Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

BACKGROUND: Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD). METHODS: Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients. RESULTS: A total of 33 Crohn's disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly. CONCLUSIONS: Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.

A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment.

Tumor progression is dependent on tumor cells and their microenvironment. It is important to identify therapies that inhibit cancer cells and activate immune cells. Arginine modulation plays a dual role in cancer therapy. Arginase inhibition induced an anti-tumor effect via T-cell activation through an increase in arginine in the tumor environment. In contrast, arginine depletion by arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG 20) induced an anti-tumor response in argininosuccinate synthase 1 (ASS1)-deficient tumor cells. ADI-PEG 20 did not cause toxicity to normal immune cells, which can recycle the ADI-degraded product citrulline back to arginine. To target tumor cells and their neighboring immune cells, we hypothesized that the combination of an arginase inhibitor (L-Norvaline) and ADI-PEG 20 may trigger a stronger anticancer response. In this study, we found that L-Norvaline inhibits tumor growth in vivo. Pathway analysis based on RNA-seq data indicated that the differentially expressed genes (DEGs) were significantly enriched in some immune-related pathways. Significantly, L-Norvaline did not inhibit tumor growth in immunodeficient mice. In addition, combination treatment with L-Norvaline and ADI-PEG 20 induced a more robust anti-tumor response against B16F10 melanoma. Furthermore, single-cell RNA-seq data demonstrated that the combination therapy increased tumor-infiltrating CD8+ T cells and CCR7+ dendritic cells. The increase in infiltrated dendritic cells may enhance the anti-tumor response of CD8+ cytotoxic T cells, indicating a potential mechanism for the observed anti-tumor effect of the combination treatment. In addition, populations of immunosuppressive-like immune cells, such as S100a8+ S100a9+ monocytes and Retnla+ Retnlg+ TAMs, in tumors were dramatically decreased. Importantly, mechanistic analysis indicated that the processes of the cell cycle, ribonucleoprotein complex biogenesis, and ribosome biogenesis were upregulated after combination treatment. This study implied the possibility of L-Norvaline as a modulator of the immune response in cancer and provided a new potential therapy combined with ADI-PEG 20.

Transcatheter closure of large postinfarct ventricular septal defect: Initial results of prototype Occlutech® device including the first-in-human.

BACKGROUND: Postinfarct ventricular septal rupture is a serious complication in delayed or failed reperfusion with a grim prognosis. The optimal timing and treatment option remain debatable in the absence of randomized controlled trials. Percutaneous device closure is a well-reported and less invasive treatment option but recent imaging studies indicate that majority of defects are too large to be adequately covered by the currently Conformite Europeenne and Food and Drug Administration approved occluder devices. METHODS: Six patients presented with large and complex postinfarct ventricular septal ruptures, considered unsuitable for the Amplatzer post-infarct ventricular septal defect Occluder, so were treated using the prototype Occlutech® 36 mm PI-VSD occluder, including the first-in-human use. RESULTS: The prototype device was successfully deployed in all patients with satisfactory immediate results and shunt reduction. Three patients (50%) in cardiogenic shock did not survive beyond discharge, of which two were complicated by device dislodgement or embolization. CONCLUSIONS: Percutaneous closure of large postinfarct ventricular septal ruptures is possible using newer device with a wider coverage. Further device refinement is necessary to improve treatment outcomes.

Low expression of cytosolic NOTCH1 predicts poor prognosis of breast cancer patients.

