Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma.

In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeutic development and optimization. In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77-6.61, p < 0.001); ( 5-year PFS 45.9% vs. 81.2%, HR: 3.22, 95%CI: 1.71-6.06, p < 0.001); ( 5-year LRRFS 74.6% vs. 87.5%, HR: 3.22, 95%CI: 1.16-8.93, p = 0.027); and ( 5-year DMFS79.2% vs. 93.2%, HR: 2.22, 95%CI: 0.91-5.39, p = 0.086). Upon multivariable analysis, COV+TIL score emerged as an independent prognostic indicator for defining survival in the training cohorts and the validation cohorts. Combining the COV+TIL score and TNM stage improved the prediction ability of the survival. In conclusion, NPC patients with high COV+TIL score showed worse prognosis.

MiR-181b Inhibits the Proliferation of Lymphoma Rajixi Cell Line by Regulating the Expression of Target Gene FAMLF.

ALCL is an aggressive lymphoma. In most cases, it is diagnosed as stage II or IV in the initial diagnosis, but it has a good response to concurrent chemotherapy with epinephrine. The six-year survival rate is about 50%. This study focused on miR-181b inhibiting the proliferation of the lymphoma Rajixi cell line by regulating the expression of the target gene FAMLF. Observe the morphology of HE with an optical microscope. Immunohistochemical staining was performed on a series of lymphocyte surface markers and cytotoxic granular membranes. In 28ALCL cases, PCR detection of immunoglobulin and T cell receptor gene recombination was performed. Summarize the characteristics of ALCL clinical pathology and the main points of diagnosis and differential diagnosis in daily business, summarize the characteristics of ALK-positive and the cytotoxicity of ALCL, and conduct a preliminary investigation on the cell source, pathological organization and tumor classification. Only four ENBAI subtypes, v-Val, P-THR, V-leu, and P-ALA were detected in lymphoma tissue, and no V-Pro subtype was found. Of the 110 positive lymphomas, 107 were single-digit Rajixi 18 (33%), and the remaining 1 (14%) were double-infected Rajixi. The results show that miR-181b can inhibit the proliferation of the lymphoma Rajixi cell line by regulating the expression of the target gene FAMLF.

Expression and clinical significance of SALL4 and LGR5 in patients with lung cancer.

Lung cancer is the most frequent cancer worldwide, in terms of incidence and mortality. Due to challenges in the diagnosis of the disease, the 5-year overall survival rate is only ~16%. Previous studies have suggested that malignant transformations originate from adult stem cells, and malignant lesions may therefore express stem-cell-associated markers. The purpose of the present study is to investigate the expression and clinical significance of the stem cell-associated markers Sal-like protein 4 (SALL4) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in lung cancer, and to provide novel diagnostic markers and targets for the treatment of lung cancer. The expression of the stem cell-associated markers SALL4 and LGR5 was analyzed by immunohistochemistry performed on 135 human lung cancer tissue specimens and 10 non-cancer lung tissue specimens. The clinical significance of the expression of these markers and correlation between their expression and clinical parameters was also assessed. SALL4 expression was highly upregulated in lung cancer tissues, but was not present in non-cancerous lung tissues, and the sensitivity and specificity of SALL4 reached 88% and 100%, respectively. By contrast, LGR5 demonstrated 97% sensitivity, but the specificity was poor. Therefore, SALL4 may be an extremely useful diagnostic marker for lung cancer, but LGR5 is not as useful.

Expression of seven stem-cell-associated markers in human airway biopsy specimens obtained via fiberoptic bronchoscopy.

BACKGROUND: Previous reports have suggested that malignant transformations originate from adult stem cells, and may thus express the stem-cell-associated markers. The purpose of this study is to investigate the differential expression and clinical significance of seven stem-cell-associated markers (Bmi1, CD133, CD44, Sox2, Nanog, OCT4 and Msi2) in lung cancer, providing new targets for the diagnosis and treatment of lung cancer. METHODS: In this study, we evaluated the differential expression of mRNA levels seven stem-cell-associated markers by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) from 112 human lung cancer and 18 non-cancer tissues obtained by bronchoscopy. We further verified the differential expression of these markers by immunohistochemistry in 50 lung cancer specimens, 30 benign inflammatory lesion tissues and 20 non-tumor adjacent lung tissues. RESULTS: With the exception of OCT4, other markers Bmi1, CD133, CD44, Sox2, Nanog and Msi2 mRNA and protein were abundantly expressed in lung cancer. Additionally, Nanog expression was highly upregulated in lung cancer tissues and rarely presented in non-cancerous lung tissues, the sensitivity and specificity of Nanog mRNA reached 63.4% and 66.7%, respectively. Nanog therefore possessed high diagnostic value, however, CD44, Bmi1 and CD133 showed poor diagnostic value in lung cancer. CONCLUSION: Nanog may serve as a promising diagnostic marker of lung cancer and potential therapeutic target in lung cancer.

