Predictive potential of dynamic contrast-enhanced MRI and plasma-derived angiogenic factors for response to concurrent chemoradiotherapy in human papillomavirus-negative oropharyngeal cancer.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascularity, which depends on the process of angiogenesis and affects tumour response to treatment. Our study explored the associations between DCE-MRI parameters and the expression of plasma angiogenic factors in human papilloma virus (HPV)-negative oropharyngeal cancer, as well as their predictive value for response to concurrent chemoradiotherapy (cCRT). PATIENTS AND METHODS: Twenty-five patients with locally advanced HPV-negative oropharyngeal carcinoma were prospectively enrolled in the study. DCE-MRI and blood plasma sampling were conducted before cCRT, after receiving a radiation dose of 20 Gy, and after the completion of cCRT. Perfusion parameters ktrans, kep, Ve, initial area under the curve (iAUC) and plasma expression levels of angiogenic factors (vascular endothelial growth factor [VEGF], connective tissue growth factor [CTGF], platelet-derived growth factor [PDGF]-AB, angiogenin [ANG], endostatin [END] and thrombospondin-1 [THBS1]) were measured at each time-point. Patients were stratified into responders and non-responders based on clinical evaluation. Differences and correlations between measures were used to generate prognostic models for response prediction. RESULTS: Higher perfusion parameter ktrans and higher plasma VEGF levels successfully discriminated responders from non-responders across all measured time-points, whereas higher iAUC and higher plasma PDGF-AB levels were also discriminative at selected time points. Using early intra-treatment measurements of ktrans and VEGF, a predictive model was created with cut-off values of 0.259 min-1 for ktrans and 62.5 pg/mL for plasma VEGF. CONCLUSIONS: Early intra-treatment DCE-MRI parameter ktrans and plasma VEGF levels may be valuable early predictors of response to cCRT in HPV-negative oropharyngeal cancer.

Cancer Immunotherapy with "Vascular-Immune" Crosstalk as Entry Point: Associated Mechanisms, Therapeutic Drugs and Nano-Delivery Systems.

Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment ("cold" environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the "cold" microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on "vascular-immune" crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and "cold" TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of "vascular-immune" crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy.

Targeting endothelial cell anergy to improve CAR T cell therapy for solid tumors.

Chimeric antigen receptor (CAR) T cell therapy presents significant results, especially for the treatment of hematologic malignancies. However, there are limitations and challenges to be overcome to achieve similar success for the treatment of solid tumors. These challenges involve selection of the target, infiltration into the tumor microenvironment and maintenance of functionality. The tumor vasculature is a major barrier for leukocytes to enter the tumor parenchyma. Due to the exposure of the vasculature to angiogenic growth factors during tumor progression, the endothelial cells become anergic to inflammatory cytokines, resulting in reduced leukocyte adhesion molecule expression. As such adhesion molecules are a prerequisite for leukocyte extravasation, endothelial cell anergy allows tumors to escape from endogenous immunity, as well as from cellular immunotherapies such as CAR T cells. Hence, overcoming endothelial cell anergy, e.g. through the administration of angiogenesis inhibitors, is believed to restore anti-tumor immunity. Concomitantly, both endogenous immune cells as well as cellular therapeutics such as CAR T cells can permeate into the tumor parenchyma. Here, we discuss how prior or concomitant treatment with an antiangiogenic drug can improve CAR T cell therapy, to become an attractive strategy for the treatment of solid tumors.

