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1.
J Surg Case Rep ; 2023(10): rjad601, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37942340

RESUMO

Spindle cell tumors exhibit a relatively low occurrence rate and can manifest in various locations within the human body, including soft tissues and bones. The process of making a diagnosis is supported by conducting pathological and immunohistochemical tests. A 50-year-old female patient visited the hospital with abdominal pain that lasted about a week. Magnetic resonance imaging of the pelvis showed that this mass was independent and was not a lymph node mass, but a retroperitoneal sarcoma type mass. As part of the treatment, the mass was surgically excised, and a supracervical hysterectomy was carried out. The tumor was wrapped in a grayish-white capsule and showed a lobulating pattern. Retroperitoneal spindle cell tumors, particularly those occurring in abdominal soft tissues, are infrequently observed. Histopathological diagnosis is done in stages, and when cases are ambiguous, immunohistochemistry can provide valuable guidance in the right direction.

2.
Stem Cell Res Ther ; 14(1): 193, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37533021

RESUMO

BACKGROUND: Peripheral artery disease is an ischemic vascular disease caused by the blockage of blood vessels supplying blood to the lower extremities. Mesenchymal stem cells (MSCs) and endothelial colony-forming cells (ECFCs) have been reported to alleviate peripheral artery disease by forming new blood vessels. However, the clinical application of MSCs and ECFCs has been impeded by their poor in vivo engraftment after cell transplantation. To augment in vivo engraftment of transplanted MSCs and ECFCs, we investigated the effects of hybrid cell spheroids, which mimic a tissue-like environment, on the therapeutic efficacy and survival of transplanted cells. METHODS: The in vivo survival and angiogenic activities of the spheroids or cell suspension composed of MSCs and ECFCs were measured in a murine hindlimb ischemia model and Matrigel plug assay. In the hindlimb ischemia model, the hybrid spheroids showed enhanced therapeutic effects compared with the control groups, such as adherent cultured cells or spheroids containing either MSCs or ECFCs. RESULTS: Spheroids from MSCs, but not from ECFCs, exhibited prolonged in vivo survival compared with adherent cultured cells, whereas hybrid spheroids composed of MSCs and ECFCs substantially increased the survival of ECFCs. Moreover, single spheroids of either MSCs or ECFCs secreted greater levels of pro-angiogenic factors than adherent cultured cells, and the hybrid spheroids of MSCs and ECFCs promoted the secretion of several pro-angiogenic factors, such as angiopoietin-2 and platelet-derived growth factor. CONCLUSION: These results suggest that hybrid spheroids containing MSCs can serve as carriers for cell transplantation of ECFCs which have poor in vivo engraftment efficiency.


Assuntos
Células-Tronco Mesenquimais , Doença Arterial Periférica , Humanos , Animais , Camundongos , Neovascularização Fisiológica , Células Endoteliais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células Cultivadas , Isquemia/terapia , Isquemia/metabolismo
3.
J Occup Health ; 65(1): e12380, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36694993

RESUMO

OBJECTIVE: This study examined the association between maternal occupational status and adverse pregnancy outcomes in the general South Korean population. METHODS: We analyzed 1 825 845 employed and non-employed women with a diagnostic code for pregnancy in the National Health Insurance Service (NHIS) database (2010-2019) of South Korea. Based on their employment status and type of occupation, we calculated risk ratios for three adverse outcomes: early abortive outcomes (miscarriage, ectopic pregnancy, and molar pregnancy), stillbirth, and no live birth (diagnosis of pregnancy with no record of live birth thereafter, which include early abortive outcomes and stillbirth) with adjusting for covariates. RESULTS: Overall, 18.0%, 0.7%, and 39.8% ended in early abortive outcomes, stillbirths, and no live births, respectively. The risk of early abortive outcomes and stillbirths was higher in non-employed women than in employed women, while no live births were more frequent in employed women. Those in the health and social work industry showed the highest risk of no live births. Manufacturing jobs (1.030, 95% CI: 1.013, 1.047) and health/social work (1.029, 95% CI: 1.012, 1.046) were associated with an increased risk of early abortive outcomes compared with financial and insurance jobs. Consistently higher risks of no live births were observed in the manufacturing, wholesale/retail trade, education, health/social work, and public/social/personal service occupation. CONCLUSION: Employment during pregnancy and several occupation types were associated with a higher risk of pregnancy loss. Additional research using detailed job activity data is needed to determine specific occupational causes of adverse pregnancy outcomes.


