Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.276
Filtrar
1.
Medicine (Baltimore) ; 100(38): e27305, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559145

RESUMO

ABSTRACT: This study aimed to retrospectively analyze risk factors for the prognosis of Chinese patients with endometrial carcinoma.Total 600 patients who were admitted to the Department of Gynecology, the Fourth Hospital of Hebei Medical University and were pathologically diagnosed as endometrial carcinoma after surgery from January 1, 1997 to December 31, 2006 were selected, and the related factors affecting their prognosis were analyzed.The survival of 600 patients with endometrial carcinoma was 2 to 136.5 months (average survival 57.39 ±â€Š33.55 months), and 109 cases (18.2%) died from endometrial cancer. The overall survival rate of 1, 3, and 5 years after surgery was 96.8%, 89.9%, and 82.1%, respectively. Univariate analysis showed that age, menopausal status, pathological type, histological grade, pathological staging, tumor size, myometrial invasion, cervical involvement, ovarian metastasis, lymph node metastasis, and treatment method were the factors affecting the prognosis of endometrial carcinoma. Multivariate regression analysis showed that pathological type, histological grade, pathological staging, and cervical involvement were independent risk factors for the prognosis of endometrial carcinoma. The patients with high-grade and deep myometrial invasion, cervical involvement, full cavity tumor, and lymph node metastasis had a high incidence of ovarian metastasis.Pathological type, histological grade, pathological staging, and cervical involvement are independent risk factors affecting the prognosis of Chinese patients with endometrial carcinoma.


Assuntos
Carcinoma/mortalidade , Neoplasias do Endométrio/mortalidade , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/terapia , China/epidemiologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
2.
Exp Cell Res ; 406(1): 112735, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265287

RESUMO

Tripartite motif containing 16 (TRIM16) is a member of the tripartite motif protein family and functions as a potential tumor suppressor in several cancers. However, the specific function and clinical significance of TRIM16 in colorectal cancer (CRC) remains unclear. In this study, we observed that low TRIM16 expression was detected frequently in primary colorectal cancer (CRC) tissues and was closely associated with a better prognosis. Functional studies demonstrate that TRIM16 overexpression notably inhibits the metastasis abilities of CRC in vivo and in vitro. Mechanistically, our results demonstrated that TRIM16 directly bound and ubiquitinated Snail family transcriptional repressor 1 (Snail), an important transcriptional factor of the epithelial-mesenchymal transition (EMT) process suppressing the EMT in CRC. Additionally, our data revealed that the inhibition effect of TRIM16 on cancer metastasis was dependent on Snail degradation. Collectively, our study is the first to report that TRIM16 plays a crucial anti-tumor role in CRC tumorigenesis. We also provided novel evidence that TRIM16 might act as a prognostic and therapeutic target to assess and inhibit CRC progression.


Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Fatores de Transcrição da Família Snail/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/secundário , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Proteólise , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Análise de Sobrevida , Proteínas com Motivo Tripartido/antagonistas & inibidores , Proteínas com Motivo Tripartido/metabolismo , Carga Tumoral , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
3.
J Comput Assist Tomogr ; 45(3): 431-441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34297512

RESUMO

INTRODUCTION: Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor with characteristic BRD4-NUTM1 translocation and a poor prognosis. The primary objective of this study was to describe the clinical and radiologic features, treatment response, and survival of NUT carcinoma (NC). MATERIALS AND METHODS: This retrospective single-center study was based on the review of medical records of NC patients with a specific genetic rearrangement or positive anti-NUT nuclear staining. Overall survival (OS) was analyzed according to primary tumor location. RESULTS: This series of 22 patients had a mean age of 36.27 ± 2.68 years with 68% women and 32% men. The median age at diagnosis was 34 years (range, 17-55 years). The primary tumor was located in the chest (n = 12/22; 55%), head and neck (n = 9/22; 40%), and 1 patient had a renal tumor. About 68% (n = 15/22) patients presented with regional lymph nodal involvement and 77% (n = 17/22) had distant metastases. All the bone metastases were lytic (100%) with mixed lytic and sclerotic metastases in 5 patients. Only 18% (n = 4/22) of the patients showed response to treatment, with progression in the remaining 18 patients. The median OS was 7 months. The OS was significantly (P = 0.024) more in patients with primary head and neck NC (n = 9; OS, 16 months) versus those with pulmonary and other locations (n = 13; OS, 6 months). CONCLUSIONS: Nuclear protein of the testis carcinoma is an aggressive disease refractory to conventional therapy. Imaging with the complementary use of computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography is important for staging, guiding management, assessing the treatment response, and surveillance.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Carcinoma/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Adolescente , Adulto , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Carcinoma/metabolismo , Carcinoma/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Adulto Jovem
4.
J Egypt Natl Canc Inst ; 33(1): 16, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241710

