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1.
Medicine (Baltimore) ; 100(10): e24995, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725875

RESUMO

BACKGROUND: Adjuvant trastuzumab improves survival outcomes of human epidermal receptor 2 positive early breast cancer patients. Currently, administration of 12 months adjuvant trastuzumab is the standard therapy. However, whether 6 months treatment is non-inferior to the standard 12 months treatment remains controversial. METHODS: Relevant records were searched in PubMed, Cochrane Library, Web of Science, and EMBASE through Jan 14, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were meta-analyzed. The primary endpoint was DFS with a non-inferiority hazard margin of 1.2 and the second was OS with 1.43. RESULTS: Three randomized clinical studies met the inclusion criteria, including 3974 patients in 6 months group and 3976 in 12 months group. HR for DFS was 1.18 (95% CI 0.97-1.44, P = .09), with the non-inferiority margin comprised in the 95% CI. HR for OS was 1.14 (95% CI 0.98-1.32, P= .08), whereas the upper limit of 95% CI did not exceed the non-inferiority hazard margin. CONCLUSION: Our analysis failed to show that 6 months treatment was non-inferior to 12 months treatment in improving the DFS. Although the non-inferiority of the 6-month adjuvant trastuzumab treatment was found for OS, considering that breast cancer patients should receive additional systematic therapies when disease progression or relapse happens, we suggest that 12 months adjuvant trastuzumab treatment should remain the standard therapeutic strategy for patients with early human epidermal receptor 2 positive breast cancer.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/epidemiologia , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Mama/imunologia , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante/métodos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Mastectomia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Fatores de Tempo
2.
Medicine (Baltimore) ; 100(12): e23794, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761628

RESUMO

ABSTRACT: Diffuse pigmented villonodular synovitis (PVNS) of knee is a rare benign disease that has a destructive clinical course. Synovectomy and adjuvant radiotherapy (RT) have been reported as treatment options but literatures reporting functional outcomes were sparse. This study aimed to evaluate the long-term functional outcomes and disease control among treatment modalities through the 22 years of experience.A single-center database was searched for patients who received synovectomy of knee with the pathologic diagnosis of PVNS. General data, treatment modalities, and recurrent status were retrospectively collected from medical records. Functional outcomes were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index through phone interviews by an independent orthopedist.From January 1995 to December 2017, 24 patients with diffuse PVNS of knee were identified, including 19 receiving open synovectomy (OP) and 5 undergoing arthroscopic surgery. Adjuvant RT was performed on 14 patients with a median dose of 35 Gy (range 20-40 Gy). After median follow up of 6 years, recurrences were recorded in 10 cases. The recurrence rate was significantly lower in the OP + RT group than the OP group (8.3% vs 57.1%, P = .038). Among those with preserved knee joints, there was no significant difference in the Western Ontario and McMaster Universities Osteoarthritis Index score and stiffness score between patients in the OP + RT and OP groups.For patients with diffuse PVNS of knee, the addition of moderate-dose adjuvant RT following OP provided excellent local control while maintaining good joint function with limited treatment-related morbidity. Our study emphasized the importance of moderate dose RT in diffuse PVNS of knee joint.


Assuntos
Artroscopia/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Sinovectomia/métodos , Sinovite Pigmentada Vilonodular/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Radioterapia Adjuvante/efeitos adversos , Amplitude de Movimento Articular , Sinovectomia/efeitos adversos , Sinovite Pigmentada Vilonodular/epidemiologia , Sinovite Pigmentada Vilonodular/patologia , Resultado do Tratamento , Adulto Jovem
3.
Life Sci ; 272: 119196, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617857

RESUMO

Senescent cancer cells contribute to tumor refractoriness. The removal of senescent cells after chemotherapy prevents or delays cancer relapse. Our study showed that GL-V9 (5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl) butoxy)-4-H-chromen-4-one), a potential anticancer drug, eliminated senescent MEFs (Mouse embryonic fibroblasts) and drug-induced senescent breast cancer cells. GL-V9 induced apoptosis in senescent MDA-MB-231 cells. Mechanistically, it alkalized lysosomes and increased the abundance of mitochondria as well as ROS (Reactive oxygen species). The senolytic effect of GL-V9 was also observed in epirubicin-treated mammary tumors in MMTV-PyMT mice. Our data thus indicated that GL-V9 is a promising senolytic drug which could be used to improve the outcome of cancer chemotherapy.


