[Correlation of NK cell RIPK1 with Prognosis of Acute Myeloid Leukemia Patients with FLT3-ITD Mutation].

OBJECTIVE: To investigate the correlation of NK cell receptor-interacting serine/threonine kinase 1（RIPK1） activity and expression with prognosis of acute myeloid leukemia (AML) patients with FLT3-ITD mutation. METHODS: A total of 132 AML patients with FLT3-ITD mutation and 136 AML patients with FLT3-WT were selected. Clinical data and the number, length and rearrangement ratio of FLT3-ITD mutations were collected. The ratio of CD4+ T cells, regulatory T cells（Tregs）, CD8+ T cells, B cells, natural killer cells（NK cells） and macrophage in peripheral blood（PB） were analyzed by flow cytometry. Correlation of NK cell ratio with FLT3-ITD mutation number, length and rearrangement ratio was analyzed by Pearson correlation analysis. Western blot and RT-qPCR were used to detect RIPK1 protein and mRNA levels in NK cells, respectively. Plasma RIPK activity was detected by ELISA, and Pearson corre-lation analysis was performed for the correlation of RIPK with FLT3-ITD mutation number, length and rearrangement ratio. Kaplan-Meier curve was used to analyze the survival rate of AML patients with FLT3-ITD mutation. RESULTS: Compared with AML patients with FLT3-WT, the white blood cell count in patients with FLT3-ITD mutation significantly increased, PB and BM blasts significantly decreased. There was no significant change in PB CD3+ T cells, Tregs, CD8+ T cells, B cells, M1 and M2 type macrophage of AML patients with FLT3-WT and FLT3-ITD mutation；Compared with AML patients with FLT3-WT, CD4+ T cells significantly decreased, NK cells significantly increased in AML patients wtih FLT3-ITD mutation. NK cells ratio in AML patients with FLT3-ITD mutation significantly positively correlated with the number of FLT3-ITD mutations and rearrangement bases. Plasma RIPK1 activity, RIPK1 protein and mRNA levels in NK cells of AML patients with FLT3-ITD were significantly lower than those of AML patients with FLT3-WT, and negatively correlated with the number of FLT3-ITD mutations, the length of rearranged bases (≥52 bp) and the ratio of rearranged bases. The survival rate of AML patients with FLT3-ITD mutation in low RIPK1 activity after Rydapt treatment was significantly higher than that in high RIPK1 activity. CONCLUSION: The prognosis of AML patients with FLT3-ITD mutation closely relates with plasma RIPK1 activity and RIPK1 expression in NK cells.

Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer.

This study aimed to identify significant immune microenvironment-related competing endogenous RNA (CeRNA) regulatory axis in gastric cancer (GC). Analysis of differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was performed for the microarray datasets. After abundance analysis of immune cell's infiltration, immune-related mRNAs and lncRNAs were obtained. Meanwhile, according to the Pearson correlation coefficient between immune-related mRNAs and lncRNAs, the co-expression mRNA-lncRNA pairs were screened. Furthermore, the target genes of co-existance miRNAs were predicted, and miRNA-lncRNA pairs were identified. Finally, the lncRNA-miRNA and miRNA-mRNA relationship regulated by the same miRNA was screened. Combining with the co-expression relationship between lncRNA and mRNA, the CeRNA network was constructed. In abundance analysis of immune cell's infiltration, a total of eight immune cells were obtained, in addition, 83 immune-related DElncRNAs and 705 immune-related DEmRNAs were screened. KEGG pathway enrichment analysis showed that these mRNAs were mainly involved in PI3K-Akt signaling pathway and human papillomavirus infection, while lncRNA were relevant to gastric acid secretion. A total of 25 miRNAs were significantly associated with immune-related mRNAs, such as hsa-miR-148a-3p, hsa-miR-17-5p, and hsa-miR-25-3p. From the mRNA-miRNA-lncRNA CeRNA network, we observed that AC104389.28─miR-17-5─SMAD5 axis and LINC01133─miR-17-5p─PBLD axis played a crucial role in the development of GC. Furthermore, resting memory CD4 T cells and plasma cells were closely associated with the pathogenesis of GC, and these immune cells might be affected by the key genes. The present study identified key genes that associated with immune microenvironment in GC, providing potential molecular targets for immunotherapy of GC.

[Research Advances on Extranodal Nasal Type NK/T Cell Lymphoma--Review].

Extranodal NK/T cell lymphoma is a relatively uncommon type of non-Hodgkin's lymphoma, which is prevalently distributed in Asia and South America, and is highly associated with Epstein-Barr virus (EBV) infection. Due to its highly aggressive course and poor response to treatment because of its multi-drug resistance, for the timebeing there is not yet a definite treatment strategy. The clinical manifestation, pathological diagnosis and the progress of treatment methods of ENTNKCL are reviewed below.

