[Stellera chamaejasme against multidrug resistance of triple-negative breast cancer MDA-MB-231 cell through Nrf2].

This study aims to investigate the effect and mechanism of Stellera chamaejasme extract(SCL) on multidrug resistance(MDR) in breast cancer. Human triple-negative breast cancer cell line MDA-MB-231 and its adriamycin-resistant cell line MDA-MB-231/ADR were used in the experiment. Cell viability was detected by methyl thiazolyl tetrazolium(MTT) assay, and cell apoptosis was detected by DAPI staining and Annexin-V/Pi double staining. Western blot(WB) was used to detect the expression levels of Keap1, Nrf2, HO-1, Bcl-2, Bax, caspase-9, and caspase-3. Immunofluorescence staining was used to observe the distribution of Nrf2 in the cell, and flow cytometry was used to detect the level of reactive oxygen species(ROS) in the cell. The results showed that the resis-tance factor of SCL was 0.69, and that of adriamycin and paclitaxel was 8.40 and 16.36, respectively. DAPI staining showed that SCL could cause nuclear shrinkage and fragmentation of breast cancer cells. Annexin-V/Pi double staining showed that the average apoptosis rate of the drug-resistant cells was 32.64% and 50.29%, respectively under medium and high doses of SCL. WB results showed that SCL could significantly reduce the expression levels of anti-apoptotic proteins Bcl-2, caspase-9, and caspase-3 and significantly increase the expression level of pro-apoptotic protein Bax. Further studies showed that SCL could significantly promote the expression of Keap1, significantly inhibit the expression of Nrf2 and HO-1, and significantly reduce the expression level of Nrf2 in the nucleus. Correspondingly, flow cytometry showed that the intracellular ROS level was significantly increased. In conclusion, SCL can significantly inhibit the proliferation of MDA-MB-231 multidrug-resistant cells of triple-negative breast cancer and cause cell apoptosis, and the mechanism is related to inhibiting Keap1/Nrf2 signaling pathway, leading to ROS accumulation in drug-resistant cells and increasing the expression of apoptosis-related proteins.

A dual-functional oncolytic adenovirus ZD55-aPD-L1 scFv armed with PD-L1 inhibitor potentiates its antitumor activity.

BACKGROUND: Clinical data indicate that a substantial portion of cancer patients, though eligible for immune checkpoint inhibitor (ICI) therapy, cannot fully benefit from ICI monotherapy due to the poor immunogenicity of tumors and lack of tumor-infiltrating lymphocytes within the 'cold' tumor microenvironment (TME). In addition to poor antibody penetrance into the TME, systemic delivery of ICIs is associated with immune-related adverse events (irAEs) among recipients, some of which are life-threatening. Oncolytic virotherapy is a potentially viable approach to improving the efficacy of ICI therapy because of their ability to selectively replicate and lyse tumor cells, release tumor-associated antigens (TAAs), induce inflammatory response and promote lymphocyte infiltration in tumors. METHODS: A recombinant oncolytic adenoviruses (OAd), denoted ZD55-aPD-L1 scFv, which carried the expression cassette for anti-PD-L1 scFv was constructed by molecular cloning. Western blot and ELISA assay were performed to detect aPD-L1 scFv expression. Flow cytometry were used to analyse PD-L1 expression and count tumor cells. Co-culture assay of human peripheral blood mononuclear cells (PBMCs) with tumor cells in vitro and triple-negative breast cancer (TNBC) MDA-MB-231 tumor-bearing model in vivo were evaluated the antitumor effects of recombinant oncolytic adenoviruses ZD55-aPD-L1 scFv. RESULTS: We found that cells infected with recombinant oncolytic adenovirus ZD55-aPD-L1 scFv can effectively express aPD-L1 scFv, which function similarly to its full-length anti-PD-L1 antibody. PBMCs have inherently very limited killing effect on tumor cells even with administration of anti-PD-L1 antibody as observed from our in vitro co-cultures. Treatment consisting of ZD55 alone or ZD55 combined with anti-PD-L1 antibody yielded mediocre antitumor efficacy in subsequent in vitro and in vivo investigations, but were all substantially surpassed by the synergistic antitumor effects observed with ZD55-aPD-L1 scFv treatment. We show that the concomitant direct oncolysis by the recombinant OAd and localized autocrine/paracrine interception of PD-1:PD-L1 checkpoint interaction mediated by ZD55-aPD-L1 scFv-infected cells is exceedingly superior to co-administration of ZD55 and anti-PD-L1 antibody in the human TNBC mice model. CONCLUSIONS: Our results provided evidence for the development of novel strategies, in this case an anti-PD-L1 scFv-armed OAd, to bolster immune responses to 'cold' tumors and to improve therapeutic responsiveness to ICIs.