Assuntos
Resultado da Gravidez , Natimorto , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Natimorto/epidemiologia , Ocupações , Indústrias , Emprego
4.
J Nanobiotechnology ; 20(1): 17, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983551

RESUMO

The topographical interface of the extracellular environment has been appreciated as a principal biophysical regulator for modulating cell functions, such as adhesion, migration, proliferation, and differentiation. Despite the existed approaches that use two-dimensional nanomaterials to provide beneficial effects, opportunities evaluating their impact on stem cells remain open to elicit unprecedented cellular responses. Herein, we report an ultrathin cell-culture platform with potential-responsive nanoscale biointerfaces for monitoring mesenchymal stem cells (MSCs). We designed an intriguing nanostructured array through self-assembly of graphene oxide sheets and subsequent lithographical patterning method to produce chemophysically defined regions. MSCs cultured on anisotropic micro/nanoscale patterned substrate were spontaneously organized in a highly ordered configuration mainly due to the cell-repellent interactions. Moreover, the spatially aligned MSCs were spontaneously differentiated into smooth muscle cells upon the specific crosstalk between cells. This work provides a robust strategy for directing stem cells and differentiation, which can be utilized as a potential cell culture platform to understand cell-substrate or cell-cell interactions, further developing tissue repair and stem cell-based therapies.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Miócitos de Músculo Liso/citologia , Nanoestruturas/química , Engenharia Tecidual/métodos , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Grafite/química , Humanos , Fenótipo , Propriedades de Superfície , Engenharia Tecidual/instrumentação
5.
BMB Rep ; 55(4): 175-180, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34814976

RESUMO

Peptides are gaining substantial attention as therapeutics for human diseases. However, they have limitations such as low bioavailability and poor pharmacokinetics. Periostin, a matricellular protein, can stimulate the repair of ischemic tissues by promoting angiogenesis. We have previously reported that a novel angiogenic peptide (amino acids 142-151) is responsible for the pro-angiogenic activity of periostin. To improve the in vivo delivery efficiency of periostin peptide (PP), we used proteins self-assembled into a hollow cage-like structure as a drug delivery nanoplatform in the present study. The periostin peptide was genetically inserted into lumazine synthase (isolated from Aquifex aeolicus) consisting of 60 identical subunits with an icosahedral capsid architecture. The periostin peptide-bearing lumazine synthase protein cage nanoparticle with 60 periostin peptides multivalently displayed was expressed in Escherichia coli and purified to homogeneity. Next, we examined angiogenic activities of this periostin peptide-bearing lumazine synthase protein cage nanoparticle. AaLS-periostin peptide (AaLS-PP), but not AaLS, promoted migration, proliferation, and tube formation of human endothelial colony-forming cells in vitro. Intramuscular injection of PP and AaLS-PP increased blood perfusion and attenuated severe limb loss in the ischemic hindlimb. However, AaLS did not increase blood perfusion or alleviate tissue necrosis. Moreover, in vivo administration of AaLS-PP, but not AaLS, stimulated angiogenesis in the ischemic hindlimb. These results suggest that AaLS is a highly useful nanoplatform for delivering pro-angiogenic peptides such as PP. [BMB Reports 2022; 55(4): 175-180].


