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1.
Cells ; 13(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38334644

RESUMO

Cachexia is a condition characterized by substantial loss of body weight resulting from the depletion of skeletal muscle and adipose tissue. A considerable fraction of patients with advanced cancer, particularly those who have been diagnosed with pancreatic or gastric cancer, lung cancer, prostate cancer, colon cancer, breast cancer, or leukemias, are impacted by this condition. This syndrome manifests at all stages of cancer and is associated with an unfavorable prognosis. It heightens the susceptibility to surgical complications, chemotherapy toxicity, functional impairments, breathing difficulties, and fatigue. The early detection of patients with cancer cachexia has the potential to enhance both their quality of life and overall survival rates. Regarding this matter, blood biomarkers, although helpful, possess certain limitations and do not exhibit universal application. Additionally, the available treatment options for cachexia are currently limited, and there is a lack of comprehensive understanding of the underlying molecular pathways associated with this condition. Thus, this review aims to provide an overview of molecular mechanisms associated with cachexia and potential therapeutic targets for the development of effective treatments for this devastating condition.


Assuntos
Neoplasias da Mama , Caquexia , Masculino , Humanos , Caquexia/metabolismo , Atrofia Muscular/metabolismo , Qualidade de Vida , Músculo Esquelético/metabolismo , Neoplasias da Mama/patologia
2.
JAMA Netw Open ; 7(2): e2355324, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38334999

RESUMO

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed. Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs. Design, Setting, and Participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed. Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. Main Outcomes and Measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated. Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs. Conclusions and Relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/patologia , Análise Custo-Benefício , Mastectomia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Salpingo-Ooforectomia
3.
Medicine (Baltimore) ; 103(6): e36810, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335394

RESUMO

BACKGROUND: The predictive value of tumor-infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) for breast cancer (BC) has received increasing attention. Here, a meta-analysis was conducted to evaluate the correlation between the expression of stromal TILs and pathological complete response (pCR) after NAC in BC patients. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched online by using a combination of keywords and free words to screen literature on the expression of stromal TILs and pCR after NAC in patients with BC. The data were extracted and evaluated for quality. Relative risk (RR) was used to evaluate the relationship between the expression of stromal TILs before NAC and pCR in BC patients. Meta-analysis was performed with Review Manager 5.3 and STATA 14.0 software. RESULTS: Eleven studies involving 6039 BC patients were included in the meta-analysis. The results showed a generally high expression of stromal TILs in BC patients, and the pCR rate after NAC in BC patients with a high expression of stromal TILs was significantly higher than that in BC patients with a low expression of stromal TILs [RR = 1.83, 95% confidence interval (CI): 1.69-1.97]. Subgroup analysis based on the molecular subtypes of BC showed that the pCR rate was significantly higher in patients with a high expression of stromal TILs in hormone receptor (HR)-positive BC [RR = 3.23, 95% CI: 2.43-4.30], human epidermal growth factor receptor 2 (HER-2)-positive BC [RR = 1.41, 95% CI: 1.25-1.60], and triple-negative BC [RR = 1.70, 95% CI: 1.53-1.90] than in those with a low expression of stromal TILs. Subgroup analysis based on expression threshold showed that the pCR rate was higher in patients with a high expression of stromal TILs than in patients with a low expression of stromal TILs at different expression thresholds (10% [RR = 1.99, 95% CI: 1.55-2.55], 20%/30% [RR = 1.57, 95% CI: 1.37-1.81], 50%/60% [RR = 1.91, 95% CI: 1.73-2.11]. CONCLUSION: TILs can be used as a predictor of pCR after NAC in patients with BC, and the appropriate high expression threshold of stromal TILs should be selected as the predictive value according to the molecular subtype of BC.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral/metabolismo , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Linfócitos/metabolismo , Prognóstico
4.
Medicine (Baltimore) ; 103(6): e37170, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335419

