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1.
Br J Radiol ; 95(1129): 20211056, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34762523

RESUMO

OBJECTIVE: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). METHODS: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. RESULTS: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade 1 artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34-13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. CONCLUSIONS: Tumor size, Grade 1 artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. ADVANCES IN KNOWLEDGE: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Abscesso Hepático/etiologia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antineoplásicos/administração & dosagem , Arteriopatias Oclusivas/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/secundário , Quimioembolização Terapêutica/efeitos adversos , Drenagem , Feminino , Artéria Hepática , Humanos , Abscesso Hepático/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral
2.
Br J Radiol ; 95(1129): 20201302, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34767476

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of a radiomics model based on multiregional and multiparametric MRI to classify paediatric posterior fossa tumours (PPFTs), explore the contribution of different MR sequences and tumour subregions in tumour classification, and examine whether contrast-enhanced T1 weighted (T1C) images have irreplaceable added value. METHODS: This retrospective study of 136 PPFTs extracted 11,958 multiregional (enhanced, non-enhanced, and total tumour) features from multiparametric MRI (T1- and T2 weighted, T1C, fluid-attenuated inversion recovery, and diffusion-weighted images). These features were subjected to fast correlation-based feature selection and classified by a support vector machine based on different tasks. Diagnostic performances of multiregional and multiparametric MRI features, different sequences, and different tumoral regions were evaluated using multiclass and one-vs-rest strategies. RESULTS: The established model achieved an overall area under the curve (AUC) of 0.977 in the validation cohort. The performance of PPFTs significantly improved after replacing T1C with apparent diffusion coefficient maps added into the plain scan sequences (AUC from 0.812 to 0.917). When oedema features were added to contrast-enhancing tumour volume, the performance did not significantly improve. CONCLUSION: The radiomics model built by multiregional and multiparametric MRI features allows for the excellent distinction of different PPFTs and provides valuable references for the rational adoption of MR sequences. ADVANCES IN KNOWLEDGE: This study emphasized that T1C has limited added value in predicting PPFTs and should be cautiously adopted. Selecting optimal MR sequences may help guide clinicians to better allocate acquisition sequences and reduce medical costs.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Infratentoriais/diagnóstico por imagem , Imageamento por Ressonância Magnética Multiparamétrica , Área Sob a Curva , Criança , Meios de Contraste , Feminino , Humanos , Neoplasias Infratentoriais/classificação , Neoplasias Infratentoriais/patologia , Masculino , Gradação de Tumores , Estudos Retrospectivos
3.
Oncol Rep ; 47(2)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34859261

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck squamous cell carcinoma (HNSCC) with a poor survival rate. In the present study, the involvement of tectonic 1 (TCTN1) in OSCC was explored. The relevance between TCTN1 and HNSCC clinicopathological features was first analyzed and it was revealed that TCTN1 was associated with the tumor clinical stage and grade. In in vitro experiments, it was demonstrated that the proliferative, migratory and invasive capacity of OSCC CAL27 cells and SCC15 cells was significantly suppressed due to TCTN1 knockdown. Additionally, the core promoter of TCTN1 was confirmed and transcription factor AP­2 alpha (TFAP2A) was suggested as a regulator of TCTN1 mRNA expression. On the whole, the present study elucidated the direct association between TCTN1 and OSCC for the first time, to the best of our knowledge, and the TFAP2A/TCTN1 axis was suggested as a potential novel therapeutic target for OSCC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Bucais/patologia , Gradação de Tumores , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
4.
Anticancer Res ; 42(1): 493-500, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969759

RESUMO

BACKGROUND/AIM: Nuclear factor I (NFI) A and NFIB are transcription factors involved in the regulation of cell differentiation and organ development. More recently, they have been implicated in the pathogenesis of cancer, acting as context-dependent tumor promoters or suppressors. MATERIALS AND METHODS: Expression of NFIA and NFIB was assessed by immunohistochemistry in 136 primary urothelial bladder cancers. RESULTS: Progressive down-regulation of NFIA was observed with increasing pT stages and higher grade of analyzed tumors. Consequently, muscle invasive cancers exhibited lower NFIA expression compared with non-muscle invasive cases. Analogous comparisons yielded negative results in the case of NFIB. Expression of neither protein was associated with patient survival. CONCLUSION: NFIA may act as a suppressor of urothelial carcinogenesis, but functional studies and understanding of post-transcriptional regulation of NFI expression is necessary to dissect its role in bladder malignancies.


