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1.
Vox Sang ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872445

RESUMO

BACKGROUND AND OBJECTIVES: A more restrictive blood donation criterion has been applied in Japan, with a maximum volume of whole blood (WB) donation of 400 mL, allowing twice a year for female donors and thrice a year for male donors. However, iron deficiency was as high as 20.5% among female donors prior to donation, increasing to 37.7% after blood donation. More than 20 years have passed since then, so we set out to investigate the present situation. MATERIALS AND METHODS: A total of 2659 (male/female: 1496/1163) donors of 400 mL WB who gave informed consent to join the study were enrolled. Serum ferritin (sFer) of first-time/reactivated (FT/RA) donors were compared with those of repeat donors, according to gender and age; those who returned for subsequent donations during the study period were also followed up. RESULTS: About one-third of FT/RA female donors had iron deficiency, possibly reflecting its high incidence among the general population. Interestingly, although sFer levels were low among pre-menopausal FT/RA female donors, these values were not much different in repeat donors, whereas significant differences were observed between FT/RA and repeat donors among post-menopausal females and in most age groups among males. As expected, donors with a normal initial sFer (≥26 ng/mL) recovered faster than those with a low initial sFer. CONCLUSION: Female donors, especially, have iron deficiency even before donation, and the rate increased compared to what was found previously. Measures to prevent iron deficiency of blood donors is required, and studies are going on in Japan.

2.
Genome Biol Evol ; 16(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38039384

RESUMO

Aquaporin (Aqp) 10 is a member of the aquaglyceroporin subfamily of water channels, and human Aqp10 is permeable to solutes such as glycerol, urea, and boric acid. Tetrapods have a single aqp10 gene, whereas ray-finned fishes have paralogs of this gene through tandem duplication, whole-genome duplication, and subsequent deletion. A previous study on Aqps in the Japanese pufferfish Takifugu rubripes showed that one pufferfish paralog, Aqp10.2b, was permeable to water and glycerol, but not to urea and boric acid. To understand the functional differences of Aqp10s between humans and pufferfish from an evolutionary perspective, we analyzed Aqp10s from an amphibian (Xenopus laevis) and a lobe-finned fish (Protopterus annectens) and Aqp10.1 and Aqp10.2 from several ray-finned fishes (Polypterus senegalus, Lepisosteus oculatus, Danio rerio, and Clupea pallasii). The expression of tetrapod and lobe-finned fish Aqp10s and Aqp10.1-derived Aqps in ray-finned fishes in Xenopus oocytes increased the membrane permeabilities to water, glycerol, urea, and boric acid. In contrast, Aqp10.2-derived Aqps in ray-finned fishes increased water and glycerol permeabilities, whereas those of urea and boric acid were much weaker than those of Aqp10.1-derived Aqps. These results indicate that water, glycerol, urea, and boric acid permeabilities are plesiomorphic activities of Aqp10s and that the ray-finned fish-specific Aqp10.2 paralogs have secondarily reduced or lost urea and boric acid permeability.


Assuntos
Aquaporinas , Glicerol , Animais , Humanos , Filogenia , Peixes/genética , Aquaporinas/genética , Ureia , Água/metabolismo
3.
Vox Sang ; 118(11): 938-946, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37671662

RESUMO

BACKGROUND AND OBJECTIVES: Japan's ageing society has increased the need for home healthcare, including home transfusions. We hence aimed to elucidate the purpose and utilization of home transfusions in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The study period was February to December 2019, and information of patients receiving home red blood cell transfusions, including patient background, pre-transfusion laboratory data and the purpose of the transfusions, was collected. RESULTS: Haematological malignancies and solid tumours accounted for 70% of the patients' underlying diseases, with the former being significantly more common in urban areas. Regarding the purpose of the home transfusions, haematologists focused on symptom improvement, whereas gastroenterology surgeons focused on life support. Furthermore, maintenance of life was more likely to be the aim in the group of patients with the lowest level of activities of daily living. The main items that were significantly associated with a low haemoglobin level before transfusion included age ≥90 years and a gastroenterologist being the physician in charge. CONCLUSION: Home transfusions were found to be performed in a restrictive and diverse manner in Japan. Life support is the second most common purpose of home transfusion in Japan, and optimizing effective home transfusion remains a challenge.


