Exploration of Immune Tolerance and Treatment for Esophageal Cancer / 肿瘤防治研究

Monoclonal antibody drugs that inhibit programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) have been widely used in esophageal cancer (EC) and yielded significant therapeutic responses. However, only a few patients obtain lasting clinical benefits due to primary or acquired drug resistance, and new treatment schemes are urgently needed. The tumor immune microenvironment is the main factor that affects patients' response to immunosuppressive agents. This article will discuss the role of immunosuppressive cells and non-cellular components in the immune process to provide ideas for the next research direction of EC.

Application of Self-assembled Nano-strategies of Traditional Chinese Medicine in Tumor Therapy： A Review / 中国实验方剂学杂志

Chinese medicine self-assembly nano-strategies（CSAN） is to utilize the self-assembly property of Chinese medicine components， so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions， and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics， and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine， which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine， which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy， and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time， traditional Chinese medicine（TCM） has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly， but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy， improve the targeting of drugs， enhance the anti-tumor efficacy， and reduce the side effects of chemotherapy， which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple， low cost， and has better safety than traditional nano-preparations， which is conducive to the promotion of the clinical transformation of nano-preparations， and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore， based on a large number of researches in this field in recent years， this paper reviewed the formation mechanism， different assembly forms， formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure（CNKI）， PubMed， WanFang data and VIP， and summarized the application of CSAN in different tumor therapies， providing a reference for further research on CSAN.

Clinicopathological features, treatment and prognosis of soft tissue sarcoma and sarcomatoid carcinoma of urinary and male reproductive system in adults / 中华泌尿外科杂志

Objective:Clinicopathological features, treatment and prognosis of urinary and male reproductive system soft tissue sarcoma (STS) and sarcomatoid carcinoma in adults were compared.Methods:A retrospective analysis was performed on the clinical data of 73 patients with STS and 15 patients with sarcomatoid carcinoma in adult urinary and male reproductive system in the First Affiliated Hospital of Zhengzhou University. There were 59 males and 14 females in STS group, with a median age of 41 (18-78)years old. The maximum tumor diameter ranged from 0.5 to 19.0 cm. The primary tumors were located in testis and peritesticular (23 cases), kidney (23 cases), prostate (15 cases), bladder (8 cases), ureter(3 cases), other parts(1 case). There were 18 cases of lymph node metastasis and 8 cases of distant metastasis. Among 73 patients with STS, 66 patients underwent surgical resection, of which 31 patients underwent radical resection. Among the 66 patients who underwent surgery, 3 patients received neoadjuvant chemotherapy; 22 patients received adjuvant chemotherapy; 5 patients were treated with adjuvant radiotherapy. Among 7 patients with STS did not receive surgical treatment, 2 patients received radiotherapy combined with chemotherapy, 2 patients received chemotherapy alone, and 3 patients received symptomatic support treatment.There were 11 males and 4 females in sarcomatoid carcinoma group, with a median age of 65 (23 - 84)years old. The measurable tumor diameter ranged from 0.4 to 16.9 cm. The primary tumors were located in kidney (6 cases), bladder (5 cases), ureter(2 cases) and prostate(2 cases). There were 2 patients of lymph node metastasis and 4 patients of distant metastasis. Of the 15 patients with sarcomatoid carcinoma, 12 patients underwent surgical resection, of which 5 patients underwent radical resection. 2 patients were treated with adjuvant therapy after operation. Among the 12 patients who received surgical treatment, 2 patients had distant metastasis before operation, all of which originated from the kidney. Among the 3 patients without surgical treatment, 1 patients received systemic chemotherapy and 2 patients received symptomatic supportive treatment. There was no significant difference in gender, tumor maximum diameter, distant metastasis and operation, chemotherapy, radiotherapy and operation combined with chemotherapy ( P>0.05) and there were significant differences in age, tumor primary location and lymph node metastasis ( P<0.05) between STS and sarcomatoid carcinoma patients.The categorical variables of the two groups were compared by χ2.With Kaplan-Meier method for univariate survival analysis, the Cox was used for multivariate analysis. Results:The median follow-up time was 18.3(0.3-90.4) months.In STS group, there were 14 patients of synovial sarcoma, 11 patients of liposarcoma, 15 patients of rhabdomyosarcoma, 16 patients of leiomyosarcoma, 10 patients of other types, and 7 patients of spindle cell sarcoma without specific classification. Among 66 patients with STS, 8 patients recurred, 14 patients metastasized after operation, 4 patients recurred and metastasized after operation. The 7 patients without surgical treatment all progressed. Among the 10 patients of sarcomatoid carcinoma without distant metastasis before operation, 3 patients recurred and 3 patients metastasized after operation. Two patients of renal sarcomatoid carcinoma with distant metastasis were treated with nephrectomy and chemotherapy. One of them had overall survival (OS) up to 2 years, and one recurred 2 months after operation. The 3 patients without surgical treatment all progressed without remission. The median OS of STS patients were 59.3 (95% CI 24.1-94.5) months and that of sarcomatoid carcinoma patients were 8.7 (95% CI 6.1-11.2) months. The OS of STS patients were better than those of sarcomatoid carcinoma patients ( HR=2.874, 95% CI 1.118-7.386, P=0.022). Conclusions:The onset age of STS in adult urinary and male reproductive system was lower than that in sarcomatoid carcinoma. The primary lesions of STS were mainly in testis, peritesticular and kidney. The primary lesions of sarcomatoid carcinoma were mainly in kidney. Among STS, leiomyosarcoma was the most common type.STS and sarcomatoid carcinoma should be diagnosed and treated with surgery quickly, and systemic therapy should be performed for patients who cannot be treated with surgery.

