ABSTRACT
ABSTRACT Background: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have long-term effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. Objective: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. Materials and methods: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. Results: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. Conclusion: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis. (REV INVEST CLIN. 2021;73(1):39-51)
Subject(s)
Animals , Rabbits , Calcium-Binding Proteins/therapeutic use , Carcinoma, Squamous Cell/blood supply , Carcinoma, Squamous Cell/therapy , Cell Adhesion Molecules/therapeutic use , Epidermal Growth Factor/therapeutic use , Discoidin Domain/genetics , Calcium-Binding Proteins/genetics , Tumor Cells, Cultured , Genetic Therapy , Cell Adhesion Molecules/genetics , Amino Acid Motifs , Epidermal Growth Factor/genetics , Mice, Nude , Neoplasm Transplantation , Neovascularization, Pathologic/therapyABSTRACT
ABSTRACT Wide-field angiography enables assessing peripheral areas with better quality and gives greater deep focus, which improves the image periphery. Some studies have proposed the usefulness of these angiographic systems in inflammatory diseases of the retina. However, few studies have evaluated this technique in Eales disease. We present a case series in which 5 eyes of 3 patients with Eales disease were evaluated by using retinal fluorescein angiography with 30º, 50º, and 150º lenses in a laser-scanning ophthalmoscope. These cases highlight the usefulness of wide-field fluorescein angiography in the diagnosis and follow-up of peripheral ischemic retinal areas in Eales disease, which enables better follow-up than possible with conventional fluorescein angiography images.
RESUMO A angiografia de campo amplo permite avaliar áreas periféricas com melhor qualidade e proporciona maior foco profundo, melhorando a imagem da periferia. Alguns estudos têm proposto a utilidade desses sistemas angiográficos nas doenças inflamatórias da retina. No entanto, poucos estudos avaliaram esta técnica na doença de Eales. Apresentamos uma série de casos em que 5 olhos de 3 pacientes com doença de Eales foram avaliados usando angiografia de fluoresceína da retina com lentes de 30º, 50º e 150º em um oftalmoscópio de varredura a laser. Esses casos destacam a utilidade da angiografia com fluoresceína de campo amplo no diagnóstico e no acompanhamento das áreas isquêmicas periféricas da retina na doença de Eales, permitindo um melhor acompanhamento do o possível com imagens por angiofluoresceinografia convencional.
Subject(s)
Humans , Male , Female , Adult , Young Adult , Fluorescein Angiography/methods , Retinal Vasculitis/diagnostic imaging , Neovascularization, Pathologic/diagnostic imaging , Retina/diagnostic imaging , Time Factors , Visual Acuity , Reproducibility of Results , Follow-Up Studies , Retinal Vasculitis/pathology , Retinal Vasculitis/therapy , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/therapyABSTRACT
Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.
Subject(s)
Animals , Platelet Membrane Glycoproteins/antagonists & inhibitors , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Neoplasms, Experimental/therapy , Combined Modality Therapy/methods , Cell Line, Tumor , Neoplasms, Experimental/pathology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/therapyABSTRACT
No Brasil, 1 milhão de acidentes com queimaduras acontecem por ano e as infecções são responsáveis por 75% dos óbitos nestes pacientes, além de deixar lesões que ocasionam deformidades nas áreas atingidas. Sendo assim, o objetivo deste trabalho é fornecer uma visão atual sobre células-tronco mesenquimais (MSCs), com ênfase nas células-tronco derivadas do tecido adiposo (ADSCs), associadas a gel de plasma, gel de fibrina e membranas (scaffold). O uso de géis e membranas tendem a auxiliar o crescimento celular visando sua possível aplicação na Cirurgia Plástica Reparadora para o tratamento pacientes queimados ou que necessitam de enxerto de pele. O presente trabalho abordou de forma exploratória e narrativa o tema células-tronco mesenquimais, células-tronco mesenquimais derivadas do tecido adiposo, gel de fibrina, gel de plasma e scaffold. O tipo de pesquisa empregada foi conduzido com coleta de informações utilizando-se a Biblioteca Virtual em Saúde (BVS) e PubMed. O número absoluto de artigos publicados relacionados ao tratamento de queimaduras é considerável. Até o momento, a quantidade de pesquisas relacionadas à terapia com células-tronco derivadas do tecido adiposo, gel de fibrina, gel de plasma e scaffold para o tratamento de queimaduras apresenta-se escassa. O autoenxerto de ADSCs associado a biocurativos torna-se uma perspectiva promissora na Cirurgia Plástica Reparadora para o tratamento e recuperação de pacientes que sofreram queimaduras ou outros acidentes que necessitam de enxerto de pele. Estes recursos podem reduzir a dor e prover a dessecação da lesão, promovendo neovascularização e a reepitelização da ferida.
