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1.
Biosens Bioelectron ; 216: 114643, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36030742

RESUMO

The transfer of redox-labelled bioelectrochemical sensors from proteins to cells is not straightforward because of the cell downward force issue on the surface of the sensors. In this paper, 20-nm-thick nanopillars are introduced to overcome this issue, in a well-controlled manner. We show on both molecular dynamics simulations and experiments that suspending cells a few nanometers above an electrode surface enables redox-labelled tethered DNA aptamer probes to move freely, while remaining at an interaction distance from a target membrane protein, i. e. epithelial cell adhesion molecule (EpCAM), which is typically overexpressed in cancer cells. By this nanopillar configuration, the interaction of aptamer with cancer cells is clearly observable, with 13 cells as the lower limit of detection. Nanoconfinement induced by the gap between the electrode surface and the cell membrane appears to improve the limit of detection and to lower the melting temperature of DNA aptamer hairpins, offering an additional degree of freedom to optimize molecular recognition mechanisms. This novel nanosupported electrochemical DNA cell sensor scheme including Brownian-fluctuating redox species opens new opportunities for the design of all-electrical sensors using redox-labelled probes.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Neoplasias , Aptâmeros de Nucleotídeos/química , DNA/química , Técnicas Eletroquímicas , Molécula de Adesão da Célula Epitelial , Oxirredução
4.
SAGE Open Med ; 9: 20503121211005992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35154758

RESUMO

OBJECTIVE: Long-term administration of dienogest, which is known to have effect on bone mineral density, is frequently done in patients with endometriosis and adenomyosis, but a few studies focused on the bone mineral density changes after finishing the long-term therapy. This study aimed to reveal the factors that adversely affect lumbar bone mineral density. METHOD: Fifty-seven premenopausal women who visited our hospital were diagnosed as either endometriosis or adenomyosis, and they were treated by dienogest for more than 115 weeks (26.5 months). Based on a previous report, bone mineral density changes less than 2% was categorized as the osteopenic group (n = 30), and the others were assigned to the unchanged group (n = 27). Bone mineral density was measured at the lumbar spine using dual-energy X-ray absorptiometry. A representative ovarian reserve marker, endogenous estradiol levels, and follicle-stimulating hormone levels were measured over time and were compared between the osteopenic and unchanged groups. RESULT: Duration of dienogest intake was 59.5 months (osteopenic group) versus 57.5 months (unchanged group). These patients experienced ovarian surgeries in a similar frequency, but the ovarian reserve in osteopenic group was impaired as suggested by the decline of endogenous estradiol level during intake of dienogest compared to that of unchanged group (p = 0.0146). Endogenous follicle-stimulating hormone level between osteopenic group and unchanged group did not reach statistically significant difference, although the osteopenic group showed relatively higher level. CONCLUSION: This study might suggest that decreased ovarian reserve as judged by endogenous estradiol level is a factor that negatively affect bone mineral density, and measurement of endogenous estradiol level during intake of dienogest could have a predictive meaning of future decreased bone mineral density level.

5.
Curr HIV Res ; 18(6): 475-479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753017

RESUMO

BACKGROUND: Dental professionals have so many opportunities to use injection needles and sharp instruments during dental treatment that they face an increased risk of needlestick injuries. This retrospective study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially exposed to HIV at the dental departments of Hiroshima University Hospital. OBJECTIVE: This study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with antiretroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital. METHODS: Data on the clinical status of HIV-infected source patients and information on HIV-exposed dental professionals from 2007 to 2018 were collected. RESULTS: Five dentists with an average experience of 5.6 years (1-15 years) were exposed. The averaged CD4-positive cell number and HIV-RNA load were 1176 (768-1898) /µl and less than 20 copies/ml, respectively, in all the patients. Two of the five HIV exposed dentists received PEP. Three months after the exposures, all of their results were negative in HIV antibody/antigen tests. CONCLUSION: ; These data might support the concept of "undetectable equals untransmittable", although HIV exposure in this study was not through sexual transmission.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ferimentos Penetrantes Produzidos por Agulha/tratamento farmacológico , Exposição Ocupacional/prevenção & controle , Profilaxia Pós-Exposição/métodos , Adulto , Clínicas Odontológicas/estatística & dados numéricos , Odontólogos/estatística & dados numéricos , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
6.
Br J Surg ; 107(13): 1811-1817, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32638367

RESUMO

BACKGROUND: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. METHODS: The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. RESULTS: The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6·0 (range 0-22·6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14·5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12·4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. CONCLUSION: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.


