Tumor Vasculature Research Articles

Transophthalmic Artery Embolization of Anterior Skull Base Meningiomas: Technical Case Series.

Preoperative embolization of anterior skull base meningiomas can facilitate surgical resection by reducing tumor vascularity. However, transophthalmic artery embolization carries risks of visual complications. This study aimed to evaluate the safety and efficacy of this technique using modern endovascular tools. This retrospective study included patients with anterior skull base meningiomas who underwent preoperative transophthalmic artery embolization followed by surgical resection between January 2022 and April 2024. Patient demographics, tumor characteristics, embolization details, surgical outcomes, and complications were analyzed. Seven patients (median age 57 years; 6 male) underwent embolization for tumors located primarily at the planum sphenoidale (58%). Unilateral embolization was performed in most cases, with one bilateral transophthalmic approach. Commonly embolized branches included the anterior and posterior ethmoidal arteries. Polyvinyl alcohol particles were the primary embolic agent (71%). Angiographic devascularization was achieved in all cases without complications. Gross total resection was achieved in 71%, with a median blood loss of 427 cc. At a 9-month follow-up, the median modified Rankin Scale score was 1. With careful patient selection, advanced microcatheter technology, and meticulous technique, preoperative transophthalmic artery embolization can be safely performed to facilitate resection of anterior skull base meningiomas. These results suggest it is a viable option for well-selected patients at experienced centers, though larger prospective studies are needed. Fr = French (unit of measurement for catheter diameter); IQR = Interquartile range; IRB = Institutional Review Board; PVA = Polyvinyl alcohol; TOAE = Transophthalmic artery embolization; WHO = World Health Organization.

PSMA-Targeting Imprinted Nanogels for Prostate Tumor Localization and Imaging.

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and tumor vasculature, making it an important biomarker. However, conventional PSMA-targeting agents like antibodies and small molecules have limitations. Antibodies exhibit instability and complex production, while small molecules show lower specificity and higher toxicity. Herein, this work develops a novel PSMA-targeting synthetic antibody to address prior limitations. This work synthesizes fluorescently labelled, N-isopropylacrylamide-based epitope imprinted nanogels (MIP-M) using a dispersion of magnetic nanoparticles as template carriers with a linear epitope from PSMA's extracellular apical domain as the template. MIP-M demonstrates high binding affinities for both the epitope template (apparent KD = 6 × 10-10 м) and PSMA (apparent KD = 2.5 × 10-9 м). Compared to reference peptides and human serum albumin, MIP-M indicates high specificity. Flow cytometry and confocal laser scanning microscopy comparing cell lines displaying normal (PC3) and enhanced (LNCaP) PSMA expression levels, revealed that MIP-M and a PSMA antibody exhibits comparable binding preferences for the latter cell line. Moreover, MIP-M demonstrates selectivity on par with the PSMA antibody for targeting PSMA-positive prostate tumor over normal tissue, enabling discrimination. This MIP-M addresses stability, production, specificity and toxicity limitations of prior targeting agents and offer a promising alternative for PSMA-directed cancer diagnosis and treatment.

A novel three-dimensional model of Infantile Haemangioma.

Infantile Haemangioma (IH) is vascular tumour in infants exhibiting rapid proliferation and angiogenesis followed by gradual involution.10% of cases are associated with disfiguring complications and requires medical interventions with β-blockers such as propranolol, surgery, or laser therapy. An in vitro IH three-dimensional (3D) model will improve our understanding of the disease mechanism(s). We have isolated and expanded CD31+ endothelial cells (HemEC) from patient-derived IH cell lines, and then grown as spheroids in StemDIFF Endothelial expansion media. These were then embedded in extracellular matrix hydrogel with reduced growth factors to initiate angiogenic sprouting. HemEC spheroids expressed CD31, GLUT1, VEGFR2, CD44, Vimentin, CD133 but not SMA, indicating their similarity to immature IH blood vessels and their angiogenic potential. Proteomic analysis revealed similar homology in terms of protein expression in spheroids and IH tissue. The high-throughput application of this 3D angiogenesis model was tested using propranolol to inhibit sprouting of spheroids with increased toxicity response. This study reports the development of a 3D model of IH that recapitulates angiogenic features of IH for molecular analysis and drug screening.

