XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion.

Lung cancer is the leading cause of cancer-related death worldwide. Glypican-5 (GPC5) is a member of heparan sulfate proteoglycans, and its biological importance in initiation and progression of lung cancer remains controversial. In the present study, we revealed that GPC5 transcriptionally enhanced the expression of CTDSP1 (miR-26b host gene) via AhR-ARNT pathway, and such up-regulation of CTDSP1 intracellularly contributed to the inhibited proliferation of lung cancer cells. Moreover, exosomes derived from GPC5-overexpressing human lung cancer cells (GPC5-OE-derived exosomes) had an extracellular repressive effect on human lymphatic endothelial cells (hLECs), leading to decreased tube formation and migration. Comparison between GPC5-WT- and GPC5-OE-derived exosomes showed that miR-26b (embedded within introns of CTDSP1 gene) was significantly up-regulated in GPC5-OE-derived exosomes and critical to the influence on hLECs. On the mechanism, we demonstrated that miR-26b transferred into hLECs directly targeted to PTK2 3'-UTR and led to PTK2 down-regulation, resulting in defects in tube formation and migration of hLECs. By uncovering the regulation network among GPC5, miR-26b, miR-26b host gene (CTDSP1), and target gene (PTK2), our findings demonstrated that GPC5 functioned as a tumor suppressor in human lung cancer.

Circular RNA hsa_circ_0000467 Promotes the Development of Gastric Cancer by Competitively Binding to MicroRNA miR-326-3p.

Circular RNAs are a class of endogenous noncoding RNAs that play an important role in gene regulation. These RNAs are involved in the development and progression of various cancers, but their roles in gastric cancer have not yet been thoroughly elucidated. This study showed that hsa_circ_0000467 expression was higher in gastric cancer tissues than in corresponding adjacent tissues (P < 0.050) and that hsa_circ_0000467 expression levels were correlated with gastric cancer histological grade (P < 0.050). In addition, hsa_circ_0000467 was remarkably upregulated in gastric cancer cell lines (P < 0.001). Cell function experiments indicated that hsa_circ_0000467 downregulation decreased the proliferation and invasion ability of BGC-823 and SGC-7901 cells and the number of cells entering the G2/M phase. A direct binding interaction was detected between hsa_circ_0000467 and miR-326-3p by dual-luciferase reporter assays. In addition, the results showed that inhibition of miR-326-3p reversed the decreases in the proliferation and invasion of BGC-823 and SGC-7901 cells caused by hsa_circ_0000647 downregulation. Inhibition of miR-326-3p also decreased the number of cells entering the G2/M phase and the expression of cyclin D1. In conclusion, hsa_circ_0000467 plays a regulatory role in the development and progression of gastric cancer by regulating miR-326-3p, and this circRNA may be a potential diagnostic marker and therapeutic target of gastric cancer.

Clinical significance of IFIT2 expression in human renal cancer tissues.

BACKGROUND: Interferon (IFN)-induced protein with tetratricopeptide repeats 2 (IFIT2) is an important member of the IFN-stimulated gene (ISG) family. It has been demonstrated that IFIT2 is important in the physiopathological processes of antiviral and antitumor activities. We previously demonstrated that IFIT2 was highly expressed in paracarcinoma tissues compared with gastric cancer tissues, and its expression level was positively correlated with a superior postoperative prognosis of the patients. METHODS: We performed immunohistochemical staining of IFIT2 in human clear cell renal cell carcinoma (ccRCC) tissues by using a tissue microarray. RNAseq data of kidney clear cell carcinoma (KIRC) samples from The Cancer Genome Atlas (TCGA) were used to perform the enrichment analyses based on the genes that were highly correlated with IFIT2. RESULTS: Weak staining of IFIT2 was located on the cytoplasm and cell membrane surface of the cancer cells, while positive staining of IFIT2 was located mainly on adjacent normal tissues. Survival analysis showed that patients with higher IFIT2 expression had better overall survival than patients with lower IFIT2 expression (P=0.030). The Cox model further demonstrated that age (P=0.002), pathological stage (P=0.000), TNM stage (P=0.005) and IFIT2 expression (P=0.003) could be used as independent prognostic predictors for ccRCC patients. Additionally, the enrichment analysis based on ccRCC expression profile data extracted from TCGA revealed that the genes highly correlated with IFIT2 were mainly related to the biological processes of virus response, T cells and the innate immune response (GO:0009615, GO:0042110, and GO:0045088) and the pathways of NLR signaling, chemokine signaling, and TLR signaling (hsa04621, hsa04062, and hsa04620). CONCLUSIONS: IFIT2 could serve as a potential prognostic marker for ccRCC patients, and the mechanism of decreased IFIT2 expression in the progression of ccRCC merits further investigation.

