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PURPOSE: Postoperatively persistent type II endoleaks (T2ELs) in abdominal endovascular aneurysm repair (EVAR) are known risk factors for long-term aneurysm enlargement. Therefore, various measures have been proposed to prevent T2ELs. Notably, the Kilt technique, which can be used in patients with dumbbell-shaped morphology, employs an aortic cuff deployed in the distal seal zone before the main body. Although previous studies have successfully applied this technique for preventing T2ELs, the mid- and long-term outcomes remain unclear. This study aimed to report the early- to mid-term outcomes in cases where an aortic cuff technique was used to prevent T2ELs. MATERIALS AND METHODS: This retrospective single-center study analyzed 9 patients (mean age, 79 years; range, 69-88 years; 8 men) with abdominal aortic aneurysms. All patients underwent EVAR using an aortic cuff to prevent T2ELs. The primary end points were technical success (successful deployment) and clinical success (no T2ELs). Secondary end points included morbidity, reintervention, and aortic remodeling during follow-up. RESULTS: The technical success rate was 100%. There were no intraprocedural or postoperative complications. No deaths or reinterventions occurred. Postoperative computed tomography showed no endoleaks in 6 patients, while T2ELs from the lumbar artery outside the aortic cuff deployment range were noted in 3 patients. However, no T2ELs were observed in the artery in the aortic cuff deployment range in any patient. The average number of successfully occluded arteries was 4.2 (range, 2-8). All patients had follow-up >6 (mean, 18.6; range, 6-36) months. Aneurysm sac shrinkage occurred in 5 patients during the follow-up period, whereas aneurysm size was stable in 3 patients. In contrast, only 1 patient showed transient dilation of the aneurysm sac enlargement; however, this dilation remained unchanged even after 1.5 years. CONCLUSION: The aortic cuff technique is a favorable endovascular method for preventing T2ELs in EVAR. The present study showed that a single aortic cuff could easily and reliably occlude arteries branched from the aneurysm sac.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Masculino , Humanos , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/complicações , Correção Endovascular de Aneurisma , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/prevenção & controle , Fatores de RiscoRESUMO
KEY MESSAGE: Cytoplasmic male sterility in sugar beet becomes thermo-sensitive when combined with specific genotypes, potentially offering a means to environmentally control pollination by this trait. The stability of cytoplasmic male sterility expression in several genetic backgrounds was investigated in sugar beet (Beta vulgaris L.). Nine genetically heterogenous plants from open-pollinated varieties were crossed with a cytoplasmic male sterile line to obtain 266 F1 plants. Based on marker analysis using a multiallelic DNA marker linked to restorer-of-fertility 1 (Rf1), we divided the F1 plants into 15 genotypes. We evaluated the phenotypes of the F1 plants under two environmental conditions: greenhouse rooms with or without daytime heating during the flowering season. Three phenotypic groups appeared: those consistently expressing male sterility, those consistently having restored pollen fertility, and those expressing male sterility in a thermo-sensitive manner. All plants in the consistently male sterile group inherited a specific Rf1 marker type named p4. We tested the potential for thermo-sensitive male sterile plants to serve as seed parents for hybrid seed production, and three genotypes were selected. Open pollination by a pollen parental line with a dominant trait of red-pigmented hypocotyls and leaf veins resulted in seed setting on thermo-sensitive male sterile plants, indicating that their female organs were functional. More than 99.9% of the progeny expressed the red pigmentation trait; hence, highly pure hybrids were obtained. We determined the nucleotide sequences of Rf1 from the three genotypes: One had a novel allele and two had known alleles, of which one was reported to have been selected previously as a non-restoring allele at a single U.S. breeding station but not at other stations in the U.S., or in Europe or Japan, suggesting environmental sensitivity.