Assuntos
Fatores de Transcrição NFI/genética , Invasividade Neoplásica/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Diferenciação Celular/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Gradação de Tumores , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
5.
Anticancer Res ; 42(1): 195-203, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969725

RESUMO

BACKGROUND: Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). PATIENTS AND METHODS: A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. RESULTS: ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). CONCLUSION: ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Linfonodos/cirurgia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia Adjuvante/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfonodos/efeitos da radiação , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Gradação de Tumores , Cuidados Pré-Operatórios/efeitos adversos
6.
J Urol ; 207(1): 61-69, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433303

RESUMO

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Hidrogéis/uso terapêutico , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Técnicas de Ablação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Feminino , Humanos , Hidrogéis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Gradação de Tumores , Invasividade Neoplásica , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
7.
Bone Joint J ; 104-B(1): 168-176, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969280

RESUMO

AIMS: The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients. METHODS: This retrospective multicentre cohort study identified 493 STS patients using clinical databases from six collaborating hospitals in three countries. Centres performed a retrospective data collection for patient demographics, preoperative blood results (CRP and albumin levels and neutrophil, leucocyte, and platelets counts), and oncological outcomes (disease-free survival, local, or metastatic recurrence) with a minimum of two years' follow-up. RESULTS: We found that increased mGPS, tumour size, grade, neutrophil/lymphocyte ratio, and disease recurrence were associated with reduced survival. Importantly, mGPS was the best at stratifying prognosis and could be used in conjunction with tumour grade to sub-stratify patient survival. CONCLUSION: This study demonstrated that prognosis of localized STS strongly correlates with mGPS, as an increasing score is associated with a poorer outcome. We note that 203 patients (41%) with an STS have evidence of systemic inflammation. We recommend the mGPS and other biochemical blood indicators be introduced into the routine diagnostic assessment in STS patients to stratify patient prognosis. Its use will support clinical decision-making, especially when morbid treatment options such as amputation are being considered. Cite this article: Bone Joint J 2022;104-B(1):168-176.


Assuntos
Sarcoma/sangue , Sarcoma/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/análise , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Albumina Sérica/análise , Análise de Sobrevida
8.
Urol Clin North Am ; 49(1): 129-152, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34776047

RESUMO

Organ sparing approaches for the management of localized prostate cancer were developed in part to overcome the morbidity associated with standard, whole gland treatment options. The first description of focal therapy was now over two decades ago and since that time much has changed. The evolution of patient selection, the approach to ablation, and surveillance after focal therapy have mirrored the technologic advancements in the field as well as the improved understanding of the biology of low-grade, low-risk prostate cancer. This review presents the evidence for the basis of focal therapy from the past to the present and future endeavors.


Assuntos
Técnicas de Ablação/métodos , Seleção de Pacientes , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Técnicas de Ablação/tendências , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Imagem Multimodal , Imageamento por Ressonância Magnética Multiparamétrica , Gradação de Tumores , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Fatores de Risco , Ultrassonografia
9.
Int J Gynecol Pathol ; 41(1): 12-19, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33720084

RESUMO

PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next-generation sequencing in identifying PTEN abnormality. IHC and tagged-amplicon next-generation sequencing PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of 5 PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% confidence interval: 62.7-85.5%), a specificity of 84.6% (95% confidence interval: 76.2%-90.9%), and accuracy of 81.2% (95% confidence interval: 74.4%-86.9%) in predicting loss of function PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared with endometrial serous carcinoma (80.0% vs. 19.4%, P<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support the use of ancillary PTEN IHC for diagnostic purposes in endometrial neoplasms. However, for clinical trial design complementary testing of both IHC and sequencing of PTEN should be considered to assess the PTEN status in endometrial carcinomas.


Assuntos
Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , PTEN Fosfo-Hidrolase/genética , Biópsia , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Estudos de Coortes , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Mutação com Perda de Função , Tipagem Molecular , Mutação , Gradação de Tumores , PTEN Fosfo-Hidrolase/metabolismo , Reprodutibilidade dos Testes , Análise de Sequência de DNA
10.
Biomolecules ; 11(12)2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34944493

