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1.
Clinics (Sao Paulo) ; 78: 100155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36681070

RESUMO

FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.


Assuntos
Neoplasias da Mama , MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Brasil , Biomarcadores Tumorais/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , Carcinogênese , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica
2.
Clinics (Sao Paulo) ; 78: 100160, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36681068

RESUMO

OBJECTIVE: This study monitors trends in access to cancer screening, focusing on mammography, Papanicolaou (Pap smear), and Prostate-Specific Antigen (PSA), assessing the magnitude of inequality in the city of São Paulo from 2003 to 2015 according to education level. METHOD: This is a cross-sectional population-based study conducted with data from the 2003, 2008, and 2015 editions of the Health Survey of the City of São Paulo (ISA-Capital). Outcome variables were the proportion of mammography, Papanicolaou (Pap smear), and Prostate-Specific Antigen (PSA) tests according to the protocols. Inequality was measured by education level according to years of study. For static analysis, Poisson regression was used to estimate proportion ratios. RESULTS: The proportion of Pap smears remained stationary at a high level (>89%) throughout the study period, while access to mammography and PSA tests significantly increased in the 2003‒2015 period. The present results indicate inequalities in access to cancer screening due to education, and being more expressive for mammography and PSA tests. However, this inequality significantly decreased over the period analyzed comparing the most educated individuals with those with the lowest educational level. In addition, an increase in the proportion of tests performed in the Brazilian Unified Health System was identified, especially for mammography and PSA tests, in the period 2003‒2015. CONCLUSIONS: The inequalities observed in the access to preventive exams were influenced by the level of education. The offer of exams was expanded, more significantly for mammography and PSA, especially among the less educated group.


Assuntos
Neoplasias da Mama , Neoplasias do Colo do Útero , Masculino , Feminino , Humanos , Detecção Precoce de Câncer , Antígeno Prostático Específico , Brasil/epidemiologia , Esfregaço Vaginal , Programas de Rastreamento , Estudos Transversais , Neoplasias do Colo do Útero/diagnóstico , Fatores Socioeconômicos , Mamografia , Neoplasias da Mama/diagnóstico
3.
Sci Rep ; 13(1): 1384, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697441

RESUMO

Breast cancer has become the most prevalent cancer, globally. Adriamycin is a first-line chemotherapeutic agent, however, cancer cells acquire resistance to it, which is one of the most common causes of treatment failure. ROS and NRF2 are essential oxidative stress factors that play a key role in the oxidative stress process and are associated with cancer. Our goal is to create novel therapeutic drugs or chemical sensitizers that will improve chemotherapy sensitivity. The optimal concentration and duration for MCF-7 and MCF-7/ADR cells in ADR and CYT were determined using the CCK-8 assay. We found that ADR + CYT inhibited the activity of MCF-7 and MCF-7/ADR cells in breast cancer, as well as causing apoptosis in MCF-7 and MCF-7/ADR cells and blocking the cell cycle in the G0/G1 phase. ADR + CYT induces apoptosis in MCF-7 and MCF-7/ADR cells through ROS generation and the P62/NRF2/HO-1 signaling pathway. In breast cancer-bearing nude mice, ADR + CYT effectively suppressed tumor development in vivo. Overall, our findings showed that CYT in combination with ADR has potent anti-breast cancer cell activity both in vivo and in vitro, suggesting CYT as the main drug used to improve chemosensitivity.


Assuntos
Neoplasias da Mama , Doxorrubicina , Humanos , Animais , Camundongos , Feminino , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Células MCF-7 , Espécies Reativas de Oxigênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Apoptose , Neoplasias da Mama/patologia
4.
BMC Cancer ; 23(1): 84, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698078