Effect of electroacupuncture intervention on angiogenesis in psoriasis mice. / ç”µé’ˆå¯¹é“¶å±‘ç— å°é¼ è¡€ç®¡ç”Ÿæˆçš„å½±å“åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Zusanli"(ST36) and"Xuehai"(SP10) on the angiogenesis of the local injured skin tissue in mice with psoriasis, so as to explore its mechanisms underlying improvement of psoriasis-induced skin lesions. METHODS: A total of 24 female BALB/c mice aged 6-8 weeks were randomly divided into control, model and EA groups, with 8 mice in each group. The psoriasis-like skin lesion model was established by application of 5% imiquimod (IMQ) cream to the mice's back skin, 62.5 mg/d, for 7 days after local depilation, and the mice of the control group received local application of an equal amount of petroleum jelly once a day for 7 days. EA stimulation (2 Hz/100 Hz) was applied to ST36 and SP10 for 30 min, once daily for 7 consecutive days. Photos of the topical injured skin at the back were taken every day, and the severity of psoriasis lesions (psoriasis area and severity index ï¼»PASIï¼½) was scaled. Following H.E. staining, the morphological changes in the injured skin tissue were observed with epidermal thickness analyzed, and the Masson staining was used to observe the proportion of collagen fibers in the injured skin tissues. Immunohistochemical method was used to detect the expression of microvascular markers CD31 and vascular endothelial growth factor (VEGF) and the microvascular density (MVD) was calculated. Western blot was used to detect the expression levels of CD31, VEGF proteins and mitogen activated protein kinases (MAPK) signaling pathway related proteins p38, phosphorylated p38 (p-p38), extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK) and p-JNK in the injured skin tissue. RESULTS: Compared with the control group, the mice in the model group showed an evident increase in the erythema score, scales score, skin thickening score and PASI score, epidermal thickness, proportion of the collagen fibers, MVD value of CD31 and VEGF, and expression levels of CD31 and VEGF proteins, and p-p38/p38, p-ERK/ERK and p-JNK/JNK ratios in the injured skin tissue (P<0.001, P<0.01). In contrast to the model group, the EA group had a significant decrease in the levels of all the indexes mentioned above (P<0.05, P<0.01, P<0.001). CONCLUSIONS: EA intervention can improve the psoriasis-like skin lesions induced by IMQ in mice, which may be related with its functions in down-regulating the expression of angiogenic related factors CD31 and VEGF proteins and MAPK signaling pathway related proteins in the topical injured skin tissue.

Oncolytic Newcastle disease virus carrying the IL24 gene exerts antitumor effects by inhibiting tumor growth and vascular sprouting.

The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.

Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer; angiogenesis and immunosuppression exacerbate GBM progression. COUP-TFII demonstrates pro-angiogenesis activity; however, its role in glioma progression remains unclear. This study revealed that COUP-TFII promotes angiogenesis in gliomas by inducing transdifferentiation of glioma cells into endothelial-like cells. Mechanistic investigation suggested that COUP-TFII as a transcription factor exerts its function via binding to the promoter of TXNIP. Interestingly, COUP-TFII knockdown attenuated tumorigenesis and tumor progression in an immunocompetent mouse model but promoted tumor progression in an immuno-deficient mouse model. As an explanation, repression of COUP-TFII induces cellular senescence and activates immune surveillance in glioma cells in vitro and in vivo. In addition, we used heparin-polyethyleneimine (HPEI) nanoparticles to deliver COUP-TFII shRNA, which regulated tumor angiogenesis and immunosuppression in an in situ GBM mouse model. This study provides a novel strategy and potential therapeutic targets to treat GBM.

Iron Oxide Nanoparticles Engineered Macrophage-Derived Exosomes for Targeted Pathological Angiogenesis Therapy.

Engineering exosomes with nanomaterials usually leads to the damage of exosomal membrane and bioactive molecules. Here, pathological angiogenesis targeting exosomes with magnetic imaging, ferroptosis inducing, and immunotherapeutic properties is fabricated using a simple coincubation method with macrophages being the bioreactor. Extremely small iron oxide nanoparticle (ESIONPs) incorporated exosomes (ESIONPs@EXO) are acquired by sorting the secreted exosomes from M1-polarized macrophages induced by ESIONPs. ESIONPs@EXO suppress pathological angiogenesis in vitro and in vivo without toxicity. Furthermore, ESIONPs@EXO target pathological angiogenesis and exhibit an excellent T1-weighted contrast property for magnetic resonance imaging. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. These findings demonstrate that a pure biological method engineered ESIONPs@EXO using macrophages shows potential for targeted pathological angiogenesis therapy.