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Beta vulgaris , Infertilidade das Plantas , Beta vulgaris/genética , Genes de Plantas , Genótipo , Melhoramento Vegetal , Infertilidade das Plantas/genética , AçúcaresRESUMO
BACKGROUND: Cytoplasmic male sterility (CMS) is a widely used trait for hybrid seed production in many crops. Sugar beet CMS is associated with a unique mitochondrial protein named preSATP6 that forms a 250-kDa complex. Restorer-of-fertility 1 (Rf1) is a nuclear gene that suppresses CMS and is, hence, one of the targets of sugar beet breeding. Rf1 has dominant, semi-dominant and recessive alleles, suggesting that it may be a multi-allelic locus; however, the molecular basis for differences in genetic action is obscure. Molecular cloning of Rf1 revealed a gene (orf20) whose protein products produced in transgenics can bind with preSATP6 to generate a novel 200-kDa complex. The complex is also detected in fertility-restored anthers concomitant with a decrease in the amount of the 250-kDa complex. Molecular diversity of the Rf1 locus involves organizational diversity of a gene cluster composed of orf20-like genes (RF-Oma1s). We examined the possibility that members of the clustered RF-Oma1 in this locus could be associated with fertility restoration. RESULTS: Six yet uncharacterized RF-Oma1s from dominant and recessive alleles were examined to determine whether they could generate the 200-kDa complex. Analyses of transgenic calli revealed that three RF-Oma1s from a dominant allele could generate the 200-kDa complex, suggesting that clustered RF-Oma1s in the dominant allele can participate in fertility restoration. None of the three copies from two recessive alleles was 200-kDa generative. The absence of this ability was confirmed by analyzing mitochondrial complexes in anthers of plants having these recessive alleles. Together with our previous data, we designed a set of PCR primers specific to the 200-kDa generative RF-Oma1s. The amount of mRNA measured by this primer set inversely correlated with the amount of the 250-kDa complex in anthers and positively correlated with the strength of the Rf1 alleles. CONCLUSIONS: Fertility restoration by sugar beet Rf1 can involve multiple RF-Oma1s clustered in the locus, implying that stacking 200-kDa generative copies in the locus strengthens the efficacy, whereas the absence of 200-kDa generative copies in the locus makes the allele recessive irrespective of the copy number. We propose that sugar beet Rf1 is a complex locus.
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Alelos , Beta vulgaris/genética , Genes de Plantas/genética , Proteínas de Plantas/genética , Fertilidade/genética , Dosagem de Genes , Genes de Plantas/fisiologia , Loci Gênicos/genética , Proteínas de Plantas/fisiologia , Plantas Geneticamente ModificadasRESUMO
INTRODUCTION: Anti-programmed cell death 1 (PD-1) therapies have shown promising clinical activity against gastric cancer (GC). We evaluated the clinical significance of immune-related gene expression in GC tissues to better understand the tumor immune microenvironment. METHODS: PD-1, PD-1 ligand 1 (PD-L1) and CD8 mRNA levels and clinicopathological factors, including survival, were examined by quantitative RT-PCR in 155 GC patients who underwent surgery. PD-1 and PD-L1 expression in tumor tissue from 24 GC patients was investigated by immunohistochemical analysis. RESULTS: PD-1, PD-L1 and CD8 mRNA levels were significantly lower in tumor tissue than in normal tissue (p < 0.0001, p < 0.05, and p < 0.0001). GC patients with low PD-1, PD-L1 and CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, PD-L1 and CD8 mRNA levels, respectively (p < 0.001, p < 0.01 and p < 0.05). Low PD-1, PD-L1 and CD8 mRNA levels were more significantly associated with poor prognosis in undifferentiated-type GC patients than in differentiated-type GC patients (PD-1: differentiated p = 0.0071 vs. undifferentiated p = 0.0024; PD-L1: p = 0.6527 vs. p < 0.0001; CD8: p = 0.4465 vs. p < 0.05). Multivariate analysis showed that lymph node metastasis, peritoneal dissemination, distant metastasis, low PD-1 mRNA levels and low CD8 mRNA levels were independent prognostic factors for worse OS (low PD-1 mRNA level: OR 2.16, 95% CI 1.10-4.58, p < 0.05; low CD8 mRNA level: OR 2.55, 95% CI 1.12-6.90, p < 0.05). PD-1 and PD-L1 mRNA levels in immune cells were significantly associated with PD-1 and PD-L1 protein levels (both p < 0.05), respectively. CONCLUSIONS: PD-1, PD-L1 and CD8 mRNA levels may reflect antitumor immunity in GC, and low PD-1 and CD8 mRNA levels are potential predictive biomarkers for poor prognosis in GC patients who underwent surgery.