Assuntos
Neoplasias da Mama/metabolismo , Senescência Celular/efeitos dos fármacos , Flavonoides/farmacologia , Envelhecimento/fisiologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Senescência Celular/fisiologia , China , Feminino , Flavonoides/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Mitocôndrias/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Espécies Reativas de Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Medicine (Baltimore) ; 100(7): e24322, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607767

RESUMO

OBJECTIVE: To investigate whether the Quxie capsule can decrease relapse, metastasis, and symptoms, as well as alleviate the side effects in colorectal cancer (CRC) patients. METHODS: A comprehensive literature search of multiple databases was performed. Two reviewers independently selected trials that assessed the relapse-metastasis rate, degree of symptoms, and side effects of Quxie capsule for CRC. The meta-analysis was performed using Review Manager 5.3. RESULTS: This meta-analysis included 6 studies, with a total of 408 cases. The quality of the included studies was generally low, with only 1 trial of high quality. A statistically significant difference was observed in the relapse-metastasis rate between the Quxie capsule and control groups after 2-years follow-up (n = 185, relative risk (RR) = 0.13, 95% confidence interval (CI) 0.04-0.46; P = .002). The Quxie capsule was found to reduce the traditional Chinese medicine symptom score as compared to the control (n = 208, weighted mean differences (WMD) = -4.15, 95% CI -7.30 to -1.00; P = .010), while it showed no significant improvement in the Karnofsky Performance Status score (n = 138, WMD = 5.05; 95% CI -2.95 to 13.04; P = .22). There was no difference in adverse events between the 2 groups (P = .66). CONCLUSION: This systematic review and meta-analysis showed no clear superiority of Quxie capsule for CRC patients receiving chemotherapy. The effect of Quxie capsule in CRC patients should be examined by high quality, large sample size, multi-center RCTs, with longer follow-up.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Antineoplásicos/efeitos adversos , Humanos , Medicina Tradicional Chinesa , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Cancer Radiother ; 25(2): 191-199, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33402287

RESUMO

PURPOSE: In breast cancer, radiotherapy is an essential component of the treatment. However, indications of irradiation of the internal mammary chain and axillary area are debatables. Axillary recurrence in patients with invasive breast carcinoma remains an issue. Currently, the substitution of axillary lymph node dissection by sentinel node biopsy leads to revisit the role of axillary irradiation. Breast irradiation including level I, II and III might decrease the risk of axillary recurrence. MATERIAL AND METHODS: A literature search was performed in PubMed and the Cochrane library to identify articles publishing data regarding dose-volume analysis of axillary levels in breast irradiation aiming to determine the potential therapeutic implications. RESULTS: Eleven articles were retained. A total of 375 treatment plans were analyzed. The results concerning the irradiation technique, initial dose prescribed to breast, delineated volumes and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I-III with 3D-conformal radiotherapy using standard fields were between 24Gy and 43.5Gy, 3Gy and 32.5Gy and between 1.0Gy and 20.5Gy respectively. The average doses delivered to axilla levels I-III with 3D-conformal radiotherapy using high tangential fields were between 38Gy and 49.7Gy, 11Gy and 47.1Gy and 5Gy 38.7Gy, 32.1Gy and 5Gy (result available for only one study) respectively. Finally, the average doses delivered to axilla levels I-III with intensity modulated radiation therapy were between 14.5Gy and 42.6Gy, 3.4Gy and 35Gy and between 1.2Gy and 25.5Gy respectively. CONCLUSIONS: Incidental axillary dose seems insufficient to be therapeutic regardless of the irradiation technique. There are meaningful differences between intensity modulated radiation therapy and 3D-conformal radiotherapy.


