RESUMO
BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.
Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Retais/cirurgiaRESUMO
BACKGROUND: The aim was to characterize end-of-life care in patients who have had a leg amputated for peripheral artery disease (PAD) or diabetes. METHODS: This was a population-based retrospective cohort study of patients with PAD or diabetes who died in Ontario, Canada, between 2011 and 2017. Those who had a leg amputation within 3 years of death were compared with a control cohort of deceased patients with PAD or diabetes, but without leg amputation. The patients were identified from linked health records within the single-payer healthcare system. Place and cause of death, as well as health services and costs within 90 days of death, were compared between the amputee and control cohorts. Among amputees, multivariable regression models were used to characterize the association between receipt of home palliative care and in-hospital death, as well as time spent in hospital at the end of life. RESULTS: Compared with 213 300 controls, 3113 amputees were less likely to die at home (15·5 versus 24·9 per cent; P < 0·001) and spent a greater number of their last 90 days of life in hospital (median 19 versus 8 days; P < 0·001). Amputees also had higher end-of-life healthcare costs across all sectors. However, receipt of palliative care was less frequent among amputees than controls (inpatient: 13·4 versus 16·8 per cent, P < 0·001; home: 14·5 versus 23·8 per cent, P < 0·001). Among amputees, receipt of home palliative care was associated with a lower likelihood of in-hospital death (odds ratio 0·49, 95 per cent c.i. 0·40 to 0·60) and fewer days in hospital (rate ratio 0·84, 0·76 to 0·93). CONCLUSION: Palliative care is underused after amputation in patients with PAD or diabetes, and could contribute to reducing in-hospital death and time spent in hospital at the end of life.
ANTECEDENTES: Caracterizar la atención al final de la vida en pacientes con amputación de la extremidad inferior por enfermedad arterial periférica (peripheral arterial disease, PAD) o diabetes. MÉTODOS: Se trata de un estudio de cohortes retrospectivo de base poblacional en sujetos fallecidos con PAD o diabetes en Ontario, Canadá (2011-2017). A partir de los registros sanitarios incluidos en un sistema de salud de una sola entidad pagadora, se identificaron los individuos con amputación de la extremidad inferior en los 3 años previos al fallecimiento y una cohorte control de fallecidos con PAD o diabetes sin amputación. Entre las cohortes de amputados y controles se comparó el lugar del fallecimiento y la causa, así como el uso de servicios sanitarios y costes en los últimos 90 días de vida. En el grupo de los amputados, se utilizaron modelos de regresión para caracterizar la asociación entre recibir cuidados paliativos domiciliarios y el fallecimiento en el hospital, así como los días de estancia hospitalaria al final de la vida. RESULTADOS: En comparación con los controles (n = 213.300), los sujetos con amputación (n = 3.113) era menos probable que fallecieran en el domicilio (16% versus 25%, P < 0,001) y pasaron un mayor número de sus últimos 90 días de vida en el hospital (mediana 19 versus 8 días, P < 0,001). Los costes de atención sanitaria al final de la vida en todos los sectores también fueron mayores para los amputados. Sin embargo, recibir cuidados paliativos fue menos frecuente en los amputados que en los controles (en el hospital 13% versus 17%, P < 0,001; domiciliarios 14% versus 24%, P < 0,001). En el grupo de los amputados, recibir cuidados paliativos domiciliarios se asociaba con una menor probabilidad de fallecimiento en el hospital (razón de oportunidades, odds ratio 0,49, i.c. del 95% 0,40-0,60) y menos días de hospitalización (tasa de riesgo 0,84, i.c. del 95% 0,76-0,93). CONCLUSIÓN: Los cuidados paliativos están infrautilizados en pacientes con PAD o diabetes y pueden contribuir a disminuir los fallecimientos en el hospital y los días de hospitalización al final de la vida.
