MicroRNAs in cancer therapeutic response: Friend and foe.

Cancer initiation and development engage extremely complicated pathological processes which involve alterations of a large number of cell signaling cascades and functional networks in temporal and spatial orders. During last decades, microRNAs (miRNAs), a class of non-coding RNAs, have emerged as critical players in cancer pathogenesis and progression by modulating many pathological aspects related to tumor development, growth, metastasis, and drug resistance. The major function of miRNAs is to post-transcriptionally regulate gene expression depending on recognition of complementary sequence residing in target mRNAs.

Elevated PIVKA-II is associated with early recurrence and poor prognosis in BCLC 0-A hepatocellular carcinomas.

Background: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection.

Materials And Methods: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013.

CDK11p58 inhibits ERα-positive breast cancer invasion by targeting integrin β3 via the repression of ERα signaling.

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.

Clinical significance of EpCAM mRNA-positive circulating tumor cells in hepatocellular carcinoma by an optimized negative enrichment and qRT-PCR-based platform.

Purpose: This study aimed to construct a novel platform for the detection of circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC) and to investigate the clinical significance of epithelial cell adhesion molecule mRNA-positive (EpCAM(mRNA+)) CTCs using this platform.

Experimental Design: An optimized platform for CTC detection was constructed by evaluating different negative enrichment, mRNA isolation, and cDNA synthesis procedures and compared with the CellSearch system. A total of 299 patients with HCC were recruited into this prospective study; of these, 157 who received curative resection, 76 who received transcatheter arterial chemoembolization (TACE), and 66 who received radiotherapy were tested using our platform.

Are changes in circulating tumor cell (CTC) count associated with the response to neoadjuvant chemotherapy in local advanced breast cancer? A meta-analysis.

Introduction: Circulating tumor cells (CTCs) represent a biomarker for tumor progression and monitoring therapeutic effects. We evaluated the association between the changes in CTC count and the pathological response to neoadjuvant chemotherapy (NCT) for local advanced breast cancer (LABC) patients.

Methods: PubMed, EBSCO, Web of Science, conference proceedings and key trials for the period 1998-2012 were searched.

Cisplatin and gemcitabine as the first line therapy in metastatic triple negative breast cancer.

No standard first-line treatment exists for patients with metastatic triple-negative breast cancer (mTNBC). In this single-arm, phase II study (NCT00601159), we evaluated the efficacy and tolerability of cisplatin and gemcitabine (GP) as the first-line therapy in mTNBC. Eligible women were those who had measurable disease with no prior chemotherapy for mTNBC.

Enriched variations in TEKT4 and breast cancer resistance to paclitaxel.

Among chemotherapeutic agents, paclitaxel has shown great efficacy against breast cancer. Prediction of paclitaxel response may improve patient outcomes. Here we show, using exome sequencing, that in comparison with pre-treatment biopsies, two TEKT4 germline variations are enriched in post-treatment tumours.

A clinicopathological study of early-stage synchronous bilateral breast cancer: a retrospective evaluation and prospective validation of potential risk factors.

Background: The aim of the present study was to investigate potential risk factors for synchronous bilateral breast cancer sBBC).

Methods: A retrospective analysis was performed of patients diagnosed and treated with operable bilateral breast cancer (BBC) between June 2007 and December 2011. Risk factors for sBBC were evaluated in this cohort and further validated in a prospective observational validation analysis of patients between January 2012 and December 2012.

Determination of carbohydrate-deficient transferrin in a Han Chinese population.

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.

Adjuvant chemotherapy increases the prevalence of fat necrosis in immediate free abdominal flap breast reconstruction.

Background: Fat necrosis is one of the most common complications following free flap breast reconstruction. Although a minor complication, fat necrosis can compromise esthetic results and confuse with cancer recurrence. Perfusion-related factors and post-operative radiotherapy are the known risks.

The role of mammographic calcification in the neoadjuvant therapy of breast cancer imaging evaluation.

Introduction: Investigate the patterns of mammographically detected calcifications before and after neoadjuvant chemotherapy (NACT) to determine their value for efficacy evaluation and surgical decision making.

Methods: 187 patients with malignant mammographic calcifications were followed to record the appearances and changes in the calcifications and to analyze their responses to NACT.

Results: Patients with calcifications had higher rates of hormonal receptor (HR) positive tumors (74.

Prognostic and predictive value of Phospho-p44/42 and pAKT in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.

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.

USP10 inhibits genotoxic NF-κB activation by MCPIP1-facilitated deubiquitination of NEMO.

DNA damage-induced activation of the transcription factor NF-κB plays an important role in the cellular response to genotoxic stress. However, uncontrolled NF-κB activation upon DNA damage may lead to deleterious consequences. Although the mechanisms mediating genotoxic NF-κB activation have been elucidated, how this signalling is terminated remains poorly understood.

Lymph node counts and ratio in axillary dissections following neoadjuvant chemotherapy for breast cancer: a better alternative to traditional pN staging.

Background: Neoadjuvant chemotherapy (NCT) for breast cancer might change the number of involved and detected nodes in axillary lymph node dissections (ALND). In this study, we analyzed whether the number of dissected nodes and the lymph node ratio (LNR, defined as the proportion of involved nodes in dissected nodes) would have a better prognostic value than traditional pN staging.