RESUMO

BACKGROUND: P D-L1 is expressed in tumor cells and plays a crucial role in tumor immune escape. Tumor-infiltrating lymphocytes (TILs) as CD8 T cells contribute to reduced tumor growth. Few studies investigated the prognostic effect of PD-L1 and CD8 TILs in ovarian high-grade serous carcinoma (HGSC). In the present study, we analyzed the expression of PD-L1 and CD8 TILs in HGSC by immunohistochemistry, and results were correlated to prognosis. It was carried on 54 cases of ovarian HGSC who attended the Oncology Centre, Mansoura University, Egypt, from 2012 till 2019. RESULTS: Nearly 60% of cases showed positive PD-L1 expression in tumor cells. Regarding the clinicopathological characteristics, higher PD-L1 expression was found among patients with residual tumor (82.4%) compared to patients with no residual tumor (54.5%), with marginal statistical significance (p 0.07). PD-L1 was significantly associated with CD8 TILs expression. Higher PD-L1 expression was found among tumors with low expression of CD8 TILs with statistically significant difference (p≤0.001). Disease-free survival (DFS) was significantly lower among the group with positive expression of PD-L1 compared to the group with negative expression of PD-L1 (p 0.01), while overall survival (OS) was not associated with PD-L1 expression. On the other hand, the overall survival (OS) in patients with high CD8 expression was significantly higher than patients with low CD8 expression (p 0.043), while DFS was not significantly different among both CD8 TILS groups. CONCLUSIONS: PD-L1 and CD8 TILs may become a promising therapeutic target for patients with ovarian HGSC. More studies are needed to further validate their prognostic effect. Precise identification of patients who will benefit from PD-L1 checkpoint blockade and TILs adaptive immunotherapy is mandatory.


Assuntos
Antígeno B7-H1 , Linfócitos T CD8-Positivos/imunologia , Carcinoma , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Ovarianas/terapia , Adulto , Antígeno B7-H1/análise , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma/mortalidade , Carcinoma/terapia , Egito , Feminino , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/química , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Prognóstico , Receptor de Morte Celular Programada 1 , Análise de Sobrevida
5.
Am J Surg Pathol ; 45(7): 969-978, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34105518

RESUMO

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly have an independent impact on patient prognosis. We reclassified a large single-center cohort of 1004 CRCs spanning 2 decades for adjusted WHO grade (low vs. high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma-like, signet-ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, undifferentiated) according to the criteria of the 2019 WHO classification. We investigated the interaction of these parameters, their connection to stage/microsatellite status, and their significance for patient survival in the different subgroups. Specific subtypes other than adenocarcinoma not otherwise specified represented one third of all CRCs and were unevenly distributed throughout stage and microsatellite subgroups. Subtypes, WHO grade and tumor budding profoundly impacted all survival parameters (P<0.001 for all analyses), with CRC subtypes and tumor budding-but not WHO grade-being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provides strong stage-independent prognostic information, arguing that they should be considered in pathology reports and in clinical trials. Of the morphology-based grading schemes included in the 2019 WHO, tumor budding outperforms WHO grade.


Assuntos
Carcinoma/patologia , Movimento Celular , Neoplasias Colorretais/patologia , Idoso , Biópsia , Carcinoma/classificação , Carcinoma/mortalidade , Carcinoma/cirurgia , Colectomia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Organização Mundial da Saúde
6.
Virchows Arch ; 479(3): 507-514, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117532

RESUMO

The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005-2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)-stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43-3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07-2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice.