Assuntos
Amputação Cirúrgica/mortalidade , Complicações do Diabetes/mortalidade , Doença Arterial Periférica/mortalidade , Assistência Terminal/métodos , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/economia , Causas de Morte , Complicações do Diabetes/economia , Complicações do Diabetes/cirurgia , Feminino , Custos de Cuidados de Saúde , Serviços de Assistência Domiciliar/economia , Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Ontário/epidemiologia , Cuidados Paliativos/economia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Doença Arterial Periférica/economia , Doença Arterial Periférica/terapia , Assistência Terminal/economia , Assistência Terminal/estatística & dados numéricosRESUMO
Enamel makes up the outermost layer of the crown and its hardness protects other dental tissues from various stimuli. Enamel cannot be regenerated once damaged because ameloblasts are lost during the tooth eruption. Since the ameloblast differentiation mechanism is still unknown, further research is essential for developing treatments for defective or damaged enamel. Previously, we have reported that osteoblast differentiation and bone formation were regulated through the runt-related transcription factor 2 (Runx2)-nuclear factor 1-C (Nfic)-osterix (Osx) pathway where Nfic directly controls Osx expression. This pathway regulates odontoblast differentiation and dentin formation as well. The aim of this study was to investigate if the same pathway is applicable for ameloblast differentiation. Structural enamel defects with disorganized ameloblasts and decreased proliferation activity of the cervical loop were observed in Nfic-/- mice incisors. Expression of the ameloblast differentiation markers was also downregulated significantly in Nfic-/- mice. Real-time PCR analyses suggested that Runx2, Nfic, and Osx regulate the expression of ameloblast differentiation markers, where Runx2 is upstream of Nfic, and Nfic controls Osx expression. Therefore, we suggest the Runx2-Nfic-Osx pathway as one of the key factors that regulate ameloblast differentiation.
Assuntos
Ameloblastos/citologia , Ameloblastos/metabolismo , Diferenciação Celular , Esmalte Dentário/metabolismo , Fatores de Transcrição NFI/metabolismo , Transdução de Sinais , Fator de Transcrição Sp7/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem Celular , Linhagem da Célula , Proliferação de Células , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Esmalte Dentário/ultraestrutura , Camundongos , Fatores de Transcrição NFI/deficiência , Dente/metabolismo , Dente/ultraestrutura , Microtomografia por Raio-XRESUMO
Diaphragmatic eventration is an uncommon condition, usually discovered incidentally in asymptomatic patients. Even in symptomatic patients, the diagnosis can be challenging and should be considered among the differential diagnoses of diaphragmatic hernia. The correct diagnosis can often only be made in surgery. We describe the case of a 31-year-old patient with diaphragmatic eventration that was misdiagnosed as a recurrent congenital diaphragmatic hernia and review the corresponding literature.
Assuntos
Eventração Diafragmática/diagnóstico , Hérnia Diafragmática/diagnóstico , Adulto , Diagnóstico Diferencial , Erros de Diagnóstico , Eventração Diafragmática/diagnóstico por imagem , Eventração Diafragmática/cirurgia , Hérnia Diafragmática/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/diagnóstico , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Humanos , Masculino , Radiografia , Recidiva , Tomografia Computadorizada por Raios XRESUMO
Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells. Our DNA nanostructure harbored complementary sequences that can hybridize with the microRNA cargo. This brings the microRNA-DNA duplex very close to the core structure such that the microRNA cargo becomes sterically shielded from RNase's degradative activity. Our novel DNA nanostructure based protector concept removes the degradative bottleneck that may plague other nucleic acid delivery strategies and presents a new paradigm towards exploiting these microRNAs for anti-cancer therapy.
RESUMO
Background: The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown. Methods: We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects. Results: A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11-0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01- 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06-0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05-0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death. Conclusion: Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.
