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1.
J Med Chem ; 67(13): 10906-10927, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38913493

RESUMO

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.


Assuntos
Antineoplásicos , Receptor Tirosina Quinase Axl , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Microambiente Tumoral , c-Mer Tirosina Quinase , Animais , Microambiente Tumoral/efeitos dos fármacos , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , c-Mer Tirosina Quinase/antagonistas & inibidores , c-Mer Tirosina Quinase/metabolismo , Camundongos , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Descoberta de Drogas , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/síntese química , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Proliferação de Células/efeitos dos fármacos
2.
J Med Chem ; 66(4): 2566-2588, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36749735

RESUMO

The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is described. First, selectivity for mutant EGFR was accomplished by replacing the (S)-2-phenylglycinol moiety of 12 with either an ethanol or an alkyl substituent. Then, the cellular potency and physicochemical properties were optimized through insights from molecular modeling studies by implanting various solubilizing groups in phenyl rings A and B. Optimized lead 52 shows 8-fold selective inhibition of H1975 (EGFRL858R/T790M overexpressing) cancer cells over A431 (EGFRWT overexpressing) cancer cells; western blot analysis further confirmed EGFR mutant-selective target modulation inside the cancer cells by 52. Notably, 52 displayed in vivo antitumor effects in two different mouse xenograft models (BaF3 transfected with mutant EGFR and H1975 tumors) with TGI = 74.9 and 97.5% after oral administration (F = 27%), respectively. With an extraordinary kinome selectivity (S(10) score of 0.017), 52 undergoes detailed preclinical development.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Pirimidinas , Animais , Humanos , Camundongos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Administração Oral , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia
3.
J Biomed Sci ; 29(1): 68, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096815

RESUMO

The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Vacinas Virais , Antivirais/farmacologia , Antivirais/uso terapêutico , Vacina BNT162 , COVID-19/prevenção & controle , Humanos , SARS-CoV-2 , Vacinas Virais/uso terapêutico
4.
Eur J Med Chem ; 224: 113673, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34303872

RESUMO

Rare oncogenic NTRK gene fusions result in uncontrolled TRK signaling leading to various adult and pediatric solid tumors. Based on the architecture of our multi-targeted clinical candidate BPR1K871 (10), we designed and synthesized a series of quinazoline compounds as selective and orally bioavailable type II TRK inhibitors. Property-driven and lead optimization strategies informed by structure-activity relationship studies led to the identification of 39, which showed higher (about 15-fold) selectivity for TRKA over AURA and AURB, as well as potent cellular activity (IC50 = 56.4 nM) against the KM12 human colorectal cancer cell line. 39 also displayed good AUC and oral bioavailability (F = 27%), excellent in vivo efficacy (TGI = 64%) in a KM12 xenograft model, and broad-spectrum anti-TRK mutant potency (IC50 = 3.74-151.4 nM), especially in the double-mutant TRKA enzymatic assays. 39 is therefore proposed for further development as a next-generation, selective, and orally-administered type II TRK inhibitor.


Assuntos
Desenho de Fármacos , Inibidores de Proteínas Quinases/química , Receptor trkA/antagonistas & inibidores , Administração Oral , Animais , Aurora Quinase A/antagonistas & inibidores , Aurora Quinase A/metabolismo , Aurora Quinase B/antagonistas & inibidores , Aurora Quinase B/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Meia-Vida , Humanos , Camundongos , Camundongos Nus , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Ratos , Receptor trkA/metabolismo , Relação Estrutura-Atividade , Transplante Heterólogo
5.
ACS Omega ; 6(9): 6100-6111, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33718701

