Cutoff of 25% for Ki67 expression is a good classification tool for prognosis in colorectal cancer in the AJCC­8 stratification.

Ki­67 expression has been widely used in clinical practice as an index to evaluate the proliferative activity of tumor cells. The cutoff for Ki67 expression in order to increase the prognostic value of Ki67 expression in colorectal cancer varies. The present study assessed the relationship between the 25% cutoff for Ki67 expression and prognosis in colorectal cancer in the AJCC­8 (American Joint Committee on Cancer 8 edition) stratification. The current trial included 1,090 colorectal cancer patients enrolled from 2006 to 2012 at Huzhou Central Hospital. Ki67 expression was classified according to 25% intervals, dividing the patients into four groups. Measurement data were analyzed by ANOVA, and count data by Crosstabs. Bivariate correlation analysis was performed to assess clinicopathological indicators based on Ki67 expression. Disease­free survival (DFS) and overall survival (OS) based on Ki67 levels were analyzed by the Kaplan­Meier method. A total of 1,090 patients of the 2,080 enrolled CRC cases were evaluated (52.4%). Invasive depth, tumor differentiation, tumor size, AJCC­8, positive number of lymph nodes and chemotherapy status showed significant differences in the various Ki67 expression groups (all P<0.05), with significant correlations (Spearman rho: 0.170, 0.456, 0.22, 0.195, 0.514 and ­0.201, respectively, all P<0.001). DFS and OS for the different Ki67 level groups based on AJCC­8 stratification were analyzed, and no significance was found in stage IV (P=0.334). DFS and OS survival rates were assessed at different Ki67 expression levels, and no significant differences were found (all P>0.05). Cox regression analysis showed that invasive depth, lymph node metastasis, tumor differentiation, AJCC­8 and Ki67 were independent factors affecting colorectal cancer (P=0.030, all others P<0.001). In conclusion, a cutoff of 25% for Ki67 expression is a good classification tool. High Ki67 has a close association with poor prognosis in colorectal cancer and independently predicts prognosis in the AJCC­8 stratification.

When do defecation function and quality of life recover for patients with non-ostomy and ostomy surgery of rectal cancer?

BACKGROUND: Rectal cancer (RC) surgery often results in permanent colostomy, seriously limiting the quality of life (QOL) in patients in terms of bowel function. This study aimed to examine defecation function and QOL in RC patients who underwent non-ostomy or ostomy surgery, at different time-points after surgery. METHODS: In total, 82 patients who underwent an ostomy and 141 who did not undergo an ostomy for the treatment of RC at our colorectal surgery department between January 2013 and January 2015 were enrolled. Surgical methods, tumor distance from the anal margin (TD), anastomosis distance from the anal margin (AD) and complications were compered between the non-ostomy and ostomy surgery groups. QOL was compared between the two groups at years 2, 3, and 4 after surgery. The Wexner score and the validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) questionnaire scores were assessed for all patients in January 2017. SPSS 21.0 was utilized for all data analyses. RESULTS: Surgical methods, TD, and AD significantly differed between the non-ostomy and ostomy surgery groups (all P < .001). However, no differences were found in the number of complications between the groups (P = .483). For the 192 patients undergoing Dixon surgery, role function (RF), global QOL (GQOL), sleep disturbance, and the incidence of constipation showed significant differences between the two groups (P = .012, P = .025, P = .036, and P = .015, respectively). In the 31 cases of permanent ostomy, we observed significant differences in GQOL scores, dyspnea incidence, and financial difficulties across the different years (P = .002, P = .036, and P < .01, respectively). Across all 223 cases, there were significant differences in social function and GQOL scores in the second year after surgery (P = .014 and P < .001, respectively). However, no differences were observed in the other indices across the three time-points. CONCLUSIONS: RC patients undergoing ostomy surgery, especially those with low and super-low RC, revealed poorer defecation function and QOL in the present study. However, 2 years after surgery, most of the defecation and QOL indicators showed recovery.

Prognostic and Therapeutic Significance of Adhesion-regulating Molecule 1 in Estrogen Receptor-positive Breast Cancer.

