RESUMO
Background: Percutaneous kyphoplasty (PKP) is an effective minimally invasive technique for the treatment of osteoporotic vertebral fracture (OVF) in recent years. This study focuses on the analysis of PKP surgery and anesthesia in osteoporotic vertebral facture patients over 90 years old with the concept of "enhanced recovery after surgery." Methods: This study reviewed 239 patients who were diagnosed with OVF retrospectively between October 2015 and June 2019. According to the method of anesthesia, these patients were divided into Group A (n = 125) and Group B (n = 114). According to the pedicle puncture approach, these patients were divided into Group C (n = 102) and Group D (n = 137). The anterior vertebral height (AVH) and local kyphosis angle (LKA) were used to evaluate the degree of vertebral damage and restoration. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) scores were used for assessing functional outcomes. Some parameters were used to assess the perioperative conditions such as operation time, amount of bone cement perfusion, intraoperative fluoroscopy times, anesthesia recovery time, time out of the bed, hospital stay, hospitalization cost, and complications. Results: The visual analogue scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height (AVH), and local kyphosis angle (LKA) 1 day, 1 year after surgery, and at the last follow-up all showed significant improvement (P < 0.05) in comparison with those before surgery both in Groups A and B and Groups C and D. The ODI 1 day after surgery was significantly better in Group B than Group A (P < 0.05). Compared with Group B, Group A required longer time of anesthesia, operation time, anesthesia recovery time, time to get out of bed, and length of hospital stay and more hospitalization costs (P < 0.05). Group D required longer operation time, longer time to get out of bed, more bone cement volume, fluoroscopy time, and more operation hospitalization costs compared with Group C (P < 0.05). Conclusion: We recommend unilateral puncture under local anesthesia for OVF in the patients aged over 90 from the perspective of rapid recovery.
Assuntos
Anestesia , Fraturas por Compressão , Cifoplastia , Cifose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos/uso terapêutico , Fraturas por Compressão/cirurgia , Humanos , Cifoplastia/métodos , Cifose/cirurgia , Fraturas por Osteoporose/cirurgia , Punções , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgiaRESUMO
BACKGROUND: The enhanced recovery after surgery (ERAS) program helps patients recover faster and better, postoperatively. The aim of this retrospective study was to assess the clinical effectiveness of the ERAS program after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures. METHODS: We enrolled patients with osteoporotic vertebral compression fracture who had undergone PKP between January 2019 and June 2021 and divided them into the control group (CG; n = 296), without the ERAS program, and the intervention group (IG; n = 306), with the ERAS program. The visual analog scale (VAS), Oswestry Disability Index (ODI), and Barthel Index scores of the 2 groups were compared on admission and 2 days and 1, 6, and 12 months postoperatively. Perioperative evaluation parameters included the mean surgery time, length of stay (LOS), and hospitalization expenses. In addition, postoperative complications were compared. RESULTS: Regarding perioperative parameters, LOS and hospitalization expenses were significantly better in IG than in CG (P < 0.001), but the mean surgery time did not differ significantly (P > 0.05). The VAS, Barthel Index, and ODI scores were significantly better in IG than in CG at 2 days and 1 month postoperatively (P < 0.001). None of the clinical effectiveness parameters (VAS, Barthel Index, and ODI scores) differed between IG and CG at 6 or 12 months postoperatively. In addition, 141 patients in CG and 56 patients in IG experienced postoperative complications, including pressure ulcers, deep vein thrombosis, nausea and vomiting, and refracture (P = 0.970, P = 0.036, P < 0.001, P = 0.002 respectively). CONCLUSIONS: For patients undergoing PKP, the ERAS program is a reliable and effective perioperative management method that can effectively reduce LOS, postoperative pain, and economic burden and promote recovery of patients.
