Chitinase 3-like 1 secreted from cancer-associated fibroblasts promotes tumor angiogenesis via interleukin-8 secretion in colorectal cancer.

The cancer­stromal interaction has been demonstrated to promote tumor progression, and cancer-associated fibroblasts (CAFs), which are the main components of stromal cells, have attracted attention as novel treatment targets. Chitinase 3-like 1 (CHI3L1) is a chitinase-like protein, which affects cell proliferation and angiogenesis. However, the mechanisms through which cells secrete CHI3L1 and through which CHI3L1 mediates tumor progression in the cancer microenvironment are still unclear. Accordingly, the present study assessed the secretion of CHI3L1 in the microenvironment of colorectal cancer and evaluated how CHI3L1 affects tumor angiogenesis. CAFs and normal fibroblasts (NFs) established from colorectal cancer tissue, and human colon cancer cell lines were evaluated using immunostaining, cytokine antibody array, RNA interference, reverse transcription-quantitative PCR (RT-qPCR), ELISA, western blotting and angiogenesis assays. The expression and secretion of CHI3L1 in CAFs were stronger than those in NFs and colorectal cancer cell lines. In addition, interleukin-13 receptor α2 (IL-13Rα2), a receptor for CHI3L1, was not expressed in colorectal cancer cell lines, but was expressed in fibroblasts, particularly CAFs. Furthermore, the expression and secretion of IL-8 in CAFs was stronger than that in NFs and cancer cell lines, and recombinant CHI3L1 addition increased IL-8 expression in CAFs, whereas knockdown of CHI3L1 suppressed IL-8 expression. Furthermore, IL-13Rα2 knockdown suppressed the enhancement of IL-8 expression induced by CHI3L1 treatment in CAFs. For vascular endothelial growth factor-A (VEGFA), similar results to IL-8 were observed in an ELISA for comparison of secretion between CAFs and NFs and for changes in secretion after CHI3L1 treatment in CAFs; however, no significant differences were observed for changes in expression after CHI3L1 treatment or IL-13Rα2 knockdown in CAFs assessed using RT-qPCR assays. Angiogenesis assays revealed that tube formation in vascular endothelial cells was suppressed by conditioned medium from CAFs with the addition of human CHI3L1 neutralizing antibodies compared with control IgG, and also suppressed by conditioned medium from CAFs transfected with CHI3L1, IL-8 or VEGFA small interfering RNA compared with negative control small interfering RNA. Overall, the present findings indicated that CHI3L1 secreted from CAFs acted on CAFs to increase the secretion of IL-8, thereby affecting tumor angiogenesis in colorectal cancer.

The vasculature: a therapeutic target in heart failure?

It is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.

Participação dos neutrófilos durante a implantação embrionária no desenvolvimento da placenta em camundongos / Participation of neutrophils during embryonic implantation in the placental development in mice

A implantação do embrião na parede uterina é um processo complexo que consiste na interação do blastocisto com as células epiteliais do útero, e depende de diferentes tipos celulares do microambiente uterino. Embora a literatura mostre a participação de neutrófilos neste processo, os dados ainda são incipientes para proposição da função exata destas células nos períodos iniciais da gestação. Dados do nosso grupo de pesquisa mostraram que neutrófilos pró-angiogênicos induzem a tolerância gestacional, e que a depleção de neutrófilos durante as fases iniciais da gestação prejudica a implantação do blastocisto e a progressão da gestação. Com base nestes resultados, o presente estudo visou investigar se a depleção de neutrófilos na fase pré-receptiva da janela de implantação do blastocisto altera a morfologia placentária. Para tanto, foi utilizado o modelo de gestação alogênica, onde camundongos fêmeas C57BL/6, após cruzamento com machos Balb/C foram tratadas com anticorpo anti-Ly6G ou isotipo no dia 1,5 da gestação (24 horas após a detecção do plug vaginal) em dose suficiente para manter a depleção de neutrófilos circulantes por 48 horas (200µg/ 500µL; i.p). No final da gestação (dia 18,5), o sangue periférico foi coletado e, em seguida, os animais foram submetidos a laparotomia para retirada da placenta, a qual foi submetida à análise histológica. As análises dos leucócitos circulantes evidenciaram a efetividade do tratamento para depleção de neutrófilos periféricos. A análise histológica mostrou alterações significativas na morfologia da placenta nos animais tratados com anti-Ly6G. Foram detectadas a redução da zona juncional, de células trofoblásticas e de fatores angiogênicos, como fator de crescimento do endotélio vascular (VEGF), e das moléculas de adesão intracelular-1 (ICAM-1) e de plaqueta e endotélio (PECAM-1). Esses dados evidenciam a importância dos neutrófilos nos primeiros dias de gestação para o desenvolvimento da placenta