Assuntos
Antraciclinas/efeitos adversos , Cardiomiopatias/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Neoplasias/complicações , Disfunção Ventricular Esquerda/tratamento farmacológico , Acetilcisteína/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Angiotensinas/antagonistas & inibidores , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/mortalidade , Cardiomiopatias/patologia , Ensaios Clínicos como Assunto , Dexrazoxano/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias/tratamento farmacológico , Metanálise em Rede , Prenilamina/uso terapêutico , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/patologiaRESUMO
AIM: The study was designed to assess the correlation between lymph node (LN) size and LN metastasis in patients with rectal neuroendocrine tumours (NETs). METHOD: Forty patients who underwent curative resection with lymphadenectomy for a rectal NET between January 2007 and December 2012 were included. The short and long diameters of entire nodes were microscopically measured using a slide gauge. RESULTS: In all, 1052 LNs were collected from the 40 patients, with 49 (4.7%) showing evidence of metastasis. Metastasis-positive LNs had significantly greater long and short diameters (P < 0.001) than metastasis-negative LNs. Of the 49 metastatic LNs, 29 (59.2%) were ≤ 5 mm in largest diameter. In five patients, the largest metastatic LN was only 2-3 mm in diameter. In clinically node-negative (cN0) patients, 18 (51.4%) patients had metastatic LNs (pN1). CONCLUSION: The size of LNs containing metastasis varied widely, with some being very small. LN size alone is therefore not a sufficient predictor of tumour metastasis in rectal NETs. Radical surgery with lymphadenectomy should be considered for patients with rectal NETs with high risk factors for LN metastasis, even those without LN enlargement.
Assuntos
Linfonodos/patologia , Metástase Linfática , Tumores Neuroendócrinos/patologia , Neoplasias Retais/patologia , Adulto , Idoso , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVE: The predictability of conventional periodontal treatments for damaged periodontal tissue is limited, particularly on the regeneration of new cementum. As signaling molecules, a range of growth factors has been used to promote periodontal regeneration on periodontal ligament (PDL) and cementum defects. A preameloblast-conditioned medium (PA-CM) was prepared from cultured murine apical bud cells, which can differentiate into ameloblasts. We examined the effect of PA-CM on PDL cells and cementoblasts in vitro and evaluated histologically the effects of PA-CM on the regeneration of experimentally induced periodontal defects in vivo. MATERIAL AND METHODS: In vitro, the effects of PA-CM on the migration of human PDL cells were examined using a scratch wound healing assay and a transwell assay. The differentiation and mineralization potential of PA-CM-treated human PDL cells and murine cementoblastic OCCM-30 cells was examined by real-time polymerase chain reaction and Alizarin red-S staining. In vivo, six mongrel dogs (12-16 kg; 6-8 mo old) were used. Twenty-four roots were replanted with either, (i) only periodontal defects (n = 12; control group), or (ii) periodontal defects and PA-CM treatment (n = 12; experimental group). In the experimental group, the PDL and cementum between notches was removed using a Gracey curette and soaked in 0.08 mL water containing 80 µg of a PA-CM for 2 min. The dogs were killed at 4 and 8 wk post-surgery. RESULTS: The in vitro results showed that PA-CM stimulated the migration of PDL cells and promoted the differentiation and mineralization of PDL cells and cementoblasts. Real-time polymerase chain reaction analysis revealed stronger expression of Runx2, Osx, OC, Bsp and Cap mRNAs in the PA-CM-treated PDL cells and cementoblasts than those in the control cells. In vivo, newly formed PDL-like tissue and cementum-like tissue were observed partially between the root surfaces and newly formed bone in the experimental group. The regenerated PDL-like tissue in the experimental group was significantly higher than that in the control group at 8 wk (p < 0.05). The replacement resorption on the experimental group was significantly lower than that in the control group at 8 wk (p < 0.05). In addition, the amount of newly formed cementum-like tissue in the experimental group was significantly higher than that in the control group at 4 and 8 wk (p < 0.05). CONCLUSION: These results suggest that PA-CM has the potential to regenerate periodontal tissues in PDL and cementum defects.
Assuntos
Cemento Dentário/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Adolescente , Animais , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ensaios de Migração Celular , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cementogênese/efeitos dos fármacos , Meios de Cultivo Condicionados , Cemento Dentário/lesões , Cães , Humanos , Camundongos Endogâmicos C57BL , Dente Serotino , Periodonto/efeitos dos fármacos , Periodonto/lesões , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Raiz Dentária/efeitos dos fármacos , Raiz Dentária/lesões , Raiz Dentária/patologia , Adulto JovemRESUMO
Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case.
Assuntos
Biópsia/instrumentação , Neoplasias Esofágicas/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Instrumentos Cirúrgicos , Biópsia/métodos , Mucosa Esofágica/patologia , Humanos , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.