microRNA-181b suppresses the metastasis of lung cancer cells by targeting sex determining region Y-related high mobility group-box 6 (Sox6).

BACKGROUND: The aim of the study was to measure the expression of microRNA (miR)-181b in patients with lung cancer, investigate its biological function and elucidate the underlying mechanisms associated with the development of lung cancer. METHODS: miR-181b expression in tissues was measured via RT-qPCR. After A549 cells were transfected with miR-181b mimic or si-Sox6, the proliferation, migration and cell cycle distribution of A549 were evaluated using cell counting kit-8 assay, transwell assay and flow cytometry. The levels of cell cycle-related proteins and Sox6 were analyzed by western blotting. Gene targets of miR-181b were predicted via bioinformatics analysis and verified using a dual-luciferase reporter gene assay. RESULTS: Expression of miR-181b was significantly downregulated in lung cancer tissues (P < 0.05), and was inversely correlated with the degree of cell differentiation and clinical stages of lung cancer (both P < 0.05). Additionally, the expression of miR-181b was significantly lower in adenocarcinoma compared with squamous cell carcinoma in the lungs (P < 0.05). Overexpression of miR-181b significantly decreased the protein level of Sox6 and significantly suppressed the cell proliferation and metastasis (both P < 0.05); this effect was also observed in A549 cells transfected with si-Sox6. The luciferase activity of a Sox6 3'-untranslated region-based reporter construct was significantly lower when transfected with miR-181b (P < 0.05), which suggests that Sox6 is a direct target of miR-181b. CONCLUSION: The results of the present study suggest that miR-181b may function as a tumor inhibitor in the development of lung cancer via targeting Sox6 to decrease the proliferation and metastasis of lung cancer cells.

Effect of C-reactive protein/albumin ratio on prognosis in advanced non-small-cell lung cancer.

AIM: Systemic inflammatory response is closely related to tumor progression. We retrospectively investigated relationships between systemic inflammatory scores, C-reactive protein/albumin (CRP/Alb) ratio (CAR) and clinical characteristics in advanced non-small-cell lung cancer (NSCLC) in 436 patients to find better clinical predictors of NSCLC prognosis. METHODS: Blood specimens were collected 1 week before treatment to test for systemic inflammatory scores and albumin. Patients' overall survival (OS) was calculated via Kaplan-Meier method. Single-factor log-rank and multivariate Cox regression analyses and receiver operating characteristic curves were used to evaluate the prognostic significance of CAR and other systemic inflammatory indexes in predicting OS. RESULTS: Kaplan-Meier method showed that Glasgow prognosis score (GPS), modified GPS (mGPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) were reliable prognostic factors for advanced NSCLC. CAR was positively correlated with GPS, mGPS, NLR, PLR and MLR in these patients. CAR was an independent risk factor for OS in advanced NSCLC, and was more closely associated with prognosis than were GPS, mGPS, NLR, PLR or MLR. CONCLUSION: In advanced NSCLC patients, CAR may be a better predictor of prognosis compared with other inflammatory markers. A prospective multicenter study is needed to verify these findings.

