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1.
Urol Clin North Am ; 47(4): 419-431, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008493

RESUMO

The management of metastatic renal cell carcinoma (RCC) has evolved rapidly in recent years with several immunotherapy-based combinations of strategies approved as first-line therapies. Targeted strategies, including systemic antiangiogenesis agents and immune checkpoint blockade, form the basis of a therapeutic approach. With rising rates of recurrence after first-line treatment, it is increasingly important to not only adopt a personalized treatment plan with minimal adverse events but also develop predictive biomarkers for response. This review discusses currently available first-line and second-line therapies in RCC and their pivotal data, with specific focus on ongoing clinical trials in the adjuvant setting, including those involving novel agents.


Assuntos
Produtos Biológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
2.
Urol Clin North Am ; 47(4): 443-456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008495

RESUMO

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Urol Clin North Am ; 47(4): 469-474, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008497

RESUMO

Multiple immunologic platforms have provided minimal impact in patients with metastatic castration-resistant prostate cancer, necessitating that novel approaches continue to be developed. Although checkpoint inhibitors have been largely ineffective, there remain small cohorts of patients who have durable responses but lack the conventional indicators for response to this class of drugs, that is, high mutational burden or significant genomic alterations, as seen in other solid tumors. This article presents an update on the evolution of immunotherapeutics that target a more lethal form of prostate cancer and provides the groundwork for future considerations as to how this field should proceed.


Assuntos
Quinases Ciclina-Dependentes/genética , Regulação Neoplásica da Expressão Gênica , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/terapia , Idoso , Produtos Biológicos/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Quinases Ciclina-Dependentes/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Fenótipo , Medicina de Precisão/métodos , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos
4.
Urol Clin North Am ; 47(4): 487-510, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008499

RESUMO

The advent of immunotherapy has revolutionized cancer treatment. Prostate cancer has an immunosuppressive microenvironment and a low tumor mutation burden, resulting in low neoantigen expression. The consensus was that immunotherapy would be less effective in prostate cancer. However, recent studies have reported that prostate cancer does have a high number of DNA damage and repair gene defects. Immunotherapies that have been tested in prostate cancer so far have been mainly vaccines and checkpoint inhibitors. A combination of genomically targeted therapies, with approaches to alleviate immune response and thereby make the tumor microenvironment immunologically hot, is promising.


Assuntos
Produtos Biológicos/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Microambiente Tumoral/efeitos dos fármacos , Idoso , Animais , Antígenos de Neoplasias/efeitos dos fármacos , Antígenos de Neoplasias/imunologia , Previsões , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/imunologia , Estadiamento de Neoplasias , Neoplasias da Próstata/genética , Resultado do Tratamento , Microambiente Tumoral/genética
5.
Medicine (Baltimore) ; 99(38): e22255, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957374

RESUMO

The expression of Cystathionine beta-synthase (CBS) and Chemokine ligand 21 (CCL21) is associated with the tumorigenesis and progression of a variety of tumors, but whether alterations in their expression levels correlates with the carcinogenesis and progression of EHCC is still unknown. This study investigated the clinicopathological significance of CBS and CCL21 expression in EHCC.We investigated the correlations between the expression of CBS and CCL21 and clinicopathological characteristics in EHCC using EnVision immunohistochemistry.The expression of CBS and CCL21 was significantly higher in EHCC tumors than in nontumor tissues (P < .05 and P < .01). EHCC patients with CBS and CCL21 expression combined with lymph node metastasis, tumor cell invasion, and TNM III/IV stage had more severe conditions than those with no lymph node metastasis, distant invasion and TNM I/II stage (P < .01). Kaplan-Meier survival analysis showed that the overall survival rates for EHCC patients with negative CBS or CCL21 reaction were significantly higher than those for patients with positive CBS or CCL21 reaction((P < .01). CBS or CCL21 expression was revealed as an independent poor prognostic factor for EHCC patients by Cox multivariate analysis.The present study indicates that CBS and CCL21 expression is closely associated with the pathogenesis of clinical, pathological and biological behaviors and poor prognosis in EHCC.