INTRODUCTION: Adhesion-regulating molecule 1 (ADRM1) is a polyubiquitin receptor on the 26S proteasome. ADRM1 is upregulated in many cancers. In this study, we evaluated the potential prognostic and predictive value of ADRM1 in breast cancer. MATERIALS AND METHODS: Individual and pooled survival analyses were performed on 19 independent breast cancer microarray datasets. Gene signatures enriched by ADRM1 were also analyzed in pooled datasets. RESULTS: Gene set enrichment analysis revealed that high expression of ADRM1 was significantly associated with aggressive breast cancer. Our findings revealed that ADRM1 mRNA levels were significantly associated with estrogen receptor (ER) status, progesterone receptor status, tumor size, lymph node status, histologic grade, and molecular subtypes. We also found that higher mRNA ADRM1 expression was significantly correlated with poor survival in patients with breast cancer. The prognostic power of ADRM1 mRNA was similar to the 70-gene wound response genes and 21 gene recurrence score; it was superior to TNM staging. The prognostic value of ADRM1 was better in ER-positive (ER+) breast cancer cases than in ER-negative breast cancer cases. In cases involving stage II breast cancer, radiotherapy significantly reduced the relative risk of OS in the ADRM1-low subgroup. CONCLUSION: ADRM1 mRNA levels were significantly related to poor outcome in our breast cancer sample population. It could serve as a prognostic biomarker, especially in ER+ breast cancer and Luminal A breast cancer cases, as well as a predictive biomarker for ER+ breast cancer.

Toxicologic evaluation of repetitive 4-week intravenous injections of midkine antisense oligonucleotide nanoliposomes in rats.

Midkine antisense oligonucleotide (MK-ASODN) nanoliposomes have previously been shown to have inhibitory activity against hepatocellular carcinoma growth. Herein we report the 4-week sub-chronic toxicity of MK-ASODN nanoliposomes in SD rats. The adverse effects included loss of body weight gain and food consumption, peri-rhinal bleeding, piloerection, peri-anal filth, and kidney, liver, spleen, thymus, lung, and injection site lesions at high doses. Macroscopic changes were observed in the kidneys of the high-dose group, accompanied by a variation in urine protein and white blood cells, blood urea nitrogen, and serum creatinine. The increased spleen and liver coefficient, and the variation in circulating white blood cells, lymphocytes, and eosinophils in the high-dose group demonstrated that inflammation was caused by MK-ASODN nanoliposomes and was consistent with the macroscopic changes in the spleen and liver. The main necropsy findings of the animals that died were macroscopic changes in the lung. No severe toxic effects or mortalities occurred in the low- and medium-dose groups. However, a No Adverse Effect Level (NOAEL) was not identified since there were changes in organs deemed to be adverse at all dose levels. Thus, the maximum tolerated dose of MK-ASODN nanoliposomes for rats was considered to be 6 mg/kg/day.

Comparison of the eighth version of the American Joint Committee on Cancer manual to the seventh version for colorectal cancer: A retrospective review of our data.

AIM: To analyze the survival trends in colorectal cancer (CRC) based on the different classifications recommended by the seventh and eighth editions of the American Joint Committee on Cancer staging system (AJCC-7th and AJCC-8th). METHODS: The database from our institution was queried to identify patients with pathologically confirmed stage 0-IV CRC diagnosed between 2006 and 2012. Data from 2080 cases were collected and 1090 cases were evaluated through standardized inclusion and exclusion criteria. CRC was staged by AJCC-7th and then restaged by AJCC-8th. Five-year disease-free survival (DFS) and overall survival (OS) were compared. SPSS 21.0 software was used for all data. DFS and OS were compared and analyzed by Kaplan-Meier and Log-rank test. RESULTS: Linear regression and automatic linear regression showed lymph node positive functional equations by tumor-node-metastasis staging from AJCC-7th and tumor-node-metastasis staging from AJCC-8th. Neurological invasion, venous infiltration, lymphatic infiltration, and tumor deposition put forward stricter requirements for pathological examination in AJCC-8th compared to AJCC-7th. After re-analyzing our cohort with AJCC-8th, the percentage of stage IVB cases decreased from 2.8% to 0.8%. As a result 2% of the cases were classified under the new IVC staging. DFS and OS was significantly shorter (P = 0.012) in stage IVC patients compared to stage IVB patients. CONCLUSION: The addition of stage IVC in AJCC-8th has shown that peritoneal metastasis has a worse prognosis than distant organ metastasis in our institution's CRC cohort. Additional datasets should be analyzed to confirm these findings.

