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1.
Support Care Cancer ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31982960

RESUMO

PURPOSE: Although docetaxel plus ramucirumab has shown superior treatment efficacy over docetaxel monotherapy for patients with non-small cell lung cancer (NSCLC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to validate the primary prophylactic use of pegfilgrastim with docetaxel and ramucirumab treatment in Japanese patients with NSCLC. METHODS: Patients with NSCLC with progression after at least one round of chemotherapy were enrolled and administered docetaxel (60 mg/m2) plus ramucirumab (10 mg/kg) intravenously on day 1, followed by pegylated-granulocyte colony-stimulating factor (3.6 mg) on day 2 of a 21-day treatment cycle. The primary study endpoint was the percentage of patients who developed FN. Secondary endpoints included overall survival, progression-free survival, overall response rate, and safety. RESULTS: Overall, 20 patients (15 men and 5 women) were enrolled, of whom one developed FN, resulting in an overall FN rate of 5%. The response and disease control rates were 40% and 85%, respectively. The median progression-free survival was 6.6 (95% confidence interval [CI], 0.5-NR) months. The median overall survival was 18.4 (95% CI, 2.2-11.0) months. Six patients aged over 75 years were included in this study, and although most adverse events were durable, ramucirumab-associated adverse events occurred more frequently in these patients. CONCLUSIONS: We observed a 5% FN rate using primary prophylactic pegylated-granulocyte colony-stimulating factor with docetaxel plus ramucirumab in Japanese patients with NSCLC. While most adverse events were durable, elderly patients should be closely monitored.

2.
Anticancer Res ; 40(1): 261-269, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892575

RESUMO

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.


Assuntos
Adenoma Pleomorfo/imunologia , Imunidade , Neoplasias Pulmonares/imunologia , Adenoma Pleomorfo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico
3.
Mol Imaging Biol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792836

RESUMO

PURPOSE: 3-[18F]Fluoro-α-methyl-L-tyrosine ([18F]FAMT) is an amino acid positron emission tomography (PET) tracer specific for cancer detection by assessment of tumor amino acid metabolism. Little is known on whether or not the uptake of [18F]FAMT within cancer cells is associated with the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody efficacy. We conducted a clinicopathological study to assess the expression of PD-L1 and the presence of tumor-infiltrating lymphocytes (TILs) in patients with non-small cell lung cancer (NSCLC) diagnosed by PET. PROCEDURES: A total of 75 patients with NSCLC who underwent [18F]FAMT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET were enrolled in the study. Tumor specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), PD-L1 (using different antibody clones including E1L3N and 28-8), CD3, CD4, and CD8. The uptake of [18F]FAMT was correlated with clinicopathological variables. RESULTS: High uptake of [18F]FAMT was significantly associated with disease staging, initial treatment (surgical resection or chemotherapy), and the expression of PD-L1 (E1L3N). The value of the maximum standardized uptake value (SUVmax) for [18F]FAMT was significantly correlated with PD-L1 (E1L3N) expression, Glut1, and the SUVmax for [18F]FDG in patients with histological results of adenocarcinoma (AC) and advanced disease. A validation cohort for anti-PD-L1 using clone 28-8 showed a statistically significant correlation between SUVmax for [18F]FAMT and the expression of PD-L1 (28-8) and between the expression of PD-L1 (E1L3N) and PD-L1 (28-8). CONCLUSIONS: The uptake of [18F]FAMT on PET imaging was significantly correlated with PD-L1 expression in NSCLC, especially in patients with AC and advanced disease.

