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1.
Gan To Kagaku Ryoho ; 51(4): 417-420, 2024 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-38644309

RESUMEN

The use of nivolumab as first-line therapy for unresectable advanced gastric cancer has now become a standard practice, and its efficacy has been established. This is the first report of a patient with advanced gastric cancer who underwent conversion surgery after first-line nivolumab combination chemotherapy. The patient was a 58-year-old woman. Her medical history included hypertension and dyslipidemia. She had advanced gastric cancer with extensive lymph node metastasis in the left supraclavicular fossa and around the abdominal aorta. After confirming the HER2-negative status and the PD-L1 CPS score to be ≥5, nivolumab was administered in combination with chemotherapy. After the treatment, she underwent a total gastrectomy with D2 dissection, combined splenectomy and pancreatic tail resection for adhesions, and para-aortic lymph node sampling as a conversion surgery. There was no obvious cancerous remnant in the resected specimen, and the pathological response was Grade 3. The patient was alive and recurrence-free at 4 months postoperatively.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Gastrectomía , Nivolumab , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Persona de Mediana Edad , Femenino , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento
2.
Geriatr Gerontol Int ; 24 Suppl 1: 102-109, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37746748

RESUMEN

AIM: This study aimed to investigate the assessment tools dementia specialists use in clinical practice, reasons for their use and assessment-related factors. METHODS: A questionnaire survey was carried out from 15 September 2021 to 20 October 2021 among 1858 dementia specialists in Japan, with responses obtained via mail or using a Web form accessed via a Web address. RESULTS: Of the 1858 specialists who were sent the questionnaire, 574 responded, yielding a response rate of 32.2%. Almost all respondents stated that the main purposes of neuropsychological testing were to identify the pathophysiology and aid diagnosis. Most respondents identified behavioral and psychological symptoms of dementia as important factors for assessment. The most commonly used tests were the Hasegawa Dementia Scale-Revised and Mini-Mental State Examination, often used as screening tools. The Mini-Mental State Examination, Clock Drawing Test and Cube Copying Test were common assessments carried out directly by specialists. Quality of life and burden of care were less commonly assessed. CONCLUSIONS: Despite the main purpose of carrying out neuropsychological tests on dementia patients is to "understand the pathophysiology" and "aid in diagnosis," many assessment methods were chosen as screening methods carried out in a short time during clinic hours. The lack of evaluation of care burden and QOL, considered important by specialists, is an issue for the future in treating people with dementia, a life disability. Geriatr Gerontol Int 2024; 24: 102-109.


Asunto(s)
Demencia , Humanos , Demencia/diagnóstico , Demencia/psicología , Calidad de Vida , Japón , Pruebas Neuropsicológicas , Pruebas de Estado Mental y Demencia
3.
Gan To Kagaku Ryoho ; 47(1): 123-125, 2020 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-32381879

RESUMEN

A 79-year-old male presented with right inguinal mass and right leg pain. Laparoscopic right hemicolectomy was performed for transverse colon cancer(type 1, muc, pSS, pN1a, pStage Ⅲa)3 years and 6 months ago. We resected the mass located in the spermatic cord and reconstructed it using the Direct Kugel Patch. Histopathological examination revealed mucinous carcinoma and was diagnosed as a metastatic lesion. Local recurrence was detected in the spermatic cord 1 year after resection, and radical inguinal orchiectomy was performed. Six months after the surgery performed for local recurrence, repeated recurrence was detected in the mesh used for reconstruction. Because this recurrence time was short, the patient opted for chemotherapy; however, this resulted in tumor growth, and surgery had to be scheduled. We performed extended resection of the abdominal wall and reconstruction using the fascia lata tensor muscle flap. Although intestinal obstruction, aspiration pneumonia, and skin flap necrosis were observed, the patient was discharged on the 85th postoperative day and remained alive without recurrence for 17 months. Mucinous carcinoma tends to cause local recurrence and requires adequate surgical margin resection. Extended excision should be considered in such cases of repeated local recurrence without distant metastases.


Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias Colorrectales , Cordón Espermático , Anciano , Humanos , Masculino , Recurrencia Local de Neoplasia
4.
Gan To Kagaku Ryoho ; 46(4): 721-724, 2019 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-31164515

RESUMEN

Combination therapy containingnab -paclitaxel(nab-PTX)and gemcitabine(GEM)is widely administered for metastatic pancreatic cancer. Recently, this regimen is likely to be applied for treatment in patients with locally advanced disease or for neoadjuvant chemotherapy(NAC)in patients with borderline resectable(BR)pancreatic cancer. We report a case of BR pancreatic cancer in a patient who was eligible for comparison of the imaging findings with the microscopic findings of the resected specimen. A 72-year-old woman was admitted to our hospital with a complaint of jaundice. Enhanced CT showed a 35mm tumor at the head of the pancreas involvingthe portal vein and in contact with the superior mesenteric artery(SMA). After 4 courses of chemotherapy containinga combination of nab-PTX and GEM, the tumor reduced in size, but was still in contact with the portal vein and SMA on imaging. The level of tumor marker CA19-9 was remarkably reduced. Subtotal stomach-preservingpancreaticoduodenectomy with portal vein reconstruction was performed. Macroscopic findings of the cut surface of the resected specimen showed that a white nodule at the pancreas head involved the portal vein and was in contact with the close-cut margin from the SMA; however, microscopic findings revealed that tumor cells had disappeared in the plexus around the SMA. R0 resection was achieved. The histological treatment effect based on Evans' classification and TNM classification were GradeⅡ and pT3N1aM0(pStage ⅡB), respectively. There has been no recurrence 15 months after the surgery. Based on the abovementioned findings, chemotherapy containing a combination of nab-PTX and GEM can be an effective option of NAC for BR-A pancreatic cancer. Even if the tumor is in contact with the SMA on imaging, when the CA19- 9 level is markedly reduced, there is a possibility of achievingR0 surgery.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Anciano , Albúminas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Humanos , Recurrencia Local de Neoplasia , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Gemcitabina
5.
Int Immunol ; 31(10): 657-668, 2019 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-30689886

RESUMEN

Cholera toxin B (CTB) is a subunit of cholera toxin, a bacterial enterotoxin secreted by Vibrio cholerae and also functions as an immune adjuvant. However, it remains unclear how CTB activates immune cells. We here evaluated whether or how CTB induces production of a pro-inflammatory cytokine, interleukin-1ß (IL-1ß). CTB induced IL-1ß production not only from bone marrow-derived macrophages (BMMs) but also from resident peritoneal macrophages in synergy with O111:B4-derived lipopolysaccharide (LPS O111:B4) that can bind to CTB. Meanwhile, when prestimulated with O55:B5-derived LPS (LPS O55:B5) that fails to bind to CTB, resident peritoneal macrophages, but not BMMs, produced IL-1ß in response to CTB. The CTB-induced IL-1ß production in synergy with LPS in both peritoneal macrophages and BMMs was dependent on ganglioside GM1, which is required for internalization of CTB. Notably, not only the NLRP3 inflammasome but also the pyrin inflammasome were involved in CTB-induced IL-1ß production from resident peritoneal macrophages, while only the NLRP3 inflammasome was involved in that from BMMs. In response to CTB, a Rho family small GTPase, RhoA, which activates pyrin inflammasome upon various kinds of biochemical modification, increased its phosphorylation at serine-188 in a GM1-dependent manner. This phosphorylation as well as CTB-induced IL-1ß productions were dependent on protein kinase A (PKA), indicating critical involvement of PKA-dependent RhoA phosphorylation in CTB-induced IL-1ß production. Taken together, these results suggest that CTB, incorporated through GM1, can activate resident peritoneal macrophages to produce IL-1ß in synergy with LPS through novel mechanisms in which pyrin as well as NLRP3 inflammasomes are involved.