Social functioning, depression, and quality of life among breast cancer patients: A path analysis.

PURPOSE: To identify associations among social functioning, depression, and quality of life in breast cancer patients. METHOD: A cross-sectional study was conducted. A total of 180 breast cancer patients were recruited from the surgical units in southern Taiwan hospital in 2021. Path analysis was employed to analyze the relationships between background information and social functioning, depression, and quality of life. Structural equation modeling (SEM) was used for examining the path analysis in this study. RESULTS: The path model showed that respondents with a religious belief (ß = 0.18, p < .000) and less severe disease (ß = -0.29, p < .01) showed better social functioning. Income did not affect social functioning directly but was directly related to the social interaction dimension (ß = 0.30, p < .000). Moreover, younger age (ß = -0.29, p < .000, lower income (ß = -0.10, p < .05) and more severe disease (ß = 0.35, p < .000) increased the level of depression. Less severe disease would also result in a better quality of life (ß = -0.45, p < .000). Breast cancer patients with better social function levels have low levels of depression (ß = -0.82, p < .000) and better quality of life (ß = 0.76, p < .000). CONCLUSION: Age, religion, income, and severity are crucial predictors of social functioning, depression, and quality of life. Furthermore, severity variables which combined clinical variables to make this variable a stronger predictor for SF, depression, and QOL.

Predictive value of PD-L1 expression to the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) have been an emerging treatment strategy for advanced triple-negative breast cancer (TNBC). Some studies have shown that high expression of programmed death-ligand 1 (PD-L1) can achieve a better response of clinical efficacy. However, the efficacy of ICIs in advanced TNBC remains controversial. In this meta-analysis, we evaluated the correlation of PD-L1 expression with the efficacy of ICIs in patients with advanced TNBC. Methods: We conducted a systematic search using four databases until March 2022 to obtain eligible randomized controlled trials (RCTs). The quality of the studies was assessed by the Cochrane risk of bias tool. Hazard ratio (HR) was extracted to evaluate the relationship between PD-L1 expression and progression-free survival (PFS) or overall survival (OS) in patients with advanced TNBC. Results: Five randomized controlled clinical trials (RCTs) with 3104 patients were included in this meta-analysis. The results demonstrated that ICIs could significantly improve the OS (HR 0.77, 95% CI 0.60-0.98, p = 0.03) in PD-L1 positive TNBC group. In the subgroup analysis, longer OS was observed (HR: 0.70, 95% CI: 0.60-0.82, p = 0.00001) in PD-L1 positive TNBC patients receiving ICIs alone or ICIs combined with nab-paclitaxel. In terms of PFS, PFS was significantly improved (HR: 0.68, 95% CI: 0.58-0.79, p < 0.00001) in PD-L1 positive patients receiving first-line ICIs and chemotherapy compared to those with ICIs alone. No significant improvement was observed for OS or PFS in PD-L1 negative group. Conclusion: Our study indicated significant improvement for OS in advanced TNBC with ICIs therapy in the PD-L1 positive status, and ICIs alone or ICIs combined with nab-paclitaxel might be a excellent choice in terms of OS. Although PFS has no significant benefit in PD-L1 positive patients, the subgroup analysis showed that ICIs combined with chemotherapy could achieve the PFS benefit in the first-line treatment. However, further clinical studies are needed to validate our conclusions due to limited relevant research.

Trastuzumab deruxtecan versus trastuzumab emtansine for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: A cost-effectiveness analysis.

BACKGROUND: DESTINY-Breast03 (NCT03529110) was the first global phase III study to assess the antitumor activity of trastuzumab deruxtecan (T-DXd) compared to trastuzumab emtansine (T-DM1) in 2022. However, the balance between efficacy and cost of T-DXd remains unclear. As a result, the present study's goal is to investigate the cost-effectiveness of T-DXd vs T-DM1 as a second-line treatment for patients with HER2-positive MBC from the US and Chinese payer's perspectives. METHODS: A Markov model with a 20-year time horizon was developed to evaluate the overall cost of patient treatment, incremental cost-effectiveness ratio (ICER), quality-adjusted life-years (QALYs), and life-years (LYs) in the US and China at WTP levels of 150,000/QALY and 37,653/QALY, respectively (3 times GDP per capita in 2021). Key data were gathered from the US government's official website, the Xiangya Hospital of Central South University, and published literature. To determine the model's stability, a sensitivity analysis was performed. A subgroup analysis was also implemented. RESULTS: Compared with T-DM1, treatment with T-DXd generated an additional 1.672 QALYs (2.796 LYs), resulting in an ICER of $13,342/QALY (US) and $186,017/QALY (China). The cost of drugs is the most influential factor in the American and Chinese models. Subgroup analysis revealed that the T-DXd and T-DM1 regimens were more cost-effective at reducing the risk of death in the US and Chinese HER2-positive MBC patients. CONCLUSION: T-DXd as second-line treatment could gain more health benefits for HER2-positive MBC patients in comparison with T-DM1, which is considered to be cost-effective in the US but not in China.