The incidence of breast cancer is increasing, and is one of the leading causes of cancer death worldwide. Dysregulation of NOTCH1 signaling is reported in breast cancer. In present study, bioinformatics was utilized to study the expression of NOTCH1 gene in breast cancer from public databases, including the Kaplan-Meier Plotter, PrognoScan, Human Protein Atlas, and cBioPortal. The relationship between NOTCH1 mRNA expression and survival of patients was inconsistent in public databases. In addition, we performed immunohistochemistry (IHC) staining of 135 specimens from our hospital. Lower cytoplasmic staining of NOTCH1 protein was correlated with cancer recurrence, bone metastasis, and a worse disease-free survival of patients, especially those with estrogen receptor-positive and human epidermal growth factor receptor 2-positive (HER2+) cancers. In TCGA breast cancer dataset, lower expression of NOTCH1 in breast cancer specimens was correlated with higher level of CCND1 (protein: cyclin D1). Decreased expression of NOTCH1 was correlated with lower level of CCNA1 (protein: cyclin A1), CCND2 (protein: cyclin D2), CCNE1 (protein: cyclin E1), CDK6 (protein: CDK6), and CDKN2C (protein: p18). In conclusion, NOTCH1 mRNA expression is not consistently correlated with clinical outcomes of breast cancer patients. Low cytoplasmic expression of NOTCH1 in IHC study is correlated with poor prognosis of breast cancer patients. Cytoplasmic localization of NOTCH1 protein failed to initial oncogenic signaling in present study. Expression of NOTCH1 mRNA was discordant with cell cycle-related genes. Regulation of NOTCH1 in breast cancer involves gene expression, protein localization and downstream signaling.

"The Continuous Shadow of My Mother's Breast Cancer": exploring the voice of daughters.

PURPOSE: Women whose mothers have been diagnosed with breast cancer are concerned about their mothers' illness and fear developing cancer themselves. This study, conducted in Taiwan, aims to understand daughters' lived experiences after their mothers were diagnosed with breast cancer. METHOD: In-depth interviews were conducted to understand daughters' emotional reactions to their mothers' diagnoses, their challenges with taking care of their mothers, and their concerns or perceptions regarding their own risks of developing breast cancer. Themes were identified using a phenomenological approach with 18 transcripts. RESULTS: Six themes were identified: "taking care of my mother is my responsibility", "desiring sufficient information/support", "feeling helplessness in providing care", "expecting a cancer diagnosis in fear", "anticipating reassurance other than surveillance", and "worrying about myself is not a priority". In addition, these themes reflected their concerns about how to support their mothers physically and psychologically, how to manage their own worries about cancer, and how to maintain their health. CONCLUSION: The daughters prioritized the responsibility of caring for their mothers physically and psychologically rather than managing their own cancer concerns. Health care professionals should be aware of these priorities to provide education regarding the care of high-risk populations and psychological support to adult daughters.

Cost-effectiveness evaluation of mammography screening program in Taiwan: Adjusting different distributions of age and calendar year for real world data.

BACKGROUND/PURPOSE: We estimated loss-of-life expectancy (LE) and lifetime medical expenditures (LME) stratified by stages to evaluate the cost-effectiveness of breast cancer (BC) screening in Taiwan. METHODS: We interlinked four national databases- Cancer Registry, Mortality Registry, National Health Insurance Claim, and Mammography Screening. A cohort of 123,221 BC was identified during 2002-2015 and followed until December 31, 2017. We estimated LE and loss-of-LE by rolling extrapolation algorithm using age-, sex-, and calendar-year-matched referents simulated from vital statistics. LME was estimated by multiplying monthly cost with survival probability and adjusted for annual discount rate. We calculated incremental cost-effectiveness ratio (ICER) by comparing the loss-of-LE of those detected by screening versus non-screening after accounting for administration fees and radiation-related excess BC. RESULTS: The LEs of stages I, II, III, and IV were 31.4, 27.2, 20.0, and 5.2 years, respectively, while the loss-of-LEs were 1.2, 4.9, 11.7, and 25.0 years with corresponding LMEs of US$ 73,791, 79,496, 89,962, and 66,981, respectively. The difference in LE between stages I and IV was 26.2 years while that of loss-of-LE was 23.8 years, which implies that a potential lead time bias may exist if diagnosis at younger ages for earlier stages were not adjusted for. The ICER of mammography seemed cost-saving after the coverage exceeded half a million. CONCLUSION: Mammography could detect BC early and be cost-saving after adjustment for different distributions of age and calendar year of diagnosis. Future studies exploring healthcare expenditure and impaired quality of life for false-positive cases are warranted.

False-negative frozen section of sentinel nodes in early breast cancer (cT1-2N0) patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data. METHODS: A case-control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections. RESULTS: A total of 20 FNSN cases and 60 matched controls from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls. CONCLUSIONS: Patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.