RESUMO

The growing body of evidence suggests that breast cancer (BC) who achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) may experience a more favorable prognosis. The objective of this study is to investigate the correlation between clinicopathologic parameters of locally advanced breast cancer (LABC) patients and the outcomes of NAC, with the aim of identifying predictive indicators for pCR. Additionally, we seek to examine the conversion of IHC markers in pCR patients following NAC and its impact on the prognosis of BC patients. We conducted a study involving 126 patients with LABC. Clinicopathological parameters associated with pCR were subjected to univariate and multivariate analysis. Kaplan-Meier (KM) curves and the log-rank test were used to compare the statistical difference in prognosis in different groups of patients. Additionally, we used difference and consistency tests to examine the conversion of immunohistochemistry (IHC) markers following NAC. The status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and molecular subtypes of BC were associated with pCR in the univariate analysis (all P < .05), which may be potential markers to predict pCR. HER2 was identified as an independent factor for predicting pCR in the multivariate analysis. The pCR rate of HER2-positive patients who received NAC combined targeted therapy was higher than that of patients who only received NAC (P = .003). The disease-free survival (DFS) rate of TNBC patients who achieved pCR was significantly higher than that of non-pCR TNBC patients (P = .026). The IHC marker conversion after NAC mainly existed in PR (P = .041). Ki67 expression decreased in the luminal B subtype and increased in the HER2 enriched subtype after NAC (all P < .001). Patients with Ki67 expression change after NAC had longer overall survival (OS) and DFS than unchanged patients (all P < .05). HER2-positive is an independent indicator for predicting pCR, and HE2-positive patients who received NAC combined targeted therapy were favorable to achieving pCR. IHC markers of BC patients exhibit varying degrees of alterations after NAC, and changes in Ki67 expression after NAC could serve as a marker to predict a better prognosis.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Antígeno Ki-67/metabolismo , Terapia Neoadjuvante/efeitos adversos , Neoplasias de Mama Triplo Negativas/patologia , Prognóstico , Receptor ErbB-2/metabolismo , China , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
5.
Neurology ; 102(5): e207959, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38335471

RESUMO

BACKGROUND AND OBJECTIVES: Hydrocephalus is a common radiologic sign in patients with leptomeningeal metastasis (LM) from solid tumors which can be assessed using the Evans index (EI). Here, we explored the prognostic value of ventricular size in LM. METHODS: We identified patients with LM from solid tumors by chart review at 3 academic hospitals to explore the prognostic associations of the EI at diagnosis, first follow-up, and progression. RESULTS: We included 113 patients. The median age was 58.3 years (interquartile range [IQR] 46.1-65.8), 41 patients (36%) were male, and 72 patients (64%) were female. The most frequent cancers were lung cancer (n = 39), breast cancer (n = 36), and melanoma (n = 23). The median EI at baseline was 0.28 (IQR 0.26-0.31); the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). Among patients with MRI follow-up, the EI increased by 0.01 or more in 16 of 31 patients (52%), including 8 of 30 patients (30%) without and 10 of 17 patients (59%) with LM progression at first follow-up. At LM progression, an increase of EI of 0.01 or more was noted in 18 of 34 patients (53%). The median survival was 2.9 months (IQR 1-7.2). Patients with a baseline EI below 0.27 had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, vs 1.3 months, IQR 0.6-4.1) (HR 1.70, 95% CI 1.135-2.534, p = 0.0099). The median survival was 3.7 months (IQR 1.4-8.3) with an EI below 0.30 vs 1.8 months (IQR 0.8-4.1) with an EI of 0.30 or more (HR 1.40, 95% CI 0.935-1.243, p = 0.1113). Among patients with follow-up scans available, the overall survival was 9.4 months (IQR 5.6-21.0) for patients with stable or decreased EI at first follow-up as opposed to 5.6 months (IQR 2.5-10.5) for those with an increase in the EI (HR 1.08, 95% CI 0.937-1.243; p = 0.300). DISCUSSION: The EI at baseline is prognostic in LM. An increase of EI during follow-up may be associated with inferior LM progression-free survival. Independent validation cohorts with larger sample size and evaluation of confounding factors will help to better define the clinical utility of EI assessments in LM.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Carcinomatose Meníngea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Carcinomatose Meníngea/diagnóstico por imagem , Carcinomatose Meníngea/secundário , Neoplasias da Mama/patologia
6.
J Pathol Clin Res ; 10(2): e12362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335502

