[Analysis of primary site and pathology on 903 patients with neuroendocrine neoplasms].

OBJECTIVE: To explore the primary site and pathological feature of neuroendocrine neoplasm (NEN), especially the NEN of digestive system. METHODS: Clinicopathological data of NEN patients at China-Japan Friendship Hospital from January 2012 to December 2016 were retrospectively analyzed. Tumor primary sites were summarized. Association between tumor site and pathological grading in gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN) was examined. RESULTS: There were a total of 903 cases of NEN. Sites of primary tumor included the digestive system in 699 cases(77.4%), the thorax(including lung, thymus and mediastinum) in 87 cases(9.6%), other sites in 60 cases (6.6%), unknown in 57 cases(6.3%). Among 699 GEP-NEN cases, the primary sites included the stomachin in 207 cases (29.6%), pancreas in 201 (28.8%), rectumin in 185 (26.5%), duodenum in 43(6.2%), jejunum and ileum in 18(2.6%), appendix in 15 (2.1%), gallbladder in 11(1.6%), esophagus in 10(1.4%), and the colon in 9 cases (1.3%). Pathologically, the tumor grading was neuroendocrine tumor (NET) G1 in 336 cases(48.1%), NET G2 in 203 cases (29.0%), neuroendocrine carcinoma (NEC) G3 in 139 cases (19.9%). All the esophagus NEN(10/10), most gallbladder NEN(9/11) and colon NEN(6/9) were poorly-differentiated NEC (G3), while all appendix NEN(15/15), most stomach NEN(147/207, 71.0%), pancreas NEN (156/201, 77.6%), rectum NEN (169/185, 91.4%), duodenum NEN (31/43, 72.1%), jejunum and ileum NEN(16/18, 88.9%) were well-differentiated NET G1 or G2. CONCLUSIONS: The most common primary site of NEN is the digestive system. The stomach, pancreas and rectum are most common primary sitesof GEP-NEN. Difference in pathological grading is quite greatin different primary sites of GEP-NEN. Most NENs fromesophagus, colon and gallbladder are poorly-differentiated NEC.

Down-regulation of microRNA-144 in air pollution-related lung cancer.

Air pollution has been classified as a group 1 carcinogen in humans, but the underlying tumourigenic mechanisms remain unclear. In Xuanwei city of Yunnan Province, the lung cancer incidence is among the highest in China, owing to severe air pollution generated by the combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis. To identify abnormal miRNAs critical for air pollution-related tumourigenesis, we performed microRNA microarray analysis in 6 Xuanwei non-small cell lung cancers (NSCLCs) and 4 NSCLCs from control regions where smoky coal was not used. We found 13 down-regulated and 2 up-regulated miRNAs in Xuanwei NSCLCs. Among them, miR-144 was one of the most significantly down-regulated miRNAs. The expanded experiments showed that miR-144 was down-regulated in 45/51 (88.2%) Xuanwei NSCLCs and 34/54 (63%) control region NSCLCs (p = 0.016). MiR-144 interacted with the oncogene Zeb1 at 2 sites in its 3' untranslated region, and a decrease in miR-144 resulted in increased Zeb1 expression and an epithelial mesenchymal transition phenotype. Ectopic expression of miR-144 suppressed NSCLCs in vitro and in vivo by targeting Zeb1. These results indicate that down-regulation of miR-144 is critical for air pollution-related lung cancer, and the miR-144-Zeb1 signalling pathway could represent a potential therapeutic target.

Tobacco smoke induces production of chemokine CCL20 to promote lung cancer.