Assuntos
Atividades Cotidianas , Neoplasias Hematológicas , Humanos , Idoso de 80 Anos ou mais , Japão , Transfusão de Sangue , Transfusão de Eritrócitos , Neoplasias Hematológicas/terapia
4.
J Clin Virol ; 168: 105598, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37748321

RESUMO

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is a blood-borne virus, and mandatory testing of donated blood for HTLV-1 antibodies has been adopted by Japanese Red Cross blood centers since 1986. A confirmatory line immunoassay was initiated in 2019 for individuals who were seroreactive in the screening test. This decreased the incidence of indeterminate individuals, however, donors with indeterminate results are not informed of their HTLV-1 seroreactivity and they can continue to donate blood. OBJECTIVES: To clarify the characteristics of indeterminate line immunoassay results among Japanese blood donors. STUDY DESIGN: Of 759,259 blood donors in the Kyushu district of Japan, an area endemic for HTLV-1, 101 cases were classified as indeterminate by line immunoassay testing. We examined these cases using alternative secondary antibodies, anti-human-Ig (IgG/IgM/IgA) and -IgM antibodies, to detect the early phase of HTLV infection. RESULTS: Using anti-human-Ig and -IgM antibodies, HTLV infection status was confirmed in 37 individuals (HTLV-1-positive, 2; HTLV-positive, 27; HTLV-negative, 8). Among the remaining 64 indeterminate individuals, we identified one HTLV-2-infected 18-year-old female. A previous blood donation from this individual showed a negative anti-HTLV screening test result (signal-to-cutoff ratio = 0.1). Therefore, this case was considered to be an HTLV-2 seroconversion case. CONCLUSIONS: These results indicate that the procedure for diagnosing HTLV infection should be reconsidered and that an accurate detection system for the early phase of HTLV infection is urgently needed for public health in Japan. Moreover, the issue of HTLV-2 infection needs a higher profile in Japan.

5.
Acta Med Okayama ; 66(4): 351-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22918208

RESUMO

In the duodenum, mixed exocrine-endocrine tumors exhibiting both neuroendocrine and glandular differentiations [cf. appendiceal goblet cell carcinoids (GCCs)] are rare. We present a Japanese case with a duodenal GCC that was found during pathologic examination of a gastrectomy specimen removed for gastric mucosal cancer. The tumor was widely distributed within both the first portion of the duodenum and the gastric antrum, although mucosal involvement was observed only in the duodenum. The tumor cells formed solid nests, trabeculae, or tubules, and some displayed a goblet cell appearance. They were immunoreactive against antibodies for both serotonin and somatostatin, and showed an argentaffin reaction (similar to a "midgut" enterochromaffin cell carcinoid). Ultra-structurally, the tumor cells had an amphicrine nature. Physicians encounter GCC in the duodenum only rarely, and its discovery may be incidental. Its diagnosis will be challenging and will require careful clinical and pathologic examinations.


Assuntos
Adenocarcinoma/patologia , Tumor Carcinoide/patologia , Duodeno/patologia , Neoplasias Gástricas/patologia , Anticorpos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Serotonina/imunologia , Somatostatina/imunologia
6.
Transfus Apher Sci ; 47(3): 319-25, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22647682

RESUMO

BACKGROUND: Vasovagal reaction (VVR) is the most frequent side effect at blood collection sites. AIMS: To protect donors, factors contributing to VVR were analysed. MATERIALS AND METHODS: Complications following whole blood and apheresis donations have been recorded and accumulated by the Japanese Red Cross Tokyo Blood Centre. A dataset of 43,948 donors who had no complications was prepared as a control by randomly selecting days in each season in the 2006 and 2007 fiscal years. Factors contributing to 4924 VVR incidents in the 2006 and 2007 fiscal years were analysed by univariate and multivariate logistic regression. RESULTS: The age, weight, body mass index (BMI), predonation systolic and diastolic pressure, and circulating blood volume were lower, and the pulse was higher, for the VVR group compared to the control group (p<0.0001). The VVR group had more female donors, less sleep, and more time since a meal than the control. In multivariate analysis, significant risk factors for 400 ml whole blood donors, which are the majority of donors, were an age <50 years, being female, a BMI <25, pulse ≥90/min, sleep duration <8 h, the time after eating ≥4 h, a first time donation and circulating blood volume of <4.3 l. Sleep duration of <6 h was shown to be a VVR risk as much as a first time donation. CONCLUSION: From our analysis, the amount of sleep obtained the previous night should be considered at the reception of donors.