Blastocyst implantation is a complex process, consisting of the interaction between blastocyst and uterine epithelial cells. Also, it is well known that the implantation site resembles an inflammatory response, with a profusion of recruited immune cells into the endometrial stroma and lumen from the blood. The role of macrophages, natural killers, and dendritic cells have been extensively studied, however, the participation of neutrophils in this process remains unclear. Data from our research group showed that pro-angiogenic neutrophils induced gestation tolerance, also peripheral neutrophils depletion at the time of active placental development led to smaller embryo sizes and abnormal placentation in mice. In this context, the present study aimed to investigate whether pharmacological depletion of neutrophils in mice in the blastocyst implantation phase alters placental morphology. Therefore, C7/BL/6 female mice, after mating with Balb/C males, were treated with an anti-Ly6G antibody or isotype on day 1 of gestation (after detection of the vaginal plug) at a dose sufficient to maintain the depletion of circulating neutrophils for 48 hours (200 µg/500µL; i.p). At the end of the gestational day (day 18), peripheral blood was collected, and then the animals were submitted to laparotomy for the placenta removal and subsequent histological analysis. The analysis of circulating leukocytes from neutrophils depleted mice showed a reduction of peripheral neutrophils up to 48 hours after antibody injection. The histological analysis showed significant alterations in the placenta morphology of the animals treated with anti-Ly6G. The morphometric analyses showed a reduction in the size of neutrophils depleted placenta due to diminished junctional zone and reduction of trophoblast cells. Also, it was observed a reduction of vascular endothelial growth factors (VEGF), reduction of adhesion molecules intracell-1 (ICAM-1), and platelets and endothelium (PECAM-1) positive cells in the junctional zone. In conclusion, these data show the importance of neutrophils on the first days of pregnancy for the development of the placenta

Formación atípica de agujero macular después de terapia Anti-VEGF para la degeneración macular asociada a la edad: ¿coincidencia o consecuencia? / Atypical macular hole formation after Anti-VEGF therapy for neovascular age-related macular degeneration: Coincidence or consequence?

Introducción y objetivos La degeneración macular asociada con la edad (DMAE) es la causa primaria de ceguera en los países desarrollados, especialmente en adultos mayores. Actualmente, la inyección intravítrea del factor de crecimiento endotelial vascular (VEGF) es el tratamiento estándar para la forma neovascular de la DMAE. Existen pocos estudios que informen sobre la creación de un agujero macular (AM) después de un tratamiento anti-VEGF, y la patogénesis exacta de AM permanece en debate. El presente estudio tiene por objetivo analizar las características clínicas de los ojos que desarrollan AM después de recibir terapia anti-VEGF para la DMAE neovascular. Materiales y métodos Los pacientes fueron tratados con agentes anti-VEGF intravítreos durante al menos un año, permaneciendo estables por, al menos, seis meses. Se evaluaron la mejor agudeza visual corregida (MAVC) y los hallazgos de tomografía de coherencia óptica. Resultado Se incluyeron en el estudio 19 ojos de 18 pacientes. La edad media de los mismos fue de 77,7 años en la primera visita. Ocho eran de sexo femenino. El número medio de inyecciones antes de la formación de un AM fue de cuatro. El AM se desarrolló después de un seguimiento medio de 5,1 meses desde la última inyección. Dieciséis ojos (84,2%) exhibieron membrana coroidal neovascular sin tracción vitreomacular anormal. Once ojos (57,8%) mostraron desprendimiento del epitelio pigmentario (DEP) de la retina, dos (10,5%) tuvieron membrana epirretinal (MER) y uno (5,2%) presentó desgarro del epitelio pigmentario de la retina (PER). La media de la MAVC fue de 1,07 ± 0,48 LogMAR (0,3 a 1,8) y 1,16 ± 0,38 logMAR (0,4 a 1,8), respectivamente (AU)