In Brazil, 1 million burn accidents occur annually, and subsequent wound infections account for 75% cases of deaths among these patients, in addition to inducing deformities in the affected areas. Therefore, the aim of this study was to discuss the current status of mesenchymal stem cells, with an emphasis on adipose-derived stem cells (ADSCs), in combination with plasma gel, glue fibrin, and membranes (scaffold). The use of gels and membranes supports cell growth, and aims at potential application in reconstructive plastic surgery for the treatment of burn patients or individuals requiring skin grafts. This study explores and discusses the role of mesenchymal stem cells, adipose-derived mesenchymal stem cells, glue fibrin, plasma gel, and the scaffold. This research collected information from the Virtual Health Library (VHL) and PubMed. A considerable number of articles have been published on burn treatment. However, there is little research on burn treatment with ADSCs, glue fibrin, plasma gel, and scaffold. An ADSC autograft combined with a biological dressing is promising in reconstructive plastic surgery for the treatment and recovery of burn patients or individuals with other injuries that require skin grafts. These features can reduce pain and aid in drying of the lesion, thus promoting neovascularization and wound reepithelialization.
Subject(s)
Humans , History, 21st Century , Skin , Transplantation, Autologous , Bioprosthesis , Burns , Cell Membrane , Review , Plastic Surgery Procedures , Mesenchymal Stem Cells , Gels , Skin/injuries , Transplantation, Autologous/methods , Bioprosthesis/adverse effects , Bioprosthesis/standards , Burns/surgery , Burns/complications , Cell Membrane/pathology , Cell Membrane/transplantation , Adipose Tissue , Adipose Tissue/surgery , Adipose Tissue/injuries , Plastic Surgery Procedures/methods , Mesenchymal Stem Cells/pathology , Gels/adverse effects , Gels/therapeutic use , Neovascularization, Pathologic , Neovascularization, Pathologic/surgery , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/therapyABSTRACT
In order to investigate signal transduction and activation of transcription 3 (STAT3) signaling on angiogenesis in colorectal carcinoma (CRC) after inhibiting STAT3 expression, we constructed the HT-29-shSTAT3 cell line by lentivirus-mediated RNAi. Cell growth was assessed with MTT and the cell cycle distribution by flow cytometry. CRC nude mouse models were established and tumor growth was monitored periodically. On day 30, all mice were killed and tumor tissues were removed. Microvessel density (MVD) was determined according to CD34-positive staining. The expression of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP2) and basic fibroblast growth factor (FGF2) was monitored by quantitative real-time PCR and Western blot analysis. Knockdown of STAT3 expression significantly inhibited cell growth in HT-29 cells, with a significantly higher proportion of cells at G0/G1 (P < 0.01). Consistently, in vivo data also demonstrated that tumor growth was significantly inhibited in mice injected with HT-29-shSTAT3 cells. MVD was 9.80 ± 3.02 in the HT-29-shSTAT3 group, significantly less than that of the control group (P < 0.01). mRNA and protein levels of VEGFA and MMP2 in the HT-29-shSTAT3 group were significantly lower than in the control group (P < 0.05), but no significant difference was observed in the mRNA or protein level of FGF2 (P > 0.05). Taken together, these results demonstrate that STAT3 signaling is important to the growth of CRC and promotes angiogenesis by regulating VEGFA and MMP2 expression.
Subject(s)
Animals , Female , Humans , Mice , Colorectal Neoplasms/blood supply , Neovascularization, Pathologic/therapy , RNA, Small Interfering/genetics , /antagonists & inhibitors , Cell Proliferation , Mice, Inbred BALB C , Mice, Nude , Real-Time Polymerase Chain Reaction , /geneticsABSTRACT
El carcinoma de células renales es responsable del 80 al 85 por cien de todas las neoplasias renales y su diagnóstico trae consigo la necesidad de intervención oportuna por las altas tasas de morbimortalidad relacionadas con esta patología. Es conocida la posibilidad de curación con el tratamiento quirúrgico cuando la enfermedad está organoconfinada, sin embargo, en un porcentaje no despreciable de pacientes aún con este tipo de intervención pueden desarrollar metástasis o recaídas posteriores a la cirugía. El desarrollo de nuevas estrategias terapéuticas enfocadas al manejo fisiopatológico de esta enfermedad comienza a demostrar en medianos plazos respuestas que son alentadoras y que se han constituido en la herramienta terapéutica más adecuada posterior al manejo quirúrgico citorreductor. Está por definirse el papel de las terapias blanco como alternativas neoadyuvantes.
