This study aimed to compare the changes and determine the clinical significance of carbohydrate antigens CA242, CA199, CA125, carcinoembryonic antigen (CEA), and tumor-specific growth factor (TSGF) before and after cryoablation by Cryocare system. Thirty-one pancreatic cancer patients were selected to receive cryoablation by Cryocare system. The serum expression levels of CA242, CA199, CA125, CEA, and TSGF before and 1 month after treatment were determined. Meanwhile, the serum level of these factors was also determined in 31 healthy volunteers. The parameter changes were analyzed with the clinical pathological data. The serum levels of CA242, CA199, CA125, CEA, and TSGF in the pancreatic cancer group were significantly higher than those of the control group both before and after the cryoablation treatment (P < 0.05). The serum CA199, CEA, and TSGF dramatically decreased 1 month after the treatment, which were statistically different (P < 0.05). The positive rates of serum CA242, CA199, CA125, and CEA in the pancreatic cancer group were much higher than those in the control group both before and after treatment (P < 0.05), and the positive rate of TSGF was significantly higher than that of the control group before the treatment (P < 0.05). The positive rate of CA199, CEA, and TSGF after the treatment was significantly lower than that before the treatment (P < 0.05). Serum level of CA242 was correlated with the tumor diameter, clinical staging, tumor differentiation, lymph node, and liver metastasis (P < 0.05). Except gender, CA199 was correlated with all the other clinical pathological parameters (P < 0.05). The serum levels of CA125 and CEA were correlated with all the other clinical pathological parameters (P < 0.05). The serum level of TSGF was only correlated with tumor differentiation (P < 0.05). Cryoablation treatment by Cryocare system can decrease the serum levels of CA199, CEA, TSGF, and the positive rate. Serum CA199, CEA, and TSGF can be important index for pancreatic cancer treatment assessment. Serum levels of CA242, CA199, CA125, and CEA are of great clinical value for metastasis assessment and prognosis in pancreatic cancer patients.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Currently, an increasing evidence showed that circular RNAs (circRNAs) play important roles in tumor progression. However, the effects and underlying mechanisms of circRNAs in CRC progression remain unclear. In the present study, through circRNA high-throughput sequencing and quantitative real-time polymerase chain reaction, we identified that hsa_circ_0136666 was significantly overexpressed in CRC tissues and cell lines. High hsa_circ_0136666 expression was associated with poor overall survival of patients with CRC. In vitro function assays showed that hsa_circ_0136666 inhibition suppressed CRC cell proliferation, migration, invasion, and arrested CRC cells in the G0/G1 phase. Furthermore, we showed that hsa_circ_0136666 inhibition reduced CRC cell growth in vivo. Mechanistically, we revealed that hsa_circ_0136666 could increase SH2B1 expression via competitively binding miR-136 in CRC cells. In addition, SH2B1 overexpression could reverse the effects of hsa_circ_0136666 inhibition on CRC cell progression. In conclusion, our data suggested that hsa_circ_0136666 could promote CRC cell progression via the miR-136/SH2B1 axis, elucidating a novel approach to improve the effectiveness of CRC treatment. K E Y W O R D Scolorectal cancer (CRC), hsa_circ_0136666, miR-136, SH2B1

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Objective To investigate tumor and pregnancy outcomes after fertility-sparing surgery for cervical cancer. Methods A total of 83 patients with cervical cancer who received fertility-sparing surgery at 10 gynecologic cancer research centers in Henan Province were enrolled from January 2010 to June 2016. Clinical data and follow-up results were collected. Of them, 78 had cervical squamous carcinoma and five had cervical adenocarcinoma. International Federation of Gynecology and Obstetrics (2009) staging showed that 26 patients had stage IA1, 11 had stage IA2, and 46 had stage IBI. Seventy-two patients underwent radical trachelectomy and retroperitoneal lymphadenectomy, whereas 11 underwent subradical trachelectomy and retroperitoneal lymphadenectomy. Moreover, 17 patients received one to two courses of preoperative neoadjuvant chemotherapy and five received two to four courses of postoperative chemotherapy. Eighty-three patients were followed up postoperatively (median follow-up duration, 36.2 months). Results With regard to tumor outcomes, one (1.2%) patient showed recurrence following fertility-sparing surgery. In 69 patients with planned pregnancy after treatment, 54 had 58 pregnancies, including 42 full-term births and eight premature births. Seventy-nine patients were satisfied with their quality of life. Conclusions Radical/subradical trachelectomy is safe and effective as fertility-sparing surgery for young patients with early cervical cancer, with good pregnancy outcomes.

Expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), signal transducer and activator of transcription-3 (STAT3) and vascular endothelial growth factor-C (VEGF-C) and their relationship with clinico-pathological features and prognostic ability was determined using immunohistochemistry in 68 cases of colorectal cancer with follow-up data. Kaplan-Meier survival analysis was performed and the prognostic value was determined using univariate analysis. PTEN, STAT3 and VEGF-C expression was detected in 32.4, 60.3 and 63.2% of colorectal carcinoma cases and 90.0, 0 and 0% of normal colon samples, respectively. PTEN and STAT3 were correlated with pathological grade (p=0.011, p=0.001, respectively), but not with tumor size, lymph node metastasis or clinical stage. VEGF-C was correlated with lymph node metastasis (p=0.002), but not with tumor size, pathological grade or clinical stage. Expression of STAT3 and VEGF-C was negatively correlated with PTEN (r=−0.402, r=−0.320, respectively), whereas STAT3 and VEGF-C expression was positively correlated with PTEN (r=0.254). The 3- and 5-year survival rates of PTEN protein-positive patients (68.1 and 50.0%, respectively) were significantly higher than those of PTEN protein-negative patients (32.6 and 19.6%, respectively; p=0.008). The 3- and 5-year survival rates of STAT3-positive (29.3 and 17.1%, respectively) were significantly lower than those of STAT3-negative patients (66.7 and 48.1%, respectively; p=0.005). The 3- and 5-year survival rates of VEGF-C-positive patients (29.3 and 17.1%, respectively) were significantly lower than the rates of VEGF-C-negative patients (66.7 and 48.1%, respectively; p=0.003, p=0.004, respectively). Multivariate analysis revealed that VEGF-C expression was an independent prognostic factor. In conclusion, this study indicates that PTEN, STAT3 and VEGF-C expression are beneficial prognostic factors, which may aid in the accurate assessment of prognosis and guide clinical treatment of colorectal cancer patients.

Compelling evidence shows that deregulated microRNAs (miRNAs) are important regulators in the progression of melanoma. miR-145-5p has been suggested to exhibit antitumorigenic activity in melanoma. However, the molecular mechanism underlying the biological activity of miR-145-5p in melanoma remains to be further understood. Herein, quantitative real-time polymerase chain reaction was used to examine the miR-145-5p expression in malignant melanoma tissues and cells. The interaction between miR-145-5p and toll-like receptor 4 (TLR4) was explored by bioinformatics analyses, luciferase reporter assay, and Western blot. The effects of miR-145-5p or combined with TLR4 on cell proliferation, colony formation, migration, and invasion abilities were investigated by (4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, colony formation, wound healing, and transwell assays, respectively. The melanoma xenograft tumor models were established to determine the biological activity of miR-145-5p in melanoma in vivo. In addition, the changes of the nuclear factor kappa B (NF-κB) pathway were analyzed by detecting the NF-κB activity and the NF-κB p65 protein level. We observed that the miR-145-5p expression was underexpressed in melanoma tissues and cells. miR-145-5p suppressed the TLR4 expression by binding to its 3′untranslated region in melanoma cells. Moreover, TLR4 overexpression abolished the inhibition of cell proliferation, colony formation, migration, and invasion abilities induced by miR-145-5p in melanoma cells. Meanwhile, miR-145-5p was confirmed to restrain melanoma tumor growth in vivo by targeting TLR4. Furthermore, miR-145-5p overexpression inactivated the NF-κB pathway in melanoma in vitro and in vivo, which was reversed by TLR4 overexpression. We concluded that miR-145-5p hindered the occurrence and metastasis of melanoma cells in vitro and in vivo by targeting TLR4 via inactivation of the NF-κB pathway. K E Y W O R D Smelanoma, miR-145-5p, the nuclear factor kappa B (NF-κB) pathway, toll-like receptor 4 (TLR4)

Human epididymis protein 4 (HE4) is well known to be a predictor of ovarian cancer clinically. HE4 is reported to play crucial roles in ovarian cancer progression and metastasis. The purpose of the present study was to explore its biological role and molecular mechanism in ovarian cancer. In our study, we found that expression levels of HE4 in tissues, serum and urine in ovarian cancer were upregulated compared to healthy and benign groups. HE4 expression was elevated in ovarian cancer cells. Knockdown of HE4 dampened cell proliferation and Ki67 expression, as well as enhanced apoptosis, caspase-3 activity and cleaved-caspase-3 expression. In addition, HE4 downregulation repressed invasion and migration capabilities of ovarian cancer cells. Western blot analyses showed that knockdown of HE4 reduced the levels of matrix metalloproteinases (MMP-2 and MMP-9) and inhibited epithelial to mesenchymal transition (EMT) in ovarian cancer cells. In vivo animal experiments revealed that HE4 downregulation constrained the growth of xenograft tumor. Mechanism research showed that knockdown HE4 inhibited the activity of JAK/STAT3 pathway in vitro and in vivo. In conclusion, our findings reported that knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway, which provides valuable insights to contribute to develop novel HE4-targeted therapies.