RESUMO

Most invasive lobular breast carcinomas (ILBCs) are luminal-type carcinomas with an HER2-negative phenotype (ERBB2 or HER2 un-amplified) and CDH1 mutations. Rare variants include ERBB2-amplified subtypes associated with an unfavorable prognosis and less response to anti-HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2-amplified ILBC and compared these characteristics with ERBB2-unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin-embedded formalin-fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast-specific markers was tested by immunohistochemistry (IHC). Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2-amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2-unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2-positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2-amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2-amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2-unamplified ILBC. CDK12/ERBB2 co-amplification may explain the poor prognosis and therapy resistance of ERBB2-amplified ILBC.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Humanos , Feminino , Prognóstico , Hibridização in Situ Fluorescente , Carcinoma Lobular/genética , Carcinoma Lobular/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Mutação , Quinases Ciclina-Dependentes/genética , Receptor ErbB-2/genética
7.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338683

RESUMO

MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences' 3' untranslated regions (3'UTR). Interleukin-6 (IL-6) is known to promote cancer progression and treatment resistance. In this study, we aimed to explore the therapeutic effects of gold nanoparticles (GNP) against IL-6 overexpression and the modulation of miRNA-26a-5p in breast cancer (BC) cells. GNP were synthesized using the trisodium citrate method and characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). To predict the binding of miR-26a-5p in the IL-6 mRNA's 3'UTR, we utilized bioinformatics algorithms. Luciferase reporter clone assays and anti-miRNA-26a-5p transfection were employed to validate the binding of miR26a-5p in the IL-6 mRNA's 3'UTR. The activity of RelA and NF-κBp50 was assessed and confirmed using Bay 11-7082. The synthesized GNP were spherical with a mean size of 28.3 nm, exhibiting high stability, and were suitable for BC cell treatment. We found that miR-26a-5p directly regulated IL-6 overexpression in MCF-7 cells activated with PMA. Treatment of MCF-7 cells with GNP resulted in the inhibition of IL-6 overexpression and secretion through the increase of miR26a-5p. Furthermore, GNP deactivated NF-κBp65/NF-κBp50 transcription activity. The newly engineered GNP demonstrated safety and showed promise as a therapeutic approach for reducing IL-6 overexpression. The GNP suppressed IL-6 overexpression and secretion by deactivating NF-κBp65/NF-κBp50 transcription activity and upregulating miR-26a-5p expression in activated BC cells. These findings suggest that GNP have potential as a therapeutic intervention for BC by targeting IL-6 expression and associated pathways.


Assuntos
Neoplasias da Mama , Nanopartículas Metálicas , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Ouro , Interleucina-6/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regiões 3' não Traduzidas
8.
Clin. transl. oncol. (Print) ; 26(2): 389-397, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230184

RESUMO

Purpose To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. Methods In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. Results Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043–1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142–2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102–3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084–12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672–28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan–Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. Conclusion To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/patologia , Receptor ErbB-2 , Intervalo Livre de Doença , Estudos Retrospectivos , Prognóstico
9.
BMJ Case Rep ; 17(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38367988

RESUMO

We present a case of an ectopic breast adenocarcinoma of the vulva with metastatic local recurrence and a total follow-up period of 19 years, the longest documented in the literature to our knowledge. Following surgical excision, radiation therapy and hormonal treatment after the recurrence, the patient has remained disease free. This case demonstrates the potential for malignant transformation in accessory breast tissue and highlights the importance of close surveillance and regular physical examinations in patients with a history of ectopic breast malignancy.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Coristoma , Neoplasias Vulvares , Feminino , Humanos , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/cirurgia , Seguimentos , Neoplasias da Mama/patologia , Vulva/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Coristoma/patologia
10.
J Clin Pathol ; 77(3): 204-210, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373781