4.
Cancers (Basel) ; 11(11)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31653009

RESUMO

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin ß3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

5.
Sci Rep ; 9(1): 14503, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601857

RESUMO

Immunotherapy targeting immune checkpoint molecules has provided remarkable clinical benefits in cancer patients but no clinically relevant biomarker for predicting treatment outcomes exists. Recently, we demonstrated that glycan structures of serum α1-acid glycoprotein (AGP) changed dramatically in cancer patients and that α1,3fucosylated AGP (fAGP) levels increased along with disease progression and decreased responding to chemotherapy treatments. Here, the fAGP was analyzed in sera prospectively obtained from 39 patients with advanced lung cancer who underwent immunotherapy with anti-PD-1 antibody, nivolumab. Twenty-three patients had significantly high fAGP levels above the cut-off value (H-fAGP) at one month after starting the treatment and 20 patients in this group, whose tumor sizes did not decrease, maintained high fAGP levels continuously and subsequently died. However, the other 16 patients, whose fAGP levels decreased or maintained below the cut-off value (L-fAGP), survived during a 2-year observation even though 5 patients in this group had no tumor shrinkage. Accordingly, the overall survival rate was found to significantly correlate with the fAGP level. Multivariate analyses revealed that the H-fAGP was an independent risk factor for cancer progression. Therefore, the fAGP level appeared to be a reliable biomarker for predicting clinical efficacy of immunotherapy with nivolumab.

6.
Front Oncol ; 9: 702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417874

RESUMO

Background and purpose: Favorable clinical outcomes of carbon-ion radiotherapy for pelvic recurrence of rectal cancer have been described by previous prospective phase I/II and II studies; however, these studies were performed at a single institution. Therefore, we conducted a prospective observational study aimed at exploring whether carbon-ion radiotherapy for post-operative pelvic recurrence of rectal cancer provides a less invasive local treatment strategy with higher cure rates than other anticancer treatments. Materials and methods: Patients (1) with pelvic recurrence of rectal cancer, as confirmed by histology or diagnostic imaging; (2) without distant metastasis; (3) who had undergone curative resection of their primary disease and regional lymph nodes, without gross or microscopic residual disease; and (4) with radiographically measurable tumors were included in this study. The total carbon-ion radiotherapy dose for all patients was 73.6 Gy [relative biological effectiveness (RBE)] administered in 16 fractions once daily for 4 days a week (Tuesday to Friday). Results: A total of 28 patients were enrolled between October 2011 and July 2017. The median follow-up duration was 38.9 months. The 3-year overall survival, local control, and progression-free survival rates were 92, 86, and 31%, respectively. At the time of the analysis, 4 patients had local recurrence, and 7 had died of rectal cancer. None of the patients developed grade 3 or higher acute toxicities. Late toxicities occurred in 2 and 7 patients who developed grade 3 pelvic infection and grade 2 peripheral neuropathy, respectively. Conclusion: Carbon-ion radiotherapy for pelvic recurrence of rectal cancer showed favorable clinical outcomes and is a highly curative and less invasive local treatment.

7.
Lung Cancer ; 134: 180-186, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31319979

RESUMO

OBJECTIVES: Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) is a clinically useful modality for cancer evaluation. The mechanism of 18F-FDG uptake within cancer cells involves the glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1 α (HIF-1α). Although recent research has shown its clinical efficacy in small-cell lung cancer (SCLC), no suitable biomarker has been identified. We conducted a clinicopathological study to examine the relationship between tumor immunity and 18F-FDG uptake in patients with SCLC. MATERIALS AND METHODS: Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student's t-test, χ2 test, non-parametric Spearman's rank test, and Kaplan-Meier method were used to evaluate associations between the variables. RESULTS: A total of 98 patients 78 men and 20 women who underwent 18F-FDG PET, were enrolled in this study. PD-L1 was expressed in 36.7% (36/98) of all patients; this was significantly associated with GLUT1 expression (p = 0.04). The accumulation of 18F-FDG was significantly higher in patients with low CD8 and CD4 TILs than in those with high TILs (p = 0.03 and p = 0.01, respectively). The uptake of 18F-FDG was not significantly associated with the expression of either Foxp3 or PD-L1. Multivariate analysis demonstrated that advanced stage, poor ECOG-PS, and high SUVmax were independent predictors of poor OS. Among patients with limited-stage disease, multivariate analysis confirmed high PD-L1 expression and a high SUVmax to be independent predictors of poor OS. However, only ECOG-PS was found to be an independent predictor of poor OS among patients with extensive-stage tumors. CONCLUSION: High SUVmax on 18F-FDG-PET is correlated with low expression of CD8(+) and CD4(+) TILs, but is an independent prognostic factor for OS, particularly in those with limited disease. Further studies are warranted to validate our findings.