Factores Predictivos de Compromiso Axilar en ocasión de Ganglio Centinela Positivo en Cáncer de Mama Temprano / Predictive Factors of Axillary Compromise on the Occasion of Positive Sentinel Lymph Node in Early Breast Cancer

Introducción: Se ha demostrado en diversos protocolos que, en gran proporción de casos con cáncer de mama en estadíos tempranos y ganglio centinela positivo, no se observa enfermedad metastásica en ganglios linfáticos no centinelas (GNC). A raíz de esto es que se han descripto diferentes factores predictores de metástasis axilar. Esto nos motivó a realizar el presente trabajo. Objetivo: Analizar diferentes factores anatomopatológicos y su influencia en el compromiso metastásico de los ganglios no centinela. Material y método: Se estudiaron casos de cáncer de mama estadíos tempranos (T1-T2) con ganglio centinela positivo y seguidas de vaciamiento axilar, operadas en IMGO entre febrero del año 2000 y diciembre de 2012. De la muestra total se identificaron dos grupos: GnC negativos y GnC positivos. Analizamos diferentes variables anatomopatológicas vinculadas a cada grupo y calculamos su grado de significancia. Finalmente, analizamos estas variables en una tabla de análisis multivariado. Resultados: De una muestra de 205 casos (20,8% del total de ganglios estudia- dos en ese período de tiempo), el 48.3% (n=99) presentaba metástasis solo en el GC. De todas las características anatomopatológicas de mal pronóstico analizadas encontramos que el tamaño tumoral 2, el subtipo lobulillar y la invasión linfovascular tuvieron correlación significativa con la cantidad de GnC comprometidos. En el análisis multivariado encontramos tres factores predictivos, la invasión linfovascular, el tamaño de la metástasis en el ganglio centinela y el número de ganglios centinelas comprometidos. Conclusiones: Los factores independientes de compromiso de ganglios no centinela (GNC) en nuestra serie fueron: la invasión linfovascular, el tamaño de la metástasis en el ganglio centinela y el número de ganglios centinelas comprometidos

Introduction: It has been shown in various protocols that pathologically negative nonsentinel lymph node (NSN) disease, is observed in the rest of the armpit in a large proportion of cases with early stage breast carcinoma and positive sentinel node. As a result of this, different pathological predictors of axillary metastasis have been described. This motivated us to carry out the present work. Objetive: To analyze different pathological factors and their influence on the metastatic involvement of nonsentinel nodes. Material and method: Early stage breast cancer cases (T1-T2) with positive sentinel node and axillary emptying, operated on in IMGO between February 2000 and December 2012, were studied. Two groups were identified from the total sample: negative GnC and positive GnC, and analyzed diffe- rent pathological variables associated with metastatic nonsentinel nodes, calculating their significance. Finally, we analyze these variables in a multivariate analysis table. Results: From a sample of 205 cases (20.8% of the total lymph nodes studied), 48.3% (n = 99) had metastasis only in the SN. Of all the anatomo-pathological characteristics analyzed, we found that tumor size two, lobular subtype, and lymphovascular invasion had a significant correlation with the amount of compromised non-sentinel node (NSN). In the multivariate analysis, we found three predictive factors: lymphovascular invasion, the size of the metastasis in the sentinel node and the number of positive sentinel nodes. Conclusions: The independent factors of nonsentinel node involvement (NSN) in our series are: lymphovascular invasion, the size of the sentinel node metastasis, and the number of sentinel nodes involved

Inhibition of platelet-derived growth factor receptor synergistically increases the pharmacological effect of tamoxifen in estrogen receptor α positive breast cancer.