Assuntos
Recuperação Pós-Cirúrgica Melhorada , Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Cifoplastia/métodos , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Estudos Retrospectivos , Fraturas por Osteoporose/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Cimentos ÓsseosRESUMO
PURPOSE: To characterize abnormal epigenetic changes and protein expression of the clusterin gene in a large series of ovarian malignant and borderline tumors. METHODS: Protein expression and promoter methylation of clusterin gene in 181 primary ovarian epithelial cancer, 40 borderline ovarian tumors, 54 ovarian cancer mesenteric metastasis, and 10 normal ovarian samples were analyzed by immunohistochemical staining and methylation-specific PCR. RESULTS: Overexpression of clusterin protein was frequently seen in various ovarian epithelial tumors, being detected in 102 of 181 (56 %) primary ovarian epithelial cancers, 21 of 37 (57 %) borderline ovarian tumors. Surprisingly, clusterin protein expression was significantly reduced in mesenteric metastasis (20 of 54; 37 % cases), as compared to primary ovarian carcinoma (p = 0.01). Overexpression of clusterin protein was significantly correlated with high-grade histology (p = 0.002) and high FIGO stages (p = 0.05). Clusterin promoter hypermethylation was detected in 24 of 181 (13 %) primary ovarian epithelial cancer, 8 of 54 (14 %) mesenteric metastasis, and 10 of 37 (27 %) borderline ovarian tumors. Overall, clusterin promoter hypermethylation was significantly correlated with decreased protein expression in these samples (p < 0.001). CONCLUSIONS: Increased clusterin expression is correlated with more aggressive biologic behavior in ovarian cancer. Promoter methylation of the clusterin gene can be readily detected, though at low frequencies, in ovarian epithelial tumors and is significantly associated with decreased protein expression of the gene.
Assuntos
Clusterina/análise , Clusterina/genética , Epigênese Genética/genética , Neoplasias Ovarianas/química , Neoplasias Ovarianas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Metilação de DNA , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Mesentério/patologia , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Neoplasias Epiteliais e Glandulares/química , Neoplasias Epiteliais e Glandulares/genética , Ovário/química , Regiões Promotoras Genéticas/genética , Análise Serial de TecidosRESUMO
STUDY DESIGN: This is an observational retrospective cohort study. OBJECTIVE: The purpose of this study is to investigate the incidence rate of depression and anxiety and the changes in patients treated with percutaneous kyphoplasty (PKP) following ERAS protocol. The incidence of depression and anxiety is not uncommon in patients with osteoporotic vertebral compression fracture (OVCF), which affects the prognosis of surgery. Enhanced recovery after surgery (ERAS) protocols can improve the perioperative stress response of patients. MATERIALS AND METHODS: Patients were treated conventionally in 2019 as the control group (CG) (n = 281), and patients were treated according to the ERAS protocol in 2020 as the intervention group (IG) (n = 251). All patients were evaluated for depression and anxiety using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 at admission, postoperative 1 week, 1 month and 3, 6, 12 months. RESULTS: The degree of depression statistically decreased in the IG at follow-up periods (p < 0.001), and the degree of anxiety statistically decreased at 1 week (p < 0.001), 1 month (p < 0.001), 3 months (p = 0.017). Patients in the IG could soothe depression and anxiety disorders faster than patients in the CG and maintain psychological stability at the follow-up periods. The percentage of moderate or above depression in the IG was statistically fewer than in the CG at follow-up periods (p < 0.01). The odds ratio (OR) was respectively 0.410, 0.357, 0.294, 0.333, 0.327 from 1 week to 12 months. While the percentage of patients with moderate or above anxiety significantly decreased in the IG at 1 week (p < 0.001), OR = 0.528, 1 month (p = 0.037), OR = 0.309 and 12 months (p = 0.040), OR = 0.554, no differences between 3 months (p = 0.187) and 6 months (p = 0.133). CONCLUSION: PKP following ERAS protocol to treat patients with OVCF had a better effect on relieving postoperative anxiety and depression than following conventional protocol.
