Intratumoral IL17-producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer.

BACKGROUND: Tumor IL17-producing (IL17A+) cells infiltration has different prognostic values among various cancers. The objective of this study was to assess the effect of IL17A+ cells in gastric cancer. PATIENTS AND METHODS: The study included two patient cohorts, the Cancer Genome Atlas cohort (TCGA, n = 351) and the Zhongshan Hospital cohort (ZSHC, n = 458). The TCGA and ZSHC were used for mRNA-related and cells infiltration-related analyses, respectively. The roles of IL17A mRNA and IL17A+ cells in overall survival (OS), response to adjuvant chemotherapy (ACT), and immune contexture were evaluated. Another independent cohort was included to identify the correlation between mRNA of IL17A and IL17A+ cells infiltration (the preliminary Zhongshan Hospital cohort, PZSHC, n = 21). RESULTS: The infiltration of IL17A+ cells was positively correlated with the expression of IL17A mRNA (Spearman's ρ = 0.811; P < 0.001). High IL17A mRNA expression and intratumoral IL17A+ cells were correlated with improved OS and remained to be significant after adjusted for confounders. Patients with TNM II/III disease whose tumor present higher intratumoral IL17A+ cells or lower peritumoral IL17A+ cells can benefit more from ACT. Elevated IL17A mRNA expression and increased intratumoral IL17A+ cells infiltration was associated with more antitumor mast cells and nature killer cells infiltration and less pro-tumor M2 macrophages infiltration. High IL17A mRNA expression represented a Th17 cells signature and immune response process and was correlated with increased cytotoxic GZMA, GZMB, IFNG, PRF1, and TNFSF11 expression. CONCLUSIONS: IL17A mRNA expression and intratumoral IL17A+ cells infiltration were correlated with antitumor immune contexture. IL17A+ cells infiltration could be used as an independent prognostic biomarker for OS and predictive biomarker for superior response to ACT, and further prospective validation needs to be conducted.

Long non-coding RNA CCAT1 promotes the migration and invasion of prostate cancer PC-3 cells.

OBJECTIVE: To investigate the effect of long non-coding RNA CCAT1 on the proliferation, migration, and invasion of prostate cancer PC-3 cells. PATIENTS AND METHODS: The expression of CCAT1 was detected by Real-time PCR. The effect of CCAT1 down-regulation on the proliferation of PC-3 cells was observed by MTT assay. The regulatory of CCAT1 low-expression on the migration ability of PC-3 cells was investigated by transwell assay. The influence of decreased CCAT1 on the invasion ability of PC-3 cells was detected by  Matrigel invasion assay. RESULTS: Increased CCAT1 was significantly related to lymph node metastasis in prostate cancer. Low-expression of CCAT1 could suppress cell proliferation. Knockdown of CCAT1 inhibited the migration of PC-3 cells. Down-regulation of CCAT1 attenuated the invasion of PC-3 cells. CONCLUSIONS: CCAT1 promoted the growth and the metastasis of prostate cancer. Our findings might provide a potential target for the diagnosis and treatment of prostate cancer.

[A cohort study of HIV incidence among injecting drug users in Dehong Prefecture, Yunnan Province].

Objective: To investigate the incidence rates of HIV among injection drug users (IDU) in Dehong Prefecture, Yunnan Province. Methods: We recruited 1 413 HIV-negative IDU attending drug rehabilitation centers and identified a further 1 830 potential participants from a historical database from 2004-2009 using the same criteria. Fingerprint recognition technology was used to confirm the identity of all participants. A total of 3 243 HIV-negative IDU were recruited by the end of 2015, of which 2 546 (78.5%) had been followed up at least once since the initial data collection and 697 (21.5%) were lost to follow-up. Epidemiological data were collected through structured face-to-face interviews which included items on knowledge of AIDS, drug use, sexual activity and history of HIV testing. We collected 3-5 ml of venous blood from each subject for HIV testing. The Chi-squared test was used to compare the characteristics of those IDUs successfully followed up and those lost to follow-up. Results: We identified 226 new HIV cases among the 2 546 respondents-representing 13 907.1 person-years of follow-up and implying an average HIV incidence rate of 1.6 per 100 person-years over the entire study period (95%CI: 1.4-1.9). The incidence rate (per 100 person-years) was 2.6 (95%CI: 2.2-3.1) for the period 2004-2009 and 1.6 (95%CI: 1.0-2.3), 1.7 (95%CI: 1.1-2.4), 1.2 (95%CI: 0.8-1.9), 0.6 (95%CI: 0.3-1.1), 0.2 (95%CI:0.0-0.7), 0.5 (95%CI: 0.1-1.4) for each year from 2010 to 2015 respectively. Conclusion: Although the incidence rate of HIV remains high among IDUs in Dehong, there was a declining trend over the period studied.

[Phenotypic characteristics of LAP(+) CD4(+) T lymphocytes in colorectal cancer tissues].