Assuntos
Nanopartículas , Neovascularização Patológica , Animais , Membro Posterior , Humanos , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Fisiológica , Peptídeos/farmacologia
6.
Mar Drugs ; 19(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922418

RESUMO

Scleroderma is an autoimmune disease caused by the abnormal regulation of extracellular matrix synthesis and is activated by non-regulated inflammatory cells and cytokines. Echinochrome A (EchA), a natural pigment isolated from sea urchins, has been demonstrated to have antioxidant activities and beneficial effects in various disease models. The present study demonstrates for the first time that EchA treatment alleviates bleomycin-induced scleroderma by normalizing dermal thickness and suppressing collagen deposition in vivo. EchA treatment reduces the number of activated myofibroblasts expressing α-SMA, vimentin, and phosphorylated Smad3 in bleomycin-induced scleroderma. In addition, it decreased the number of macrophages, including M1 and M2 types in the affected skin, suggesting the induction of an anti-inflammatory effect. Furthermore, EchA treatment markedly attenuated serum levels of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, in a murine scleroderma model. Taken together, these results suggest that EchA is highly useful for the treatment of scleroderma, exerting anti-fibrosis and anti-inflammatory effects.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Naftoquinonas/farmacologia , Escleroderma Sistêmico/prevenção & controle , Pele/efeitos dos fármacos , Actinas/metabolismo , Animais , Bleomicina , Colágeno/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Fibrose , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/imunologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Fosforilação , Células RAW 264.7 , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/metabolismo , Pele/imunologia , Pele/metabolismo , Pele/patologia , Proteína Smad3/metabolismo , Vimentina/metabolismo
7.
Molecules ; 26(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669590

RESUMO

Nitroreductases belong to a member of flavin-containing enzymes that can reduce nitroaromatic compounds to amino derivatives with NADH as an electron donor. NTR activity is known to be elevated in the cancerous environment and is considered an advantageous target in therapeutic prodrugs for the treatment of cancer. Here, we developed a ratiometric fluorescent molecule for observing NTR activity in living cells. This can provide a selective and sensitive response to NTR with a distinct increase in fluorescence ratio (FI530/FI630) as well as color changes. We also found a significant increase in NTR activity in cervical cancer HeLa and lung cancer A549 cells compared to non-cancerous NIH3T3. We proposed that this new ratiometric fluorescent molecule could potentially be used as a NTR-sensitive molecular probe in the field of cancer diagnosis and treatment development related to NTR activity.


Assuntos
Ensaios Enzimáticos/métodos , Corantes Fluorescentes/química , Sondas Moleculares/química , Nitrorredutases/metabolismo , Células A549 , Animais , Morte Celular , Cromatografia Líquida de Alta Pressão , Endocitose , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Sondas Moleculares/síntese química , Células NIH 3T3 , Espectrometria de Fluorescência
8.
Stem Cells Transl Med ; 10(3): 414-426, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33174379

RESUMO

Critical limb ischemia is a condition in which tissue necrosis occurs due to arterial occlusion, resulting in limb amputation in severe cases. Both endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are needed for the regeneration of peripheral arteries in ischemic tissues. However, it is difficult to isolate and cultivate primary EC and SMC from patients for therapeutic angiogenesis. Induced pluripotent stem cells (iPSCs) are regarded as useful stem cells due to their pluripotent differentiation potential. In this study, we explored the therapeutic efficacy of human iPSC-derived EC and iPSC-derived SMC in peripheral artery disease model. After the induction of mesodermal differentiation of iPSC, CD34+ progenitor cells were isolated by magnetic-activated cell sorting. Cultivation of the CD34+ progenitor cells in endothelial culture medium induced the expression of endothelial markers and phenotypes. Moreover, the CD34+ cells could be differentiated into SMC by cultivation in SMC culture medium. In a murine hindlimb ischemia model, cotransplantation of EC with SMC improved blood perfusion and increased the limb salvage rate in ischemic limbs compared to transplantation of either EC or SMC alone. Moreover, cotransplantation of EC and SMC stimulated angiogenesis and led to the formation of capillaries and arteries/arterioles in vivo. Conditioned medium derived from SMC stimulated the migration, proliferation, and tubulation of EC in vitro, and these effects were recapitulated by exosomes isolated from the SMC-conditioned medium. Together, these results suggest that iPSC-derived SMC enhance the therapeutic efficacy of iPSC-derived EC in peripheral artery disease via an exosome-mediated paracrine mechanism.