Assuntos
Neoplasias da Mama/radioterapia , Irradiação Linfática/métodos , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/radioterapia , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Radioterapia Conformacional/normas , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/normas , Biópsia de Linfonodo Sentinela
6.
Cancer Sci ; 112(3): 1275-1288, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33426736

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. High recurrence rates after curative resection and the lack of specific biomarkers for intrahepatic metastases are major clinical problems. Recently, exosomal microRNAs (miRNAs) have been reported to have a role in the formation of the pre-metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. A highly intrahepatic metastatic cell line (HuH-7M) was established by in vivo selection. HuH-7M showed increased proliferative ability and suppression of apoptosis and anoikis. HuH-7M and the parental cell (HuH-7P) showed the similar expression of epithelial-mesenchymal transition markers and cancer stem cell markers. In vivo, mice treated with exosomes derived from HuH-7M showed increased tumorigenesis of liver metastases. Exosomes from HuH-7M downregulated endothelial cell expression of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) in non-cancerous regions of liver and increased the permeability of FITC-dextran through the monolayer of endothelial cells. The miRNAs (miR-638, miR-663a, miR-3648, and miR-4258) could attenuate endothelial junction integrity by inhibiting VE-cadherin and ZO-1 expression. In patients with HCC, higher serum exosomal miR-638 expression was associated with tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancer cell can promote vascular permeability via downregulation of endothelial expression of VE-cadherin and ZO-1. Serum exosomal miR-638 expression holds potential for serving as a significant and independent prognostic marker in HCC.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/metabolismo , Caderinas/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Proteína da Zônula de Oclusão-1/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Células Endoteliais/patologia , Transição Epitelial-Mesenquimal/genética , Exossomos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Células Endoteliais da Veia Umbilical Humana , Humanos , Fígado/citologia , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Período Pré-Operatório
7.
Nat Commun ; 12(1): 422, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462236

RESUMO

Drug tolerant/resistant leukemic stem cell (LSC) subpopulations may explain frequent relapses in acute myeloid leukemia (AML), suggesting that these relapse-initiating cells (RICs) persistent after chemotherapy represent bona fide targets to prevent drug resistance and relapse. We uncover that calcitonin receptor-like receptor (CALCRL) is expressed in RICs, and that the overexpression of CALCRL and/or of its ligand adrenomedullin (ADM), and not CGRP, correlates to adverse outcome in AML. CALCRL knockdown impairs leukemic growth, decreases LSC frequency, and sensitizes to cytarabine in patient-derived xenograft models. Mechanistically, the ADM-CALCRL axis drives cell cycle, DNA repair, and mitochondrial OxPHOS function of AML blasts dependent on E2F1 and BCL2. Finally, CALCRL depletion reduces LSC frequency of RICs post-chemotherapy in vivo. In summary, our data highlight a critical role of ADM-CALCRL in post-chemotherapy persistence of these cells, and disclose a promising therapeutic target to prevent relapse in AML.


Assuntos
Adrenomedulina/metabolismo , Antineoplásicos/farmacologia , Proteína Semelhante a Receptor de Calcitonina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Animais , Antineoplásicos/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Proteína Semelhante a Receptor de Calcitonina/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Cultura Primária de Células , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto
8.
BJOG ; 128(1): 25-35, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32558987

RESUMO

BACKGROUND: The efficacy of hormonal regimens for the prevention of endometrioma recurrence in women who have undergone conservative surgery is still controversial. OBJECTIVE: To compare the efficacy of different hormonal regimens in this context and to rank them. SEARCH STRATEGY: MEDLINE and Scopus databases were searched through January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cohorts, comparing the effect of any pair of interventions (i.e. cyclic oral contraceptives [OC], continuous OC, gonadotropin-releasing hormone agonist [GnRHa], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNG-IUS] and expectant management) on endometrioma recurrence were selected. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA) and ranked in descending order. MAIN RESULTS: Six RCTs (675 patients) and 16 cohorts (3089 patients) were included. NMA of the RCTs involving expectant management, cyclic OC, continuous OC, GnRHa and GnRHa + LNG-IUS, showed that all hormonal regimens had a nonsignificant lower risk of endometrioma recurrence compared with expectant management. NMA of the cohorts involving expectant, cyclic OC, continuous OC, GnRHa, DNG, LNG-IUS, GnRHa + OC, and GnRHa + LNG-IUS indicated that LNG-IUS, DNG, continuous OC, GnRHa + OC and cyclic OC had a significantly lower risk of endometrioma recurrence than expectant management. LNG-IUS was ranked highest, followed by DNG and GnRHa + LNG-IUS. Long-term use of hormonal treatment either OC or progestin had a significantly lower risk of endometrioma recurrence than expectant treatment. CONCLUSION: In the NMA of RCTs, there was no evidence supporting hormonal treatment for postoperative prevention of endometrioma recurrence. This was at odds with the cohort evidence, which found the protective effect of OC and progestin regimens, especially long-term treatment. Large-scale RCTs of these agents are still required. TWEETABLE ABSTRACT: Hormonal regimens given as long-term treatment tend to reduce risk of endometrioma recurrence after conservative surgery.