Expression of microRNA-17-5p in esophageal squamous cell carcinoma and its effects on cell proliferation and invasion / 中华肿瘤杂志

Objective@#To explore the expression of microRNA-17-5p (miR-17-5p) in esophageal squamous cell carcinoma (ESCC) and its effects on cell proliferation and invasion ability.@*Methods@#Real-time quantitative PCR (RT-qPCR) was used to detect the miR-17-5p level in ESCC tissues and cells. MiR-17-5p inhibitor and negative control (NC) were transfected into EC9706 and TE1 cells, and miR-17-5p expression was examined by using RT-qPCR. Cell counting kit-8 (CCK-8) and EdU were conducted to detect cell proliferation and Transwell chamber was used to investigate cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-17-5p and retinoblastoma-like protein-2 (RBL2). Western blot and RT-qPCR were used to detect the expression of RBL2 in ESCC tissues, respectively. Finally, the correlation between RBL2 and miR-17-5p was analyzed.@*Results@#The miR-17-5p level in ESCC tissues was 4.222±0.392, significantly higher than 1.081±0.046 in normal esophageal epithelial tissues (P<0.001). The expressions of miR-17-5p in ESCC cells, including EC9706, Eca109, TE1, KYSE450, KYSE70 and KYSE520, were 13.84±1.266, 6.453±0.293, 11.41±0.520, 2.613±0.548, 5.251±0.239 and 4.251±0.195, respectively, all obviously higher than (1.007±0.079) in normal esophageal epithelial cell Het-1A (P<0.05). The miR-17-5p level in patients with ESCC Ⅲ~Ⅳ was 5.094±0.562, markedly higher than 2.934±0.364 in patients with ESCCⅠ~Ⅱ(P<0.01). Moreover, the miR-17-5p level in ESCC patients with lymph node metastasis was 5.523±0.634, markedly higher than 3.533±0.461 in ESCC patients without lymph node metastasis (P<0.05). The survival ratio of ESCC patients with higher miR-17-5p level was evidently lower than that of ESCC patients with lower miR-17-5p level (P<0.05). MiR-17-5p inhibitor significantly downregulated the miR-17-5p expression in EC9706 and TE1, which suppressed cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of 3′ untranslated region-wild type (3′UTR-WT) of RBL2 and miR-17-5p mimic significantly reduced luciferase activity in EC9706 and TE1 cells (P<0.01), which implicated that RBL2 was the direct target of miR-17-5p. The result of western blot revealed that RBL2 protein expressions in miR-17-5p group of EC9706 and TE1 cells were 0.936±0.055 and 0.923±0.048, obviously higher than 0.087±0.019 and 0.102±0.010 in control group (P<0.001). The expression of RBL2 in ESCC tissues was 0.219±0.510, markedly lower than 0.983±0.324 in normal esophageal epithelial tissues (P<0.001). The miR-17-5p level exhibited a negative correlation with RBL2 level in ESCC tissues (r=-0.462, P<0.001). Downregulation of RBL2 reversed the miR-17-5p inhibitor induced suppression of cell proliferation and invasion ability.@*Conclusion@#MiR-17-5p participates in the carcinogenesis and development of ESCC, thus may be a potential therapeutic target for ESCC patients.