Assuntos
Transformação Celular Neoplásica/genética , Proteína Forkhead Box M1/genética , Fígado/metabolismo , Peroxirredoxinas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Células NIH 3T3 , Peptídeos/farmacologia , Peroxirredoxinas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transplante HeterólogoRESUMO
BACKGROUND: This case represents the earliest appearance of de novo HCC after liver transplantation (OLT) compared with cases of previously reported literatures. CASE REPORT: A 45-year-old man underwent deceased donor OLT owing to decompensated liver cirrhosis. He had YMDD viral mutation and hepatitis B (HBV) and C (HCV) coinfection but no tumor was found in the liver on MRI before OLT. The donor was a healthy young female donor who was HCV and HBV negative. There was no tumor in the explant liver. After OLT, HCV RNA and hepatitis B surface antigen became undetectable with DNA-positive HBV. Nine months after OLT, a computed tomography (CT) scan was performed owing to abdominal pain, detecting a mass occupying the right lobe that depicted enhanced characteristics typical of HCC. The chest CT demonstrated metastatic lung nodules in the right basal lower lobe. Fluorescence in situ hybridization showed tumor cells from the recipient. CONCLUSIONS: To the best of our knowledge, this is the first report of de novo hepatocellular carcinoma that has emerged within a short period of undergoing OLT.
Assuntos
Carcinoma Hepatocelular/patologia , Falência Hepática/cirurgia , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Transplantados , Aloenxertos , Carcinoma Hepatocelular/etiologia , Feminino , Seguimentos , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Falência Hepática/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
The peptide GSFSIQYTYHV derived from human semenogelin I forms a transparent hydrogel through spontaneous self-assembly in water at neutral pH. Linear rheology measurements demonstrate that the gel shows a dominating elastic response over a large frequency interval. CD, fluorescence and FTIR spectroscopy and cryo-TEM studies imply long fibrillar aggregates of extended ß-sheet. Dynamic light scattering data indicate that the fibril lengths are of the order of micrometers. Time-dependent thioflavin T fluorescence shows that fibril formation by GSFSIQYTYHV is a nucleated reaction. The peptide may serve as basis for development of smart biomaterials of low immunogenicity suitable for biomedical applications, including drug delivery and wound healing.
Assuntos
Hidrogel de Polietilenoglicol-Dimetacrilato/química , Peptídeos/química , Proteínas Secretadas pela Vesícula Seminal/química , Humanos , Concentração de Íons de Hidrogênio , Estrutura Secundária de Proteína , Reologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Three tocopherol analogues methoxytocopherol (1), α-tocopherol (2) and γ-tocopherol (3) were isolated from the peels of Citrus unshiu Marcovich. The protective effects of the isolated compounds against tert-butyl hydroperoxide-induced hepatotoxicity in human liver-derived HepG2 cells and glutamate-induced oxidative stress in HT22-immortalised hippocampal cells were evaluated. Compounds 1-3 were significantly protective in HepG2 cells with EC50 values of 21.22 ± 2.01, 25.21 ± 2.11 and 25.25 ± 1.21 µM, respectively, and in HT22 cells, compounds 1-3 had EC50 values of 20.62 ± 1.36, 6.44 ± 1.65 and 9.52 ± 1.54 µM, respectively.