Assuntos
Neoplasias dos Ductos Biliares/genética , Quimiocina CCL21/genética , Colangiocarcinoma/genética , Cistationina beta-Sintase/genética , Regulação Neoplásica da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico
6.
N Engl J Med ; 383(14): 1340-1348, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997908

RESUMO

BACKGROUND: The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. METHODS: We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother's country of birth, and maternal disease history. RESULTS: During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. CONCLUSIONS: Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).


Assuntos
Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Programas de Imunização , Incidência , Invasividade Neoplásica , Sistema de Registros , Suécia/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Vacinação , Adulto Jovem
7.
Zhonghua Zhong Liu Za Zhi ; 42(8): 635-643, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867454

RESUMO

Objective: To investigate the effects of microRNA-182-5p (miR-182-5p) on cell proliferation and invasion of esophageal squamous cell carcinoma (ESCC) and its related molecular mechanisms. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to detect the miR-182-5p expression in ESCC tissues and cells. MiR-182-5p inhibitor, miR-182-5p mimic and negative control (NC) were transfected into ESCC Eca109 and TE1 cells, and miR-182-5p expression after transfection was examined using RT-qPCR. Cell counting kit-8 (CCK-8) was utilized to investigate the cell proliferation and Transwell chamber was used to detect the cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-182-5p and cell adhesion molecule 2 (CADM2), RT-qPCR was employed to detect CADM2 expression in ESCC tissues, the correlation between CADM2 and miR-182-5p was also examined. Finally, western blot was used to detect the protein expressions of CADM2, focal adhesion kinase (FAK), p-Akt and Akt after transfection. Results: The miR-182-5p level in ESCC tissues was (2.180±1.295), significantly higher than (0.890±0.284) in normal esophageal epithelial tissues (P<0.001). The survival ratio of ESCC patients with high miR-182-5p level was evidently lower than that of ESCC patients with low miR-182-5p level (P<0.05). MiR-182-5p expression was significantly associated with TNM staging and lymph node metastasis (P<0.05). The expressions of miR-182-5p in ESCC cells including EC9706, Eca109, TE1, KYSE450 and KYSE70 were (2.449±0.082), (2.965±0.088), (4.873±0.258), (1.338±0.045) and (1.999±0.082), respectively, obviously higher than (0.989±0.087) in normal esophageal epithelial cell Het-1A (all P<0.01). Besides, miR-182-5p inhibitor significantly downregulated the miR-182-5p expression in Eca109 and TE1, and suppressed cell proliferation and invasion ability. Conversely, miR-182-5p mimic significantly upregulated the miR-182-5p expression in Eca109 and TE1, and promoted cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of CADM2-3'UTR-WT and miR-182-5p mimic significantly reduced the luciferase activities in Eca109 and TE1 cells (P<0.01), and CADM2 was the direct target of miR-182-5p. The expression of CADM2 in ESCC tissues was (0.190±0.143), markedly lower than (0.845±0.327) in normal esophageal epithelial tissues (P<0.001). The miR-182-5p level exhibited negative correlation with CADM2 level in ESCC tissues (r=-0.5004, P<0.001). In addition, CADM2 expression was closely correlated with TNM staging and lymph node metastasis (P<0.05). The survival ratio of ESCC patients with high CADM2 level was evidently higher than that of ESCC patients with low CADM2 level (P<0.05). MiR-182-5p inhibitor significantly upregulated the expression of CADM2 protein, but suppressed the protein expressions of FAK, p-Akt and Akt, whereas miR-182-5p mimic markedly downregulated the expression of CADM2 protein, but promoted the protein expressions of FAK, p-Akt and Akt. Conclusion: MiR-182-5p is implicated in the carcinogenesis and development of ESCC, and thus may be a potential molecular target for ESCC patients.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Invasividade Neoplásica , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos
8.
Anticancer Res ; 40(10): 5557-5566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988879