Assuntos
Endometriose/prevenção & controle , Terapia de Reposição de Estrogênios , Recidiva Local de Neoplasia/prevenção & controle , Doenças Ovarianas/prevenção & controle , Ovariectomia , Complicações Pós-Operatórias/prevenção & controle , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
J Surg Res ; 257: 213-220, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32858322

RESUMO

Angiosarcomas (AS) are a diverse group of soft tissue sarcomas, arising from blood and lymphatic vessels. They frequently present in the elderly, and in patients with previous radiation or lymphedema. A wide range of genetic derangements contribute to their development, and AS histology is often high-grade in keeping with aggressive disease biology. The clinical presentation, while often innocuous, is marked by its infiltrative and aggressive nature, with a proclivity for metastatic spread, and outcomes are often poor. Surgery is performed for localized, resectable cases. A multidisciplinary approach, appropriately employing surgery, radiation, chemotherapy, or potentially recently approved immune-oncology agents, can result in positive outcomes.


Assuntos
Hemangiossarcoma/terapia , Recidiva Local de Neoplasia/prevenção & controle , Equipe de Assistência ao Paciente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vasos Sanguíneos/patologia , Vasos Sanguíneos/efeitos da radiação , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Hemangiossarcoma/genética , Hemangiossarcoma/mortalidade , Hemangiossarcoma/patologia , Humanos , Vasos Linfáticos/patologia , Vasos Linfáticos/efeitos da radiação , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Radioterapia Adjuvante , Procedimentos Cirúrgicos Operatórios
10.
J Urol ; 205(1): 78-85, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32614274

RESUMO

PURPOSE: The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma. MATERIALS AND METHODS: The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. RESULTS: A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death. CONCLUSIONS: In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Nefrectomia/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Canadá/epidemiologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Nefrectomia/normas , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Radiografia/estatística & dados numéricos , Fatores de Tempo , Tempo para o Tratamento/normas , Triagem/normas , Triagem/estatística & dados numéricos
11.
J Urol ; 205(1): 145-151, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32755338

RESUMO

PURPOSE: A map of pelvic lymph node metastasis in patients with penile cancer helps to clarify the pattern of pelvic spread and define the reasonable limits of dissection, and it has not been established. We aim to provide an accurate map of lymph node metastasis in patients with penile cancer and determine the reasonable extent of pelvic lymph node dissection. MATERIALS AND METHODS: We enrolled patients with penile cancer undergoing pelvic lymph node dissection (128) at our institution from 1999 to 2018. The numbers of removed lymph nodes and positive lymph nodes at 10 distinct regions were recorded. The chi-square and Fisher exact tests were used. RESULTS: The median number of pelvic lymph nodes retrieved was 18 (IQR 10-30), with the majority being from the external iliac package (43.0%) and obturator package (31.9%). Pelvic lymph node metastasis was present in 57/128 (44.5%) patients. The median number of positive pelvic lymph nodes removed was 2 (IQR 1-4), with the majority being from the external iliac package (50.0%) and obturator package (36.6%). Advanced T-stage was related to higher risk of pelvic lymph node metastasis, which was present in 30.3%, 44.2%, 59.0% and 58.3% of patients with pT1, pT2, pT3 and pT4, respectively. Notably, 2 patients had crossover metastasis from 1 inguinal region to the contralateral pelvic region. CONCLUSIONS: We present a detailed map of pelvic lymph node metastasis in patients with penile carcinoma. The external iliac and obturator packages appear to be most commonly involved. Optimal pelvic lymph node dissection may extend to the common iliac artery, including common iliac, external iliac, internal iliac and obturator lymph nodes. Extranodal extension in inguinal nodes may not be as important as previously thought.