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Antígeno B7-H1/genética , Antígenos CD8/genética , Expressão Gênica/imunologia , Receptor de Morte Celular Programada 1/genética , Neoplasias Gástricas/genética , Microambiente Tumoral/imunologia , Idoso , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: The Fitzgerald classification expresses the extension of hematoma from the ruptured abdominal aortic aneurysm (rAAA) and is related to a patient's preoperative status. The objective of this study was to propose a new decision-making method for emergency surgeries, endovascular aortic repair (EVAR), or open repair (OR) for rAAA based on the Fitzgerald classification using preoperative computed tomography images. MATERIALS AND METHODS: A multicenter observational study was performed with a questionnaire survey of rAAA from August 2010 to July 2015 in Hokkaido, Japan, and sent to 20 institutions participating in the Hokkaido Society of Aortic Stent Graft. We included 205 patients who could be stratified by the Fitzgerald classification as the subjects of this study. We categorized these patients into Fitzgerald classes I and II (first category, n = 72) and classes III and IV (second category, n = 133). The short-term results of both EVAR and OR cases were examined in the 2 categories. RESULTS: In the first category, patients in the EVAR group were older than those in the OR group. Nonetheless, the in-hospital mortality rate was lower in the EVAR group than in the OR group (0% vs. 18%; P = 0.019). In the second category, there was no difference in preoperative factors between the groups. The EVAR group showed a higher incidence rate of postoperative abdominal compartment syndrome than the OR group (12% vs. 2%; P = 0.042). The in-hospital mortality rate was comparable between the groups (24% vs. 25%; P = 0.80). Although there were no deaths in the EVAR group without preoperative shock, in-hospital mortality in the EVAR group of the second category with shock was 41% (vs. 28% in the OR group; P = 0.27). Furthermore, mortality in the EVAR group with Fitzgerald class IV was 100% (vs. 29% in the OR group; P = 0.049). CONCLUSIONS: EVAR is recommended in Fitzgerald class I or II and also in Fitzgerald class III or IV without shock because the results of EVAR were better than those of OR. Because all patients who underwent EVAR died in Fitzgerald class IV, OR would be beneficial in this patient population.
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Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Aortografia , Implante de Prótese Vascular , Angiografia por Tomografia Computadorizada , Técnicas de Apoio para a Decisão , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/classificação , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/classificação , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Tomada de Decisão Clínica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: Extended pancreatectomy for locally advanced pancreatobiliary malignancy often involves combined major arterial resection (AR) and reconstruction (ARc). By limiting candidate inflow for ARc after combined resection of the celiac arterial system over a long distance, we evaluated whether great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arterial inflow. METHODS: ARc with GSVG conduit was undertaken prior to resection. GSVG was harvested and anastomosed end-to-side with the reconstructing artery and then mostly passed via the retroperitoneal para-inferior vena cava route. Side-to-end anastomosis of GSVG inflow was established with the right common iliac artery or abdominal aorta. RESULTS: Among 468 consecutive pancreatobiliary surgeries, ARc with GSVG was undertaken in seven cases. Primary cancers were in the pancreas in six patients and distal bile duct in one. Radical surgery was performed with pancreaticoduodenectomy in six patients and total pancreatectomy in one. Hepatic artery (HA) was concomitantly resected and reconstructed by GSVG in six patients or by the jejunal artery in one patient. Median operative time and intraoperative blood loss were 763 min and 350 ml, respectively. Serum level of AST, ALT, and LDH in patients with HA reconstruction by GSVG peaked by the second postoperative day and promptly normalized. Postoperative morbidity (CD ≥ III) was encountered in one patient. No surgical mortality was observed. Postoperative serum liver enzymes promptly decreased in ARc patients with GSVG to HA. CONCLUSION: Arterial reconstruction with GSVG prior to resection was performed securely and might help to reduce postoperative liver dysfunction.