8.
Cancer Sci ; 110(9): 2933-2940, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278877

RESUMO

Chemotherapy has been the treatment of choice for unresectable peritoneal dissemination; however, it is difficult to eradicate such tumors because of poor drug delivery. To solve this issue, we developed FF-10832 as liposome-encapsulated gemcitabine to maintain a high concentration of gemcitabine in peritoneal tumors from the circulation and ascites. A syngeneic mouse model of peritoneal dissemination using murine Colon26 cell line was selected to compare the drug efficacy and pharmacokinetics of FF-10832 with those of gemcitabine. Despite the single intravenous administration, FF-10832 treatment enabled long-term survival of the lethal model mice as compared with those treated with gemcitabine. Pharmacokinetic analysis clarified that FF-10832 could achieve a more effective gemcitabine delivery to peritoneal tumors owing to better stability in the circulation and ascites. The novel liposome-encapsulated gemcitabine FF-10832 may be a curative therapeutic tool for cancer patients with unresectable peritoneal dissemination via the effective delivery of gemcitabine to target tumors.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Ascite/metabolismo , Desoxicitidina/análogos & derivados , Neoplasias Peritoneais/tratamento farmacológico , Peritônio/patologia , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Ascite/etiologia , Linhagem Celular Tumoral/transplante , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Feminino , Humanos , Injeções Intravenosas , Estimativa de Kaplan-Meier , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Distribuição Tecidual , Resultado do Tratamento
9.
Medicine (Baltimore) ; 98(26): e16126, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261532

RESUMO

Ultrasound-guided central venous catheterization may cause lethal mechanical complications intraoperatively. We developed a novel device to prevent such complications. It works as a needle guide to supplement the operator's skill. We evaluated the utility of this device in terms of the success rate and visualization of the needle tip while penetrating the target vessel using a simulator.This study was approved by the local ethics committee. The new device - an optical skill-assist device - has a slit and a mirror in the center. The operator can see the needle's reflection in the mirror through the slit and can thus ensure that the needle is directed in line with the ultrasound beam. Participants were recruited by placing an advertisement for a hands-on seminar on ultrasound-guided vascular access. They received hands-on training on the in-plane approach for 2 hours. Pre-test and post-test without the device and an additional test using the device were performed to evaluate the proficiency of ultrasound-guided vascular access. An endoscope inserted into the simulated vessel was used to detect the precise location of the needle tip in the vessel.The primary outcomes were the success rate of the procedure. The secondary outcome was visualization of the needle tip while penetrating the simulated vessel. The chi-squared test was used for comparing the success rate and needle tip visualization between the different tests. P < .05 was considered to indicate significant differences.Forty-two participants were enrolled in this study. The success rate did not increase after the simulation training (P = .1). Using the optical skill-assist device, the rate improved to 100%. There was a significant difference in success rate between the pre-test and additional test using the optical skill-assist device (P = .003). Needle tip visualization significantly improved with the use of the optical skill-assist device compared to the pre-test (P < .001) and post-test (P = .001).Simulation training improved participants' skill for ultrasound-guided vascular access, but the improvement depended on each participant. However, further, improvement was achieved with the use of the optical skill-assist device.The optical skill-assist device is useful for supplementing the operator's skill for ultrasound-guided central venous catheterization.