Assuntos
Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Metástase Linfática/terapia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Penianas/cirurgia , Intervalo Livre de Doença , Seguimentos , Humanos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Pelve , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Estudos Retrospectivos , Análise de Sobrevida
12.
Cancer Sci ; 112(3): 1209-1224, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33340428

RESUMO

Cancer stem-like cells (CSCs) induce drug resistance and recurrence of tumors when they experience DNA replication stress. However, the mechanisms underlying DNA replication stress in CSCs and its compensation remain unclear. Here, we demonstrate that upregulated c-Myc expression induces stronger DNA replication stress in patient-derived breast CSCs than in differentiated cancer cells. Our results suggest critical roles for mini-chromosome maintenance protein 10 (MCM10), a firing (activating) factor of DNA replication origins, to compensate for DNA replication stress in CSCs. MCM10 expression is upregulated in CSCs and is maintained by c-Myc. c-Myc-dependent collisions between RNA transcription and DNA replication machinery may occur in nuclei, thereby causing DNA replication stress. MCM10 may activate dormant replication origins close to these collisions to ensure the progression of replication. Moreover, patient-derived breast CSCs were found to be dependent on MCM10 for their maintenance, even after enrichment for CSCs that were resistant to paclitaxel, the standard chemotherapeutic agent. Further, MCM10 depletion decreased the growth of cancer cells, but not of normal cells. Therefore, MCM10 may robustly compensate for DNA replication stress and facilitate genome duplication in cancer cells in the S-phase, which is more pronounced in CSCs. Overall, we provide a preclinical rationale to target the c-Myc-MCM10 axis for preventing drug resistance and recurrence of tumors.


Assuntos
Neoplasias da Mama/genética , Proteínas de Manutenção de Minicromossomo/metabolismo , Recidiva Local de Neoplasia/genética , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Dano ao DNA/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Proteínas de Manutenção de Minicromossomo/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/efeitos dos fármacos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Esferoides Celulares , Células Tumorais Cultivadas , Regulação para Cima
13.
Laryngoscope ; 131(3): E1029-E1034, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33319385

RESUMO

OBJECTIVES/HYPOTHESIS: Nodal involvement is frequent in patients with differentiated thyroid cancers (DTCs), but its prognostic relevance is not univocal. Some characteristics of nodal metastases can increase the risk of recurrence. We attempted to quantify the impact on survival of nodal factors included in the American Thyroid Association (ATA) risk stratification system in N1b patients with DTC. STUDY DESIGN: Retrospective study. METHODS: A retrospective analysis of patients affected by DTC who underwent therapeutic lateral neck dissection (ND) was performed. The impact on the prognosis of the number of positive lymph nodes (LNs), dimension of nodal metastasis, and microscopic and macroscopic extranodal extension (miENE and maENE, respectively) was investigated. RESULTS: The study included 347 N1b patients who underwent 401 therapeutic lateral NDs. Mean number of positive LNs was nine, mean nodal ratio was 0.27, and mean diameter of metastasis was 15.5 mm. ENE was detected in 25.9% of patients (22.5% miENE and 3.5% maENE). In univariate analysis, the presence of maENE had an impact on disease specific survival (DSS) (P = .023); increasing number of positive LNs affected DSS and locoregional control (LRC) (P = .009 and =.006, respectively); increasing metastatic node dimension was a risk factors for overall survival, DSS, and metastases free survival (MFS) (P = .05, =.013 and =.016). In multivariate analysis, number of positive LNs and LN dimension were independent risk factors for LRC and MFS, respectively (HR 1.1, P = .028; HR 1.1, P = .026). CONCLUSIONS: In our analysis on a cohort of N1b patients, the number of positive LNs and LN dimension were confirmed as independent risk factors for locoregional and distant recurrence, respectively. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1029-E1034, 2021.


