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1.
Clin Breast Cancer ; 24(1): 72-78.e4, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37867114

RESUMO

BACKGROUND: Sexual well-being is a key determinant of quality of life. Sexual dysfunction in patients with metastatic breast cancer (MBC) is understudied. PATIENTS AND METHODS: Patients were eligible for this study if they participated in the Mayo Clinic Breast Disease Registry (MCBDR), had a diagnosis of de novo MBC, and responded to a question about sexual dysfunction at the baseline MCBDR survey. Participants reported their sexual dysfunction on a scale of 0 (no dysfunction) to 10 (severe dysfunction) at baseline and then annually for 4 years. Participants answered additional sexual symptom questions in years 2 and 4. Associations between patient attributes and the presence and severity of sexual dysfunction, changes in sexual dysfunction from baseline to subsequent surveys, and associations between specific sexual symptoms and severity of sexual dysfunction were assessed. RESULTS: One hundred three patients with de novo MBC answered the sexual dysfunction question at baseline. The prevalence of any sexual dysfunction (score of 1-10) was 56.3% at baseline (n = 103), 57.1 % at year 1 (n = 77), 80.4% at year 2 (n = 46), 65.8% at year 3 (n = 38), and 85% at year 4 (n = 20). Vaginal dryness was reported by approximately 49% and 39% of patients in years 2 and 4 respectively. Vaginal dryness was associated with higher severity of sexual dysfunction. CONCLUSIONS: Self-reported sexual dysfunction is frequent in women with de novo MBC. Vaginal dryness is a frequently reported treatable symptom associated with higher severity of sexual dysfunction. Clinicians should assess patients with MBC for sexual dysfunction and discuss potential treatment strategies.


Assuntos
Neoplasias da Mama , Doenças Vaginais , Humanos , Feminino , Neoplasias da Mama/patologia , Qualidade de Vida , Comportamento Sexual , Doenças Vaginais/patologia , Inquéritos e Questionários , Vagina/patologia
2.
Heliyon ; 9(7): e17712, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37483787

RESUMO

Background: Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC. Methods: A total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used. Results: The rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55-3.76, 1.81-12.45, 1.75-4.07, 1.39-9.35, 1.38-3.30, and 1.71-3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D' = 0.912, r2 = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models. Conclusion: Our case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

3.
Am Soc Clin Oncol Educ Book ; 43: e390464, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37335956

RESUMO

Triple-negative breast cancer (TNBC) is a very heterogeneous and aggressive breast cancer subtype with a high risk of mortality, even if diagnosed early. The mainstay of early-stage breast cancer includes systemic chemotherapy and surgery, with or without radiation therapy. More recently, immunotherapy is approved to treat TNBC, but managing immune-rated adverse events while balancing efficacy is a challenge. The purpose of this review is to highlight the current treatment recommendations for early-stage TNBC and the management of immunotherapy toxicities.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Imunoterapia
4.
Nat Commun ; 14(1): 3306, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286539

RESUMO

High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Fígado/metabolismo , Metilação de DNA , Humanos
5.
Sci Transl Med ; 15(698): eade8732, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37256936

RESUMO

Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1KO) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). Using mouse models of brain metastatic BRAFV600E/PTEN-/- and BRAFV600E/wt/PTEN-/- mutant melanomas, we show that locoregional delivery of TSCs releasing oHSV and GM-CSF (TSC-G) activated dendritic cell- and T cell-mediated immune responses. In addition, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the TSCs composed of SC-oHSV and SCN1KO-releasing GM-CSF and single-chain variable fragment anti-PD-1 (TSC-G/P) had therapeutic efficacy in both syngeneic and patient-derived humanized mouse models of leptomeningeal metastasis. Our findings provide a promising allogeneic SC-based immunotherapeutic strategy against melanomas in the CNS and a road map toward clinical translation.


Assuntos
Neoplasias Encefálicas , Melanoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Camundongos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Edição de Genes , Proteínas Proto-Oncogênicas B-raf , Melanoma/terapia , Melanoma/patologia , Simplexvirus/genética , Vírus Oncolíticos/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Imunoterapia , Células-Tronco , Melanoma Maligno Cutâneo
6.
Genes (Basel) ; 14(4)2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-37107577

RESUMO

Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2 (rs1219648, rs2420946, and rs2981582) variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 (aOR = 2.87, p < 0.0001), additive model 2 (aOR = 5.62, p < 0.0001), the dominant model (aOR = 2.87, p < 0.0001), the recessive model (aOR = 4.04, p < 0.0001), and the allelic model (OR = 2.16, p < 0.0001). This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 (aOR = 2. 60, p = 0.010), the recessive model (aOR = 2.47, p = 0.006), and the allelic model (OR = 1.39, p = 0.016). However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model (aOR = 0.62, p = 0.048). Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/patologia , Predisposição Genética para Doença , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene
7.
BMC Cancer ; 23(1): 172, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36809986