Asunto(s)
Toxina del Cólera/farmacología , Inflamasomas/efectos de los fármacos , Interleucina-1beta/biosíntesis , Macrófagos Peritoneales/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Pirina/inmunología , Animales , Humanos , Inflamasomas/inmunología , Macrófagos Peritoneales/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología
6.
Retina ; 39(7): 1377-1384, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29689025

RESUMEN

PURPOSE: To determine the efficacy of the combination therapy of intravitreal ranibizumab (IVR) and 577-nm yellow laser subthreshold micropulse laser photocoagulation (SMLP) for macular edema secondary to branch retinal vein occlusion cystoid macular edema. METHODS: Retrospective, consecutive, case-control study. Forty-six eyes of 46 patients with treatment-naive branch retinal vein occlusion cystoid macular edema were enrolled. The IVR + SMLP group consisted of 22 patients who had undergone both SMLP and IVR. Intravitreal ranibizumab group consisted of 24 patients who had undergone IVR monotherapy. Intravitreal ranibizumab therapy was one initial injection and on a pro re nata in both groups, and SMLP was performed at 1 month after IVR in the IVR + SMLP group. Preoperatively and monthly, best-corrected visual acuity and central retinal thickness were evaluated using swept source optical coherence tomography. RESULTS: Best-corrected visual acuity and central retinal thickness significantly improved at 6 months in IVR + SMLP and IVR groups. Best-corrected visual acuity and central retinal thickness were not significantly different between the two groups at any time points. The number of IVR injections during initial 6 months in IVR group (2.3 ± 0.9) was significantly greater (P = 0.034) than that in IVR + SMLP group (1.9 ± 0.8). CONCLUSION: The combination therapy of IVR and SMLP can treat branch retinal vein occlusion cystoid macular edema effectively, by decreasing the frequency of IVR injections while maintaining good visual acuity.


Asunto(s)
Fotocoagulación/métodos , Mácula Lútea/patología , Edema Macular/terapia , Ranibizumab/administración & dosificación , Oclusión de la Vena Retiniana/complicaciones , Agudeza Visual , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Estudios de Casos y Controles , Femenino , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/terapia , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
7.
Stem Cell Res Ther ; 8(1): 61, 2017 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-28279187

RESUMEN

BACKGROUND: Experiments have previously demonstrated the therapeutic potential of mobilized dental pulp stem cells (MDPSCs) for complete pulp regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in pulpectomized teeth. METHODS: Five patients with irreversible pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into pulpectomized teeth. RESULTS: The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric pulp test (EPT) of the pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. CONCLUSIONS: Human MDPSCs are safe and efficacious for complete pulp regeneration in humans in this pilot clinical study.


Asunto(s)
Pulpa Dental/crecimiento & desarrollo , Pulpitis/terapia , Regeneración/genética , Trasplante de Células Madre , Diente/crecimiento & desarrollo , Adulto , Diferenciación Celular/genética , Proliferación Celular/genética , Pulpa Dental/diagnóstico por imagen , Pulpa Dental/patología , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Masculino , Pulpitis/patología , Pulpitis/cirugía , Células Madre/citología , Diente/diagnóstico por imagen , Diente/patología , Diente/cirugía
8.
Int Immunol ; 29(3): 133-143, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28338984

RESUMEN

IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well associate with autoimmune inflammatory responses. In the generation of Th17 cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. We speculated additional regulation in Il17a transcription and randomly screened a 6344 clone cDNA library to identify specific modulators for Il17a promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase Il17a promoter activity in a T-cell line and to promote Th17 development ex vivo. This enhancement was a consequence of enhanced expression of hypoxia-inducible factor-1α (HIF-1α) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1α, both ubiquitin ligases had little effect on Th17 cell differentiation. These results suggest that the SIAH1 and SIAH2 play a pivotal role to promote Th17 cell differentiation through maintaining the stability of HIF-1α protein.


Asunto(s)
Diferenciación Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Th17/citología , Células Th17/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/deficiencia , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ubiquitina-Proteína Ligasas/genética
9.
Gan To Kagaku Ryoho ; 42(12): 1472-4, 2015 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-26805067

RESUMEN

A 60-year-old man who had bloody stools after sigmoid colonoscopy was admitted to our hospital. A digital examination and sigmoid colonoscopy showed a type 2 circular tumor at location Rb with incomplete mobility and tumor hemorrhage, and the result of a biopsy was moderately differentiated adenocarcinoma (tub2). Computed tomography and magnetic resonance imaging suggested a possibility of invasion of the primary rectal tumor to the sacrum. The clinical stage was cT4bN0M0H0P0, cStage Ⅱ, which is generally not treatable by surgery. Sigmoid colostomy was performed, and a central venous port was implanted. After a preoperative treatment consisting of 3 courses of mFOLFOX6 and radiation therapy, the clinical stage changed to ycT2N0M0H0P0, ycStageⅠ. Super-low anterior resection and covering ileostomy were performed 46 days after the preoperative treatment. A pathological examination revealed no residual cancer cells in the primary lesion and lymph node (Grade 3, pCR). The patient has been disease-free for 4 years and 9 months after the operation.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Terapia Combinada , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Inducción de Remisión , Tomografía Computarizada por Rayos X
10.
Gan To Kagaku Ryoho ; 42(12): 1509-11, 2015 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-26805079