Clinical biological characteristics of metastatic carcinoma of the thyroid: a report of 30 cases / 中华普通外科杂志

Objectives To study the clinical characteristics,diagnosis,treatment and prognosis of cancer metastases to the thyroid gland.Methods At Tianjin Medical University Cancer Hospital,from 1980 to 2016 30 patients were identified with a metastatic malignant tumor of the thyroid gland.Results Primary tumor sites were in the esophagus (26.7％),lung (16.7％),and kidney (13.3％).The median age at discovery of thyroid metastasis was 56 years old.The time lapse ranged from 0 to 108 months.There were 18 patients with metachronous metastasis with median survival of 36 months,12 patients were with synchronous metastasis,and the median survival was 8 months (P ＜ 0.01).20 patients were treated with thyroid surgery,and of which 15 patients were given post-op radiotherapy and chemotherapy.Patients who underwent thyroid resection had a median survival of 15 months,while that was 8 months in those without thyoid surgery (P ＜ 0.01).Conclusions Metastases to the thyroid gland is a rare clinical phenomenon,the prognosis of patients is mainly related to the biological behavior of primary tumors,but surgical resection and combined treatment can increase the survival rate.

A Paired Case Controlled Study Comparing the Short-term Outcomes of Da Vinci RATS and VATS Approach for Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Da Vinci Surgical System is one of the greatest inventions of the 20th century, which represents the development direction of the precise minimally invasive surgical techniques, the aim of this study was to comparing the short-term outcomes between da Vinci robot-assisted lobectomy and video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer.@*METHODS@#45 pairs of non-small cell lung cancer patients underwent pulmonary lobectomy with da Vinci Robotic assisted thoracoscopic (RATS) and VATS approach during the same period from January 2014 to January 2017. The operative time, estimated blood loss (EBL), total number and total groups of dissected lymph nodes, postoperative duration of drainage, the first day volume of drainage, total volume of drainage were compared.@*RESULTS@#No perioperative death and convertion to thoracotomy occured in both groups. There were significant difference between RATS group and VATS group in EBL [(50.30±32.33) mL vs (208.60±132.63) mL], the first day volume of drainage [(275.00±145.42) mL vs (347.60±125.80) mL], the dissected total number [(22.67±9.67) vs (15.51±5.41)] and total team [(6.31±1.43) vs (4.91±1.04)] of lymph node. There were no significant difference in other outcomes.@*CONCLUSIONS@#RATS is safe and effective and took better short-outcomes than VATS in non-small cell lung cancer.

Relationship between clinicopathological features and prognosis of Klatskin tumor and expression of MACC1 / 中国现代普通外科进展

Objective:To investigate the expression of MACC1 in Klatskin tumor and the relationship between the clinicopathological features and prognosis and the expression of MACC1.Methods:Immunohistochemistry staining was employed to assess the expression of MACC1 protein in Klatskin tumor tissues and matched adjacent non-tumor bile duct tissues.Quantitative real-time PCR was performed to examine MACC1 mRNA expression in Klatskin tumor tissues and the adjacent non-tumor bile duct tissues and normal bile duct tissues.The correlation between MACC1 expression and the clinicopathological features and prognosis was analyzed.Results:The positive rate of MACC1 in Klatskin tumor tissues was significantly higher than that in matched adjacent non-tumor bile duct tissues(P＜0.05).MACC1 mRNA expression in carcinoma tissues was significantly higher than that in the non-tumor bile duct tissues and normal bile duct tissues(P＜0.05).MACC1 expression in Klatskin tumor tissues was related to tumor size,recurrence and lymphatic metastasis(P＜0.05).Survival analysis indicated that the 1-year,3-year,5-year survival rate were with significantly differences between the two groups (P＜0.05).Conclusion:MACC1 expression was significantly higher in Klatskin tumor and it was related to the tumor size,recurrence and lymphatic metastasis.It would affect the prognosis of patients.