Oral Propranolol in the Treatment of Cutaneous Infantile Hemangioma in Children: A 3-Years Retrospective Study

Background: Infantile hemangioma is the most common vascular tumor in children. The primary pharmacological agent currently utilized for its treatment is propranolol, which demonstrates efficacy and minimal and non-severe side effects. Objective: To investigate the therapeutic outcomes and adverse effects of orally administered propranolol in the treatment of infantile hemangioma. Additionally, to explore patient data regarding disease manifestations and progression. Material and Methods: Retrospective data collection from medical records of patients diagnosed with cutaneous infantile hemangioma and treated at the National Children’s Health Institute for a duration of three years, between January 1, 2018 and December 31, 2020, was done. Results: The present study included 180 patients with infantile hemangioma. The male-to-female ratio was 1 to 2.3. The median age at diagnosis and treatment initiation was four months, ranging from 1 week to 18 months. Premature infants accounted for 28 cases (15.6%). The most common locations were the head, face, and neck with 67.8%, trunk with 16.1%, and limbs with 16.1%. The most prevalent complications were ulcerations for 12.2% and visual field defects for 0.6%. The average duration of propranolol treatment was 13.01 months. Favorable response was noted in 173 patients (96%) at the 2-week follow-up. By the 6-month follow-up, all patients exhibited positive treatment responses. Adverse effects were reported in two cases, including hypoglycemic seizure and irritability. Conclusion: Oral propranolol demonstrates favorable outcomes in treating infantile hemangioma. However, vigilant monitoring for severe adverse effects, particularly hypoglycemia-induced seizures must be done. Guardians must be informed and deeply concerned not to administer propranolol on an empty stomach, in the presence of poor feeding, or in poor physical condition. Keywords: Oral propranolol; Infantile hemangioma; Adverse events; Hypoglycemia

“Think Beyond Trauma!” Multiple Epidural Hematoma in Sickle Cell Disease: A Conundrum

Epidural hematoma is conventionally thought to occur secondary to trauma. Atraumatic/spontaneous epidural hematoma is of rare occurrence and the etiology spans from dural vascular malformations, neoplasms, and coagulopathy to sinus, middle ear, and orbital infections. Occurrence of atraumatic epidural hematoma in sickle cell disease is rarely reported as opposed to frequent neurological complications, such as ischemic stroke seen in 54% of cases, followed by intracerebral, subarachnoid, intraventricular, or subdural hemorrhages. This study reports the case of an eight-year-old male with Sickle cell disease (SCD). He suffered from fever followed by splenic sequestration and multiple spontaneous epidural hematomas without mass effect and successfully managed with conservative treatment.

Case report: Paraganglioma masquerading as angiosarcoma: diagnostic‐dilemma in vascular tumors

Paragangliomas originating from blood vessels are exceptionally rare, presenting diagnostic challenges due to their histological resemblance to other vascular neoplasms. We present a case study of a 60-year-old woman with underlying hypertension and dyslipidemia with obesity, initially diagnosed with angiosarcoma based on imaging and histological characteristics viewed via CT-guided biopsy. Intraoperative exploration revealed a lobulated tumor located between the inferior vena cava (IVC) and aorta measuring 7 cm × 8 cm, during which the patient developed transient hemodynamic instabilities. Histopathological examination and immunohistochemical staining using neuroendocrine markers (chromogranin, synaptophysin, S-100 protein, and CD-56) later confirmed the tumor as a retroperitoneal paraganglioma. Retroperitoneal paraganglioma was initially misdiagnosed as angiosarcoma due to the overlapping imaging characteristics between the two tumors. This highlights the importance of raising suspicion on the possibility of retroperitoneal paraganglioma when imaging examination indicates angiosarcoma and to incorporate histopathological examination and immunohistochemistry in the diagnosis to avoid misdiagnosis.

