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Background: Fine-needle aspiration (FNA) is a frequently utilized method for the diagnosis of thyroid nodules. Although the technique has clear advantages, the injury caused by the aspiration needle can induce various histological alterations. Herein, we report a case of follicular adenoma showing histological alterations possibly caused by FNA biopsy. Furthermore, the histological appearance of the lesion mimicked those of medullary thyroid carcinoma, particularly in the frozen section. Case presentation: Ultrasonography of a thyroid nodule in a 39-year-old man revealed a mass (2.2 cm in diameter) in the right thyroid lobe. FNA was performed three times on the mass, and the results of the cytology were atypia of undetermined significance. Thereafter, the patient underwent right hemithyroidectomy. The histological findings of the operative frozen section analysis indicated medullary thyroid carcinoma. However, after evaluation and immunohistochemical staining of the permanent section, the mass was diagnosed as follicular adenoma with extensive fibrosis. Conclusion: The histological alterations observed in the follicular adenoma are believed to have been caused by injury during the repeated FNA procedures. [ABSTRACT FROM AUTHOR]

We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60–2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67–0.98) for recurrence and 0.85 (0.76–0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation. [ABSTRACT FROM AUTHOR]

Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs. [ABSTRACT FROM AUTHOR]

Simple Summary: Core needle biopsy (CNB) and fine needle aspiration (FNA) are the most commonly used non-surgical tissue sampling methods for breast cancer diagnosis. CNB has higher diagnostic accuracy and enables molecular subtype determination for neoadjuvant chemotherapy, and is more widely used than FNA. However, FNA is less invasive and provides faster results, and is still performed by many clinicians. This study was conducted to investigate the prognosis and application criteria of the two methods in real clinical practice. We found that patients who were diagnosed with breast cancer using FNA had significantly worse survival rates than those diagnosed using CNB. In the subgroup analysis, FNA showed worse survival rates in cases of highly suspicious lesions, nonpalpable tumors, or centrally located tumors. Our study may help in choosing the appropriate tissue sampling method for suspected breast cancer cases. (1) Background: Breast core needle biopsy (CNB) is preferred over fine needle aspiration (FNA) as it has higher sensitivity and specificity and enables immunohistochemical evaluation. However, breast FNA remains widely used because of its low cost, minimally invasive nature, and quick results. Studies analyzing the effects of each test on the prognoses of patients with breast cancer are scarce and controversial, and the criteria for test selection remain unknown. (2) Methods: This study included adult female patients who underwent breast cancer surgery at 102 general hospitals. The trend of breast biopsies over time was analyzed, and the prognoses of patients with breast cancer who underwent CNB and FNA were compared. (3) Results: This study included 73,644 patients who underwent FNA (n = 8027) and CNB (n = 65,617). A multivariate Cox regression analysis showed that patients diagnosed using FNA had significantly worse overall survival (OS) and breast-cancer-specific survival (BCSS) than those diagnosed using CNB. In the subgroup analysis, patients with breast imaging reporting and data system (BI-RADS) 5 lesions, palpable tumors, or centrally located tumors had significantly worse OS and BCSS with FNA than with CNB. (4) Conclusions: CNB should be performed preferentially instead of FNA in patients with BI-RADS 5 lesions and nonpalpable or centrally located tumors. [ABSTRACT FROM AUTHOR]

Aim: This study examined the associations of body mass index (BMI) and weight change with inflammatory markers among breast cancer survivors in Korea. Methods: A total of 495 women were included who had been diagnosed with primary breast cancer and survived for at least 6 months since the surgery. Information on the body weight and height of the participants was collected both at the study enrollment and diagnosis. The plasma levels of inflammatory markers were measured, including high‐sensitivity C‐reactive protein, interleukin (IL)‐6, IL‐8, tumor necrosis factor‐α, and adiponectin. A summary z‐score was calculated by summing up the z‐scores of each biomarker. The least‐square means and 95% confidence intervals (CIs) were calculated using a generalized linear model and odds ratios (ORs) and 95% CIs for the elevated levels of inflammatory markers with a multivariate logistic regression model. Results: Participants with a BMI ≥27.5 kg/m2 at the study enrollment and at diagnosis were significantly associated with elevated summary z‐scores compared to those with a BMI < 23 kg/m2; the ORs (95% CIs) were 5.42 (2.15–13.71) for current BMI and 3.66 (1.68–7.98) for BMI at diagnosis, respectively. Additionally, a weight loss > 5% since diagnosis was associated with a lower prevalence of high summary z‐scores; the OR (95% CI) was.20 (.08–.52) compared to a stable weight. Conclusions: A high BMI at diagnosis and current BMI with a greater degree were associated with unfavorable levels of inflammatory markers among breast cancer survivors. Additionally, weight loss since diagnosis was inversely associated with these markers. [ABSTRACT FROM AUTHOR]