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy.

This review focuses on the immunosuppressive effects of tumor angiogenesis and coagulation on the tumor microenvironment (TME). We summarize previous research efforts leveraging these observations and targeting these processes to enhance immunotherapy outcomes. Clinical trials have documented improved outcomes when combining anti-angiogenic agents and immunotherapy. However, their overall survival benefit over conventional therapy remains limited and certain tumors exhibit poor response to anti-angiogenic therapy. Additionally, whilst preclinical studies have shown several components of the tumor coagulome to curb effective anti-tumor immune responses, the clinical studies reporting combinations of anticoagulants with immunotherapies have demonstrated variable treatment outcomes. By reviewing the current state of the literature on this topic, we address the key questions and future directions in the field, the answers of which are crucial for developing effective strategies to reprogram the TME in order to further the field of cancer immunotherapy.

The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism.

Type IIA topoisomerase (TOP2A) is significantly associated with malignant tumor development, invasion, treatment and its prognosis, and has been shown to be a therapeutic target against cancer. In contrast, the role of TOP2A in the immunotherapy of non-small cell lung cancer as well as in Vasculogenic mimicry (VM) formation and its potential mechanisms are unclear. The aim of this study was to investigate the role of TOP2A in proliferation, skeleton regulation, motility and VM production in non-small cell lung cancer and its mechanisms by using bioinformatics tools and molecular biology experiments. Subgroup analysis showed that the low-risk group had a better prognosis, while the high-risk group was positively correlated with high tumor mutational load, M1-type macrophage infiltration, immune checkpoint molecule expression, and immunotherapy efficacy. As confirmed by further clinical specimens, the presence of TOP2A and VM was significantly and positively correlated with poor prognosis. Our study established a model based on significant co-expression of TOP2A genes, which significantly correlated with mutational load and immunotherapy outcomes in patients with non-small cell lung cancer. Further mechanistic exploration suggests that TOP2A plays an important role in immunotherapy and VM formation in NSCLC through upregulation of Wnt3a and PD-L1 expression.

Tumor Radiosensitization by Gene Electrotransfer-Mediated Double Targeting of Tumor Vasculature.

Targeting the tumor vasculature through specific endothelial cell markers involved in different signaling pathways represents a promising tool for tumor radiosensitization. Two prominent targets are endoglin (CD105), a transforming growth factor ß co-receptor, and the melanoma cell adhesion molecule (CD1046), present also on many tumors. In our recent in vitro study, we constructed and evaluated a plasmid for simultaneous silencing of these two targets. In the current study, our aim was to explore the therapeutic potential of gene electrotransfer-mediated delivery of this new plasmid in vivo, and to elucidate the effects of combined therapy with tumor irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice in the syngeneic murine mammary adenocarcinoma tumor model TS/A. Histological analysis of tumors (vascularization, proliferation, hypoxia, necrosis, apoptosis and infiltration of immune cells) was performed to evaluate the therapeutic mechanisms. Additionally, potential activation of the immune response was evaluated by determining the induction of DNA sensor STING and selected pro-inflammatory cytokines using qRT-PCR. The results point to a significant radiosensitization and a good therapeutic potential of this gene therapy approach in an otherwise radioresistant and immunologically cold TS/A tumor model, making it a promising novel treatment modality for a wide range of tumors.

In vitro and in vivo Evidence on Intra-tumor Injection of Allogeneic Serum for Immunotherapy in a Mouse Model of Colon Cancer.