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Pancreatectomia , Neoplasias Pancreáticas , Artéria Hepática/cirurgia , Humanos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Veia SafenaRESUMO
BACKGROUND: There is growing evidence that patients with metastatic breast cancer whose disease progresses from a new metastasis (NM) have a worse prognosis than that of patients whose disease progresses from a pre-existing metastasis. The aim of this pilot study is to identify a blood biomarker predicting NM in breast cancer. METHODS: The expression of epithelial (cytokeratin 18/19) or mesenchymal (plastin-3, vimentin, and N-cadherin) markers in the peripheral blood (PB) of recurrent breast cancer patients undergoing chemotherapy with eribulin or S-1 was measured over the course of treatment by RT-qPCR. The clinical significance of preoperative N-cadherin expression in the PB or tumor tissues of breast cancer patients undergoing curative surgery was assessed by RT-qPCR or using public datasets. Finally, N-cadherin expression in specific PB cell types was assessed by RT-qPCR. RESULTS: The expression levels of the mesenchymal markers N-cadherin and vimentin were high in the NM cases, whereas that of the epithelial marker cytokeratin 18 was high in the pre-existing metastasis cases. High preoperative N-cadherin expression in PB or tumor tissues was significantly associated with poor recurrence-free survival. N-cadherin was expressed mainly in polymorphonuclear leukocytes in PB. CONCLUSION: N-cadherin mRNA levels in blood may serve as a novel prognostic biomarker predicting NM, including recurrence, in breast cancer patients.
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Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Caderinas/genética , Ácidos Nucleicos Livres , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Terapia Combinada , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , PrognósticoRESUMO
We report a case of axillary arterial bleeding after administration of bevacizumab plus paclitaxel in a patient with recurrent breast cancer.A 50-year-old woman with invasive ductal carcinoma of the left breast underwent mastectomy and sentinel node biopsy.She was administered 4 courses of docetaxel and cyclophosphamide as adjuvant chemotherapy.Twenty -eight months after the surgery, she developed axillary lymph node recurrence with pain and upper-limb paralysis.Initially, radiation therapy was performed in the axilla combined with the oral administration of TS-1.However, the response was inadequate. Subsequently, bevacizumab plus paclitaxel was administered.After 2 courses, we observed remarkable shrinkage of the axillary tumor.However, she experienced massive bleeding from the axillary artery.As the bleeding recurred, we ligated the axillary artery.Caution is required while administrating bevacizumab in cases of tumors located close to the major blood vessels.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama , Axila , Bevacizumab , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , PaclitaxelRESUMO
KEY MESSAGE: The sugar beet Rf1 locus has a number of molecular variants. We found that one of the molecular variants is a weak allele of a previously identified allele. Male sterility (MS) caused by nuclear-mitochondrial interaction is called cytoplasmic male sterility (CMS) in which MS-inducing mitochondria are suppressed by a nuclear gene, restorer-of-fertility. Rf and rf are the suppressing and non-suppressing alleles, respectively. This dichotomic view, however, seems somewhat unsatisfactory to explain the recently discovered molecular diversity of Rf loci. In the present study, we first identified sugar beet line NK-305 as a new source of Rf1. Our crossing experiment revealed that NK-305 Rf1 is likely a semi-dominant allele that restores partial fertility when heterozygous but full fertility when homozygous, whereas Rf1 from another sugar beet line appeared to be a dominant allele. Proper degeneration of anther tapetum is a prerequisite for pollen development; thus, we compared tapetal degeneration in the NK-305 Rf1 heterozygote and the homozygote. Degeneration occurred in both genotypes but to a lesser extent in the heterozygote, suggesting an association between NK-305 Rf1 dose and incompleteness of tapetal degeneration leading to partial fertility. Our protein analyses revealed a quantitative correlation between NK-305 Rf1 dose and a reduction in the accumulation of a 250 kDa mitochondrial protein complex consisting of a CMS-specific mitochondrial protein encoded by MS-inducing mitochondria. The abundance of Rf1 transcripts correlated with NK-305 Rf1 dose. The molecular organization of NK-305 Rf1 suggested that this allele evolved through intergenic recombination. We propose that the sugar beet Rf1 locus has a series of multiple alleles that differ in their ability to restore fertility and are reflective of the complexity of Rf evolution.