Background: Women from Asian and western countries have vastly different ages of onset of breast cancer, with the disease tending to occur at an older age in the West. Through an investigation of the patterns of old-onset breast cancer (OBC) in Korean women, we aimed to identify the characteristics of Korean OBC and evaluate whether these patterns are changing in relation to increasing westernization.Methods: This study retrospectively evaluated 102,379 patients who underwent surgical treatment of primary breast cancer between January 1, 2000 and December 31, 2013 in Korea. We used hospital -based breast cancer registry and analyzed data from these patients using multiple linear regression analysis to compare the characteristics and chronologically changing patterns between OBC (70 years of age or older) and non-OBC (40-69 years of age) patients in Korea.Results: A total of 6% of the 102,379 patients had OBC. Overall, OBC had more favorable biological features, such as a higher incidence of luminal A subtype, than did non-OBC, except for a higher incidence rate of triple-negative breast cancer (TNBC). However, OBC also presented with a higher overall disease stage, including higher T and M stages. Although the incidence rates of both OBC and non-OBC have increased overtime, the relative proportion of OBC patients has slightly increased, whereas that of non-OBC has slightly decreased. The increase in the incidence of both OBC and non-OBC was primarily due to the luminal A subtype.Conclusions: Based on a hospital-based registry, overall, Korean OBC had favorable biological features but showed a higher rate of TNBC and advanced cancer stages. The incidence trend of breast cancer in Korea is slowly shifting toward an older age at onset, largely due to the luminal A subtype. Our results may provide novel insights into OBC in Asia, and aid in the development of optimal management of the disease in Asia.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-γ (PPAR-γ) acts as a key factor in breast cancer metastasis. Notably, PPAR-γ can inhibit metalloproteinase (MMP), which is involved in cancer metastasis. Our previous study revealed that PPAR-γ was related to breast cancer metastasis. The present study aimed to investigate whether the PPAR-γ ligand 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) mediated suppression of cell invasion and reduced the expression of MMP-9 in breast cancer cells. The results indicated that CDDO reduced MMP-9 expression, cell migration and invasion of breast cancer cells by inhibiting TPA-induced phosphorylation of mitogen-activated protein kinases, and downregulating the activities of activator protein-1 and nuclear factor κB. Notably, knock-out of PPAR-γ by small interfering RNA in MCF-7 cells revealed that TPA-induced MMP-9 expression occurred through a PPAR-γ-independent pathway. These data indicated that the downregulatory effect of CDDO on MMP-9 expression was affected by a mechanism independent of PPAR-γ. In conclusion, the findings of the present study suggested that CDDO may act as a key agent in the regulation of breast cancer metastasis, suggesting CDDO as a new targeted therapy for breast cancer. [ABSTRACT FROM AUTHOR]

Background: The role of lipid metabolism in obesity and cancer manifestations cannot be underestimated, but whether alterations in lipid metabolism can manipulate the vasculature to promote obesity among breast cancer (BC) survivors is yet to be clearly understood. This study quantified plasma lipid and particle sizes using high-throughput proton (1H) nuclear magnetic resonance (NMR) and tested their associations with obesity among breast cancer (BC) survivors. Methods: A total of 348 (225 premenopausal and 123 postmenopausal) BC survivors enrolled from five hospitals in Korea were included. We assessed thirty-four plasma lipid biomarkers using 1H NMR, and obesity status was defined as a body mass index (BMI) of 25 kg/m2 or greater. Generalized linear and logistic regression models were applied to estimate the least-square means of BMI (kg/m2) and odds ratio (OR)s of obesity, respectively, and the corresponding 95% confidence interval (CI)s across plasma lipid levels. Results: Mean (SD) values of BMI was 23.3 (3.2) kg/m2 and 90 (25.9%) had BMI of ≥ 25 kg/m2. BMI levels increased with increasing total triglycerides (TG), TG in lipoproteins and very-low-density lipoprotein (VLDL) subfractions. However, BMI levels decreased with increasing tertiles of high-density lipoprotein (HDL)-cholesterol (C) and HDL particle size (HDL-p). Similar associations were observed in the logistic regression models. The increasing and decreasing BMI trends with TG and HDL profiles respectively were predominantly limited to premenopausal BC survivors. Conclusions: Increasing levels of plasma total TG and TG in lipoproteins were associated with increasing levels of BMI among premenopausal BC survivors. High HDL-C levels and large HDL-p were inversely associated with obesity among premenopausal BC survivors. Due to the cross-sectional design of this study, longitudinal studies are necessary to examine the association between obesity and lipid profile among BC survivors. [ABSTRACT FROM AUTHOR]

