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Purpose: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. Methods: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. Results: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). Conclusions: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids. [ABSTRACT FROM AUTHOR]

Background: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines.Methods: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution.Results: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations.Conclusion: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics. [ABSTRACT FROM AUTHOR]

Background: This study was carried out to determine the prognostic significance of preoperative peripheral epithelial cell adhesion molecule- positive (EpCAM (+)) circulating tumor cell (CTC) and T regulatory (Treg) cell levels in hepatocellular carcinoma (HCC) patients for the prediction of postoperative recurrence following curative resection.Methods: A total of 49 patients about to undergo curative resection for HCC were recruited into the study. PCR and FACS were used to detect the preoperative levels of EpCAM (mRNA+) CTCs and CD4(+)CD25(+)Foxp3(+) Treg cells. The prognostic value of EpCAM (mRNA+) CTCs, CD4(+)CD25(+)Foxp3(+) Treg cells, and other clinicopathological factors were analyzed by applying the Kaplan-Meier method and the multivariate Cox proportional hazards model.Results: The number of EpCAM (mRNA+) CTCs and Treg/CD4(+) cells showed significant correlation as prognostic factors of postoperative HCC recurrence: EpCAM (mRNA+) CTC ≥ 2.22 (P = 0.001) and Treg/CD4(+) ≥ 5.07 (P = 0.045), with EpCAM (mRNA+) CTC ≥ 2.22 (P = 0.003, HR = 6.668) being the most important indicator. Patients with high CTC/Treg levels showed a significantly higher risk of developing postoperative HCC recurrence than those with low CTC/Treg levels (66.7 % vs. 10.3 %, P < 0.001). The high CTC/low Treg group also presented higher 1-year recurrence rates compared with the low CTC/low Treg level group (50.0 % vs. 10.3 %, P = 0.004).Conclusions: Elevated EpCAM (mRNA+) CTC and Treg/CD4(+) levels were associated with early recurrence of HCC, indicative of poor clinical outcome. The combined detection of EpCAM (mRNA+) CTC and Treg/CD4(+) may therefore provide a novel prognostic predictor for HCC patients. [ABSTRACT FROM AUTHOR]

Background: CDK11(p58), a Ser/Thr kinase that belongs to the cell division cycle 2-like 1 (CDC2L1) subfamily, is associated with cell cycle progression, tumorigenesis and apoptotic signaling. CDK11(p58) is also involved in the regulation of steroid receptors, such as androgen and estrogen receptors. We previously found that CDK11(p58) was abnormally expressed in prostate cancer. However, its role in breast cancer remains unclear.Methods: CDK11(p58) expression was evaluated by immunohistochemical staining in a tissue array. A Transwell assay was used to detect invasion and metastasis in breast cancer cells. The TaqMan® Metastasis Gene Expression Assay was used to search for potential downstream factors in the CDK11(p58) signaling pathway. qRT-PCR was used to evaluate mRNA levels, and the dual luciferase array was used to analyze promoter activity. Western blotting was used to detect the protein level.Results: CDK11(p58) expression was negatively correlated with node status (P = 0.012), relapse status (P = 0.002) and metastasis status (P = 0.023). Kaplan-Meier survival curves indicated that the disease-free survival (DFS) was significantly poor in breast cancer patients with low CDK11 expression. Interestingly, using the breast cancer cell lines ZR-75-30 and MDA-MB-231, we found that CDK11(p58) was capable of repressing the migration and invasion of ERα-positive breast cancer cells, but not ERα-negative breast cancer cells, in a kinase-dependent manner. Gene expression assays demonstrated that integrin β3 mRNA was dramatically repressed by CDK11(p58), and luciferase results confirmed that the integrin β3 promoter was inhibited by CDK11(p58) through ERα repression. The expression of integrin β3 was highly related to ERα signaling; ERα overexpression stimulated integrin β3 expression, whereas siRNA-mediated knockdown of ERα attenuated integrin β3 expression.Conclusions: These data indicate that CDK11(p58) is an anti-metastatic gene in ERα-positive breast cancer and that the regulation of integrin β3 by CDK11(p58) via the repression of ERα signaling may constitute part of a signaling pathway underlying breast cancer invasion. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma has high incidence and mortality worldwide. Liver is the site of most metabolic biotransformation, which could reflect the status of cells. Most plasma apolipoproteins, endogenous lipids and lipoproteins are synthesized in the liver. Therefore, the effects of lipid metabolites on prognosis of HCC deserved to be explored., Methods: We prospectively included 58 healthy donors (HD), 50 chronic hepatitis (CH) patients and a training cohort of 189 patients with HCC who underwent curative resections at Zhongshan Hospital from January 2012 to August 2012. We identified the optimal HDL PO cutoff value at 0.98 mmol/L and used it to stratify patients into low- or high-HDL PO groups for the entire cohort and four low-recurrent-risk subgroups. We also included an independent validation group of 182 HCC patients to validate this cutoff value. Prognostic values of HDL PO and other factors were determined by Kaplan-Meier curves and the Cox proportional hazards model., Results: The low-HDL PO group had a higher median tumor grade (P = 0.020) and a higher recurrence rate (P = 0.032). Results of multivariate analysis showed that preoperative γ-glutamyl transpeptidase (GGT) and HDL PO were independent predictors of recurrence. Moreover, the predictive value of HDL PO was retained in four low-recurrent-risk subgroups. As expected, clinicopathologic characteristics and predictive values were similar in the validation and training cohorts., Conclusions: HDL PO is an accessible predictor of HCC recurrence after liver resections that can help identify patients who need more careful monitoring and follow-up care.