RESUMO

BACKGROUND: Breast cancer patients of American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) Group 2 were all HER2-negative according to the 2018 guideline, not HER2-positive as defined in the 2013 guideline. METHODS: We aims to elucidate the unique clinicopathological features of ASCO/CAP Group 2 patients by comparing with classic HER2-nonamplified cancers, and reveal the efficacy of the former to anti-HER2 therapy. The clinicopathological features, treatment and prognosis information of 99 patients between 2014 and 2018 were collected. HER2 status was re-defined using the updated recommendations. RESULTS: Of the 99 ASCO/CAP Group 2 tumors, 25.5% (25/99) tumors were immunohistochemical (IHC) 0/1+ and 74.7% (74/99) tumors were IHC 2+. According to the updated 2018 guideline, all of them were HER2 negative. When compared to ASCO/CAP Group 5, patients of ASCO/CAP Group 2 displayed higher ratio of histological grade 3 (P = .03), high Ki67 proliferation index (P = .03) and pN3 (more than 9 lymph nodes metastasis, P = .02), and lower estrogen receptor (ER) positivity (P = .04). There was no statistical difference in the survival of patients received anti-HER2 therapy and patients not received anti-HER2 therapy. CONCLUSIONS: Patients of ASCO/CAP Group 2 did not received apparent benefit from anti-HER2 treatment. Although according to the updated guidelines and latest reports, HER2 is negative, but when compared with classic HER2-nonamplified cancers, patients of this group seemed to be more aggressive. We suggest that this group still be regarded as an independent category, in order to accumulate more cases in the future to expand the scope of research.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Receptor ErbB-2/análise , Hibridização in Situ Fluorescente , Variações do Número de Cópias de DNA , China/epidemiologia , Análise de Sobrevida , Biomarcadores Tumorais/análise
5.
Obesity (Silver Spring) ; 31(2): 479-486, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36628617

RESUMO

OBJECTIVE: This study tested the hypothesis that obesity and metabolic abnormalities correlate with background parenchymal enhancement (BPE), the volume and intensity of enhancing fibroglandular breast tissue on dynamic contrast-enhanced magnetic resonance imaging. METHODS: Participants included 59 premenopausal women at high risk of breast cancer. Obesity was defined as BMI ≥ 30 kg/m2 . Metabolic parameters included dual-energy x-ray absorptiometry-quantified body composition, plasma biomarkers of insulin resistance, adipokines, inflammation, lipids, and urinary sex hormones. BPE was assessed using computerized algorithms on dynamic contrast-enhanced magnetic resonance imaging. RESULTS: BMI was positively correlated with BPE (r = 0.69; p < 0.001); participants with obesity had higher BPE than those without obesity (404.9 ± 189.6 vs. 261.8 ± 143.8 cm2 ; Δ: 143.1 cm2 [95% CI: 49.5-236.7]; p = 0.003). Total body fat mass (r = 0.68; p < 0.001), body fat percentage (r = 0.64; p < 0.001), visceral adipose tissue area (r = 0.65; p < 0.001), subcutaneous adipose tissue area (r = 0.60; p < 0.001), insulin (r = 0.59; p < 0.001), glucose (r = 0.35; p = 0.011), homeostatic model of insulin resistance (r = 0.62; p < 0.001), and leptin (r = 0.60; p < 0.001) were positively correlated with BPE. Adiponectin (r = -0.44; p < 0.001) was negatively correlated with BPE. Plasma biomarkers of inflammation and lipids and urinary sex hormones were not correlated with BPE. CONCLUSIONS: In premenopausal women at high risk of breast cancer, increased BPE is associated with obesity, insulin resistance, leptin, and adiponectin.


Assuntos
Neoplasias da Mama , Resistência à Insulina , Humanos , Feminino , Leptina , Adiponectina , Obesidade/metabolismo , Lipídeos , Inflamação
6.
Clin Med (Lond) ; 23(1): 65-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36697006

RESUMO

Cancers contain a plethora of mutations, few of which are critical to maintaining a state of malignancy. With our ever-expanding understanding of the genomic complexity of cancer, potentially actionable biomarkers whose inhibition could cripple cancer growth are increasingly being elucidated. Modern cancer drug development has largely switched from cytotoxic agents to targeted therapies and immunotherapy, with noteworthy success in several cancer types including non-small-cell lung cancer (NSCLC), breast cancer and melanoma. Next-generation sequencing offers high-throughput, widescale genomic interrogation in a far more efficient and affordable manner than previous sequencing methods. This facilitates detection of potentially actionable mutations and fusions for individual patients and contributes to the identification of novel predictive and prognostic biomarkers in a population. Challenges in the technical aspects of biopsy and sequencing, interpretation, and development of targeted therapies against common genomic aberrations will need to be addressed for personalised medicine to become a reality for more patients with cancer.


