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The prognosis for patients with head and neck cancer (HNC) remains poor, owing to uncontrolled tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) serves an important role in this invasion and metastasis, and transient receptor potential polycystic 2 (TRPP2) enhances metastasis and invasion by regulating EMT in human laryngeal squamous cell carcinoma. The present study examined whether exosomes/TRPP2 small interfering RNA (siRNA) complexes were able to reduce EMT by suppressing TRPP2 expression in FaDu cells, a cell line of human pharyngeal squamous cell carcinoma. Using agarose gel electrophoresis, it was determined that exosome/TRPP2 siRNA complexes were stable in the presence of nucleases and serum. A fluorescence assay and western blotting analysis was performed, and it was reported that the FaDu cells took up exosomes, the exosomes effectively delivered TRPP2 siRNA into FaDu cells and that exosome/TRPP2 siRNA complexes significantly suppressed TRPP2 protein expression levels in FaDu cells. Furthermore, expression levels of E-cadherin were significantly increased, whereas expression levels of N-cadherin and vimentin were significantly decreased in FaDu cells transfected with TRPP2 siRNA. Thus, exosome/TRPP2 siRNA complexes markedly suppressed TRPP2 expression and EMT in FaDu cells. These results suggested that further development of exosome/TRPP2 siRNA complexes for use as an RNA-based gene therapy in the treatment of HNC is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer (CRC), one of the most aggressive gastrointestinal malignancies, is a frequently diagnosed life-threatening cancer worldwide. Most CRC patients have poor prognosis mainly because of frequent metastasis and recurrence. Thus, it is crucial to find out some new biomarkers and to show deeper insights into the mechanisms of CRC. MLLT10, Myeloid/lymphoid or mixed-lineage leukemia translocated to 10, also known as AF10, a recurrent MLL partner. In this study, we found that MLLT10 promotes CRC tumor invasion and metastasis both in vitro and in vivo. Methods: Here, the expression of MLLT10 was evaluated by immunohistochemistry. Then, the plasmid and lentivirus particles for MLLT10 overexpression or knockdown were designed and constructed into SW620 and HT29 cells. Finally, cell proliferation assay, cell adhesion assay, transwell migration, and invasion assay were used to detect the migration and invasion ability of MLLT10 in CRC cells. A tail vein injection assay was employed to evaluate the role of MLLT10 in tumor metastases. Results: MLLT10 expression was significantly higher in CRC tissues than in noncancerous tissues and was associated with some clinicopathological factors. In vitro, the overexpression of MLLT10 promoted CRC cell migration and invasion, while after MLLT10 was knocked down, the opposite results were observed. Furthermore, we used animal metastasis models to detect the function of MLLT10 in vivo, the results are same with the outcomes in vitro. In lung metastasis sites, the knockdown of MLLT10 in SW620 cells significantly inhibited Vimentin expression, whereas the E-Cadherin was increased. Conclusions: These results indicate that MLLT10 regulates the metastasis of CRC cells via EMT. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P=0.017) and higher baseline platelet count (P=0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P=0.037). The median RNG was 3.01, with a range of 1.19–16.84. RNG level was significantly associated with lymph node metastasis of these patients (P=0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P=0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT. [ABSTRACT FROM AUTHOR]

Objective: To report the feasibility of laparoscopic resection with intraoperative radiotherapy for local advanced rectal cancer in an Asian man. Patient and Methods: A 55-year-old man with adenocarcinoma of the rectum presented at Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. The tumor, with a size of 5×5 cm, was located 3 cm from the anus and covered a circular area around approximately two-thirds of the bowel. The carcinoembryonic antigen level was 29.86 ng/mL; a nodule was detected, but no distant metastasis was detected. Preoperative staging was T4N1M0. After the patient signed the consent form, laparoscopic resection with intraoperative radiotherapy was performed. Results: The operation time was about 180 minutes, intraoperative blood loss was 100 mL, and postoperative hospital stay was 8 days. The patient had no postoperative complications. Conclusions: Performance of laparoscopic resection with intraoperative radiotherapy for local advanced rectal cancer is feasible in selected patients. [ABSTRACT FROM AUTHOR]

