RESUMO
BACKGROUND: Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. Insights into mechanisms of resistance to selective RET inhibitors remain limited. PATIENTS AND METHODS: This study was performed at five institutions. Tissue and/or cell-free DNA was obtained from patients with RET fusion-positive NSCLC after treatment with selpercatinib or pralsetinib and assessed by next-generation sequencing (NGS) or MET FISH. RESULTS: We analyzed a total of 23 post-treatment tissue and/or plasma biopsies from 18 RET fusion-positive patients who received an RET-selective inhibitor (selpercatinib, n = 10; pralsetinib, n = 7; pralsetinib followed by selpercatinib, n = 1, with biopsy after each inhibitor). Three cases had paired tissue and plasma samples, of which one also had two serial resistant tissue specimens. The median progression-free survival on RET inhibitors was 6.3 months [95% confidence interval 3.6-10.8 months]. Acquired RET mutations were identified in two cases (10%), both affecting the RET G810 residue in the kinase solvent front. Three resistant cases (15%) harbored acquired MET amplification without concurrent RET resistance mutations, and one specimen had acquired KRAS amplification. No other canonical driver alterations were identified by NGS. Among 16 resistant tumor specimens, none had evidence of squamous or small-cell histologic transformation. CONCLUSIONS: RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis , Piridinas , Pirimidinas , TirosinaAssuntos
Neoplasias Pulmonares/tratamento farmacológico , Rituximab/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Encefalite/líquido cefalorraquidiano , Encefalite/induzido quimicamente , Humanos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/líquido cefalorraquidiano , Neoplasias Pulmonares/patologia , Masculino , Nivolumabe , Carcinoma de Pequenas Células do Pulmão/líquido cefalorraquidiano , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment strategy for KRAS mutant non-small cell lung cancers (NSCLC) and colorectal carcinomas that harbor wild-type TP53. The combination of pimasertib (MEK inhibitor) and SAR405838 (MDM2 inhibitor) was synergistic and induced the expression of PUMA and BIM, led to apoptosis and growth inhibition in vitro, and tumor regression in vivo. Acquired resistance to the combination commonly resulted from the acquisition of TP53 mutations, conferring complete resistance to MDM2 inhibition. In contrast, resistant clones exhibited marked variability in sensitivity to MEK inhibition, which significantly impacted sensitivity to subsequent treatment with alternative MEK inhibitor-based combination therapies. These results highlight both the potential promise and limitations of combining MEK and MDM2 inhibitors for treatment of KRAS mutant NSCLC and colorectal cancers.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , MAP Quinase Quinase Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Células A549 , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Neoplasias Colorretais/genética , Sinergismo Farmacológico , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Indóis , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Nus , Mutação , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Interferência de RNA , RNA Interferente Pequeno , Compostos de Espiro , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Phosphatidylcholine-polymer-coated plastic slides were utilized for the fabrication of peptide microarrays for cellular kinome analysis. According to the non-fouling features of the surface, the signal-to-noise ratio of the detection of phosphorylated peptides improved by about 100-fold from that of a peptide microarray fabricated on a glass slide blocked by a commercial BSA-based reagent. When the phosphatidylcholine-polymer-coated peptide microarray was applied to the analysis of the kinome of HCC827 cells, hyperactivation of c-Src and EGFR were successfully detected.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Vidro/química , Fragmentos de Peptídeos/análise , Fosfatidilcolinas/química , Polímeros/química , Análise Serial de Proteínas , Proteínas Quinases/análise , Corantes Fluorescentes , Humanos , Neoplasias Pulmonares/metabolismo , Fragmentos de Peptídeos/química , Fosfoproteínas/análise , Fosforilação , Células Tumorais CultivadasRESUMO
AIMS: To evaluate and compare the reductions of human viruses and F-specific coliphages in a full-scale wastewater treatment plant based on the quantitative PCR (qPCR) and plate count assays. METHODS AND RESULTS: A total of 24 water samples were collected from four locations at the plant, and the relative abundance of human viruses and F-RNA phage genogroups were determined by qPCR. Of the 10 types of viruses tested, enteric adenoviruses were the most prevalent in both influent and effluent wastewater samples. Of the different treatment steps, the activated sludge process was most effective in reducing the microbial loads. Viruses and F-RNA phages showed variable reduction; among them, GI and GIII F-RNA phages showed the lowest and the highest reduction, respectively. CONCLUSIONS: Ten types of viruses were present in wastewater that is discharged into public water bodies after treatment. The variability in reduction for the different virus types demonstrates that selection of adequate viral indicators is important for evaluating the efficacy of wastewater treatment and ensuring the water safety. SIGNIFICANCE AND IMPACT OF THE STUDY: Our comprehensive analyses of the occurrence and reduction of viruses and indicators can contribute to the future establishment of appropriate viral indicators to evaluate the efficacy of wastewater treatment.