Introduction and objectives Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries, particularly in older adults. Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection is the current standard treatment for neovascular form of AMD. Studies reporting macular hole (MH) formation following anti-VEGF treatment are limited, and the exact pathogenesis is still under discussion. With the present study, we aim to analyse the clinical features of eyes developing MH after anti-VEGF therapy for neovascular AMD. Materials and methods Patients were treated with intravitreal anti-VEGF agents for at least one year and stable for at least six months. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. Results Nineteen eyes of 18 patients were included in this study. Patients had an average age of 77.7 years at first visit and eight were female. The average number of injections before the MH formation was four. MH developed after a mean follow-up of 5.1 months after the last injection. Sixteen eyes had (84.2%) had choroidal neovascular membrane without any abnormal vitreomacular traction. Eleven eyes (57.8%) had retinal pigment epithelium detachment (PED), two (10.5%) had an epiretinal membrane (ERM), and one (5.2%) had retinal pigment epithelium (RPE) tear. The mean first and last BCVA was 1.07 ± 0.48 LogMAR (0.3-1.8) and 1.16 ± 0.38 logMAR (0.4-1.8), respectively. Conclusions A macular hole can be observed in AMD patients receiving anti-VEGF therapy. Increased fibrovascular scar tissue due to subretinal fluid resolution, neovascular membrane contraction, and the presence of PED, RPE tear, and ERM may contribute to MH formation (AU)

MACULAR HOLE FORMATION FOLLOWED BY SPONTANEOUS CLOSURE AFTER PNEUMATIC RETINOPEXY IN A PATIENT WITH DIABETIC MACULAR EDEMA.

PURPOSE: To report early formation and spontaneous closure of a full-thickness macular hole that developed after successful pneumatic retinopexy in a patient who had been undergoing treatment for diabetic macular edema. METHODS: Case report of a 68-year-old man with bilateral nonproliferative diabetic retinopathy who was currently undergoing anti-vascular endothelial growth factor treatment for bilateral diabetic macular edema. RESULTS: On presentation, visual acuity was 20/200 in the left eye, and examination revealed a bullous, macula-off retinal detachment with a single horseshoe tear at 12 o'clock in the left eye. Pneumatic retinopexy was performed followed by laser augmentation 3 days later. Three weeks postoperatively, he returned with visual acuity of 20/50 and a full-thickness macular hole in the left eye. Although he elected for initial observation, he returned 2 weeks later with visual acuity of 20/50 in both eyes and a retinal detachment with a single break at 10 o'clock in the right eye. The macular hole in the left eye had spontaneously resolved. Pneumatic retinopexy was performed to the right eye. Over 1 year after bilateral pneumatic retinopexy, his retina remains without recurrence of a macular hole in the left eye. CONCLUSION: In the early postoperative period after pneumatic retinopexy to repair a retinal detachment, a macular hole can form and spontaneously close.

Microchannel network hydrogel induced ischemic blood perfusion connection.

Angiogenesis induction into damaged sites has long been an unresolved issue. Local treatment with pro-angiogenic molecules has been the most common approach. However, this approach has critical side effects including inflammatory coupling, tumorous vascular activation, and off-target circulation. Here, the concept that a structure can guide desirable biological function is applied to physically engineer three-dimensional channel networks in implant sites, without any therapeutic treatment. Microchannel networks are generated in a gelatin hydrogel to overcome the diffusion limit of nutrients and oxygen three-dimensionally. Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect is guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. Multiple-site implantation reveals hypoxia and neighboring vessels as major causative factors of the beneficial function. This technique may contribute to the development of therapeutics for hypoxia/inflammatory-related diseases.