Methods: A total of 569 patients with stage II, III breast cancer were included in this retrospective study.

[Prospective multi-center study of one-step nucleic acid amplification assay for the detection of sentinel lymph nodes metastases in breast cancer patients].

Objective: To evaluate the roles of Sysmex RD100i one-step nucleic acid amplification (OSNA) assay in the intraoperative assessments of breast cancer sentinel lymph nodes (SLNs).

Methods: A total of 552 consecutive prospective patients were enrolled from five centers nationwide from February to December 2010. And SLNs were sliced into alternating 2 mm blocks.

COX-2 promotes breast cancer cell radioresistance via p38/MAPK-mediated cellular anti-apoptosis and invasiveness.

Radioresistance is one of the major barriers to improve the survival rate of breast cancer patients. Cyclooxygenase 2 (COX-2) is usually overexpressed in highly invasive and metastatic breast cancer, which may indicate an association with breast cancer radioresistance. The function role of COX-2 was investigated by using a radioresistant breast cancer cell line MDA-MB-231/RR10 and its parental cell line MDA-MB-231 cells before or after COX-2 was silenced by a specific small hairpin RNA (shRNA).

Weekly paclitaxel/carboplatin/trastuzumab therapy improves pathologic complete remission in aggressive HER2-positive breast cancers, especially in luminal-B subtype, compared with a once-every-3-weeks schedule.

Background: The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB-IIIC) breast cancers were evaluated in this phase II trial.

Methods: Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla.

Utility of one-step nucleic acid amplification (OSNA) assay in detecting breast cancer metastases of sentinel lymph nodes in a Chinese population.

Background: The one-step nucleic acid amplification (OSNA) assay is an innovative method for the diagnosis of sentinel lymph node (SLN) metastases in breast cancer patients. The aim of the present study was to clinically validate the OSNA assay and compare its results with postoperative serial sectioning in a Chinese breast cancer population.

Methods: A prospective study of 370 consecutive SLNs from 115 patients was conducted at our institution.

Nrf2 is associated with the regulation of basal transcription activity of the BRCA1 gene.

BRCA1 is closely related to the pathogenesis of breast cancer. The activity of BRCA1 promoter is regulated by transcriptional factors. The transcription factor Nrf2 (Nuclear factor-erythroid-2p45-related factor 2) is a potent transcriptional activator and plays a central role in inducible expression of many cytoprotective genes.

MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer.

Purpose: The process of metastases involves the dissociation of cells from the primary tumor, penetration into the basement membrane, invasion, and exiting from the vasculature to seed and colonize distant tissues. miR-200a is involved in this multistep metastatic cascade. This study aimed to test the hypothesis that miR-200a promotes metastasis through increased anoikis resistance in breast cancer.

GeneSearch™ BLN Assay could replace frozen section and touch imprint cytology for intra-operative assessment of breast sentinel lymph nodes.

Background: Breast cancer sentinel lymph node (SLN) biopsy has become a common procedure. The GeneSearch™ Breast Lymph Node Assay is a real-time reverse-transcriptase polymerase chain reaction assay for detecting nodal metastases larger than 0.2 mm.

Effect of large tumor size on cancer-specific mortality in node-negative breast cancer.

Objective: To examine the relationship between large tumor size and breast cancer-specific mortality (BCSM), especially in a subset of patients with negative lymph nodes (LNs).

Patients And Methods: We used the Surveillance, Epidemiology and End Results registry to identify 107,705 female patients diagnosed from January 1, 1990, through December 31, 2003, as having invasive breast cancer and treated with surgery and LN dissection. Relevant issues unclear in the database were studied in an additional 335 patients with locally advanced disease treated with neoadjuvant chemotherapy.

Hazard of breast cancer-specific mortality among women with estrogen receptor-positive breast cancer after five years from diagnosis: implication for extended endocrine therapy.

Purpose: More than half of the patients with estrogen receptor (ER)-positive breast cancers will relapse and die from breast cancer at 5-10 yr after diagnosis despite 5-yr endocrine therapy. Subpopulations of ER-positive patients at high risk of breast cancer-specific mortality (BCSM) at 5-10 yr are undetermined.

Methods: Using the Surveillance, Epidemiology, and End-Results program (1990-2003), we analyzed the relative hazard ratio (HR) and absolute HR of BCSM and the cumulative 10-yr breast cancer-specific survival (BCSS) in 111,993 breast cancer patients, stratified by ER, age, and lymph node (LN), and adjusted for other prognostic factors.

Influence of a family history of breast and/or ovarian cancer on breast cancer outcomes.

Various published studies have been inconclusive in attempting to relate a family history of breast and/or ovarian cancer (BOC) to the survival of breast cancer patients. The aim of the study was to investigate the association of a family history of BOC with tumor characteristics, treatment response and the difference between the prognosis of familial breast cancer (FBC) patients and sporadic breast cancer (SBC) patients. Data on 348 operable FBC patients and 345 SBC patients were retrospectively analyzed.

Predicting sentinel lymph node metastasis in a Chinese breast cancer population: assessment of an existing nomogram and a new predictive nomogram.

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011.