Assuntos
Colífagos/isolamento & purificação , Fagos RNA/isolamento & purificação , Águas Residuárias/virologia , Colífagos/genética , Japão , Reação em Cadeia da Polimerase/métodos , Fagos RNA/genética , Esgotos/virologia , Instalações de Eliminação de Resíduos , Águas Residuárias/microbiologia , Microbiologia da Água , Purificação da ÁguaRESUMO
PURPOSE: To determine the incidence of Herpes zoster in patients with one of 17 specific underlying diseases compared with that in patients with other underlying diseases. METHODS: We conducted a retrospective hospital-based cohort study using data from patients' electronic medical records for the period 2001-2007 of the Kitano Hospital Research Database. These analyses included 55,492 patients with one of 17 underlying diseases, which were those reported as related to the contraction of Herpes zoster. Of these, 769 patients contracted Herpes zoster. The main outcome measure was the clinical diagnosis of Herpes zoster. RESULTS: The adjusted hazard ratios (95% confidence interval) for Herpes zoster in patients with the 17 diseases were compared with other patients, with the following results: brain tumor [3.84 (2.51-5.88)], lung cancer [2.28 (1.61-3.22)], breast cancer [2.41 (1.52-3.82)], esophageal cancer [4.19 (2.16-8.11)], gastric cancer [1.95 (1.39-2.72)], colorectal cancer [1.85 (1.33-2.56)], gynecologic cancer [3.45 (2.08-5.70)], malignant lymphoma [8.23 (6.53-10.38)], systemic lupus erythematosus [3.90 (2.66-5.70)], rheumatoid arthritis [2.00 (1.60-2.50)], diabetes mellitus [2.44 (2.10-2.85)], hypertension [2.04 (1.75-2.38)], renal failure [2.14 (1.65-2.79)], and disk hernia [2.18 (1.52-3.13)]. CONCLUSIONS: Patients with diabetes mellitus, renal failure, and malignancies have a 1.8-8.4-fold higher risk of a Herpes zoster event than patients with other diseases. Future studies should investigate alteration of the immune system in the underlying diseases and approaches for Herpes zoster prevention.
Assuntos
Complicações do Diabetes/epidemiologia , Herpes Zoster/epidemiologia , Neoplasias/complicações , Insuficiência Renal/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Feminino , Hospitais , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Cranio-lenticulo-sutural dysplasia (CLSD) is a rare autosomal recessive syndrome manifesting with large and late-closing fontanels and calvarial hypomineralization, Y-shaped cataracts, skeletal defects, and hypertelorism and other facial dysmorphisms. The CLSD locus was mapped to chromosome 14q13-q21 and a homozygous SEC23A F382L missense mutation was identified in the original family. Skin fibroblasts from these patients exhibit features of a secretion defect with marked distension of the endoplasmic reticulum (ER), consistent with SEC23A function in protein export from the ER. We report an unrelated family where a male proband presented with clinical features of CLSD. A heterozygous missense M702V mutation in a highly conserved residue of SEC23A was inherited from the clinically unaffected father, but no maternal SEC23A mutation was identified. Cultured skin fibroblasts from this new patient showed a severe secretion defect of collagen and enlarged ER, confirming aberrant protein export from the ER. Milder collagen secretion defects and ER distention were present in paternal fibroblasts, indicating that an additional mutation(s) is present in the proband. Our data suggest that defective ER export is the cause of CLSD and genetic element(s) besides SEC23A may influence its presentation.