Assuntos
Doadores de Sangue , Síncope Vasovagal/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Risco , Adulto Jovem
7.
Acta Med Okayama ; 63(4): 217-21, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19727207

RESUMO

We present a middle-aged, heterosexual Japanese man with mixed infections including human intestinal spirochetosis, which led us to the detection of human immunodeficiency virus (HIV) infection. The patient had syphilis without related physical or neurological findings. An examination for the serum antibody for HIV performed 9 years previously was negative. In a complete medical checkup at the present time, human intestinal spirochetosis and unspecified entamebic cysts were suggested by histological examination of colonic biopsy material and parasitic examination of the intestinal fluid, respectively. Moreover, a serological test for the antibody for HIV was positive. In specimens obtained by colonoscopy, Brachyspira aalborgi was diagnosed by ultrastructural study and the polymerase chain reaction method for bacterial 16S ribosomal deoxyribonucleic acid. Although HIV infection remains at low prevalence in Japan, we recommend examination for HIV infection in patients with human intestinal spirochetosis, especially when other co-infections are apparent.


Assuntos
Brachyspira/isolamento & purificação , Infecções por HIV/complicações , Enteropatias/etiologia , Intestinos/microbiologia , Infecções por Spirochaetales/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
8.
Arch Pathol Lab Med ; 132(6): 958-64, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18517279

RESUMO

CONTEXT: The 2 chief pathways implicated in colorectal carcinogenesis, microsatellite instability and chromosomal instability, are not present in 20% to 37% of cases. OBJECTIVE: To determine whether the CpG island methylator phenotype (CIMP) pathway, characterized by simultaneous methylation of several known tumor suppressor genes, is the principal underlying mechanism in cases without chromosomal or microsatellite instability, and to determine the significance of CIMP pathway and BRAF mutations in microsatellite-stable (MSS) cases. DESIGN: Clinicopathologic features and chromosomal instability status by loss of heterozygosity analysis were determined in 83 cases of colorectal cancer in which microsatellite instability, CIMP status, BRAF mutations, and KRAS mutations were previously known. RESULTS: Microsatellite instability was present in 14 cases (17%). Of the 69 MSS cases (83%), chromosomal instability manifested by LOH involving at least one locus was observed in 53 cases (64%). Hence, 16 (19%) of 83 colorectal cancer cases showed neither microsatellite instability nor chromosomal instability. These cases had a low incidence of CIMP (3/16; 19%) and BRAF mutation (1/16; 6%). The 5-year survival in these cases was significantly better compared with MSS cases with chromosomal instability (80% vs 54%, P = .02). BRAF mutations were identified in 10 MSS cases (15%). BRAF mutation in MSS cases correlated significantly with high-level chromosomal instability (P = .009) and poor 5-year survival (0% vs 70%, P < .001). CONCLUSIONS: CIMP does not appear to play a key role in colorectal cancer without microsatellite instability and chromosomal instability. These cases have a better survival, probably related to absence of significant chromosomal instability. BRAF mutations in MSS cases are associated with high levels of chromosomal instability that are likely responsible for the adverse outcomes in these cases.