Assuntos
Isquemia Crônica Crítica de Membro , Células Endoteliais , Células-Tronco Pluripotentes Induzidas , Miócitos de Músculo Liso , Doença Arterial Periférica , Animais , Antígenos CD34 , Diferenciação Celular , Células Cultivadas , Isquemia Crônica Crítica de Membro/terapia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/transplante , Humanos , Camundongos , Miócitos de Músculo Liso/transplante , Doença Arterial Periférica/terapia
9.
Stem Cells Transl Med ; 8(3): 236-246, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30474937

RESUMO

Circulating angiogenic cells (CACs) have been implicated in the repair of ischemic tissues, and their mobilization from bone marrow is known to be regulated by the activations of chemokine receptors, including CXCR2 and CXCR4. This study was conducted to investigate the role of N-acetylated proline-glycine-proline (Ac-PGP; a collagen-derived chemotactic tripeptide) on CAC mobilization and its therapeutic potential for the treatment of peripheral artery diseases. Ac-PGP was administered daily to a murine hind limb ischemia model, and the effects of Ac-PGP on blood perfusion and CAC mobilization (Sca1+ Flk1+ cells) into peripheral blood were assessed. Intramuscular administration of Ac-PGP significantly improved ischemic limb perfusion and increased limb salvage rate by increasing blood vessel formation, whereas Ac-PGP-induced blood perfusion and angiogenesis in ischemic limbs were not observed in CXCR2-knockout mice. In addition, Ac-PGP-induced CAC mobilization was found to occur in wild-type mice but not in CXCR2-knockout mice. Transplantation of bone marrow from green fluorescent protein (GFP) transgenic mice to wild-type mice showed bone marrow-derived cells homed to ischemic limbs after Ac-PGP administration and that GFP-positive cells contributed to the formation of ILB4-positive capillaries and α smooth muscle actin (α-SMA)-positive arteries. These results suggest CXCR2 activation in bone marrow after Ac-PGP administration improves blood perfusion and reduces tissue necrosis by inducing CAC mobilization. These findings suggest a new pharmaceutical basis for the treatment of critical limb ischemia. Stem Cells Translational Medicine 2019;8:236&246.


Assuntos
Neovascularização Fisiológica/fisiologia , Peptídeos/metabolismo , Receptores de Interleucina-8B/metabolismo , Animais , Capilares/metabolismo , Membro Posterior/metabolismo , Isquemia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos/metabolismo
10.
Wound Repair Regen ; 26(2): 116-126, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29802745

RESUMO

Atrial natriuretic peptide (ANP) is a powerful vasodilating peptide secreted by cardiac muscle cells, and endothelial progenitor cells (EPCs) have been reported to stimulate cutaneous wound healing by mediating angiogenesis. To determine whether ANP can promote the EPC-mediated repair of injured tissues, we examined the effects of ANP on the angiogenic properties of EPCs and on cutaneous wound healing. In vitro, ANP treatment enhanced the migration, proliferation, and endothelial tube-forming abilities of EPCs. Furthermore, small interfering RNA-mediated silencing of natriuretic peptide receptor-1, which is a receptor for ANP, abrogated ANP-induced migration, tube formation, and proliferation of EPCs. In a murine cutaneous wound model, administration of either ANP or EPCs had no significant effect on cutaneous wound healing or angiogenesis in vivo, whereas the coadministration of ANP and EPCs synergistically potentiated wound healing and angiogenesis. In addition, ANP promoted the survival and incorporation of transplanted EPCs into newly formed blood vessels in wounds. These results suggest ANP accelerates EPC-mediated cutaneous wound healing by promoting the angiogenic properties and survival of transplanted EPCs.