Assuntos
Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Mutação , Sequenciamento de Nucleotídeos em Larga Escala , Biomarcadores Tumorais/genética , Terapia de Alvo Molecular
7.
Anticancer Res ; 43(2): 733-739, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697057

RESUMO

BACKGROUND/AIM: Mastectomy is the standard treatment of in-breast-recurrence of breast cancer after breast conserving surgery (BCS) and external beam radiation therapy (EBRT). In selected cases, it is possible to preserve the breast if targeted intraoperative radiotherapy (TARGIT-IORT) can be given during the second lumpectomy. This is a comparative analysis of overall survival and quality of life (QoL). PATIENTS AND METHODS: Patients in our database with in-breast-recurrence and either mastectomy or BCS and TARGIT-IORT were included. Identified patients were offered participation in a prospective QoL-analysis using the BREAST-Q questionnaire. The cohorts were compared for confounding parameters, overall survival, and QoL. RESULTS: Thirty-six patients treated for in-breast-recurrence were included, 21 had received a mastectomy and 16 patients had received BCS with TARGIT-IORT. Mean follow-up was 12.8 years since primary diagnosis and 4.2 years since recurrence. Both groups were balanced regarding prognostic parameters. Overall survival was numerically longer for BCS and TARGIT-IORT, but the numbers were too small for formal statistical analysis. No patient had further in-breast-recurrence. Psychosocial and sexual wellbeing did not differ between both groups. Physical wellbeing was significantly superior for those whose breast could be preserved (p-value=0.021). Patient-reported incidence and severity of lymphedema of the arm was significantly worse in the mastectomy group (p=0.007). CONCLUSION: Preserving the breast by use of TARGIT-IORT was safe with no re-recurrence and no detriment to overall survival in our analysis and led to a statistically significant improvement in physical wellbeing and incidence of lymphedema. These data should increase the confidence in offering breast preservation after in-breast-recurrence of breast cancer.


Assuntos
Neoplasias da Mama , Linfedema , Neoplasias Mamárias Animais , Humanos , Animais , Feminino , Mastectomia , Mastectomia Segmentar/efeitos adversos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Qualidade de Vida , Estudos Prospectivos , Recidiva Local de Neoplasia/cirurgia , Cuidados Intraoperatórios , Radioterapia
8.
Anticancer Res ; 43(2): 603-611, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697070

RESUMO

BACKGROUND/AIM: Hypoxia is significantly associated with the development of drug resistance, and endocrine therapy is ineffective against hormone receptor (HR)-positive breast cancer in hypoxic tumor environments. Eribulin has a unique anticancer effect in breast cancer cells and improves tumor hypoxia by vascular remodeling. Therefore, we investigated the effect of eribulin on HR-positive breast cancer cells that were resistant to endocrine blockade. MATERIALS AND METHODS: We established hypoxia-resistant breast cancer cell lines by continuous culture in a hypoxic environment. Parental and hypoxia-resistant cell lines were treated with eribulin and/or tamoxifen, and estrogen receptor (ER)-, epithelial-mesenchymal transition-, and hypoxia-related gene and protein expression changes in each surviving cell line were assessed. In addition, proliferation was assessed after eribulin treatment in the parental and hypoxia-resistant cell lines. We also assessed the effect of eribulin in vivo using subcutaneous xenograft models. RESULTS: Hypoxia-resistant cell lines showed significantly decreased expression of epithelial and ER-related markers and exhibited a higher level of resistance to tamoxifen. Conversely, eribulin treatment increased epithelial and ER-related gene and protein expression in hypoxia-resistant cell lines and enhanced the anticancer effect of tamoxifen. In in vivo xenograft models, eribulin treatment of hypoxia- and tamoxifen-resistant tumors slightly induced the re-expression of ER. In addition, hypoxia-resistant tumors treated with eribulin tended to respond better to tamoxifen. CONCLUSION: Eribulin ameliorated the aggressive behavior caused by hypoxia and induced the re-expression of ER in hypoxia-resistant breast cancer cells. Eribulin treatment of HR-positive breast cancer may resensitize cells to hormone blockade.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptores de Estrogênio/metabolismo , Linhagem Celular Tumoral , Tamoxifeno/farmacologia , Hipóxia , Hormônios/farmacologia , Hormônios/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Receptor alfa de Estrogênio/genética
9.
Anticancer Res ; 43(2): 707-711, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697064