Assuntos
Carcinoma/patologia , Neoplasias do Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma/mortalidade , Carcinoma/terapia , Bases de Dados Factuais , Dinamarca , Progressão da Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Coloração e Rotulagem
7.
BMC Cancer ; 21(1): 667, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34088300

RESUMO

BACKGROUND: Cervical cancer is one of the most common malignancies among women. Appropriate and timely treatment of these patients can reduce the complications and increase their survival. The objective of this study was to compare neoadjuvant chemotherapy plus radical hysterectomy (NACTRH) and chemo-radiotherapy (CRT) in patients with bulky cervical cancer (stage IB3 & IIA2). MATERIAL AND METHODS: The medical records of patients with bulky cervical cancer (stage IB3 & IIA2) that received NACTRH or CRT between 2007 and 2017 were evaluated for therapeutic effects. Demographic characteristics, complications of chemo-radiotherapy and neoadjuvant chemotherapy, were collected in a researcher-made questionnaire. Our primary outcome was comparison of overall survival (OS), and disease-free survival (DFS) between two groups receiving NACTRH and CRT modalities. RESULTS: One-hundred and twenty three patients were enrolled in the study. The median age and the proportion of patients with stage IIA2 were higher in the CRT group compared to the NACTRH group (p < 0.05). The medians (95% CI) OS were 3.64 (3.95-6.45) and 3.9 (3.53-4.27) years in the NACTRH and CRT groups, respectively (P = 0.003). There were 16 (34.8%) and 22 (43.1%) recurrences in the NACTRH and CRT group, respectively (P = 0.4). The median (95% CI) DFS was 4.5 (3.88-5.12) years in the NACTRH group and 3.6 (2.85-4.35) years in the CRT group (P = 0.004). The 3-year OS rate in NACTRH and CRT groups were 97 and 90% respectively. The 3-year DFS rate in NACTRH and CRT groups were 88 and 66% respectively. CONCLUSIONS: NACTRH is associated with a higher OS and DFS compared to CRT.


Assuntos
Carcinoma/terapia , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Histerectomia , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias do Colo do Útero/terapia , Adulto , Carcinoma/diagnóstico , Carcinoma/mortalidade , Carcinoma/patologia , Colo do Útero/patologia , Colo do Útero/cirurgia , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga Tumoral , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
8.
BMC Cancer ; 21(1): 636, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051734

RESUMO

BACKGROUND: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. METHODS: We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. RESULTS: Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. CONCLUSION: Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.


Assuntos
Hidrolases de Éster Carboxílico/genética , Carcinoma/genética , Neoplasias do Seio Maxilar/genética , Recidiva Local de Neoplasia/epidemiologia , Proteínas de Fusão Oncogênica/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Superfície Celular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/terapia , Linhagem Celular Tumoral , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias do Seio Maxilar/mortalidade , Neoplasias do Seio Maxilar/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Estudos Retrospectivos , Adulto Jovem
9.
Clin Transl Gastroenterol ; 12(3): e00303, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939382

RESUMO

INTRODUCTION: Molecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC. METHODS: In this retrospective multicentre study, 5,931 LNs from 342 stage I-III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry. RESULTS: One-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001). DISCUSSION: The implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A512).


Assuntos
Carcinoma/mortalidade , Neoplasias Colorretais/mortalidade , Linfonodos/patologia , Metástase Linfática/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Carcinoma/secundário , Carcinoma/cirurgia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/cirurgia , Metástase Linfática/patologia , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Carga Tumoral
10.
Lancet Oncol ; 22(7): 931-945, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34051178

RESUMO

BACKGROUND: PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. METHODS: KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov, number NCT02853305. FINDINGS: Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7-36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5-8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4-7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65-0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5-19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3-16·7) in the chemotherapy group (0·86, 0·72-1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1-17·9] with pembrolizumab vs 14·3 months [12·3-16·7] with chemotherapy; HR 0·92, 95% CI 0·77-1·11) and the population with CPS of at least 10 (16·1 months [13·6-19·9] with pembrolizumab vs 15·2 months [11·6-23·3] with chemotherapy; 1·01, 0·77-1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. INTERPRETATION: The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. FUNDING: Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/efeitos dos fármacos , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma/imunologia , Carcinoma/mortalidade , Carcinoma/patologia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Fatores de Tempo , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/imunologia , Urotélio/patologia
11.
J Cardiothorac Surg ; 16(1): 121, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933129