RESUMO

G9a protein methyltransferase is a potential epigenetic drug target in different cancers and other disease conditions overexpressing the enzyme. G9a is responsible for the H3K9 dimethylation mark, which epigenetically regulates gene expression. Arg8 and Lys9 of the H3 substrate peptide are the two crucial residues for substrate-specific recognition and methylation. Several substrate competitive inhibitors are reported for the potent inhibition of G9a by incorporating lysine mimic groups in the inhibitor design. In this study, we explored the concept of arginine mimic strategy. The hydrophobic segment of the reported inhibitors BIX-01294 and UNC0638 was replaced by a guanidine moiety (side-chain moiety of arginine). The newly substituted guanidine moieties of the inhibitors were positioned similar to the Arg8 of the substrate peptide in molecular docking. Additionally, improved reactivity of the guanidine-substituted inhibitors was observed in density functional theory studies. Molecular dynamics, molecular mechanics Poisson-Boltzmann surface area binding free energy, linear interaction energy, and potential mean force calculated from steered molecular dynamics simulations of the newly designed analogues show enhanced conformational stability and improved H-bond potential and binding affinity toward the target G9a. Moreover, the presence of both lysine and arginine mimics together shows a drastic increase in the binding affinity of the inhibitor towards G9a. Hence, we propose incorporating a guanidine group to imitate the substrate arginine's side chain in the inhibitor design to improve the potency of G9a inhibitors.

6.
Acta Pharm Sin B ; 10(7): 1309-1320, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32874830

RESUMO

Hepsin, a transmembrane serine protease abundant in renal endothelial cells, is a promising therapeutic target against several cancers, particularly prostate cancer. It is involved in the release and polymerization of uromodulin in the urine, which plays a role in kidney stone formation. In this work, we design new potential hepsin inhibitors for high activity, improved specificity towards hepsin, and promising ADMET properties. The ligands were developed in silico through a novel hierarchical pipeline. This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA (human hepatocyte growth factor activator). We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions. The ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental studies. The computational pipeline proposed is remarkably cost-efficient and can be easily adapted for designing inhibitors against new drug targets.

7.
Bioorg Chem ; 98: 103689, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171993

RESUMO

In an effort to develop new cancer therapeutics, we have reported clinical candidate BPR1K871 (1) as a potentanticancercompound in MOLM-13 and MV4-11 leukemia models, as well as in colorectal and pancreatic animal models. As BPR1K871 lacks oral bioavailability, we continued searching for orally bioavailable analogs through drug-like property optimization. We optimized both the physicochemical properties (PCP) as well as in vitro rat liver microsomal stability of 1, with concomitant monitoring of aurora kinase enzyme inhibition as well as cellular anti-proliferative activity in HCT-116 cell line. Structural modification at the 6- and 7-position of quinazoline core of 1 led to the identification of 34 as an orally bioavailable (F% = 54) multi-kinase inhibitor, which exhibits potent anti-proliferative activity against various cancer cell lines. Quinazoline 34 is selected as a promising oral lead candidate for further preclinical evaluation.


Assuntos
Antineoplásicos/farmacologia , Aurora Quinases/antagonistas & inibidores , Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Aurora Quinases/metabolismo , Disponibilidade Biológica , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Masculino , Estrutura Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/química , Quinazolinas/administração & dosagem , Quinazolinas/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
10.
Brain Pathol ; 19(2): 333-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19291000

RESUMO

Lipoastrocytomas are rare and only four cases have been reported previously. Our case is in the fourth ventricle of a 32 year-old man.Many areas showed tumor cells with a signet-ring appearance and focally formed perivascular arrangements. Eosinophilic granular bodies were frequent. There was strong positive immunoreactivity to GFAP and S-100 protein, even in those vacuolated tumor cells.The proliferation index was less than 10%. Ultrastructural studies showed that the signet-ring cells had large lipid droplets as well as intermediate filaments. Ultrastructural features characteristic of ependymomas were not seen. These findings confirm that the vacuoles were lipid droplets in astrocytic tumor cells. The features noted are suggestive of a probable better prognosis in this variant of low-grade astrocytoma.


Assuntos
Astrocitoma/patologia , Neoplasias do Ventrículo Cerebral/patologia , Adulto , Astrocitoma/diagnóstico , Neoplasias do Ventrículo Cerebral/diagnóstico , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Proteínas S100/metabolismo
11.
Cancer Biol Ther ; 7(5): 777-82, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18376139