Background: This study was carried out to determine the prognostic significance of preoperative peripheral epithelial cell adhesion molecule- positive (EpCAM (+)) circulating tumor cell (CTC) and T regulatory (Treg) cell levels in hepatocellular carcinoma (HCC) patients for the prediction of postoperative recurrence following curative resection., Methods: A total of 49 patients about to undergo curative resection for HCC were recruited into the study. PCR and FACS were used to detect the preoperative levels of EpCAM (mRNA+) CTCs and CD4(+)CD25(+)Foxp3(+) Treg cells. The prognostic value of EpCAM (mRNA+) CTCs, CD4(+)CD25(+)Foxp3(+) Treg cells, and other clinicopathological factors were analyzed by applying the Kaplan-Meier method and the multivariate Cox proportional hazards model., Results: The number of EpCAM (mRNA+) CTCs and Treg/CD4(+) cells showed significant correlation as prognostic factors of postoperative HCC recurrence: EpCAM (mRNA+) CTC ≥ 2.22 (P = 0.001) and Treg/CD4(+) ≥ 5.07 (P = 0.045), with EpCAM (mRNA+) CTC ≥ 2.22 (P = 0.003, HR = 6.668) being the most important indicator. Patients with high CTC/Treg levels showed a significantly higher risk of developing postoperative HCC recurrence than those with low CTC/Treg levels (66.7 % vs. 10.3 %, P < 0.001). The high CTC/low Treg group also presented higher 1-year recurrence rates compared with the low CTC/low Treg level group (50.0 % vs. 10.3 %, P = 0.004)., Conclusions: Elevated EpCAM (mRNA+) CTC and Treg/CD4(+) levels were associated with early recurrence of HCC, indicative of poor clinical outcome. The combined detection of EpCAM (mRNA+) CTC and Treg/CD4(+) may therefore provide a novel prognostic predictor for HCC patients.

Background: A capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. CDK11(p58), a Ser/Thr kinase that belongs to the Cell Division Cycle 2-like 1 (CDC2L1) subfamily is associated with cell cycle progression, tumorigenesis, sister chromatid cohesion and apoptotic signaling. However, its role in breast cancer proliferation and angiogenesis remains unclear., Methods: Tumorigenicity assays and blood vessel assessment in athymic mice were used to assess the function of CDK11(p58) in tumor proliferation and angiogenesis. CCK-8 assay was used to detect breast cancer cell growth. Immunohistochemistry was used to detect the expression of vascular endothelial growth factor (VEGF), CD31 and CD34 in CDK11 positive patient breast cancer tissues. Dual-Luciferase array was used to analyze the function of CDK11(p58) in the regulation of VEGF promoter activity. Western blot was used to detect related protein expression levels., Results: CDK11(p58) inhibited breast cancer growth and angiogenesis in breast cancer cells and in nude mice transplanted with tumors. Immunohistochemistry confirmed that CDK11(p58) was negatively associated with angiogenesis-related proteins such as VEGF, CD31 and CD34 in breast cancer patients. Real-time PCR and dual-luciferase assay showed CDK11(p58) inhibited the mRNA levels of VEGF and the promoter activity of VEGF. As CDK11(p58) is a Ser/Thr kinase, the kinase-dead mutant failed to inhibit VEGF mRNA and promoter activity. Western blot analysis showed the same pattern of related protein expression. The data suggested angiogenesis inhibition was dependent on CDK11(p58) kinase activity., Conclusion: This study indicates that CDK11(p58) inhibits the growth and angiogenesis of breast cancer dependent on its kinase activity.