RESUMEN

The patient was a 39-year-old woman who was referred to our hospital with suspicion of locally-advanced breast cancer. After several tests, she received a diagnosis of cT4bN1M1 (liver), Stage Ⅳbreast cancer. The liver metastasis was located in S4, and was 1 cm in size. Core needle biopsy was performed on the breast tumor; the pathological diagnosis was invasive ductal carcinoma (scirrhous carcinoma), nuclear Grade (NG) 3, and HER2-positive. She received epirubicin plus cyclophosphamide (EC) followed by docetaxel (DOC) plus pertuzumab (PER) plus trastuzumab (HER). After chemotherapy, the liver metastasis and axillary lymph node metastases had disappeared on imaging findings, showing a complete response (CR), but the primary breast tumor remained, showing a partial response (PR). She underwent mastectomy and axillary lymph node dissection for local control. After surgery, no metastases including liver metastases were seen on CT. The patient is currently receiving tamoxifen and anti-HER2 therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/cirugía , Terapia Combinada , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Terapia de Reemplazo de Estrógeno , Femenino , Humanos , Neoplasias Hepáticas/secundario , Mastectomía , Estadificación de Neoplasias , Tamoxifeno/uso terapéutico
11.
Biochem Biophys Res Commun ; 451(2): 215-21, 2014 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-25088998

RESUMEN

IL-27 is a heterodimeric cytokine that regulates both innate and adaptive immunity. The immunosuppressive effect of IL-27 largely depends on induction of IL-10-producing Tr1 cells. To date, however, effects of IL-27 on regulation of immune responses via mediators other than cytokines remain poorly understood. To address this issue, we examined immunoregulatory effects of conditional medium of bone marrow-derived macrophages (BMDMs) from WSX-1 (IL-27Rα)-deficient mice and found enhanced IFN-γ and IL-17A secretion by CD4(+) T cells as compared with that of control BMDMs. We then found that PGE2 production and COX-2 expression by BMDMs from WSX-1-deficient mice was increased compared to control macrophages in response to LPS. The enhanced production of IFN-γ and IL-17A was abolished by EP2 and EP4 antagonists, demonstrating PGE2 was responsible for enhanced cytokine production. Murine WSX-1-expressing Raw264.7 cells (mWSX-1-Raw264.7) showed phosphorylation of both STAT1 and STAT3 in response to IL-27 and produced less amounts of PGE2 and COX-2 compared to parental RAW264.7 cells. STAT1 knockdown in parental RAW264.7 cells and STAT1-deficiency in BMDMs showed higher COX-2 expression than their respective control cells. Collectively, our result indicated that IL-27/WSX-1 regulated PGE2 secretion via STAT1-COX-2 pathway in macrophages and affected helper T cell response in a PGE2-mediated fashion.


Asunto(s)
Dinoprostona/biosíntesis , Interleucinas/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Línea Celular , Medios de Cultivo Condicionados , Ciclooxigenasa 2/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Interferón gamma/biosíntesis , Interleucina-17/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Citocinas/deficiencia , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Receptores de Interleucina , Factor de Transcripción STAT1/deficiencia , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Transducción de Señal , Linfocitos T Colaboradores-Inductores/metabolismo
12.
Rapid Commun Mass Spectrom ; 28(13): 1453-8, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24861594

RESUMEN

RATIONALE: Visualization of the spatial distribution of phosphatidylcholine (PC) in tissues by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) provides insights into key physiological and pathophysiological processes. In MALDI-IMS analysis, the heterogeneity of adduct ions formed from PC lowers the specificity of detection of PC molecular species and poses a challenge in the identification of these species. To solve this problem, modified matrix solution and desalting with ammonium acetate (NH4 Ac) buffer have been employed. However, the utility of these methods is limited to the analysis of brain sections. METHODS: The MALDI signal intensities of [PC+H], [PC+Na] and [PC+K] were compared after three different pretreatments (modified matrix solution, desalting with 150 mM ammonium acetate, treatment with 150 mM potassium acetate). RESULTS: Pretreatment of tissue sections with 150 mM potassium acetate resulted in an increase in the signal intensity of [PC+K] ions produced from cryosections of the pancreas, brain, and liver tissues. CONCLUSIONS: Pretreatment with potassium acetate can be a simple, improved, and highly useful method for the reliable analysis of PC in tissues.