RESUMO

BACKGROUND: Dishevelled paralogs (DVL1, 2, 3) are key mediators of Wnt pathway playing a role in constitutive oncogenic signaling influencing the tumor microenvironment. While previous studies showed correlation of ß-catenin with T cell gene expression, little is known about the role of DVL2 in modulating tumor immunity. This study aimed to uncover the novel interaction between DVL2 and HER2-positive (HER2+) breast cancer (BC) in regulating tumor immunity and disease progression. METHODS: DVL2 loss of function studies were performed with or without a clinically approved HER2 inhibitor, Neratinib in two different HER2+ BC cell lines. We analyzed RNA (RT-qPCR) and protein (western blot) expression of classic Wnt markers and performed cell proliferation and cell cycle analyses by live cell imaging and flow cytometry, respectively. A pilot study in 24 HER2+ BC patients was performed to dissect the role of DVL2 in tumor immunity. Retrospective chart review on patient records and banked tissue histology were performed. Data were analyzed in SPSS (version 25) and GraphPad Prism (version 7) at a significance p < 0.05. RESULTS: DVL2 regulates the transcription of immune modulatory genes involved in antigen presentation and T cell maintenance. DVL2 loss of function down regulated mRNA expression of Wnt target genes involved in cell proliferation, migration, invasion in HER2+ BC cell lines (±Neratinib). Similarly, live cell proliferation and cell cycle analyses reveal that DVL2 knockdown (±Neratinib) resulted in reduced proliferation, higher growth arrest (G1), limited mitosis (G2/M) compared to non-targeted control in one of the two cell lines used. Analyses on patient tissues who received neoadjuvant chemotherapy (n = 14) further demonstrate that higher DVL2 expression at baseline biopsy pose a significant negative correlation with % CD8α levels (r = - 0.67, p < 0.05) while have a positive correlation with NLR (r = 0.58, p < 0.05), where high NLR denotes worse cancer prognosis. These results from our pilot study reveal interesting roles of DVL2 proteins in regulating tumor immune microenvironment and clinical predictors of survival in HER2+ BC. CONCLUSION: Our study demonstrates potential immune regulatory role of DVL2 proteins in HER2+ BC. More in-depth mechanistic studies of DVL paralogs and their influence on anti-tumor immunity may provide insight into DVLs as potential therapeutic targets benefiting BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Proteínas Desgrenhadas/genética , Estudos Retrospectivos , Projetos Piloto , Via de Sinalização Wnt , Imunidade Celular , Proliferação de Células , Microambiente Tumoral
8.
Heliyon ; 8(12): e11843, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36478837

RESUMO

This research aims to extract essential oils from the peel of two varieties of Citrus maxima- White pomelo and Red pomelo of Bangladeshi origin by hydrodistillation (HD) method and characterization of the extracted oils. The study also looked into the effect of different conditions, such as type of peels, and extraction time, on the yield amount. To determine the chemical components of oil, the Gas Chromatography-mass spectrum (GC-MS) technique has been used. The three major components were, for white pomelo, limonene (67.58%), ß-linalool (7.53%) and Neral (6.61%), and for red pomelo, limonene (73.82%), ß-linalool (5.42%) and Neral (4.11%). The morphological changes in the oil glands of the peels of both varieties were compared to understand changes before and after the extraction. The result showed that white pomelo (WP) provides a slightly higher yield percentage in similar extraction time than red pomelo (RP), 1.09 and 0.96%, respectively. GC-MS results showed that the presence of limonene is the highest for both pomelos, although the amount is higher in RP than that of WP. However, the digital microscopy showed the drawbacks of the hydrodistillation process. The pressure in the oil glands during the distillation is too low to rupture the oil glands fully. This study will be able to broaden the path for future studies on related physicochemical and biochemical properties of pomelo varieties of Bangladesh.