RESUMO

Krüppel-like factor 4 (KLF4) is a transcription factor regulating cell growth and differentiation. It has been postulated as a tumor suppressor gene in several tumors including colon cancer and prostate cancer; whereas, it is activated in other tumors such as breast cancer and oropharyngeal carcinomas. To understand the significance KLF4 on clinicopathologic implications in human squamous cell carcinoma skin (SCC) progression, thirty six formalin-fixed paraffin-embedded samples of cutaneous SCC and 28 samples of Bowen's disease were stained with anti-KLF4 antibodies. A semiquantitative evaluation of the degree of staining intensity and localization of expression were analyzed and correlated with histological and clinical features. Nuclear KLF4 staining was seen in differentiated epithelium including suprabasal keratinocyte of non-lesional skin. Strong nuclear KLF4 staining was observed in tumor parts of both SCC and Bowen's disease, when compared with their non-tumor parts (p = 0.001). Increased expression of KLF4 protein and mRNA were found in squamous cell carcinoma cell line studies and fresh skin tissue respectively, using western blotting and semi-quantitative real time polymerase chain reaction (PCR). SCC with moderately and poorly differentiated tumors tend to have maturation independent (MI) staining pattern (p = 0.0004), compared to maturation dependent (MD) staining in well-differentiated tumors. Finally, constitutive nuclear KLF4 staining pattern was significantly associated with moderately and poorly differentiated tumors (p = 0.0006), and tumor metastasis (p = 0.024). We propose that KLF4 expression is associated with human skin SCC progression and metastases.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Cutâneas/metabolismo , Idoso , Diferenciação Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Progressão da Doença , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
12.
J Clin Neurosci ; 12(8): 930-3, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16326273

RESUMO

Interleukin-6 (IL-6) is frequently produced in gliomas and has been implicated as a mediator of growth control in several human neoplasms. In this study, IL-6 expression was examined in 11 surgically resected glioblastomas and a cell line U87MG by immunohistochemical staining and quantitative real-time RT-PCR. The relationships between IL-6 expression level and clinical presentation, survival, imaging findings, age and preoperative Karnofsky performance status were analyzed. The median survival times were 16 months in patients with negative IL-6 expression and 7 months in those with positive IL-6 expression (P = 0.075). Three of these patients with a relatively longer survival time (> 1 year) did not express IL-6 in the tumor. Relatively more severe peri-focal edema on imaging was also noted in the glioblastomas with IL-6 expression. IL-6 was also found in the cytoplasm of endothelial cells of newly formed vessels and infiltrating inflammatory cells. These preliminary results implicate IL-6 expression as a possible prognostic indicator in glioblastoma. This cytokine may also play a role in tissue edema, angiogenesis and inflammation of this tumor, but whether IL-6 expression promotes malignancy is uncertain.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Interleucina-6/biossíntese , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Expressão Gênica , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Prognóstico , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
J Clin Gastroenterol ; 39(1): 50-5, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15599211

RESUMO

BACKGROUND: Although Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the two major causes of gastric ulcer, their interaction remains controversial. We constructed a prospective cohort study to evaluate how these two factors influence the expression of COX-2 mRNA in gastric antral, corpus mucosa, and gastric ulcer. METHODS: Tissues were obtained by endoscopic biopsy of gastric antral, corpus mucosa, and gastric ulcer. The presence of H. pylori was determined by culture or histology using Giemsa stain. NSAID use was assessed by structured questionnaire and medical record review. The expression of COX-2 mRNA was detected by the TaqMan quantitative RT-PCR system. RESULTS: H. pylori infection was associated with increased COX-2 expression only in antral mucosa (0.77 +/- 0.13 vs. 0.31 +/- 0.07, P < 0.01). NSAID use was significantly associated with decreased COX-2 expression in ulcer (4.49 +/- 1.50 vs. 9.82 +/- 2.48, P < 0.05) but not in antral or corpus mucosa. Regarding the interaction between H. pylori and NSAID, we found that H. pylori infection was associated with increased COX-2 expression in antral mucosa for both NSAID users and nonusers. In NSAID users, H. pylori infection was not associated with increased COX-2 expression in ulcer edge. CONCLUSION: H. pylori infection was associated with increased COX-2 expression in gastric antral mucosa for both NSAID users and nonusers, but not in gastric ulcer, where the effect of NSAID inhibition plays a major role. With these observations, we can interpret indirectly that H. pylori eradication does not interfere with gastric ulcer healing in NSAID users.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Infecções por Helicobacter/complicações , Helicobacter pylori , Prostaglandina-Endoperóxido Sintases/genética , Antro Pilórico , RNA Mensageiro/biossíntese , Úlcera Gástrica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ciclo-Oxigenase 2 , Feminino , Mucosa Gástrica , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade
14.
Pediatr Neurol ; 31(5): 374-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15519124