Asunto(s)
Imagen Molecular/métodos , Fosfatidilcolinas/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Química Encefálica , Humanos , Hígado/química , Masculino , Ratones , Páncreas/química , Fosfatidilcolinas/química , Acetato de Potasio
13.
Gan To Kagaku Ryoho ; 41(4): 455-9, 2014 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-24743360

RESUMEN

BACKGROUND: Eribulin mesylate, a novel non-taxane inhibitor of microtubule dynamics, results in a significant improvement in the overall survival of heavily pretreated patients with metastatic breast cancer(MBC). In the present study, we aimed to clarify the efficacy and safety of eribulin mesylate for the treatment of MBC. PATIENTS AND METHODS: We examined 18 patients with MBC who received eribulin mesylate in our hospital from October 2011 to May 2013. The patients were assessed for therapeutic response and adverse events with this treatment; in addition, these parameters were assessed in patients undergoing a combination treatment of eribulin mesylate and trastuzumab. RESULTS: The mean age of the patients in this study was 68.7 years(range, 60-85 years). All patients exhibited metastases to lymph nodes and distant sites. The mean number of prior regimens was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment administered was 7.2(range, 2- 17). The objective response rate and clinical benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the median progression-free survival was 6 months. The Grade 3/4 adverse events occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1 patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who received the combination treatment of trastuzumab and eribulin mesylate experienced no adverse events. CONCLUSIONS: eribulin mesylate appears to demonstrate an acceptable tumor response in patients with MBC, and it can be safely administered to elderly patients if myelosuppression is carefully managed.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Furanos/efectos adversos , Humanos , Cetonas/efectos adversos , Persona de Mediana Edad , Pronóstico , Tomografía Computarizada por Rayos X
14.
Gan To Kagaku Ryoho ; 41(12): 1663-4, 2014 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-25731288

RESUMEN

A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy.


Asunto(s)
Carcinoma Adenoescamoso/complicaciones , Venas Mesentéricas/patología , Neoplasias del Colon Sigmoide/patología , Trombosis de la Vena/etiología , Anciano , Anticoagulantes/uso terapéutico , Carcinoma Adenoescamoso/cirugía , Humanos , Masculino , Neoplasias del Colon Sigmoide/complicaciones , Neoplasias del Colon Sigmoide/cirugía , Tomografía Computarizada por Rayos X , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/patología , Warfarina/uso terapéutico
15.
Arterioscler Thromb Vasc Biol ; 33(5): 935-42, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23471233

RESUMEN

OBJECTIVE: Macrophage (Mϕ) migration rests on the adhesion/detachment between Mϕ surface components and extracellular matrixes, and the contribution of numerous inflammatory disorders. Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, influences Mϕ motility through an action distinct from its classical modulation of the plasmin-based fibrinolytic process. We rely here on a small molecule PAI-1 inhibitor (TM5275) to investigate the role of PAI-1 in Mϕ migration in the pathogenesis of renal injury. APPROACH AND RESULTS: Mϕ migration was inhibited both in vitro and in vivo by TM5275. It was also reduced in T-cell-deficient nude mice, but not in PAI-1-deficient mice. Mϕ migration hinged on the interaction of PAI-1 with low-density lipoprotein receptor-related protein, an interaction prevented by TM5275, but not with vitronectin, urokinase-type plasminogen activator, or tissue-type plasminogen activator. Fed to rats with anti-Thy-1-induced nephritis, TM5275 significantly decreased Mϕ accumulation and ameliorated the progression of renal injury. CONCLUSIONS: These findings suggest that a small molecule PAI-1 inhibitor represents a novel class of anti-inflammatory agents targeting Mϕ migration by the inhibition of the interaction of PAI-1 with low-density lipoprotein receptor-related protein.


