RESUMO
The cholecystokinin (CCK)/gastrin family peptides are involved in regulation of feeding and digestion in vertebrates. In the ascidian Ciona intestinalis type A (Ciona robusta), cionin, a CCK/gastrin family peptide, has been identified. Cionin is expressed exclusively in the central nervous system (CNS). In contrast, cionin receptor expression has been detected in the CNS, digestive tract, and ovary. Although cionin has been reported to be involved in ovulation, its physiological function in the CNS remains to be investigated. To elucidate its neural function, in the present study, we analyzed the expression of cionin and cionin receptors in the CNS. Cionin was expressed mainly in neurons residing in the anterior region of the cerebral ganglion. In contrast, the gene expressin of the cionin receptor gene CioR1, was detected in the middle part of the cerebral ganglion and showed a similar expression pattern to that of VACHT, a cholinergic neuron marker gene. Moreover, CioR1 was found to be expressed in cholinergic neurons. Consequently, these results suggest that cionin interacts with cholinergic neurons as a neurotransmitter or neuromodulator via CioR1. This study provides insights into a biological role of a CCK/gastrin family peptide in the CNS of ascidians.
Assuntos
Colecistocinina , Ciona intestinalis , Neuropeptídeos , Animais , Feminino , Colecistocinina/genética , Colecistocinina/metabolismo , Gastrinas , Ciona intestinalis/genética , Ciona intestinalis/metabolismo , Sequência de Aminoácidos , Sistema Nervoso CentralRESUMO
Donor-derived hematological malignancies have been recognized as rare but serious late complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Most cases in the literature were diagnosed as myelodysplastic syndrome or acute leukemia, with very few malignant lymphoma reported. We herein present another case of donor-derived Burkitt lymphoma that occurred 9 years after allo-HSCT under continued administration of immunosuppressants for chronic graft-versus-host disease (GVHD). The patient achieved a partial response after rituximab-combined intensive chemotherapy. To reduce the risk of relapse and to avoid organ toxicities due to repeated chemotherapies, we performed upfront high-dose chemotherapy followed by stem cell rescue using donor-derived CD34+ cells, called pseudo-autologous HSCT (pASCT), and adjusted immunosuppressants appropriately. The patient remained disease-free for 23 months after pASCT without exacerbation of cGVHD. Although the observation period has been relatively short and longer follow-up is needed, pASCT may be a feasible option for donor-derived lymphoma even in patients with active cGVHD.
Assuntos
Linfoma de Burkitt , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Linfoma , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , Linfoma de Burkitt/etiologia , Linfoma de Burkitt/terapia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Transplante Homólogo/efeitos adversos , Linfoma/complicações , Imunossupressores , Leucemia Mieloide Aguda/complicaçõesRESUMO
Adenomatous polyposis coli (APC) is a tumor-suppressing protein whose inactivation triggers the formation of colorectal polyps. Numerous studies using cell lines or genetically engineered mice have revealed its role in suppressing Wnt/ß-catenin signaling pathway and regulating cell proliferation and differentiation. Here, we performed genetic analyses of APC using a three-dimensional organoid culture of mouse colon epithelia, which enables the detailed examination of epithelial properties. Analyses of Apc-knockout colon organoids not only confirmed the importance of APC in suppressing Wnt/ß-catenin signaling and regulating cell differentiation, but also revealed several novel features: a significant decrease in proliferating speed and an increase in cross-sectional area of cells. Moreover, we found a significant number of lysozyme-positive Paneth-like cells, which were never observed in wild-type colon tissues or organoids, but have been reported to emerge in colon cancers. Therefore, APC autonomously suppresses ectopic differentiation into lysozyme-positive cells, specifically in the colon epithelia. Colon organoids would be an ideal material to investigate the molecular mechanism and biological importance of the ectopic differentiation associated with cancer development.
Assuntos
Polipose Adenomatosa do Colo/metabolismo , Células Epiteliais/metabolismo , Organoides/metabolismo , Proteína da Polipose Adenomatosa do Colo/metabolismo , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Colo/citologia , Neoplasias do Colo/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Via de Sinalização WntRESUMO
BACKGROUND: Infected aortic aneurysm secondary to streptococcal toxic shock syndrome caused by Streptococcus pyogenes is uncommon and associated with high mortality. CASE PRESENTATION: A 75-year-old man with metastatic lung cancer and an abdominal aortic aneurysm presented with high fever for 3 days. He was diagnosed with septic shock and was admitted to our hospital. The blood culture was positive for S. pyogenes, and streptococcal toxic shock syndrome was diagnosed. During treatment, enhanced computed tomography revealed an increase in the size of the abdominal aortic aneurysm, leading to the diagnosis of an infected aortic aneurysm. Replacement of the aneurysm with a synthetic graft was carried out successfully. The patient gradually recovered after the surgery. CONCLUSION: We successfully managed an infected aortic aneurysm secondary to streptococcal toxic shock syndrome. Infected aortic aneurysms should be considered in patients with a medical history of aortic aneurysms and presenting with streptococcal toxic shock syndrome.