Assuntos
Recuperação Pós-Cirúrgica Melhorada , Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Cifoplastia/métodos , Fraturas por Compressão/etiologia , Estudos Retrospectivos , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/etiologia , Resultado do Tratamento , Fraturas da Coluna Vertebral/etiologia , Estresse Psicológico , Cimentos ÓsseosRESUMO
BACKGROUND: With the withdrawal of paraquat from the market, diquat is widely used, so the treatment of diquat poisoning has become one of the focuses of emergency poisoning diagnosis and treatment. CASE SUMMARY: We studied the case of a 17-year-old male patient who drank 200 mL (20 g/100 mL) of diquat solution two hours before arriving at the hospital. Despite the use of treatments such as gastric lavage, hemoperfusion, continuous hemodialysis, glucocorticoids, and organ support, the patient's condition rapidly progressed to multiorgan failure, and he died 23.5 h after admission. CONCLUSION: We summarized the clinical characteristics and treatment strategies of diquat poisoning through this case and performed a literature review to provide a basis and direction for clinical treatment.
RESUMO
Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection. Transgene integration was analyzed by PCR. Transgene expression was measured by RT-PCR and Western blot analysis. Mitochondrial DNA damage was analyzed by mutational analyses and measurement of mtDNA copy number. Total fat content was measured by a whole-body scan using dual-energy X-ray absorptiometry. The hOGG1 overexpression in mitochondria increased the abundance of intracellular free radicals and major deletions in mtDNA. Obesity in hOGG1 TG mice resulted from increased fat content in tissues, produced by hyperphagia. The molecular mechanisms of obesity involved overexpression of genes in the central orexigenic (appetite-stimulating) pathway, peripheral lipogenesis, down-regulation of genes in the central anorexigenic (appetite-suppressing) pathway, peripheral adaptive thermogenesis, and fatty acid oxidation. Diffuse hepatosteatosis, female infertility, and increased frequency of malignant lymphoma were also seen in these hOGG1 TG mice. High levels of hOGG1 expression in mitochondria, resulting in enhanced oxidative DNA damage processing, may be an important factor in human metabolic syndrome, infertility, and malignancy.
Assuntos
DNA Glicosilases/genética , Fígado Gorduroso/patologia , Fígado/patologia , Mitocôndrias/metabolismo , Obesidade/metabolismo , Oxigênio/metabolismo , Animais , Glicemia/metabolismo , Dano ao DNA , DNA Mitocondrial/genética , Feminino , Deleção de Genes , Camundongos , Camundongos Transgênicos , Obesidade/genética , Oxigênio/química , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants and have been detected in human blood, adipose tissue, and breast milk. Both in vitro and in vivo studies have shown that the effects of PBDEs are similar to the known human developmental neurotoxicants such as polychlorinated biphenyls (PCBs) on a molar basis. Previously, we reported that PBDE mixtures and congeners, perturbed calcium homeostasis which is critical for the development and function of the nervous system. In the present study, we tested whether environmentally relevant PBDE/PCB mixtures and congeners affected mitogen-activated protein kinase (MAPK) pathways, which are down-stream events of calcium signaling in cerebellar granule neuronal cultures. In this study, phosphorylated extracellular signal-regulated kinase (pERK)1/2, a widely studied MAPK cascade and known to be involved in learning and memory, levels were quantitated using western blot technique with phospho-specific antibodies. Glutamate (a positive control) increased pERK1/2 in a time- and concentration-dependent manner reaching maximum activation at 5-30min of exposure and at doses > or =10microM. Both Aroclor 1254 (a commercial penta PCB mixture) and DE-71 (a commercial penta PBDE mixture) elevated phospho-ERK1/2, producing maximum stimulation at 30min and at concentrations > or =3microg/ml; Aroclor 1254 was more efficacious than DE-71. DE-79 (an octabrominated diphenyl ether mixture) also elevated phospho-ERK1/2, but to a lesser extent than that of DE-71. PBDE congeners 47, 77, 99, and 153 also increased phospo-ERK1/2 in a concentration-dependent manner. The data indicated that PBDE congeners are more potent than the commercial mixtures. PCB 47 also increased phospho-ERK1/2 like its structural analog PBDE 47, but to a lesser extent, suggesting that these chemicals affect similar pathways. Cytotoxicity, measured as %LDH release, data showed that higher concentrations (>30microM) and longer exposures (>30min) are required to see cell death. These results show that PBDE mixtures and congeners activate MAPK pathway at concentrations where no significant cytotoxicity was observed, suggesting that perturbed intracellular signaling including MAPK pathway might be involved in the initiation of adverse effects, including learning and memory, related to these persistent chemicals.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Neurônios/enzimologia , Bifenilos Policlorados/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cerebelo/citologia , Citotoxinas/toxicidade , Humanos , Neurônios/efeitos dos fármacosRESUMO
DNA methylation at cytosines is a widely studied epigenetic modification. Methylation is commonly detected using bisulfite modification of DNA followed by PCR and additional techniques such as restriction digestion or sequencing. These additional techniques are either laborious, require specialized equipment, or are not quantitative. Here we describe a simple algorithm that yields quantitative results from analysis of conventional four-dye-trace sequencing. We call this method Mquant and we compare it with the established laboratory method of combined bisulfite restriction assay (COBRA). This analysis of sequencing electropherograms provides a simple, easily applied method to quantify DNA methylation at specific CpG sites.