RESUMO

BACKGROUND/AIM: E- and P-cadherin (E-cadh, P-cadh) control tumor cell invasion, metastatic or stemness potential and chemotherapy resistance. The study aimed to assess E- and P-cadherin expression in breast cancer molecular subtypes. MATERIALS AND METHODS: Immunohistochemistry for E-cadh and P-cadh was performed for 97 breast cancer cases. Membrane (M), cytoplasmic (C) or mixed (MC) patterns of E-cadh and P-cadh were considered in our evaluation. RESULTS: E-cadh and P-cadh C pattern was significantly correlated in the HER2 subtype (p=0.031). P-cadh M pattern was highly specific for the HER2 subtype (p=0.002). Only P-cadh C characterized the triple negative breast cancer subtype (p=0.015). For Luminal B/HER2 cases, P-cadh M pattern was strongly coexpressed with the E-cadh MC pattern (p=0.012). Progesterone receptor (PR) expression influenced E-cadh M pattern in the Luminal B/HER2 subtype (p=0.042). CONCLUSION: E- and P-cadherins define distinct subgroups within breast cancer molecular subtypes. Our findings support the inclusion of E- and P-cadherin into breast cancer molecular classification.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/genética , Caderinas/genética , Neoplasias de Mama Triplo Negativas/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/metabolismo , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/patologia
9.
Anticancer Res ; 40(10): 5593-5600, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988883

RESUMO

BACKGROUND: Despite improved treatment for gastric cancer (GC), the prognosis of advanced disease remains poor. Further investigation of the oncogenic sequence for GC is needed. MATERIALS AND METHODS: The expression of TYRO3 protein tyrosine kinase in five GC cell lines was confirmed using western blotting. TYRO3 knockdown in GC cells, and bromodeoxyuridine and Transwell assays were used to examine the functions of TYRO3 in tumor proliferation and invasion. Finally, TYRO3 expression in 138 patients who underwent curative gastric resection for advanced GC (Union for International Cancer Control stage II/III) was tested by immunohistochemistry, and the association between prognosis and TYRO3 expression was analyzed. RESULTS: TYRO3 was detected at various levels in all the tested GC cell lines. Deleting TYRO3 significantly suppressed proliferation and invasion. Immunohistochemistry revealed TYRO3 expression was an independent prognostic factor for overall survival in patients with GC. CONCLUSION: TYRO3 appears to mediate tumor progression and predict prognosis of patients with GC.


Assuntos
Biomarcadores Tumorais/genética , Prognóstico , Receptores Proteína Tirosina Quinases/genética , Neoplasias Gástricas/genética , Idoso , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
10.
Anticancer Res ; 40(10): 5611-5620, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988885

RESUMO

BACKGROUND/AIM: Cancer stem cell characteristics and drug resistance of colorectal cancer are associated with failure of cancer treatment. In this study, we investigated the effects of PrPC on cancer stem cell characteristics, migration, invasion, and drug resistance of 5FU-resistant CRC cells. MATERIALS AND METHODS: PrPC negative and PrPC positive cells were isolated from 5FU-resistant CRC cells using magnetic activated cell sorting. Sphere formation, cancer stem cell marker expression, migration, invasion, and drug resistance were analyzed. RESULTS: PrPC positive cells showed increased sphere formation capacity and increased expression of cancer stem cell markers compared to PrPC negative cells. In addition, PrPC positive cells showed increased migration, invasion and drug resistance compared to PrPC negative cells. Furthermore, knockdown of PrPC abolished these effects. CONCLUSION: PrPC expression is important in CRC cell behavior, such as sphere formation, migration, invasion, and drug resistance. PrPC is an important therapeutic target for the treatment of CRC.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Proteínas Priônicas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos
11.
Anticancer Res ; 40(10): 5861-5868, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988916

RESUMO

AIM: To evaluate our experience with radical radiotherapy and chemotherapy in patients with muscle-invasive bladder cancer. PATIENTS AND METHODS: The study consisted of 27 patients treated with cisplatin-based chemoradiation (CCRT), 48 treated with radiation alone (RT), and 42 with locally advanced disease treated with neoadjuvant chemotherapy and radiation (neoCRT). RESULTS: The incidence of acute grade 3 or more genitourinary (GU) toxicity in the RT, CCRT and neoCRT groups was: 25%, 11% and 19%, respectively (p=0.029). The 3-year freedom from grade 2 or more GU toxicity was: 81%, 89%, 54%, respectively (p=0.36). The long-term outcomes of 3-year local control, overall survival, and disease-free survival were as follows: RT group: 74%, 61% and 55%; CCRT group: 76%, 76% and 56%; neoCRT group: 31%, 43% and 18%, respectively. CONCLUSION: The preferable bladder-conserving approach is CRT, however RT alone might also be an option for appropriately selected patients. NeoCRT for those with locally advanced tumors remain unsatisfactory; adequate selection of patients for radical treatment is of importance.


