Purpose: To assess the feasibility and therapeutic effects of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on the fusion imaging of magnetic resonance imaging (MRI) and computed tomography (CT) as a dose-intensive technique in patients with brain metastases (BM) of non-small cell lung cancer (NSCLC). Methods and materials: Forty-six NSCLC patients with 1 to 7 brain metastases were enrolled in this retrospective study between November, 2011 and February, 2017. Thirty-one patients (67.4%) had 1-3 metastases (oligometastases), otherwise, more than 3 metastases were seen in only 15 patients (32.6%). GTV (Gross tumor volume) contouring was based on the fusion imaging of MRI-CT, WBRT was prescribed in 37.5 Gy/15 fractions with a simultaneous boost in the metastatic lesions of 52.5 Gy/15 fractions. Results: The median overall survival (OS) and intracranial progression free survival (PFS) for all the patients were 20.0 months and 11.0 months, respectively. The 6-month and 1-year OS were 87.0% and 69.6% respectively, while the 6-month and 1-year PFS were 78.3% and 43.5% respectively. Until the end of the follow-up, 16 patients (34.8%) were alive. No evidence of intracranial progress or recurrence was found in 6 patients (13.0%) during the follow-up. Conclusion: SIB-IMRT with the dose/fractionation based on the fusion imaging of MRI-CT is feasible and safe. It is beneficial to the NSCLC patients with BM and can reduce the overall costs of treatment.

Objective: The lack of effective therapeutic targets poses a leading challenge to prolong survival and improve the quality of life for pancreatic cancer patients. Proteasome 26S subunit ATPase 2 (PSMC2), a recently discovered gene, has been implicated in certain human carcinogenesis. However, limited data is available concerning the functional significance of PSMC2 in cancer cell growth, and whether it plays a role in pancreatic carcinogenesis remains unknown. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was performed to assess mRNA expression levels of PSMC2 in different pancreatic cancer cell lines. Knockdown of PSMC2 was achieved by using short hairpin RNA (shRNA). The effects of PSMC2 silencing on pancreatic cancer cell proliferation and apoptosis were evaluated by the MTT cell proliferation assay, Celigoassays, Annexin V fluorescence-activated cell sorting (FACS) assay and Caspase-3/7 array. Results: High expression of PSMC2 was detected in three pancreatic cancer cell lines (SW1990, PANC-1, and AsPC-1). Knockdown of PSMC2 in SW1990 cells inhibited proliferation and enhanced apoptosis. Conclusions: Our primary study suggests that PSMC2 might be involved in the progression of pancreatic cancer and may serve as a potential therapeutic target.

Objective: The objective was to identify and validate C-X-C motif chemokine ligand 1(CXCL1) for diagnosis and prognosis in colon adenocarcinoma (COAD). Methods: Our current study had enrolled one The Cancer Genome Atlas (TCGA) cohort and two Guangxi cohorts to identify and verify the diagnostic and prognostic values of CXCL1 in COAD. Functional enrichment was performed by gene set enrichment analysis (GSEA). Results: In TCGA cohort, the expression of CXCL1 was significantly up-regulated in tumor tissues and decreased as the tumor stage developed. The receiver operating characteristic (ROC) curve showed that CXCL1 had a high diagnostic value for COAD. The result of Kaplan-Meier survival analysis showed that CXCL1 gene expression (P=0.045) was significantly correlated with overall survival (OS) of COAD. Results of Guangxi cohort also verified the diagnostic value of CXCL1 in COAD, and sub-group survival analyses also suggested that patients with high CXCL1 expression were related to a favorable OS (Corrected P=0.005). GSEA revealed that CXCL1 high expression phenotype was related to cytokine activity, cell apoptosis, P53 regulation pathway, and regulation of autophagy in COAD. Conclusions: In this study, we found that CXCL1 gene might be a potential diagnostic biomarker for COAD, and might serve as a prognostic biomarker for specific subgroup of COAD.

Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisplatin-resistant ovarian cancer cells by inducing apoptosis. And YSY01A treatment enhances the cytotoxicity of cisplatin in drug-resistant ovarian cancer cells. Specifically, YSY01A abrogates regulatory proteins important for cell proliferation and anti-apoptosis including NF-κB p65 and STAT3, resulting in down-regulation of Bcl-2. A dramatic increase in cisplatin uptake was also observed by inductively coupled plasma-mass spectrometry following exposure to YSY01A. Taken together, YSY01A serves as a potential candidate for further development as anticancer therapeutics targeting the proteasome.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disorder and a frequent side effect of endocrine therapy (ET) for breast cancer treatment. This was the first meta-analysis to investigate the impact of NAFLD on breast cancer survival. Material and Methods: We searched Pubmed, Embase and Cochrane Central Register of Controlled Trials database for relevant studies that investigated the correlation between NAFLD and breast cancer survival. Fixed- and random-effect meta-analyses were conducted according to the heterogeneity of enrolled studies. Subgroup analyses were performed based on whether NAFLD was induced by ET administration Results: Eight cohorts from six studies including 3684 breast cancer patients were enrolled. NAFLD was significantly associated with advanced age (p < 0.001), obesity (p < 0.001), lymph node metastases (p = 0.003) and hormone receptor positivity (p < 0.001). NAFLD had no significant impact on disease free survival (DFS) [hazard ratio (HR) 1.07, 95% confidence interval (CI) = 0.64-1.77, p = 0.81] and overall survival (OS) (HR 1.29, 95% CI = 0.68-2.44, p = 0.44). In subgroup analyses, ET-associated NAFLD showed no significant impact on DFS and OS. Nonetheless, non-ET-associated NAFLD had a strong prognostic correlation with poor OS (HR 1.92, 95% CI = 1.09-3.41, p = 0.02). Conclusion: NAFLD had no significant impact on breast cancer survival. However, non-ET-associated NAFLD implied increasing death risk. Future large-scale studies are warranted to further elucidate the correlation between NAFLD and breast cancer prognosis.

Given that the proteasome is essential for multiple cellular processes by degrading diverse regulatory proteins, inhibition of the proteasome has emerged as an attractive target for anti-cancer therapy. YSY01A is a novel small molecule compound targeting the proteasome. The compound was found to suppress viability of MCF-7 cells and cause limited cell membrane damage as determined by sulforhodamine B assay (SRB) and CytoTox 96(®) non-radioactive cytotoxicity assay. High-content screening (HCS) further shows that YSY01A treatment induces cell cycle arrest on G2 phase within 24 hrs. Label-free quantitative proteomics (LFQP), which allows extensive comparison of cellular responses following YSY01A treatment, suggests that various regulatory proteins including cell cycle associated proteins and PI3K/Akt pathway may be affected. Furthermore, YSY01A increases p-CDC-2, p-FOXO3a, p53, p21(Cip1) and p27(Kip1) but decreases p-Akt, p-ERα as confirmed by Western blotting. Therefore, YSY01A represents a potential therapeutic for breast cancer MCF-7 by inducing G2 phase arrest via ERα and PI3K/Akt pathways.

It has been demonstrated that microRNA-98 (miR-98) is dysregulated in multiple types of solid tumors, but its expression and impact in acute myeloid leukemia (AML) is unclear. To explore the prognostic role of miR-98 in AML, 164 AML patients with the miR-98 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. First, patients were divided into chemotherapy-only (chemotherapy) group and allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was then divided in two groups by the median expression level of miR-98. In chemotherapy group, high miR-98 expression was associated with longer event-free survival (EFS, P = 0.003) and overall survival (OS, P = 0.004), but in allo-HSCT group, EFS and OS were not significantly different between high and low miR-98 expressers. Second, All patients were divided in two groups by the median expression level of miR-98. In low miR-98 expressers, those treated with allo-HSCT had longer EFS (P = 0.001) and OS (P < 0.001) than chemotherapy, but in high miR-98 expressers, survival was independent from treatment modalities. Gene ontology enrichment analysis indicated that the genes associated with miR-98 expression were mainly concentrated in "definitive hemopoiesis", "negative regulation of myeloid cell differentiation" and "signaling pathways regulating pluripotency of stem cells" pathways. In conclusion, our results indicated that high miR-98 expression confers good prognosis in AML patients treated with chemotherapy alone. Patients with low miR-98 expression may benefit from allo-HSCT.