It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor. Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line.  The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory status, we evaluated matrix metalloproteinase-2 (MMP)-2 and 9, vascular endothelial growth factor (VEGF)-A, Cluster of Designation (CD) 31, CD38 and interleukine (IL)-10. An in vitro experiment showed that heat-inactivated C57BL/6 serum had significantly lower cytotoxic effects on BALB/c-derived CT26 cells than intact C57BL/6 serum or BALB/c serum. In vivo experiments revealed that tumor size, HIF-1α, MMP-2, and MMP-9 levels were significantly lower in the experimental group than in the control group. In contrast to control animals, allogeneic serum treatment led to marked reductions in CD31, VEGF-1, CD38, and IL-10 levels. A new approach to serum or plasma therapy and allogeneic vaccines for cancer is intra-tumor injection of allogeneic serum. In light of the ease and availability of allogeneic immunotherapies, allogeneic serum and plasma therapy could potentially be used as an alternative monotherapy or in combination with other therapies.

Transarterial chemoembolization (TACE) plus apatinib vs. TACE alone for hepatocellular carcinoma.

OBJECTIVE: Transarterial chemoembolization (TACE) is a common therapy for hepatocellular carcinoma (HCC), while TACE-induced tumor angiogenesis would increase progression and metastasis risk. Besides, apatinib possesses the capability of inhibiting tumor angiogenesis. Thus, this study aimed to explore the efficacy and safety of TACE plus apatinib compared to TACE alone in HCC patients. METHODS: Ninety-six intermediate-advanced HCC patients were retrospectively enrolled and classified into TACE plus apatinib group (N = 45) and TACE group (N = 51) based on the treatment. RESULTS: Objective response rate (68.9% vs. 47.1%) was increased in TACE plus apatinib group than in TACE group (P = 0.031). However, no difference was found in disease-control rate between groups (95.6% vs. 86.3%) (P = 0.167). Progression-free survival (PFS) (median PFS (95% confidence interval (CI)): 20.0 (13.2-26.8) vs. 14.0 (8.3-19.7) months) was enhanced in TACE plus apatinib group compared with TACE group (P = 0.030), while no difference was found in overall survival between groups (P = 0.060). Additionally, multivariate Cox's analysis presented that TACE plus apatinib (vs. TACE alone) independently associated with prolonged PFS (P = 0.043, hazard ratio = 0.617). Regarding safety profile, no difference in liver function indexes (albumin, total bilirubin, alanine aminotransferase and aspartate aminotransferase) was found after treatment between two groups; meanwhile, only the incidence of hand-foot skin reaction (24.4% vs. 7.8%) was higher in TACE plus apatinib group compared to TACE group (P = 0.025), while no difference was found in other adverse events between two groups (all P > 0.05). CONCLUSION: TACE plus apatinib illustrates a superior efficacy with tolerable safety than TACE alone in intermediate-advanced HCC patients.

Anti-VEGFR2 monoclonal antibody(MSB0254) inhibits angiogenesis and tumor growth by blocking the signaling pathway mediated by VEGFR2 in glioblastoma.

Angiogenesis is a key physiological process that plays a key role in glioblastoma (GBM) progression and displays therapeutic resistance to antiangiogenic therapies. In this study, we aimed to identify whether vascular endothelial growth factor receptor 2(VEGFR2)monoclonal antibodies(mab)could inhibit tumorigenicity and the formation of vascular mimicry (VM) in GBM. The bioinformatic analysis from TCGA, CGGA, and TCPA databases and Immunohistochemistry (IHC) revealed that VEGFR2 is highly expressed in glioma tissues and results in a poor prognosis and is positively associated with VM markers (CD34 and PAS). The anti-VEGFR2 monoclonal antibodies(MSB0254)could inhibit the invasion, migration, and VM formation of U251 and primary glioma cells in vitro. In vivo, MSB0254 (m) could not only inhibit the growth of transplanted tumors of U251 and GL261 cells, but also significantly inhibit the expression of CD34, VEGFR2, Ki67, MMP2, MMP9 and reduce the expression of CD34/PAS and inhibit VM formation. The VEGFR2 monoclonal antibody could inhibit the angiogenesis and tumor growth of GBM by blocking the signaling pathway mediated by VEGFR2. It may become a new supplementary treatment for GBM.