Assuntos
Fator Natriurético Atrial/farmacologia , Células Progenitoras Endoteliais/fisiologia , Neovascularização Fisiológica/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/patologia , Animais , Proliferação de Células/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo Real
11.
BMC Cancer ; 17(1): 481, 2017 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-28701190

RESUMO

BACKGROUND: This study aimed to evaluate the perioperative outcomes and prognostic impact of the consecutive steps of imaging, frailty assessment, and diagnostic laparoscopy (DLS) in patients with advanced epithelial ovarian cancer (EOC). METHODS: Patients diagnosed with EOC during 2012-2015 were analyzed retrospectively. Surgical and survival outcomes were compared between three treatment groups: patients without high tumor dissemination (HTD) who underwent primary debulking surgery (PDS group); patients with HTD who underwent DLS (DLS group); and patients with HTD diagnosed by cytological confirmation of malignancy followed by neoadjuvant chemotherapy (NACT group). RESULTS: Of 181 patients, 85, 38, and 58 underwent PDS, DLS, and NACT, respectively. Among the 38 consecutive patients who initially underwent DLS, 6 were considered suitable for PDS; the remaining 32 were eligible for NACT followed by interval debulking surgery. The median operative times of debulking surgery in the PDS, DLS, and NACT groups were 365 min (interquartile range [IQR]: 216.5-476.5 min), 266.2 min (IQR: 160.3-193.5 min), and 339.0 min (IQR: 205-425 min; P = 0.042), respectively, with respective median estimated blood loss volumes of 962.2 mL (IQR: 300-1037.5 mL), 267.1 mL (IQR: 150-450 mL), and 861.7 mL (IQR: 150-1200 mL; P = 0.023). The DLS group had significantly reduced transfusion requirements and intensive care unit admission rates (P = 0.006). The Kaplan-Meier survival analysis indicated significantly poor PFS in the NACT group. However, there was no significant difference in OS among the three groups. CONCLUSIONS: The consecutive steps of imaging, frailty assessment, and DLS might facilitate rapid assessments of peritoneal disease extent and resectability; this novel algorithm might also be used to individualize treatment.


Assuntos
Fragilidade/epidemiologia , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Fragilidade/patologia , Humanos , Estimativa de Kaplan-Meier , Laparoscopia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Resultado do Tratamento
12.
BMB Rep ; 50(10): 504-509, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28539159

RESUMO

Ischemia is a serious disease, characterized by an inadequate blood supply to an organ or part of the body. In the present study, we evaluated the effects of the anti-microbial peptide SR-0379 on the stem cell-mediated therapy of ischemic diseases. The migratory and tube-forming abilities of human endothelial progenitor cells (EPCs) were enhanced by treatment with SR-0379 in vitro. Intramuscular administration of SR-0379 into a murine ischemic hindlimb significantly enhanced blood perfusion, decreased tissue necrosis, and increased the number of blood vessels in the ischemic muscle. Moreover, co-administration of SR-0379 with EPCs stimulated blood perfusion in an ischemic hindlimb more than intramuscular injection with either SR-0379 or EPCs alone. This enhanced blood perfusion was accompanied by a significant increase in the number of CD31- and α-SMApositive blood vessels in ischemic hindlimb. These results suggest that SR-0379 is a potential drug candidate for potentiating EPC-mediated therapy of ischemic diseases. [BMB Reports 2017; 50(10): 504-509].


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Indutores da Angiogênese/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/transplante , Terapia Genética , Membro Posterior/irrigação sanguínea , Humanos , Isquemia/terapia , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/efeitos dos fármacos , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/terapia , Transplante de Células-Tronco/métodos , Células-Tronco/fisiologia
13.
J Surg Oncol ; 116(3): 329-336, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28542980

RESUMO

BACKGROUND AND OBJECTIVE: The therapeutic role of systematic lymph node dissection (LND) remains unclear in advanced epithelial ovarian cancer (EOC), especially during interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NAC). We analyzed the therapeutic and prognostic roles of systematic LND in advanced EOC patients. METHODS: Data from consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV disease, who underwent optimal IDS (<1cm) after NAC, were obtained via a retrospective chart review. Patients were classified into a lymph node sampling (LNS; node count <20) group and an LND (node count ≥20) group. RESULTS: Among 133 study patients, 65 and 68 underwent LND and LNS, respectively, during IDS. Overall survival (OS) was significantly better in the LND group than in the LNS group. In subgroup analysis with negative lymphadenopathy on preoperative imaging, progression-free survival (PFS) and OS were significantly better in the LND group than in the LNS group. Follow-up of subsequent recurrences showed significantly lower nodal and peritoneal recurrence rates among patients who underwent LND. Multivariate analysis identified LND as an independent prognostic factor for PFS and OS. CONCLUSION: Systematic LND may have therapeutic value in advanced EOC patients treated with NAC and IDS.