Assuntos
Cateterismo Venoso Central/instrumentação , Ultrassonografia de Intervenção/instrumentação , Cateterismo Venoso Central/métodos , Competência Clínica , Educação Médica , Humanos , Complicações Intraoperatórias/prevenção & controle , Aprendizagem , Imagem Óptica/instrumentação , Médicos , Complicações Pós-Operatórias/prevenção & controle , Dados Preliminares , Treinamento por Simulação , Ultrassonografia de Intervenção/métodos
10.
Anticancer Res ; 39(5): 2535-2543, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092450

RESUMO

BACKGROUND/AIM: L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers. However, the clinicopathological significance of LAT1 and 4F2 cell surface antigen (4F2hc) in patients with colorectal cancer (CRC) is unknown. The aim of this study was to clarify the prognostic significance of LAT1 expression in CRC patients who underwent surgical resection. MATERIALS AND METHODS: Samples from one hundred and forty-seven patients were examined by immunohistochemistry. The expression of LAT1 and 4F2hc, and the Ki-67 labeling index were assessed using resected tumor specimens. RESULTS: The positive expression of LAT1 and 4F2c was 80% (118/147) and 58% (86/147) (p<0.01), respectively. The expression of LAT1 was identified as an independent significant marker linked to worse prognosis in patients with CRC, and was correlated with tumor cell proliferation, tumor aggressiveness, and metastasis. Moreover, LAT1 was closely associated with the expression of 4F2hc and phosphorylation of the mTOR pathway. CONCLUSION: LAT1 is a significant molecular marker used to predict prognosis after surgical resection of CRC patients.


Assuntos
Neoplasias Colorretais/cirurgia , Cadeia Pesada da Proteína-1 Reguladora de Fusão/genética , Transportador 1 de Aminoácidos Neutros Grandes/genética , Prognóstico , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade
11.
Medicine (Baltimore) ; 98(8): e14665, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813212

RESUMO

BACKGROUND: A high-fidelity task simulator for cricothyroidotomy was created using data from a 3-dimensional (3D) computed tomography scan using a 3D printer. We hypothesized that this high-fidelity cricothyroidotomy simulator results in increased proficiency for needle cricothyroidotomy compared with conventional simulators. METHODS: Cricothyroidotomy-naive residents were recruited and randomly assigned to 2 groups, including simulation training with a conventional simulator (Group C) and with a high-fidelity simulator (Group 3D). After simulation training, participants performed cricothyroidotomy using an ex vivo porcine larynx fitted with an endoscope to record the procedure. The primary outcomes were success rate and procedure time. The secondary outcome was a subjective measure of the similarity of the simulator to the porcine larynx. RESULTS: Fifty-two residents participated in the study (Group C: n = 27, Group 3D: n = 25). There was no significant difference in the success rate or procedure time between the 2 groups (success rate: P = .24, procedure time: P = .34). There was no significant difference in the similarity of the simulators to the porcine larynx (P = .81). CONCLUSION: We developed a high-fidelity simulator for cricothyroidotomy from 3D computed tomography data using a 3D printer. This anatomically high-fidelity simulator did not have any advantages compared with conventional dry simulators.


Assuntos
Anestesiologia/educação , Treinamento com Simulação de Alta Fidelidade/métodos , Internato e Residência/métodos , Músculos Laríngeos/cirurgia , Traqueotomia/educação , Manuseio das Vias Aéreas/métodos , Simulação por Computador , Avaliação Educacional/métodos , Humanos , Japão , Modelos Anatômicos , Materiais de Ensino/normas
12.
Anticancer Res ; 39(3): 1455-1461, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842182