Assuntos
Anormalidades Múltiplas/genética , Colágeno/metabolismo , Anormalidades Craniofaciais/genética , Anormalidades Múltiplas/diagnóstico , Sequência de Aminoácidos , Sequência de Bases , Anormalidades Craniofaciais/diagnóstico , Retículo Endoplasmático/metabolismo , Família , Fibroblastos/metabolismo , Heterozigoto , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Proteínas de Transporte Vesicular/genéticaRESUMO
We report a case of successful treatment of a methicillin resistant Staphylococcus aureus (MRSA) mediastinitis by vacuum assisted closure (VAC) using SB VAC system as a portable aspirator. A 67-year-old male with intellectual disability and diabetes mellitus suffered from angina pectoris and underwent on-pump coronary artery bypass grafting. He had a MRSA mediastinitis following the surgery. We started vancomycin administration and VAC. It was expected that using wall suction for VAC would be difficult because of his intellectual disability. So we performed VAC using SB VAC system as a portable aspirator. VAC therapy for mediastinitis after cardiac surgery is effective and SB VAC system can be used as a portable aspirator.
Assuntos
Mediastinite/microbiologia , Mediastinite/cirurgia , Complicações Pós-Operatórias/cirurgia , Infecções Estafilocócicas , Curetagem a Vácuo/instrumentação , Curetagem a Vácuo/métodos , Idoso , Angina Pectoris/cirurgia , Ponte de Artéria Coronária , Humanos , Masculino , Resistência a Meticilina , Técnicas de SuturaRESUMO
BACKGROUND AND AIMS: A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn's disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17,000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population. PATIENTS AND METHODS: A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including IRGM, NKX2-3 and PTPN2, were genotyped using the TaqMan assay or the invader assay. RESULTS: A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of NKX2-3 (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near IL12B and rs10761659 on 10q21. Further genotype-phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD. CONCLUSIONS: The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities.
Assuntos
Povo Asiático/genética , Doença de Crohn/genética , Proteínas de Homeodomínio/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adolescente , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Doenças do Colo/genética , Doença de Crohn/classificação , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Doenças do Íleo/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , FenótipoAssuntos
Neuropatias Amiloides Familiares/genética , Amiloide/genética , Mutação de Sentido Incorreto , Pré-Albumina/genética , Substituição de Aminoácidos , Europa (Continente) , Efeito Fundador , Frequência do Gene , Haplótipos , Humanos , Japão , Repetições de Microssatélites , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Granulysin, a lytic protein present in cytolytic granules of human natural killer and cytotoxic T cells, entered cells infected with varicella-zoster virus (VZV). Exposure to granulysin accelerated death of infected cells as assessed by apoptosis markers. The functional domain of granulysin that mediated its antiviral effects was amino acid 23-51; this domain also mediates the additional antitumor cell effects of granulysin. Because granulysin is a product of natural killer cells and T lymphocytes, it is possible that its antiviral activity may act as a mediator of innate and adaptive immune mechanisms.
Assuntos
Anti-Infecciosos/farmacologia , Antígenos de Diferenciação de Linfócitos T/farmacologia , Apoptose/efeitos dos fármacos , Herpesvirus Humano 3/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Clorometilcetonas de Aminoácidos/farmacologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Caspases/fisiologia , Herpesvirus Humano 3/fisiologia , HumanosAssuntos
Neoplasias/genética , Fator de Crescimento Transformador beta/fisiologia , Animais , Divisão Celular , Proteínas de Ligação a DNA/genética , Humanos , Camundongos , Modelos Biológicos , Mutação , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais , Proteína Smad4 , Transativadores/genéticaRESUMO
Although the best treatment for gastric malignant lymphoma remains a controversial matter, surgery is the first choice for localized malignant lymphoma without lymph node metastasis and invasion to the adjacent organ. We report a case of gastric malignant lymphoma that was managed with laparoscopy-assisted distal gastrectomy. A 47-year-old man was referred to our department for management of gastric lymphoma. After preoperative examination revealed a tumor confined to the gastric wall but no lymph node metastasis, we performed laparoscopy-assisted Billroth I gastrectomy. Histopathologic examination confirmed that the tumor was follicular center lymphoma limited to the submucosa with no lymph node metastasis. The postoperative course was good. This is the first reported case of laparoscopic gastrectomy-treated gastric malignant lymphoma. Because it involves minimal access and invasiveness, this procedure may be an effective method of treatment of localized malignant lymphoma of the stomach.