Assuntos
Cisplatino/uso terapêutico , Músculo Esquelético/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
12.
Zhonghua Yan Ke Za Zhi ; 56(9): 681-687, 2020 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-32907301

RESUMO

Objective: To evaluate the potential association between optic nerve invasion and optic nerve obscuration during treatment of advanced retinoblastoma. Methods: Retrospective case series study. Medical records of 77 patients (77 eyes) with advanced retinoblastoma (Group D/E) who were treated with primary or secondary enucleation in the Ophthalmology Department of Peking University People's Hospital from January 1st 2012 to December 31th 2015 were retrospectively reviewed. RetCam photographs under general anesthesia at diagnosis and each subsequent follow-up were evaluated for complete obscuration of the optic nerve. The primary endpoints included prelaminar invasion, postlaminar invasion and optic nerve transection invasion. Group difference was calculated with chi-square. Results: There were 46 boys and 31 girls in the study. The mean age at the first diagnosis was (27.1±22.1) months. The optic nerve was obscured in 62 eyes (80.5%) at the first diagnosis and 61 eyes (79.2%) at the last ocular examination prior to enucleation. Twenty-nine eyes (37.7%) underwent primary enucleation. Forty-eight eyes (62.3%) were treated with eye-preserving therapy, followed by enucleation. Fourteen eyes (18.2%) were in Group D and 63 eyes (81.8%) were in Group E. Histopathologic analysis of enucleated eyes without optic nerve obscuration (16 eyes) showed prelaminar invasion in 7 eyes, postlaminar invasion in 2 eyes and optic nerve transection invasion in 0 eyes. Histopathologic analysis of enucleated eyes with optic nerve obscuration (61 eyes) showed prelaminar invasion in 26 eyes, postlaminar invasion in 9 eyes and optic nerve transection invasion in 4 eyes. The difference between two groups did not achieve statistical significance (P=0.935, 1.000, 0.296). Histopathologic analysis of enucleated eyes with persistent complete obscuration of the optic nerve showed a high risk factor in 10 eyes (10/40), while in 1 eye (1/8) the optic nerve was visible at the initial presentation and obscured before secondary enucleation (P=0.529). Conclusion: Optic nerve obscuration at the last examination prior to enucleation may not be associated with postlaminar optic nerve invasion in advanced retinoblastoma. (Chin J Ophthalmol, 2020, 56: 681-687).


Assuntos
Neoplasias da Retina/cirurgia , Retinoblastoma/cirurgia , Pré-Escolar , Enucleação Ocular , Feminino , Humanos , Lactente , Masculino , Invasividade Neoplásica , Nervo Óptico/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco
13.
PLoS One ; 15(9): e0237925, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32911496

RESUMO

BACKGROUND: Invasive Breast Cancer (IBC) risk estimates continue to be based on data collated from cancer registries, i.e., retrospective research that excludes disease-free women. For women without a prior diagnosis, these estimates inflate both risk and screening frequency recommendations and inadvertently increase recently recognized harms from overdiagnosis and overtreatment. OBJECTIVE: To estimate the likelihood that pre or postmenopausal women with no prior diagnosis will remain free of IBC in order to enable evidence-based screening recommendations. METHODS: Prospective data from 21 studies of 2,402,672 women were analyzed, updating our previously published systematic search of 19 studies. This second systematic search included PubMed and The Cochrane Library from 2012 through April 2019. Inclusion criteria: only studies reporting the number of women enrolled, length of follow-up, and number of women diagnosed with IBC. Linear regression was used to estimate the percentage of women expected to remain free from an IBC diagnosis based on follow-up duration. To minimize non-response bias and selective outcome bias, only studies reporting outcomes for all enrolled women followed for similar, specific lengths of time were included. Sensitivity analyses confirm that the overall findings were unchanged by age at enrollment, menopausal status, screened women, variation in sample size, duration of follow-up, and heteroskedasticity. RESULTS: The calculated percentage of women remaining IBC-free after follow-ups of 5, 10, 15, 20 and 25 years decreases uniformly by about one-fourth of one percent per year, i.e., 0.255% (95% CI: -0.29, -0.22; p < .0001). At 25 years, the expected percentage of women with no invasive breast cancer is 93.41% (95% CI: 92.75, 94.07). CONCLUSIONS: Over 99.7% of pre/postmenopausal women with no prior diagnosis continued with no IBC each year, with 93.41% still free after 25 years. Our study supports the medical justification for reducing the frequency of mammograms for menopausal women with no prior IBC diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Pós-Menopausa/fisiologia , Viés , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Invasividade Neoplásica , Probabilidade , Fatores de Risco , Tamanho da Amostra , Reino Unido
14.
Am J Chin Med ; 48(6): 1491-1509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32924531

RESUMO

Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial-mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.


