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1.
J Plast Surg Hand Surg ; 53(5): 288-294, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31066603

RESUMO

Excess scar formation can occur after skin injurふy and lead to abnormal scar formation, such as keloids and hypertrophic scars, which are characterised by substantial deposition of extracellular matrix in the dermis. Periostin, an extracellular matrix protein that plays a crucial role in skin development and maintaining homeostasis, is also involved in skin disorders such as systemic/limited scleroderma, wound closure, and abnormal scar formation. However, the mechanism of periostin involvement in abnormal scar formation is not yet fully understood. In this study, we investigated the mechanism by which periostin is involved in abnormal scar formation. Treatment of human dermal fibroblasts (HDFs) with IL-4 and IL-13, which are cytokines of Th2 type immune responses that are up-regulated in abnormal scars, dramatically elevated the levels of periostin mRNA and protein, and also promoted the secretion of periostin by HDFs. Transforming growth factor-ß1 (TGF-ß1) had the same effect on HDFs as IL-4 and IL-13. Stimulation of HDFs with periostin promoted RhoA/ROCK pathway-mediated TGF-ß1 secretion from HDFs. Our results suggest that IL-4 and IL-13 induce periostin expression and secretion, and in turn, secreted periostin induces RhoA/ROCK pathway-mediated TGF-ß1 secretion. Secreted TGF-ß1 then induces further periostin production and secretion, thereby promoting abnormal scar formation.

2.
Asian Pac J Cancer Prev ; 20(5): 1389-1392, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31127897

RESUMO

Objective: Bacillus Calmette-Guèrin (BCG) intravesical therapy is currently established using a low dose because of the high incidence of side-effects. Moreover, shortening the dwell time of BCG is conducted in some facilities owing to the complications associated with a long dwell time after injection. The method of BCG administration varies in each facility and even with each doctor. We evaluated whether the dwell-time and dose differences in patients who underwent intravesical BCG therapy is related to completion rates, adverse effects, and nonrecurrence rates. Methods: From November 2006 to April 2016, a total of 173 patients who received intravesical BCG therapy after transurethral resection of bladder tumor or transurethral biopsy were evaluated retrospectively. We allocated them into 4 groups based on the dose (40 or 80 mg BCG) and the dwell time (1 or 2 hours). Completion rate, side effects, and nonrecurrence rates were evaluated. Results: No significant improvement in the completion rate or reduction in side-effects was observed in any of the regimens. Although nonrecurrence rates for the 1-hour dwell time tended to be lower than the 2-hour dwell time, the difference was not significant. Conclusion: Our study suggests that reducing the BCG dose or shortening the dwell time does not reduce adverse effects or affect the nonrecurrence rate.

3.
Asian Pac J Cancer Prev ; 20(4): 1271-1273, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030505

RESUMO

Objective: UroVysion (Abbott Molecular, Inc., Illinois, USA) is based on multicolor fluorescence in situ hybridization (FISH). It has been used successfully in the USA following its Food and Drug Administration approval in 2001. However, the technology was not approved for use in Japan until 2017. Cystoscopy and urine cytology are the most frequently used examinations to detect bladder cancer in Japan, and there are only a few reports regarding the performance of UroVysion. Therefore, the aim of this study is to examine the diagnostic accuracy of UroVysion FISH in Japanese patients whose tumors are detected by cystoscopy before transurethral resection of bladder tumor (TURBT). Methods: From April 2018 to July 2018, a total of 40 patients who were diagnosed as having bladder tumors by cystoscopy, and therefore underwent TURBT were registered in this study. One day before TURBT, urine cytology and UroVysion FISH were used in order to compare the accuracy with which they could detect bladder carcinoma, as confirmed by pathological results of TURBT. Results: The pathological results of TURBT showed urothelial carcinoma in 33 cases. Urine cytology showed positive results for 0 cases (0%), suspicious results for 10 cases (30.3%), and negative results for 23 cases (69.7%). On the other hand, UroVysion FISH indicated 9 positive cases (27.3%) and 24 negative cases (72.7%). There were 19 cases of urothelial carcinoma (57.6%) that were not detected by either method. Conclusion: We conclude that UroVysion FISH alone is insufficient to detect bladder cancer and that cystoscopy is essential for the optimum detection or follow up of bladder cancer cases in our hospital.