From darkness, a light shall spring: Zero-fluoroscopic ablation of supraventricular tachycardia in a pregnant lady.

Our case illustrated zero-fluoroscopic approach on AVNRT ablation in a pregnant lady.

The prognosis of early-stage breast cancer in extremely young female patients.

ABSTRACT: Breast cancer at a young age is associated with poor outcomes. However, few reports have compared the outcomes of breast cancer between extremely young patients and elderly patients.We retrospectively collected information on patients diagnosed with breast cancer before 30 years of age. This case-control study employed matched operative methods, stage, and subtypes with a case-to-control ratio of 1:3. The primary endpoint was disease-free survival, and the secondary endpoint was overall survival. We analyzed potential prognostic factors in univariate and multivariate analyses.This analysis included 18 patients in the young group with a median age of 28.5 years and 54 patients in the control group with a median age of 71 years. The 5-year disease-free survival rate was 68.8% in the former group and 84.6% in the latter group (P = .080). The 5-year overall survival was 87.1% and 91.2% in the young and old groups, respectively (P = .483). Multivariate analysis showed that tumor size and triple-negative breast cancer was major prognostic factors of poorer disease-free survival in the young group.Extremely young breast cancer patients had a trend to develop a poorer disease-free survival than old patients, but not a poorer overall survival. Aggressive treatment for young patients at early stages of disease would improve survival.

Inhibitory effect of PPARγ on NLRP3 inflammasome activation.

Rationale: Stimulation of the NLRP3 inflammasome by metabolic byproducts is known to result in inflammatory responses and metabolic diseases. However, how the host controls aberrant NLRP3 inflammasome activation remains unclear. PPARγ, a known regulator of energy metabolism, plays an anti-inflammatory role through the inhibition of NF-κB activation and additionally attenuates NLRP3-dependent IL-1ß and IL-18 production. Therefore, we hypothesized that PPARγ serves as an endogenous modulator that attenuates NLRP3 inflammasome activation in macrophages. Methods: Mouse peritoneal macrophages with exposure to a PPARγ agonist at different stages and the NLRP3 inflammasome-reconstituted system in HEK293T cells were used to investigate the additional anti-inflammatory effect of PPARγ on NLRP3 inflammasome regulation. Circulating mononuclear cells of obese patients with weight-loss surgery were used to identify the in vivo correlation between PPARγ and the NLRP3 inflammasome. Results: Exposure to the PPARγ agonist, rosiglitazone, during the second signal of NLRP3 inflammasome activation attenuated caspase-1 and IL-1ß maturation. Moreover, PPARγ interfered with NLRP3 inflammasome formation by decreasing NLRP3-ASC and NLRP3-NLRP3 interactions as well as NLRP3-dependent ASC oligomerization, which is mediated through interaction between the PPARγ DNA-binding domain and the nucleotide-binding and leucine-rich repeat domains of NLRP3. Furthermore, PPARγ was required to limit metabolic damage-associated molecular pattern-induced NLRP3 inflammasome activation in mouse macrophages. Finally, the mature caspase-1/PPARγ ratio was reduced in circulating mononuclear cells of obese patients after weight-loss surgery, which we define as an "NLRP3 accelerating index". Conclusions: These results revealed an additional anti-inflammatory role for PPARγ in suppressing NLRP3 inflammasome activation through interaction with NLRP3. Thus, our study highlights that PPARγ agonism may be a therapeutic option for targeting NLRP3-related metabolic diseases.

Long-term outcomes of metabolic surgery in overweight and obese patients with type 2 diabetes in Asia.