Assuntos
Algoritmos , Ilhas de CpG , Metilação de DNA , Genômica/métodos , Sulfitos/química , Animais , Eletroforese em Gel de Ágar , Corantes Fluorescentes , Camundongos , Reação em Cadeia da Polimerase , Timina/análiseRESUMO
BACKGROUND: Clonorchis sinensis, a fluke dwelling in the intrahepatic bile ducts causes clonorchiasis, which affect about 15 million people wide-distributed in eastern Asia. During C. sinensis infection, worm-host interaction results in activation of patterns recognition receptors (PRRs) such as Toll-like receptors (TLRs) and further triggers immune responses, which determines the outcome of the infection. However, the mechanisms by which pathogen-associated molecules patterns from C. sinensis interact with TLRs were poorly understood. In the present study, we assumed that the molecules from C. sinensis may regulate host immune responses via TLR2 signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have identified a ~34 kDa CsHscB from C. sinensis which physically bound with TLR2 as demonstrated by molecular docking and pull-down assay. We also found that recombinant CsHscB (rCsHscB) potently activates macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-α, and IL-10, but rCsHscB failed to induce IL-10 in macrophages from Tlr2-/- mice. Moreover, ERK1/2 activation was required for rCsHscB-induced IL-10 production in macrophages. In vivo study revealed that rCsHscB triggered a high production of IL-10 in the wild-type (WT) but not in Tlr2-/- mice. Consistently, the phosphorylation of ERK1/2 was also attenuated in Tlr2-/- mice compared to the WT mice, after the treatment with rCsHscB. CONCLUSIONS/SIGNIFICANCE: Our data thus demonstrate that rCsHscB from C. sinensis interacts with TLR2 to be endowed with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology.
Assuntos
Clonorquíase/imunologia , Clonorchis sinensis/imunologia , Proteínas de Choque Térmico/metabolismo , Interleucina-10/metabolismo , Animais , Clonorquíase/parasitologia , Proteínas de Helminto/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Simulação de Acoplamento Molecular , Proteínas Recombinantes , Receptor 2 Toll-LikeRESUMO
CFTRDeltaF508 exhibits a correctable protein-folding defect that leads to its misfolding and premature degradation, which is the cause of cystic fibrosis (CF). Herein we report on the characterization of the CFTRDeltaF508 biogenic intermediate that is selected for proteasomal degradation and identification of cellular components that polyubiquitinate CFTRDeltaF508. Nonubiquitinated CFTRDeltaF508 accumulates in a kinetically trapped, but folding competent conformation, that is maintained in a soluble state by cytosolic Hsc70. Ubiquitination of Hsc70-bound CFTRDeltaF508 requires CHIP, a U box containing cytosolic cochaperone. CHIP is demonstrated to function as a scaffold that nucleates the formation of a multisubunit E3 ubiquitin ligase whose reconstituted activity toward CFTR is dependent upon Hdj2, Hsc70, and the E2 UbcH5a. Inactivation of the Hsc70-CHIP E3 leads CFTRDeltaF508 to accumulate in a nonaggregated state, which upon lowering of cell growth temperatures, can fold and reach the cell surface. Inhibition of CFTRDeltaF508 ubiquitination can increase its cell surface expression and may provide an approach to treat CF.