Background: Cyclin D3, which induces progression through the G1 phase of the cell cycle, is a regulator of Cyclin-dependent kinases 4 and 6. Previous studies revealed that abnormal expression of Cyclin D3 was found in many different cancers. However, the role of Cyclin D3 in breast cancer (BC) remains unknown. The aim of this study is to examine the expression pattern of Cyclin D3 in BC and to evaluate its biological role and clinical significance in prognosis prediction. The mechanism involved is also evaluated., Methods: Immunohistochemical staining was used to detect the expression of Cyclin D3. qRT-PCR was used to detect the mRNA level of Cyclin D3 in BC tissues and BC cell lines. Transwell assay was used to examine the role of Cyclin D3 in the migration and invasion of BC cells. Mass Spectrometry was used to search for the interacting protein with Cyclin D3. Co-Immunoprecipitation assay and GST-Pull Down assay were used to validate the interaction of Cyclin D3 and its interaction protein., Results: Through detecting Cyclin D3 expression in 243 breast cancer patients' tissue array, we found Cyclin D3 expression was correlated with ER status (p = 0.000), PR status (p = 0.001), HER2 status (p = 0.002) and tumor differentiation (p = 0.045). The Kaplan-Meier survival curves indicated that the disease free survival (DFS) was significantly poor in high Cyclin D3 expression BC patients (p = 0.004). Furthermore, expression of Cyclin D3 was significantly associated with BC prognosis and was shown to be an independent prognostic marker in breast cancer (p = 0.028). By IHC staining and qPCR detection, Cyclin D3 expression was found to be down-regulated both in BC tissues and in BC cell lines compared with the corresponding normal controls. Further investigation showed Cyclin D3 was involved in the metastasis of BC cells and physically interacted with actin in vivo and in vitro., Conclusion: Our studies revealed that Cyclin D3 was upregulated in breast cancer and represented a novel predictor of BC prognosis.

Background: Accumulating studies have focused on the oncogenic and tumor suppressive roles of the newly identified lncRNAs. A novel lncRNA BC040587 in 3q13.31 locus which exists frequent copy number alterations was found to be associated with poor survival of osteosarcoma patients. However, its role in breast cancer (BC) remains unknown. The aim of this study was to examine the expression pattern of BC040587 in BC and to evaluate its biological role and clinical significance in prediction of prognosis., Methods: Expression of BC040587 was analyzed in 20 pairs of BC cancer tissues and adjacent noncancerous tissues (ANCT), also in 151 BC tissues, 9 BC cell lines and one normal breast cell line by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Differences between groups were tested for significance using Student's t-test (two-tailed). Then we analyzed the potential relationship between BC040587 expression and clinic pathological features of BC patients. The correlation was analyzed by SPSS software., Results: It showed that BC040587 expression was down regulated both in BC samples and in BC cell lines compared with corresponding normal control. BC040587 expression was correlated with menopausal status (p = 0.040) and tumor differentiation (p = 0.035). The Kaplan-Meier survival curves indicated that the overall survival (OS) was significantly poor in low BC040587 expression BC patients (p = 0.023). Furthermore, expression of BC040587 was significantly associated with worse prognosis and was shown to be an independent prognostic marker breast cancer (p = 0.032). Our studies indicate that BC040587 may represent a new marker of prognosis in breast cancer., Conclusion: Our studies indicate that BC040587 is significantly down-regulated in BC tissues and BC cell lines. BC040587 may represent a new marker of prognosis in breast cancer.

Background: Carbohydrate-deficient transferrin (CDT) is a widely used alcohol biomarker. Because of the high prevalence of chronic alcohol abuse in many countries, CDT plays an important role in the areas of traffic, clinical, and forensic medicine. However, CDT levels have not been determined in the Han Chinese population. Therefore, we investigated the frequency of genetic transferrin variants and the relationship between CDT levels and alcohol consumption in this population. From this data, we established a CDT cut-off for Han Chinese and evaluated the analytical performance of the CDT capillary zone electrophoresis system., Results: The prevalence of transferrin variants was 4.14%. The mean CDT level of the reference group was 0.73%. We recommended CDT level >1.5% as cut off standard of alcohol intake to ensuring the specificity was best. The CDT test total precision for 0.5%, 0.7%, and 1.55% was 14.4%, 11.5%, and 7.2%, respectively. The data showed good linearity in the studied range of 0.6% to 8.2%., Conclusions: These results demonstrate that CDT is a useful marker to detect heavy daily alcohol consumption. We proposed and evaluated the first CDT cut-off for the Han Chinese population, and we showed that the CDT capillary zone electrophoresis system is a reliable analytic method.

