Robotic Versus Conventional or Endoscopic-assisted Nipple-sparing Mastectomy and Immediate Prosthesis Breast Reconstruction in the Management of Breast Cancer: A Prospectively Designed Multicenter Trial Comparing Clinical Outcomes, Medical Cost, and Patient-reported Outcomes (RCENSM-P).

OBJECTIVE: To compare the clinical and patient-reported outcomes of minimal access and conventional nipple-sparing mastectomy (C-NSM). The secondary outcomes investigated included medical costs and oncological safety. BACKGROUND: Minimal-access NSM has been increasingly applied in the treatment of patients with breast cancer. However, prospective multicenter trials comparing robotic-assisted NSM (R-NSM) versus C-NSM or endoscopic-assisted NSM (E-NSM) are lacking. METHODS: A prospectively designed 3-arm multicenter, nonrandomized trial (NCT04037852) was conducted from October 1, 2019 to December 31, 2021, to compare R-NSM with C-NSM or E-NSM. RESULTS: A total of 73 R-NSM, 74 C-NSM, and 84 E-NSM procedures were enrolled. The median wound length and operation time of C-NSM was (9 cm, 175 minutes), (4 cm, and 195 minutes) in R-NSM, and (4 cm and 222 minutes) in E-NSM. Complications were comparable among the groups. Better wound healing was observed in the minimal-access NSM group. The R-NSM procedure was 4000 and 2600 United States Dollars more expensive than C-NSM and E-NSM, respectively. Wound/scar and postoperative acute pain evaluation favored the use of minimal access NSM over C-NSM. Quality of life in terms of chronic breast/chest pain, mobility, and range of motion of the upper extremity showed no significant differences. The preliminary oncologic results showed no differences among the 3 groups. CONCLUSIONS: R-NSM or E-NSM is a safe alternative if compared with C-NSM in terms of perioperative morbidities, especially with better wound healing. The advantage of minimal access groups was higher wound-related satisfaction. Higher costs remain one of the major limiting factors in the widespread adoption of R-NSM.

Monitoring trends in the absolute lymphocyte count and the neutrophil-to-lymphocyte ratio in patients with breast cancer receiving eribulin.

BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.

Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting.

BACKGROUND: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. METHODS: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. RESULTS: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). CONCLUSIONS: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.

Comparison of the Diagnostic Accuracy of Magnetic Resonance Imaging with Sonography in the Prediction of Breast Cancer Tumor Size: A Concordance Analysis with Histopathologically Determined Tumor Size.

BACKGROUND: In order to effectively treat patients with breast cancer, it is important to know the precise tumor size. We compared the rates of concordance of magnetic resonance imaging (MRI)-derived and sonography-derived breast cancer tumor size with histopathologically determined tumor size. METHODS: Accuracy of MRI and sonography in establishing tumor size was evaluated by comparing preoperative images with postoperative pathologic findings. The accuracy of MRI and sonography was graded as concordance, underestimation, or overestimation and was compared in different subgroups. RESULTS: A total of 682 patients comprised the study cohort. Mean tumor size was 3.64 ± 1.8 cm via MRI, 2.12 ± 1.0 cm via sonography, and 2.78 ± 1.7 cm via pathologic examination. The difference between breast sonography and MRI to pathologic tumor field size was -0.68 ± 1.4, and 0.85 ± 1.25 cm, respectively (P < 0.001). Sonography had a concordance rate of 54.3 %, an overestimated rate of 9.8 %, and an underestimated rate of 35.9 %. For MRI, the concordance rate was 44.1 %, the overestimated rate was 52.5 %, and the underestimated rate was 3.4 %. In subgroup analysis, breast MRI had a higher concordance rate in patients with T3 (>5 cm) lesions. When the results of MRI and sonography were considered together, the concordance rate increased from 54.3 to 62.2 %. CONCLUSION: MRI tends to overestimate the actual tumor size, while sonography frequently underestimates it. Combined sonography and MRI increases the accuracy of tumor size prediction.

DNA methylation markers and serum α-fetoprotein level are prognostic factors in hepatocellular carcinoma.