RESUMO

BACKGROUND/AIM: A subset of patients with estrogen receptor (ER)-positive, HER2-negative, and node-negative breast cancer experience recurrences. Predicting patients who will have recurrences within 5 years of surgery is essential so that patients can be selected to receive adjuvant chemotherapy. The 95-gene classifier (95-GC) has been validated as a method to differentiate patients into high and low-risk groups for early recurrence. PATIENTS AND METHODS: In this study, we performed 95-GC analysis on 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients who underwent surgery for ER-positive, HER2-negative, and node-negative breast cancer and did not receive adjuvant chemotherapy. We associated the obtained high- and low-risk groups with clinicopathological characteristics and recurrence-free survival (RFS). RESULTS: We classified 12 out of 56 patients into the high-risk recurrence group. We found significantly higher KI67 scores in patients in the high-risk group. Other clinicopathological characteristics were not associated with the 95-GC risk groups. Patients in the 95-GC low-risk group had a significantly better prognosis than those in the high-risk group (p=0.0387). The 5-year RFS rate was 97.6% in the low-risk group and 74.1% in the high-risk group, while the 10-year RFS rates were 90.1% and 74.1%, respectively. CONCLUSION: The 95-GC score can accurately predict RFS within 5 years of surgery for ER-positive, HER2-negative, and node-negative breast cancer using FFPE tissue samples. These prediction models could help assign patients to the most effective treatment regimen.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/genética , Inclusão em Parafina , Receptores de Estrogênio , Recidiva Local de Neoplasia/patologia , Prognóstico , Formaldeído , Quimioterapia Adjuvante
10.
Anticancer Res ; 43(2): 849-856, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697094

RESUMO

BACKGROUND/AIM: Smoking has been a proven carcinogenic risk factor for various cancers, including breast cancer. Furthermore, smoking has been recognized as a prognostic factor of breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) used in combination with chemotherapy to treat breast cancer. We, herein, investigated the effect of smoking on the prognosis of unresectable breast cancer patients who received bevacizumab plus weekly paclitaxel. PATIENTS AND METHODS: From April 2011 to June 2022, 131 patients received bevacizumab plus weekly paclitaxel for unresectable breast cancer. At their first visit to our hospital, smoking status (i.e., period of smoking and amount of smoking per day) was evaluated by interview, and packs-years were calculated. RESULTS: Time to treatment failure (TTF) was significantly longer in the high packs-years group than the low packs-years group (p=0.010, log-rank). The log-rank test showed that the high packs-years group had a significantly longer overall survival than the low packs-years group (p=0.049, log-rank). Multivariate analysis of TTF revealed that progesterone receptor (p=0.005, HR=0.408) and packs-years (p=0.007, HR=0.391) were independent factors. CONCLUSION: A history of smoking may impact prognosis of combination chemotherapy with bevacizumab for advanced breast cancer treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Bevacizumab/uso terapêutico , Neoplasias da Mama/metabolismo , Prognóstico , Fator A de Crescimento do Endotélio Vascular , Fumar/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Paclitaxel/uso terapêutico
11.
Anticancer Res ; 43(2): 523-535, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36697093