ANTECEDENTES: La quimioterapia intraperitoneal con paclitaxel se considera una terapia experimental para el tratamiento de la carcinomatosis peritoneal. Este estudio tuvo como objetivo determinar la dosis recomendada y evaluar la eficacia clínica y la seguridad de la combinación de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal en pacientes con cáncer de páncreas y metástasis peritoneales. MÉTODOS: Se evaluaron las frecuencias de las toxicidades limitantes de la dosis, y la dosis recomendada se determinó en la fase I. El objetivo principal de la fase II fue la tasa de supervivencia global a 1 año. Los objetivos secundarios fueron los efectos antitumorales, los efectos de alivio de los síntomas, la seguridad y la supervivencia global. RESULTADOS: Las dosis recomendadas de gemcitabina intravenosa, nab-paclitaxel intravenoso y paclitaxel intraperitoneal fueron de 800, 75 y 20 mg/m2 , respectivamente. De los 46 pacientes incluidos en la fase II del estudio, la mediana de tiempo hasta el fracaso del tratamiento fue de 6,0 meses (rango, 0-22,6). Las tasas de respuesta y de control de la enfermedad fueron del 45% y 95%, respectivamente. La ascitis desapareció en el 40% de los pacientes, y la citología se negativizó en el 39% de los pacientes. La mediana del tiempo de supervivencia fue de 14,5 meses y la tasa de supervivencia global a 1 año del 60,9%. La cirugía de rescate se realizó en ocho (17%) pacientes, y los que se sometieron a cirugía sobrevivieron significativamente más tiempo que los que no fueron tratados quirúrgicamente (mediana de supervivencia no alcanzada versus 12,4 meses). Las toxicidades hematológicas de grado 3/4 ocurrieron en el 76% de los pacientes, mientras que los eventos adversos no hematológicos se presentaron en el 15% de los pacientes. CONCLUSIÓN: Agregar paclitaxel intraperitoneal tuvo eficacia clínica con una tolerabilidad aceptable. (UMIN000018878).


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/secundário , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Idoso , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Neoplasias Peritoneais/mortalidade , Análise de Sobrevida , Resultado do Tratamento
10.
Anaesthesia ; 74(12): 1558-1562, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31535722

RESUMO

Thoracic interfascial plane blocks are effective for post-mastectomy acute analgesia. However, their effects on chronic pain are uncertain. We randomly allocated 80 women equally to pectoral nerve-2 (PECS 2) block or serratus plane block. The pectoral nerve-2 block reduced the rate of moderate or severe chronic pain from 13/40 (33%) with the serratus plane block to 4/40 (10%), p = 0.03, adjusted odds ratio (95%CI) 0.23 (0.07-0.80), p = 0.02. The rates of pain-free women at six postoperative months were indeterminate, 10/40 (25%) after serratus plane block vs. 19/40 (48%) after pectoral nerve-2 block, p = 0.06, adjusted odds ratio (95%CI) 2.9 (1.1-7.5), p = 0.03. Health-related quality of life at six postoperative months was similar after serratus plane and pectoral nerve-2 blocks, mean (SD) EQ-5D-3L scores 0.87 (0.15) vs. 0.91 (0.14), respectively, p = 0.21. The pectoral nerve-2 block reduced median (IQR [range]) morphine consumption in the first 24 postoperative hours from 6 (3-9 [1-25]) mg to 4 (2-7 [0-37]) mg, p = 0.04. However, acute pain scores after serratus plane and pectoral nerve-2 blocks were similar, median (IQR [range]) 23 (11-35 [0-70]) mm vs. 18 (11-27 [0-61]) mm, respectively, p = 0.44. Pectoral nerve-2 block reduced chronic pain 6 months after mastectomy compared with serratus plane block.


Assuntos
Mastectomia/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/terapia , Nervos Torácicos , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Dor Crônica/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Ultrassonografia de Intervenção , Adulto Jovem
11.
Oral Oncol ; 93: 107-113, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31109690

RESUMO

OBJECTIVES: The prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy. MATERIALS AND METHODS: We retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models. RESULTS AND CONCLUSION: Variables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike's information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P < 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0-1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0-12.2; P < 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.