RESUMO

BACKGROUND/AIM: No definitive biomarker exists for predicting treatment efficacy or response to therapy with antibody to programmed cell death-1 (PD1) for patients with advanced non-small cell lung cancer (NSCLC). Hence, we investigated whether the Glasgow prognostic score (GPS) predicted anti-PD1 treatment response for advanced NSCLC. PATIENTS AND METHODS: This study retrospectively identified 47 patients with NSCLC treated with anti-PD1 and assessed the prognostic value of the GPS. The GPS was calculated using C-reactive protein and albumin concentrations 1 month after starting anti-PD1 treatment. Kaplan-Meier method and Cox proportional hazard models were used to examine differences in progression-free (PFS) and overall (OS) survival, and clinical response. RESULTS: The post-treatment GPS independently predicted anti-PD1 treatment efficacy, as a good post-treatment GPS (GPS 0-1) was significantly associated with improved PFS. Intra-treatment GPS change was associated with clinical response. CONCLUSION: The post-treatment GPS independently predicted efficacy of anti-PD1 treatment for NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Albumina Sérica/análise , Resultado do Tratamento
13.
Medicine (Baltimore) ; 98(6): e14413, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732193

RESUMO

RATIONALE: A peripherally inserted central catheter (PICC) is typically inserted with the patient in the supine position. Here, we placed a PICC in a patient in the sitting position, in order to treat congestive heart failure. PATIENT CONCERNS: A 65-year-old man was diagnosed with end-stage lung cancer. He had experienced septic shock and was medicated with continuous infusion of noradrenaline through a peripheral vein, in order to maintain sufficient blood pressure. However, indwelling peripheral venous catheters were difficult to place and maintain. DIAGNOSIS: The patient experienced orthopnea due to congestive heart failure and could not assume any other position. INTERVENTIONS: An anesthesiologist performed PICC placement while the patient was in the sitting position, using ultrasound guidance. OUTCOMES: The patient's orthopnea was slightly ameliorated, and he was able to sleep at night. LESSONS: The technique of inserting a PICC in the sitting position is simple and feasible. This approach may be useful for patients in whom central venous access is needed, but the supine position cannot be achieved.


Assuntos
Cateterismo Periférico/métodos , Insuficiência Cardíaca/terapia , Postura Sentada , Idoso , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino
14.
Medicine (Baltimore) ; 98(3): e14208, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653177

RESUMO

RATIONALE: Obtaining venous access in a patient with extensive postburn scar contractures is a challenge. PATIENT CONCERNS: A 39-year-old woman suffered a burn 2 years previously with a total body surface area burn of 93%, and a burn index of 85. Reconstructive surgery was previously performed 39 times. Split-thickness skin grafting to the neck was planned. She had no accessible peripheral veins. DIAGNOSIS: Difficult venous access due to excessive burn scar contractures. INTERVENTIONS: Central venous catheterization was considered impossible even with ultrasound guidance. We placed a midline catheter for intraoperative venous access in a patient with extensive burn scar contractures. The midline catheter is a peripheral venous catheter placed in an arm vein. OUTCOMES: We successfully placed a midline catheter in the right brachial vein. This catheter was used for 24 days without difficulty. LESSONS: The midline catheter is a viable choice in patients with difficult vascular access due to extensive postburn scar contractures.


Assuntos
Queimaduras/complicações , Cateterismo Periférico/métodos , Cicatriz/complicações , Contratura/etiologia , Ultrassonografia de Intervenção/métodos , Adulto , Cicatriz/cirurgia , Feminino , Humanos , Transplante de Pele/métodos , Dispositivos de Acesso Vascular
15.
Int J Oncol ; 54(3): 833-844, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628666

RESUMO

Using whole transcriptome analysis and a lentiviral short hairpin RNA screening library, carboxypeptidase A4 (CPA4) was identified as a novel marker in breast cancer and a therapeutic target in triple­negative breast cancer (TNBC) in the present study. Immunohistochemistry was used to evaluate the presence of CPA4, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki67, epidermal growth factor receptor, cytokeratin 5/6, aldehyde dehydrogenase 1, cluster of differentiation (CD)44, CD24, claudins, E­cadherin, vimentin and androgen receptor in 221 cases of breast cancer, including 68 TNBC cases. The effects of CPA4 on the viability and migration ability of TNBC cells were analyzed using RNA interference methods. Increased CPA4 expression, specifically in the cytoplasm of cancer tissue cells, was detected. Furthermore, high CPA4 expression in TNBC cases was associated with low expression of E­cadherin and with the expression of cancer stem cell markers (high CD44/low CD24). Patients with TNBC and high levels of CPA4 expression had a significantly poorer prognosis compared with those with low CPA4 expression. Notably, viability and migration were reduced, but E­cadherin expression was upregulated in CPA4­suppressed TNBC cells. The present data suggested that CPA4 may be a novel inducer for epithelial­mesenchymal transition, which is characterized by the downregulation of E­cadherin and mesenchymal phenotypes. To conclude, CPA4 may be a marker for poor prognosis and a promising therapeutic target in TNBC with aggressive phenotypes.