Assuntos
Instabilidade Cromossômica , Neoplasias Colorretais/genética , Ilhas de CpG/genética , Instabilidade de Microssatélites , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Metilação de DNA , Análise Mutacional de DNA , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Reação em Cadeia da Polimerase
9.
Eur J Cancer ; 44(9): 1290-301, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18486467

RESUMO

INTRODUCTION: Accumulation of genetic and epigenetic alterations contribute to malignant transformation of normal colonic mucosa to cancer. However, the frequency and the pattern of these alterations in proximal and distal colon cancers have not been examined in detail. METHODS: In this study, we examined methylation frequencies and patterns using 14 marker genes in 31 proximal and 43 distal colorectal cancers. We also analysed the relationship between these parameters and clinical characteristics, MSI, mutations of BRAF, KRAS and p53, LOH and global hypomethylation. RESULTS: Three groups of tumours with varying degrees of methylation frequencies were identified: very high (9%), high (22%) and low (69%) methylation. Tumours with very high and high methylation showed more frequent proximal location, MSI, BRAF mutations and less frequent LOH and global hypomethylation. The methylation markers could be classified into 3 types based on methylation frequencies, MSI status and location. Proximal tumours showed more frequent methylation of Type 2 markers, CIMP+, MSI, BRAF mutations and lower frequencies of LOH and global hypomethylation, whilst Type 3 marker, MGMT methylation was more frequently associated with distal tumours, better survival and G to A mutation in non-CpG sites in KRAS and p53 genes. CONCLUSION: These data showed that proximal and distal colorectal cancers have distinct gene-specific methylation profiles and molecular and clinical characteristics.


Assuntos
Neoplasias Colorretais/genética , Metilação de DNA , Genes Neoplásicos/genética , Proteínas de Neoplasias/genética , Idoso , Ilhas de CpG/genética , Feminino , Deleção de Genes , Marcadores Genéticos , Humanos , Perda de Heterozigosidade , Masculino , Fenótipo
10.
Jpn J Thorac Cardiovasc Surg ; 54(7): 314-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16898649

RESUMO

We report an extended parasternal approach to aortic and tricuspid valves used in a 31-year-old man. The patient presented with a deformed sternum and severe adhesion between the sternum and right ventricular outflow tract, caused by postoperative mediastinitis, which lasted for 4 years after a radical operation for tetralogy of Fallot during his childhood. The extended parasternal approach provided a safe and excellent exposure of both aortic and tricuspid valves without postoperative chest wall instability.


Assuntos
Insuficiência da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Esterno/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Adulto , Insuficiência da Valva Aórtica/complicações , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Comunicação Interventricular/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Masculino , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Reoperação , Tetralogia de Fallot/cirurgia , Insuficiência da Valva Tricúspide/complicações
11.
J Gastroenterol ; 41(3): 209-16, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16699854

RESUMO

BACKGROUND: Although dendritic cells (DCs) play significant roles in intestinal immune responses, little is known regarding the direct effects of luminal foods on DC functions in the intestinal mucosa. In this study, we examined the effects of fatty acids (FAs) with various chain length on the phagocytic function, antigen presentation, and chemotaxis of intestinal DCs. METHODS: DCs obtained from the thoracic duct lymph of mesenteric lymphadenectomized rats were cultured with long [arachidonic acid (AA) or oleic acid] or medium (octanoic acid) chain FAs with interleukin-4 and granulocyte macrophage-colony stimulating factor. Tumor necrosis factor-alpha was added in the maturation group. Phagocytic function was examined by the intake of fluorescent microbeads. The expression of cell surface molecules was determined by immunocytochemistry or fluorescence-activated cell sorting (FACS). Antigen presentation ability was evaluated by coincubating keyhole limpet hemocyanin (KLH)-sensitized spleen lymphocytes and KLH-pulsed DCs. Migratory ability of DCs toward the chemokines CC chemokine ligand (CCL) 20 and CCL21 was also assessed. RESULTS: There was a maturation-induced decrease in phagocytic function, and an increased expression of major histocompatibility complex (MHC) class II molecules. Exposure of DCs to both long- and medium-chain FAs maintained phagocytic ability. The expression of MHC class II molecules was significantly suppressed only by long-chain FAs. The expression of costimulatory factors was suppressed only by AA. Long- but not medium-chain FAs suppressed the antigen presentation ability of DCs induced by maturation. Chemotactic ability of mature DCs toward CCL21 was abrogated only by long-chain FAs. CONCLUSIONS: The data suggest that intraluminal exposure to long- and medium-chain FAs may differentially modulate the immune functions of intestinal DCs.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Ácidos Graxos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Animais , Apresentação de Antígeno/efeitos dos fármacos , Separação Celular , Quimiocinas CC/metabolismo , Quimiotaxia/efeitos dos fármacos , Células Dendríticas/imunologia , Ácidos Graxos/metabolismo , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/efeitos dos fármacos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Ratos Wistar
12.
Int J Cancer ; 118(12): 2999-3005, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16425274