Prognostic factors influencing event-free survival and treatments in desmoid-type fibromatosis: analysis from a large institution.

BACKGROUND: Prognostic factors and optimal management of desmoid tumors have been discussed for decades. The authors present the results of a large series of patients with desmoid tumors treated at a single institution to investigate the prognostic factors influencing event-free survival (EFS) and suitable treatments for these rare tumors. METHODS: Two hundred fourteen patients with desmoid tumors admitted to the surgical department were included, of whom 20 were recommended for a policy of watchful waiting. The following clinical parameters were studied: admission status, age, sex, tumor site, tumor size, margin status, and therapeutic strategy. Univariate and multivariate analysis were performed for EFS. RESULTS: Forty-two patients had local recurrence. One patient died of intra-abdominal disease. The 5-year and 10-year EFS rates were 78.8% and 77.9%, respectively. In univariate analysis, admission status, tumor site, tumor size, and group (R0 vs R1 and R0 vs R2) had significant impacts on EFS. EFS discrepancy was not significant between R1 and R2 or biopsy groups. In multivariate analysis, tumor size and admission status had independent value. The median delay to progression for patients undergoing watchful waiting was comparable with that for the surgical group. CONCLUSIONS: This study demonstrates that tumor size and a history of recurrence are independent predictors of EFS. Surgery is warranted if it can be R0 and function sparing. Nonsurgical modalities or a policy of watchful waiting may be a better choice for unresectable disease.

Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer.

AIM: To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI) in patients with stage II gastric cancer. METHODS: From January 2001 to December 2006, 487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage II gastric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node (LN) dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathological findings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure (subtotal resection vs total resection), and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS: The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years (range: 23-88 years). The 5-year overall survival rates were 50.7% and the median survival time was 62 mo. Stage IIa cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three T1N2, and stage IIb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one T1N3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% (51/269) and 42.5% (71/167) in LN-negative and LN-positive patients, respectively. In 218 patients (50.0%), there was neither a histopathologically detectable LBVI nor LN metastases (LBVI(-)/LN(-), group I); in 51 patients (11.7%), LBVI with no evidence of LN metastases was detected (LBVI(+)/LN(-), group II). In 167 patients (38.3%), LN metastases were found. Among those patients, LBVI was not determined in 96 patients (22.0%) (LBVI(-)/LN(+), group III), and was determined in 71 patients (16.3%) (LBVI(+)/LN(+), group IV). Correlation analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI (P < 0.001). The overall 5-year survival was significantly longer in LN-negative patients compared with LN-positive patients (56.1% vs 42.3%, P = 0.015). There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI-negative tumors (39.6% vs 54.8%, P = 0.006). Overall 5-year survival rates in each group were 58.8% (I), 45.8% (II), 45.7% (III) and 36.9% (IV), and there was a significant difference in overall survival between the four groups (P = 0.009). Multivariate analysis in stage II gastric cancer patients revealed that LBVI independently affected patient prognosis in LN-negative patients (P = 0.018) but not in LN-positive patients (P = 0.508). CONCLUSION: In LN-negative stage II gastric cancer patients, LBVI is an additional independent prognostic marker, and may provide useful information to identify patients with poorer prognosis.

[Value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer].

OBJECTIVE: To investigate the value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer. METHODS: Clinical data of 229 gastric cancer patients were analyzed retrospectively. Lesions were divided into three parts: the cardiac, the body, and the antrum. The diagnostic accuracy of localization and the extent of tumor between gastroscopy alone and gastroscopy plus barium contrast were compared with the results of surgical findings. RESULTS: The diagnostic accuracy of localization and the extent of tumor for gastroscopy in the cardiac, the body and the antrum cancers were 100% and 78.4%, 94.6% and 86.5%, 98.1% and 84.6%, respectively, while for gastroscopy plus barium contrast were 100% and 84.8%, 100% and 91.9%, 99.0% and 90.4%, respectively. The diagnostic accuracy of both the localization and the extent of tumor were not significantly different between gastroscopy alone and gastroscopy plus barium contrast (P>0.05). Diagnostic accuracy of the length of esophagus infiltrated by cardiac cancer in gastroscopy was 60.6%, while in gastroscopy plus barium contrast was 90.9%, which was significantly different (P<0.05). Gastroscopy plus barium contrast was more accurate in predicting the possibility of thoracotomy in cardiac cancer infiltrating the lower esophagus. CONCLUSIONS: It is necessary to perform preoperative barium contrast examination in cardiac cancer patients, so as to identify whether the lower esophagus is infiltrated and to measure the length of lesion, which can provide evidences for making a decision of thoracotomy. For gastric body and antrum cancer, there is no indication for barium contrast examination if gastroscopy findings are satisfied.