Assuntos
Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Excisão de Linfonodo , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
Stem Cells ; 35(3): 654-665, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27790799

RESUMO

Increasing evidence suggests that circulating angiogenic cells (CACs) promote repair of ischemic tissues. Activation of formyl peptide receptor 2 (Fpr2) has been reported to stimulate repair of ischemic heart. This study was conducted to investigate the role of Fpr2 on CAC mobilization and cardiac protection in myocardial infarction (MI). WKYMVm, a strong agonist for Fpr2, was administered in a murine model of acute MI, and mobilization of CACs including endothelial progenitor cells (CD34+ Flk1+ or Sca1+ Flk1+ cells) in peripheral blood was monitored. CAC mobilization by daily injection of WKYMVm for the first 4 days after MI was as efficient as granulocyte colony-stimulating factor and provided myocardial protection from apoptosis with increased vascular density and preservation of cardiac function. Transplantation of bone marrow (BM) from green fluorescent protein mice showed that BM-derived cells homed to ischemic heart after WKYMVm treatment and contributed to tissue protection. Transplantation of BM from Fpr2 knockout mice showed that Fpr2 in BM cells is critical in mediation of WKYMVm-stimulated myocardial protection and neovascularization after MI. These results suggest that activation of Fpr2 in BM after WKYMVm treatment provides cardiac protection through mobilization of CACs after MI, which may lead to the development of a new clinical protocol for treating patients with ischemic heart conditions. Stem Cells 2017;35:654-665.


Assuntos
Células Progenitoras Endoteliais/citologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Neovascularização Fisiológica , Receptores de Formil Peptídeo/metabolismo , Regeneração , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Cardiotônicos/farmacologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Testes de Função Cardíaca , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Regeneração/efeitos dos fármacos
15.
Oncotarget ; 8(23): 37807-37816, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-27906676

RESUMO

The prognostic significance of pelvic and para-aortic lymphadenectomy during primary debulking surgery for advanced-stage ovarian cancer remains unclear. This study aimed to evaluate the survival impact of lymph node dissection (LND) in patients treated with optimal cytoreduction for advanced ovarian cancer. Data from 158 consecutive patients with stage IIIC-IV disease who underwent optimal cytoreduction (<1 cm) were obtained via retrospective chart review. Patients were classified into two groups: (1) lymph node sampling (LNS), node count <20; and (2) LND, node count ≥20. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Among the included patients, 96 and 62 patients underwent LND and LNS as primary debulking surgery, respectively. There were no differences in the extent of debulking surgical procedures, including extensive upper abdominal surgery, between the groups. Patients who underwent LND had a marginally significantly improved PFS (P = 0.059) and significantly improved OS (P < 0.001) compared with those who underwent LNS. In a subgroup with negative lymphadenopathy on preoperative computed tomography scans, revealed LND correlated with a better PFS and OS (P = 0.042, 0.001, respectively). Follow-ups of subsequent recurrences observed a significantly lower nodal recurrence rate among patients who underwent LND. A multivariate analysis identified LND as an independent prognostic factor for PFS (hazard ratio [HR], 0.629; 95% confidence interval [CI], 0.400-0.989) and OS (HR, 0.250; 95% CI, 0.137-0.456). In conclusion, systematic LND might have therapeutic value and improve prognosis for patients with optimally cytoreduced advanced ovarian cancer.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Excisão de Linfonodo/métodos , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico
16.
Clin Nucl Med ; 41(9): 677-82, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27276204