Introduction: L: -plastin, an actin-binding protein, is upregulated in many tumours, including colorectal carcinoma. This study evaluated the expression of L: -plastin in plasma and colorectal tumour tissue and analysed the correlation between clinicopathological staging and prognosis.Materials and Methods: Enzyme-linked immunosorbent assay was used to detect L: -plastin in the plasma of 120 colorectal carcinoma patients and 40 control subjects. Immunohistochemistry analyses were also used.Results: The rate of positive L: -plastin expression was significantly higher in colorectal carcinoma patients than in control subjects, and was significantly higher in tumour tissues than in the tissues surrounding the tumour. L: -Plastin expression also is correlated with tumour grade and size, and lymph node metastasis. However, there was no correlation with the extent of tumour invasion or distant metastasis.Conclusion: L: -Plastin may be a useful marker for screening colorectal carcinoma and determining the prognosis of patients with colorectal carcinoma, and for genetic therapy and targeted therapy of colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Primary tumour resection (PTR) is still a selection for patients with low tumour burden and good condition, especially with conversion therapy purpose for colorectal liver-limited metastases (CRLMs). The objective was to evaluate whether pre-PTR chemotherapy could improve progression-free survival (PFS) for patients with asymptomatic synchronous unresectable CRLMs. Patients with asymptomatic synchronous unresectable CRLMs were randomly assigned to receive pre-PTR chemotherapy (arm A) or upfront PTR (arm B). Chemotherapy regimens of mFOLFOX6 plus cetuximab, mFOLFOX6 plus bevacizumab or mFOLFOX6 alone were chosen according to the RAS genotype. The primary end-point was PFS; secondary end-points included overall survival (OS), tumour response, disease control rate (DCR), liver metastases resection rate, surgical complications and chemotherapy toxicity. Three hundred and twenty patients were randomly assigned to arm A (160 patients) and arm B (160 patients). Patients in arm A had significantly improved the median PFS compared with arm B (10.5 versus 9.1 months; P = 0.013). Patients in arm A also had significantly better DCR (84.4% versus 75.0%; P = 0.037). The median OS (29.4 versus 27.2 months; P = 0.058), objective response rate (ORR) (53.1% versus 45.0%; P = 0.146) and liver metastases resection rate (21.9% versus 18.1%; P = 0.402) were not significantly different. The Clavien–Dindo 3–4 complications post PTR (4.5% versus 3.8%, P = 0.759) and the incidence of grade 3/4 chemotherapy events (42.2% versus 40.4%, P = 0.744) reached no statistical significance. For asymptomatic synchronous unresectable CRLMs, Pre-PTR chemotherapy improved the PFS compared with upfront PTR. • It was the first RCT to evaluate the PFS of pre-PTR chemotherapy for CRLMs. • Pre-PTR chemotherapy improved the PFS compared with upfront PTR. • This trial provided evidence to confirm the advantages of pre-PTR chemotherapy. [ABSTRACT FROM AUTHOR]

Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo . High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

As CDKN2B-AS1 is demonstrated to exert promotive effects on thyroid cancer (TC), this research aims to investigate the role of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in TC and the underlying regulatory mechanism. Specifically, CDKN2B expression and the correlation of CDKN2B with CDKN2B-AS1 in TC were determined via bioinformatics analysis and further verified by qRT-PCR. After transfection or co-culture with CSCs-derived exosomes, viability, migration, and invasion of TPC-1 and SW579 cells were evaluated by CCK-8, wound healing, and transwell assays, respectively. The uptake of exosomes by TC cells was detected by PKH67 labeling. In vivo tumor formation and metastasis models were established. Tumor volume and weight were calculated. Metastasis loci in lung tissues were observed by hematoxylin-eosin staining. The expression levels of CDKN2B-AS1, CDKN2B, and epithelial-mesenchymal transition- and TGF-β1/Smad2/3 signaling-related factors were detected by qRT-PCR or Western blot. Concretely, CDKN2B and CDKN2B-AS1 were highly expressed in TC, and there was a positive correlation between the two. In addition, CDKN2B-AS1 promoted the translation and stability of CDKN2B. Furthermore, CDKN2B-AS1 was highly expressed in CSCs and CSCs-derived exosomes which could be absorbed by TC cells. CDKN2B silencing inhibited viability, migration, invasion, protein levels of CDKN2B, N-cadherin and Vimentin, and TGF-β1/Smad2/3 signaling, while promoting E-cadherin expression in TC cells. CSCs-derived exosomal CDKN2B-AS1 did oppositely and reversed the effects of CDKN2B silencing on TC cells. CDKN2B silencing impeded tumor growth and metastasis in TC mice, while TGF-β1 performed inversely and impaired the effects of CDKN2B silencing. Collectively, CSCs-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote growth and metastasis of TC via TGF-β1/Smad2/3 signaling. [ABSTRACT FROM AUTHOR]