Angiogenesis in diabetic mouse model with critical limb ischemia; cell and gene therapy.

PURPOSE: Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease that diabetes mellitus is one of its major risk factors. MiR-126 as an endothelial cells specific miRNA plays a main role in angiogenesis. The objective of this study was to find a promising treatment by increasing therapeutic potential of adipose tissue mesenchymal stem cells (AT-MSCs) with microRNA-126 in diabetic mouse model with critical limb ischemia. AT-MSCs were isolated from male C57BL/6 mouse and characterized. METHODS: The cells were infected with miR-126 recombinant lentiviral vectors. Diabetes mellitus type 1 was induced and CLI was created in the animals. Animals were divided in different groups to receive PBS, MSCs, miR-126, and MSCmiR-126 and after the experiment, behavioural tests, cell survival, real-time PCR, and histopathological analysis were assessed. RESULTS: The results of function scores, VEGF-A level, and histopathology data demonstrated that the miR-126 treated group was better than PBS and MSCs groups. The expression of PIK3R2 and SPRED1 were decreased in miR-126 group compared to the control group. Our results showed that MSCsmiR-126 can live longer than MSCs in the gastrocnemius muscle. We conclude that mice treated with MSCsmiR-126 in functional tests showed better results and also the expression of VEGF-A and Microvessel density in them were higher than other groups. CONCLUSIONS: This study suggested that AT-MSCs overexpressing miR-126 could be an efficient therapeutic approach for angiogenesis in CLI with diabetes by downregulating SPRED1 and PIK3R2 and increasing secretion of angiogenic cytokines which can prolong the MSC survival.

Relieving immunosuppression by Endo@PLT targeting anti-angiogenesis to improve the efficacy of immunotherapies.

Low levels of immune infiltrates in the tumor milieu hinder the effectiveness of immunotherapy against immune-cold tumors. In the current work, a tumor-targeting drug delivery system composed of Endo-loaded platelets (Endo@PLT) was developed to relieve immunosuppression by achieving tumor vascular normalization. Endo@PLT reprogrammed the immunostimulatory phenotype, achieving excellent PD-1 immunotherapy in vivo.

Tumors resurrect an embryonic vascular program to escape immunity.

Tumors can escape immunity through multiple mechanisms, one of which is by enforcing a state of unresponsiveness of the tumor vasculature to inflammatory cytokines. This results in a lack of adhesiveness of angiogenic endothelial cells for immune cells and thus compromised immunity. This type of escape from immunity, called tumor endothelial cell anergy, is the result of exposure to angiogenic growth factors. Angiogenesis is a hallmark not only of cancer but also of embryonic development. It is assumed that angiogenesis-induced suppression of adhesion molecules is a regulatory function to provide an embryo with immune privileged conditions and allow uninterrupted growth and development. It is becoming clear that similar conditions are used by tumors to evade the immune system and ensure progressive growth. Gaining enhanced insight into these immune-privileged conditions is important as endothelial cell anergy can be overcome by angiogenesis inhibitors, an application that is rapidly emerging as a successful strategy to improve immunotherapy. The literature on endothelial adhesion molecule expression and leukocyte-vessel wall interactions during embryonic and fetal development is sparse, but available data allow the hypothesis that tumors, through angiogenesis, enforce an embryonic-like gene expression program in endothelial cells to suppress leukocyte infiltration and compromise antitumor immunity.

Targeted therapy of angiogenesis using anti-VEGFR2 and anti-NRP-1 nanobodies.