9.
Breast ; 66: 272-277, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36375388

RESUMO

BACKGROUND: Few studies have examined detailed features of pregnancy and the postpartum period as potential risk factors for early onset breast cancer (BC) by molecular subtype. These data may have value for improving risk assessment and prevention. METHODS: We surveyed parous enrollees in the prospective Mayo Clinic Breast Disease Registry (MCBDR) who had been diagnosed with BC at age <55 years between 2015 and 2020. Summary statistics were used to describe survey responses and reproductive risk factors by BC subtype (defined by estrogen/progesterone receptors and human epidermal growth factor receptor expression, nurse-abstracted from the medical record). Associations were assessed with Kruskal-Wallis and Chi-Square tests, followed by age-adjusted linear and logistic regression models. We compared results from this parous cohort to those from a separate cohort of nulliparous MCBDR participants with BC diagnosed at age <55 years. RESULTS: In 436 parous respondents with subtype data abstracted, we identified a higher frequency of BRCA1 mutation, earlier age at diagnosis, and lower BI in patients with triple negative BC. Comparing parous to nulliparous young women with breast cancer, the proportion with TNBC was larger in the latter (12.2% vs. 15.1%, p = 0.03). CONCLUSIONS: Early age at diagnosis and deleterious BRCA1 mutation were more frequent among TNBC patients. In addition, parous young women with TNBC had a lower BI than those with other BC subtypes, a hypothesis-generating finding that supports the need for additional research on the cycle of pregnancy-lactation-postpartum involution and BC etiology.


Assuntos
Doenças Mamárias , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Gravidez , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Neoplasias de Mama Triplo Negativas/etiologia , Neoplasias de Mama Triplo Negativas/genética , Estudos Prospectivos , Fatores de Risco , Mama/metabolismo , Medição de Risco , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo
10.
Rev. argent. microbiol ; 54(3): 61-70, set. 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1407196

RESUMO

Resumen Este estudio tuvo como objetivo aislar, caracterizar e identificar bacterias de control biológico que poseen actividad antifúngica de amplio espectro de la filosfera de diferentes cultivos, incluidos el maíz, el trigo y la papa, así como evaluar su actividad en la promoción del crecimiento. En este estudio, 14/113 bacterias de control biológico mostraron actividad antifúngica. Los aislamientos bacterianos M11 y M33 (de maíz), del total de 113, fueron reseleccionados debido a su fuerte actividad antifúngica de amplio espectro (más del 50%) después de su evaluación contra cuatro hongos fitopatógenos que afectan cultivos de alta importancia económica, entre ellos, Alternaría alternata, Rhizoctonia solani, Fusarium oxysporum y Fusarium verticillioides. Los aislamientos se evaluaron, adicionalmente, para determinar los rasgos que promueven el crecimiento de las plantas, es decir, producción de ácido indolacético, solubilización de fosfato, producción de celulasa, compuestos orgánicos volátiles microbianos, cianuro de hidrógeno y sideróforos. Las 14 cepas aisladas mostraron resultados positivos para la producción de la hormona ácido indolacético y la enzima celulasa; 10 cepas fueron positivas para la producción de cianuro de hidrógeno. Además, se observó producción de sideróforos en el caso de 7 cepas, mientras que 5 pudieron solubilizar fosfato inorgánico. Los compuestos orgánicos volátiles microbianos solo fueron sintetizados por los aislamientos M11 y M33, que fueron identificados como Bacillus amyloliquefaciens y Bacillus subtilis, respectivamente, mediante secuenciación del gen ARNr 16S. El estudio de supervivencia mostró que las bacterias de control biológico, es decir, B. amyloliquefaciens y B. subtilis, tienen la capacidad de sobrevivir sobre un sustrato a base de melasa, por un período de tres meses.

11.
Genet Res (Camb) ; 2022: 1740768, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620275

RESUMO

POLD1 (DNA polymerase delta 1, catalytic subunit) is a protein-coding gene that encodes the large catalytic subunit (POLD1/p125) of the DNA polymerase delta (Polδ) complex. The consequence of missense or nonsynonymous SNPs (nsSNPs), which occur in the coding region of a specific gene, is the replacement of single amino acid. It may also change the structure, stability, and/or functions of the protein. Mutation in the POLD1 gene is associated with autosomal dominant predisposition to colonic adenomatous polyps, colon cancer, endometrial cancer (EDMC), breast cancer, and brain tumors. These de novo mutations in the POLD1 gene also result in autosomal dominant MDPL syndrome (mandibular hypoplasia, deafness, progeroid features, and lipodystrophy). In this study, genetic variations of POLD1 which may affect the structure and/or function were analyzed using different types of bioinformatics tools. A total of 17038 nsSNPs for POLD1 were collected from the NCBI database, among which 1317 were missense variants. Out of all missense nsSNPs, 28 were found to be deleterious functionally and structurally. Among these deleterious nsSNPs, 23 showed a conservation scale of >5, 2 were predicted to be associated with binding site formation, and one acted as a posttranslational modification site. All of them were involved in coil, extracellular structures, or helix formation, and some cause the change in size, charge, and hydrophobicity.