Assuntos
Cistoscopia/métodos , Citodiagnóstico/métodos , Hibridização in Situ Fluorescente/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Urina/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Kit de Reagentes para Diagnóstico , Urina/citologia
4.
J Pharmacol Exp Ther ; 368(3): 535-544, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30602591

RESUMO

Despite the requirement for effective medication against neuropathic pain associated with type 2 diabetes mellitus (T2DM), mechanism-based pharmacotherapy has yet to be established. Given that long-lasting neuroinflammation, driven by inflammatory macrophages in the peripheral nerves, plays a pivotal role in intractable pain, it is important to determine whether inflammatory macrophages contribute to neuropathic pain associated with T2DM. To generate an experimental model of T2DM, C57BL/6J mice were fed a high-fat diet (HFD) ad libitum. Compared with control diet feeding, obesity and hyperglycemia were observed after HFD feeding, and the mechanical pain threshold evaluated using the von Frey test was found to be decreased, indicating the development of mechanical allodynia. The expression of mRNA markers for macrophages, inflammatory cytokines, and chemokines were significantly upregulated in the sciatic nerve (SCN) after HFD feeding. Perineural administration of saporin-conjugated anti-Mac1 antibody (Mac1-Sap) improved HFD-induced mechanical allodynia. Moreover, treatment of Mac1-Sap decreased the accumulation of F4/80+ macrophages and the upregulation of inflammatory mediators in the SCN after HFD feeding. Inoculation of lipopolysaccharide-activated peritoneal macrophages in tissue surrounding the SCN elicited mechanical allodynia. Furthermore, pharmacological inhibition of inflammatory macrophages by either perineural or systemic administration of TC-2559 [4-(5-ethoxy-3-pyridinyl)-N-methyl-(3E)-3-buten-1-amine difumarate], a α4ß2 nicotinic acetylcholine receptor-selective agonist, relieved HFD-induced mechanical allodynia. Taken together, inflammatory macrophages that accumulate in the SCN mediate the pathophysiology of neuropathic pain associated with T2DM. Inhibitory agents for macrophage-driven neuroinflammation could be potential candidates for novel pharmacotherapy against intractable neuropathic pain.

5.
Asian Pac J Cancer Prev ; 19(12): 3495-3500, 2018 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-30583675

RESUMO

Objective: In recent years, although reduced port surgeries (RPS) have been reported for many urological diseases, there have been no reports regarding simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS. Therefore, the aim of this study was to evaluate outcomes and complications of simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS. Methods: We performed a preliminary case series of 4 patients with synchronous upper urinary tract (UUT) tumor and invasive bladder cancer who underwent simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS between 2014 and 2017 at our hospital. Demographic data, pathologic features, the surgical technique, and outcomes were retrospectively analyzed. Result: All 4 patients were men whose median age was 79 years (range 65-85 years) and median body mass index was 24.2 kg/m2 (range 21.5-27.3 kg/m2). The laparoscopic approach was technically successful in all 4 patients without the need for open conversion. The median total operative time was 434 minutes (range 372-481 minutes). The median estimated blood loss was 773 ml (range 153-923 ml), median interval to resuming oral intake was 2 days (range 1-7 days), and median hospital stay was 16 days (range 13-20 days). Conclusion: The reduced port approach is technically feasible in terms of many outcome measures, with significant cosmetic advantages. This method can be performed safely and recommended as a viable option for patients with concomitant UUT and bladder cancer.


Assuntos
Cistectomia/efeitos adversos , Laparoscopia/efeitos adversos , Nefroureterectomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Humanos , Tempo de Internação , Masculino , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia , Sistema Urinário/cirurgia
6.
Neuropsychopharmacol Rep ; 38(3): 145-148, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30175527