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Chaperonas Moleculares/metabolismo , Dobramento de Proteína , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Retículo Endoplasmático/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSC70 , Humanos , Proteínas de Ligação ao Ferro/genética , Proteínas de Ligação ao Ferro/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Head and neck squamous cell carcinoma (HNSCC) typically affects male smokers older than 55 years. Recently, an increase in the incidence of HNSCC in young adults has been recognized, many of them nonsmokers and females. Functional inactivation of p16 is known to be a common event in HNSCC, mainly by either deletion or methylation. A previous study by this group has shown that p16 deletions in HNSCC are significantly associated with age. The primary objective of this study was to evaluate additional molecular alterations of p16 in HNSCC, specifically in relation to age, site, and human papillomavirus (HPV) status. Patients ranging in age from 22 to 76 years with HNSCC were prospectively identified (n = 24). Methylation-specific polymerase chain reaction and immunohistochemistry were used to evaluate p16 gene inactivation and p16 protein expression, respectively. HPV 16 status was determined for each case. Overall, p16 inactivation was a frequent event detected in 46% of cases. Methylation of p16 was more often detected in females than males (P = .05). All cases showing p16 methylation were from the anterior tongue, and 75% of them were young patients. The results indicate that p16 methylation is a more common event in those younger than 40 years in contrast to p16 deletions, which are more common in those older than 40 years. Consequently, it appears that specific modes of inactivation of p16 in HNSCC are related to specific patient risk profiles. Interestingly, HPV 16 messenger RNA was detected exclusively in HNSCC from the base of tongue lesions and was only found in males. This differs from the patient profile of HNSCC in the young, which affects the anterior tongue and commonly females, thus, making it highly unlikely that this virus is a primary causative agent of HNSCC in these young adults.
Assuntos
Carcinoma de Células Escamosas/genética , Epigênese Genética , Genes p16 , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/patologia , DNA Viral/isolamento & purificação , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , RNA Mensageiro/análise , Fatores Sexuais , Fumar/efeitos adversosRESUMO
BACKGROUND: One major risk factor for cutaneous melanoma is chronic sun-exposure and oxidative stress. Among various oxidative DNA damages, 8-oxoquanine is the most abundant and is potentially mutagenic if not sufficiently repaired. The human 8-oxoquanine DNA glycosylase 1 (hOGG1) gene specifically repairs 8-oxoguanine, and this gene shows frequent loss of heterozygosity (LOH) in human tumors. In this study, we investigate whether hOGG1 LOH occurs in melanoma in situ (MIS) and adjacent atypical melanocytic hyperplasia (AMH). METHODS: Twelve skin biopsies with MIS and adjacent AMH were included. DNA samples derived from manual microdissection of tissues were subjected to polymerase chain reaction amplification using three fluorescent-labeled microsatellite makers, followed by fragment analysis. RESULTS: Five of 12 cases were informative for both telomeric (3S1297) and centromeric (3S1289 or 3S1300) markers, bordering the hOGG1 locus. Among them, four (80%) MIS and three (60%) AMH showed hOGG1 LOH at both markers. CONCLUSIONS: These results shows that LOH at hOGG1 gene is associated with MIS and AMH and suggest that the hOGG1 gene may play a role in melanocytic tumor progression.