RESUMO

BACKGROUND: The overall survival (OS) remains unsatisfactory in patients with esophageal squamous cell carcinoma (ESCC) after extended esophagectomy with two-field lymphadenectomy. Therefore, this retrospective study aimed to identify the risk factors that contribute to the low survival of patients with pT1-3N0M0 ESCC. METHODS: Patients with pT1-3N0M0 ESCC who only underwent R0 esophagectomy with two-field lymphadenectomy in our department from January 2008 to December 2012 were retrospectively enrolled in this study and medical records were reviewed. Postoperative OS, disease-free survival (DFS), recurrence-free survival (RFS), and locoregional recurrence-free survival (LRFS) were analyzed sequentially. RESULTS: This study recruited a total of 488 patients, whose follow-up visits were completed at the end of December 2019. The five-year OS, DFS, RFS and LRFS rates were 62.1, 53.1, 58.3 and 65.6%, respectively. Multivariate Cox analysis identified patient age, site of the lesion, small mediastinal lymph nodes in CT imaging (SLNs in CT), dissected lymph nodes (LNs), and stage of esophageal malignancy as independent risk factors for OS of the patients. Of these factors, the site of the lesion, SLNs in CT and stage of the cancer were determined to be independent factors for DFS, RFS and LRFS. Based on all five factors, the recursive partitioning analysis (RPA) score system was developed to stratify the patients into low-, medium- and high-risk groups, which were found to possess significantly different rates of OS, DFS, RFS and LRFS (p < 0.001). CONCLUSIONS: Several factors were associated with the survival of patients with pT1-3 N0M0 ESCC who underwent extended esophagectomy with two-field lymphadenectomy. These factors contributed to the RPA scoring system, which could stratify the risk of postoperative survival and may expedite the initiation of postoperative adjuvant therapy.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Humanos , Linfonodos/patologia , Masculino , Mediastino/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
12.
Int J Surg Oncol ; 2021: 2476527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953982

RESUMO

Background: The standard treatment for breast cancer is breast-conserving surgery (BCS) with radiotherapy. If external beam radiation therapy (EBRT) can be safely replaced with intraoperative radiotherapy (IORT), it will help patients to save their breast and to have equivocal or better results in DFS and overall survival (OS). Methods: A total of 2022 patients with breast cancer treated during 6 years were enrolled in the current study. A total of 657, 376, and 989 patients received EBRT, radical, and boost dose by IORT, respectively, according to the IRIORT consensus protocol. The primary endpoint was recurrence and death. The secondary endpoint was the role of variables in recurrence and death. Results: With a mean follow-up of 34.5 and 40.18 months for the IORT and EBRT groups, respectively, there was a significant difference in DFS between electron boost and X-ray boost groups (P=0.037) and the electron radical group compared with EBRT (P=0.025), but there was no significant difference between other boost and radical groups in DFS and OS. Conclusions: IORT can be a preferred treatment modality because of its noninferior outcomes, and in some special conditions, it has superior outcomes compared to EBRT, particularly in delivering radical dose with IORT.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma/radioterapia , Carcinoma/cirurgia , Cuidados Intraoperatórios/métodos , Mastectomia Segmentar/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Carcinoma/mortalidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Doses de Radiação , Radioterapia Adjuvante , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
13.
Int J Surg Oncol ; 2021: 8851751, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976936