RESUMO

AIM: We have previously demonstrated that upregulation of CC chemokines through dopamine receptor signaling in the prefrontal cortex (PFC) underlies methamphetamine (Meth)-induced reward. Given the common pharmacological property of Meth and cocaine (Coca), which are highly addictive psychostimulants, we hypothesized that chemokines may also contribute to Coca-induced reward. The aim of this study was to identify a key chemokine-mediating Coca-induced reward in mice. METHODS: The mRNA expression levels of chemokines were measured by reverse transcription-quantitative polymerase chain reaction. Coca-induced reward was evaluated by conditioned place preference test. RESULTS: We found that mRNA expression levels of CC chemokine ligand 2 (CCL2), CCL7, and CXC chemokine ligand 1 (CXCL1) were upregulated in the PFC after a single administration of Coca (20 mg/kg, s.c.). Upregulation of CXCL1, but not CCL2 and CCL7, mRNA in the PFC was also observed after repeated administration of Coca. A single administration of dopamine D1 receptor agonist SKF 81297 (10 mg/kg, s.c.), but not D2 receptor agonist sumanirole, upregulated CXCL1 mRNA in the PFC. Coca-induced reward was attenuated by the pretreatment of SB 225002 (5 mg/kg, s.c.), a selective antagonist of CXC chemokine receptor 2 (CXCR2, cognate receptor for CXCL1). CONCLUSIONS: Collectively, we identified CXCL1 as a key regulator in Coca-induced reward and propose that pharmacological approach targeting CXCL1 could be a novel pharmacotherapy for Coca-induced reward.

7.
J Neuroinflammation ; 15(1): 96, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587798

RESUMO

BACKGROUND: Neuro-immune interaction underlies chronic neuroinflammation and aberrant sensory processing resulting in neuropathic pain. Despite the pathological significance of both neuroinflammation-driven peripheral sensitization and spinal sensitization, the functional relationship between these two distinct events has not been understood. METHODS: In this study, we determined whether inhibition of inflammatory macrophages by administration of α4ß2 nicotinic acetylcholine receptor (nAChR) agonists improves neuropathic pain and affects microglial activation in the spinal dorsal horn (SDH) in mice following partial sciatic nerve ligation (PSL). Expression levels of neuroinflammatory molecules were evaluated by RT-qPCR and immunohistochemistry, and PSL-induced mechanical allodynia was defined by the von Frey test. RESULTS: Flow cytometry revealed that CD11b+ F4/80+ macrophages were accumulated in the injured sciatic nerve (SCN) after PSL. TC-2559, a full agonist for α4ß2 nAChR, suppressed the upregulation of interleukin-1ß (IL-1ß) in the injured SCN after PSL and attenuated lipopolysaccharide-induced upregulation of IL-1ß in cultured macrophages. Systemic (subcutaneous, s.c.) administration of TC-2559 during either the early (days 0-3) or middle/late (days 7-10) phase of PSL improved mechanical allodynia. Moreover, local (perineural, p.n.) administration of TC-2559 and sazetidine A, a partial agonist for α4ß2 nAChR, during either the early or middle phase of PSL improved mechanical allodynia. However, p.n. administration of sazetidine A during the late (days 21-24) phase did not show the attenuating effect, whereas p.n. administration of TC-2559 during this phase relieved mechanical allodynia. Most importantly, p.n. administration of TC-2559 significantly suppressed morphological activation of Iba1+ microglia and decreased the upregulation of inflammatory microglia-dominant molecules, such as CD68, interferon regulatory factor 5, and IL-1ß in the SDH after PSL. CONCLUSION: These findings support the notion that pharmacological inhibition of inflammatory macrophages using an α4ß2 nAChR agonist exhibit a wide therapeutic window on neuropathic pain after nerve injury, and it could be nominated as a novel pharmacotherapy to relieve intractable pain.

8.
Sci Transl Med ; 10(429)2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29467297

RESUMO

Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show that RIF is mediated by eosinophil interactions with α-smooth muscle actin-positive (α-SMA+) stromal cells. Abdominal irradiation caused RIF especially in the submucosa (SM) of the small intestine, which was associated with the excessive accumulation of eosinophils in both human and mouse. Eosinophil-deficient mice showed markedly ameliorated RIF, suggesting the importance of eosinophils. After abdominal irradiation, chronic crypt cell death caused elevation of extracellular adenosine triphosphate, which in turn activated expression of C-C motif chemokine 11 (CCL11) by pericryptal α-SMA+ cells in the SM to attract eosinophils in mice. Inhibition of C-C chemokine receptor 3 (CCR3) by genetic deficiency or neutralizing antibody (Ab) treatment suppressed eosinophil accumulation in the SM after irradiation in mice, suggesting a critical role of the CCL11/CCR3 axis in the eosinophil recruitment. Activated α-SMA+ cells also expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) to activate eosinophils. Transforming growth factor-ß1 from GM-CSF-stimulated eosinophils promoted collagen expression by α-SMA+ cells. In translational studies, treatment with a newly developed interleukin-5 receptor α-targeting Ab, analogous to the human agent benralizumab, depleted intestinal eosinophils and suppressed RIF in mice. Collectively, we identified eosinophils as a crucial factor in the pathogenesis of RIF and showed potential therapeutic strategies for RIF by targeting eosinophils.