Assuntos
Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Metástase Linfática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Laríngeas/patologia , Laringectomia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Estadiamento de Neoplasias , Análise de Regressão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
12.
Breast Cancer Res Treat ; 173(1): 1-9, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30242579

RESUMO

BACKGROUND: Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast cancer (BC); however, we lack head-to-head pairwise assessment of survival or cardiotoxicity for specific combinations. We sought to identify optimal combinations. METHODS: We searched PubMed, updated October 2017, using keywords "Breast Neoplasms/drug therapy," "Trastuzumab," and "Clinical Trial" and searched Cochrane Library. Our search included randomized trials of adjuvant H plus chemotherapy for early-stage HER2+ BC, and excluding trials of neoadjuvant therapy or without data to obtain hazard ratios (HRs) for outcomes. Following PRISMA guidelines, one investigator did initial search; two others independently confirmed and extracted information; and consensus with another investigator resolved disagreements. Before gathering data, we set outcomes of overall survival (OS), event-free survival (EFS), and severe cardiac adverse events (SCAEs). Analyzing 6 trials and 13,621 patients, we made direct and indirect comparisons using network meta-analysis on HR for OS or EFS and on odds ratio (OR) for SCAE; ranked therapy was done based on outcomes using p scores. RESULTS: Compared with anthracycline-cyclophosphamide with taxane (ACT), ACT with concurrent H (ACT+H) showed best OS (HR 0.63, 95% confidence interval [CI] 0.55, 0.72), followed by taxane and carboplatin (TC) with concurrent H (TC+H) (HR 0.77, 95% CI 0.59, 1) and ACT with sequential H (ACT-H) (HR 0.85, 95% CI 0.68, 1.05). Pairwise comparisons showed statistically significant OS benefit for ACT+H over others; similar results for EFS. TC+H showed statistically significant lower SCAE risk compared to ACT+H (OR 0.13, 95% CI 0.03, 0.61). CONCLUSIONS: Concurrent H with ACT or TC showed most clinical benefit for early-stage HER2+ BC; TC+H had lowest cardiotoxicity.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Resultado do Tratamento
13.
Scand J Rheumatol ; 48(2): 87-94, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30269670

RESUMO

OBJECTIVE: Serum interleukin-18 (IL-18) levels are increased in patients with interstitial lung disease (ILD). In addition, IL-18 levels are increased in patients with rheumatoid arthritis (RA) and are associated with arthritis activity. We determined whether increased IL-18 levels are associated with ILD in RA. METHOD: RA patients were enrolled using an RA cohort database. Plasma IL-18 levels were measured by enzyme-linked immunosorbent assay. ILD was determined by a pulmonologist and a radiologist based on chest radiography and computed tomography findings. IL-18 levels for RA with ILD and RA without ILD were compared. Associations between ILD and various markers including IL-18 and confounding factors (e.g. smoking history) were investigated by logistic regression analysis. Diagnostic values of IL-18 for the presence of ILD were investigated using receiver operating characteristics curve analysis. RESULTS: ILD was complicated in 8.2% (n = 26) of the study population (N = 312). Plasma IL-18 levels were higher for RA patients with ILD than for RA patients without ILD (721.0 ± 481.4 vs 436.8 ± 438.9 pg/mL, p < 0.001). IL-18, Krebs von den Lungen-6, and anti-cyclic citrullinated peptide antibody titre and glucocorticoid doses were independently associated with the presence of ILD during multivariate logistic regression analysis. Sensitivity and specificity of IL-18 levels for the detection of ILD in RA patients were 65.3% and 76.3%, respectively (area under the curve = 0.73). CONCLUSION: Plasma IL-18 levels were higher for RA patients with ILD than for those without ILD. Increased IL-18 levels were associated with the presence of ILD.


