoperatively found throughout the peritoneum, and the infiltrating mass had penetrated the range of serosal and right side of the peritoneum, widely planting in the peritoneum, omentum, and surface of peritoneal cavities. Necrotic tissue sample was delivered for examination, and quick pathology revealed malignancy. In addition, 2.0 cm×1.5 cm×1.0 cm omental tissue was cut for detection during surgery. Histology revealed a well-differentiated epithelioid malignant mesothelioma. It was positive for HBME-1, CK5/6, CK7, and calretinin, supporting the diagnosis of MPM. After surgery, the patient was referred to the Department of Medical Oncology. Our patient recovered well after the operation, and he had successfully accepted 2 cycles of chemotherapy of pemetrexed combined with carboplatin; unfortunately, he did not tolerate the therapy, and the disease progressed with the appearance of ascites and rectum occupation revealed by abdominal and pelvic CT. However, there are no significant abnormalities found in colonoscopy. We deemed that rectum occupation was caused by the compression of swelling lymph nodes. Oxaliplatin and capecitabine were adjusted to the following treatment, and he felt symptoms released at present. MPM is an uncommon, fatal disease arising from the peritoneum with an increasing incidence of 7–40/million and a negative prognosis of within 12 months [1]. The main risk factor for MPM is asbestos exposure, and the onset of about 60 % of MPM patients was correlated with direct or indirect asbestos contact. In addition, exposure to radiation, talc, mica, erionite, Thorotrast, SV40, and Hodgkin’s disease has also been reported to be related to MPM [2]. The most common presentations of MPM are abdominal pain and distension which resulted from the accumulation of tumors and ascites, while constipation is exceptional. MPM is usually diagnosed at advanced stage due to its nonspecific clinical and S. B. Cao and S. Jin contributed equally to this work. S. B. Cao : S. Jin : J. Y. Cao : J. Shen : J. W. Zhang :Y. Yu (*) Department of Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Hapin Road, 150081 Harbin, China e-mail: yuyan_hrb@126.com

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

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.

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.