9.
Neurosci Lett ; 665: 33-37, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29174638

RESUMO

We previously showed that the CC-chemokine ligand 2 (CCL2)-CC-chemokine receptor 2 (CCR2) system is responsible for conditioned place preference (CPP) by methamphetamine (Meth). In this study, we investigated the roles for other chemokines mediating Meth-induced CPP and the upstream factors upregulating chemokines in mice. We found that CCL7 mRNA level was upregulated in the prefrontal cortex (PFC) after Meth administration (3mg/kg, subcutaneous), and increased CCL7 immunoreactivity was localized to the PFC NeuN-positive neurons. Meth-induced CPP was blocked by the dopamine D1 receptor antagonist SCH 23390 but not by the D2 receptor antagonists raclopride or haloperidol. The D1 receptor agonist SKF 81297 alone elicited CPP, suggesting a critical role of D1 receptor signaling in Meth-induced reward. Consistent with these results, the Meth-induced upregulation of CCL7 and CCL2 were attenuated by SCH 23390, and a single administration of SKF 81297 upregulated mRNA expression levels of CCL7 and CCL2 in the PFC. Furthermore, Meth-induced CPP was prevented by INCB 3284, a selective antagonist of CCR2, a receptor that binds both CCL7 and CCL2. Collectively, we identified two CC-chemokines (i.e., CCL7 and CCL2) as key regulatory factors in Meth-induced reward. Pharmacological inhibitors of these chemokines may warrant development as novel therapeutics for ameliorating Meth addiction.


Assuntos
Comportamento Aditivo/tratamento farmacológico , Quimiocina CCL2/metabolismo , Quimiocina CCL7/metabolismo , Receptores de Dopamina D1/metabolismo , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Operante/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Masculino , Metanfetamina/farmacologia , Camundongos Endogâmicos C57BL , Recompensa , Regulação para Cima/efeitos dos fármacos
10.
Int J Mol Sci ; 18(11)2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29104252

RESUMO

Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1) macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain.


Assuntos
Descoberta de Drogas , Inflamação/complicações , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Neuralgia/complicações , Neuralgia/tratamento farmacológico , Animais , Citocinas/imunologia , Descoberta de Drogas/métodos , Humanos , Inflamação/patologia , Ligantes , Macrófagos/imunologia , Macrófagos/patologia , Neuralgia/patologia , Receptores Nicotínicos/imunologia
11.
Sci Rep ; 7(1): 8536, 2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819198

RESUMO

The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers, we demonstrated a direct contribution of CCR7 homodimerization to CCR7-dependent cell migration and signaling. Induction of stable CCR7 homodimerization resulted in enhanced CCR7-dependent cell migration and CCL19 binding, whereas induction of CXCR4/CCR7 heterodimerization did not. In contrast, dissociation of CCR7 homodimerization by a novel CCR7-derived synthetic peptide attenuated CCR7-dependent cell migration, ligand-dependent CCR7 internalization, ligand-induced actin rearrangement, and Akt and Erk signaling in CCR7-expressing cells. Our study indicates that CCR7 homodimerization critically regulates CCR7 ligand-dependent cell migration and intracellular signaling in multiple cell types.

12.
Adv Urol ; 2017: 1404610, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28634489

RESUMO

OBJECTIVES: Primary mediastinal germ cell tumors (PMGCTs) are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. METHODS: We examined 6 patients (median age: 25 years, range: 19-27 years) with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8-84 months). RESULTS: Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin (EP)). One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. CONCLUSIONS: Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

13.
J Rural Med ; 11(2): 59-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27928457

RESUMO

Objective: There are few reports of the long-term outcomes of elderly patients with prostate cancer. We analyzed data from our institution from the past 12 years, including the patient history, treatment methods, and prognosis of patients with prostate cancer aged 80 years or more. Patients and Methods: A total of 179 cases of prostate cancer in patients aged 80 years or more were retrospectively evaluated. We divided them chronologically into groups A, B, C, and D: Group A included 40 cases from 2002-2004; Group B, 48 cases from 2005-2007; Group C, 46 cases from 2008-2010; and Group D, 45 cases from 2011-2013. Results: Sixty-one (30%) patients changed treatment course. Interestingly, no cancer deaths occurred in the patients who changed treatment course. Although 14 (7.8%) cancer deaths occurred (A: B: C: D = 4: 4: 6: 0, respectively), all occurred in 2011 or later. Conclusion: In our study, over 50 patients who underwent treatment survived for 5 years or more. By treating prostate cancer in elderly patients when appropriate, we can lower the mortality rate due to prostate cancer. Our results support the active treatment of prostate cancer in elderly patients.