Sirtuin 6 (SIRT6) regulation is involved in carcinogenesis. However, its role in breast cancer (BC) metastasis remains unclear. We investigated the effects of SIRT6 on protein kinase C activator- and cytokine-mediated cancer cell invasion and migration in MCF-7 and MDA-MB-231 cells and the association between SIRT6 and matrix metalloproteinase-9 (MMP-9) expression. To assess MMP-9 and SIRT6 expression in patients, protein levels in BC tissues were analyzed. MCF-7 and MDA-MB-231 cell viability was analyzed using MTT assays. SIRT6 was silenced in both cell lines and protein secretion, expression, and mRNA levels were analyzed. Transcription factor DNA activity was investigated using luciferase assays. Matrigel invasion assays were used to assess the effects of SIRT6 in both cell lines. SIRT6 and MMP-9 expression in cancer tissues was significantly higher than in paired normal breast tissues. 12-O-tetradecanoylphorbol-13-acetate (TPA) or tumor necrosis factor-α (TNF-α) increased MMP-9 expression and cell invasion and migration, but SIRT6 knockdown abolished these effects. SIRT6 overexpression additively increased TPA- and TNF-α-induced MMP-9 expression. SIRT6 knockdown suppressed the mitogen-activated protein kinase (MAPK) signaling pathway and thus TPA- and TNF-α-induced MMP-9 expression. SIRT6 silencing suppressed TPA- and TNF-α-induced nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) expressions in both cell lines, and treatment with MAPK, NF-κB, and AP-1 inhibitors reduced MMP-9 expression. The anti-invasive effects of SIRT6 in BC cells might be mediated by suppression of MAPK phosphorylation and reduction in NF-κB and AP-1 DNA activities, leading to MMP-9 downregulation, suggesting that SIRT6 modulation has the potential to target BC metastasis. [ABSTRACT FROM AUTHOR]

Background: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups. Methods: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival. Results: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012–1.788; p = 0.041). Conclusions: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes. [ABSTRACT FROM AUTHOR]

Objective: We investigated the contribution of supplement use to total nutrient intake, the prevalence of inadequate nutrient intake and the factors associated with supplement use among breast cancer survivors. Methods: A total of 701 Korean breast cancer survivors were included. We calculated the contribution of dietary supplements to total nutrient intake and the proportion of the population below the estimated average requirements (EARs) or exceeding the tolerable upper intake levels (ULs). Stepwise logistic regression was used to identify factors associated with dietary supplement use. Results: A total of 66.5% of the survivors used dietary supplements, with multivitamins and minerals being the most commonly consumed ones. The per cent contribution of supplement to the total intake was the highest for vitamin C. 28.2%–55.4% of the non‐users consumed below the EAR of riboflavin, folate and calcium; 6.1%, 4.9% and 6.5% of the supplement users consumed above the UL of vitamins A and C, and iron, respectively. Supplement users had higher education levels or longer survival time. Conclusion: 66.5% of Korean breast cancer survivors used dietary supplements. A higher education level or prolonged survival time was associated with higher use of dietary supplements. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine profiles of depressive symptoms and the association with anxiety and quality of life (QOL) in breast cancer survivors.Methods: A cross-sectional multicenter survey involving 5 hospitals in Korea was implemented between February 2015 and January 2017. A self-report survey included the Patient Health Questionnaire-9, Short Form 36, and State and Trait Anxiety Scale. Data from 347 patients were analyzed.Results: Latent profile analysis identified five profiles of depressive symptoms: (1) "no depression" (63.98%); (2) "mild depression with sleep problems" (16.43%); (3) "mild depression" (8.65%); (4) "moderate depression with anhedonia" (7.78%); and (5) "moderately severe depression" (3.17%). Results from Fisher's exact test and analysis of variance (ANOVA) to examine whether sociodemographic and clinical characteristics distinguish the classes indicated that marital status, income and education as well as C-reactive protein distinguished a few classes. Multivariate analysis of covariance and analysis of covariance results indicated that both types of anxiety as well as several dimensions of QOL differed between the identified classes.Conclusions: The current results suggest that although identified classes were characterized overall by severity of depression, a few classes also reflected pronounced individual symptom patterns, warranting tailored interventions for these symptom patterns, along with overall severity of depression. [ABSTRACT FROM AUTHOR]