RESUMO

BACKGROUND/AIM: Intramedullary spinal cord metastases (ISCM) are deemed extremely aggressive, as confirmed by the low life expectancy since the diagnosis. Up to 26.5% of total ISCM stem from breast cancer (BC), representing the second most frequent primary site after the lung. The increasing incidence of BC and the widespread use of MRI for the diagnosis could therefore lead to an earlier diagnosis and, therefore, to a progressively longer survival in patients affected by ISCM from BC. This systematic review is intended to provide an orientation through a management algorithm for the most appropriate therapeutic approach in these patients. MATERIALS AND METHODS: The research strategy initially relied on title and abstract analysis. The article's full text was retrieved for further investigation if the title and abstract met the inclusion criteria. The extracted data included the following: authors, publication time, study design, patient characteristics, ISCM location, treatment modalities, time interval from initial cancer diagnosis to ISCM diagnosis, clinical outcomes, and survival time. RESULTS: This systematic search regarding ISCM from BC yielded 574 articles. After screening, a total of 44 studies were included in this systematic review. A total of 123 patients were evaluated. The mean patient age was 53.2 years with a standard deviation of 10.4 years. Female patients were 122. There was only one male patient. CONCLUSION: ISCM from BC have a better prognosis than lung metastases and, thanks to recent advances in diagnostic imaging and intraoperative planning and neuromonitoring, an early diagnosis and a prompt multidisciplinary treatment may be accomplished. Prospective studies to generate evidence-based data regarding the most appropriate treatment for ISCM are mandatory.


Assuntos
Neoplasias da Mama , Neoplasias da Medula Espinal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/patologia , Estudos Prospectivos , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/terapia , Prognóstico
12.
Artigo em Inglês | MEDLINE | ID: mdl-36673982

RESUMO

Breast cancer, with an overall poor clinical prognosis, is one of the most heterogeneous cancers. DNA damage repair (DDR) and epithelial-mesenchymal transition (EMT) have been identified to be associated with cancer's progression. Our study aimed to explore whether genes with both functions play a more crucial role in the prognosis, immune, and therapy response of breast cancer patients. Based on the Cancer Genome Atlas (TCGA) cancer database, we used LASSO regression analysis to identify the six prognostic-related genes with both DDR and EMT functions, including TP63, YWHAZ, BRCA1, CCND2, YWHAG, and HIPK2. Based on the six genes, we defined the risk scores of the patients and reasonably analyzed the overall survival rate between the patients with the different risk scores. We found that overall survival in higher-risk-score patients was lower than in lower-risk-score patients. Subsequently, further GO and KEGG analyses for patients revealed that the levels of immune infiltration varied for patients with high and low risk scores, and the high-risk-score patients had lower immune infiltration's levels and were insensitive to treatment with chemotherapeutic agents. Furthermore, the Gene Expression Omnibus (GEO) database validated our findings. Our data suggest that TP63, YWHAZ, BRCA1, CCND2, YWHAG, and HIPK2 can be potential genetic markers of prognostic assessment, immune infiltration and chemotherapeutic drug sensitivity in breast cancer patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Transição Epitelial-Mesenquimal , Mama , Reparo do DNA , Bases de Dados Factuais , Proteínas de Transporte , Proteínas Serina-Treonina Quinases , Proteínas 14-3-3
13.
Methods Cell Biol ; 173: 133-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36653080

RESUMO

Adoptive natural killer (NK) cell-based immunotherapy poses a promising treatment approach in cancer. Despite minimal toxicities associated with NK cell infusion, the potential of NK cell therapy is inhibited by the immunosuppressive tumor microenvironment (TME). Multiple approaches to improve anti-cancer NK cell effector functions are being investigated. While much of this preclinical research is currently performed with commercially available tumor cell lines, this approach lacks the influence of the TME and heterogeneity of the primary tumor in patients. Here, we describe a comprehensive protocol for NK cell cytotoxicity- and degranulation assays against tumor cells derived from primary breast cancer tissue. Treatments to boost NK cell anti-tumor effector functions can be implemented in this model. Moreover, by using culture supernatants in follow up assays or by including additional cell types in the co-culture system, other NK cell effector mechanisms that further orchestrate innate and adaptive immunity could be studied.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Feminino , Neoplasias da Mama/terapia , Células Matadoras Naturais/metabolismo , Neoplasias/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Microambiente Tumoral
14.
Methods Mol Biol ; 2608: 281-303, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36653714