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Beta vulgaris/genética , Beta vulgaris/fisiologia , Genes Dominantes , Genes de Plantas , Infertilidade das Plantas/genética , Alelos , Genótipo , Proteínas Mitocondriais/genética , Plantas Geneticamente Modificadas/fisiologiaRESUMO
A 74-year-old man had undergone two-vessel coronary artery bypass grafting (CABG), 19 years ago, with the left internal mammary artery (LITA) to the left anterior descending artery and the saphenous vein graft (SVG) to the posterior descending artery. In outpatient care, a thoracic aortic aneurysm was suspected by the chest X-ray. In the computed tomography, appeared the distal arch aortic aneurysm, abdominal aortic aneurysm (AAA), and giant right coronary artery aneurysm (rCAA). The diameter of rCAA was 70 mm and it oppressed the right atrium and ventricle of the heart. The patient was referred to our hospital. After the initial treatment of distal arch aneurysm and AAA, surgical treatment for the rCAA was performed. The rCAA was resected completely and CABG with new SVG was performed without cardiopulmonary bypass. The histopathology of rCAA wall revealed that the etiology was an atherosclerotic change. The postoperative course was good, the oppressed right heart system was released and the hemodynamics of the tricuspid valve showed improvement.
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Aneurisma Coronário/cirurgia , Ponte de Artéria Coronária/métodos , Vasos Coronários/cirurgia , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Doença da Artéria Coronariana/complicações , Vasos Coronários/diagnóstico por imagem , Humanos , Masculino , Veia Safena/transplante , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Genetic diversity of Japanese sugar beet elite inbred line diversity (JSBDIV) set consisting of 63 lines was investigated using 33 cleaved amplified polymorphic sequence and 38 simple sequence repeat analyses. JSBDIV set was significantly subdivided into six (pedigree information), seven (Neighbor-Joining method) or 12 (population structure analysis) groups. The highest value of a pairwise population differentiation estimate, Φ PT value, among groups was yielded from population structure analysis with explained variation 32%. Some of the groups defined in this study exhibited close association with ancestral open-pollinated varieties (OPVs), suggesting that inter-OPV cross was rare during the establishment of JSBDIV set. On the other hand, low Φ PT values between some groups suggest that genetic backgrounds of ancestral OPVs had historically overlapped to some extent. Phenotypic traits showed significant differences both among and within groups. A nearly identical group was identified as the highest sugar content group irrespective of the grouping methods. Groups with Aphanomyces root rot resistance are associated with an OPV 'Tmm-1', suggesting it as a source of this trait. 'Tmm-1' is also associated with Cercospora leaf spot resistance, but an exceptional resistant line with no association of 'Tmm-1' supports a notion that different genetic resources exist for this trait.