RESUMO

Background: In peritoneal carcinomatosis (PC), increased life span and disease-free survival times are shown in patients with hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (SRC). In this study, our main objective was to present our experience of performing SRC and perioperative intraperitoneal chemotherapy (HIPEC and EPIC) on patients with PC, in light of the literature. Methods: Demographic data, follow-up results, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CCR) score, and morbidity and mortality rates of 180 patients treated with SRC + HIPEC + EPIC for PC at the Department of Surgical Oncology at Sivas Cumhuriyet University between January 2008 and July 2020 were analyzed retrospectively. Results: Distribution of 180 PC cases according to primary organs included 53 ovarian, 39 colorectal, 33 stomach, 25 primary peritoneum, 10 uterus, 10 tuba, five soft tissue, and five appendix originated carcinoma. The average PCI of the cases detected preoperatively was 21 (5-30). Completeness of cytoreduction scores of CCR-0 in 102 cases, CCR-1 in 67 cases, CCR-2 in eight cases, and CCR-3 in three cases was obtained. Median operation time was 300 (200-540) minutes. Perioperative morbidity rate was 47.0%, and perioperative mortality rate was 13.5%. Conclusion: The peritonectomy procedure is a difficult, long-lasting, troublesome intervention, but it is the most important treatment option with acceptable morbidity and mortality rates in patients selected for PC treatment in experienced centers.


Assuntos
Carcinoma/secundário , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/mortalidade , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
World Neurosurg ; 152: e45-e50, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33892166

RESUMO

BACKGROUND: Choroid plexus carcinoma is a central nervous system tumor pathologically corresponding to World Health Organization grade III. Choroid plexus carcinoma mainly affects pediatric patients with a poor prognosis. Due to its rarity, standardized treatment has not yet been outlined. METHODS: We retrospectively analyzed 11 patients with histopathologically diagnosed choroid plexus carcinoma between January 2008 and December 2016. They were treated with surgical resection with or without adjuvant therapies. The clinical profiles and outcomes were analyzed. RESULTS: The mean age at diagnosis was 16.0 years (median, 7.0 years; range, 4 months to ∼59 years). Gross total resection was achieved in 9 cases, and subtotal resection in 2 cases. Seven patients received adjuvant radiotherapy, and 2 patients underwent chemotherapy. The mean overall survival was 34.8 months, and the mean progression-free survival was 24.5 months. During the follow-up period, 4 patients succumbed to central nervous system dissemination of choroid plexus carcinoma including 2 patients with malignant transformation from atypical choroid plexus papilloma to choroid plexus carcinoma and 1 patient treated with the combined chemotherapy protocol. CONCLUSIONS: In this study, we described the clinicoradiologic characteristics of choroid plexus carcinomas. Surgical resection is the mainstream treatment. Due to the paucity of clinical evidence, the standard regimen of adjuvant therapies still needs further research.


Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/cirurgia , Neoplasias do Plexo Corióideo/diagnóstico por imagem , Neoplasias do Plexo Corióideo/cirurgia , Adolescente , Adulto , Carcinoma/mortalidade , Criança , Pré-Escolar , Neoplasias do Plexo Corióideo/mortalidade , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências
15.
Medicine (Baltimore) ; 100(16): e25452, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879677

RESUMO

BACKGROUND: Currently, an increasing number of long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Some studies have been carried out to investigate the influence of the expression of LncRNA human urothelial carcinoma associated 1 (UCA1) on prognosis and clinical significance in patients with esophageal cancer, but the results are contradictory and uncertain. A meta-analysis and was conducted with controversial data to accurately assess the issue. We collected relevant TCGA data to further testify the result. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma. METHODS: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were thoroughly searched for relevant information. Two reviewers independently performed data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were applied to evaluate the relationship between LncRNA UCA1 and clinicopathological characteristics of esophageal carcinoma patients. Hazard ratios and its 95% confidence intervals were adopted to assess the prognostic effects of LncRNA UCA1 on overall survival and disease-free survival. Meta-analysis was performed with Stata 14.0 software. To further assess the function of LncRNA UCA1 in esophageal carcinoma, relevant data from The Cancer Genome Atlas (TCGA) database was collected. Three databases, miRWalk, TargetScan, and miRDB, were used for prediction of target genes. Genes present in these 3 databases were considered as predicted target genes of LncRNA UCA1. Venny 2.1 were used for intersection analysis. Subsequently, GO, KEGG, and PPI network analysis were conducted based on the overlapping target genes of LncRNA UCA1 to explore the possible molecular mechanism in esophageal carcinoma. RESULTS: This study provides a high-quality medical evidence for the correlation between LncRNA UCA1 expression and overall survival, and between disease-free survival and clinicopathological features. Based on bioinformatics analysis, this study enhanced the understanding of the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma. CONCLUSION: The study provides updated evidence to evaluate whether the expression of LncRNA UCA1 is in association with poor prognosis in patients with esophageal carcinoma. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/8MCHW.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma/mortalidade , Neoplasias Esofágicas/mortalidade , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/análise , Carcinoma/genética , Carcinoma/patologia , Biologia Computacional , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Metanálise como Assunto , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/análise , Revisões Sistemáticas como Assunto
16.
Surgery ; 170(2): 462-468, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33648765