Assuntos
Gastrectomia , Laparoscopia , Linfoma/cirurgia , Neoplasias Gástricas/cirurgia , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: The proportion of low birthweight babies (LBW: 1500-2499 g) in Japan decreased steadily from 1950 to the 1970s. However, since then it has started to increase consistently, the reason for which has not been discussed in detail. METHODS: Trends of birthweight and the two known factors for low birthweight (maternal smoking, and pre-pregnancy weight) were analysed with vital statistics, national nutritional and smoking prevalence survey data. RESULTS: Increase in term LBW due to intrauterine growth retardation, is the major risk factor for the overall increase since the 1970s. The increase of smoking prevalence in women in their thirties started in the 1970s, while that for women in their twenties started in the 1960s. The decrease of body mass index for women in their thirties also began in the 1970s, while that for women in their twenties began in the 1960s. The ratio of delivery to mothers in their thirties to mothers in their twenties has increased more than threefold compared to the late 1970s. CONCLUSIONS: Since the 1970s increase in smoking prevalence and decrease in body mass index in young women, especially those in their thirties, appeared to be the major factors involved in the increase in LBW babies.
Assuntos
Retardo do Crescimento Fetal/complicações , Recém-Nascido de Baixo Peso , Adulto , Índice de Massa Corporal , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Masculino , Gravidez , Prevalência , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
We investigated the effects of advanced glycation end products (AGEs) on the expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only the gene expression of two major OxLDL receptors, macrophage scavenger receptor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-density lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs increased transcriptional activities of AP-1, NF-kappaB, and peroxisome proliferator-activated receptor gamma. These findings indicate that AGEs-induced enhancement of these transcriptional activities might be involved in increased levels of mRNA for some of OxLDL receptors in THP-1-cells treated with PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involved in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of individuals with diabetes.
Assuntos
Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/farmacologia , Macrófagos/metabolismo , Proteínas de Membrana , Monócitos/metabolismo , Receptores Imunológicos/biossíntese , Receptores de Lipoproteínas , Tiazolidinedionas , Northern Blotting , Antígenos CD36/metabolismo , Linhagem Celular , Células Cultivadas , Cromanos/farmacologia , DNA Complementar/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Humanos , Imuno-Histoquímica , Microscopia de Fluorescência , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Receptores de LDL/biossíntese , Receptores de LDL/genética , Receptores de LDL Oxidado , Receptores Depuradores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptores Depuradores Classe A , Receptores Depuradores Classe B , Receptores Depuradores Classe E , Acetato de Tetradecanoilforbol/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Tiazóis/farmacologia , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Ativação Transcricional , Troglitazona , Fator de Necrose Tumoral alfa/metabolismo , Raios Ultravioleta , Regulação para CimaRESUMO
BACKGROUND: Several recent studies have demonstrated the low yield of anatomically based computed tomography scans in evaluating Stage III (American Joint Committee on Cancer) patients with malignant melanoma. The purpose of this study was to investigate the efficacy and clinical utility of functionally based positron emission tomography (PET) scans in the same patient population. METHODS: A prospective evaluation of 106 whole body PET scans obtained after injection of 2-fluorine-18, 2-fluoro-2-deoxy-D-glucose (FDG) was performed in 95 patients with clinically evident Stage III lymph node and/or in-transit melanoma. Areas of abnormality on FDG PET scanning were identified visually as foci of increased metabolic activity compared with background, and all positive foci were assessed pathologically. RESULTS: In this patient population, there were 234 areas that were evaluated pathologically of which 165 were confirmed histologically to be melanoma. PET scanning identified 144 of the 165 areas of melanoma for a sensitivity of 87.3%. The 21 areas of melanoma that were missed included 10 microscopic foci, 9 foci less than 1 cm, and 2 foci greater than 1 cm. There were 39 areas of increased PET activity that were not associated with malignancy for a 78.6% predictive value of a positive test. Of the 39 false-positive areas (false-positive rate of 56.5%), 13 could be attributed to recent surgery, 3 to arthritis, 3 to infection, 2 to superficial phlebitis, 1 to a benign skin nevus, and 1 to a colonic polyp. Pathologic evaluation of the remaining false-positive areas failed to reveal a definitive etiology for their increased activity on PET scan. With the application of pertinent clinical information, the predictive value of a positive PET scan could be improved to 90. 6%. The specificity of PET scanning in this study was only 43.5% because very few prophylactic lymph node dissections were performed. Thirty-six of the total 183 abnormal areas (19.7%) on PET scanning proved to be unsuspected areas of metastatic disease. These findings led to a change in the planned clinical management in patients after 16 of the 106 PET scans (15.1%). CONCLUSIONS: FDG PET scanning can be helpful in managing patients with Stage III melanoma in whom further surgery is contemplated. Although false-positive areas are not uncommon, PET scans did change the management of patients 15% of the time. PET's inability to identify microscopic disease suggests that it is of limited use in evaluating patients with Stage I-II disease.