RESUMO

CD44, a non-kinase cell surface transmembrane glycoprotein, has been widely implicated as a cancer stem cell (CSC) marker in several cancers. Cells overexpressing CD44 possess several CSC traits, such as self-renewal and epithelial-mesenchymal transition (EMT) capability, as well as a resistance to chemo- and radiotherapy. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The interaction of such isoforms with ligands, particularly hyaluronic acid (HA), osteopontin (OPN) and matrix metalloproteinases (MMPs), drive numerous cancer-associated signalling. However, there are contradictory results regarding whether high or low CD44 expression is associated with worsening clinicopathological features, such as a higher tumour histological grade, advanced tumour stage and poorer survival rates. Nonetheless, high CD44 expression significantly contributes to enhanced tumourigenic mechanisms, such as cell proliferation, metastasis, invasion, migration and stemness; hence, CD44 is an important clinical target. This review summarises current research regarding the different CD44 isoform structures and their roles and functions in supporting tumourigenesis and discusses CD44 expression regulation, CD44-signalling pathways and interactions involved in cancer development. The clinical significance and prognostic value of CD44 and the potential of CD44 as a therapeutic target in cancer are also addressed.


Assuntos
Processamento Alternativo , Receptores de Hialuronatos/genética , Neoplasias/patologia , Progressão da Doença , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias/genética , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Análise de Sobrevida
11.
Nat Commun ; 12(1): 7349, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34934057

RESUMO

Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.


Assuntos
Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Plasticidade Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Longo não Codificante/metabolismo , Antagonistas de Androgênios/uso terapêutico , Animais , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/tratamento farmacológico , Linhagem Celular Tumoral , Linhagem da Célula/genética , Núcleo Celular/metabolismo , Proliferação de Células/genética , Estudos de Coortes , Metilação de DNA/genética , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética/efeitos dos fármacos , Genoma Humano , Histonas/metabolismo , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Organoides/metabolismo , Organoides/patologia , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Filogenia , Complexo Repressor Polycomb 2/metabolismo , Regiões Promotoras Genéticas/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Longo não Codificante/genética , Receptores Androgênicos/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Transcrição Genética/efeitos dos fármacos
12.
Bull Cancer ; 108(9S1): S33-S38, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34955160

RESUMO

Oncogenetic testing is now part of standard management in high grade ovarian cancer, including at least mutational status of BRCA1/BRCA2 genes. If necessary, tumor genetic testing is followed by constitutional testing to either confirm the constitutional origin of variants identified in BRCA1/2 genes or detect variants in other predisposition genes. The whole process including prescription of tumoral testing, retrieval of analysis report and communication of results must be formalized, as well as information on possible consequences of the results for the patient and her family. Tumor material must meet criteria of size and cellularity to allow high-quality analysis. These samples are processed during the preanalytical phase with two major steps : time of cold ischemia and fixation. Only pathogenic (Class V) and likely pathogenic (Class IV) variants shown in tumor tissue are mentioned in the report. Currently, only BRCA1 and BRCA2 genes are routinely studied but, in the future, analysis will be extended to other genes involved in homologous recombination repair. In patients without BRCA mutation, other biomarkers reflecting sensitivity to PARP inhibitors, such as HRD scores (homologous recombination deficiency) that appeared recently, will have to be implemented in routine practice in order to better select patients for these treatments and choose optimal therapy.


Assuntos
Genes BRCA1 , Genes BRCA2 , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Distúrbios no Reparo do DNA , Feminino , Testes Genéticos , Humanos , Mutação , Gradação de Tumores , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Fixação de Tecidos/métodos
13.
Bull Cancer ; 108(9S1): S5-S12, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34955161

RESUMO

In early stages, standard treatment is adjuvant chemotherapy, consisting of platinum-based combination for 6 cycles, especially in serous and endometrioid high grade carcinomas. In advanced stages, indication of neoadjuvant chemotherapy must be discussed on a case-by-case basis in multidisciplinary meetings (MDM). Bevacizumab can also be considered in the neoadjuvant setting in some circumstances, always after discussion in MDM. Carboplatin plus paclitaxel every 21 days, with or without bevacizumab remains the standard of care for first-line chemotherapy. Inhibitors of poly-(ADP-riboses) polymerases (PARPi) have been approved and are reimbursed as maintenance monotherapy in tumors carrying BRCA1 or BRCA2 mutation after complete or partial response to chemotherapy. Two recent studies demonstrated the efficacy of PARPi on progression free survival, one for niraparib single-agent in patients with high-grade ovarian carcinoma regardless of BRCA status, the other one for the combination of bevacizumab and olaparib in patients with high grade carcinoma, with positive test for homologous recombination DNA repair deficiency (regardless of BRCA status). These two new modalities of maintenance therapy are now available in compassionate use programs or post compassionate use programs. Depending on pending decisions upon reimbursement, these indications might be somewhat modified.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Algoritmos , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Indazóis/uso terapêutico , Quimioterapia de Manutenção , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/uso terapêutico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Piperidinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
14.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(6): 1062-1071, 2021 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-34970888