14.
Opt Express ; 24(9): 9757-65, 2016 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-27137590

RESUMO

In semiconductor and optics fields, some devices are constructed with layered systems including two or three individual layers. Measurement of polarization properties of the individual components of these layered systems is often desired. In this paper, we present methods allowing the simultaneous extraction of the polarization parameters of the individual components by analyzing spectroscopic Mueller matrices (measured at two wavelengths). We have studied both retarder-retarder and retarder-polarizer-retarder systems. The validities of the methods were successfully tested using both simulations and real polarization systems.

15.
Elife ; 5: e10561, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26830463

RESUMO

Lymph nodes (LNs) are highly confined environments with a cell-dense three-dimensional meshwork, in which lymphocyte migration is regulated by intracellular contractile proteins. However, the molecular cues directing intranodal cell migration remain poorly characterized. Here we demonstrate that lysophosphatidic acid (LPA) produced by LN fibroblastic reticular cells (FRCs) acts locally to LPA2 to induce T-cell motility. In vivo, either specific ablation of LPA-producing ectoenzyme autotaxin in FRCs or LPA2 deficiency in T cells markedly decreased intranodal T cell motility, and FRC-derived LPA critically affected the LPA2-dependent T-cell motility. In vitro, LPA activated the small GTPase RhoA in T cells and limited T-cell adhesion to the underlying substrate via LPA2. The LPA-LPA2 axis also enhanced T-cell migration through narrow pores in a three-dimensional environment, in a ROCK-myosin II-dependent manner. These results strongly suggest that FRC-derived LPA serves as a cell-extrinsic factor that optimizes T-cell movement through the densely packed LN reticular network.


Assuntos
Movimento Celular , Fibroblastos/metabolismo , Lisofosfolipídeos/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/fisiologia , Animais , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Análise de Sequência de DNA , Proteína rhoA de Ligação ao GTP/metabolismo
16.
J Biochem ; 159(3): 305-12, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26491063

RESUMO

Reelin is a secreted glycoprotein whose function is regulated by proteolysis. One of the specific cleavage sites of Reelin, called C-t, is located approximately between the sixth and seventh Reelin repeat but its exact site was unknown. We here show that a metalloprotease present in the culture supernatant of cerebellar granular neurons (CGN) cleaves Reelin between Ala2688 and Asp2689. A Reelin mutant in which Asp2689 is replaced by Lys (Reelin-DK) is resistant to C-t cleavage by culture supernatant of CGN. From biochemical characteristics and the cleavage site preference, meprin α and meprin ß were suggested candidate proteases and both were confirmed to cleave Reelin at the C-t site. Meprin α cleaved Reelin-DK but meprin ß did not. Actinonin, a meprin α and meprin ß inhibitor, did not inhibit the Reelin-cleaving activity of CGN and the amount of Reelin fragments in brains of meprin ß knock-out mice was not significantly different from that of the wild-type, indicating that meprin ß does not play a major role in Reelin cleavage under basal conditions. We propose that meprin α and meprin ß join the modulators of Reelin signalling as they cleave Reelin at a specific site and are upregulated under specific pathological conditions.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Córtex Cerebral/citologia , Proteínas da Matriz Extracelular/metabolismo , Metaloendopeptidases/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/enzimologia , Proteólise , Serina Endopeptidases/metabolismo , Animais , Células COS , Técnicas de Cultura de Células , Cercopithecus aethiops , Células HEK293 , Humanos , Ácidos Hidroxâmicos/farmacologia , Metaloendopeptidases/antagonistas & inibidores , Metaloendopeptidases/genética , Camundongos , Camundongos Knockout , Transdução de Sinais
17.
Asian Pac J Cancer Prev ; 16(15): 6353-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26434842