Assuntos
Carboxipeptidases A/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carboxipeptidases A/genética , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Fenótipo , Prognóstico , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/genética
16.
Hum Pathol ; 84: 142-149, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30300664

RESUMO

Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients with pulmonary pleomorphic carcinoma (PPC) remainsunknown. The aim of this study is to clarify the prognostic impact of these amino acid transporters in PPC. One hundred five patients with surgically resected PPC were assessed by immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index were investigated using specimens of the resected tumors. LAT1 and 4F2hc were highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48% of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58% of patients with a nonadenocarcinoma component (n = 57, P = .18), respectively. A high LAT1 expression was significantly related to advanced disease, lymphatic permeation, tumor cell proliferation, and 4F2hc expression. By multivariate analysis, LAT1 and 4F2hc were identified as significant independent markers for predicting a worse prognosis. LAT1 is highly expressed in PPC, and high LAT1 expression can serve as a significant predictor linked to a worse prognosis in patients with PPC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Cadeia Pesada da Proteína-1 Reguladora de Fusão/biossíntese , Transportador 1 de Aminoácidos Neutros Grandes/biossíntese , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Anticancer Res ; 39(1): 395-403, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30591486

RESUMO

BACKGROUND/AIM: The ß2-adrenergic receptor (ß2AR) is highly expressed in various human cancers and has been linked to tumor growth and metastases. Although ß2AR is considered a novel therapeutic target of human neoplasms, the clinicopathological significance of ß2AR expression in patients with pulmonary pleomorphic carcinoma (PPC) remains unclear. The aim of this study was to clarify the prognostic impact of ß2AR in PPC. PATIENTS AND METHODS: One hundred and five Japanese patients with surgically resected PPC were included in the study. The expression levels of ß2AR were assessed by immunohistochemistry in specimens from the resected tumors, and their association with patient survival, as well as with tumor characteristics was investigated. RESULTS: ß2AR was highly expressed in 63% of all patients, irrespective of adenocarcinoma components present. The ß2AR expression was significantly associated with lymph node metastasis, lymphatic permeation and tumor cell proliferation in PPC patients with early-stage disease (stage I or II). A high ß2AR expression was identified as a significant predictor of worse prognosis for PPC patients during early stages of the disease. Multivariate analysis confirmed that ß2AR expression was an independent factor for predicting the overall survival of PPC patients. CONCLUSION: ß2AR can serve as a significant predictor of tumor aggressiveness and poor survival for PPC patients, especially those with early-stage disease.


Assuntos
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Prognóstico , Receptores Adrenérgicos beta 2/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Estadiamento de Neoplasias
18.
Anticancer Res ; 38(10): 5909-5916, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30275218

RESUMO

BACKGROUND/AIM: To determine the most reliable predictor for pathologic complete response (pCR) in patients who underwent preoperative chemoradiotherapy and regional hyperthermia (HCRT) for rectal cancer. PATIENTS AND METHODS: Thirty-six patients were enrolled. The local control status of the patients was assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), magnetic resonance imaging (MRI), and colonoscopy before and after HCRT. The relationships between various parameters of these clinical examinations and pCR were analyzed. RESULTS: Ten (28%) patients achieved pCR. The accuracies of predicting pCR using FDG-PET/CT, MRI, and colonoscopy were 78%, 61%, and 75%, respectively. FDG-PET/CT was the only independent predictive modality for pCR (p=0.021). The maximum standardized uptake value (SUVmax) and SUVmax normalized to liver uptake (SLR) after HCRT showed the highest sensitivity (90%) and the decreasing rate of SUVmax and SLR demonstrated the highest specificity (89%) for pCR. CONCLUSION: SUVmax-based parameters of FDG-PET/CT after HCRT were the most reliable predictors for pCR.