The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer-A retrospective cohort study.

PURPOSE: Tissue carcinoembryonic antigen (t-CEA) and serum carcinoembryonic antigen (s-CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s-CEA and t-CEA in CRC. METHODS: A total of 517 patients from January 2006 to December 2010 with stages I-III CRC were retrospectively examined, with 5-year postoperative follow-up and death as end-points. T-CEA expression, s-CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan-Meier method was used to analyze the 5-year disease-free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t-CEA and s-CEA expression. RESULTS: Tumor differentiation and the number of positive lymph node harvests were significantly different among the t-CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s-CEA and t-CEA expression had a significantly poorer prognosis than those with low s-CEA (P = 0.021) and t-CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t-CEA was an independent prognostic factor in CRC (P < 0.001), but s-CEA was not (P = 0.339). The 5-year disease-free survival rates among the t-CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s-CEA groups, this difference was observed only in stage III (P = 0.014). CONCLUSION: This study shows that postoperative t-CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s-CEA expression.

MiR-1260b promotes the migration and invasion in non-small cell lung cancer via targeting PTPRK.

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases which cause most of cancer-related deaths globally. As our previous study discovered miR-1260b can be regarded as a specific signature for metastasis in NSCLC patients. However, the molecular mechanisms of miR-1260b underlying NSCLC progression and metastasis remain dismal. METHODS: The expression of miR-1260b in NSCLC tissues and cell lines were examined by real-time PCR, the effects of miR-1260b on cell migration, invasion and proliferation were evaluated in vitro. Furthermore, luciferase reporter assay was performed to identify the targets of miR-1260b, and the association between miR-1260b and its target gene was determined by real-time PCR and western blot assay. RESULTS: The results showed that miR-1260b was significantly upregulated in NSCLC cell lines. The inhibition of miR-1260b expression decreased the migratory and invasive rates in A549 cells while miR-1260b overexpression had the opposite effect. Furthermore, PTPRK was identified as a direct target of miR-1260b, and PTPRK expression was inversely correlated with miR-1260b in NSCLC cell lines and clinical tissues. CONCLUSIONS: These results suggested that miR-1260b may play an important role in NSCLC metastasis progression and could serve as a putative target for diagnosis and treatment of NSCLC.

Development of hybrid-type modified chitosan derivative nanoparticles for the intracellular delivery of midkine-siRNA in hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Most of the patients with HCC lose the surgical opportunity at the time of diagnosis. Some novel therapeutic modalities, like gene therapy, are promising for the treatment of HCC. However, the success of gene therapy depends on two aspects: efficient gene materials and gene delivery vectors. The present study was to develop new chitosan-based nanoparticles for a midkine-siRNA (anti-HCC gene drug) delivery. METHODS: The novel gene delivery vector (MixNCH) was synthesized by hybrid-type modification of chitosan with 2-chloroethylamine hydrochloride and N, N-dimethyl-2-chloroethylamine hydrochloride. The chemical structure of MixNCH was characterized by FT-IR and 1HNMR. The cytotoxicity of MixNCH was determined by MTS assay. The gene condensation ability and size, zeta potential and morphology of MixNCH/MK-siRNA nanoparticles were measured. The in vitro transfection and gene knockdown efficiency of midkine by MixNCH/MK-siRNA nanoparticles was detected by qRT-PCR and Western blotting. Gene knockdown effect at the molecule level on the proliferation of HepG2 in vitro was determined by MTS assay. RESULTS: MixNCH was successfully acquired by aminoalkylation modification of chitosan. The MixNCH could condense MK-siRNA well above the weight ratio of 3. The average size of MixNCH/MK-siRNA nanoparticles was 100-200 nm, and the surface charge was about +5 mV. Morphologically, MixNCH/MK-siRNA nanoparticles were in regular spherical shape with no aggregation. Regarding to the in vitro transfection of nanoparticles, the MixNCH/MK-siRNA nanoparticles reduced MK mRNA level to 14.03%+/-4.03%, which were comparable to Biotrans (8.94%+/-3.77%). MixNCH/MK-siRNA effectively inhibited the proliferation of HepG2 in vitro. CONCLUSION: MixNCH/MK-siRNA nanoparticles could be effective for the treatment of hepatocellular carcinoma.