RESUMO

Cancer-derived organoids and three-dimensional (3D) extracellular matrix (ECM) are taking center stage as in vitro models to study neoplastic cell behavior, since they recapitulate the heterogeneous cellular composition of tumors and their extracellular environment. In combination with imaging and molecular/biochemical techniques, 3D organoid models have contributed substantially to our knowledge about the cellular and molecular mechanisms that regulate the growth of tumors and invasion into the surrounding tissue. We here outline a set of protocols that describe culturing of cancer-derived organoids in 3D matrices and various strategies that allow modeling of tumor growth, tumor cell penetration into basement membranes, and invasion into Collagen I-rich ECM. Furthermore, we specify protocols for subsequent handling of organoids cultured in 3D ECM for confocal microscopy and analysis of gene expression at the protein and mRNA level. Although we here use breast cancer-derived organoids, these protocols can be directly applied or adapted for organoids derived from other cancer types or healthy tissues. Thus, in addition to investigating cell behavior of multiple cancer types, the combination of protocols described here may be used to study processes such as cell differentiation and migration during homeostasis and normal development.


Assuntos
Neoplasias da Mama , Matriz Extracelular , Humanos , Feminino , Matriz Extracelular/metabolismo , Colágeno Tipo I/metabolismo , Neoplasias da Mama/patologia , Membrana Basal , Organoides
15.
J Clin Pathol ; 76(2): 73-75, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36600573

RESUMO

The partner and localiser of BRCA2 (PALB2) gene, located on chromosome 16, functions as a tumour suppressor that plays a critical role in homologous recombination repair after DNA double-strand breaks. It encodes proteins involved in the BRCA2 and BRCA1, and RAD51 pathways. Heterozygous germline mutations in PALB2 have been implicated in the development of breast, pancreatic and ovarian cancers. Whereas biallelic mutations of PALB2 have been associated with Fanconi anaaemia. Currently, 604 distinct PALB2 variants have been discovered. However, only 140 variants are thought to be pathogenic and approximately 400 are variants of unknown significance. Further studies are needed before the presence of PLAB2 mutations can be implemented as a routine clinical biomarker.


Assuntos
Neoplasias da Mama , Proteínas Supressoras de Tumor , Feminino , Humanos , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Nucleares/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Proteína BRCA1/genética , Reparo do DNA , Mutação , Neoplasias da Mama/genética , Predisposição Genética para Doença
16.
Cien Saude Colet ; 28(1): 223-230, 2023 Jan.
Artigo em Português | MEDLINE | ID: mdl-36629566

RESUMO

The scope of this study was to evaluate the impacts of COVID-19 on breast cancer screening in Brazil. Data were collected from the Ambulatory Information System relating to "bilateral screening mammography" from January/2015 to December/2021. Analyses were performed by region and for Brazil. The average of exams in each month of the year was calculated based on 2015-2019 data, which was compared, monthly, with the number of exams in 2020 and 2021, obtaining the gross and percentage difference between these values. The same analysis was performed for the total number of exams in 2020 and 2021, individually, and for the two years combined. In 2020 there were reductions in the number of exams, which ranged from 25% (North) to 48% (Northeast), resulting in 1.749 million fewer exams than expected in the country (a drop of 44%). In 2021, the Midwest region presented a number of exams 11% higher than expected, while the other regions presented drops between 17% (North) and 27% (Southeast/South), resulting in 927 thousand exams fewer than expected in Brazil (reduction of 23%). In the joint analysis (2020/2021), reductions varied by region from 11% (Midwest) to 35% (Southeast/South), culminating in 2.676 million exams fewer than expected in Brazil (reduction of 33%).