RESUMO

The pathological assessment of a breast surgical specimen starts with macroscopic evaluation, arguably one of the most critical steps, as only a small percentage of the tissue is examined microscopically. To properly evaluate and select tissue sections from breast specimens, it is essential to correlate radiological findings, prior biopsies, procedures and treatment with the gross findings. Owing to its fatty nature, breast tissue requires special attention for proper fixation to ensure appropriate microscopic evaluation and performance of ancillary studies. In addition, knowledge of the information necessary for patient management will ensure that these data are collected during the macroscopic evaluation, and appropriate sections are taken to obtain the information needed from the microscopic evaluation. Herein, we present a review of the macroscopic evaluation of different breast specimen types, including processing requirements, challenges and recommendations.


Assuntos
Neoplasias da Mama , Mama , Humanos , Feminino , Mama/patologia , Biópsia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia
11.
Cancer Rep (Hoboken) ; 7(2): e1974, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38351535

RESUMO

BACKGROUND: Breast cancer is a highly prevalent disease worldwide, and early diagnosis and treatment could reduce the mortality rate of breast cancer patients. microRNAs (miRNA) have been shown to regulate the occurrences and progression of many types of cancers. Thus, it is crucial to find novel biomarkers in breast cancer. miR-449c-5p acted as a biomarker in non-small cell lung cancer, gastric carcinoma, and so forth. ERBB2 is an ideal target for breast cancer therapy. However, the molecular mechanisms between miR-449c-5p and ERBB2 in breast cancer remain poorly understood. Our study focused on the regulatory role of miR-449c-5p in breast cancer and its targeting relationship with ERBB2. METHODS: The miR-449c-5p expression in breast cancer tissue and normal tissue was searched from the online database (Starbase). The clinical prognosis of miR-449c-5p and ERBB2 was predicted by using the Kaplan-Meier analysis method. The expression of miR-449c-5p mimics and inhibitors was measured by qRT-PCR. T47D cells were transfected with miR-449c-5p mimics and miR-449c-5p inhibitors. After that, CCK-8, colony formation assays and Transwell assays were used to evaluate the cell proliferation ability, migration and invasion. Whether ERBB2 was the target gene of the miR-449c-5p was predicted by Starbase and verified by dual-luciferase activity assay. In addition, protein levels and the relationship between signalling pathways were measured and validated using western blotting analysis. RESULTS: We confirmed that miR-449c-5p was highly expressed in breast cancer tissue, and its downregulation was linked with poor prognosis. Overexpression of miR-449c-5p inhibited the proliferation, migration and invasion of breast cancer cells. ERBB2 was a target of miR-449c-5p. The invasion, migration, and proliferation of breast cancer cells were inhibited by miR-449c-5p/ERBB2 through JAK-STAT. CONCLUSION: This study demonstrated that miR-449c-5p inhibits breast cancer cell proliferation, migration and invasion by targeting ERBB2 via JAK/STAT, which means miR-449c-5p, is a potential biomarker for breast cancer and provides a novel insight for diagnosis.


Assuntos
Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Feminino , Humanos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Janus Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição STAT/metabolismo
12.
Cancer Rep (Hoboken) ; 7(2): e1988, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38351553