Review of the Current Basic Science Strategies to Treat Critical Limb Ischemia.

Critical limb ischemia (CLI) is a highly morbid disease with many patients considered poor surgical candidates. The lack of treatment options for CLI has driven interest in developing molecular therapies within recent years. Through these translational medicine studies in CLI, much has been learned about the pathophysiology of the disease. Here, we present an overview of the macrovascular and microvascular changes that lead to the development of CLI, including impairment of angiogenesis, vasculogenesis, and arteriogenesis. We summarize the randomized clinical controlled trials that have used molecular therapies in CLI, and discuss the novel imaging modalities being developed to assess the efficacy of these therapies.

Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives.

OBJECTIVES: Adenosine concentration significantly increases in tumour microenvironment contributing to tumorigenic processes including cell proliferation, survival, invasion and of special interest in this review angiogenesis. KEY FINDINGS: This review summarizes the role of pharmacological adenosine receptor agonist and antagonist in regulating angiogenesis for a better understanding and hence a better management of angiogenesis-associated disorders. SUMMARY: Depending upon the pharmacological characteristics of adenosine receptor subtypes, adenosine elicits anti- or pro-angiogenic responses in stimulated cells. Inhibition of the stimulatory effect of adenosine signalling on angiogenesis using specific pharmacological adenosine receptor agonist, and antagonist is a potentially novel strategy to suppress angiogenesis in tumours.

Angiogenic Growth Factors for Coronary Artery Disease: Current Status and Prospects.

Although there have been advances in coronary artery bypass grafting and percutaneous coronary intervention, some patients who have ischemic coronary artery disease (CAD) are ineligible for revascularization due to suboptimal anatomy. Cardiac angiogenesis is not only a physiological response to ischemia or hypoxia but also a potential target of therapeutic strategies. Preclinical studies have shown a great enthusiasm on therapeutic angiogenesis for ischemic CAD. However, the latest trials provided the limited evidence on its efficacy. This article aims to discuss the physiological process of angiogenesis, the characteristic of angiogenic growth factors, delivery system, and clinical and preclinical studies, which can provide a novel insight into the therapeutic angiogenesis for CAD.

Chronic limb-threatening ischemia could benefit from growth hormone therapy for wound healing and limb salvage.

Revascularization for chronic limb-threatening ischemia (CLTI) is necessary to alleviate symptoms and wound healing. When it fails or is not possible, there are few alternatives to avoid limb amputation in these patients. Although experimental studies with stem cells and growth factors have shown promise, clinical trials have demonstrated inconsistent results because CLTI patients generally need arteriogenesis rather than angiogenesis. Moreover, in addition to the perfusion of the limb, there is the need to improve the neuropathic response for wound healing, especially in diabetic patients. Growth hormone (GH) is a pleiotropic hormone capable of boosting the aforementioned processes and adds special benefits for the redox balance. This hormone has the potential to mitigate symptoms in ischemic patients with no other options and improves the cardiovascular complications associated with the disease. Here, we discuss the pros and cons of using GH in such patients, focus on its effects on peripheral arteries, and analyze the possible benefits of treating CLTI with this hormone.

Novel molecular targets for coronary angiogenesis and ischemic heart disease.

Coronary artery disease (CAD) is the number one cause of death among men and women in the USA. Genetic predisposition and environmental factors lead to the development of atherosclerotic plaques in the vessel walls of the coronary arteries, resulting in decreased myocardial perfusion. Treatment includes a combination of revascularization procedures and medical therapy. Because of the high surgical risk of many of the patients undergoing revascularization procedures, medical therapies to reduce ischemic disease are an area of active research. Small molecule, cytokine, endothelial progenitor cell, stem cell, gene, and mechanical therapies show promise in increasing the collateral growth of blood vessels, thereby reducing myocardial ischemia.