RESUMO

Regional DNA hypermethylation and global DNA hypomethylation are 2 epigenetic alterations associated with colorectal cancers. However, their correlation with microsatellite instability (MSI) and chromosomal instability (CIN) in colorectal cancer, and their relationship with chromatin conformation and histone modification are not clear. In this study, we analyzed regional and global methylation in 16 cell lines and 64 primary colorectal cancers. We found that MSI and CIN are 2 alternative events in most cell lines and tumors. Furthermore, regional hypermethylation and global hypomethylation are also alternative events in most cases. We also observed a strong correlation between MSI and regional hypermethylation and between CIN and global hypomethylation. We further analyzed chromatin conformation and histone acetylation in cell lines with CIN or MSI. CIN cancers had open chromatin conformation and enriched histone acetylation in repetitive as well as in gene-specific regions. MSI cancers, on the other hand, had closed chromatin conformation and low levels of histone acetylation. After a MSI cell line was treated with 5-aza-2'-deoxycytidine or trichostatin A, the closed chromatin conformation became open, and histone acetylation was enriched. These observations support our hypothesis that in colorectal cancer, regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation, which might have a causal correlation with MSI and CIN, respectively.


Assuntos
Cromatina/metabolismo , Instabilidade Cromossômica , Neoplasias Colorretais/metabolismo , Metilação de DNA , Histonas/metabolismo , Repetições de Microssatélites , Acetilação , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , DNA de Neoplasias/metabolismo , Epigênese Genética , Humanos , Ácidos Hidroxâmicos/farmacologia , Imunoprecipitação , Perda de Heterozigosidade , Conformação Proteica
13.
Int J Cancer ; 118(11): 2765-71, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16381005

RESUMO

Mucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non-mucinous CRC are not known. Activating mutations of BRAF and KRAS and their relationship with MSI and CIMP were examined in 83 sporadic CRC specimens (26 mucinous and 57 non-mucinous CRC). MSI, CIMP, BRAF and KRAS mutation were observed in 17, 24, 25 and 36% of the tumors, respectively. BRAF mutation was highly correlated with MSI (p < 0.001) and CIMP (p < 0.001). A higher incidence of MSI (27% vs. 12%), CIMP (38% vs. 18%, p < 0.05) and BRAF mutation (46% vs. 16%, p < 0.01) was observed in mucinous CRC. KRAS mutation (27% vs. 40%) was observed more frequently in non-mucinous CRC. Significantly higher percentages of mucinous CRC (54%, p < 0.05) had MSI or CIMP or BRAF mutations. Concordant occurrence of 2 or more of these alterations was observed in 39% of mucinous CRC and only 11% of non-mucinous CRC (p < 0.01). The more frequent occurrence and closer association among MSI, CIMP and BRAF mutation in mucinous CRC observed in our study further supports the idea that its pathogenesis may involve distinct genetic and epigenetic changes.


Assuntos
Adenocarcinoma Mucinoso/genética , Neoplasias do Colo/genética , Ilhas de CpG/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma Mucinoso/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Metilação de DNA , Análise Mutacional de DNA , Epigênese Genética , Feminino , Instabilidade Genômica , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Fenótipo
14.
Clin Cancer Res ; 11(24 Pt 1): 8564-9, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16361538

RESUMO

PURPOSE: The relationship between global hypomethylation, chromosomal instability (CIN), and microsatellite instability (MSI) remains unclear in colorectal cancer. The aim of this study was to investigate the relationship between global methylation status, loss of heterozygosity (LOH), and MSI in sporadic colorectal cancer. EXPERIMENTAL DESIGN: We determined global methylation levels in 80 sporadic colorectal cancers, 51 adjacent normal tissues, and 20 normal tissues using the long interspersed nucleotide elements-combined bisulfite restriction analysis method. We also analyzed 80 colorectal cancers for MSI status and LOH at chromosomes 5q21, 8p12-22, 17p13, and 18q21. RESULTS: We identified 14 cases of MSI (17.5%) and 58 cases of LOH (72.5%). LOH was observed more frequently in microsatellite stable (MSS) cancers than in MSI cancers at all loci. Colorectal cancers showed significantly lower global methylation levels than did normal tissues (41.0+/-9.7% versus 54.3+/-6.5%; P<0.001). MSS cancers showed significantly lower global methylation levels when compared with MSI cancers (39.5+/-9.4% versus 48.2+/-8.2%; P=0.003). Tumors with global hypomethylation (with