INTRODUCTION: Hypermethylation of relevant genes may affect the prognosis of patients with cancer. The purpose of this study was to analyze whether methylation of the promoter regions of cell cycle regulators as well as elevated α-Fetoprotein (AFP) levels are useful prognostic factors for patients with hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Nested methylation-specific PCR (nested-MSP) was used to analyze methylation status of the promoter regions of p15, p16, p21, p27, and ras-association domain family 1 (RASSF1A) genes in tumor specimens from 50 patients with HCC. RESULTS: Promoter methylation was most common in the RASSF1A gene (96%), followed by the p16 gene (56%), the p21 gene (44%), the p15 gene (28%), and the p27 gene (2%). Patients with a serum AFP level < 400 ng/mL and an unmethylated p21 promoter had a better prognosis than patients with a serum AFP level ≥ 400 ng/mL and a methylated p21 promoter (overall survival, p = 0.076; disease-free survival, p = 0.016). In addition, patients with full methylation of the promoter region of RASSF1A had a better prognosis than patients with a partially methylated or unmethylated RASSF1A promoter region if their serum AFP level was ≥ 400 ng/mL (overall survival, p = 0.028; disease-free survival, p = 0.078). CONCLUSION: A partially methylated or unmethylated RASSF1A promoter as well as elevated serum AFP level or methylation of p21 in addition to elevated serum AFP level might be associated with poor prognosis in patients with hepatocellular carcinoma.

Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of heterozygosity at Xq25 in relation to breast cancer risk.

BACKGROUND: The aim of this study was to examine the association of non-random X chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with breast cancer development. METHODS: Seventy-nine breast cancer patients, 39 female lung cancer patients, 30 other cancer patients and 77 healthy females were analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The androgen receptor (AR) gene was chosen as an XCI marker. RESULTS: LOH of at least one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined, while only 10/25 cancers of other origins demonstrated LOH in this region (p = 0.014). The critical deletion region in breast cancer was around marker DXS1047 (47.23%). Moreover, we found that tissues from eight breast cancers showed LOH at all of the informative loci tested at Xq25, while the other 38 showed partial (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of XCI of these eight breast cancers tended to be non-random. We estimated the frequencies of AR alleles and found that women with two long AR alleles (≥21 CAG repeats) had an increased risk of developing breast cancer, while those with two short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069). CONCLUSIONS: The extraordinary high frequencies of LOH at Xq25 found in this study strongly imply that there might be one or more tumour suppressor genes (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese female population.

Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer.

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC.

Quality of care in the course of subcutaneous versus intravenous trastuzumab administration in patients with breast cancer: an integrated time-motion study with mixed-methods research.

OBJECTIVES: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC). DESIGN: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses. SETTING: Outpatient and inpatient administration units of a single medical centre in Taiwan. PARTICIPANTS: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses. RESULT: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak. CONCLUSION: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.

Short-term effect of internet-delivered mindfulness-based stress reduction on mental health, self-efficacy, and body image among women with breast cancer during the COVID-19 pandemic.

Background and aim: During the COVID-19 pandemic, an Internet-Mindfulness-Based Stress Reduction (iMBSR) program was delivered and may be better than an in-person approach. Our study evaluated the effects of iMBSR intervention on mental health, self-efficacy, and body image in women with breast cancer in Taiwan. Materials and methods: Sixty-seven women with breast cancer were allocated to a 6-week iMBSR (n = 41) program or a waitlist control group (n = 26), without heterogeneity between group characteristics. Patients from both groups were measured at baseline and postintervention using three scales: Depression, Anxiety, and Stress Scale (DASS-21), General self-efficacy scale, and Body Image Scale. Descriptive dataset analysis, paired t-test, and Student's t-test were used to evaluate the data. Results: Although iMBSR did not significantly improve depression and stress between groups, iMBSR could improve anxiety (Δmean: -2.0 vs. -0.4, p = 0.041) with medium effect sizes. Significant benefits were found for body image (Δmean: -3.6 vs. 0.9, p = 0.003) and self-efficacy (Δmean: 4.2 vs. 1.5, p = 0.004), with large effect sizes (Cohen's d = 0.73). Conclusion: Our preliminary study supports iMBSR as a program that can improve mental health, body image, and self-efficacy in women with breast cancer. During the COVID-19 pandemic, medical professionals can use Internet-based clinical health education.

Semi-quantitative expression of tissue inhibitor of matrix metalloproteinase-2 in cancer of uterine cervix.