Subject(s)
Humans , Vascular Endothelial Growth Factor Receptor-1 , Carcinoma, Renal Cell/therapy , Angiogenesis Inhibitors/therapeutic use , Kidney Neoplasms/therapy , Neovascularization, Pathologic/therapyABSTRACT
Se trataron con infiltración intralesional de interferón Ó 2b, 10 lesiones en los miembros inferiores en seis pacientes con angiosarcoma de Kaposi clásico. Las lesiones menores de 2 cm de diámetro fueron tratadas con 3 MUI y las mayores con 5 MUI, en todos los casos tres veces por semana, día por medio. La dosis media efectiva intralesional de INF Ó 2b fue de 134,4 MUI para los tumores nodulares y de 66,2 MUI para las placas y máculas, aplicadas en una media de tiempo de 15,9 y 13,6 semanas respectivamente. La dosis total media de INF fue de 100,3 MUI, en una media total de tiempo aplicado de 14,75 semanas, y mostrando un efecto antitumoral medio del 81 por ciento de las lesiones tratadas. En cinco tumores se observó resolución completa y en las restantes cinco lesiones hubo una resolución parcial del 80 al 90 por ciento, lo que facilitaría emplear un tratamiento coadyuvante posterior de limpieza quirúrgica y crioterapia. Con las dosis utilizadas, todos los pacientes pudieron concretar el tratamiento sin complicaciones y buena tolerancia, a corto plazo; los tumores no tratados disminuyeron su tamaño entre un 30-50 por ciento, manteniendo estable el progreso de la enfermedad mientras duraba éste tratamiento. Por lo tanto creemos que ésta modalidad terapéutica puede ser un tratamiento de elección en el ASK clásico, con múltiples lesiones y/o extendido, o compromiso visceral, y que una vez controlada la enfermedad, una terapia a largo plazo podría estabilizar ésta patología multicéntrica, a demostrar en futuros trabajos, experiencia que estamos desarrollando
Subject(s)
Humans , Male , Aged , Interferon-alpha , Sarcoma, Kaposi , Hemangiosarcoma , Injections, Intralesional , Interferon-alpha , Interferons , Neovascularization, Pathologic/therapy , Treatment OutcomeABSTRACT
We studied the effect of topical and systemic hybrid recombinant human interferon [rHuINF] apha A/D on corneal vascularization following an alkali burn with 1.0% sodium hydroxide. Thirty-six long-Evans male rats were divided randomly into two groups. In Group A [24 rats], 12 received one drop [60 000 U per drop] of rHuIFN alpha A/D four times per 5 day for 5 days; 12 control eyes received saline drops. In Group B [12 rats], six rats were given rHuIFN alpha A/D in a subcutaneous injection [3 000 000 U per m2 of skin surface] on alternate days for 3 weeks; the other six rats were used as controls. Eyes were examined by penlight and biomicroscopy. In Group A, ten treated eyes developed corneal vascularization compared with eight eyes in the control group. In Group B, two eyes in the treated group developed corneal vascularization compared with three eyes in the control group. There was no statistically significant difference [P > 0.1] in Group A or Group B between the treated group and the control group. We were unable to prevent corneal vascularization with topical or systemic rHuIFN alpha A/D in injured rat eyes
Subject(s)
Animals, Laboratory , Interferon alpha-2 , Cytokines , Neovascularization, Pathologic/therapyABSTRACT
O surgimento de membranas neo-vasculares sub-retinianas é considerado atualmente como um processo causado pelo afastamento do epitelio pigmentar da membrana de Bruch secundário à formaçäo de drusas ou outras patologias. O reconhecimento clínico destas membranas se faz com a biomicroscopia e com a angiofluoresceinografia. O tratamento convencional é feito pela fotocoagulaçäo com laser de argonio ou kriptonio. Recentemente tem se experimentado o tratamento cirúrgico através da remoçäo mecânica destas membranas