Establishing and identification of an immortal cell line of familial papillary thyroid carcinoma with MLH1 R217C/BRAF V600E mutations / 天津医药

Objective To establishing an immortal cell line of familial papillary thyroid carcinoma (FPTC), and explore a new approach for studying familial non-medullary thyroid carcinoma (FNMTC). Methods The specimen from a patient with FPTC was selected, separated, and the primary cells were cultured using DMEM/F12 medium (with TSH, T3, EGF and hydrocortisone). To inducing cell immortalization, the exogenous genes SV40T/TERT were transfected into cells by two ways. RT-PCR was used to detect the expressions of thyroid peroxidase (TPO), thyroid globulin (TG), thyroid stimulating hormone receptor (TSHR) and sodium/iodide co-transporter (NIS). Immunofluorescence method was used to detect the expressions of TPO and GPC3. In order to detect the genomic mutations, the peripheral blood DNA of the patient was extracted. The cell genome was detected. Results The FPTC cells adhered to the plate and showed an irregular polygon shape. The cells can stably grow for six months, FPTC-S (with SV40T transfected) passaged to p26, FPTC cells passaged to p23 and FPTC-ST (with SV40T/TERT transfected) passaged to p19. Both FPTC-S and FPTC-ST can stably express TPO, TG and TSHR in mRNA level. MLH1 R217C mutation existed in the peripheral blood of the patient, and BRAF V600E mutation existed in the primary cultured cells. Either the primary or the immortal cells showed MLH1 R217C mutation. Conclusion This study preliminarily established an immortal cell line of familial papillary thyroid carcinoma with MLH 1 R217C and BRAF V600E mutations. This cell line provides a research model for studying these mutations in FPTC.

miR-10a inhibits cell proliferation and promotes cell apoptosis by targeting BCL6 in diffuse large B-cell lymphoma

The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6. We further identified an inverse correlation between miR-10a levels and BCL6 protein levels, but not mRNA levels, in DLBCL tumor tissue samples. By overexpressing or knocking down miR-10a in DLBCL cells, we experimentally validated that miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulated BCL6 expression. Furthermore, we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells.

Association of rs2228314 polymorphism in SREBP2 with serum lipid levels and obesi-ty among children and adolescents / 北京大学学报(医学版)

Objective:To study the relationship between rs 2228314 polymorphism in sterol regulatory element binding protein 2 gene (SREBP2) and obesity, serum lipid levels in children and adolescents . Methods:In our study , 2 030 children and adolescents aged from 7 to 18 years participated .Anthropo-metric measurements, including height and weight, were performed.Their serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol ( HDL-C) were detected .The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS ) was used to detect rs2228314 genotypes.Results: The GC/CC genotypes of rs2228314 polymorphisms had lower HDL-C levels than GG genotype [(0.10 ±0.35) mmol/L vs. (0.14 ±0.36) mmol/L, P=0.020].The rs2228314 polymorphism was associated with the abnormal HDL-C level under the dominant model after adjustment for study samples , sex and age ( OR=1.400, 95%CI:1.027-1.907, P=0.033).The rs2228314 polymorphism was not associated with obesity un-der the dominant model after adjustment for study samples , sex, age and HDL-C level ( OR=1.178, 95%CI: 0 .971 -1 .430 , P =0 .096 ) . Conclusion: The GC/CC genotype carriers of SREBP2 rs2228314 polymorphism have higher risk of abnormal HDL-C level than the individuals with GG geno-type among children and adolescents .

High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory marginal zone non-Hodgkin' s lymphoma / 白血病·淋巴瘤

Objective To evaluate the role of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory marginal zone lymphomas. Methods The transplant database was reviewed retrospectively from Tianjin Medical University Cancer Hospital identified 12 patients who underwent high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation. Results Among the twelve patients who underwent autologous hematopoietic stem cell transplantation, the median duration of progression-free survival (PFS) was 104 months and the median duration overall survival (OS) was 117 months; 6 patients were still alive with disease-free. Conclusion High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation is feasible to patients with relapsed/refractory marginal zone lymphomas, particularly to those insensitive to rituximabincluded combined chemotherapy.