Prognostic value of interim (18)F-FDG-PET in diffuse large B cell lymphoma treated with rituximab-based immune-chemotherapy: a systematic review and meta-analysis.

The prognostic value of an interim fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for diffuse large B-cell lymphoma (DLBCL) has been assessed by different groups. However, studies have suggested that the use of rituximab could limit the predictive value of interim (18)F-FDG PET for DLBCL. To clarify the prognostic value of interim (18)F-FDG PET in DLBCL patients treated with rituximab based immunochemotherapy, we searched for relevant studies in PubMed, the Cochrane Library and EMBASE. A random versus fixed effects model was applied according to the heterogeneity. According to the literature search strategies, 11 studies were identified. The pooled HR comparing PFS between patients with positive and negative results was 2.96 (95% CI=2.25-3.89). The patients in interim (18)F-FDG PET negative group had a higher CR rates than that in interim (18)F-FDG PET positive group (RR=5.53, 95% CI=2.59-11.80). Consistent evidence favoring interim (18)F-FDG PET-based treatment assessment should be considered in the management of patients with DLBCL.

The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). PATIENTS AND METHODS: We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. RESULTS: Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). CONCLUSIONS: PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.

High expression of CD11c indicates favorable prognosis in patients with gastric cancer.

AIM: To determine the relationship between CD11c expression level and prognosis in patients with gastric cancer (GC). METHODS: This retrospective survival study was performed from July 31, 2008 to June 30, 2014. Our study inclusion criteria included all the patients with GC who underwent surgical resection between January 1998 and December 2009 in the Third Affiliated Hospital of Soochow University. CD11c expression levels in 140 patients with GC at different UICC stages were evaluated using immunohistochemistry, and GC tissues from 16 cases were further verified by qRT-PCR. The χ (2) test was used to compare the patient- and disease-related factors between the low CD11c expression group and the high expression group. Univariate probabilities of overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The log rank test was used to compare survival curves. Different multivariate COX models were used to estimate the association between CD11c expression and both death and recurrence risk in GC patients. RESULTS: The average CD11c expression level was 5.1 ± 1.8/high power field (HPF) in 10 gastritis samples, 4.5 ± 2.3/HPF in 10 gastric polyp samples and 9.7 ± 6.3/HPF in 140 gastric cancer samples, respectively. The CD11c expression level was significantly decreased from UICC stage I to stage IV (stage I: 16.0 ± 7.4, stage II: 10.4 ± 5.5, stage III: 9.4 ± 6.1, stage IV: 5.3 ± 3.2, P < 0.001). Patients in the high CD11c expression group had a greater 3- and 5-year OS probability and longer median survival time compared with the low CD11c expression group, (67.7% vs 39.2%; 51.4% vs 29.0%; 67.0 mo vs 28.0 mo; χ(2) = 6.80, P = 0.009), and had a greater 3- and 5-year DFS probability and longer median DFS time (63.7% vs 24.0%; 49.1% vs 11.9%; 64.0 mo vs 18.0 mo; χ (2) = 15.39, P < 0.001). Patients with high CD11c high expression had a reduced risk of death (HR = 0.56, 95%CI: 0.33-0.98, P < 0.05) and relapse (HR = 0.39, 95%CI: 0.23-0.67, P < 0.01) compared with patients with low CD11c expression after adjustment of potential confounders, with the exception of tumor size. However, the protective effect related to death (HR = 0.90, 95%CI: 0.49-1.67, P = 0.749) and relapse (HR = 0.65, 95%CI: 0.36-1.19, P = 0.160) disappeared when tumor size was incorporated into the model. CONCLUSION: High expression of CD11c decreased the risk of death and relapse, and may be regarded as an alternative indicator of favorable prognosis in patients with GC.

Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma.

