BackgroundThis randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer.MethodsSixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60–90 min. The primary end point was overall survival, and the secondary end points were safety profiles.ResultsMajor clinicopathological characteristics were balanced between the 2 groups. The PC index was 2–36 (median 15) in the CRS + HIPEC and 3–23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0–1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5–83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8–8.2 months) in CRS and 11.0 months (95% confidence interval 10.0–11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0–1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival.ConclusionsFor synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.
Background Tumor-associated macrophages (TAMs) are major components of tumor microenvironment that frequently associated with tumor metastasis in human cancers. Circulating tumor cell (CTC), originating from primary tumor sites, is considered to be the precursors of tumor metastasis. However, the regulatory mechanism of TAMs in CTC-mediated tumor metastasis still remains unclear. Methods Immunohistochemical staining was used to detect the macrophages infiltration (CD68 and CD163), epithelial–mesenchymal transition (EMT) markers (E-cadherin and Vimentin) expression in serial sections of human colorectal cancer (CRC) specimens. Then, the correlations between macrophages infiltration and clinicopathologic features, mesenchymal CTC ratio, and patients’ prognosis were analyzed. A co-culture assay in vitro was used to evaluate the role of TAMs on CRC EMT, migration and invasion, and ELISA, luciferase reporter assay and CHIP were performed to uncover the underlying mechanism. Furthermore, an in vivo model was carried out to confirm the effect of TAMs on mesenchymal CTC-mediated metastasis. Results Clinically, CD163 + TAMs infiltrated in invasive front was associated with EMT, mesenchymal CTC ratio, and poor prognosis in patients with CRC. CRC–conditioned macrophages regulated EMT program to enhance CRC cells migration and invasion by secreting IL6. TAMs-derived IL6 activated the JAK2/STAT3 pathway, and activated STAT3 transcriptionally inhibited the tumor suppressor miR-506-3p in CRC cells. miR-506-3p, a key miRNA regulating FoxQ1, was downregulated in CRC cells, resulting in increased FoxQ1 expression, which in turn led to the production of CCL2 that promoted macrophage recruitment. Inhibition of CCL2 or IL6 broke this loop and reduced macrophage migration and mesenchymal CTC-mediated metastasis, respectively. Conclusions Our data indicates that TAMs induce EMT program to enhance CRC migration, invasion, and CTC-mediated metastasis by regulating the JAK2/STAT3/miR-506-3p/FoxQ1 axis, which in turn leads to the production of CCL2 that promote macrophage recruitment, revealing a new cross-talk between immune cells and tumor cells in CRC microenvironment. Electronic supplementary material The online version of this article (10.1186/s12943-019-0976-4) contains supplementary material, which is available to authorized users.
A nanostructured platform that combines electrospun TiO(2) nanofibers (TiNFs)-deposited substrate and cell-capture agent realizes significant capture of circulating tumor cells (CTCs). The enhanced local topographic interactions between the horizontally packed TiNFs deposited substrates and extracellular matrix scaffolds, in addition to anti-EpCAM/EpCAM biological recognition, contributes to the significantly enhanced capture efficiency compared to flat surfaces.
A platform for capture and release of circulating tumor cells (CTCs) is demonstrated by utilizing aptamer grafted silicon nanowires. Here, single‐stranded DNA‐aptamers are generated via the Cell‐SELEX process to serve as capture agents, allowing specific capture and release of non‐small cell lung cancer (NSCLC) CTCs from whole‐blood samples with minimum contamination and negligible disruption to CTC viability and functions.
A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires. In this platform, integration of ligand‐receptor recognition, nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells. Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.
The aim of this study was to determine a role of microRNA-21 (miR-21) in colorectal cancer (CRC) and to elucidate the regulation of phosphatase and tensin homologue (PTEN) gene by miR-21. MiR-21 expression was investigated in 30 CRC samples and five CRC cell lines. In this study, we show that the expression of miR-21 was overexpressed in CRC compared with adenomas and normal tissues. Patients with poor differentiation, lymph node metastasis and advanced TNM stage showed significantly high expression of miR-21. Inhibition of miR-21 in the HCT116 cell line reduced cellular proliferation, migration and invasion, induced apoptosis and inhibited cell cycle progression. The PTEN protein levels in CRC tissues and cells had an inverse correlation with miR-21 expression. Anti-miR-21-transfected cells increased PTEN protein expression without changing the PTEN mRNA level and increased a luciferase-reporter activity. MiR-21 targets PTEN at the post-transcriptional level and regulates cell proliferation and invasion in CRC. It may serve as a novel therapeutic target in CRC.