Objetivou-se avaliar os impactos da COVID-19 no rastreamento do câncer de mama no Brasil. Coletaram-se dados do Sistema de Informações Ambulatoriais referentes a "mamografia bilateral para rastreamento" de janeiro/2015 a dezembro/2021. As análises foram feitas por região e para o Brasil. Calculou-se a média de exames em cada mês do ano com base nos dados de 2015 a 2019, a qual foi comparada, mensalmente, com o quantitativo de exames em 2020 e 2021, obtendo-se a diferença bruta e percentual entre esses valores. A mesma análise foi realizada para o número total de exames em 2020 e 2021, individualmente, e para os dois anos em conjunto. Em 2020 houve quedas no número de exames que variaram de 25% (Norte) a 48% (Nordeste), culminando em 1,749 milhão de exames a menos no país (queda de 44%). Em 2021, a região Centro-Oeste apresentou quantitativo de exames 11% superior ao esperado, enquanto as demais regiões apresentaram quedas entre 17% (Norte) e 27% (Sudeste/Sul), culminando em negativo de 927 mil exames no país (redução de 23%). Na análise conjunta (2020/2021), encontraram-se reduções que variaram de 11% (Centro-Oeste) a 35% (Sudeste/Sul), culminando em negativo de 2,676 milhões de procedimentos no Brasil (queda de 33%).


Assuntos
Neoplasias da Mama , COVID-19 , Feminino , Humanos , Brasil/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , COVID-19/epidemiologia , Detecção Precoce de Câncer , Mamografia , Pandemias
17.
Anal Chem ; 95(2): 1095-1105, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36600563

RESUMO

Exosome-based liquid biopsies highlight potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. However, the existing techniques are severely limited for practical applications due to the complications of high cost, low sensitivity, tedious procedures, and large sample consumption. Herein, we report a microstructured optical fiber sensor for fast, sensitive, and accurate quantification of exosomes in blood samples of breast cancer patients. Numerical simulations are applied to demonstrate that hollow-core microstructured antiresonant fibers (HARFs) can stringently confine light in the fiber core, ensuring strong light-matter interaction and thus maximumly amplifying the signal. Taking this advantage, a AuNPs-dsDNA assembly containing gold nanoparticles, a recognizing DNA aptamer, and a fluorescent reporter DNA sequence is fabricated followed by immobilization on the fiber wall to form a AuNPs-dsDNA-HARF sensor. Cancer-derived exosomes can be recognized and captured in the fiber channel and generate dose-dependent fluorescent signals for quantification. The microfiber sensor demonstrates enhanced sensitivity and specificity, enabling the detection of single digits of exosome particles at the nanoliter sample level. In addition, by tracking exosome phenotypic changes, the proposed fiber sensor can facilitate precise drug treatment monitoring. This work provides a robust platform for exosome-based biopsy for cancer diagnosis and prediction of therapeutic outcomes.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Exossomos , Nanopartículas Metálicas , Humanos , Feminino , Fibras Ópticas , Ouro , Neoplasias da Mama/diagnóstico , Biópsia Líquida , Técnicas Biossensoriais/métodos
18.
Epidemiol Serv Saude ; 31(3): e2022440, 2023.
Artigo em Inglês, Português | MEDLINE | ID: mdl-36629594

RESUMO

OBJECTIVE: to analyze the temporal trend of mortality due to malignant neoplasms of the breast and cervix from 1999 to 2019 in Passo Fundo, Rio Grande do Sul, Brazil. METHODS: this was a time-series study based on data from the Mortality Information System; standardized rates were calculated according to age and schooling, and the temporal trend was assessed using Prais-Winsten regression. RESULTS: the overall mortality coefficients for cervical cancer (ß = -0.03; 95%CI -0.08;0.02) and for breast cancer (ß = -0.006; 95%CI -0.02;0.01) were stable over the time series; in both types of neoplasms, a rising trend was identified in women with up to 7 years of schooling; on the other hand, a stationary trend was found in the majority of the age strata analyzed. CONCLUSION: older women and those with low levels of schooling had the worst prognosis.