INTRODUCTION: The 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system for esophageal cancer defined N classification based on the number of metastatic lymph nodes (LNs). However, this classification might neglect the extent of LNs metastasis. This study aimed to revise N classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous-cell carcinoma (ESCC). METHODS: We retrospectively reviewed 1993 ESCC patients who underwent curative resection. The proposed N categories based on the number of LNs metastasis stations were compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio χ statistics and Akaike information criterion calculations. RESULTS: The survival differences were not significant for N2 versus N3 category (p = 0.231) and stages IIIB versus IIIC (p = 0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio χ scores and smaller Akaike information criterion values than the 7th AJCC staging system, which represented the optimum prognostic stratification. CONCLUSIONS: The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result.

Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response.

Radiofrequency ablation (RFA) causes coagulative necrosis of tumor tissue and the production of local tumor protein debris. These fragments of tumor protein debris contain a large number of various antigens, which can stimulate a specific cellular immune response. In the present study, dendritic cells (DCs) were loaded with tumor protein lysate antigens that were produced in situ by RFA, and were used to treat murine colon carcinoma in combination with cytokine-induced killer (CIK) cells. Subsequent to the treatment of murine colon carcinoma by RFA, the in situ supernatant of tumor lysis was collected and the DCs were loaded with the lysate antigen to generate Ag-DCs. CIK cells induced from the spleen cells of mice were co-cultured with Ag-DCs to generate Ag-DC-CIK cells. The results revealed that the Ag-DC-CIK cells exhibited strong antitumor activity in vitro and in vivo. The morphology and immunophenotypes of these cells were determined using microscopy and flow cytometry, respectively. The cytotoxic activity of Ag-DC-CIK cells was determined using a CCK-8 assay. To establish a mouse model, mice were randomized into Ag-DC-CIK, DC-CIK, CIK and PBS control groups and monitored for tumor growth and survival time. ANOVA was used to compare the trends in the three groups for implanted tumor volumes. The log-rank test was used to compare the survival time. The present findings indicated that DCs loaded with the protein lysate antigens of tumors, produced in situ by RFA, combined with CIK cells may be a novel strategy for cancer treatment.

PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation.

Immunotherapy has become a crucial modality for non-small-cell lung cancer treatment. Recently, two immune checkpoints, PD-1 and PD-L1, have emerged as important targets for immunotherapy. Their antitumor efficacy has been confirmed by in vitro and in vivo studies. But the correlation between PD-1/PD-L1 expression and EGFR expression was controversial and needs more evidences to support the combination of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors.

Serum ferritin is elevated in advanced non-small cell lung cancer patients and is associated with efficacy of platinum-based chemotherapy.

AIM: The aim of this study was to determine the expression levels of serum ferritin (SF) and investigate the correlation between SF expression levels and clinical characteristics as well as the efficacy to platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Electrochemiluminescence method was used to determine the expression levels of SF in the peripheral blood of 46 advanced NSCLC patients and 63 healthy subjects. RESULTS: The expression levels of SF in healthy subjects were significantly lower than those in patients with advanced NSCLC patients (t = -3.279,P = 0.001). There was a statistically significant difference between SF expression levels and distant metastasis, regional lymph node metastasis, respectively (P < 0.05). However, there was no correlation between SF expression levels and sex, age, eastern cooperative oncology group performance status, smoking history, pathological type, tumor location and tumor-node-metastasis stage (All P > 0.05). The overall response rate to platinum-based chemotherapy was 57.1% (12/21) in normal SF expression levels group, which was significantly higher than that was 28% (7/25) in high SF expression levels group (χ² = 3.998,P = 0.046). CONCLUSIONS: SF may be a valuable blood marker for predicting the tumor progression and the efficacy of platinum-based therapies for advanced NSCLC patients.

Evaluation of tumor response to cytokine-induced killer cells therapy in malignant solid tumors.