Assuntos
Instabilidade Cromossômica , Neoplasias Colorretais/genética , Metilação de DNA , Perda de Heterozigosidade , Repetições de Microssatélites , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Int J Cancer ; 117(3): 499-505, 2005 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-15906361

RESUMO

Most cases of pancreatic cancer are inoperable when diagnosed. Since immunotherapy and antiangiogenic therapy have been reported to be promising for pancreatic cancer, we examined whether the combination of immunotherapy with dendritic cells (DCs) and the antiangiogenic drug TNP-470 induces tumor regression. Syngeneic mouse pancreatic adenocarcinoma cells were orthotopically inoculated into C57/BL6 mice. DCs with or without tumor lysate (TL) were administered i.p. at 4 and 5 weeks. TNP-470 was injected s.c. into tumor-bearing mice every other day from 4 weeks to 6 weeks. We compared anticancer effects in 6 groups: NT (no treatment), DC/TL- (DCs without TL), DC/TL+ (DCs pulsed with TL), TNP (TNP-470 alone), DC/TL-TNP (DC/TL- plus TNP-470) and DC/TL+TNP (DC/TL+ plus TNP-470). We measured tumor volume, mean vascular density (MVD) and vessel diameter by FITC-dextran using an intravital microscope; degrees of proliferation and apoptosis of cancer cells by PCNA and TUNEL; infiltrating lymphocytes and expression levels of VEGF and MMP-9 by immunohistochemistry and immunoblotting. Tumor volume and MVD were significantly suppressed in the treatment groups with prolonged survival rate, especially in the DC/TL+TNP group. There were no significant differences in apoptosis among the 6 groups except DC/TL+. The number of infiltrating CD4+ cells in the DC/TL+ group was higher than that in the NT group. VEGF expression was significantly suppressed in the treatment groups containing TNP-470, and MMP-9 was also suppressed in the groups containing DC/TL+. Our data suggested that TL-pulsed DCs combined with TNP-470 induced regression of mouse pancreatic cancer, possibly through induction of immune responses and suppression of angiogenesis.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Células Dendríticas/imunologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Sesquiterpenos/uso terapêutico , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Divisão Celular , Sobrevivência Celular , Terapia Combinada , Cicloexanos , Modelos Animais de Doenças , Imunoterapia , Ativação Linfocitária , Transfusão de Linfócitos , Camundongos , O-(Cloroacetilcarbamoil)fumagilol , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/patologia , Baço/imunologia
16.
J Gastroenterol ; 39(2): 176-80, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15069626

RESUMO

An autopsy case of adenosquamous pancreatic cancer in a 61-year-old male patient with an elevated serum level of parathyroid hormone-related protein (PTH-rP) is reported. He was admitted to our hospital with a 1-month-long history of abdominal discomfort and progressive abdominal fullness. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass, approximately 10 cm in diameter, involving the pancreas, with round enhancement on contrast examination. Histological examination of a specimen taken by CT-guided needle biopsy suggested squamous cell carcinoma or transitional cell carcinoma. Laboratory data on admission revealed a high serum calcium level and high PTH-rP level. The calcium level initially responded to intravenous hydration, furosemide, calcitonin, and bisphosphonates, decreasing from 15.0 to 9.0 mg/dl. However, the hypercalcemia recurred after 10 days. The patient developed carcinomatous peritonitis and acute renal failure, and died on the 25th hospital day. Autopsy revealed a mass in the pancreatic body to tail, invading the retroperitoneum, with progressive carcinomatous peritonitis. Histological examination of the mass revealed infiltrating carcinoma, showing squamous differentiation with focal intracytoplasmic lumina formation, consistent with pancreatic adenosquamous carcinoma. Immunohistological examination showed positive staining for PTH-rP. Adenosquamous carcinoma of the pancreas is relatively rare; only a few cases associated with hypercalcemia and for which PTH-rP has been identified as a causative factor have been reported. This is the first case in which immunohistochemistry proved localized PTH-rP in adenosquamous pancreatic cancer cells, associated with persistent hypercalcemia.