The platelet-derived growth factor (PDGF) family, a complex and imperative group of proangiogenic factors, acts as strong cell growth chemokines and is essential for the progression of malignancy in humans. In the present study, it was observed that aberrant PDGFB expression is associated with survival rates in patients with estrogen receptor-positive (ER+) breast cancer unlike other subtypes, including PDGFA, PDGFC and PDGFD. Accordingly, the effect of specific PDGF receptor (PDGFR) inhibitors on ER-α+ breast cancer cells was investigated. To block the PDGF-BB signaling pathway, PDGFR inhibitors (sunitinib or ponatinib) were employed. Sunitinib and ponatinib were found to arrest the cell cycle at the G0-G1 phase. In addition, the two PDGFR inhibitors were revealed to significantly inhibit cell growth and decrease the expression of matrix metalloproteinase-1, which is one of the metastasis-related genes. Finally, the combined effects of the two PDGFR inhibitors with tamoxifen were investigated. The results demonstrated that the combination of two PDGFR inhibitors with tamoxifen inhibited the growth of cells more consistently, compared with the effect mediated by tamoxifen alone. Therefore, it is proposed that PDGFR inhibitors, including sunitinib and ponatinib, should be applied effectively to treat ER-α+ breast cancer.

Sexualidad de la mujer con cáncer de mama en fase perioperatoria: consulta de enfermería / Sexuality of women with perioperative breast cancer: nursing consultation

Objetivo: Proponer una consulta de enfermería en sexualidad para mujeres con cáncer de mama en fase perioperatoria para una institución oncológica. Metodología: Revisión integrativa de literatura. Se llevó a cabo una búsqueda de literatura en las bases de datos LILACS, SpringerLink, ClinicalKey, Biblioteca Virtual en Salud (BVS), Scopus, SAGE Journals y búsquedas secundarias en revistas científicas en Taylor & Francis Online. Se encontraron 35 artículos, los cuales se organizaron y se caracterizaron por año de publicación, idioma, país, edad promedio de la muestra, tipos de tratamiento, metodología, perspectiva disciplinar, enfoque, diseño y tendencia temática. Esta estrategia permitió desarrollar los objetivos. Resultados: La tendencia de investigación identificada se agrupó en cuatro categorías de necesidades en cuanto a la sexualidad: Respuesta sexual fisiológica; Adaptación psicológica a los sentimientos; Pérdida del atractivo físico y Salud sexual y reproductiva. Se propuso una consulta de enfermería con base en el modelo PLISSIT para abordar la sexualidad, de modo que fuera factible otorgar respuestas a las necesidades reales de la mujer con cáncer de mama. Conclusiones: La sexualidad en mujeres con cáncer de mama es un factor importante en la fase perioperatoria, pues permanentemente se ve alterada por la enfermedad y los tratamientos, afectando tanto a la mujer como a su pareja. De este modo, se requiere realizar intervenciones en una consulta de enfermería especializada en sexualidad para mujeres con cáncer de mama.

Objective: To propose a sexuality nursing consultation for women with breast cancer in the perioperative phase in an oncological institution. Methodology: Integrative literature review. A literature search was carried out in databases LILACS, SpringerLink, ClinicalKey, Virtual health Library (BVS), Scopus, and SAGE Journals; a secondary literature searches also was carried out in several scientific journals in Taylor & Francis Online. 35 articles were found and they were put together and characterized in accordance with publication year, language, publication country, average age of the sample, forms of treatment, methodology, field of study outlook, approach, design, and trending topic. This framework enabled to sort the objective out. Results: The trending research topic identified was clustered into four categories of requirements about sexuality: Physiological sexual response; Psychological adjustment to feelings; Loss of attractiveness; and Sexual and reproductive health. A nursing consultation was proposed based on the PLISSIT model of sex therapy in order to give responses to the real needs of women with breast cancer. Conclusions: Sexuality of women with breast cancer is a significant feature in the perioperative phase; it is permanently disrupted by disease and treatments, impacting both the woman and her partner. Therefore, it is necessary to carry out interventions in a sexuality nursing consultation for women with breast cancer

Pre-clinical effects of metformin and aspirin on the cell lines of different breast cancer subtypes.

Background Breast cancer is highly prevalent among women worldwide. It is classified into three main subtypes: estrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2+), and triple negative breast cancer (TNBC). This study has evaluated the effects of aspirin and metformin, isolated or in a combination, in breast cancer cells of the different subtypes. Methods The breast cancer cell lines MCF-7, MDA-MB-231, and SK-BR-3 were treated with aspirin and/or metformin (0.01 mM - 10 mM); functional in vitro assays were performed. The interactions with the estrogen receptors (ER) were evaluated in silico. Results Metformin (2.5, 5 and 10 mM) altered the morphology and reduced the viability and migration of the ER+ cell line MCF-7, whereas aspirin triggered this effect only at 10 mM. A synergistic effect for the combination of metformin and aspirin (2.5, 5 or 10 mM each) was observed in the TNBC cell subtype MDA-MB-231, according to the evaluation of its viability and colony formation. Partial inhibitory effects were observed for either of the drugs in the HER2+ cell subtype SK-BR-3. The effects of metformin and aspirin partly relied on cyclooxygenase-2 (COX-2) upregulation, without the production of lipoxins. In silico, metformin and aspirin bound to the ERα receptor with the same energy. Conclusion We have provided novel evidence on the mechanisms of action of aspirin and metformin in breast cancer cells, showing favorable outcomes for these drugs in the ER+ and TNBC subtypes.