RESUMO

BACKGROUND: Remnant radioiodine ablation is discouraged in low-risk differentiated thyroid cancer because it confers no survival advantage. The impact of remnant radioiodine ablation on health-related quality of life in these patients is not well described. We hypothesized remnant radioiodine ablation is associated with lower health-related quality of life in early-stage differentiated thyroid cancer survivors. METHODS: A retrospective matched-pair analysis was conducted in stage I differentiated thyroid cancer survivors recruited from a thyroid cancer support group. Respondents self-reported via online survey. Dysphonia and dysphagia were reported via Likert scale. Health-related quality of life was evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile. Respondents who received remnant radioiodine ablation were matched for age, sex, race, and years since diagnosis with respondents who did not receive remnant radioiodine ablation. PROMIS t-scores were compared between remnant radioiodine ablation and nonremnant radioiodine ablation groups, and among those with or without surgical complications. RESULTS: One hundred and twenty-two pairs were matched. There was no significant difference in incidence of self-reported hypocalcemia, infection, dysphonia, or dysphagia between remnant radioiodine ablation and no remnant radioiodine ablation groups. There was no significant difference in mean PROMIS t-scores. Of respondents reporting normal preoperative voice and swallowing, there were no significant differences in postprocedural outcomes or PROMIS scores. Regardless of remnant radioiodine ablation treatment, those with surgical complications of hypocalcemia, dysphonia, or dysphagia reported worse PROMIS scores across multiple domains. Remnant radioiodine ablation-associated xerostomia was associated with worse PROMIS scores across multiple domains. CONCLUSION: This is the first study to use PROMIS measures to evaluate the association between remnant radioiodine ablation and health-related quality of life in early-stage differentiated thyroid cancer survivors treated surgically. Surgical and remnant radioiodine ablation-associated complications were associated with significantly worse PROMIS scores across multiple domains.


Assuntos
Carcinoma/radioterapia , Carcinoma/cirurgia , Radioisótopos do Iodo/uso terapêutico , Qualidade de Vida , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Carcinoma/mortalidade , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medidas de Resultados Relatados pelo Paciente , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia
17.
BMC Cancer ; 21(1): 279, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726691

RESUMO

BACKGROUND: Thymic tumors are unusual neoplasms, representing 0.2 to 1.5% of tumors in humans, but correspond to 20% of mediastinal tumors and 50% of those that occur in the anterior mediastinum. They tend to appear around the fourth and fifth decades of life without gender predilection. Up to 30% of patients are asymptomatic, therefore many are incidentally diagnosed. Radical thymectomy is the treatment of choice with high survival rates when detected in the early stages. METHODS: This was a retrospective descriptive study, including 18 adult patients' diagnosis of thymic neoplasm, who were managed with surgical resection from 2011 to 2019. Information about demographics, clinical characteristics, imaging findings, surgical and medical management, plus histological findings was obtained and reported. RESULTS: 18 patients with thymic tumors were included, of which specific histologic studies reveled thymomas, carcinomas, neuroendocrine tumors, thymolipoma and thymic cyst. Mean age was 52.7 years, with a predominance of male population. The main symptom was dyspnea, followed by cough and chest pain. Paraneoplastic syndromes such as myasthenia gravis, aplastic anemia and Cushing syndrome were reported. 89% of cases were treated by radical thymectomy alone, while only 2 cases required chemotherapy and radiotherapy. There were no surgical complications. Mean hospital stay length was 11. 9 days, with only 1 mortality during hospital admission. 5-year survival rate was 81%. CONCLUSIONS: The treatment of choice is radical thymectomy, which has been shown to positively impact patient mortality. Early detection is key to improve patient outcomes.