Assuntos
Adenocarcinoma/patologia , Astragalus propinquus/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Neoplasias Pulmonares/patologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Fitoterapia , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Células A549 , Adenocarcinoma/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Neoplasias Pulmonares/metabolismo , Camundongos SCID , Invasividade Neoplásica , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico
15.
Nat Commun ; 11(1): 4498, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908142

RESUMO

The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.


Assuntos
Macrófagos/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Idoso , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Anilidas/farmacologia , Anilidas/uso terapêutico , Biópsia , Buffy Coat/citologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Quimioterapia Adjuvante , Técnicas de Cocultura , Intervalo Livre de Doença , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/prevenção & controle , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Intervalo Livre de Progressão , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Procedimentos Cirúrgicos Robóticos , Transdução de Sinais/imunologia , Análise de Célula Única , Células THP-1 , Compostos de Tosil/farmacologia , Compostos de Tosil/uso terapêutico
16.
Medicine (Baltimore) ; 99(37): e22115, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925757

RESUMO

Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy.This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12-26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P = .04).Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Artéria Celíaca/cirurgia , Artéria Hepática/cirurgia , Artéria Mesentérica Superior/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Taxa de Sobrevida
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(6): 893-898, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895194

RESUMO

OBJECTIVE: To analyze the association of integrinα5 (ITGA5) with grading of liver cancer and the overall patient survival and investigate the effects of integrin α5 (ITGA5) silencing on the proliferation, invasion and migration abilities of human liver cancer Bel-7404 cells. METHODS: UALCAN was used to analyze the expression of ITGA5 in liver cancer tissues and normal tissues, and expression in different grades of liver cancer tissues. GEPIA was used to analyze the relationship between ITGA5 expression and the survival of liver cancer patients through.The ITGA5 shRNA lentiviral vector was used to infect Bel-7404 cells to establish a cell line with stable ITGA5 silencing verified by Western blotting. Plate clone formation assay and Transwell assay were used to detect the proliferation, invasion and migration of Bel-7404 cells. The correlation between ITGA5 and PI3K in liver cancer tissues and control tissues was analyzed using Oncomine cancer specimen database. RESULTS: The expression of ITGA5 was significantly higher in liver cancer than in normal tissues (P < 0.05). The expression of ITGA5 was significantly lower in grade 1 than in grade 2 liver cancer, and also lower in grade 2 than in grade 3 liver cancer (P < 0.05). The patients with high ITGA5 expression had a significantly lower overall survival rate than those with low ITGA5 expression (P < 0.05). Plate clone formation assay showed that the clone formation rate was significantly lowered in Bel-7404 cells with ITGA5 silencing compared with the blank and negative control cells (P < 0.05). ITGA5 silencing significantly attenuated the migration of Bel-7404 cells as shown by Transwell assay (P < 0.05). ITGA5 and PI3K were both highly expressed and showed a positive correlation in liver cancer tissues (P < 0.05). CONCLUSIONS: ITGA5 is closely related to the progression of liver cancer and the patients' prognosis. ITGA5 silencing inhibits the proliferation, invasion and migration of liver cancer cells. ITGA5 promotes the liver cancer growth and metastasis possibly by regulating the PI3K signaling pathway.