RESUMO

BACKGROUND: Breast cancer (BC) metastases to the abdomen and pelvis affect the liver, mesentery, retroperitoneum, peritoneum, bladder, kidney, ovary, and uterus. The study documented the radiological pattern and features of the chest, bone, abdominal and pelvic (AP) metastases among advanced BC patients. AIM: The aim is to document the radiological pattern and features of breast cancer metastasis in the chest, abdomen, pelvis and bones. MATERIALS AND RESULTS: Chest, abdominal, and pelvic computed tomography scan images of 36 patients with advanced BC were collated from Cape Coast Teaching Hospital and RAAJ Diagnostics. The images were prospectively assessed for metastasis to the organs of the chest, AP soft tissues, and bones. Radiologic features of metastasis of the lungs, liver, lymph nodes (LNs), and bones were documented. Patients' demographics, clinical data, and histopathology reports were also collected. The data were captured using UVOSYO and exported to Microsoft Excel templates. The data obtained were descriptively analyzed. Only 2.8% of BCs exhibited metaplastic BC, whereas 97.2% had invasive ductal BC. Triple-negative cases were 55.6%. Of 36 patients, 31 (86.1%), 21 (58.3%), and 14(38.8%) were diagnosed of chest, AP, and bone tissues metastasis, respectively. LN involvement was reported in 26 (72.2%) patients. Majority, 21 (58.3%) were diagnosed of multiple sites metastasis with 15 (41.7%) showing single site. Lungs (77.4%, 24/31) and liver (47.6%, 10/21) were the most affected distant organs. Most bone metastases were lytic lesions (92.9%, 13/14) with the vertebrae (85.7%, 12/14) been the most affected. CONCLUSION: According to the study, advanced BC patients have a higher-than-average radiologic incidence of lung, liver, bone, and LN metastases.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Linfonodos/patologia
13.
Proc Natl Acad Sci U S A ; 121(7): e2311854121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38319971

RESUMO

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.


Assuntos
Neoplasias da Mama , Relógios Circadianos , Humanos , Feminino , Neoplasias da Mama/patologia , Relógios Circadianos/genética , Ritmo Circadiano , Estrogênios , Prognóstico
14.
Sci Rep ; 14(1): 3778, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38355711

RESUMO

Our research found that vitamin D3 (VD3) treatment increased lung metastasis in mice with 4T1 murine breast cancer (BC). This study aims to investigate the impact of VD3 on the activation of tumor-associated macrophages (TAMs) in BC. Mice bearing 4T1, E0771, 67NR BC cells, and healthy mice, were fed diets with varying VD3 contents (100-deficient, 1000-normal, and 5000 IU/kg-elevated). Some mice in the 1000 and 100 IU/kg groups received calcitriol. We studied bone metastasis and characterized TAMs and bone marrow-derived macrophages (BMDMs). 4T1 cells had higher bone metastasis potential in the 5000 IU/kg and calcitriol groups. In the same mice, an elevated tumor osteopontin level and M2 polarization of TAMs (MHCIIlow CD44high phenotype) were observed. Gene expression analysis confirmed M2 polarization of 4T1 (but not 67NR) TAMs and BMDMs, particularly in the 100 IU + cal group (increased Mrc1, Il23, and Il6). This polarization was likely due to COX-2/PGE2 induction in 4T1 calcitriol-treated cells, leading to increased proinflammatory cytokines like IL-6 and IL-23. Future studies will explore COX-2/PGE2 as a primary mediator of calcitriol-stimulated inflammation in the BC microenvironment, especially relevant for BC patients with VD3 deficiency and supplementation.


Assuntos
Neoplasias da Mama , Glândulas Mamárias Humanas , Humanos , Animais , Camundongos , Feminino , Citocinas/metabolismo , Calcitriol/farmacologia , Macrófagos Associados a Tumor/metabolismo , Ciclo-Oxigenase 2/genética , Glândulas Mamárias Humanas/metabolismo , Linhagem Celular Tumoral , Neoplasias da Mama/patologia , Microambiente Tumoral
15.
BMC Womens Health ; 24(1): 120, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360619