Assuntos
Quimiorradioterapia , Fluordesoxiglucose F18/metabolismo , Hipertermia Induzida , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Compostos Radiofarmacêuticos/metabolismo , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/metabolismo , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do Tratamento
19.
Eur J Cancer ; 101: 181-190, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30077123

RESUMO

2-Deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET) is a useful modality for the assessment of tumour glucose metabolism by upregulation by hypoxia. Little is known whether the uptake of 18F-FDG within cancer cells is linked to the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody. We conducted a clinicopathological study to assess the expression of PD-L1 and tumour-infiltrating lymphocytes (TILs) in patients with surgically resected pulmonary adenocarcinoma (AC) who received preoperative 18F-FDG PET. A total of 315 patients with lung AC who received 18F-FDG PET were enrolled in the study. Tumour specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), hypoxia-inducible factor-1α (HIF-1α), PD-L1, CD4 and CD8. We assessed whether the uptake of 18F-FDG was correlated with clinicopathological variables. PD-L1 was highly expressed in 60% of all patients with AC, and the expression level was significantly correlated with 18F-FDG uptake, glucose metabolism and hypoxia. PD-L1 and the maximum standardised uptake value (SUVmax) were identified as independent prognostic predictors by multivariate analysis. In particular, PD-L1 could be a significant marker for predicting worse outcomes in AC patients with high 18F-FDG uptake but not in those with low 18F-FDG uptake. According to the epidermal growth factor receptor (EGFR) mutation status, the expression of PD-L1 was significantly correlated with SUVmax in patients with EGFR mutation, whereas, PD-L1 was a significant predictive negative factor in those with wild-type EGFR. 18F-FDG uptake was significantly correlated with PD-L1 expression, and the latter was closely linked to the presence of glucose metabolism and hypoxia in patients with pulmonary AC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Antígeno B7-H1/biossíntese , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação
20.
PLoS One ; 13(7): e0200749, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30020986

RESUMO

In a surgical operation requiring endoscopy, it is essential to obtain a clear endoscopic view. However, it is often disturbed by the contamination on the lens during the surgery. No device can clean the lens surface simply and completely. Many surgeons are hampered by the impaired view and the distraction by the repeated cleaning of the lens. Therefore, we developed a novel endoscope cleaning device to address this problem. The device was made of 3D-printed rubber-like plastic. It contains a syringe filled with saline and an aspiration system. It would be used intraoperatively to wash the lens surface in a few seconds with rapid flow of water and air. The cleaning ability of the device was evaluated using mayonnaise with adenosine triphosphate (ATP) as a model contaminant. The gauze-wiping maneuver was selected as control. After each maneuver, the clarity of the endoscopic view was evaluated, and residual contaminants were assessed quantitatively with ATP assay. The cleaning device obtained a crisp and clear view and eliminated the contaminant on the lens every time after a single cleaning maneuver. The gauze-wiping maneuver required for the lens to be wiped at least three times to obtain a clear view, and even then, some contaminants remained. Repeated contamination and cleaning using gauze led to accumulation of contaminants on the lens, which resulted in difficulty in cleaning the lens as the operation proceeded. The cleaning device did not show such accumulation. Our novel cleaning device with air and water flow has been shown to wash out the lens contaminants completely and immediately in a simple manner. It is expected to improve the safety and cost-effectiveness of endoscopic surgery.


Assuntos
Ar , Endoscopia/métodos , Contaminação de Equipamentos/prevenção & controle , Lentes , Água
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