Assuntos
Metástase Linfática/patologia , Esvaziamento Cervical/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
14.
Cochrane Database Syst Rev ; 12: CD007245, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33348436

RESUMO

BACKGROUND: Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. OBJECTIVES: To determine the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. SEARCH METHODS: We searched the following databases on 29 June 2020; The Cochrane Gynaecology and Fertility Group specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature. We searched the Cochrane Breast Cancer Group specialised register on 4 March 2020. We also searched two trials registers, checked references for relevant trials and contacted study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with breast cancer on adjuvant tamoxifen that compared the effectiveness of the LNG-IUS with endometrial surveillance versus endometrial surveillance alone on the incidence of endometrial pathology. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer), diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. We rated the overall certainty of evidence using GRADE methods. MAIN RESULTS: We included four RCTs (543 women analysed) in this review. We judged the certainty of the evidence to be moderate for all of the outcomes, due to imprecision (i.e. limited sample sizes and low event rates). In the included studies, the active treatment arm was the 20 µg/day LNG-IUS plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS probably reduces the incidence of endometrial polyps compared to the control group over both a 12-month period (Peto odds ratio (OR) 0.22, 95% confidence interval (CI) 0.08 to 0.64, I² = 0%; 2 RCTs, n = 212; moderate-certainty evidence) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). For long-term follow-up, this suggests that if the incidence of endometrial polyps following endometrial surveillance alone is assumed to be 23.5%, the incidence following LNG-IUS with endometrial surveillance would be between 3.8% and 10.7%.  The LNG-IUS probably slightly reduces the incidence of endometrial hyperplasia compared with controls over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). This suggests that if the chance of endometrial hyperplasia following endometrial surveillance alone is assumed to be 2.8%, the chance following LNG-IUS with endometrial surveillance would be between 0.1% and 1.9%. However, it should be noted that there were only six cases of endometrial hyperplasia. There was insufficient evidence to reach a conclusion regarding the incidence of endometrial cancer in tamoxifen users, as no studies reported cases of endometrial cancer. At 12 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting compared to the control group (Peto OR 7.26, 95% CI 3.37 to 15.66; I² = 0%; 3 RCTs, n = 376; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 1.7%, the chance following LNG-IUS with endometrial surveillance would be between 5.6% and 21.5%. By 24 months of follow-up, abnormal vaginal bleeding or spotting occurs less frequently than at 12 months of follow-up, but is still more common in the LNG-IUS group than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10; I² = 0%; 2 RCTs, n = 233; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 4.2%, the chance following LNG-IUS with endometrial surveillance would be between 4.4% and 23.9%. By 60 months of follow-up, there were no cases of abnormal vaginal bleeding or spotting in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). As a result, there is probably little or no difference in these outcomes between the LNG-IUS treatment group and the control group.  AUTHORS' CONCLUSIONS: The LNG-IUS probably slightly reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. Data were lacking on whether the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available RCTs that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.


Assuntos
Neoplasias da Mama/prevenção & controle , Hiperplasia Endometrial/prevenção & controle , Neoplasias do Endométrio/prevenção & controle , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/prevenção & controle , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Intervalos de Confiança , Anticoncepcionais Femininos/administração & dosagem , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/epidemiologia , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Levanogestrel/efeitos adversos , Recidiva Local de Neoplasia/mortalidade , Pólipos/induzido quimicamente , Pólipos/epidemiologia , Pólipos/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamoxifeno/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Hemorragia Uterina/epidemiologia , Útero/efeitos dos fármacos
16.
Magy Onkol ; 64(4): 371-383, 2020 Dec 14.
Artigo em Húngaro | MEDLINE | ID: mdl-33313611

RESUMO

The radiotherapy (RT) expert panel revised and updated the RT guidelines accepted in 2016 at the 3rd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional WBI. Following mastectomy RT significantly decreases the risk of LR and improves overall survival of patients having 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by BCS WBI is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.


Assuntos
Neoplasias da Mama , Mastectomia , Radioterapia Adjuvante , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Humanos , Hungria , Mastectomia Segmentar , Recidiva Local de Neoplasia/prevenção & controle
17.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370960

RESUMO

Solitary fibrous tumours (SFT) is an encompassing terminology comprising of tumours with proliferating CD34 positive specialised fibroblasts. Orbital SFTs are rare slowly progressive highly vascular neoplasms. Complete surgical excision is considered the mainstay treatment. Incomplete resection is a known risk factor for recurrence and malignant transformation. Recently preoperative embolisation of SFT has shown promising results in reducing the vascularity of these tumours rendering them amenable to complete surgical excision. Less than 10 cases of embolisation of orbital solitary fibrous tumours have been described in literature. Our patient underwent an attempted surgical excision elsewhere with significant intraoperative haemorrhage which precluded its complete excision. Herein, we report successful outcome in a case of hypervascular orbital SFT managed with preoperative embolisation, surgical resection and adjuvant radiotherapy along with a review of relevant literature.