Asunto(s)
Macrófagos/efectos de los fármacos , Piperazinas/farmacología , Inhibidor 1 de Activador Plasminogénico/fisiología , para-Aminobenzoatos/farmacología , Animales , Antiinflamatorios/farmacología , Movimiento Celular/efectos de los fármacos , Glomerulonefritis/patología , Isoanticuerpos/farmacología , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/fisiología , Macrófagos/fisiología , Ratones , Ratas
16.
Biochem Biophys Res Commun ; 431(4): 772-6, 2013 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-23333329

RESUMEN

The CXCL12/CXCR4 axis is involved in many cellular responses for host homeostasis, and malfunction of this signaling pathway is associated with a variety of diseases. It is now known that CXCL12 also binds to another newly identified chemokine receptor, CXCR7, which does not couple with a G-protein. CXCR7 can form homodimers, or heterodimers with CXCR4, and is believed to sequester the chemokine CXCL12, although the CXCL12/CXCR7 axis activates MAP kinases through ß-arrestin. Therefore, it has not been well defined how CXCR7 activation affects CXCL12-induced cellular events. To elucidate the function of CXCR7, we prepared CXCR7 agonist Compound 1. Compound 1 is a selective and potent CXCR7 agonist that clearly has the activity to recruit ß-arrestin toward CXCR7. It also activates MAP kinases Akt and ERK. Using this compound, we confirmed that the CXCR7 agonist, but not an antagonistic antibody, did inhibit CXCL12 induced HUVEC tube formation, suggesting that activation of CXCR7 ameliorates CXCL12 induced cellular events, probably by affecting on CXCR4 function. We show that ß-arrestin recruitment to CXCR4 is reduced by over-expression of CXCR7 and activation of CXCR7 by agonist treatment reduces the protein level of CXCR4. Based on our results, together with reported information, we propose that CXCR7, when up-regulated upon inflammation, can act as a negative regulator of CXCR4 by heterodimerizing with CXCR4, inducing its internalization and degradation. This mechanism suggests that CXCR7 agonists can have a therapeutic effect on CXCL12 causing diseases by countering the effects of CXCL12.


Asunto(s)
Quimiocina CXCL12/antagonistas & inhibidores , Piridinas/farmacología , Quinolonas/farmacología , Receptores CXCR4/metabolismo , Receptores CXCR/agonistas , Regulación hacia Abajo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Piridinas/química , Quinolonas/química
17.
Clin J Gastroenterol ; 6(6): 476-9, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26182140

RESUMEN

Acute pancreatitis reportedly occurs in about 15 % of cases of branch duct (BD)-intraductal papillary mucinous neoplasms (IPMNs), with two-thirds of BD-IPMNs being located in the head or uncinate process of the pancreas. However, the surgical indications and optimal treatment methods for BD-IPMNs have not been established. A 59-year-old Japanese male with epigastralgia was admitted to our hospital. A multidetector row computed tomography (MDCT) scan disclosed grade I acute pancreatitis. Magnetic resonance cholangiopancreatography disclosed a 1.5-cm BD-IPMN in the uncinate process. Two months after discharge, the epigastralgia recurred, and MDCT again revealed grade I pancreatitis. Due to the repeated episodes of pancreatitis, we performed ductal branch-oriented pancreatic resection. To detect the inferior branch of the Wirsung duct and avoid the development of a pancreatic fistula, we injected indigo carmine into the tumor which confirmed ligation of the inferior branch. Histopathologically, the tumor proved to be an adenoma. The postoperative course was uneventful in both the short- and long-term follow-up and, to date, there has been no recurrence of pancreatitis, or diabetes mellitus during the 6 years since pancreatectomy. This procedure is one of the methods that can be used for the successful resection of a BD-IPMN in the uncinate process that caused recurrent acute pancreatitis.