OBJECTIVE: To analyze the phenotypic characteristics of LAP(+) CD4(+) T lymphocytes and investigate their molecular mechanisms in colorectal cancer (CRC) microenvironment. METHODS: Fifty colorectal cancer patients treated in our two hospitals from January 2014 to May 2014 were included in this study. Their tumor tissues and adjacent normal tissues, peripheral blood samples, and peripheral blood samples of 25 healthy donors (HD) were collected to isolate the lymphocytes. The different expressions of CCR7, CD45RA, Foxp3, CTLA-4, CCR4 and CCR5 in LAP(+) CD4(+) T and LAP(-)CD4(+) T lymphocytes were analyzed by flow cytometry (FCM). RESULTS: The FCM assay detected that the percentage of LAP(+) CD4(+) T cells in peripheral blood of the CRC patients were significantly higher than that of HD [(9.44±3.18)% versus (1.49±1.00)%, P<0.001]. In addition, significantly more LAP(+) CD4(+) T cells were also recruited into tumor tissue than those in the tumor-adjacent normal tissue [(11.76±3.74)% versus (3.87±1.64)%, P<0.001]. LAP(+) CD4(+) T cells in the tumor-adjacent normal tissue and peripheral blood of both HDs and CRC patients mainly displayed a central memory phenotype. However, effector memory lymphocytes were predominant in the tumor tissue.In the tumor tissue, the expression of Foxp3 in the LAP(+) CD4(+) T cells was (3.87±1.12)%, significantly lower than that in the LAP(-)CD4(+) T cells (16.70±2.61)%, (P<0.001); the expression of CTLA-4 in the LAP(+) CD4(+) T cells was (36.36±19.14)%, significantly higher than the (19.60±8.91)% in the LAP(-)CD4(+) T cells (P<0.001); the expression of CCR4 in the LAP(+) CD4(+) T cells was (37.72±11.14)%, significantly higher than the (30.06±9.14)% in the LAP(-)CD4(+) T cells (P<0.001); and the expression of CCR5 in the LAP(+) CD4(+) T cells was (18.86±7.10)%, significantly higher than the (13.92±3.31)% in the LAP(-)CD4(+) T cells (P<0.001). CONCLUSIONS: LAP(+) CD4(+) T cells with low expression of Foxp3 and high expressions of CTLA-4, CCR4 and CCR5 are tend to be enriched and accumulated in the tumor tissue. The unique phenotypic characteristics make these cells a distinct subset of lymphocytes, apparently different from the traditional CD4(+) CD25(+) Treg cells.

[Multiple primary lung cancer].

From November 1957 to June 1984, 30 patients with multiple primary lung cancer were diagnosed, basing on clinical features, diagnostic means, histologic type, treatment and prognosis. Out of 3,815 cases of resected primary lung cancer, the incidence of multiple primary cancer was 0.8%. There were 10 synchronous and 20 metachronous cases. There were 17 unilateral, only 1 simultaneous bilateral and 12 contralateral after resection of cancer in the opposite lung. Four of the 10 synchronous cases were definitely diagnosed preoperatively. Among the 20 metachronous cases, 9 were definitely diagnosed as a second primary lesion and the other 11 were proved by thoracotomy. Pathologically, 19 had identical types (15 squamous cell and 4 adenocarcinoma) but 11 had double types (9 squamous cell + adenocarcinoma, 2 squamous cell + anaplastic). The average survival of these 30 patients was 27.1 months, that in the synchronous group was 29 months and that in the metachronous group was 26.2 months. The 5 year survival rate of the synchronous cases was 35%, that of the metachronous cases was 42%. The clinicopathological criteria of multiple primary lung cancer, early diagnostic and operative procedure are also discussed.

[CMC chemotherapy regimen combined with surgery of small cell lung cancer (SCLC)].

From Dec. 1982 to Oct. 1984, 35 patients with SCLC proved by pathology or cytology, were treated by cyclophosphamide + methotrexate + CCNU (CMC) regimen combined with surgery in our hospital. All the patients received chemotherapy for more than 2 courses and the overall response rate was 85.7%, complete remission (CR) rate was 14.3%. Toxic reactions were tolerable to the patients. Treatment result was better in SCLC with localized than extensive disease. Operation was done for 9 out of 21 patients with localized lesions which had responded to chemotherapy. Of them, 1 died of postoperative complication, 2 were lost in follow-up and the rest 6 were disease-free for 8-32 months with a median survival time of 19 months. The 1 year survival rate was 75%. The results indicate that in limited disease of SCLC, successful chemotherapy combined with surgery can prolong the survival time. For patients with an limited disease which has given a CR, surgical resection should be strived for.

[Chemotherapy combined with selective resection in small cell lung cancer--analysis of 239 patients].

From 1957 to 1976, 143 patients with small cell lung cancer (SCLC) were treated with surgical resection followed by chemotherapy. The 5 year survival rates were 38.7%, 8.7% and 3.5% in stages I, II and III. The prognostic factors were clinical stage and chemotherapy. 4 stage I and 1 stage II patients without chemotherapy have survived for more than 5 years. It seems to suggest that SCLC in stage I be indicated for surgery. 4 stage III have survived for more than 5 years, all of whom had received postoperative chemotherapy for more than 4 courses. From 1980 to 1982, 96 patients with SCLC were treated, 37 of whom by chemotherapy combined with surgery. 11/37 patients were alive for more than 2 years, 7 for more than 3 years and 4 for more than 4 years. In the preoperative chemotherapy followed by selective resection plus postoperative chemotherapy group (13 patients), the mean survival time was 22.7 months, but in the postoperative chemotherapy group (24 patients), it was 11.0 months. It indicates that full-dose chemotherapy before and after operation may be superior to the postoperative chemotherapy alone.