AIM: To assess the outcomes of metabolic surgery in overweight and obese patients in Asia with type 2 diabetes (T2D). MATERIALS AND METHODS: The treatment outcomes of 1999 patients from the Asian Diabetes Surgery Summit database were analysed. The changes in treatment effects across time were assessed with respect to the surgical procedures performed by using generalized estimating equations. RESULTS: The most commonly performed procedure was the single-anastomosis gastric bypass (32.6%). Weight (from 106.2 ± 25.1 to 77.9 ± 18.8 kg), body mass index (BMI; from 38.7 ± 7.9 to 28.5 ± 5.9 kg/m2 ), blood sugar (from 9.3 ± 4.1 to 5.7 ± 1.8 mmol/L) and HbA1c (from 8.4% ± 1.8% to 6.0% ± 1.1%) significantly improved from baseline to 1 year (P < .001) and remained stable at 5 years (weight, 86.3 ± 23.3 kg; BMI, 31.7 ± 7.9 kg/m2 ; blood sugar, 5.8 ± 1.8 mmol/L, and HbA1c, 6.4% ± 1.2%; all P < .001 vs. baseline). Blood pressure and most lipid disorders also improved significantly. Of the treatment procedures, single-anastomosis gastric bypass had the most satisfactory outcomes with statistical significance for most disorders, whereas adjustable gastric banding displayed the least satisfactory outcomes. CONCLUSIONS: Metabolic surgery remarkably improved body weight, T2D and other metabolic disorders in Asian patients. However, the efficacy of individual procedures varied substantially.

Long-term effectiveness of an E-based survivorship care plan for breast cancer survivors: A quasi-experimental study.

OBJECTIVE: The purpose of this study was to evaluate the effect of a web-based survivorship care plan (SCP) computerized application (APP): (SCP-A) on women's unmet needs, fear of recurrence, symptom distress, anxiety, depression, and quality of life (QoL). METHODS: Women diagnosed with breast cancer, who had completed their primary treatment but less than 5 years without a sign of recurrence (N = 165) were randomized to a SCP-A or a control group. Self-reported questionnaires were completed by the both groups at baseline (T0), 5 weeks (T1), 3 months (T2), 6 months (T3), and 12 months (T4). RESULTS: Controlling for relevant covariates, mixed effect model analyses revealed a significant decrease in women in the SCP-A group compared to the control group for total unmet needs since T3 (p < .004) and fear of recurrence since T4 (p = .02). Women in the SCP-A group also reported significant improvements in QoL at T4 (p < .001) relative to those in the control group. CONCLUSION: Providing SCP using an information website application for women with breast cancer can decrease unmet needs, fear of recurrence, and improve quality of life during short-term and long-term use. PRACTICE IMPLICATIONS: Web-based information that provides survivorship care plans for breast cancer survivors are beneficial.

Mutation of the PTCH1 gene predicts recurrence of breast cancer.

Breast cancer is the most common cancer in women, and some patients develop recurrence after standard therapy. Effective predictors are urgently needed to detect recurrence earlier. The activation of Hedgehog signaling in breast cancer is correlated with poor prognosis. PTCH1 is an essential membrane receptor of Hedgehog. However, there are few reports about mutations in Hedgehog genes in breast cancer. We conducted a comprehensive study via an experimental and bioinformatics approach to detect mutated genes in breast cancer. Twenty-two breast cancer patients who developed recurrence within 24 months postoperatively were enrolled with 22 control cancer patients. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the mutated genes. Mutations were identified in 44 breast cancer specimens, and the most frequently mutated genes were BRCA2, APC, ATM, BRCA1, NF1, TET2, TSC1, TSC2, NOTCH1, MSH2, PTCH1, TP53, PIK3CA, FBXW7, and RB1. Mutation of these genes was correlated with protein phosphorylation and autophosphorylation, such as peptidyl-tyrosine and protein kinase C phosphorylation. Among these highly mutated genes, mutations of PTCH1 were associated with poor prognosis and increased recurrence of breast cancer, especially mutations in exons 22 and 23. The public sequencing data from the COSMIC database were exploited to predict the functions of the mutations. Our findings suggest that mutation of PTCH1 is correlated with early recurrence of breast cancer patients and will become a powerful predictor for recurrence of breast cancer.

The oncogenic role of MST3 in human gastric cancer.