Assuntos
Proliferação de Células , Neoplasias Hepáticas , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfa5 , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(6): 869-875, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895200

RESUMO

OBJECTIVE: To investigate the effect of miR-204 on the invasion and metastasis of breast cancer by targeted regulation of HNRNPA2B1. METHODS: The bioinformatics database was used to obtain data of the expressions of miR-204 in breast cancer patients and the survival rate of the patients. RT-qPCR was used to detect the expression of miR-204 in breast cancer cell lines. The expression vector GV369-miR-204 was used to overexpress miR-204 in MDA-MB-231 cells. Transwell assay was performed to detect the effect of miR-204 on the migration and invasion ability of the breast cancer cells. The key genes (hub genes) of miR-204 were determined by bioinformatics method. A dual luciferase assay was used to analyze the targeting relationship between miR-204 and HNRNPA2B1. The expression of HNRNPA2B1 in MDA-MB-231 cells after miR-204 overexpression was detected by Western blotting, and Transwell assay was used to examine the changes in the cell invasion ability. RESULTS: The expression of miR-204 was decreased in both breast cancer tissues, and was significantly lower in breast cancer MDA-MB-231 cells than in MCF-10A cells (P < 0.05). The decreased expression of miR-204 was associated with poorer prognosis of breast cancer patients (P < 0.05). Upregulation of miR-204 in MDA-MB-231 cells significantly inhibited the invasion and migration of the cells (P < 0.05). Analysis of the data from the Starbase revealed that the expression of miR-204-5p was negatively correlated with the expression of HNRNPA2B1, and the expression of HNRNPA2B1 was increased in breast cancer patients (P < 0.05) in association with a poorer prognosis of the patients (P < 0.05). Dual luciferase assay demonstrated that miR-204 could bind to HNRNPA2B1 in a target-specific manner. Western blotting and Transwell assay showed that miR-204 significant inhibited the migration and invasion ability of breast cancer cells by targeting HNRNPA2B1 (P < 0.05). CONCLUSIONS: miR-204 expression is decreased in breast cancer tissues and cells, and its overexpression can inhibit the invasion and metastasis of breast cancer cells by targeted regulation of HNRNPA2B1.


Assuntos
Neoplasias da Mama , MicroRNAs/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(5): 661-669, 2020 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-32897196

RESUMO

OBJECTIVE: To investigate serum levels of long non-coding RNA (lncRNA) TUSC7 in patients with esophageal squamous cell carcinoma (ESCC), its association with clinicopathological parameters and its role in promoting tumor metastasis and invasion. METHODS: Serum samples were collected from 60 patients with ESCC admitted between January, 2017 and May, 2019, with 60 age- and gender-matched healthy subjects as the control group. Serum level of TUSC7 in ESCC patients and its expression in 4 ESCC cell lines was detected with RT-qPCR. The association of serum TUSC7 level with the clinicopathological features of the patients was analyzed. KYSE-30 cell models with TUSC7 overexpression or knockdown were established, and the proliferation of the cells was examined with MTT assay and their migration and invasion were assessed using wound healing and Transwell assays. Western blotting was used to detect the cellular expressions of the proteins associated with epithelial-mesenchymal transition (EMT). RESULTS: The patients with ESCC had significantly lower serum TUSC7 level than the healthy control subjects (P < 0.05). The ESCC cell lines also expressed lower levels of TUSC7 than normal cells (P < 0.05). Serum TUSC7 level was negatively correlated with tumor staging, lymph node metastasis and infiltration (P < 0.05) but was not significantly correlated with other clinicopathological parameters in ESCC patients. In the invitro cell experiment, overexpression of TUSC7 in KYSE-30 cells significantly inhibited cell migration and invasion (P < 0.05), enhanced the expression of the EMT marker protein E-cadherin and lowered the expressions of N-cadherin, Vimentin and MMP9 (P < 0.05); knocking down TUSC7 in the cells produced the opposite effects. CONCLUSIONS: The down-regulation of TUSC7 expression in the serum of ESCC patients and in ESCC cell lines is associated with the metastasis of ESCC and promotes tumor cell migration and invasion by promoting EMT, indicating the potential of serum TUSC7 level as a molecular marker for diagnosis, treatment and metastasis monitoring of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica
20.
Int J Nanomedicine ; 15: 6451-6468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922011

RESUMO

Background: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse. Purpose: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG2000-MAL and CPP-PVGLIG-PEG5000, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration. Methods and Results: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency. Conclusion: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Microambiente Tumoral , Células A549 , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Morte Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Galinhas , Endocitose/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Hidrólise , Lipossomos , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Microambiente Tumoral/efeitos dos fármacos , Vinorelbina/farmacologia , Vinorelbina/uso terapêutico
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