RESUMO

Glioma is the most common malignant brain tumor and classification of low grade glioma (LGG) and high grade glioma (HGG) is an important reference of making decisions on patient treatment options and prognosis. This work is largely done manually by pathologist based on an examination of whole slide image (WSI), which is arduous and heavily dependent on doctors' experience. In the World Health Organization (WHO) criteria, grade of glioma is closely related to hypercellularity, nuclear atypia and necrosis. Inspired by this, this paper designed and extracted cell density and atypia features to classify LGG and HGG. First, regions of interest (ROI) were located by analyzing cell density and global density features were extracted as well. Second, local density and atypia features were extracted in ROI. Third, balanced support vector machine (SVM) classifier was trained and tested using 10 selected features. The area under the curve (AUC) and accuracy (ACC) of 5-fold cross validation were 0.92 ± 0.01 and 0.82 ± 0.01 respectively. The results demonstrate that the proposed method of locating ROI is effective and the designed features of density and atypia can be used to predict glioma grade accurately, which can provide reliable basis for clinical diagnosis.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Gradação de Tumores , Máquina de Vetores de Suporte
15.
Cells ; 10(12)2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34944094

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y ≤ 40 years) and elderly (E ≥ 75 years) patients. METHODS: Open access mutational data (WGS or WES) were collected for TNBC and HGSOC patients. Potential driver genes were those that were present in the Cancer Gene Census-CGC, the Candidate Cancer Gene Database-CCGD, or OncoKB and those that were considered pathogenic in variant effect prediction tools. RESULTS: Mutational signature 3 (homologous repair defects) was the only gene that was represented in all four subgroups. The median number of mutated CGCs per sample was similar in HGSOC (Y:3 vs. E:4), but it was higher in elderly TNBC than it was in young TNBC (Y:3 vs. E:6). At least 90% of the samples from TNBC and HGSOC from Y and E patients presented at least one known affected TSG. Besides TP53, which was mutated in 67-83% of the samples, the affected TSG in TP53 wild-type samples were NF1 (yHGSOC and yTNBC), PHF6 (eHGSOC and yTNBC), PTEN, PIK3R1 and ZHFX3 (yTNBC), KMT2C, ARID1B, TBX3, and ATM (eTNBC). A few samples only presented one affected oncogene (but no TSG): KRAS and TSHR in eHGSOC and RAC1 and PREX2 (a regulator of RAC1) in yTNBC. At least ⅔ of the tumors presented mutated oncogenes associated with tumor suppressor genes; the Ras and/or PIK3CA signaling pathways were altered in 15% HGSOC and 20-35% TNBC (Y vs. E); DNA repair genes were mutated in 19-33% of the HGSOC tumors but were more frequently mutated in E-TNBC (56%). However, in HGSOC, 9.5% and 3.3% of the young and elderly patients, respectively, did not present any tumors with an affected CGC nor did 4.65% and none of the young and elderly TNBC patients. CONCLUSION: Most HGSOC and TNBC from young and elderly patients present an affected TSG, mainly TP53, as well as mutational signature 3; however, a few tumors only present an affected oncogene or no affected cancer-causing genes.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Mutação/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Análise Mutacional de DNA , Reparo do DNA/genética , Feminino , Genes Supressores de Tumor , Variação Genética , Humanos , Gradação de Tumores , Oncogenes
16.
Cells ; 10(12)2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34944101