MST3 (mammalian STE20-like kinase) is one of the protein kinase of the GCK III subfamily STE 20, and is known to play a role in cell growth and apoptosis. Our laboratory has demonstrated that MST3 promotes tumorigenicity through the VAV2/Rac1 signal axis in breast cancer. In this report, we further investigated the potential oncogenic role of MST3 in gastric cancer. Examination of tissue samples from 101 gastric cancer patients revealed that higher expression of MST3 was observed in tumor part with immunohistochemistry. Furthermore, high expression of MST3 predicts poor prognosis in gastric cancer patients. To investigate the function of MST3 in vitro, MKN45 and NCI-N87 cell lines were transfected with the MST3 shRNA and stable clones were established. Downregulation of MST3 inhibited cell proliferation. The p21 expression was enhanced by MST3 shRNA in MKN45 gastric cancer cell line. Finally, downregulation of MST3 attenuated the anchorage-independent growth in soft agar and tumor growth in NOD/SCID mice. Altogether, our results indicate that MST3 potentially plays an oncogenic role in gastric cancer.

Fear of Recurrence as a Predictor of Care Needs for Long-Term Breast Cancer Survivors.

BACKGROUND: The improved survival rate for breast cancer has increased the number of women living with the diagnosis for more than 5 years. Limited studies have focused on the care needs for long-term healthy survivors of breast cancer. OBJECTIVE: The aims of this study were to understand the care needs of long-term breast cancer survivors and identify related factors that influence these needs. METHODS: A convenience sampling with a correlational study design was used. Women at least 20 years old, who were given a diagnosis of breast cancer at least 5 years, were recruited from 2 hospital clinics in southern Taiwan. A self-administered questionnaire measuring cancer survivors' unmet needs was administered after obtaining informed consent. Binary logistic regression was used to examine variables associated with unmet care needs. RESULTS: Of the 192 women participating, the highest unmet needs related to existential survivorship. The most frequently endorsed unmet need was for an ongoing case manager. Fear of recurrence was associated with 3 aspects including existential survivorship, comprehensive cancer, and quality-of-life unmet needs (odds ratio, 1.14-1.21). CONCLUSIONS: Even 5 years after the diagnosis and completion of therapy, women continue to report unmet needs. Evaluating women's fear of recurrence to identify high-risk women with unmet needs is critical to providing quality care. IMPLICATION FOR PRACTICE: Developing appropriate survivorship care programs combined with managing concerns regarding recurrence by a nursing case manager is needed.

PSMB5 plays a dual role in cancer development and immunosuppression.

Tumor progression and metastasis are dependent on the intrinsic properties of tumor cells and the influence of microenvironment including the immune system. It would be important to identify target drug that can inhibit cancer cell and activate immune cells. Proteasome ß subunits (PSMB) family, one component of the ubiquitin-proteasome system, has been demonstrated to play an important role in tumor cells and immune cells. Therefore, we used a bioinformatics approach to examine the potential role of PSMB family. Analysis of breast TCGA and METABRIC database revealed that high expression of PSMB5 was observed in breast cancer tissue and that high expression of PSMB5 predicted worse survival. In addition, high expression of PSMB5 was observed in M2 macrophages. Based on our bioinformatics analysis, we hypothesized that PSMB5 contained immunosuppressive and oncogenic characteristics. To study the effects of PSMB5 on the cancer cell and macrophage in vitro, we silenced PSMB5 expression with shRNA in THP-1 monocytes and MDA-MB-231 cells respectively. Knockdown of PSMB5 promoted human THP-1 monocyte differentiation into M1 macrophage. On the other hand, knockdown PSMB5 gene expression inhibited MDA-MB-231 cell growth and migration by colony formation assay and boyden chamber. Collectively, our data demonstrated that delivery of PSMB5 shRNA suppressed cell growth and activated defensive M1 macrophages in vitro. Furthermore, lentiviral delivery of PSMB5 shRNA significantly decreased tumor growth in a subcutaneous mouse model. In conclusion, our bioinformatics study and functional experiments revealed that PSMB5 served as novel cancer therapeutic targets. These results also demonstrated a novel translational approach to improve cancer immunotherapy.

Mesh migration into the sigmoid colon mimics a colon tumor, a rare complication after herniorrhaphy: case report.

INTRODUCTION: Tension-free mesh repair is a widely used hernioplasty technique. However, mesh migration is a severe complication that may induce colon inflammation or perforation and can occur several months to several years following hernioplasty. CASE REPORT: We present a case where mesh migrated into the sigmoid colon 12 years postoperation and was mistaken for a colon tumor.

HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells.

Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan-Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.