Assuntos
DNA Glicosilases/genética , Reparo do DNA/genética , Perda de Heterozigosidade , Melanoma/genética , Lesões Pré-Cancerosas/genética , Neoplasias Cutâneas/genética , Biópsia , Centrômero/genética , DNA de Neoplasias/análise , Marcadores Genéticos , Humanos , Hiperplasia , Melanócitos/patologia , Melanoma/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/patologia , Telômero/genéticaRESUMO
The kidney is constantly exposed to free radicals due to its active metabolism and processing of toxic metabolites. Among 20 or so free radical-induced DNA lesions, 8-oxoquanine is the most abundant and is potentially mutagenic if not sufficiently removed. The human 8-oxoquanine DNA glycosylase 1 (hOGG1) gene repairs 8-oxoguanine and resides at 3p25-26, which has frequent loss of heterozygosity (LOH) in clear cell-renal cell carcinoma (CC-RCC). Even though some studies found similar genetic alterations between renal papillary adenomas (PA) and papillary RCC (PRCC), no studies have been conducted to compare the alterations of hOGG1 gene in PA, PRCC and CC-RCC. To further explore the relationship between CC-RCC, PRCC and PA at the genetic level LOH of hOGG1 gene was investigated in these three groups. It was found that 8/8 PRCC (100%) and 8/9 CC-RCC (88%) had evidence of hOGG1 LOH, whereas all four PA (0%) were devoid of hOGG1 LOH. It is concluded that deletion of hOGG1 gene occurs commonly in PRCC and CC-RCC but not in renal cortical PA. Further studies are warranted to further explore the exact roles of hOGG1 gene in the development and progression of RCC.
Assuntos
Adenoma/genética , Carcinoma de Células Renais/genética , DNA Glicosilases/genética , Reparo do DNA/genética , Neoplasias Renais/genética , Adenoma/metabolismo , Adenoma/patologia , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , DNA Glicosilases/metabolismo , DNA de Neoplasias/análise , Feminino , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and its receptor (VEGF-R2) in port-wine stains (PWSs). DESIGN: An immunohistochemistry (IHC) study on formalin-fixed, paraffin-embedded specimens. METHODS: Representative sections from surgical resection specimens of 12 PWS patients and 12 control specimens stained with routine IHC by using polyclonal anti-VEGF and anti-VEGF-R2 antibodies. Slides were evaluated semiquantitatively for the intensity of staining for VEGF and VEGF-R2 by using a scoring system varying from 0 to 3+. RESULTS: PWS specimens showed statistically significant overexpression of both VEGF and VEGF-R2 molecules when compared with control specimens (P < 0.005). CONCLUSIONS: VEGF and its receptor may play an important role in the pathogenesis of PWS. It is possible that PWS may progress by hyperplasia in addition to hypertrophy. VEGF-R blockade may have a potential role as a targeted approach in the treatment of this disfiguring condition in the future.
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Mancha Vinho do Porto/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Inclusão em ParafinaRESUMO
Chordomas are rare tumors of notochordal origin that arise along the vertebral axis. These slowly growing yet highly destructive tumors are associated with an alarming rate of recurrence, although surgical resection followed by proton, proton/photon, or conventional radiotherapy has been somewhat successful in terms of recurrence-free survival. Still, recurrent disease as a result of metastasis or surgical pathway seeding does occur. We retrospectively reviewed the case of a 64-year-old woman who presented with a left neck mass at level II. She had a history of recurrent chordomas involving the occipital portion of the clivus that had been treated with multiple resections and proton-beam irradiations over a period of several years. The new mass was found to have infiltrated the superior end of the sternocleidomastoid muscle. Neck dissection was performed. Pathology revealed no lymphoid tissue in the main specimen and no evidence of chordoma in any of the lymph nodes. We believe that this latest clival chordoma might have occurred as a result of surgical pathway seeding during a previous operation anterior to the sternocleidomastoid muscle, although metastasis cannot be ruled out. We also review the literature on clival and skull base chordomas as it relates to recurrence, metastasis, and seeding.