Assuntos
Embolização Terapêutica , Órbita/cirurgia , Neoplasias Orbitárias/terapia , Cuidados Pré-Operatórios/métodos , Tumores Fibrosos Solitários/terapia , Feminino , Humanos , Imagem por Ressonância Magnética , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Órbita/diagnóstico por imagem , Órbita/patologia , Neoplasias Orbitárias/irrigação sanguínea , Neoplasias Orbitárias/diagnóstico , Neoplasias Orbitárias/patologia , Tumores Fibrosos Solitários/irrigação sanguínea , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologia
18.
Nat Commun ; 11(1): 5696, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173046

RESUMO

Poorly immunogenic tumors, including triple negative breast cancers (TNBCs), remain resistant to current immunotherapies, due in part to the difficulty of reprogramming the highly immunosuppressive tumor microenvironment (TME). Here we show that peritumorally injected, macroporous alginate gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) for concentrating dendritic cells (DCs), CpG oligonucleotides, and a doxorubicin-iRGD conjugate enhance the immunogenic death of tumor cells, increase systemic tumor-specific CD8 + T cells, repolarize tumor-associated macrophages towards an inflammatory M1-like phenotype, and significantly improve antitumor efficacy against poorly immunogenic TNBCs. This system also prevents tumor recurrence after surgical resection and results in 100% metastasis-free survival upon re-challenge. This chemo-immunotherapy that concentrates DCs to present endogenous tumor antigens generated in situ may broadly serve as a facile platform to modulate the suppressive TME, and enable in situ personalized cancer vaccination.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Imunoterapia/métodos , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antígenos de Neoplasias/metabolismo , Biotecnologia/métodos , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Fatores Imunológicos/metabolismo , Fatores Imunológicos/uso terapêutico , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias de Mama Triplo Negativas/imunologia , Microambiente Tumoral/imunologia
19.
Nat Commun ; 11(1): 4909, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999291

RESUMO

Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha (SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.


Assuntos
Micropartículas Derivadas de Células/imunologia , Imunoterapia/métodos , Macrófagos/imunologia , Melanoma/terapia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antígeno CD47/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Melanoma/imunologia , Melanoma/secundário , Proteínas de Membrana/agonistas , Proteínas de Membrana/imunologia , Camundongos , Nanopartículas/administração & dosagem , Recidiva Local de Neoplasia/imunologia , Nucleotídeos Cíclicos/administração & dosagem , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia
20.
Can J Surg ; 63(5): E468-E474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33107816

RESUMO

BACKGROUND: The implementation of quality-of-care indicators aiming to improve colorectal cancer (CRC) outcomes has been previously described by Cancer Care Ontario. The aim of this study was to assess the quality-of-care indicators in CRC at a referral centre in a developing country and to determine whether improvement occurred over time. METHODS: We performed a retrospective study of our prospectively collected database of patients after CRC surgery from 2001 to 2016. We excluded patients who underwent local transanal excision, pelvic exenteration or palliative procedures. We evaluated trends over time using the Cochran-Armitage test for trend. RESULTS: A total of 343 patients underwent surgical resection of CRC over the study period. There was improvement of the following indicators over time: the proportion of patients detected by screening (p = 0.03), the proportion of patients with preoperative liver imaging (p = 0.001), the proportion of patients with stage II or III rectal cancer who received neoadjuvant chemotherapy (p = 0.03), the proportion of patients with pathology reports that indicated the number of lymph nodes examined and the number of positive nodes (p = 0.001), and the proportion of patients with pathology reports describing the details on margin status (p = 0.001). CONCLUSION: This study showed the feasibility of applying the Cancer Care Ontario indicators for evaluating outcomes in CRC treatment at a single centre in a developing country. Although there was an improvement of some of the quality-of-care indicators over time, policies and interventions must be implemented to improve the fulfillment of all indicators.


Assuntos
Neoplasias Colorretais/cirurgia , Países em Desenvolvimento , Recidiva Local de Neoplasia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Estudos de Viabilidade , Feminino , Seguimentos , Implementação de Plano de Saúde/organização & administração , Implementação de Plano de Saúde/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , México , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Estudos Retrospectivos , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
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