Assuntos
DNA Polimerase III , Lipodistrofia , DNA Polimerase III/química , DNA Polimerase III/genética , DNA Polimerase III/metabolismo , Humanos , Lipodistrofia/complicações , Lipodistrofia/genética , Lipodistrofia/patologia , Mutação , Polimorfismo de Nucleotídeo Único/genética , Síndrome
12.
J Clin Oncol ; 40(15): 1604-1610, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35226513

RESUMO

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias da Mama/terapia , Feminino , Humanos , Oncologia
13.
Viruses ; 13(9)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34578321

RESUMO

Herpes simplex virus (HSV) can be genetically altered to acquire oncolytic properties so that oncolytic HSV (oHSV) preferentially replicates in and kills cancer cells, while sparing normal cells, and inducing anti-tumor immune responses. Over the last three decades, a better understanding of HSV genes and functions, and improved genetic-engineering techniques led to the development of oHSV as a novel immunovirotherapy. The concept of in situ cancer vaccination (ISCV) was first introduced when oHSV was found to induce a specific systemic anti-tumor immune response with an abscopal effect on non-injected tumors, in the process of directly killing tumor cells. Thus, the use of oHSV for tumor vaccination in situ is antigen-agnostic. The research and development of oHSVs have moved rapidly, with the field of oncolytic viruses invigorated by the FDA/EMA approval of oHSV talimogene laherparepvec in 2015 for the treatment of advanced melanoma. Immunovirotherapy can be enhanced by arming oHSV with immunomodulatory transgenes and/or using them in combination with other chemotherapeutic and immunotherapeutic agents. This review offers an overview of the development of oHSV as an agent for ISCV against solid tumors, describing the multitude of different oHSVs and their efficacy in immunocompetent mouse models and in clinical trials.


Assuntos
Imunoterapia/métodos , Neoplasias/prevenção & controle , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Vacinação , Animais , Produtos Biológicos , Herpes Simples/genética , Herpesvirus Humano 1 , Humanos , Melanoma , Camundongos , Vírus Oncolíticos , Transgenes
14.
Cureus ; 13(5): e15282, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34194883

RESUMO

Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Ado-trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate, consisting of trastuzumab and a microtubule inhibitor DM1, which has been approved for HER2-positive breast cancer. T-DM1 has also been found to cause significant PN, including PSN. Methods We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials using T-DM1 in the experimental arm and a taxane-based regimen in the control arm to determine the relative risk of PN and PSN associated with T-DM1 as compared to taxanes. A total of 1,857 patients were included in the analysis. The Cochran-Mantel-Haenszel method and the random-effects model were used to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI) for all-grade and grade ≥3 PN and PSN.  Results The relative risks of all-grade PN and all-grade PSN were lower with T-DM1 compared to taxanes. The pooled RR of all-grade PN was 0.59, 95% CI: 0.39-0.89, P = 0.01, and the pooled RR of all-grade PSN was 0.58, 95% CI: 0.46-0.74, P < 0.0001. Conclusions Our meta-analysis demonstrated that T-DM1 is associated with a relatively lower risk of all-grade PN and PSN than the taxane-based regimens for HER2-positive cancers. It could be an area of consideration in selecting therapy for HER2-positive breast cancer patients at high risk of developing or having pre-existing PN and PSN.

15.
Mol Cell Endocrinol ; 531: 111324, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34000352

RESUMO

Approximately 70%-85% of breast cancers express androgen receptors (ARs). The role of AR in breast cancer pathogenesis is currently in exploration. Both androgens and anti-androgens have demonstrated variable inhibitory and stimulatory effects in AR-positive breast cancer depending on estrogen receptor and HER2 co-expression. Androgen signaling pathways interact with other critical cellular pathways, such as the PI3K/AKT/mTOR, Ras/Raf/MAPK/ERK, Wnt/ß-catenin, and estrogen signaling pathways. Therapeutic exploitation of AR has been the crux of management of prostate cancer for decades. In recent years there has been increasing interest in AR as a novel therapeutic target in breast cancer. There have been many early phase clinical trials evaluating the safety and efficacy of various AR-targeted agents in breast cancer. Some of these studies have shown promising clinical benefits. Studies of biomarkers to identify the patients likely to benefit from AR-targeted therapies are currently in progress. Besides, AR expression may be an important prognostic and predictive marker for breast cancer, which needs to be defined better in future studies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Receptores Androgênicos/metabolismo , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos
16.
Cureus ; 13(3): e13854, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33859904