BACKGROUND AND OBJECTIVE: Because matrix metalloproteinase-2 (MMP-2) is associated with tumor progression and tissue inhibitor of MMP-2 (TIMP-2) selectively inhibits MMP-2, we investigate the implication of TIMP-2 in carcinogenesis of uterine cervix. METHODS: Twenty-six cervical cancer tissues and their normal counterparts were collected to evaluate semi-quantitative mRNA expression of TIMP-2. Eighty-two cervical cancer, 26 high-grade and 26 low-grade dysplasia, and 26 normal tissues were collected to construct tissue microarrays for immunohistochemical study. We evaluated TIMP-2 immunoreactivity using H scores in cervical carcinogenesis. Semi-quantitative expression of MMP-2 was also detected for comparison. RESULTS: Cervical cancer tissues exhibited statistically lower semi-quantitative TIMP-2 (P = 0.028) or higher MMP-2 (P = 0.036) mRNA expression than their normal counterparts. None of cervical cancer tissues exerted elevated TIMP-2 and reduced MMP-2 mRNA expression simultaneously. Cancer tissues have significantly lower TIMP-2 or higher MMP-2 H scores than high-grade and low-grade dysplasia or normal tissues of uterine cervix. CONCLUSIONS: Low expression of TIMP-2 or high expression of MMP-2 is semi-quantitatively demonstrated in cancer of uterine cervix. TIMP-2 is implicated in cervical carcinogenesis.

Antitumor Actions of Intratumoral Delivery of Membrane-Fused Mitochondria in a Mouse Model of Triple-Negative Breast Cancers.

BACKGROUND: The transfer of whole mitochondria has been demonstrated to be beneficial for treating breast cancer because it induces apoptosis and drug sensitivity; however, in vivo evidence of this benefit remains scant. The present study compared the transplantation of mitochondria with instinctive (Mito) and membrane-fused morphologies induced by Pep-1 conjugation (P-Mito) using a mouse model of triple-negative breast cancers. MATERIALS AND METHODS: Mice with advanced severe immunodeficiency received orthotopic implantation of MDA-MB-231 human breast cancer cells followed by transplants of 5-bromo-2'-deoxyuridine (BrdU)-labeled Mito or P-Mito (200 µg [10 µg/µL]) through intratumoral injection at multiple points once a week for 4 weeks. RESULTS: After 1 month of consecutive treatment, 8.2% and 14.2% of the BrdU-labeled mitochondria were preserved in tumors of the Mito and P-Mito groups, respectively. Both Pep-1 and P-Mito treatments reduced tumor weight (21.7% ± 2.43% vs 40.6% ± 2.28%) and led to marked inhibition of Ki67 staining and angiogenesis. However, only the P-Mito group exhibited obvious necrosis and DNA fragmentation accompanied by an altered tumor microenvironment, which included reduced oxidative stress and size of cancer-associated fibroblast populations and enhanced immune cell infiltration. Transmission electron microscopy images further revealed an elongated network of perinuclear mitochondria fused with a few peripheral mitochondria in the nonnecrotic area in the P-Mito group as well as increases in mitochondrial fusion proteins and parkin compared with mitochondrial fission proteins. CONCLUSION: In this study, the results of mitochondrial transplantation emphasized that the facilitation of mitochondrial fusion is a critical regulator in breast cancer therapy.

Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a significant pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloid. It has been shown to exert biological activities (anticarcinogenic, antimutagenic and chemopreventive) in many cancer cell lines. It was found that capsaicin induces dose-dependent growth inhibition of MCF-7 cells, which does not express caspase-3. In this study, we investigated the molecular mechanism of capsaicin-induced apoptosis in MCF-7 cells. Treatment with capsaicin for 24 h resulted in dose-dependent apoptosis in these cells. After the addition of capsaicin, the levels of reactive oxygen species were reduced slightly in the earlier stage of treatment. Interestingly, an elevation of intracellular calcium ion concentration was detected in the MCF-7 cells. In time course and dosage studies, the mitochondrial membrane potential of MCF-7 cells decreased. However, the change was not significant. It is worth noting that the apoptosis-inducing factor translocated into the cytosol and nucleus from the mitochondria. Our results suggest that capsaicin induces cellular apoptosis through a caspase-independent pathway in MCF-7 cells, and that reactive oxygen species and intracellular calcium ion fluctuation has a minimal role in the process.