Tobacco kills nearly 6 million people each year, and 90% of the annual 1.59 million lung cancer deaths worldwide are caused by cigarette smoke. Clinically, a long latency is required for individuals to develop lung cancer since they were first exposed to smoking. In this study, we aimed to identify clinical relevant inflammatory factors that are critical for carcinogenesis by treating normal human lung epithelial cells with tobacco carcinogen nicotine-derived nitrosaminoketone (NNK) for a long period (60 days) and systematic screening in 84 cytokines/chemokines. We found that a chemokine CCL20 was significantly up-regulated by NNK, and in 78/173 (45.1%) patients the expression of CCL20 was higher in tumor samples than their adjacent normal lung tissues. Interestingly, CCL20 was up-regulated in 48/92 (52.2%) smoker and 29/78 (37.2%) nonsmoker patients (p = 0.05), and high CCL20 was associated with poor prognosis. NNK induced the production of CCL20, which promoted lung cancer cell proliferation and migration. In addition, an anti-inflammation drug, dexamethasone, inhibited NNK-induced CCL20 production and suppressed lung cancer in vitro and in vivo. These results indicate that CCL20 is crucial for tobacco smoke-caused lung cancer, and anti-CCL20 could be a rational approach to fight against this deadly disease.

Proteomic characterization of the possible molecular targets of pyrrolizidine alkaloid isoline-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are distributed in plants worldwide including medicinal herbs or teas. In the present study, we investigated the effects of isoline, which is a retronecine-type PA isolated from traditional Chinese medicinal herb Ligularia duciformis, on mouse liver proteins by using proteomic approaches. Firstly, our results showed that 110mg/kg isoline increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum, and hepatic tissue pathological observation further confirmed isoline-induced liver injury. Proteomic analysis showed that the liver samples from mice of isoline group demonstrated about 13 differentially expressed proteins compared with normal group, and those proteins may be involved in isoline-induced liver injury in mice. Next, all these 13 protein spots were identified by MALDI-TOF-TOF MS or LTQ MS; and among them 9 differentially expressed proteins are involved in the process of oxidative stress or cellular energy metabolism. Further lipid peroxidation analysis and ATPase assay confirmed the existing of oxidative injury induced by isoline and consequent disruption of energy metabolism. Furthermore, an in silico drug target searching program INVDOCK identified 2 potential protein targets of isoline, and the results are in support of proteomic analysis. In summary, the possible signaling molecules related with isoline-induced liver injury were demonstrated in this study.

Antitumor activity of Dioscorea bulbifera L. rhizome in vivo.

Antitumor activities of water extract (fraction A), ethanol extract (fraction B), ethyl acetate extract (fraction C), non-ethyl acetate extract (fraction D) and compound diosbulbin B isolated from Dioscorea bulbifera L. (DB) were investigated in vivo in this present study. The results showed that fractions B and C both decreased tumor weight in S180 and H22 tumor cells bearing mice, while fractions A and D had no such effect. Furthermore, fraction C altered the weight of spleen and thymus, and the amounts of total leukocytes, lymphocytes and neutrophils in tumor-bearing mice. Further results showed that compound diosbulbin B demonstrated anti-tumor effects in the dose-dependent manner at the dosage of 2 to 16 mg/kg without significant toxicity in vivo. Furthermore, on the basis of chemical analysis of the above extracts by high-performance liquid chromatography (HPLC) with a diode array detector (DAD), diosbulbin B was found to be the major antitumor bioactive component of DB. These results suggest that DB has potential anti-tumor effects which may be related to influencing the immune system for the first time, and the compound diosbulbin B is the major antitumor component of DB.

[The cryosurgery of central lung cancer by rigid bronchoscopy].