RESUMO

Chondroitin sulfate (CS) is a major component of the extracellular matrix found to be abnormally accumulated in several types of cancer tissues. Previous studies have indicated that CS synthases and modification enzymes are frequently elevated in human gliomas and are associated with poor prognosis. However, the underlying mechanisms of CS in cancer progression and approaches for interrupting its functions in cancer cells remain largely unexplored. Here, we have found that CS was significantly enriched surrounding the vasculature in a subset of glioma tissues, which was akin to the perivascular niche for cancer-initiating cells. Silencing or overexpression of the major CS synthase, chondroitin sulfate synthase 1 (CHSY1), significantly regulated the glioma cell invasive phenotypes and modulated integrin expression. Furthermore, we identified CD44 as a crucial chondroitin sulfate proteoglycan (CSPG) that was modified by CHSY1 on glioma cells, and the suppression of CS formation on CD44 by silencing the CHSY1-inhibited interaction between CD44 and integrin ß1 on the adhesion complex. Moreover, we tested the CS-specific binding peptide, resulting in the suppression of glioma cell mobility in a fashion similar to that observed upon the silencing of CHSY1. In addition, the peptide demonstrated significant affinity to CD44, promoted CD44 degradation, and suppressed integrin ß1 expression in glioma cells. Overall, this study proposes a potential regulatory loop between CS, CD44, and integrin ß1 in glioma cells, and highlights the importance of CS in CD44 stability. Furthermore, the targeting of CS by specific binding peptides has potential as a novel therapeutic strategy for glioma.


Assuntos
Sulfatos de Condroitina/metabolismo , Glioma/metabolismo , Glioma/patologia , Receptores de Hialuronatos/metabolismo , Integrina beta1/metabolismo , Animais , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Glioma/irrigação sanguínea , Glioma/genética , Glucuronosiltransferase/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Enzimas Multifuncionais/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Peptídeos/metabolismo , Fenótipo , Proteólise
17.
Biomolecules ; 11(12)2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34944438

RESUMO

BACKGROUND AND AIMS: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. MATERIALS AND METHODS: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA M.expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression, and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. RESULTS: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signalling pathways in prostate cancer. SUMMARY AND CONCLUSIONS: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Neoplasias da Próstata/patologia , Fatores de Transcrição/genética , Regulação para Cima , Antagonistas de Androgênios/farmacologia , Antineoplásicos/farmacologia , Bases de Dados Genéticas , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Terapia de Alvo Molecular , Gradação de Tumores , Neoplasias da Próstata/genética , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos
19.
Anticancer Res ; 41(11): 5569-5575, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732427

RESUMO

BACKGROUND/AIM: While controversial, cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) and early postoperative intra-peritoneal chemotherapy (EPIC) remains the mainstay of treatment for low grade appendiceal neoplasm with pseudomyxoma peritonei (PMP). Our study aimed to investigate the difference in survival when administering HIPEC alone vs. HIPEC + EPIC. Additionally, we examined whether the duration of EPIC affects survival. PATIENTS AND METHODS: We compared the difference in survival in 238 patients who underwent CRS + HIPEC alone vs. CRS + HIPEC/EPIC combination for low grade appendiceal cancer. We also compared short course (1-2 days) vs. long course (3-5 days) of EPIC. RESULTS: HIPEC/EPIC combination group (n=179) showed a significantly better 5-year survival of 95% compared to 71% in HIPEC alone (n=59). There was no statistically significant difference in 5-year survival between short course (n=22) and long course of EPIC (n=157). CONCLUSION: Combined use of HIPEC and EPIC improves 5-year survival in low-grade appendiceal neoplasm. Two days of EPIC are sufficient.


Assuntos
Neoplasias do Apêndice/terapia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Pseudomixoma Peritoneal/mortalidade , Pseudomixoma Peritoneal/secundário , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Anticancer Res ; 41(11): 5611-5616, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732433

RESUMO

BACKGROUND/AIM: Brain metastasis is a rare condition among patients with soft tissue sarcoma (STS), and its precise incidence remains unclear. The aim of this study was to investigate which patients should be screened for brain metastasis. PATIENTS AND METHODS: We identified all patients with STS diagnosed between 2010 and 2015 in the SEER database. Incidence of brain metastasis at initial presentation and higher incidence of brain metastasis by histological subtype were investigated. In addition, risk factors for brain metastasis were examined. RESULTS: A total of 26,676 patients were included for analysis, of whom 162 patients (0.6%) had brain metastasis. Alveolar soft part sarcoma (6.3%), malignant hemangioendothelioma (3.1%) and malignant schwannoma (2.6%) showed higher incidence of brain metastasis. Deep-rooted tumor, trunk tumor, and histological high-grade tumor tended to show higher incidence of brain metastasis. CONCLUSION: Risk factors for brain metastasis were deep location, trunk development and histologically high-grade tumor, or specific histological subtypes.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Sarcoma/epidemiologia , Sarcoma/secundário , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/patologia , Neoplasias Encefálicas/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Medição de Risco , Fatores de Risco , Programa de SEER , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Fatores de Tempo , Estados Unidos/epidemiologia
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