Assuntos
Artrite Reumatoide/complicações , Interleucina-18/sangue , Doenças Pulmonares Intersticiais/complicações , Idoso , Artrite Reumatoide/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Masculino , Pessoa de Meia-Idade
14.
Transplant Proc ; 50(9): 2640-2644, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30401366

RESUMO

BACKGROUND: Portal vein (PV) reconstruction is a crucial factor in successful living donor liver transplantation (LDLT). In LDLT using the right liver grafts with anatomic PV variations, we sometimes encounter dual PV anastomosis. In this study we describe PV variations of donor liver in detail as well as our experiences with PV reconstruction in right liver grafts with PV variations. METHODS: We performed LDLT in 149 recipients between 2002 and 2016. PV variations of donor liver were classified into 3 major anatomic patterns, and we retrospectively analyzed the procedure and postoperative complications of PV anastomosis. RESULTS: PV variations in donor livers were classified as type A (normal type) in 125 patients, type B (trifurcation type) in 7 (4.7%), and type C (caudal origin of the right posterior branch) in 17 (11.4%). Among 75 right liver grafts, 10 (13.3%) had anatomic PV variations. In 9 of 10 recipients, dual PV of the graft were anastomosed to dual PV branches of the recipient in direct end-to-end fashion. In the remaining recipient, the posterior portal branch of the graft was anastomosed to the recipient portal trunk through the interposed venous graft in end-to-end fashion and the anterior portal branch of the graft was anastomosed to the side wall of the interposed venous graft. These 10 recipients did not develop any postoperative complications associated with PV anastomosis, although 3 of the 149 recipients (2.0%) developed complications associated with PV anastomosis, such as thrombosis and necrosis. CONCLUSION: Dual PV anastomosis of the right liver graft is safe and feasible in LDLT, even in anatomic PV variations.


Assuntos
Transplante de Fígado/métodos , Fígado/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Veia Porta/cirurgia , Transplantes/cirurgia , Adolescente , Adulto , Anastomose Cirúrgica/métodos , Estudos de Viabilidade , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Transplant Proc ; 50(9): 2699-2704, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30401380

RESUMO

OBJECTIVE: In patients with living donor liver transplantation (LDLT), late-onset complications sometimes develop because of long-term use of immunosuppressive drugs. One of the immunosuppressive drug-related complications is de novo malignancies resulting in reduced survival. PATIENTS AND METHODS: Among 153 patients undergoing LDLT, we retrospectively reviewed the medical records of 97 adult recipients (February 2002 to May 2017), who had been followed-up at our hospital for more than one year after LDLT. The median age was 52 years old (20-70) and the median observational period was 6.9 years (2.4-15.3). RESULTS: De novo malignancy after adult LDLT developed in 11.3% (11/97) of patients, including posttransplantation lymphoproliferative disorder (PTLD) (n = 4) (2 in the brain and 2 in abdominal lymph nodes), lung cancer (n = 1), pancreatic cancer (n = 1), gastric cancer (n = 1), laryngeal cancer (n = 1), lower gingival cancer (n = 1), bladder cancer (n = 1), and melanoma (n = 1). Age at cancer diagnosis ranged from 36 to 70 years old with an average age of 61 years. The interval from LDLT to cancer diagnosis was 8.3 years (3.9-12.2). Four patients (36.6%) including PTLD (n = 2), lung cancer (n = 1), and pancreatic cancer (n = 1) died of cancer and all of them were diagnosed with cancer within 10 years after LDLT. Six patients were diagnosed with cancer more than 10 years after LDLT and all of them survived after treatment of cancer. CONCLUSION: De novo malignancy was found in 11.3% of LDLT patients, and more than half of this population subset developed tumors 10 years after LDLT. Long-term close follow-up should be performed by taking any kinds of de novo malignancy into consideration.


Assuntos
Hospedeiro Imunocomprometido , Transplante de Fígado , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/imunologia , Adulto , Idoso , Feminino , Humanos , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/imunologia , Estudos Retrospectivos , Adulto Jovem
16.
Br J Oral Maxillofac Surg ; 56(8): 732-738, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30131193

RESUMO

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO32-) in its crystal structure.


Assuntos
Compostos de Bifenilo/farmacologia , Densidade Óssea/efeitos dos fármacos , Catepsina K/antagonistas & inibidores , Mandíbula/efeitos dos fármacos , Animais , Feminino , Mandíbula/diagnóstico por imagem , Ratos , Ratos Wistar , Tomografia Computadorizada por Raios X
17.
Ann Oncol ; 29(5): 1280-1285, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788166

RESUMO

Background: The 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Testes Genéticos/métodos , Modelos Genéticos , Recidiva Local de Neoplasia/diagnóstico , Algoritmos , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/métodos , Análise Custo-Benefício , Feminino , Seguimentos , Testes Genéticos/economia , Humanos , Incidência , Mastectomia , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco/economia , Medição de Risco/métodos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral/genética
18.
Br J Surg ; 105(10): 1349-1358, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29741294

