US-guided PMC of small solitary breast cancers is feasible. Nevertheless, larger-scale clinical trials are still needed to validate PMC for adoption into a standard clinical practice.
We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro. The capacities for mammosphere formation and STAT3 expression of CD44+CD24−/low MCF-7 and MCF-7 were observed. The CD44+CD24−/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant (TAM-R) cells. Cell cycle, apoptosis, STAT3 and phospho-STAT3 changes were observed after treatment with tamoxifen. Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed. CD44+CD24−/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7. The CD44+CD24−/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7. Cell cycle changes, anti-apoptotic effects and STAT3 changes were also found. Meanwhile, the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen. It is concluded that STAT3 plays an essential role in breast cancer stem cells, which correlated with tamoxifen resistance.
Objectives:The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort.Methods:C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia.Results:A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.055%), all with a positive family history of neurodegenerative dementia, amyotrophic lateral sclerosis, or atypical parkinsonism, while no carriers were detected with typical sporadic or familial PD. Meta-analysis revealed a small increase in risk of PD with an increasing number of (G4C2)n repeats; however, we could not detect a robust association between the C9orf72 (G4C2)n repeat and PD, and the population attributable risk was low.Conclusions:Together, these findings indicate that expansions in C9orf72 do not have a major role in the pathogenesis of PD. Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease.
Nipple discharge is a common complaint of patients with breast disease. The color of nipple discharge is always the first alarming symptom for patients. It is controversial whether the discharge color is an indicator of an underlying malignancy. The electronic database PubMed was searched for relevant articles. A meta-analysis about the association between the color of nipple discharge and breast cancer risk was conducted. Eight studies, including 3,110 patients, were eligible for this meta-analysis. Compared with patients in non-bloody nipple discharge group (179/1,478), patients in bloody nipple discharge group (404/1,632) had a markedly higher breast cancer risk (OR: 2.27, 95% CI: 1.32-3.89, P < 0.001 for heterogeneity). Compared with patients in clear/serous group (71/575), patients in bloody nipple discharge group (326/1,271) also had a higher risk (OR: 2.49, 95% CI: 1.25-4.93, P = 0.011 for heterogeneity). Furthermore, compared with patients in the colored group (55/448), patients in bloody nipple discharge group (296/1,124) (OR: 2.00, 95% CI: 0.74-5.45, P = 0.009 for heterogeneity) had no significant difference. Besides, there was no significant difference between patients in colored group (55/448) and clear/serous group (61/470) (OR: 1.35, 95% CI: 0.83-2.18, P = 0.707 for heterogeneity). Therefore, bloody nipple discharge could be a predictor of breast cancer risk among different colors of discharges. The symptom of bloody nipple discharge is helpful to the stratification of preoperative patients.
Objective: To explore the therapeutic effects of early enteral nutrition (EEN) on patients with sepsis on mechanical ventilation. Methods: Patients with sepsis on mechanical ventilation in the medical intensive care unit (ICU) from January 2013 to March 2016 were treated with enteral nutrition. Patients treated within 48 hours of initiation of mechanical ventilation were assigned to the EEN group, and the rest were assigned to the delayed enteral nutrition (DEN) group. Peripheral blood Th17 cells and Treg cells, endotoxin (ET) level, 28-day mortality, duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-acquired weakness (ICU-AW) were analyzed between the 2 groups. Results: The proportion of Th17 cells and ET levels in the EEN group were significantly lower than those in the DEN group, whereas the proportion of Treg cells in the EEN group was remarkably higher than that in the DEN group ( P < .05). The duration of mechanical ventilation, lengths of ICU stay and hospital stay, and incidence of ICU-AW were higher in the DEN group than in the EEN group ( P < .05), but there was no significant difference in the 28-day mortality between the 2 groups. Conclusion: Patients with sepsis mainly present with an increased proportion of Th17 cells in the early stage, manifesting as enhanced immune response. Early enteral nutrition can inhibit the excessive immune response, shorten the duration of mechanical ventilation, lengths of ICU stay and hospital stay, and reduce the incidence of ICU-AW, but it has no obvious effect on 28-day mortality.
Breast cancer usually initially metastases to the sentinel lymph nodes (SLNs). Recent studies have demonstrated that tumor cells induce SLN lymphangiogenesis before metastasis in several malignancies. In addition, tumor-derived VEGF-C or VEGF-D may induce lymphangiogenesis and promote lymph node metastasis. To explore the mechanisms of lymph node metastasis in breast cancer, we investigated whether primary tumors induce SLN lymphangiogenesis before metastasis and determined the function of tumor-derived VEGF-C and VEGF-D in SLN lymphangiogenesis. Expression of VEGF-C and VEGF-D was examined using immunohistochemistry in 63 primary breast tumors. No significant relationships between VEGF-C and VEGF-D (P=0.420), and VEGF-C or VEGF-D expression and clinical parameters (age, tumor size, grade, hormonal receptor status, her-2 status) were observed (P>0.05). Expression of the lymphatic-specific markers VEGFR-3, Prox-1 and LYVE-1 was measured using quantitative real-time RT-PCR in uninvolved SLNs from 63 patients and compared to control lymph nodes from patients with benign breast disease. Expression of Prox-1 and LYVE-1 mRNA was significantly higher in uninvolved SLNs from breast cancer patients than that in control lymph nodes (P<0.01). Interestingly, expression of VEGFR-3, Prox-1 and LYVE-1 was significantly higher in SLNs from patients with high VEGF-C-expressing tumors than low VEGF-C-expressing tumors (P<0.05), but not VEGF-D-high-expressing tumors (P>0.05). This study demonstrates that primary breast tumors induce SLN lymphangiogenesis before metastasis occurs and that tumor-derived VEGF-C, but not VEGF-D, plays an important role in SLN lymphangiogenesis in breast cancer.
BackgroundDespite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported.MethodsThe clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed.ResultsOf 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor.ConclusionsMWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.
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