PURPOSE: Targeted therapy in cancer researches is a promising approach that can resolve drawbacks of systematic therapeutics. Nanobodies are potent therapeutics due to their high specificity and affinity to the target. METHODS: In this study, we evaluated the effect of the combination of anti-vascular endothelial growth factor receptor 2 (anti-VEGFR2) and anti-neuropilin-1 (anti-NRP1) nanobodies both in vitro (MTT, and tube formation assay) and in vivo (chick chorioallantoic membrane (CAM), and Nude mice treatment assay). RESULTS: Our results showed that the combination of two nanobodies (anti-VEGFR2/NRP-1 nanobodies) significantly inhibited proliferation as well as tube formation of human endothelial cells effective than a single nanobody. In addition, the mixture of both nanobodies inhibited vascularization of chick chorioallantoic membrane ex ovo CAM assay as compared to a single nanobody. Moreover, the mixture of both nanobodies significantly inhibited tumor growth of the mice (tumor volume and weight) higher than individual nanobodies (P < 0.05). CONCLUSION: Our results offer a promising role of combination therapies in cancer therapy as well as angiogenesis.

Chronic subdural hematoma recurrence due to contralateral neovascularization following middle meningeal artery embolization.

INTRODUCTION: Chronic subdural hematoma (CSDH) is one of the most commonly encountered neurosurgical diseases. Middle meningeal artery embolization (MMAE) is a technique for the management of CSDH that has elicited promising results. Despite the encouraging results of MMAE, recurrence does occur. One uncommon mechanism for recurrence of CSDH is by means of neovascularization of the contralateral middle meningeal artery (MMA). We describe two cases of CSDH recurrence by means of contralateral middle meningeal artery neovascularization treated with contralateral MMAE. METHODS: We identified two cases of recurrent subdural hematoma secondary to neovascularization following treatment with contralateral MMAE. RESULTS: Two patients initially treated with MMAE were identified with CSDH recurrence secondary to contralateral MMA neovascularization. There was no traumatic or coagulopathic contribution to CSDH recurrence. In both cases, patients underwent contralateral MMAE. Both patients were neurologically intact with radiographic improvement of CSDH at follow up. CONCLUSIONS: Re-accumulation of SDH following MMAE by means of contralateral MMA neovascularization is a rare subtype of subdural hematoma (SDH) recurrence following MMAE. Within the context of re-accumulation of SDH following MMAE, catheter angiography is an important diagnostic investigation to elucidate the etiology of the recurrence. Furthermore, when angiography reveals neovascularization of the contralateral MMA, embolization of the contralateral MMA achieves good clinical and radiographic result.

Coil Embolization and Left Ventricular Assist Device After Arterial Switch Operation.

Aortopulmonary collateral arteries are frequently found in patients with transposition of the great arteries after catheterization. Although most of them are asymptomatic, it may cause heart failure or pulmonary hemorrhage after an arterial switch operation. Here we report a case of symptomatic aortopulmonary collateral arteries after arterial switch, which necessitated support with a centrifugal pump and left ventricular assistive device because of severe mitral regurgitation and left atrial hypertension and emergent coil embolization. Hemodynamics dramatically improved after embolization. The postoperative period was uneventful, and the infant was released from the hospital on the 14th day.

Tumor radiosensitization by photobiomodulation.

PURPOSE: To investigate the safety of photobiomodulation therapy (PBM) in tumors and its potential as a radiosensitizer when combined with radiotherapy. METHODS: We have performed in vitro experiments in A431 cells to assess proliferation and cell cycle after PBM, as well as clonogenic assay and H2AX-gamma immunolabeling to quantify double strand breaks after the combination of PBM and radiation. In vivo experiments in xenografts included Kaplan-Meier survival analysis, optical coherence tomography (OCT) and histological analysis. RESULTS: PBM did not induce proliferation in vitro, but increased the G2/M fraction by 27% 24h after illumination, resulting in an enhancement of 30% in radiation effect in the clonogenic assay. The median survival of the PBM-RT group increased by 4 days and the hazard ratio was 0.417 (CI 95%: 0.173-1.006) when compared to radiation alone. OCT analysis over time demonstrated that PBM increases tumor necrosis due to radiation, and histological analysis showed that illumination increased cell differentiation and angiogenesis, which may play a role in the synergetic effect of PBM and radiation. CONCLUSION: PBM technique may be one of the most appropriate approaches for radiosensitizing tumors while protecting normal tissue because of its low cost and low training requirements for staff.