Orthodontic tensile strain induces angiogenesis via type IV collagen degradation by matrix metalloproteinase-12.

BACKGROUND AND OBJECTIVE: During orthodontic tooth movement (OTM), periodontal ligament (PDL) is remodeled dynamically, which requires sufficient blood supply for the regeneration of PDL. However, little is known about the remodeling of blood vessels during OTM. In this study, we hypothesized that the orthodontic tensile strain upregulates matrix metalloproteinase-12 (MMP-12) expression in the tension zone and induces angiogenesis via degradation of type IV collagen (Col-IV) in vascular endothelial basement membrane during the early stage of OTM. MATERIAL AND METHODS: Temporal and spatial MMP-12 expression in the tension zone of PDL, during the early stage of OTM, were examined by immunohistochemistry in rats. Continuous tensile strain was applied to cultured human immortalized PDL cell lines (HPL cells) and MMP-12 expression was examined in vitro. Colocalization of MMP-12 and Col-IV in vivo were examined by immunohistochemistry. To investigate whether MMP-12 produced by HPL cells could degrade Col-IV, recombinant Col-IV was incubated in the culture supernatants of HPL cells. Intact Col-IV in vitro was also examined by western blot analysis. Finally, the changes in blood vessels in the PDL were examined by micro-computed tomography analysis with perfused contrast agents and by conventional histological analysis. RESULTS: Orthodontic tensile strain induced MMP-12 expression in PDL cells in vivo and in vitro. Immunohistochemistry revealed that MMP-12-positive cells were observed adjacent to the Col-IV-positive tubular area in the tension zone of PDL. MMP-12 in culture supernatant of HPL cells degraded recombinant Col-IV, and specific MMP-12 inhibitor blocked the Col-IV degradation. Micro-computed tomography analysis and conventional histological analysis demonstrated that the areas of blood vessels were increased in the tension zone of the PDL after OTM. CONCLUSION: We discovered that the orthodontic tensile strain upregulates MMP-12 expression in the tension zone of PDL and induces angiogenesis via degradation of Col-IV in the vascular endothelial basement membrane.

Phytochemicals enhance antioxidant enzyme expression to protect against NSAID-induced oxidative damage of the gastrointestinal mucosa.

The gastrointestinal (GI) mucosa provides the first protective barrier for digested food and xenobiotics, which are easily attacked by toxic substances. Nonsteroidal anti-inflammatory drugs, including aspirin, diclofenac, indomethacin, and ketoprofen, are widely used in clinical medicine, but these drugs may cause oxidative stress, leading to GI damage such as ulcers. Lansoprazol, omeprazole, and other clinical drugs are widely used to treat duodenal and gastric ulcers and have been shown to have multiple biological functions, such as antioxidant activity and the ability to upregulate antioxidant enzymes in vivo. Therefore, the reduction of oxidative stress may be an effective curative strategy for preventing and treating nonsteroidal anti-inflammatory drug induced ulcers of the GI mucosa. Phytochemicals, such as dietary phenolic compounds, phenolic acids, flavan-3-ols, flavonols, flavonoids, gingerols, carotenes, and organosulfur, are common antioxidants in fruits, vegetables, and beverages. A large amount of evidence has demonstrated that natural phytochemicals possess bioactivity and potential health benefits, such as antioxidant, anti-inflammatory, and antibacterial benefits, and they can prevent digestive disease processes. In this review, we summarize the literature on phytochemicals with biological effects, such as angiogenic, antioxidant, antiapoptotic, anti-inflammatory, and antiulceration effects, and their related mechanisms are also discussed.

[A Case of Severe Hematological Toxicity in Response to Pazopanib].