RESUMO

PURPOSE: To investigate whether the ratio of SUVs measured with F-FDG PET/CT between pretreatment and posttreatment has prognostic value in patients with locally advanced cervical cancer treated with primary chemoradiation therapy. METHODS: Cases of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics stages IB1 to IVA) treated with a nonsurgical curative modality (172 cases including chemoradiation or radiation therapy) were reviewed. F-FDG PET/CT parameters, including SUVmax and SUVmean, were evaluated by F-FDG PET/CT performed prior to treatment and 6 weeks after the end of treatment. Metabolic response was evaluated according to the European Organization for Research and Treatment of Cancer guidelines and was compared with radiologic response measured according to the Response Evaluation Criteria In Solid Tumours (RECIST). RESULTS: In total, 142 patients receiving chemoradiation showed radiologic responses (median 56% decrease in maximal diameter), whereas 160 and 146 patients showed metabolic responses measured with SUVmax and SUVmean, respectively (73% decrease in SUVmax; 48% decrease in SUVmean). Radiologic response and metabolic response were significantly correlated for SUVmax and SUVmean (P = 0.0009; P = 0.0457, respectively). Kaplan-Meier analysis revealed significant differences in overall survival and progression-free survival between the responder and nonresponder groups, based on the European Organization for Research and Treatment of Cancer criteria (both P < 0.001), whereas no significant difference was found when using RECIST criteria (P = 0.058, P = 0.088, respectively). CONCLUSIONS: F-FDG PET/CT parameters are good prognostic markers for the response of cervical cancer patients to concurrent chemoradiation therapy, as compared with the RECIST criteria.


Assuntos
Quimiorradioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Análise de Regressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias do Colo do Útero/metabolismo
17.
PLoS One ; 10(7): e0131785, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26148001

RESUMO

Endothelial progenitor cells (EPCs) can be isolated from human bone marrow or peripheral blood and reportedly contribute to neovascularization. Aptamers are 40-120-mer nucleotides that bind to a specific target molecule, as antibodies do. To utilize apatmers for isolation of EPCs, in the present study, we successfully generated aptamers that recognize human CD31, an endothelial cell marker. CD31 aptamers bound to human umbilical cord blood-derived EPCs and showed specific interaction with human CD31, but not with mouse CD31. However, CD31 aptamers showed non-specific interaction with CD31-negative 293FT cells and addition of polyanionic competitor dextran sulfate eliminated non-specific interaction without affecting cell viability. From the mixture of EPCs and 293FT cells, CD31 aptamers successfully isolated EPCs with 97.6% purity and 94.2% yield, comparable to those from antibody isolation. In addition, isolated EPCs were decoupled from CD31 aptamers with a brief treatment of high concentration dextran sulfate. EPCs isolated with CD31 aptamers and subsequently decoupled from CD31 aptamers were functional and enhanced the restoration of blood flow when transplanted into a murine hindlimb ischemia model. In this study, we demonstrated isolation of foreign material-free EPCs, which can be utilized as a universal protocol in preparation of cells for therapeutic transplantation.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Células Progenitoras Endoteliais/fisiologia , Isquemia/terapia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Animais , Anticorpos/imunologia , Diferenciação Celular/fisiologia , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Células HEK293 , Membro Posterior/irrigação sanguínea , Membro Posterior/metabolismo , Membro Posterior/fisiologia , Humanos , Isquemia/metabolismo , Camundongos , Neovascularização Fisiológica/fisiologia , Transplante de Células-Tronco/métodos
18.
Wound Repair Regen ; 23(4): 575-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25973651

RESUMO

Diabetes is one of the most common human diseases and 15% of the 200 million diabetics worldwide suffer from diabetic wounds. Development of new therapeutic agents is needed for treatment of diabetic wounds. Wound healing is mediated by multiple steps, including inflammation, epithelialization, neoangiogenesis, and granulation. Formyl peptide receptor 2 has been known to stimulate angiogenesis, which is essential for tissue repair and cutaneous wound healing. In this study, we explored the therapeutic effects of WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2), a synthetic peptide agonist of formyl peptide receptor 2, on cutaneous wounds in streptozotocin-induced diabetic rats. Topical application of WKYMVm onto cutaneous wounds stimulated formation of von Willebrand factor-positive capillary and α-smooth muscle actin-positive arteriole with a maximal stimulation on day 6, suggesting WKYMVm-stimulated angiogenesis. Infiltration of immune cells could be detected on early phase during wound healing and WKYMVm treatment acutely augmented infiltration of CD68-positive macrophages. In addition, reepithelialization and granulation tissue formation were accelerated by treatment with WKYMVm. These results suggest that WKYMVm has therapeutic effects on diabetic wounds by stimulating angiogenesis and infiltration of immune cells.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Receptores de Formil Peptídeo/agonistas , Úlcera Cutânea/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Fatores Quimiotáticos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/patologia , Úlcera Cutânea/etiologia , Úlcera Cutânea/metabolismo , Resultado do Tratamento
19.
Obstet Gynecol Sci ; 57(5): 386-92, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25264529