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Citrus/química , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tocoferóis/química , Animais , Linhagem Celular , Frutas/química , Células Hep G2 , Humanos , Camundongos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Tocoferóis/farmacologia , terc-Butil HidroperóxidoRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation are considered mutually exclusive in nonsmall-cell lung cancer (NSCLC). However, sporadic cases having concomitant EGFR and ALK alterations have been reported. The present study aimed to assess the prevalence of NSCLCs with concomitant EGFR and ALK alterations using mutation detection methods with different sensitivity and to propose an effective diagnostic and therapeutic strategy. PATIENTS AND METHODS: A total of 1458 cases of lung cancer were screened for EGFR and ALK alterations by direct sequencing and flourescence in situ hybridization (FISH), respectively. For the 91 patients identified as having an ALK translocation, peptide nucleic acid (PNA)-clamping real-time PCR, targeted next-generation sequencing (NGS), and mutant-enriched NGS assays were carried out to detect EGFR mutation. RESULTS: EGFR mutations and ALK translocations were observed in 42.4% (612/1445) and 6.3% (91/1445) of NSCLCs by direct sequencing and FISH, respectively. Concomitant EGFR and ALK alterations were detected in four cases, which accounted for 4.4% (4/91) of ALK-translocated NSCLCs. Additional analyses for EGFR using PNA real-time PCR and ultra-deep sequencing by NGS, mutant-enriched NGS increased the detection rate of concomitant EGFR and ALK alterations to 8.8% (8/91), 12.1% (11/91), and 15.4% (14/91) of ALK-translocated NSCLCs, respectively. Of the 14 patients, 3 who were treated with gefitinib showed poor response to gefitinib with stable disease in one and progressive disease in two patients. However, eight patients who received ALK inhibitor (crizotinib or ceritinib) showed good response, with response rate of 87.5% (7/8 with partial response) and durable progression-free survival. CONCLUSIONS: A portion of NSCLC patients have concomitant EGFR and ALK alterations and the frequency of co-alteration detection increases when sensitive detection methods for EGFR mutation are applied. ALK inhibitors appear to be effective for patients with co-alterations.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , Genes erbB-1 , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe , Feminino , Gefitinibe , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Quinazolinas/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Sulfonas/uso terapêutico , Translocação GenéticaRESUMO
OBJECTIVES: To examine the immune cell profile in the bone marrow of systemic lupus erythematosus (SLE) patients and to assess its clinical relevance. METHODS: Sixteen bone marrow samples from 14 SLE patients were compared with seven healthy control samples. The numbers of immune cells and apoptotic cells in the bone marrow were examined by immunohistochemistry. The association between immune cell subsets and clinical features was investigated. RESULTS: CD4+ T cells, macrophages and plasma cells were more common in the bone marrow of SLE patients than in healthy controls (p=0.001, p=0.004 and p<0.001, respectively). Greater numbers of CD4+ T cells and macrophages were associated with high-grade bone marrow damage. The percentage of apoptotic cells in bone marrow of SLE patients was significantly higher than that in controls (p<0.001) and was positively correlated with the number of plasmacytoid dendritic cells (p=0.013). Increased number of plasma cells along with high interleukin-6 expression was correlated with anti-double stranded DNA antibody levels and the SLE disease activity index (p=0.031 and 0.013, respectively). CONCLUSION: Bone marrow from SLE patients showed a distinct immune cell profile and increased apoptosis. This, coupled with a correlation with disease activity, suggests that the bone marrow may play a critical role in the pathogenesis of SLE.
Assuntos
Apoptose , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Exame de Medula Óssea , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , DNA/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Humanos , Imuno-Histoquímica , Interleucina-6/análise , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Plasmócitos/patologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
Mesenchymal stem cells (MSCs) have immunomodulatory functions such as the suppression of T and B cells. MSCs suppress immunoglobulin (Ig) production by B cells via cell-cell contact as well as via secretion of soluble factors. Our study showed that the conditioned medium (CM) of MSCs infected with a mycoplasma strain, Mycoplasma arginini, has marked inhibitory effects on Ig production by lipopolysaccharide/interleukin-4-induced B cells compared with mycoplasma-free MSC-CM. We analyzed mycoplasma-infected MSC-CM by fast protein liquid chromatography and liquid chromatography to screen the molecules responsible for Ig inhibition. Complement C3 (C3) was the most critical molecule among the candidates identified. C3 was shown to be involved in the suppression of the Ig production of B cells. C3 was secreted by mycoplasma-infected MSCs, but not by mycoplasma-free MSCs or B cells. It was able to directly inhibit Ig production by B cells. In the presence of a C3 inhibitor, Ig inhibition by MSC-CM was abrogated. This inhibitory effect was concomitant with the downregulation of B-cell-induced maturation protein-1, which is a regulator of the differentiation of antibody-secreting plasma cells. These results suggest that C3 secreted from mycoplasma-infected MSCs has an important role in the immunomodulatory functions of MSCs. However, its role in vivo needs to be explored.