RESUMO

BACKGROUND: To explore the safety, efficacy, and oncological outcome of 3-port laparoscopic radical cystectomy (LRC) compared to open radical cystectomy (ORC) in patients older than 75 years. MATERIALS AND METHODS: From June 2010 to July 2014, we analyzed 16 radical cystectomies in patients older than 75 years (LRC group=8; ORC group=8). Demographic parameters, operative variables, and perioperative outcome in the 2 groups were retrospectively collected, analyzed, and compared. RESULTS: Patients in both groups had comparable preoperative characteristics. A significantly longer operating time (476 vs. 303 min, P=0.0002) and less estimated blood loss (627 vs. 2,106 mL, P=0.021) were observed in the LRC group compared to the ORC group. Infection and ileus were the most common early complications after surgery. Patients who underwent ORC suffered from more postoperative infection (22.2% vs. 0.0%, P=0.054) and ileus (25.0% vs. 12.5%, P=0.521) than the LRC group, but the difference was not significant. CONCLUSIONS: Judging from this initial trial, 3-port LRC can be safely carried out in elderly patients. We suggest 3-port LRC as the primary intervention to treat muscle-invasive or high-risk nonmuscle-invasive bladder cancer in elderly patients with an otherwise relatively long life expectancy.


Assuntos
Cistectomia/métodos , Laparoscopia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Cistectomia/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Íleus/etiologia , Infecção/etiologia , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Duração da Cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
18.
Case Rep Oncol ; 8(1): 205-11, 2015 Jan-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26034481

RESUMO

Primitive neuroectodermal tumor (PNET) is a member of the Ewing's sarcoma family of tumors (ESFT). We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide) chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.

19.
PLoS One ; 10(2): e0117454, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25688986

RESUMO

During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in vitro as well as cell trafficking into the lymph nodes in vivo. In this study, we report that a recombinant form of a viral CXCR4 ligand, X4-tropic HIV-1 gp120, enhanced the CD4 T cell response to CCR7 ligands in a manner dependent on CXCR4 and CD4, and that this effect was recapitulated by HIV-1 virions. HIV-1 gp120 significantly enhanced CCR7-dependent CD4 T cell migration from the footpad of mice to the draining lymph nodes in in vivo transfer experiments. We also demonstrated that CXCR4 expression is required for stable CCR7 expression on the CD4 T cell surface, whereas CXCR4 signaling facilitated CCR7 ligand binding to the cell surface and increased the level of CCR7 homo- as well as CXCR4/CCR7 hetero-oligomers without affecting CCR7 expression levels. Our findings indicate that HIV-evoked CXCR4 signaling promotes CCR7-dependent CD4 T cell migration by up-regulating CCR7 function, which is likely to be induced by increased formation of CCR7 homo- and CXCR4/CCR7 hetero-oligomers on the surface of CD4 T cells.


Assuntos
Linfócitos T CD4-Positivos/citologia , Proteína gp120 do Envelope de HIV/metabolismo , HIV-1/metabolismo , Receptores CCR7/metabolismo , Receptores CXCR4/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Movimento Celular/efeitos dos fármacos , Quimiocina CCL21/farmacologia , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/farmacologia , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Multimerização Proteica , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores CCR7/antagonistas & inibidores , Receptores CCR7/genética , Receptores CXCR4/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Vírion/fisiologia
20.
Vasc Cell ; 6: 15, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25114787

RESUMO

BACKGROUND: Magnetite used in an 8-MHz radiofrequency (RF) capacitive heating device can increase the temperature of a specific site up to 45°C. When treating a metastatic lesion around large abdominal vessels via hyperthermia with magnetite, heating-induced adverse effects on these vessels need to be considered. Therefore, this study examined hyperthermia-induced damage to blood vessel walls in vitro. METHODS: A large agar phantom with a circulatory system consisting of a swine artery and vein connected to a peristaltic pump was prepared. The blood vessels were placed on the magnetite-containing agar piece. Heating was continued for 30 min at 45°C. After heating, a histological study for injury to the blood vessels was performed. RESULTS: The inner membrane temperature did not reach 45°C due to the cooling effect of the blood flow. In the heated vessels, vascular wall collagen degenerated and smooth muscle cells were narrowed; however, no serious changes were noted in the vascular endothelial cells or vascular wall elastic fibers. The heated vessel wall was not severely damaged; this was attributed to cooling by the blood flow. CONCLUSIONS: Our findings indicate that RF capacitive heating therapy with magnetite may be used for metastatic lesions without injuring the surrounding large abdominal vessels.

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