Assuntos
Neoplasias da Mama , Neoplasias do Colo do Útero , Humanos , Feminino , Idoso , Neoplasias do Colo do Útero/epidemiologia , Brasil/epidemiologia , Escolaridade , Neoplasias da Mama/epidemiologia , Fatores de Tempo
19.
Rev Bras Epidemiol ; 26: e230008, 2023.
Artigo em Português, Inglês | MEDLINE | ID: mdl-36629620

RESUMO

OBJECTIVE: To identify spatial variability of mortality from breast and cervical cancer and to assess factors associated in the city of São Paulo. METHODS: Between 2009 and 2016, 10,124 deaths from breast cancer and 2,116 deaths from cervical cancer were recorded in the Mortality Information System among women aged 20 years and over. The records were geocoded by address of residence and grouped according to Primary Health Care coverage areas. A spatial regression modeling was put together using the Bayesian approach with a Besag-York-Mollié structure to verify the association of deaths with selected indicators. RESULTS: Mortality rates from these types of cancer showed inverse spatial patterns. These variables were associated with breast cancer mortality: travel time between one and two hours to work (RR - relative risk: 0.97; 95%CI - credible interval: 0.93-1.00); women being the head of the household (RR 0.97; 95%CI 0.94-0.99) and deaths from breast cancer in private health institutions (RR 1.04; 95%CI 1.00-1.07). The following variables were associated with mortality from cervical cancer: travel time to work between half an hour and one hour (RR 0.92; 95%CI 0.87-0.98); per capita household income of up to 3 minimum wages (RR 1.27; 95%CI 1.18-1.37) and ratio of children under one year of age related to the female population aged 15 to 49 years (RR 1.09; 95%CI 1.01-1.18). CONCLUSION: The predicted RR for mortality from these cancers were calculated and associated with the socioeconomic conditions of the areas covered.


OBJETIVO: Identificar a variabilidade espacial da mortalidade por câncer de mama e colo do útero e avaliar fatores associados à mortalidade por esses cânceres no município de São Paulo. MÉTODOS: Entre 2009 e 2016 foram registrados, no Sistema de Informações sobre Mortalidade, 10.124 óbitos por câncer de mama e 2.116 óbitos por câncer do colo do útero em mulheres com 20 anos e mais. Os registros foram geocodificados por endereço de residência e agregados segundo território adstrito. Foram realizadas modelagens de regressão espacial utilizando-se a abordagem bayesiana com estrutura de Besag-York-Mollié para verificar a associação dos óbitos com indicadores selecionados. RESULTADOS: As taxas de mortalidade por esses cânceres apresentaram padrões espaciais inversos. As variáveis associadas à mortalidade por câncer de mama foram: tempo de deslocamento para o trabalho entre uma e duas horas (risco relativo ­ RR 0,97; intervalo de credibilidade ­ IC95% 0,93­1,00); mulheres responsáveis pelo domicílio (RR 0,97; IC95% 0,94­0,99) e óbitos por câncer de mama ocorridos em estabelecimentos privados (RR 1,04; IC95% 1,00­1,07). À mortalidade por câncer do colo do útero, estiveram associados: tempo de deslocamento para o trabalho entre meia e uma hora (RR 0,92; IC95% 0,87­0,98); rendimento domiciliar até três salários-mínimos (RR 1,27; IC95% 1,18­1,37); e razão de menores de um ano em relação à população feminina de 15 a 49 anos (RR 1,09; IC95% 1,01­1,18). CONCLUSÃO: Foram calculados os RR preditos para a mortalidade por esses cânceres, que estiveram associados às condições socioeconômicas das áreas de abrangência.


Assuntos
Neoplasias da Mama , Neoplasias do Colo do Útero , Criança , Humanos , Feminino , Teorema de Bayes , Brasil/epidemiologia , Cidades/epidemiologia , Fatores Socioeconômicos
20.
JCO Precis Oncol ; 7: e2200372, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36634296

RESUMO

PURPOSE: Circulating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) next to CTCs. METHODS: We applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy. RESULTS: CTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001). CONCLUSION: This study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.


Assuntos
Neoplasias da Mama , Células Neoplásicas Circulantes , Feminino , Humanos , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Prognóstico , Estudos Prospectivos , Ensaios Clínicos como Assunto
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