RESUMO

OBJECTIVE: The purpose of this study was to compare clinical and surgical outcomes between laparo-endoscopic single-site (LESS) surgery and traditional multiport laparoscopic (TML) surgery for treatment of adnexal tumors. METHODS: Medical records were reviewed for patients undergoing surgery for benign adnexal tumors between January 2008 and April 2012 at our institution. All procedures were performed by the same surgeon. Clinical and surgical outcomes for patients undergoing LESS surgery using Glove port were compared with those patients undergoing TML surgery. RESULTS: A review of 129 patient cases undergoing LESS surgery using Glove port and 100 patient cases undergoing TML surgery revealed no significant differences in the baseline characteristics of the two groups. The median operative time was shorter in the LESS group using Glove port at 44 minutes (range, 19-126 minutes) than the TML group at 49 minutes (range, 20-196 minutes) (P=0.0007). There were no significant differences between in the duration of postoperative hospital stay, change in hemoglobin levels, pain score or the rate of complications between the LESS and TML groups. CONCLUSION: LESS surgery showed comparable clinical and surgical outcomes to TML surgery, and required less operative time. Future prospective trials are warranted to further define the benefits of LESS surgery for adnexal tumor treatment.

20.
J Pediatr ; 165(4): 849-54.e1, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25108543

RESUMO

OBJECTIVE: To investigate the association between serum vitamin D levels, sensitization to food allergens, and the severity of atopic dermatitis in infants. STUDY DESIGN: We investigated serum 25-hydroxyvitamin D (25[OH]D) and specific immunoglobulin E levels to common or suspected food allergens in 226 infants with atopic dermatitis or food allergy. The severity of atopic dermatitis by the Scoring Atopic Dermatitis index and amount of vitamin D intake was measured in subcohort children. Sensitization to food allergen was categorized by the number (non-, mono-, and poly-) of sensitized allergens and the degree (undetected-, low-, and high-level) of sensitization. RESULTS: Significant differences in 25(OH)D levels were found between groups on number (P = .006) and degree (P = .005) of food sensitization. The polysensitization group had significantly lower levels of 25(OH)D than the nonsensitization (P = .001) and monosensitization (P = .023) group. High-level sensitization group had significantly lower 25(OH)D levels compared with undetected (P = .005) and low-level (P = .009) sensitization group. Vitamin D deficiency increased the risk of sensitization to food allergens (OR 5.0; 95% CI 1.8-14.1), especially to milk (OR 10.4; 95% CI 3.3-32.7) and wheat (OR 4.2; 95% CI 1.1-15.8). In addition, the Scoring Atopic Dermatitis index was independently related to 25(OH)D levels after adjusting for the level of sensitization (adjusted R(2) = 0.112, P = .031). CONCLUSIONS: Our results suggest that vitamin D deficiency increases the risk of sensitization to food allergens and that atopic dermatitis may be more severe in infants with vitamin D deficiency.


Assuntos
Alérgenos/imunologia , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Hipersensibilidade Alimentar/imunologia , Vitamina D/sangue , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Dermatite Atópica/etiologia , Meio Ambiente , Feminino , Alimentos , Habitação , Humanos , Hipersensibilidade , Imunoglobulina E/sangue , Lactente , Recém-Nascido , Modelos Lineares , Masculino , República da Coreia , Fatores de Risco , Índice de Gravidade de Doença , Poluição por Fumaça de Tabaco , Vitamina D/análogos & derivados , Deficiência de Vitamina D/imunologia
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