CIK cells therapy has been evaluated as an adoptive cell immunotherapy for cancer patients, but there still have not been any standardized systems for evaluating the antitumor efficacy yet. The WHO and RECIST criteria have already been established for a few years but not sufficient to fully characterize the activity of immunotherapy. Based on these two criteria, the irRC was proposed for evaluating the efficacy of immunotherapy. A variety of bioassays for immune monitoring including the specific and non-specific methods, have been established. We recommend detect levels of various immunocytes, immune molecules and soluble molecules to find the correlations among them and clinicopathological characteristics to establish criteria for immunological classification. We also recommend a paradigm shift for the oncologists in the evaluation of immune therapies to ensure assessment of activity based on clinically relevant criteria and time points.

Clinical application of serum alpha-fetoprotein-IgM complexes on the diagnosis of primary hepatocellular carcinoma in Kazakh and Han populations.

AIMS AND BACKGROUND: We detected serum AFP-IgM levels in patients with primary hepatocellular carcinoma in Kazakh and Han populations to investigate the clinical significance of AFP-IgM in the diagnosis of hepatocellular carcinoma. METHODS AND STUDY DESIGN: Serum AFP-IgM levels were examined in 28 cases of hepatocellular carcinoma and 164 controls in the Kazakh population and in 85 cases of hepatocellular carcinoma and 187 controls in the Han population. AFP-IgM was detected with the ELISA assay. RESULTS: In general, serum AFP-IgM levels of hepatocellular carcinoma patients in the Han population and hepatocellular carcinoma patients in the Kazakh population were statistically higher than those of controls, but there was no statistical significance between hepatocellular carcinoma patients in the Han and hepatocellular carcinoma patients in the Kazakh population. CONCLUSIONS: AFP-IgM is an encouraging serological marker and may be useful in the diagnosis of hepatocellular carcinoma.

Characteristic analysis of α-fetoprotein-producing gastric carcinoma in China.

α-Fetoprotein-producing gastric cancer (AFPGC) is a rare type of gastric cancer. The largest population of patients with AFPGC is found in China. In the present study, a total of 4,779 GC patients, including 317 AFPGC patients, from 11 clinical studies in China with a general AFPGC/GC ratio of 6.63% were summarized and analyzed. On the basis of analysis of the clinical data, the patients with AFPGC had larger tumor size, weaker cell differentiation, worse histopathological types, deeper serosal infiltration, more lymph node and liver metastases, poorer stages, shorter survival time and more positive expression of vascular endothelial growth factors than the patients without AFPGC. Our observation is consistent with previous results reported in studies of AFPGC. Overall, AFPGC is a subtype of GC with a poor prognosis.

Relationship between glutathione S-transferase P1 (GSTP1), X-ray repair cross complementing group 1 (XRCC1) and 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene polymorphisms and response to chemotherapy in advanced gastric cancer.

BACKGROUND: Our study aimed to investigate the relationship between glutathione S-transferase P1 (GSTP1), 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) and X-ray repair cross complementing group 1 (XRCC1) gene polymorphisms and the response to chemotherapy in advanced gastric cancer. PATIENTS AND METHODS: 59 cases of advanced gastric cancer were enrolled. All patients were treated with the DCF regimen comprising docetaxel, cisplatin, and 5-fluorouracil. All patients' genotypes regarding GSTP1, XRCC1, and 5,10-MTHFR were analyzed by polymerase chain reaction/ligase detection reaction (PCR-LDR). RESULTS: There were 15 (25.42%) cases of G/G genotype, 21 (35.59%) of G/A genotype, and 23 (38.98%) of A/A genotype for GSTP1, 16 (27.12%) cases of A/A genotype, 18 (30.51%) of G/A genotype, and 25 (42.37%) of G/G genotype for XRCC1, and 21 (35.59%) cases of C/C genotype, 22 (37.29%) of C/T genotype, and 16 (27.12%) of T/T genotype for 5,10-MTHFR. After 2 cycles of chemotherapy, there were 4 cases of complete remission, 14 of partial remission, 19 of stable disease, and 22 of advanced disease, with a total effective rate of 30.51%. Better survival was shown for GSTP1 G/G genotype, XRCC1 A/A genotype, and 5,10-MTHFR T/T genotype (p < 0.05). CONCLUSION: The gene polymorphisms of GSTP1 G/G, XRCC1 A/A, and 5,10-MTHFR T/T have clinical value for predicting the response to the DCF regimen for advanced gastric cancer.