Assuntos
Cálcio/sangue , Carcinoma Adenoescamoso/sangue , Hipercalcemia/sangue , Neoplasias Pancreáticas/sangue , Proteína Relacionada ao Hormônio Paratireóideo/sangue , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/patologia , Humanos , Hipercalcemia/complicações , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X
18.
J Gastroenterol Hepatol ; 18(9): 1081-8, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12911667

RESUMO

BACKGROUND AND AIM: The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients. METHODS: Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer. RESULTS: In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients. CONCLUSION: There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC.


Assuntos
Colite Ulcerativa/metabolismo , Colo/citologia , Colo/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Receptores CCR5/biossíntese , Receptores Imunológicos/biossíntese , Receptores de Prostaglandina , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Gastrointest Endosc ; 57(3): 336-42, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12612512

RESUMO

BACKGROUND: Infrared light can penetrate tissue more deeply than visible light. Therefore, an infrared video endoscope may be useful for assessment of gastric submucosal vessels. However, the resolution of currently available infrared video endoscope systems has been unsatisfactory. A new infrared video endoscope system was developed and its clinical utility assessed for diagnosis of early stage gastric cancer. METHODS: Twenty-five patients with early stage gastric cancer and 8 with gastric adenoma underwent endoscopy with the infrared video endoscope system after intravenous injection of indocyanine green. RESULT: Indocyanine green pooling did not appear in adenomas and some intramucosal gastric cancers, whereas it was noted in all submucosally invasive gastric cancers. Tumors not exhibiting indocyanine green pooling were intramucosal, well-differentiated adenocarcinomas of low height (flat-type cancers). CONCLUSION: These results suggest that our new infrared video endoscope provides valuable information about the submucosal aspect of early stage gastric cancer. Infrared video endoscopy may become a powerful technique for determining whether to perform endoscopic mucosal resection.


Assuntos
Adenoma/diagnóstico , Endoscopia Gastrointestinal/métodos , Neoplasias Gástricas/diagnóstico , Gravação em Vídeo , Desenho de Equipamento , Gastroscópios , Humanos , Verde de Indocianina , Raios Infravermelhos
20.
Gastrointest Endosc ; 57(2): 242-6, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12556795

RESUMO

BACKGROUND: Endoscopic mucosal resection with a cap-fitted panendoscope is a useful, effective, and safe technique. The effectiveness and safety of a newly designed larger but softer cap was compared in this study with the conventional hard cap. The soft cap has a significantly larger diameter (18 mm) compared with that of the hard cap (16.5 mm). METHODS: Eighty-three patients who underwent mucosal resection of gastric lesions were included in analysis. The diameter, resection specimen depth, and the rate of en bloc resection were compared. The operability of the endoscope with the cap attached, patient tolerance, and safety of the procedure were analyzed. RESULTS: Mean diameter (+/- SEM) of specimens resected with the soft cap was larger: 22.1 (+/- 0.7) versus 15.8 (+/- 0.3) mm (p < 0.001). The specimen was also thicker: 1.54 (+/- 0.10) versus 1.08 (+/- 0.11) mm (p < 0.001). Use of the soft cap led to higher rate of en bloc resection: 66.7% versus 43.2% (p < 0.05). The operability of the endoscope with the larger, softer cap attached was similar to that when the hard cap was used. Both caps were equally safe. CONCLUSION: The soft cap is safe and useful for mucosal resection of larger gastric lesions. Its use increases the rate of en bloc resection.


Assuntos
Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscópios , Gastroscopia/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Coortes , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Satisfação do Paciente , Probabilidade , Medição de Risco , Sensibilidade e Especificidade , Gastropatias/patologia , Gastropatias/cirurgia , Resultado do Tratamento
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