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PURPOSE: Recent developments in molecular-targeted therapies have improved the clinical outcome of cancer patients; however, the issue of adverse effects due to treatments has often gone unconsidered. We herein report the results of a clinical trial of dual genomic analyses for healthy longevity in a postoperative cancer patient. METHODS: We performed dual genomic analyses for a representative 79-year-old rectal cancer patient who relapsed with liver metastasis. First, we determined single-nucleotide polymorphisms according to the constitution and disease risk in the genomic DNA from the patient's saliva by referring to the data of 10,000 Japanese patients obtained from Yahoo Japan Corporation. Second, we conducted whole-exome sequencing to detect druggable mutations in the primary tumour. RESULTS: Forty of 59 determinable characters related to the constitution were consistent with the clinical phenotype. Several diseases classified as 'high risk' diseases actually occurred during the patient's clinical course. Of the 129 significant mutations, we identified somatic mutations in BRAF, PIK3CA, and SMAD4 as targets. CONCLUSION: The dual genomic examination will improve the follow-up observation system to support primary care doctors in the social community for taking care of postoperative cancer patients.
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Ensaios Clínicos como Assunto , Longevidade , Neoplasias Retais/genética , Idoso , Classe I de Fosfatidilinositol 3-Quinases/genética , DNA/genética , Genoma Humano/genética , Humanos , Neoplasias Hepáticas/secundário , Masculino , Mutação , Recidiva Local de Neoplasia , Polimorfismo de Nucleotídeo Único , Período Pós-Operatório , Proteínas Proto-Oncogênicas B-raf/genética , Qualidade de Vida , Neoplasias Retais/mortalidade , Risco , Sobrevida , Sequenciamento do ExomaRESUMO
Endovascular therapy has been advanced in recent years. Thoracic endovascular aneurysm repair (TEVAR) has become the standard treatment for descending aortic aneurysm. For endovascular treatment, there are many pitfalls not found in conventional surgery. From now on, it is necessary not only to master open surgery, but also to master endovascular technique for those who aim at getting qualified as specialist in vascular surgery.
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Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. METHODS: The correlation between the preoperative PD-1, PD-L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. RESULTS: The PD-1, PD-L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P < 0.0001). GC patients with low PD-1, high PD-L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, low PD-L1, and high CD8 mRNA levels, respectively (P < 0.01, P < 0.05, and P < 0.05, respectively). Multivariate analysis showed that low PD-1 and high PD-L1 mRNA levels were independent poor prognostic factors for OS (PD-1: HR 2.38, 95% CI 1.27-4.78, P < 0.01; PD-L1: HR 1.81, 95% CI 1.15-2.78, P < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. CONCLUSIONS: The PD-1, PD-L1, and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD-1 and high PD-L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.
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Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Antígenos CD8/genética , Receptor de Morte Celular Programada 1/genética , Neoplasias Gástricas/patologia , Estudos de Casos e Controles , Seguimentos , Humanos , Metástase Linfática , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: In gastric cancer (GC), peritoneal dissemination (PD) occurs frequently and is incurable. In this study, we aimed to identify PD-associated genes in GC. METHODS: We identified a PD-associated gene using three GC datasets: highly disseminated peritoneal GC cell lines, the Singapore dataset and The Cancer Genome Atlas (TCGA) dataset. We assessed the clinicopathological significance of the gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and performed immunohistochemical analysis for the gene in our patient cohort. We also performed survival analyses of the gene in our patient cohort, the Singapore dataset and the GSE62254 datasets. Moreover, gene set enrichment analysis (GSEA) was performed using the Singapore and TCGA datasets. Finally, in vitro experiments such as invasion/migration assays, immunofluorescence staining of actin filaments, epidermal growth factor (EGF) treatment analysis, and gene expression analysis were conducted using three gene-knockdown GC cell lines (AGS, 58As9, MKN45). RESULTS: ADP-ribosylation factor-like 4c (ARL4C) was identified as a PD-associated gene, and immunohistochemical analysis showed that ARL4C was overexpressed in GC cells. High ARL4C expression was associated with the depth of invasion (p < 0.01) and PD (p < 0.05) and was a poor prognostic factor (p < 0.05) in our patient cohort, the Singapore dataset and the GSE62254 dataset. ARL4C expression positively correlated with the epithelial-mesenchymal transition (EMT) gene set in GSEA. Moreover, ARL4C knockdown reduced invasion/migration capacity, SLUG expression, and the formation of lamellipodia or filopodia in AGS and 58As9 cells. Finally, EGF treatment increased ARL4C expression in MKN45 cells. CONCLUSIONS: ARL4C was associated with PD and was a poor prognostic factor in GC, possibly through promoting invasive capacity by activation of both EMT and motility.