The patient(woman, approximately 46 years old)began pazopanib (PAZ) treatment (800 mg/day)f ollowing the recurrence of retroperitoneal leiomyosarcoma. Prior to treatment, the patient's platelet count was 18.6×10(4)/µl and her neutrophil count was 1.61×10(3)/µl . The platelet count decreased to 9.2×10(4)/µl on day 7 and to 5.4×10(4)/µl on day 21 after commencement of treatment. The neutrophil count was 0.97×10(3)/µl on day 28 and 0.68×10(3)/µl on day 35 after commencement of treatment. Thus, PAZ treatment was stopped on day 35. The blood sampling results on day 42 after commencement of treatment showed that the platelet count was 13.0×10(4)/µl and that the neutrophil count had recovered to 1.28×10(3)/µl . At that time, PAZ treatment was resumed at a reduced dose of 600 mg/day. By day 84 after commencement of treatment, the platelet count had increased from 12.7 to 13.8×10(4)/µl and the neutrophil count had increased from 1.02 to 1.34×10(3)/µl ; treatment was subsequently continued. The main adverse effects that have been reported for PAZ are hypertension and frequent liver dysfunction; these reports also indicate that the incidence of severe cytopenia(thrombocytopenia, neutropenia)is quite low. However, our patient exhibited cytopenia after commencement of PAZ treatment and her blood cell counts recovered once treatment was ceased, independent of other possible medications. Our findings suggest that cytopenia should be considered as an adverse effect of PAZ.

Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-µg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

Impact of anesthesia on cancer recurrence / Impacto de la anestesia en la recurrencia de cáncer

Surgery remains the mainstay treatment in the majority of solid cancers. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system, inflammation and angiogenesis, and have a direct effect on cancer cells that could ultimately modify oncological outcomes. For instance, volatile anesthetics and opioid analgesics have shown predominantly pro-tumor effects, while propofol, non-steroid anti-inflammatory drugs have mostly anticancer effects. Researchers have been especially interested in investigating the association between the use of regional anesthesia techniques and the postoperative survival of patients with cancers. Since the results of the current retrospective studies are conflicting, several researchers are conducting prospective randomized trials (AU)

Las intervenciones quirúrgicas siguen siendo el tratamiento de elección de muchos tumores solidos. Los anestésicos y analgésicos usados en la actualidad tienen efectos en el sistema inmunológico, inflamatorio y angiogénico de los pacientes así como también en células malignas. Los anestésicos inalatorios y los opiáceos tiene un efecto predominantemente protumoral mientras que los agentes anti-inflamatorios no esteroideos y propofol parecen tener acciones antitumorales. Es por esto que diferentes grupos de investigadores han tratado de estudiar la posible asociación entre el uso de anestésicos y analgésicos con la supervivencia postoperatoria de pacientes oncológicos. Desafortunadamente, los resultados son controvertidos por lo que estudios prospectivos aleatorios controlados se están llevando acabo en diferentes centros (AU)

Expression of IMP3 and IGF2 in giant cell tumor of spine is associated with tumor recurrence and angiogenesis

Purpose. Giant cell tumor (GCT) of bone is a vessel-rich and infiltrative tumor, but the fundamental knowledge of its biological behavior remains unknown now. Methods. In this study, we evaluated the expression levels of Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3), Insulin-like growth factor 2 (IGF2) and CD105 in 38 patients with GCT of spine by Immunohistochemical staining. Additionally, we also analyzed their correlations with clinicopathological factors of giant cell tumor of spine. Results. The results showed that positive expression of IMP3 and IGF2 was tightly related to the tumor extension and local recurrence of GCT (P < 0.05), but it did not indicate any association with patients’ age, gender, tumor location and size. The mean microvessel densities (MVDs) of IMP3 and IGF2 were significantly higher in positive group than negative group (P < 0.05). Moreover, a significant correlation was found between IMP3 and IGF2 expression (r = 0.355, P = 0.029). The log-rank test revealed that local recurrence-free survival time was significantly shorter in the IMP3 positive group (P = 0.004), and the difference in the IGF2 positive group and negative group was also statistically significant (P = 0.008). Conclusion. IMP3 and IGF2 might be potential biomarkers for GCT of spine in regulating the angiogenesis of giant cell tumor of bone and predicting the patients’ prognosis (AU)

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