RESUMO

BACKGROUND: Despite the significant weight of difficulty, Ethiopia's survival rate and mortality predictors have not yet been identified. Finding out what influences outpatient breast cancer patients' survival time was the major goal of this study. METHODS: A retrospective study was conducted on outpatients with breast cancer. In order to accomplish the goal, 382 outpatients with breast cancer were included in the study using information obtained from the medical records of patients registered at the University of Gondar referral hospital in Gondar, Ethiopia, between May 15, 2016, and May 15, 2020. In order to compare survival functions, Kaplan-Meier plots and the log-rank test were used. The Cox-PH model and Bayesian parametric survival models were then used to examine the survival time of breast cancer outpatients. The use of integrated layered Laplace approximation techniques has been made. RESULTS: The study included 382 outpatients with breast cancer in total, and 148 (38.7%) patients died. 42 months was the estimated median patient survival time. The Bayesian Weibull accelerated failure time model was determined to be suitable using model selection criteria. Stage, grade 2, 3, and 4, co-morbid, histological type, FIGO stage, chemotherapy, metastatic number 1, 2, and >=3, and tumour size all have a sizable impact on the survival time of outpatients with breast cancer, according to the results of this model. The breast cancer outpatient survival time was correctly predicted by the Bayesian Weibull accelerated failure time model. CONCLUSIONS: Compared to high- and middle-income countries, the overall survival rate was lower. Notable variables influencing the length of survival following a breast cancer diagnosis were weight loss, invasive medullar histology, comorbid disease, a large tumour size, an increase in metastases, an increase in the International Federation of Gynaecologists and Obstetricians stage, an increase in grade, lymphatic vascular space invasion, positive regional nodes, and late stages of cancer. The authors advise that it is preferable to increase the number of early screening programmes and treatment centres for breast cancer and to work with the public media to raise knowledge of the disease's prevention, screening, and treatment choices.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Teorema de Bayes , Estudos Retrospectivos , Etiópia/epidemiologia , Modelos de Riscos Proporcionais
16.
Cell Commun Signal ; 22(1): 127, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360674

RESUMO

All-trans retinoic acid (ATRA) is the most relevant and functionally active metabolite of Vitamin-A. From a therapeutic standpoint, ATRA is the first example of pharmacological agent exerting its anti-tumor activity via a cell differentiating action. In the clinics, ATRA is used in the treatment of Acute Promyelocytic Leukemia, a rare form of myeloid leukemia with unprecedented therapeutic results. The extraordinary effectiveness of ATRA in the treatment of Acute Promyelocytic Leukemia patients has raised interest in evaluating the potential of this natural retinoid in the treatment of other types of neoplasias, with particular reference to solid tumors.The present article provides an overview of the available pre-clinical and clinical studies focussing on ATRA as a therapeutic agent in the context of breast cancer from a holistic point of view. In detail, we focus on the direct effects of ATRA in breast cancer cells as well as the underlying molecular mechanisms of action. In addition, we summarize the available information on the action exerted by ATRA on the breast cancer micro-environment, an emerging determinant of the progression and invasive behaviour of solid tumors. In particular we discuss the recent evidences of ATRA activity on the immune system. Finally, we analyse and discuss the results obtained with the few ATRA-based clinical trials conducted in the context of breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Leucemia Promielocítica Aguda , Humanos , Feminino , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Neoplasias da Mama/patologia , Tretinoína/farmacologia , Tretinoína/metabolismo , Linhagem Celular Tumoral , Diferenciação Celular , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Microambiente Tumoral
17.
Oncol Res ; 32(3): 477-487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361760

RESUMO

Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation, growth, and therapy resistance. The hallmarks of cancer-fibroblast interactions, consisting of caveolin 1 (Cav1) and mono-carboxylate transporter 4 (MCT4) (metabolic coupling markers), along with IL-6, TGFß, and lactate secretion, are considered robust biomarkers predicting recurrence and metastasis. In order to promote a novel phenotype in normal fibroblasts, we predicted that breast cancer cells could be able to cause loss of Cav1 and increase of MCT4, as well as elevate IL-6 and TGFß in nearby normal fibroblasts. We created a co-culture model using breast cancer (4T1) and normal fibroblast (NIH3T3) cell lines cultured under specific experimental conditions in order to directly test our theory. Moreover, we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cav1 and gain of MCT4 in adjacent fibroblasts and increase lactate secretion. These results were validated using the monoculture of each group separately as a control. In this system, we show that metformin inhibits IL-6 and TGFß secretion and re-expresses Cav1 in both cells. However, MCT4 and lactate stayed high after treatment with metformin. In conclusion, our work shows that co-culture with breast cancer cells may cause significant alterations in the phenotype and secretion of normal fibroblasts. Metformin, however, may change this state and affect fibroblasts' acquired phenotypes. Moreover, mitochondrial inhibition by metformin after 8 days of treatment, significantly hinders tumor growth in mouse model of breast cancer.