RESUMO

Breast cancer is the most common malignancy affecting women worldwide, and early diagnosis of breast cancer is the key to its successful and effective treatment. Traditional imaging techniques such as mammography and ultrasound are used to detect and configure breast abnormalities; unfortunately, these modalities have low sensitivity and specificity, particularly in young patients with dense breast tissue, breast implants, or post-surgical scar/architecture distortions. Therefore, breast magnetic resonance imaging (MRI) has been superior in the characterization and detection of breast cancer, especially that with invasive features. This review article explores the importance of breast MRI in the early detection of invasive breast cancer versus traditional tools, including mammography and ultrasound, while also analyzing the use of MRI as a screening tool for high-risk women. We will also discuss the different MRI features for invasive ductal carcinoma and lobular carcinoma and the role of breast MRI in the detection of ductal carcinoma in situ with a focus on the utilization of new techniques, including MR spectroscopy and diffusion-weighted imaging.

17.
Mol Cell Endocrinol ; 530: 111284, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33882282

RESUMO

Breast cancer (BC) is the most common non-cutaneous malignancy among women worldwide and is a significant cause of morbidity, mortality, and national health care expenditure. Unfortunately, with few exceptions like alcohol consumption, obesity, and physical activity, most BC risk factors are unmodifiable. Antiestrogen endocrine therapy, commonly known as BC chemoprevention, is an effective method of BC prevention. In multiple randomized trials, two selective estrogen receptor modulators - tamoxifen and raloxifene, and two aromatase inhibitors - exemestane and anastrozole have reduced BC incidence by 50%-65% in high-risk women. An estimated 15% of the US women between 35 and 79 years of age may qualify as high risk for BC, yet a small percentage of these women will ever have a formal BC risk assessment or a discussion of endocrine prevention options. The etiology of underutilization of endocrine prevention of BC is multifactorial - infrequent use of BC risk assessment tools in the primary care settings, insufficient knowledge of BC risk assessment tools and antiestrogen agents among primary care providers, concerns of side effects, inadequate time for counseling during primary care visit, and lack of predictive biomarkers may play significant roles. Many small studies incorporating risk assessment tools and decision-making aids showed minimal success in enhancing endocrine prevention. One critical factor for underutilization of endocrine prevention is low uptake of endocrine prevention by high-risk women even when appropriately recommended. Furthermore, adherence to BC endocrine prevention is unsatisfactorily low. Despite the current infrequent usage, endocrine prevention has the potential to reduce the public health burden of BC significantly. Innovative approaches like finding new agents, alternative dosing and schedule of currently available agents, transdermal medication delivery, increased public and professional awareness, and policymakers' commitments may bring the desired changes.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Cooperação e Adesão ao Tratamento
18.
Psychooncology ; 30(6): 970-978, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33484026

RESUMO

OBJECTIVE: Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS: We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS: Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS: BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Idoso , Cognição , Feminino , Humanos , Sobreviventes
19.
J Chemother ; 33(2): 116-121, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32619151

RESUMO

Docetaxel is an anti-microtubule agent and a highly effective treatment of locally advanced and metastatic breast cancer. There are several adverse effects associated with docetaxel, such as myelosuppression, peripheral neuropathy, fluid retention, and asthenia. One of the most well-known side-effects of this medication is mild to moderate myalgia. Here, we report a case of a 49-year-old female with stage 3 breast cancers who developed severe acute myositis following docetaxel use. The mechanism of docetaxel-induced myositis remains unclear; however, physicians still need to be aware of the possibility of this complication in patients with cancer and a history of exposure to this medication.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Docetaxel/efeitos adversos , Miosite/induzido quimicamente , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade
20.
Cureus ; 12(11): e11598, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33364119

RESUMO

Heart failure is a life-threatening condition that affects millions worldwide and is only expected to get worse with an ageing population. Current treatment regimens rely on medical therapy and heart transplantation as a last resort. Stem cells have been undergoing clinical trials worldwide as a hope for a new and safe clinical treatment. Skeletal myoblasts and bone marrow-derived stem cells are two types of stem cells being tested. The objective is to evaluate the efficacy of these two types of stem cells for heart failure therapy. Data were searched in PubMed using both regular and Medical Subject Heading (MeSH) keywords (stem cells, therapy, heart failure) and then filtered using inclusion/exclusion criteria (language, species, publication date, and age). In total, 31 research articles were reviewed (14 clinical trials, four randomized control trials, nine review articles, one case report, one comparative study, one systematic review, and one categorized as a systematic review and meta-analysis). Both skeletal myoblasts and bone marrow-derived stem cells showed mixed results in improving left ventricular ejection fraction in heart failure patients in the majority of studies. Larger studies need to be done to further investigate the efficacy of stem cells as a therapy for heart failure.

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