Assuntos
Cordoma/secundário , Neoplasias de Cabeça e Pescoço/secundário , Recidiva Local de Neoplasia/etiologia , Inoculação de Neoplasia , Neoplasias da Base do Crânio/patologia , Cordoma/cirurgia , Evolução Fatal , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Pessoa de Meia-Idade , Esvaziamento Cervical , Fatores de RiscoRESUMO
BACKGROUND: Estrogen plays a role in infantile hemangioma (IH) development, but the underlying mechanism remains unclear. This study aimed to assess estrogen and estrogen receptor (ER) localization and expression levels in IH. In addition, the unexpected relationship between mast cells (MCs) and estrogen in human IH was discussed. METHODS: IH (n = 29), vascular malformation (VMs, n = 33) and normal skin (n = 15) specimens were assessed. IH was classified into proliferative (n = 9; age, 3.56 ± 1.01 months), early involuting (n = 10; age, 8.90 ± 2.69 months) and late involuting (n = 10; age, 20.10 ± 4.93 months) groups. Estradiol (E2), ER-a, ER-ß, and tryptase (MC marker) levels were determined immunohistochemically and/or by double immunofluorescence staining. Quantification and localization of tryptase, ER-a, and E2 were assessed for each specimen. RESULTS: ER-a, E2, and tryptase were expressed in the cytoplasm and nucleus of MCs in IH. The IH specimens showed significantly more tryptase, ER-a, and E2 positive MCs (30.6 ± 12.7, 9.7 ± 5.6, and 19.8 ± 8.7 cells/high-power field [HPF], respectively) compared with VM specimens (9.0 ± 9.8, 1.5 ± 2.4, and 2.5 ± 4.1 cells/HPF, respectively) and normal skin (6.1 ± 8.5, 0.5 ± 1.2, and 1.9 ± 3.4 cells/HPF, respectively). Proliferating IH displayed fewer E2 positive MCs (14.0 6.3 cells/HPF) compared with early (22.3 ± 10.2 cells/HPF, P = 0.023) and late (22.4 ± 6.8 cells/HPF, P = 0.006) involuting specimens. In addition, proliferating IH showed fewer tryptase positive MCs (24.7 ± 10.8 cells/HPF) compared with early involuting specimens (35.7 ± 15.3 cells/HPF, P = 0.043). All IH specimens were ER-a positive and ER-ß negative. CONCLUSIONS: E2 and ER-a are expressed on MCs and not on IH endothelial cells. Furthermore, activated MCs may be involved in IH regression.
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Estradiol/metabolismo , Hemangioma/metabolismo , Hemangioma/patologia , Mastócitos/fisiologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Regulação da Expressão Gênica , Humanos , Lactente , Transporte Proteico , Triptases/genética , Triptases/metabolismoRESUMO
BACKGROUND: Histopathology, which is one of the most important routines of all laboratory procedures used in pathology, is decisive for the diagnosis of cancer. Experienced histopathologists review the histological slides acquired from biopsy specimen in order to outline malignant areas. Recently, improvements in imaging technologies in terms of histological image analysis led to the discovery of virtual histological slides. In this technique, a computerized microscope scans a glass slide and generates virtual slides at a resolution of 0.25 mum/pixel. As the recognition of intrinsic cancer areas is time consuming and error prone, in this study we develop a novel method to tackle automatic squamous cell carcinoma of the head and neck detection problem in high-resolution, wholly-scanned histopathological slides. RESULTS: A density-based clustering algorithm improved for this study plays a key role in the determination of the corrupted cell nuclei. Using the Support Vector Machines (SVMs) Classifier, experimental results on seven head and neck slides show that the proposed algorithm performs well, obtaining an average of 96% classification accuracy. CONCLUSION: Recent advances in imaging technology enable us to investigate cancer tissue at cellular level. In this study we focus on wholly-scanned histopathological slides of head and neck tissues. In the context of computer-aided diagnosis, delineation of malignant regions is achieved using a powerful classification algorithm, which heavily depends on the features extracted by aid of a newly proposed cell nuclei clustering technique. The preliminary experimental results demonstrate a high accuracy of the proposed method.