Mitochondrial transplantation regulates antitumour activity, chemoresistance and mitochondrial dynamics in breast cancer.

BACKGROUND: The transfer of whole mitochondria that occurs during cell contact has been found to support cancer progression. However, the regulatory role of mitochondria alone is difficult to elucidate due to the complex microenvironment. Currently, mitochondrial transplantation is an available approach for restoring mitochondrial function in mitochondrial diseases but remains unclear in breast cancer. Herein, effects of mitochondrial transplantation via different approaches in breast cancer were investigated. METHODS: Whole mitochondria (approximately 10.5 µg/ml) were transported into MCF-7 breast cancer cells via passive uptake or Pep-1-mediated delivery. Fresh mitochondria isolated from homeoplasmic 143B osteosarcoma cybrids containing mitochondrial DNA (mtDNA) derived from health individuals (Mito) or mtDNA with the A8344G mutation (Mito8344) were conjugated with cell-penetrating peptide Pep-1 (P-Mito) or not conjugated prior to cell co-culture. Before isolation, mitochondria were stained with MitoTracker dye as the tracking label. After 3 days of treatment, cell viability, proliferation, oxidative stress, drug sensitivity to Doxorubicin/Paclitaxel and mitochondrial function were assessed. RESULTS: Compared with P-Mito, a small portion of Mito adhered to the cell membrane, and this was accompanied by a slightly lower fluorescent signal by foreign mitochondria in MCF-7 cells. Both transplantations induced cell apoptosis by increasing the nuclear translocation of apoptosis-inducing factor; inhibited cell growth and decreased oxidative stress in MCF-7 cells; and increased the cellular susceptibility of both the MCF-7 and MDA-MB-231 cell lines to Doxorubicin and Paclitaxel. Mitochondrial transplantation also consistently decreased Drp-1, which resulted in an enhancement of the tubular mitochondrial network, but a distinct machinery through the increase of parkin and mitochondrial fusion proteins was observed in the Mito and P-Mito groups, respectively. Furthermore, although there were no differences in energy metabolism after transplantation of normal mitochondria, metabolism was switched to the energetic and glycolytic phenotypes when the mitochondria were replaced with dysfunctional mitochondria, namely, Mito8344 and P-Mito8344, due to dramatically induced glycolysis and reduced mitochondrial respiration, respectively. Consequently, transplant-induced growth inhibition was abolished, and cell growth in the Mito8344 group was even higher than that in the control group. CONCLUSION: This study reveals the antitumour potential of mitochondrial transplantation in breast cancer via distinct regulation of mitochondrial function.

Radical Scavenging and Antiproliferative Effects of Cordycepin-Rich Ethanol Extract from Brown Rice-Cultivated Cordyceps militaris (Ascomycetes) Mycelium on Breast Cancer Cell Lines.

The yield and efficacy of bioactive compounds from Cordyceps militaris fruiting bodies and its fermented grains usually vary with the strain used. In this study, we compared the antiproliferative, apoptotic, and antioxidative properties of ethanolic extracts of fruiting bodies and solid-stated fermented rice (FRE) from two wild-type strains of C. militaris applied to human breast cancer cell lines. We observed that FRE of the Zhangzhou strain (FRE-Z) produced a high level of cordycepin and exhibited comprehensive in vitro antioxidant activity against the oxidation of 2,2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radicals and low-density lipoprotein. Only FRE-Z exhibited dose-dependent inhibition of cell proliferation in MCF-7 (0.7 mg/mL) and MDA-MB-231 cells (1 mg/mL) after culturing for 24 h. The antiproliferative effects of FRE-Z were associated with an early stage of apoptosis induction at 4 h of treatment with 0.5 mg/mL FRE-Z in MCF-7 cells. The antiproliferative effect was determined to occur through p53 activation but not through the release of mitochondrial apoptosis-inducing factor or caspase-9 activation for an initial culture period of 16 h. In addition to a transient increase in cellular antioxidant enzyme, Cu/Zn superoxide dismutase was identified in MCF-7 cells after 2 h of treatment with FRE-Z. Therefore, FRE-Z, which exhibits various dose- and exposure time-dependent activities, has potential application in breast cancer chemoprevention.

2-Phenylnaphthyridin-4-one Derivative LYF-11 Inhibits Interleukin-6-mediated Epithelial-to-Mesenchymal Transition via the Inhibition of JAK2/STAT3 Signaling Pathway in MCF-7 Cells.