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Fatores de Ribosilação do ADP/metabolismo , Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células em Anel de Sinete/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Fatores de Ribosilação do ADP/antagonistas & inibidores , Fatores de Ribosilação do ADP/genética , Adenocarcinoma Mucinoso/metabolismo , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células em Anel de Sinete/metabolismo , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Estudos de Coortes , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Neoplasias Peritoneais/metabolismo , Prognóstico , RNA Interferente Pequeno/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Transcriptoma , Células Tumorais CultivadasRESUMO
OBJECTIVE: MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. METHODS: The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFß2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. RESULTS: Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFß2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. CONCLUSIONS: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.
Assuntos
Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/genética , Feminino , Via de Sinalização Hippo , Humanos , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Knockout , Pessoa de Meia-IdadeRESUMO
KEY MESSAGE: Only three variants of nonrestoring alleles for sugar beet Rf1 were found from the US maintainer lines which were the selections from a broad range of genetic resources. Cytoplasmic male sterility is widely used for hybrid breeding of sugar beets. Specific genotypes with a nonsterility-inducing cytoplasm and a nonrestoring allele of restorer-of-fertility gene (rf) are called maintainers. The infrequent occurrence of the maintainer genotype evokes the need to diagnose rf alleles. Molecular analysis of Rf1, one of the sugar beet Rfs, revealed a high level of nucleotide sequence diversity, but three variants were tightly associated with maintainer selection in Japan. The question was raised whether this small number of variants would be seen in cases where a wider range of genetic resources was used for maintainer selection. Fifty-seven accessions registered as maintainers in the USDA germplasm collection were characterized in this study. Mitochondrial DNA types (mitotypes) of 551 plants were diagnosed based on minisatellite polymorphism. A mitotype associated with sterility-inducing (S) cytoplasm was identified in 58 plants, indicating S-cytoplasm contamination. The organization of rf1 was investigated by two PCR markers and DNA gel blot analysis. Eight haplotypes were found among the US maintainers, but subsequently two haplotypes were judged as restoring alleles after a test cross and another haplotype was not inherited by the progeny. Nucleotide sequences of rf1 regions in the remaining five haplotypes were compared, and despite the sequence diversity of the gene-flanking regions, the gene-coding regions were identified to be three types. Therefore, there are three rf1 variants in US maintainers, the same number as in the Japanese sugar beet germplasm collection. The implications of having a small repertoire of rf1 variants are discussed.
Assuntos
Beta vulgaris/genética , Genes de Plantas , Infertilidade das Plantas/genética , Alelos , DNA Mitocondrial/genética , DNA de Plantas/genética , Marcadores Genéticos , Genótipo , Haplótipos , Repetições Minissatélites , Análise de Sequência de DNARESUMO
BACKGROUND: Obtaining dedifferentiated cells (callus) that can regenerate into whole plants is not always feasible for many plant species. Sugar beet is known to be recalcitrant for dedifferentiation and plant regeneration. These difficulties were major obstacles for obtaining transgenic sugar beets through an Agrobacterium-mediated transformation procedure. The sugar beet line 'NK-219mm-O' is an exceptional line that forms callus efficiently and is easy to regenerate, but the inheritance of these characters was unknown. Another concern was whether these characters could coexist with an annual habitat that makes it possible to breed short life-cycle sugar beet suitable for molecular genetic analysis. FINDINGS: Five sugar beet lines including NK-219mm-O were crossed with each other and subjected to in vitro culture to form callus. F1s with a NK-219mm-O background generally formed callus efficiently compared to the others, indicating that efficient callus formation is heritable. The regeneration potential was examined based on the phenotypes of calli after placement on regeneration medium. Five phenotypes were observed, of which two phenotypes regenerated shoots or somatic embryo-like structures. Vascular differentiation was evident in regenerable calli, whereas non-regenerable calli lacked normally developed vascular tissues. In a half-diallel cross, the callus-formation efficiency and the regeneration potential of reciprocal F1s progeny having a NK-219mm-O background were high. Finally, we crossed NK-219mm-O with an annual line that had a poor in vitro performance. The callus-formation efficiency and the regeneration potential of reciprocal F1 were high. The regenerated plants showed an annual habitat. CONCLUSIONS: Efficient callus formation and the high plant regeneration potential of NK-219mm-O were inherited and expressed in the F1. The annual habitat does not impair these high in vitro performances.