18.
J Forensic Sci ; 58 Suppl 1: S253-7, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22900716

RESUMEN

A previously healthy 23-year-old woman was admitted to hospital with abdominal pain at 39 weeks 0 days of pregnancy. The patient suffered sudden cardiopulmonary arrest during the observation and unfortunately died. An autopsy was performed to determine the cause of death. Opening of the peritoneal cavity revealed 2220 mL of blood and a subcapsular hematoma weighing 1060 g on the anterior surface of the right hepatic lobe. A lesion of c. 1 cm in diameter was noted at the center of the front surface of the right hepatic lobe, which was shown on histological examination to be a focal nodular hyperplasia-like lesion. The cause of death was found to be hypovolemic shock caused by bleeding of the rupture of the hepatocellular hyperplastic nodule. Although some previous case reports describe hemorrhage from such lesions, forensic pathologists should be aware that they can lead to severe bleeding and sometimes death.


Asunto(s)
Hiperplasia Nodular Focal/patología , Hemorragia/patología , Complicaciones del Embarazo , Adulto , Femenino , Patologia Forense , Hematoma/patología , Hemorragia/etiología , Humanos , Embarazo , Rotura/patología , Choque/etiología
19.
Int Immunol ; 24(9): 539-50, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22914861

RESUMEN

Spleen tyrosine kinase (Syk) is associated with Fcγ receptors (FcγRs) and transmits activation signals through FcγRs in myeloid cells. Thus, application of drugs to inhibit Syk activity can affect the development of immune diseases mediated by autoantibodies, while unexpected systemic effects by the inhibition may be concerned because Syk has multiple physiological functions. We used tamoxifen-inducible systemic conditional Syk knockout (KO) mice to evaluate the role of Syk in the pathogenesis of autoimmune arthritis and to investigate the systemic effects of Syk deletion. In a collagen antibody-induced arthritis model, Syk KO mice were almost completely protected from disease induction and showed significantly attenuated accumulation of neutrophils and macrophages in the joints. Syk-deleted macrophages showed less IL-6 and MCP-1 production upon FcγR ligation and exhibited reduced FcγR-mediated phagocytosis in vitro. Syk-deleted macrophages produce more RANTES upon FcγR ligation, indicating a Syk-independent signaling through the FcγR. We further found that both wild-type and Syk-deleted macrophages induced neutrophil chemotaxis upon FcγR ligation in vitro, and air-pouch model demonstrated that Syk-deleted neutrophils have a potential to infiltrate into local tissues in response to collagen and anti-collagen antibodies. However, Syk-deleted neutrophils exhibited greatly decreased neutrophil extracellular traps formation and FcγR-mediated phagocytosis. Our results indicated that Syk deficiency rendered mice completely unresponsive to immune activation by anti-collagen antibodies with disabling one pathway of FcγR-mediated signaling that was crucial for arthritis induction.


Asunto(s)
Artritis Experimental/inmunología , Autoanticuerpos/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/inmunología , Neutrófilos/inmunología , Proteínas Tirosina Quinasas/metabolismo , Animales , Autoanticuerpos/inmunología , Movimiento Celular/genética , Movimiento Celular/inmunología , Células Cultivadas , Colágeno/inmunología , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/efectos de los fármacos , Fagocitosis , Proteínas Tirosina Quinasas/genética , Receptores de IgG/metabolismo , Transducción de Señal/genética , Transducción de Señal/inmunología , Quinasa Syk
20.
Masui ; 61(5): 549-52, 2012 May.
Artículo en Japonés | MEDLINE | ID: mdl-22702100

RESUMEN

We detected congenital aqueductal stenosis from CT images taken for the differential diagnosis of a post-dural puncture headache. A history of multiple spinal taps for anesthesia and the nature of headaches led us to a suspected diagnosis of headache caused by intracranial hypotension at variance with image findings diagnostic of hydrocephalus, perplexing us in the differential diagnosis. Hydrocephalus was of congenital type, having no causal relationship with past multiple spinal taps. Congenital aqueductal stenosis varies in severity from infancy-onset one to accidental one diagnosed from images like the current case. Since treatment may differ between hydrocephalus and intracranial hypotension which are diametrically opposite to each other in pathophysiology, it is essential to differentiate a headache in an overall view of a history, physical examination, and image findings.


Asunto(s)
Hidrocefalia/congénito , Hidrocefalia/diagnóstico por imagen , Cefalea Pospunción de la Duramadre/diagnóstico , Tomografía Computarizada por Rayos X , Adulto , Diagnóstico Diferencial , Femenino , Humanos
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