RESUMO
OBJECTIVES: To (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intratumoral abundance of various specific tumor-infiltrating lymphocytes (TILs) is a prognostic indicator in women with Stage II and III cervical cancer who undergo treatment with cisplatin-based concurrent chemoradiotherapy (CCRT), and (iii) investigate subtypes of FOXP3+ T cells in 15 fresh samples of cervical cancer. METHODS: In this retrospective study, intratumoral lesions in colposcopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT at our institution were subjected to automatic immunological staining using the following six mouse monoclonal antibodies: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and various clinicopathological characteristics were analyzed, as were associations between the abundance of various specific types of TIL and survival. Subtypes of FOXP3+ TILs in 15 additional fresh tumor samples were also investigated using flow cytometry. RESULTS: Infiltration with CD8+ TILs was associated with pelvic lymph node metastasis. Abundant infiltration by CD3+, CD4+, CD8+, CD206+, and FOXP3+ TILs were statistically significant indicators of better progression-free and overall survival. Regarding subtypes of FOXP3+ TILs, non-Tregs (Fr-III) were found in all samples tested for this. CONCLUSIONS: The abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT.
Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias do Colo do Útero/terapia , Adulto , Linfócitos T CD8-Positivos , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Microambiente Tumoral , Neoplasias do Colo do Útero/patologiaRESUMO
Proteins whose synthesis is enhanced by polyamines at the level of translation were identified in a polyamine-requiring mutant cultured in the presence of 0.1% glucose and 0.02% glutamate instead of 0.4% glucose as an energy source. Under these conditions, enhancement of cell growth by polyamines was almost the same as that in the presence of 0.4% glucose. It was found that synthesis of RpoN, Cra, and H-NS was enhanced by polyamines at the level of translation at the early logarithmic phase of growth (A(540) of 0.15). The effects of polyamines on synthesis of RpoN, H-NS, and Cra were due to the existence of unusual Shine-Dalgarno sequences (RpoN and H-NS) and an inefficient GUG initiation codon (Cra) in their mRNAs. Thus, rpoN, cra, and hns genes were identified as new members of the polyamine modulon. Because most of the polyamine modulon genes thus far identified encode transcription factors (RpoS [sigma(38)], Cya, FecI [sigma(18)], Fis, RpoN [sigma(54)], Cra, and H-NS), DNA microarray analysis of mRNA expressed in cells was performed. At the early logarithmic phase of growth, a total of 97 species of mRNAs that were up-regulated by polyamines more than twofold were under the control of seven polyamine modulon genes mentioned above.
Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Poliaminas/farmacologia , Biossíntese de Proteínas , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Códon de Iniciação , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Glucose/metabolismo , Glucose/farmacologia , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Poliaminas/metabolismo , RNA Polimerase Sigma 54/química , RNA Polimerase Sigma 54/genética , RNA Polimerase Sigma 54/metabolismo , RNA Bacteriano/química , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Polypeptide release factor 2 (RF2) in Escherichia coli is known to be synthesized by a +1 frameshift at the 26th UGA codon of RF2 mRNA. Polyamines were found to stimulate the +1 frameshift of RF2 synthesis, an effect that was reduced by excess RF2. Polyamine stimulation of +1 frameshift of RF2 synthesis was observed at the early logarithmic phase, which is the important phase in determination of the overall rate of cell growth. A Shine-Dalgarno-like sequence was necessary for an efficient +1 frameshift of RF2 synthesis, but not for polyamine stimulation. Spectinomycin, tetracycline, streptomycin, and neomycin reduced polyamine stimulation of the +1 frameshift of RF2 synthesis. The results suggest that a structural change of the A site on 30 S ribosomal subunits is important for polyamine stimulation of the +1 frameshift. The level of mRNAs of ribosomal proteins and elongation factors having UAA as termination codon was enhanced by polyamines, and OppA synthesis from OppA mRNA having UAA as termination codon was more enhanced by polyamines than that from OppA mRNA having a UGA termination codon. Furthermore, synthesis of ribosomal protein L20 and elongation factor G from the mRNAs having a UAA termination codon was enhanced by polyamines at the level of translation and transcription. The results suggest that some protein synthesis from mRNAs having a UAA termination codon is enhanced at the level of translation through polyamine stimulation of +1 frameshift of RF2 synthesis. It is concluded that prfB encoding RF2 is a new member of the polyamine modulon.
Assuntos
Proteínas de Escherichia coli/biossíntese , Mudança da Fase de Leitura do Gene Ribossômico , Fatores de Terminação de Peptídeos/biossíntese , Poliaminas/metabolismo , Sequência de Bases , Códon , Escherichia coli/genética , Escherichia coli/fisiologia , Proteínas de Escherichia coli/fisiologia , Dados de Sequência Molecular , Fatores de Terminação de Peptídeos/fisiologia , Biossíntese de Proteínas , RNA Mensageiro/análiseRESUMO
We reported previously that the synthesis of specific proteins such as OppA, Cya, and RpoS (sigma(38)), which are important for cell growth and viability, is stimulated by polyamines at the level of translation. In this study we found that the synthesis of FecI and Fis was also stimulated by polyamines at the level of translation. The FecI and Fis proteins enhance the expression of mRNAs that are involved in iron uptake and energy metabolism and the expression of rRNA and some tRNAs. The Shine-Dalgarno (SD) sequence of their mRNAs was not obvious or was not located at the usual position. When the SD sequences were created at the normal position on these mRNAs, protein synthesis was no longer influenced by polyamines. Thus, the common characteristic of these mRNAs was to have a weak or ineffective SD sequence. We propose that a group of genes whose expression is enhanced by polyamines at the level of translation be referred to as a "polyamine modulon." By DNA microarray, we found that 309 of 2,742 mRNA species were upregulated by polyamines. Among the 309 up-regulated genes, transcriptional enhancement of at least 58 genes might be attributable to increased levels of the transcription factors Cya, RpoS, FecI, and Fis, which are all organized in the polyamine modulon. This unifying molecular mechanism is proposed to underlie the physiological role of polyamines in controlling the growth of Escherichia coli.