RESUMO

This report describes a child having the syndrome of overlapping phenotypic features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Mitochondrial DNA analysis revealed a point mutation at position A3243G, whereas activity of thymidine phosphorylase and its corresponding gene analysis were normal. The most striking feature of this case was paralysis of one segment of the terminal ileum observed on laparotomy. The electron microscopic findings of the resected ileum and colon by limited right hemicolectomy disclosed accumulation of numerous enlarged mitochondria with ill-defined cristae which were similar to mitochondria reported in three previous MELAS cases and one MNGIE case with intestinal dysmotility. We emphasize that the MELAS and MNGIE phenotypes overlapped in this case and that the mechanism of acute ileus in MELAS was associated with functional paralysis of the intestine.


Assuntos
Pseudo-Obstrução Intestinal/etiologia , Pseudo-Obstrução Intestinal/patologia , Síndrome MELAS/complicações , Síndrome MELAS/patologia , Doença Aguda , Adolescente , Encéfalo/patologia , Humanos , Intestino Delgado/patologia , Síndrome MELAS/genética , Imageamento por Ressonância Magnética , Masculino , Mitocôndrias/patologia , Fenótipo , Mutação Puntual
15.
Artigo em Inglês | MEDLINE | ID: mdl-12686931

RESUMO

We report a case of amyloidosis localized to the medium-sized arteries of the face and presenting as prominent perioral swelling. The condition was identified as primary AL-type amyloidosis on the basis of immunohistochemical reactivity, predominantly for anti-lambda light chain antibody within amyloid deposits. Subsequent radiographic and laboratory evaluation of the patient disclosed multiple myeloma. Although amyloid deposits were subsequently detected in the temporal arteries, evidence of widespread amyloidosis has not been observed after 1 year of follow-up. To the best of our knowledge, this is the first report of myeloma-associated amyloidosis mainly localized to the medium-sized arteries of the face.


Assuntos
Amiloidose/diagnóstico , Face/irrigação sanguínea , Boca/irrigação sanguínea , Artérias/patologia , Diagnóstico Diferencial , Seguimentos , Humanos , Cadeias lambda de Imunoglobulina/análise , Imuno-Histoquímica , Lábio/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Artérias Temporais/patologia , Doenças Vasculares/diagnóstico
16.
Cancer Lett ; 188(1-2): 199-205, 2002 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-12406565

RESUMO

This study was designed to elucidate the possible relationship between the expression of cytosolic carbonic anhydrase (CA) and non-small cell lung cancer (NSCLC). The activity and protein expression patterns of carbonic anhydrase I (CAI) and II (CAII) of 70 NSCLC patients were analyzed by CA activity analysis, immunoblotting and immunohistochemical staining. The results showed that the CA activity and protein expression were significantly decreased in both squamous cell carcinoma (SCC) and adenocarcinoma (AD) (P<0.001 and P<0.001). From our study, it was suggested that the reduction of CAI and CAII in both SCC and AD patients may promote tumor cell motility and contribute to tumor growth and metastasis.


Assuntos
Biomarcadores Tumorais/metabolismo , Anidrase Carbônica II/metabolismo , Anidrase Carbônica I/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Neoplasias Pulmonares/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Citosol , Regulação para Baixo , Feminino , Humanos , Immunoblotting , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Zhonghua Yi Xue Za Zhi (Taipei) ; 65(10): 494-7, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12523815

RESUMO

Collagenous spherulosis (CS) is a rare benign lesion which typically presents as an incidental microscopic finding accompanying other breast lesions. Pathologists who are not familiar with this entity occasionally misdiagnose CS as adenoid cystic carcinoma (ACC), cribriform ductal carcinoma in situ (C-DCIS), or atypical intraductal hyperplasia (AIH), especially when it presents as a mass. It is of utmost importance to differentiate benign CS from its malignant mimics in order to avoid unnecessary treatment. We report an unusual case of CS manifested as a mass in the right breast of a 45-year-old female and discuss the problems of differential diagnosis and histogenesis.


Assuntos
Doenças Mamárias/patologia , Mama/patologia , Colágeno/metabolismo , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Adenoide Cístico/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade
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