Background Robotic surgery has been used successfully in many branches of surgery, but there is little evidence in the literature on its use in rectal cancer (RC). We conducted this meta-analysis of randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) to evaluate whether the safety and efficacy of robotic total mesorectal excision (RTME) in patients with RC are equivalent to those of laparoscopic TME (LTME). Methods Pubmed, Embase, Cochrane Library, Ovid, and Web of Science databases were searched. Studies clearly documenting a comparison of RTME with LTME for RC were selected. Operative and recovery outcomes, early postoperative morbidity, and oncological parameters were evaluated. Results Eight studies were identified that included 1229 patients in total, 554 (45.08 %) in the RTME group and 675 (54.92 %) in the LTME group. Compared with LTME, RTME was associated with lower conversion rate (OR 0.23, 95 % CI [0.10, 0.52]; P= 0.0004), lower positive rate of circumferential resection margins (CRM) (2.74 % vs 5.78 %, OR 0.44, 95 % CI [0.20, 0.96], P= 0.04), and lesser incidence of erectile dysfunction (ED) (OR 0.09, 95 % CI [0.02, 0.41]; P=0.002). Operation time, estimated blood loss, recovery outcome, postoperative morbidity and mortality, length of hospital stay, number of lymph nodes harvested, distal resection margin (DRM), proximal resection margin (PRM), and local recurrence had no significant differences between the two groups. Conclusions RTME is safe and feasible and may be an alternative treatment for RC. More international multicenter prospective large sample RCTs investigating the long-term oncological and functional outcomes are needed to determine the advantages of RTME over LTME in RC.
Background: The interaction and crosstalk between tumor-associated macrophages (TAMs) and epithelial-mesenchymal transition (EMT) has been demonstrated to play a critical role in the progression and metastasis of multiple cancers. However, the roles of the M2-polarized TAMs in different tumor location in EMT and prognosis of colorectal cancer (CRC) have not been elucidated. Therefore, the present study was designed to set up a reliable ratio of CD163 + /CD68 + to assess M2-polarized TAMs infiltration in the tumor center (TC) and tumor invasive front (TF) and to further evaluate their prognostic value and biological effects on tumor cells in CRC. Methods: TAMs markers (CD68 and CD163) and EMT markers (E-cadherin and Vimentin) expression were evaluated by immunohistochemistry in 81 patients with CRC. Circulating tumor cells (CTCs) of peripheral blood from above patients was also isolated. The correlation of CD163 + /CD68 + ratio in different locations, EMT and CTCs counts were further analyses. Kaplan-Meier and the model analyses of univariate Cox proportional hazards were utilized to compare the survival of patients with high CD163 + /CD68 + ratio with those with low CD163 + /CD68 + ratio. Furthermore, the effects of the M2-polarized TAMs on growth, migration and invasion of CRC cells were explored in vivo and in vitro co-culture system. Results : The results showed that the level of CD163 + /CD68 + ratio in TF was significant higher than that in TC, and higher CD163 + /CD68 + TF ratio were closely correlated with enhanced lymphovascular invasion, tumor invasion and TNM stage. Interestingly, higher CD163 + /CD68 + TF ratio were also significantly associated with EMT program and CTCs counts. Meanwhile, Kaplan-Meier analysis showed that CD163 + /CD68 + TF was associated with both recurrence-free survival (RFS) and overall survival (OS) of patients with CRC. Multivariate Cox regression analyses demonstrated that CD163 + /CD68 + TF remained an independent prognostic factor for RFS and OS. Further receiver operating characteristic (ROC) curve analysis found that CD163 + /CD68 + TF was a better prognosticator compared with CD68 + TF and CD163 + TF for CRC patients. What's more, M2-polarized TAMs secreted TGF-β to facilitate the EMT, growth, proliferation and invasion of CRC cells by in vivo and ...
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