OBJECTIVE: To evaluate the method and effectiveness of rigid-bronchoscopic cryosurgery for advanced central lung cancer. METHODS: Forty-eight patients were enrolled in this study from June 2002 to December 2008, including 33 male and 15 female. The average age was 70 years (ranged from 45 to 83 years old). For the 48 patients, 38 cases were patients with advanced central lung cancer who were not suitable for surgery, and the remaining 10 cases were patients with local recurrence in trachea or main bronchus postoperatively. Cryosurgery was performed 120 times for all patients, 2.5 times per patient on average. The trachea or bronchus station, symptom such as dyspnea, hemoptysis, respiratory function and quality of life were observed. RESULTS: The unblocked ratio of trachea and bronchi was 97%. All patients got satisfied improvement ratio of symptoms, 87.5% for dyspnea, 72.9% for cough, 93.8% for hemoptysis and 62.5% for chest pain. Respiratory function tests showed that both the mean forced expiratory volume in first second and forced vital capacity got an improvement from (1.03+/-0.05) L to (1.85+/-0.13) L and from (1.69+/-0.18) L to (2.96+/-0.14) L respectively (P<0.01). Karnofsky score also got no less than 20 scores improvement. The Follow-up time was 6 to 62 months. The longest survival was 62 months. The median survival time was 20 months. There was no severe perioperative complications and mortality except for 3 cases of moderate exeduation. CONCLUSIONS: Cryosurgery is easy to perform with minimal complications. Not only could it provide an effective and rapid control of symptoms caused by central lung cancer, it could also unobstructed bronchus promptly and improve patients' quality of life.

[Results of unilateral lung volume reduction surgery in twenty-five patients with chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the effectiveness of unilateral lung volume reduction surgery (LVRS) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The follow-up data of 25 patients with COPD who had underwent unilateral LVRS between January 1996 to December 2002 in department of thoracic surgery, China-Japan friendship hospital were analyzed retrospectively. The operative target was determined by pre-operative CT and pulmonary ventilation-perfusion (V/Q) scintigraphy. LVRS was performed in 21 patients through video assisted thoracoscopy surgery (VATS) or VATS with adjuvant small lateral thoracotomy. In 4 patients LVRS was performed through posterolateral thoracotomy. Destroyed pulmonary tissue was resected by liner stapler or Endo GIA. To evaluate the effectiveness of unilateral LVRS, the changing of dyspnea score, pulmonary function and the quality of life were analyzed. RESULTS: The postoperative follow-up interval range was 2 years. The mean postoperative FEV(1) increased by (35 +/- 9)%, and six minute walking distance (6MWD) increased by (88 +/- 22)%. For dyspnea score, among 16 patients with a preoperative grade of IV, 4 patients improved to grade I, 12 improved to grade II; among 9 patients with a preoperative grade of V, 1 improved to grade I, 1 improved to grade II, 4 improved to grade III, and the other 3 improved to grade IV. Karnofsky score increased by (44 +/- 10) in average. One and two year survival rates was 96% and 92%, respectively. There was no perioperative death in this group, and the total postoperative morbidity was 32%. CONCLUSIONS: Unilateral LVRS shows significant clinical benefits for the majority of patients with COPD. It is associated with lower operative mortality and morbidity, and has a wide range of indications. The key points of the operation are to resect dysfunctional lung tissues as much as possible and to prevent pulmonary air leak. Preoperative and postoperative breathing training plays a very important role in the postoperative recovering of lung function.

[Late-stage emphysema treated with lung volume reduction: report of 22 cases].

OBJECTIVE: To Summarize the clinical experience in the treatment of late-stage emphysema by lung volume reduction (LVR) in 5 years. METHODS: We retrospectively studied the indications, contraindications, operation procedures and complications of LVR in 22 patients. RESULTS: Before operation, the average FEV(1) was 24.5%, RV 196.8%, and TLC 130.5%; after operation they were 27.8%, 148.8% and 112.5%, respectively. 16 patients needed inhaling oxygen before operation, and 5 after operation. 16 patients finished 6-minute walking test with an average of 198 m, all patients walked much longer with an average of 256 m after operation. 3-degree lung function was observed in 14 patients, and 4-degree before operation in 8 patients; but 2-degree lung function in 5 patients, 3-degree in 13, and 4-degree in 4 after operation. CONCLUSIONS: Heterogeneous type emphysema with clear target area, especially bullous emphysema is the best indication for LVR. Lung function and life quality could be much improved postoperatively. Homogeneous type could also be treated with LVR in highly selected cases. TLCO < 20% is not an absolute contraindication, others standards need further investigation. Video-assistant thoracoscopic surgery (VATS) with subaxillary small incision for LVR is safe, reliable and effective. Application of stapler buttressing with bovine pericardia could decrease air leakage postoperatively.