Clinical significance of CD44 variants expression in colorectal cancer.

AIMS AND BACKGROUND: We designed the present study to observe CD44s and CD44v6 expressions in colorectal cancer and evaluate their clinical value. METHODS: CD44s and CD44v6 expression in colorectal cancer tissues were examined by an immunohistochemical test. Survival analysis was performed with the Kaplan-Meier method, and the differences between the CD44-positive and -negative groups were evaluated with the logrank test. RESULTS: The positive rates of CD44s and CD44v6 were 66.7% and 63.2%, respectively. There were significant associations between CD44s positive expression and Dukes' stage or tumor differentiation. There were significant associations between CD44v6 positive expression and tumor differentiation, Dukes' stage and lymph node metastasis. There was a significant difference in the 5-year survival rates between CD44v6-positive and CD44v6-negative groups (52.78% and 80.95%, respectively), but not between CD44s-positive and CD44s-negative groups (55.26% and 78.95%, respectively). Multivariate analysis indicated that CD44v6 positive expression predicts a poor prognosis. CONCLUSIONS: CD44s and CD44v6 play important roles in the infiltration and metastasis of colorectal cancer. CD44v6 positive expression can be a predictor for a poor prognosis.

Mechanism of T cell regulation by microRNAs.

MicroRNAs (miRNAs) are small, non-coding single-stranded RNAs that can modulate target gene expression at post-transcriptional level and participate in cell proliferation, differentiation, and apoptosis. T cells have important functions in acquired immune response; miRNAs regulate this immune response by targeting the mRNAs of genes involved in T cell development, proliferation, differentiation, and function. For instance, miR-181 family members function in progression by targeting Bcl2 and CD69, among others. MiR-17 to miR-92 clusters function by binding to CREB1, PTEN, and Bim. Considering that the suppression of T cell-mediated immune responses against tumor cells is involved in cancer progression, we should investigate the mechanism by which miRNA regulates T cells to develop new approaches for cancer treatment.

Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer.

In the present study, we studied the expression of T-bet, a key marker for type 1 immune responses, within the tumor microenvironment of gastric cancer, and analyzed its association with clinicopathological parameters. One hundred and fifty-two archival paraffin-embedded gastric tumor tissues were collected, and the expression of T-bet in these cancer tissue specimens was examined by immunohistochemistry. T-bet(+) tumor-infiltrating lymphocytes (TILs) in some gastric cancer tissues were further characterized by flow cytometric analysis. The density of T-bet(+) TILs in gastric cancer tissues in relation to patient's clinicopathological parameters and postoperative prognosis has been analyzed. Herein, we have found significant increases in T-bet(+) lymphocytes in tumor tissues as compared with normal stomach tissues, gastritis tissues or gastric polyp specimens. T-bet(+) cells mainly consisted of CD4(+), CD8(+) and CD56(+) TILs. In addition, lower numbers of T-bet(+) TILs were associated with poor clinicopathological parameters such as invasion to muscular layer, larger tumor size and advanced cancer stages. Moreover, patients with higher numbers of T-bet(+) TILs have longer disease-free survival and overall survival. Thus, our study supports the idea that tumor growth elicits spontaneous type 1 cellular immune responses and tumor progression is associated with suppression of antitumor immunity. T-bet expression within tumor can serve as a prognostic indicator for gastric cancer and a potential biomarker for immunotherapy.