Assuntos
Neoplasias da Mama , Metformina , Animais , Camundongos , Humanos , Feminino , Metformina/farmacologia , Metformina/metabolismo , Técnicas de Cocultura , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Células NIH 3T3 , Estresse Oxidativo , Neoplasias da Mama/patologia , Fibroblastos/metabolismo , Fenótipo , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral
18.
Breast Dis ; 43(1): 9-17, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363601

RESUMO

BACKGROUND: Breast cancer (BC) patients' diagnosis and management was affected by a global reorganization after the Coronavirus disease 2019 (COVID-19). Our study aimed to assess the impact of the pandemic on the pathological stage of newly diagnosed patients with BC compared to pre-pandemic and to identify predictive factors of tumor advanced stage. METHODS: Pathological records of all consecutive newly operated BC patients between March 2020 and December 2021 were reviewed retrospectively. Clinical and pathological prognostic factors of BC were collected and compared between pre-pandemic and pandemic periods. Then, predictive factors of tumor advanced stage were identified. RESULTS: Of the 225 cases included in the analysis, 98.7% were females and 1.3% were males. The median time from first histological diagnosis to first surgical treatment was enlarged by 42 days with a significant difference between the two periods (p = 0.002). Newly diagnosed BC patients during the COVID-19 pandemic were operated at a more advanced stage (54.1% vs 36.2%, p = 0.007), had a greater lymphovascular invasion (p = 0.002), lymph node metastasis (p = 0.015) and are more commonly of IBC NST histological type (p = 0.005). Moreover, multivariate analyses showed that the pandemic period (AOR = 2.28; p = 0.016) and the lympho-vascular invasion (p < 0.001) were independently associated with advanced stage of tumors. CONCLUSION: Our findings proved an increase in alarming rates of advanced stage BC associated with the COVID-19 crisis. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm.


Assuntos
Neoplasias da Mama , COVID-19 , Masculino , Feminino , Humanos , COVID-19/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Pandemias , Estudos Retrospectivos , Teste para COVID-19
19.
Breast Dis ; 43(1): 1-8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363600

RESUMO

BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival. OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes. METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify ER and PR results. RESULTS: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC. CONCLUSIONS: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama Masculina , Neoplasias da Mama , Carcinoma Ductal de Mama , Humanos , Masculino , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , Prognóstico , Linfonodos/patologia , Carcinoma Ductal de Mama/patologia , Receptores de Progesterona
20.
Exp Oncol ; 45(4): 421-431, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38328848

RESUMO

BACKGROUND: Breast cancer (BC) in young women remains a significant public health concern. While progress has been made in understanding the etiology, diagnosis, and treatment of BC in this population, challenges persist. The identification and utilization of prognostic biomarkers offer valuable tools for tailoring treatment strategies and improving outcomes for BC patients. AIM: To evaluate the relationship between the expression of tumor-associated microRNAs and the clinical and pathological features of BC in young patients. MATERIALS AND METHODS: The work is based on the results of the examination and treatment of 50 women younger than 45 years with stage I-II BC. miR-145, -182, -21, -27a, -29b, and -34a expression in tumor samples was analyzed by the real-time reverse transcription polymerase chain reaction. RESULTS: Higher expression of miR-182, -21, and -29b and lower levels of miR-27a were associated with tumor stage in young BC patients. Patients without lymph node metastases (N0) had significantly higher levels of miR-182, -27a, and -34a and lower levels of miR-29b compared to N1 cases (p < 0.05). Expression of miR-145, -182, -21, -27a, and -29b was associated with molecular BC subtypes. CONCLUSION: Obtained results show that a high malignancy degree of BC in young women is associated with an increase in the miR-182, -21, -29b, and -34a expressions and a decrease in the miR-27a level in the tumor tissue, which indicates the prospects of the use of them for predicting the aggressiveness of the disease.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica
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