Assuntos
Linfócitos B/metabolismo , Complemento C3/metabolismo , Imunoglobulinas/biossíntese , Células-Tronco Mesenquimais/microbiologia , Mycoplasma/imunologia , Animais , Linfócitos B/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Regulação para Baixo/efeitos dos fármacos , Imunoglobulina E/biossíntese , Lipopolissacarídeos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Mycoplasma/efeitos dos fármacosRESUMO
AIM: Serum antithyroglobulin antibody (TgAb) has been reported as a surrogate marker for differentiated thyroid cancer (DTC) in some conditions. We investigated changes in serum TgAb levels after stimulation with thyroid-stimulating hormone (TSH) and the clinical implications for monitoring DTC. PATIENTS, METHODS: We retrospectively enrolled 53 DTC patients who had undergone total thyroidectomy and were negative for serum Tg and positive for TgAb. Patients underwent high-dose radioactive iodine treatment, and serum TgAb was measured before (TgAbBAS) and after TSH stimulation (TgAbSTIM). TgAb was followed up 6 to 12 months later (TgAbF/U). The change in TgAb after TSH stimulation (∆TgAbSTIM) was calculated as a percentage of the baseline level. Patient disease status was classified into no residual disease (ND) and residual or recurred disease (RD) by follow-up imaging studies and pathologic data. The characteristics and diagnostic value of serum TgAb levels and ∆ TgAbSTIM were investigated with respect to disease status. RESULTS: 38 patients were in the ND group and 15 were in the RD group. TgAbBAS, TgAbSTIM and TgAbF/U were significantly higher in the RD compared to the ND group (p = 0.0008, 0.0002, and < 0.0001, respectively). ∆TgAbSTIM was also significantly higher in the RD group (p = 0.0009). In the patients who presented with obviously high (≥ 50%) or low (< -50%) ∆ TgAbSTIM, the proportions in the RD group were markedly different at 100% and 7%, respectively. ∆ TgAbSTIM had significant diagnostic value for RD (p < 0.001). CONCLUSION: The change in serum TgAb level after TSH stimulation is different between the RD and ND groups, and thus, it may be used as a surrogate diagnostic marker for DTC when the serum Tg is negative and TgAb is positive.
Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Tireotropina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVES: While socio-economic status (SES) is considered a key social-environment factor affecting health outcomes, sex differences in the association between SES and the risk of type 2 diabetes remain unclear. The aims of this study were: (1) to identify risk factors associated with type 2 diabetes in a representative sample of Korean adults with a focus on socio-economic determinants; and (2) to examine how the association between SES and type 2 diabetes is affected by sex. STUDY DESIGN: Cross-sectional study. METHODS: This study used data obtained from 3870 Korean adults (age ≥35 years) who participated in the 2005 Korean National Health and Nutritional Examination Survey (KNHANES III). The risk of type 2 diabetes in relation to SES was calculated, after controlling for other risk factors such as medical characteristics (hypertension, family history, body mass index, triglyceride, total cholesterol, high-density lipoprotein cholesterol), lifestyle factors (body mass index, smoking, alcohol intake, exercise) and perceived stress. Odds ratios (ORs) were calculated separately for Korean men and women using multivariate logistic regression. RESULTS: Compared with individuals with ≥13 years of education, those with ≤6 years of education or 7-12 years of education had higher ORs for the risk of type 2 diabetes - 2.10 (95% confidence interval (CI) 1.27-3.48) and 1.62 (95% CI 1.04-2.52), respectively - after adjusting for age, sex, medical characteristics, lifestyle factors and stress level. The OR for women with ≤6 years of education was particularly high (OR 10.16, 95% CI 2.08-49.53), even after adjusting for the study covariates. However, this increasing trend in the OR was not observed for men. CONCLUSIONS: SES significantly influences the risk of type 2 diabetes in Korean adults, and there are interactions with sex. Korean women with a low level of education represent a particularly high-risk group for type 2 diabetes. Future interventions should incorporate more targeted diabetes prevention efforts for women with a low level of education.