Assuntos
Beta vulgaris/crescimento & desenvolvimento , Beta vulgaris/genética , Padrões de Herança , Regeneração/genética , Cruzamentos Genéticos , Genótipo , Fenótipo , Melhoramento VegetalRESUMO
Objectives: Colorectal perforation is associated with high morbidity and mortality rates after surgery. We investigated various clinical features of patients who underwent emergency surgery for colorectal perforation and explored the risk factors for postoperative complications and hospital mortality. Methods: Data from 147 patients who underwent surgery for colorectal perforation were retrospectively reviewed. We investigated various clinical and operative factors, including inflammation-based prognostic scores (IBPSs), and evaluated the risk factors for postoperative complications and hospital mortality due to colorectal perforation. Results: Among 147 patients, the most frequent postoperative complication was wound infection (32 cases, 21.8%), followed by intra-abdominal abscesses (27 cases, 18.4%) after surgery for colorectal perforation. Time from onset to surgery ≥ 2 days (Hazard ratio [HR] = 2.810, p = 0.0383) and prognostic nutritional index (PNI) < 30 (HR = 3.190, p = 0.0488) were identified as risk factors for intra-abdominal abscess, while neutrophil-lymphocyte ratio (NLR) < 6.15 (HR = 5.020, p = 0.0009) was identified as a risk factor for wound infection. Time from onset to surgery ≥ 2 days (HR = 7.713, p = 0.0492), severe postoperative complications (Clavien-Dindo grade ≥ IIIa) (HR = 10.98, p = 0.0281), and platelet-lymphocyte ratio (PLR) < 144 (HR = 18.84, p = 0.0190) were independent predictive factors for hospital mortality. Conclusions: Time from onset to surgery and IBPSs such as PNI, NLR, and PLR, may be associated with postoperative complications and hospital mortality due to colorectal perforation.
RESUMO
INTRODUCTION: This study aimed to clarify the validity of laparoscopic surgery for lower gastrointestinal perforation by comparing the clinical outcomes of laparoscopic and open emergency surgery. METHODS: We reviewed the data of patients who underwent surgery for lower gastrointestinal perforation. Patients were categorized into two groups: the laparoscopic group who underwent laparoscopic surgery, and the open group who underwent laparotomy. Clinical and operative outcomes between the two groups were evaluated. RESULTS: A total of 219 patients were included in the study. There were 66 and 153 patients with small bowel and colorectal perforations, respectively. The median operative time in the laparoscopic group was shorter than that in the open group (126 min vs. 146 min, p = .049). The mean amount of intraoperative blood loss was significantly lower in the laparoscopic group (50.4 mL vs. 400.1 mL, p < .001). The incidence of postoperative complication was higher in the open group (20.0% vs. 66.5%, p < .001), especially wound infection (0% vs. 26.3%, p = .002). Median hospital stays were 14 days and 24 days in the laparoscopic and open groups, respectively (p < .001). In the laparoscopic group, hospital mortality was 0%. CONCLUSIONS: The laparoscopic approach for small bowel and colorectal perforation in an emergency setting is a safe procedure in carefully selected patients and may contribute to decreased intraoperative blood loss, shortened hospital stay, and decreased incidence of postoperative complications, especially wound infection.