[Summary about the progress and specifications of FDA regarding intravascular catheters].

This article summarizes the progress and specifications of FDA regarding intravascular catheters, and hope this would be helpful to people concerned.

Expression localization of Bmi1 in mice testis.

B cell-specific Moloney murine leukaemia virus integration site 1 (Bmi1), known as the first functional member of PcG (Polycomb Group) family, is supposed to be a key regulator of stem cell self-proliferation. In this study, we investigated its expression in testis and its impact on spermatogonia proliferation for better understanding of its role in spermatogenesis. Results showed that Bmi1 was expressed in undifferentiated spermatogonia (A(s), A(pr) and A(al) spermatogonia). Overexpression of BMI1 could promote spermatogonia proliferation, while repression of endogenous Bmi1 by RNAi resulted in inhibition of the proliferation.

17beta-estradiol stimulates proliferation of spermatogonia in experimental cryptorchid mice.

AIM: To investigate whether estrogen stimulates the proliferation of spermatogonia or induces spermatogenesis in cryptorchid mice. METHODS: Mice were surgically rendered cryptorchid, then treated with different doses of 17beta-estradiol (E2) s.c. once a day. Mice were killed at sexual maturity (45 days of age), and histological analysis and immunofluorescence were performed. Serum follicle stimulating hormone (FSH), estradiol, testosterone and luteinizing hormone (LH) were measured. RESULTS: Low doses of E2 had no notable effect on spermatogonia, but at higher doses, E2 stimulated the proliferation of spermatogonia. CONCLUSION: E2 has a dose-related mitogenic effect on spermatogonia.

[Differential analysis of proteomic profiles between cryptorchid and normal mouse testes].

To screen factors related to spermatogonial stem cell (SSC) proliferation, and to investigate the mechanism of infertility caused by cryptorchidism, ten-day-old Kunming (KM) mice were used and experimental cryptorchidism was conducted. On the 35th day after cryptorchid operation, the left testes were fixed in Bouin's fluid and used for histological analysis. The testes of 45-day-old mice were subjected to the same histological analysis, and it was found that they contained germ cells at every stage of development, from SSCs to sperm, indicating that the animals were fully sexually mature at this age. While in experimental cryptorchid mice, the spermatogenesis was arrested at the stage of spermatocytes, and only spermatogonia and primary spermatocytes were present in cryptorchid testes. The proportion of spermatogonia to other types of germ cells was much higher than that in sexually mature mice. On the other hand, the right testes were used for proteomic analysis. The total protein in testes was extracted on the 35th day after cryptorchid operation. The differentially expressed proteins in cryptorchid mice and sexually mature mice were screened and compared by the proteomic techniques. Through the separation of two-dimensional gel electrophoresis (2-DE), 20 differential protein spots were found, and 9 of them were digested and identified by the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrum. In cryptorchid mice, 6 out of 9 proteins were down-regulated, and 3 were up-regulated. Among these proteins, 4 proteins were identified, and they were Stathmin, phosphatidylethanolamine-binding protein1 (PEBP1), HES-related basic helix-loop-helix protein (HERP), and one unnamed protein (we temporarily named it Px). More Stathmin, PEBP1 and Px were expressed in sexually mature mice than in experimental cryptorchid mice. But HERP1 was the other way round. In the present study, we have screened 4 proteins related to cryptorchidism. It is helpful to study the mechanism of SSC proliferation and infertility caused by cryptorchidism.

[Cloning of Bmi1 cDNA from mouse testis and its expression in E. coli BL21].

OBJECTIVE: To produce BMI1 polyclonal antibody, mouse Bmi1 cDNA was cloned from mouse testis and expressed in E. coli BL21. METHODS: Bmi1 gene was amplified from mouse testis by RT-PCR and inserted into the prokaryotic expression vector pET-28c(+). Subsequently the recombined vector was transformed and expressed in E. coli BL21 (DE3) and the immunogenicity of recombined protein BMI1 (rBMI1) was tested by Western blot. RESULTS: Mouse Bmi1 cDNA of 975 bp was successfully cloned and recombined. E. coli BL21 strains expressed rBMI1 were screened. The expression protein amounted to 12% of the total bacterial protein after induced with IPTG, which included inclusion body and soluble protein. Inclusion body was the major pattern of the expression that amounted to 71% of the insoluble protein. Western blot analysis showed that rBMI1 could be specially recognized by mouse monoclonal IgG1 anti-BMI1 and His-tag antibody. CONCLUSION: There was expression of Bmi1 gene in mouse testis. Mouse Bmi1 cDNA was successfully cloned and expressed prokaryoticly.