RESUMO

BACKGROUND: Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. METHODS: Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein was determined in gastric tissues from patients with gastric cancer. RESULTS: Synaptotagmin XIII (SYT13) was expressed at significantly higher levels in patients with peritoneal recurrence, but not in those with hepatic or distant lymph node recurrence. Inhibition of SYT13 expression in a gastric cancer cell line transfected with SYT13-specific siRNA (siSYT13) was associated with decreased invasion and migration ability of the cells, but not with proliferation and apoptosis. Intraperitoneal administration of siSYT13 significantly inhibited the growth of peritoneal nodules and prolonged survival in mice. In an analysis of 200 patients with gastric cancer, SYT13 expression in primary gastric cancer tissues was significantly greater in patients with peritoneal recurrence or metastasis. A high level of SYT13 expression in primary gastric cancer tissues was an independent risk factor for peritoneal recurrence. CONCLUSION: SYT13 expression in gastric cancer is associated with perioneal metatases and is a potential target for treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Sinaptotagminas/metabolismo , Idoso , Animais , Biomarcadores Tumorais/antagonistas & inibidores , Linhagem Celular Tumoral , Biologia Computacional , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/prevenção & controle , Interferência de RNA , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Sinaptotagminas/antagonistas & inibidores , Transcriptoma
19.
Int J Oral Maxillofac Surg ; 47(9): 1206-1213, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29550280

RESUMO

Bone quality is defined by structural and material characteristics. Most studies on the mandible have focused on the analysis of structural characteristics, with insufficient investigation of material characteristics. This study tested whether zoledronate affects the material characteristics of newly formed mandibular bone. Thirty-six female Wistar rats were assigned to three groups: sham-ovariectomized rats (SHAM, n=12), ovariectomized rats (OVX, n=12), and ovariectomized rats treated with zoledronate (ZOL, n=12). The left side of the mandibular ramus of all rats was drilled bicortically. Twenty-eight days after surgery, all surviving rats were euthanized and all mandibles were removed. Raman microspectroscopy was performed, and five spectra per specimen of newly formed mandibular bone were analysed. Compared with OVX rats, the mineral/matrix ratio in ZOL rats was significantly increased (5.43±1.88 vs. 7.86±2.05), while crystallinity (0.055±0.002 vs. 0.050±0.002), relative proteoglycan content (0.43±0.10 vs. 0.31±0.05), and collagen structural integrity (1.16±0.21 vs. 0.72±0.06) were significantly decreased. These changes in material characteristics may explain why rats that received zoledronate exhibited peculiar biological phenomena such as bisphosphonate-related osteonecrosis of the jaw.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Mandíbula/efeitos dos fármacos , Mandíbula/ultraestrutura , Ácido Zoledrônico/farmacologia , Animais , Biomarcadores/análise , Densidade Óssea/efeitos dos fármacos , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Imageamento Tridimensional , Mandíbula/diagnóstico por imagem , Ovariectomia , Ratos , Ratos Wistar , Análise Espectral Raman , Microtomografia por Raio-X
20.
BJOG ; 125(4): 487-493, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28294527

RESUMO

OBJECTIVE: To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). DESIGN: Retrospective case series study. SETTING: Tertiary perinatal care centre at a university hospital. POPULATION: Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. METHODS: The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. MAIN OUTCOME MEASURES: Obstetrical management and complication including the incidence of AD throughout the peripartum period. RESULTS: Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi-square test). CONCLUSIONS: Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. TWEETABLE ABSTRACT: MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.


Assuntos
Doenças da Aorta/cirurgia , Dissecção Aórtica , Síndrome de Marfan , Complicações Pós-Operatórias , Complicações Cardiovasculares na Gravidez , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/etiologia , Dissecção Aórtica/prevenção & controle , Dissecção Aórtica/terapia , Doenças da Aorta/diagnóstico , Doenças da Aorta/etiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/epidemiologia , Período Periparto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/prevenção & controle , Complicações Cardiovasculares na Gravidez/terapia , Resultado da Gravidez , Gravidez de Alto Risco , Estudos Retrospectivos , Risco Ajustado/métodos , Procedimentos Cirúrgicos Vasculares/métodos
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