Background: To evaluate the predictive and prognostic value of various molecular factors associated with the Ras/MAPK and PI3K/Akt signaling pathways in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy (NAC)., Methods: A total of 113 patients were recruited in this retrospective study. Core needle biopsies and excision samples were assessed through immunohistochemistry for various biomarkers, including IGF-1R, Phospho-p44/42, Ki67, pAKT, PTEN, p27, and cyclinD1. The changes in these biomarkers after NAC and their predictive and prognostic values were investigated., Results: Significant decreases in Ki67, Phospho-p44/42, and pAKT expression were observed after treatment (30.7% vs. 18.1%, 36.4% vs. 18.9%, and 35.1% vs. 16.4%, respectively). The decreases in Phospho-p44/42, pAKT, and Ki67 expression were strongly associated with the response to anthracycline treatment (P = 0.027, P = 0.031, and P = 0.008, respectively). In a multivariate survival analysis, Phospho-p44/42 expression after neoadjuvant chemotherapy and lymph node status were significant independent prognostic factors of both relapse-free survival and overall survival., Conclusions: Reductions in Ki-67, Phospho-p44/42, and pAKT expression are related to the clinical response to anthracycline-based NAC in HER2-positive breast cancer patients. High pAKT expression prior to NAC had a better clinical response. Phospho-p44/42 expression and lymph node status after NAC could be useful for determining relapse-free survival and overall survival.

Background: We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between ILC and infiltrating ductal carcinoma (IDC) using a large database., Methods: Clinicopathologic features, overall survival (OS), and recurrence/metastasis-free survival (RFS) were compared between 2,202 patients with IDC and 215 patients with ILC., Results: ILC was significantly more likely to be associated with a favorable phenotype, but the incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (8.4% vs. 3.9%; P=0.001). The frequencies of recurrence/metastasis (P = 0.980) and death (P = 0.064) were similar among patients with IDC and patients with ILC after adjustment for tumor size and nodal status. The median follow-up was 42.8 months., Conclusions: Chinese women with ILCs do not have better clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.

Background: This study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC)., Methods: One-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67)., Results: Patients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively)., Conclusion: This study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.

Background: It has been reported that triple negative phenotype is characterized by aggressive clinical history in Western breast cancer patients, however its pattern of metastatic spread had never been reported in the Chinese population. Considering racial disparities, we sought to analyze the spread pattern for different sites of first recurrence in Chinese triple negative breast cancers., Methods: A retrospective study of 1662 patients was carried out from a large database of breast cancer patients undergoing surgery between January 1, 2000 and March 31, 2004 at the Cancer Hospital, Fudan University, Shanghai, China. Survival curves were generated using the Kaplan-Meier method and annual relapse hazards were estimated by the hazard function., Results: We found a statistically significant difference in relapse-free survival (RFS) for locoregional and visceral recurrence (P = 0.007 and P = 0.025, respectively) among the triple negative, ERBB2+ and HR+/ERBB2- subgroups in univariate analysis. In the multivariate Cox proportional hazards regression analysis, RFS for either locoregional or visceral relapse in the triple negative category was inferior to that in HR+/ERBB2- patients (P = 0.027 and P = 0.005, respectively), but comparable to that in ERBB2+ women (both P >0.05). Furthermore, the early relapse peak appeared later in the triple negative group than that in the ERBB2+ counterpart for both locoregional and visceral relapse. On the other hand, when compared with triple negative breast cancers, a significantly lower risk of developing bone relapse was discerned for ERBB2+ women (P = 0.048; HR = 0.384, 95% CI 0.148-0.991), with the borderline significance for HR+/ERBB2- breast cancers (P = 0.058; HR = 0.479, 95% CI 0.224-1.025). In terms of bone metastasis, the hazard rate remained higher for the triple negative category than that for the ERBB2+ subtype., Conclusion: Based on the site-specific spread pattern in different subgroups, the triple negative category of breast cancers in the Chinese population exhibits a different pattern of relapse, which indicates that different organotropism may be due to the different intrinsic subtypes. A better knowledge of the triple negative category is warranted for efficacious systemic regimens to decrease and/or delay the relapse hazard.