Assuntos
Síndromes Paraneoplásicas/epidemiologia , Timectomia , Timo/patologia , Neoplasias do Timo/cirurgia , Idoso , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/mortalidade , Carcinoma/cirurgia , Colômbia/epidemiologia , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Lipoma/complicações , Lipoma/diagnóstico , Lipoma/mortalidade , Lipoma/cirurgia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/cirurgia , Síndromes Paraneoplásicas/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Timoma/complicações , Timoma/diagnóstico , Timoma/mortalidade , Timoma/cirurgia , Timo/diagnóstico por imagem , Timo/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/mortalidade
18.
BMC Cancer ; 21(1): 286, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726701

RESUMO

BACKGROUND: In this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method. METHODS: We investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available. RESULTS: The strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs (r = 0.177; p < 0.001), CD8+ TILs (r = 0.085; p = 0.002), and FOXP3+ TILs (r = 0.0043; p = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs (r = 0.012; p = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival (p < 0.001) and overall survival (p < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis. CONCLUSIONS: CD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.


Assuntos
Carcinoma/terapia , Linfócitos do Interstício Tumoral/imunologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias de Mama Triplo Negativas/terapia , Linfócitos B/imunologia , Mama/citologia , Mama/imunologia , Mama/patologia , Carcinoma/imunologia , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Medição de Risco/métodos , Subpopulações de Linfócitos T/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
19.
Genet Test Mol Biomarkers ; 25(2): 116-123, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33596142

RESUMO

Aim: To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. Materials and Methods: MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Results: Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age (p = 0.004), tumor location (p < 0.001), and intestinal-type of Lauren classification (p < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were HSP110 (84.6%), EGFR (30.8%), BRCA2 (23.1%), MRE11 (23.1%), and MSH3 (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4; p = 0.014) as an independent indicator of poor prognosis in our population. Conclusions: This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.


Assuntos
Instabilidade de Microssatélites , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Marrocos , Fenótipo , Modelos de Riscos Proporcionais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade
20.
J Cancer Res Clin Oncol ; 147(6): 1631-1646, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33616717

RESUMO

INTRODUCTION: Identification of genetic determinants such as exosomal content that drives progression and metastasis of colorectal cancer (CRC) has received considerable attention. The present study aims to identify a suitable biomarker in CRC tissues and exosomes based on bioinformatics data to evaluate its expression patterns in CRC tissues as well as its clinicopathological significance. MATERIALS AND METHODS: Protein-protein interaction (PPI) network and enrichment analysis were applied to identify up-regulated genes that contributed in CRC exosomes to select the marker. The expression patterns and clinical significance of selected exosomal marker were evaluated in tissue microarrays (TMAs) of 445 CRC tumors and 39 adjacent normal tissues using immunohistochemistry method. RESULTS: Based on bioinformatics data, TSG101 gene was prominent amongst the tumor tissues and exosomes. Expression of TSG101 was significantly up-regulated in tumor cells compared to adjacent normal tissues (p-value = 0.04). Moreover, higher expressions of TSG101 (cytoplasmic and nuclear) were significantly associated with tumor differentiation (p-value = 0.042) and distant metastasis (p-value = 0.027). A significant association was found in the cytoplasmic expression of TSG101 between well and moderate tumor differentiation (p-value = 0.005) as well as moderate and poor differentiation (p-value = 0.050). CONCLUSION: These findings indicate that the exploration of crosstalk between exosome content and CRC may be valuable for the development of novel exosomal biomarkers. Increased expression of TSG101, as a promising exosome marker, is more associated with more aggressive tumor behaviors, metastasis, and progression of CRC, which paves the way for therapeutic strategies and CRC management. However, further investigations are warranted to clarify the molecular mechanisms of TSG101 in CRC.


Assuntos
Carcinoma/patologia , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/mortalidade , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Estudos Transversais , Feminino , Humanos , Imuno-Histoquímica , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Mapeamento de Interação de Proteínas , Análise Serial de Tecidos , Regulação para Cima , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...