Background: There is a controversy about late-onset congestive heart failure (CHF) among breast cancer survivors. This study investigated the incidence rate and risk factors of late-onset CHF more than 2 years after the breast cancer diagnosis.Methods: A nationwide, retrospective study was conducted with the National Health Information Database. With 1:3 age- and sex-matched noncancer controls, Cox proportional hazard regression models were used to analyze the incidence and risk factors of late CHF. The cumulative incidence rate of late CHF was evaluated with a Kaplan-Meier analysis and a log-rank test.Results: A total of 91,227 cases (286,480 person-years) and 273,681 controls (884,349 person-years) were evaluated between January 2007 and December 2013. The risks of late CHF were higher in cases than controls (hazard ratio [HR], 1.396; 95% confidence interval [CI], 1.268-1.538). Younger survivors (age ≤ 50 years) showed a higher risk of late CHF than their younger counterparts (HR, 2.903; 95% CI, 2.425-3.474). Although older age was a risk factor for late CHF, older survivors (age ≥ 66 years) showed no difference in the risk of late CHF in comparison with their counterparts (HR, 0.906; 95% CI, 0.757-1.084). Anthracyclines and taxanes were risk factors for late CHF, although trastuzumab, radiation, and endocrine therapy were not.Conclusions: Young breast cancer survivors have a greater risk of late CHF than the young population without cancer. More attention should be paid to young breast cancer survivors who receive taxane- or anthracycline-based regimens over the long term. [ABSTRACT FROM AUTHOR]

Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been considered to represent an important factor in mammary tumorigenesis. Increased expression of matrix metalloproteinase‑9 (MMP‑9) via nuclear factor‑κB (NF‑κB) activation has been demonstrated to promote breast cancer cell invasion. In the present study, the involvement of CK2 in protein kinase C (PKC) induced cell invasion in MCF‑7 breast cancer cells was investigated as well as the underlying molecular mechanisms. The mRNA and protein levels of MMP‑9 in MCF‑7 cells were investigated using reverse transcription‑quantitative polymerase chain reaction, western blot analyses and a zymography assay. Cell invasiveness was investigated using a Matrigel invasion assay, and it was revealed that small interfering RNA specific for CK2 suppressed PKC induced cell invasion by regulating MMP‑9 expression via activation of the p38 kinase/c‑Jun N‑terminal kinase/NF‑κB pathway. In addition, it was demonstrated that CK2 inhibitors [apigenin (20 μM), emodin (20 μM) or 2‑dimethylamino‑4,5,6,7‑tetrabromo‑1H‑benzimidazole (2 μM)] suppressed PKC induced cell invasion and MMP‑9 expression. The results of the present study suggested that CK2 is an important factor involved in the induction of MCF‑7 breast cancer cell invasion by PKC. Therefore, CK2 may represent novel candidates for therapy intended to inhibit invasion in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Endoscopic thyroidectomy has been applied to solve the cosmetic problems that resulted from conventional thyroidectomy. The aim of this study was to evaluate and compare the surgical outcomes of conventional and endoscopic thyroidectomies via axillo-bilateral-breast approach (ABBA) in patients with papillary thyroid carcinoma (PTC).Methods: Between May 2007 and February 2011, 1003 patients with PTC underwent thyroidectomies. The eight hundred and thirty patients underwent conventional thyroidectomy and 173 patients underwent endoscopic thyroidectomy via ABBA. Clinicopathologic characteristics, complications, and surgical completeness were analyzed.Results: The mean age was 49.53 years who received a conventional thyroidectomy and 38.90 years in endoscopic thyroidectomy (P < 0.0001). The conventional thyroidectomy group underwent more extensive surgery than the endoscopic thyroidectomy group but the operation time was longer in the endoscopic thyroidectomy group (P < 0.0001). The mean hospitalization length was 6.98 days following open thyroidectomy and 6.40 days after endoscopic thyroidectomy (P = 0.003). The tumor size was larger in the conventional thyroidectomy group than the endoscopic thyroidectomy group and a lesser number of lymph nodes were retrieved in the endoscopic thyroidectomy group compared to the conventional thyroidectomy group (P < 0.0001). The postoperative complications and thyroglobulin levels in both groups were not significantly different.Conclusion: These results suggest that conventional and endoscopic thyroidectomy via ABBA has similar surgical outcomes in PTC patients. Therefore, endoscopic thyroidectomy via ABBA may be an appropriate surgical alternative to conventional thyroidectomy for treating PTC in selected patients. [ABSTRACT FROM AUTHOR]

Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3′,4′,7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12- O -tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown.Methods: We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma.Results: Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time.Conclusions: This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients. [ABSTRACT FROM AUTHOR]

Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis. [Copyright &y& Elsevier]

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been identified as a potential source of therapy for human cancers. However, PPARγ ligands have a limitation for breast cancer therapy, since estrogen receptor α (ERα) negatively interferes with PPARγ signaling in breast cancer cells. Here we show that ERα inhihits PPARγ transactivity and ERα-mediated inhibition of PPARγ transactivity is blocked by tamoxifen, an estrogen receptor blocker. The activation of ERα with 17-β-estradiol blocked PPRE transactivity induced by troglitazone, a PPARγ ligand, indicating the resistance of ERα-positive breast cancer cells to troglitazone. Indeed, troglitazone inhibited the growth of ERα-negative MDA-MB-231 cells more than that of ERα-positive MCF-7 cells. Combination of troglitazone with tamoxifen led to a marked increase in growth inhibition of ERα-positive MCF-7 cells compared to either agent alone. Our data indicates that troglitazone enhances the growth inhibitory activity of tamoxifen in ERα-positive MCF-7 cells. [Copyright &y& Elsevier]

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPARγ ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor α negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPARγ ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G1 arrest in MDA-MB-231 cells exposed to troglitazone. An apoptotic effect by troglitazone demonstrated that apoptotic cells elevated by 2.5-fold from the control level at 10μM, to 3.1-fold at 50μM and to 3.5-fold at 75μM. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D1, cyclin D2, cyclin D3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G1 arrest and apoptotic death of MDA-MB-231 cells. [Copyright &y& Elsevier]

Abstract: Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-α (ERα) and estrogen receptor-β (ERβ). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP3), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17β-estradiol (E2) up-regulates PI3K in an ERα-dependent manner, but not ERβ, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ERα-positive MCF-7 cells and ERα-negative MDA-MB-231 cells with 10nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP3 level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ERα-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ERα-dependent mechanism in MCF-7 cells. [Copyright &y& Elsevier]

Background: Identification of specific needs in patients with cancer is very important for the provision of patient-centered medical service. The aim of this study was to investigate the unmet needs and related factors of Korean breast cancer survivors.Methods: A multicenter, cross-sectional, interview survey was performed among 332 Korean breast cancer survivors. The Comprehensive Needs Assessment Tool for cancer patients was administered to survivors who gave written informed consent to participate. Data were analyzed using t-test, ANOVA and multiple regression analysis.Results: The level of unmet needs was highest in the domain 'Information and education' (mean ± SD; 1.70 ± 1.14) and the item with the highest level of unmet needs was 'Needed help in coping with fear of recurrence' (2.04 ± 1.09). Unmet needs were correlated with age, stage, multiplicity, HER2, treatment state, marital status, employment, psychosocial status, and problems in EQ-5D dimensions. In multiple regression analysis, the 50-59 age group showed a higher level of recognition for physical symptom needs and the unemployed group expressed greater needs for information and education. Survivors with multiplicity had greater needs in the domains of healthcare staff and physical symptom. The stress group showed high levels of needs in all domains except religious support. The group with thoughts of suicide showed higher levels of unmet needs for physical symptom.Conclusion: Most prevalent unmet needs in Korean breast cancer survivors were found in the 'information and education' domain. The 50-59 age group, unemployment, multiplicity, stress and suicidal thoughts were associated with higher levels of unmet needs among Korean breast cancer survivors. Our findings revealed more vulnerable breast cancer survivors with unmet needs and physicians should take a precision approach to satisfy unmet needs of these survivors. [ABSTRACT FROM AUTHOR]