Study on changes of serum adiponectin level in patients with breast cancer and its clinical significance / 国际检验医学杂志

Objective To analysis the changes of serum adiponectin level in patients with breast cancer and its clinical signifi‐cance .Methods 35 cases of serum adiponectin levels in breast cancer patients using enzyme‐linked immunosorbent assay ,and 35 healthy serum adiponectin level in peripheral blood of women ,analysis of significance of changes of serum adiponectin levels in breast cancer patients .Results Average serum adiponectin level in patients with breast cancer group(6 .13 ± 1 .55)μg/mL ,health group average serum adiponectin levels (8 .72 ± 1 .86)μg/mL ,the difference was statistically significant(P<0 .05) .Postmenopausal women in breast cancer group and health group compared with premenopausal women ,the serum adiponectin levels were signifi‐cantly increased ,there was a statistically significant difference(P<0 .05) .Lymph node metastasis of breast cancer serum adiponec‐tin levels were significantly lower in patients without lymph node metastasis in patients with breast cancer ,the difference was statis‐tically significant(P<0 .05) .Serum adiponectin level in breast cancer patients with stage Ⅱ and Ⅲ were significantly lower than breast cancer patients with stage Ⅰ ,there was a statistically significant difference(P<0 .05) .Conclusion Serum adiponectin levels as an important marker in the diagnosis of breast cancer ,serum adiponectin level and grade of the tumor ,lymph node metastases . Significantly reduced serum adiponectin level in patients with breast cancer ,and not under the influence of patients with menopause .

Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer.

The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer.

Clinical efficacy and safety of abraxane in alternative chemotherapy plan of metastatic breast cancer / 中国综合临床

Objective To investigate the therapy effect and adverse reaction of the abraxane chemotherapy as a alternative plan in metastatic breast cancer.Methods Twenty-one patients with advanced metastatic breast cancer were selected as our subject.All the patients received rescue chemotherapy after relapse and metastasis.Abraxane were administrated with 260 mg/m2 3 weeks/time,and evaluated the effect in every two course of radiotherapy.Results Of 21 cases,4 cases were remission and 8 cases were with stable progress of cancer.No allergic reaction occurred.The majority adverse reaction were granulocytopenia and nerve toxicity.Conclusion Abraxane migh be considered as the altemate therapy medicine of metastatic breast cancer due to good curative effect,less toxicity reaction and no allergic reaction.

Diagnostic Accuracy of Quantitative Scintimammography Using Tc-99m MIBI According to ROC Curve Analysis for Breast Cancer

BACKGROUND: Technetium-99m sestamibi scintimammography (SMM) has been shown to be a useful diagnostic test in the detection of breast cancer, and the receiver operating characteristic (ROC) curve analysis provides detailed information about the diagnostic test. A ROC curve analysis was performed to evaluate the feasibility of Tc-99m sestamibi quantitative scintimammography (qSMM) for differentiating malignant from benign breast lesions. METHODS: Prone anterior, lateral planar, and supine SPECT imagings were performed on 75 female patients (mean age=43.4 yr) with breast masses (size> or =0.8 cm) after intravenous injection of 30 mCi of Tc-99m sestamibi. 45 malignant and 30 benign lesions were histologically proven. Three regions of interest (ROIs) were drawn over designated areas: lesion (L), normal breast opposite to the lesion (NL), and right chest wall (CW). L/NL and the L/CW ratios on both the SPECT and the planar images were analyzed. RESULTS: ROC curve analysis revealed that planar L/NL ratio and the SPECT L/NL and L/CW ratios provide better diagnostic accuracies for detecting breast cancer than the planar L/CW ratio did (p<0.05). From the qSMM (mean), which was an arithmetic mean of the planar L/NL, ratio the SPECT L/NL ratio and the SPECT L/CW ratio, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy were 84%, 77%, 84%, 77%, and 81%, respectively. Presence of axillary lymph-node metastasis showed a higher qSMM (mean) value (4.09 {n=17} vs 3.09 {n=28}, p=0.06). CONCLUSIONS: qSMM (mean) is a useful objective method for differentiating malignant from benign breast lesions.