Unresolved inflammation, due to insufficient production of proresolving anti-inflammatory lipid mediators, can lead to tumorigenesis. Among these mediators, lipoxin A4 (LXA4) has potent anti-carcinogenic properties, and may serve as key target for modulating inflammation-associated cancer like colorectal cancer. The purpose of present study was to clarify the roles of LXA4 in colorectal cancer. We investigated the effects and underlying mechanisms of LXA4 in colorectal cancer and its relationship with tumor-associated inflammation and immune microenvironment by employing clinical samples and mouse colorectal cancer cell line CT26-bearing tumor model as well as colorectal cancer cells. It was found that colorectal cancer is associated with dysregulation of immune microenvironment and deficiency of LXA4 that could play different roles at different stages of tumor growth: inhibiting early but promoting late tumor growth. Analysis of peripheral immune cells in subcutaneous xenograft mice model disclosed that early LXA4 treatment induced lymphocytes and inhibited neutrophils and monocytes, while late LXA4 treatment induced neutrophils but inhibited lymphocytes. Detailed analysis of tumor microenvironment revealed that early LXA4 treatment could inhibit inflammatory mediators expressions and leukocytes infiltration into tumor. Furthermore, LXA4 could suppress the expressions of p-ERK, p-P38 and NF-κB in subcutaneous xenograft. Additionally, LXA4 could inhibit the proliferation and migration of colorectal cancer cells, and, meanwhile, inhibit the proliferation and migration of colorectal cancer cells stimulated by activated macrophage-conditioned media. These findings suggest that colorectal cancer is associated with a deficiency of LXA4 that could suppress colorectal cancer via modulating tumor-associated inflammation and immune microenvironment as well as inhibiting colorectal cancer cell development.

Serum cancer biomarker has been proven to be very valuable in cancer diagnosis, disease monitoring and prognosis assessment, despite there is still a lack of serum biomarker for penile cancer (PC). Our initial analysis on public GEO dataset identified CCL20 as a top C-C motif ligand (CCL) gene enriched in PC. The patients with PC exhibited markedly higher preoperative serum CCL20 level than healthy control. The area under the curve (AUC) was 0.855 with the sensitivity of 72.4%, and specificity of 93.5% to distinguish PC. Preoperative serum CCL20 level was significantly associated with clinicopathological characteristics including T stage (P=0.005), nodal status (P=0.008), and pelvic lymph node metastasis (P=0.007). PC Patients with high serum CCL20 level had shorter disease-free survival compared to those with low level (P<0.001). Cox regression analysis showed that serum CCL20 level could serve as an independent prognostic factor for disease-free survival with a HR of 3.980 (95% CI: 1.209-13.098, P=0.023). Furthermore, CCL20 expression was observed in PC tissues and cell lines. Knockdown of CCL20 expression markedly suppressed malignant phenotypes (cell proliferation, clonogenesis, apoptosis escape, migration and invasion), attenuated STAT3 and AKT signaling and reduced MMP2/9 secretion in PC cell lines. Consistently, CCL20 and its receptor CCR6 exhibited correlated expression pattern in PC tissues. In conclusion, serum CCL20 level might serve as a potential diagnostic and prognostic cancer biomarker for PC. CCL20 might activate multiple downstream oncogenic signaling pathways (STAT3, AKT, MMP2/9) to promote malignant progression of PC, which may warrant further investigation in the future.

DOCK family proteins are evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase with different cellular functions. It has been demonstrated that DOCK1 had adverse prognostic effect in acute myeloid leukemia (AML). We first analyzed data of 85 AML patients who were treated with chemotherapy and had available DOCK1 to DOCK11 expression information and found that DOCK1 and DOCK2 had prognostic significance in AML. In view of the known prognosis of DOCK1 in AML, we then explored the prognostic role of DOCK2. One hundred fifty-six AML patients with DOCK2 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. Patients were divided based on treatment modality into the chemotherapy group and the allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was divided into two groups by the median expression levels of DOCK2. In the chemotherapy group, high DOCK2 expression was associated with longer event-free survival (EFS, P=0.001) and overall survival (OS, P=0.007). In the allo-HSCT group, EFS and OS were not significantly different between high and low DOCK2 expression groups. Multivariate analysis showed that high DOCK2 expression was an independent favorable prognostic factor for both EFS and OS in all patients (all P<0.05). In conclusion, our results indicated that high DOCK2 expression, in contrast to DOCK1, conferred good prognosis in AML.