Assuntos
Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Fluordesoxiglucose F18 , Humanos , Melanoma/secundário , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Cutâneas/patologiaAssuntos
Formaldeído/química , Gelatina/química , Resorcinóis/química , Adesivos Teciduais/química , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/cirurgia , Combinação de Medicamentos , Formaldeído/uso terapêutico , Gelatina/uso terapêutico , Humanos , Resorcinóis/uso terapêutico , Adesivos Teciduais/uso terapêuticoRESUMO
BACKGROUND: Gastrointestinal foregut carcinoids make up a small percentage (3% to 6%) of all reported carcinoids. Because these tumors are so uncommon, comparisons between the subtypes have been difficult. The goal of this study was to compare the hormonal and clinical characteristics of gastric, duodenal, and pancreatic carcinoids. METHODS: A prospective database of approximately 750 carcinoid patients seen by one author over 25 years was reviewed, and the 104 patients with gastric (33), duodenal (17), or pancreatic (54) carcinoids were selected as the subgroup for analysis. These patients were compared with regard to hormone levels, clinical course, treatment, and survival. RESULTS: Duodenal carcinoids exhibited significantly lower serotoninergic hormone levels than did the gastric and pancreatic carcinoids (urine 5-hydroxyindoleacetic acid [mg/24 h], 5 +/- 1 vs 16 +/- 5 and 47 +/- 12, respectively, P = .03). Pancreatic carcinoids presented with more advanced stage (distant metastases 87% vs 42% and 20% for gastric and duodenal, respectively) and had worse outcomes than patients with gastric and duodenal tumors with 10-year survivals of 10%, 59%, and 58%, respectively (P = .003). CONCLUSIONS: Pancreatic carcinoids produce higher levels of serotoninergic hormones and have a significantly higher stage and worse outcome than other foregut carcinoids. This study demonstrates that the organ of origin is an important determinant of hormonal activity and clinical course for patients with foregut carcinoids.
Assuntos
Tumor Carcinoide/química , Tumor Carcinoide/diagnóstico , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/diagnóstico , Adulto , Distribuição por Idade , Idoso , Análise de Variância , Tumor Carcinoide/mortalidade , Neoplasias Duodenais/química , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Ácido Hidroxi-Indolacético/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Serotonina/sangue , Distribuição por Sexo , Neoplasias Gástricas/química , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Análise de SobrevidaRESUMO
Osteoporosis, a condition characterized by low bone mineral density (BMD) leading to bone fragility [1], is a major public health concern in Japan as well as in other countries. Although genetic predisposition seems to be a factor in the pathogenesis of osteoporosis [2-4], the precise cohort of genes that may be involved is not well defined. The COLIA1 and COLIA2 genes encode polypeptide constituents of collagen type Ialpha1 and Ialpha2, respectively. Both are important candidates as genetic regulators of BMD, since mutations in either gene result in osteogenesis imperfecta, a disorder characterized by severe osteoporosis [5]. Some patients with adult osteoporosis also carry mutations in COLIA1 or COLIA2 genes [6].http://link.springer-ny. com/link/service/journals/00223/bibs/65n5p352.html++ +hea