BACKGROUND/AIM: Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial-mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. MATERIALS AND METHODS: MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. RESULTS: In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6-induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. CONCLUSION: Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.

Multi-center study on patient selection for and the oncologic safety of intraoperative radiotherapy (IORT) with the Xoft Axxent® eBx® System for the management of early stage breast cancer in Taiwan.

BACKGROUND: In this multi-center study, we report the patient selection criteria for and preliminary oncologic outcomes associated with intraoperative radiotherapy (IORT) delivered by the Xoft Axxent® eBx® system for early-stage breast cancer in Taiwan. METHODS: Patients with early breast cancer in Taiwan received breast conserving surgery and received IORT with Xoft Axxent® eBx® System during 2013-2015 was search from database of Taiwan IORT study cooperative group (T-IORTSCG). Patients' clinicopathologic characteristics and early post-operative results were collected and reported. RESULTS: During the study period, 26 hospitals in Taiwan performed a total of 261 Xoft IORT procedures for breast cancer. The mean age of them was 52.9 ± 9.8 years (37-72), and tumor size was 1.5 ± 0.8 cm (0.1-4.2 cm) for invasive cancer and 1.2 ± 0.8 cm (range, 0.2-3.0 cm) for ductal carcinoma in situ (DCIS) lesions. Lymph node metastasis was found in 6 (2.3%) patients. The patients received IORT in Taiwan differed markedly from those used in the ELIOT and TARGIT-A studies. Specifically, patients selected for IORT in Taiwan tended to be younger, their tumors tended to be larger and the prevalence of lymph node metastasis tended to be lower. Among these 261 patients, 8 (3.1%) patients required whole breast radiotherapy. During a mean follow up of 15.6 months, locoregional recurrence was observed in 2 (0.8%) patients. CONCLUSION: In real world experience, patients received IORT differed quite significantly with criteria formulated by trials. The preliminary results of IORT in Taiwan showed it is well acceptable by patients and clinicians.

Expression of glucose transporter-1 in Taiwanese patients with breast carcinoma--a preliminary report.

Malignant cells show increased glucose uptake in vitro and in vivo. High expression of the glucose transporter-1 gene (GLUT1) has been found in many human tumor tissues. The aim of this study was to investigate the correlation between GLUT1 expression in breast carcinomas of Taiwanese patients and clinical prognostic parameters. Twenty-eight (71.8%) of the 39 breast carcinomas analyzed showed positive GLUT1 expression with different intensities: 1+, 19 cases (48.7%); 2+, 6 cases (15.4%), 3+, 3 cases (7.7%). No significant correlation was seen between GLUT1 expression and clinical prognostic parameters such as tumor size (p = 0.085), age (p = 0.4528), axillary lymph node metastasis (p = 0.9562), nuclear grade (p = 0.6895), estrogen receptor-positive (p = 1.0000), and progesterone receptor-positive (p = 0.9689).

Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells.

There has been considerable evidence recently demonstrating the anti-tumour effects of flavonols. Quercetin, an ubiquitous bioactive flavonol, inhibits cells proliferation, induces cell cycle arrest and apoptosis in different cancer cell types. The precise molecular mechanism of quercetin-induced apoptosis in human breast cancer cells is unclear. The purpose of this study was to investigate effects of quercetin on cell viability and to determine its underlying mechanism in human breast cancer MDA-MB-231 cells. Quercetin decreased the percentage of viable cells in a dose- and time-dependent manner, which was associated with cell cycle arrest and apoptosis. Quercetin did not increase reactive oxygen species generation but increased cytosolic Ca(2+) levels and reduced the mitochondrial membrane potential (DeltaPsi(m)). Quercetin treatment promoted activation of caspase-3, -8 and -9 in MDA-MB-231 cells. Caspase inhibitors prevented the quercetin-induced loss of cell viability. Quercetin increased abundance of the pro-apoptotic protein Bax and decreased the levels of anti-apoptotic protein Bcl-2. Confocal laser microscope examination indicated that quercetin promoted apoptosis-inducing factor (AIF) release from mitochondria and stimulated translocation to the nucleus. Taken together, these findings suggest that quercetin results in human breast cancer MDA-MB-231 cell death through mitochondrial- and caspase-3-dependent pathways.