Assuntos
Algoritmos , Inteligência Artificial , Neoplasias de Cabeça e Pescoço/patologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Reconhecimento Automatizado de Padrão/métodos , Análise por Conglomerados , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The onset and progression of cancer is associated with the methylation-dependent silencing of specific genes, however, the mechanism and its regulation have not been established. We previously demonstrated that reduction of mitochondrial DNA content induces cancer progression. Here we found that mitochondrial DNA-deficient LNrho0-8 activates the hypermethylation of the nuclear DNA promoters including the promoter CpG islands of the endothelin B receptor, O6-methylguanine-DNA methyltransferase, and E-cadherin. These are unmethylated and the corresponding gene products are expressed in the parental LNCaP containing mitochondrial DNA. The absence of mitochondrial DNA induced DNA methyltransferase 1 expression which was responsible for the methylation patterns observed. Inhibition of DNA methyltransferase eliminated hypermethylation and expressed gene products in LNrho0-8. These studies demonstrate loss or reduction of mitochondrial DNA resulted in the induction of DNA methyltransferase 1, hypermethylation of the promoters of endothelin B receptor, O6-methylguanine-DNA methyltransferase, and E-cadherin, and reduction of the corresponding gene products.
Assuntos
Núcleo Celular/genética , Ilhas de CpG/genética , Metilação de DNA , DNA Mitocondrial/genética , DNA de Neoplasias/genética , Mitocôndrias/genética , Neoplasias da Próstata/genética , Linhagem Celular Tumoral , Humanos , MasculinoRESUMO
OBJECTIVES: To determine the methylation status of gene promoter regions using methylation-specific polymerase chain reaction in genes encoding for thyrotropin receptor (TSHR), E-cadherin (ECAD), sodium iodide symporter protein (NIS-L), ataxia telangiectasia mutated (ATM), and death-associated protein kinase (DAPK) proteins and if methylation status correlates with patient variables, tumor factors, or outcome measures among patients with papillary thyroid carcinoma. DESIGN: Database query and retrospective medical chart review for patients with well-differentiated thyroid cancer and nonmalignant thyroid conditions treated at our institutions (1996-2004). Methylation-specific polymerase chain reaction was performed, and results were compared with controls for these genes. Methylation status was then compared with patient variables, tumor factors, and outcome measures for patients with thyroid carcinoma and controls. PATIENTS: The study population comprised 32 patients with papillary thyroid carcinoma and 27 controls. RESULTS: In our patients, all 5 genes were methylated more frequently in papillary thyroid carcinoma than in controls. NIS-L trended toward a more advanced stage at presentation. NIS-L methylation in cancer cells was not associated with methylation in adjacent benign tissue, unlike the other 4 genes. Neither age nor sex affected methylation status, and methylation status did not correlate with extent of the primary tumor or presence of nodal metastasis at diagnosis. Tumors recurred less frequently in patients with TSHR methylation than in patients with unmethylated TSHR promoter regions. CONCLUSIONS: Promoter methylation may be a marker for malignancy in thyroid carcinoma. Furthermore, methylation status of tumors as determined by methylation-specific polymerase chain reaction may help in determining patient prognosis.
Assuntos
Carcinoma Papilar/genética , DNA de Neoplasias/genética , Receptores da Tireotropina/metabolismo , Simportadores/metabolismo , Neoplasias da Glândula Tireoide/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Feminino , Humanos , Iodo , Masculino , Metilação , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Regiões Promotoras Genéticas/fisiologia , Receptores da Tireotropina/genética , Estudos Retrospectivos , Simportadores/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
OBJECTIVE: Perineural spread (PNS) is an important risk factor for locoregional failure and is correlated with reduced survival rates in squamous cell carcinoma of the larynx. PNS may extend proximally and/or distally in the nerve sheath by leaving uninvolved nerve segments. This method of extension may preclude obtaining tumor-free surgical margins, which may be responsible for recurrent disease. The purpose of this study is to investigate the presence or absence of PNS in extralaryngeal superior and inferior laryngeal nerves in patients who underwent total laryngectomy for squamous cell carcinoma of the larynx. METHODS: Extralaryngeal segments of superior and inferior laryngeal nerves were resected bilaterally during 15 consecutive laryngectomies. Laryngectomy specimens and the harvested proximal nerve segments were histopathologically examined for the presence or absence of PNS. RESULTS: Ten of 15 laryngectomy specimens showed PNS; however, none of the extralaryngeal superior or inferior laryngeal nerve segments revealed perineural involvement. CONCLUSION: Extralaryngeal extension of PNS is highly unlikely in squamous cell carcinoma of the larynx.