Engineering the Hydrophilic-Hydrophobic Interface of Polymeric Micelles by Cationic Blocks for Enhanced Chemotherapy.

The cationic surface charge critically influences the biological functions and therapeutic outcomes of the cancer nanomedicines. However, the basic correlation between the cationic group categories and their therapeutic efficacy has not been elucidated. In this study, cationic polymeric nanoparticles with amino groups (primary, tertiary, and quaternary amines) as the single variable were leveraged to investigate the various effects of amino species for enhanced antitumor chemotherapy. The nanoparticles were constructed from a series of triblock polymers with varying cationic repeating units at the hydrophilic-hydrophobic interface. Our results suggested that quaternary ammonium outperforms its primary and tertiary counterparts in destroying mitochondrial membranes to induce apoptosis, penetrating deep inside the tumor tissue, and damaging tumor vasculatures. As a result, we were able to effectively inhibit tumor growth in mice by a quaternary ammonium conjugate without causing significant toxicity. Our work demonstrated that the chemical structures played vital roles in regulating their biological functions and provided valuable information for designing cationic drug delivery systems.

Understanding Permeability Changes in Vestibular Schwannomas as Part of the Dynamic Response to Radiosurgery Using Golden-Angle Radial Sparse Parallel Imaging: A Retrospective Study

BACKGROUND AND OBJECTIVES: Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on postcontrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. METHODS: Consecutive patients with vestibular schwannoma who underwent SRS between 2017 and 2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 18, and 30 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS (https://gravis-imaging.org/gravis/), an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. RESULTS: The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 18, and 30 months after SRS (corrected P < .05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak (P = .013) and AUC (P = .029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at a median of 62 months. These patients showed a strong correlation between peak, AUC, and wash-in phase slope changes at 6 months and tumor volume at the last follow-up. CONCLUSION: After SRS and loss of internal contrast uptake within vestibular schwannomas, a slow vascular permeability dynamic persisted, suggesting the presence of postradiation processes such as fibrosis. We show for the first time, using GRASP, a quantitative assessment of the vascular radiobiological effect.

Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers.

The response rates to immunotherapy vary widely depending on the type of cancer and the specific treatment used and can be disappointingly low for many solid tumors. Fortunately, due to their complementary mechanisms of action, immunotherapy and anti-angiogenic therapy have synergistic effects in cancer treatment. By normalizing the tumor vasculature, anti-angiogenic therapy can improve blood flow and oxygenation to facilitate better immune cell infiltration into the tumor and enhance the effectiveness of immunotherapy. It also reduces immunosuppressive factors and enhances immune activation, to create a more favorable environment for immune cells to attack the tumor. Their combination leverages the strengths of both therapies to enhance anti-tumor effects and improve patient outcomes. This review discusses the vasculature-immunity crosstalk in the tumor microenvironment and summarizes the latest advances in combining anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system tumors.

CD105-microvessel density analysis and its clinical value in urothelial carcinoma of bladder patients

Background Endoglin/CD105-microvessel density (CD105-MVD) is identified as one of the most potential methods for semi-quantification of angiogenesis in human cancer tissues. Present study aimed to examine the diagnosticand prognostic value of CD105-MVD in two clinically distinct subtypes of urothelial carcinoma of bladder (UCB) namely non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) patients. Methods Message expression of endoglin was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and MVD measurement was done by immunohistochemical staining in 90 UCB [NMIBC: 60; MIBC: 30] patients. SEM studies were carried out to examine tumor vasculature and extent of neoangiogenesis in NMIBC and MIBC patients. Results Elevated message expression of CD105 showed statistical significance with tumor stage, grade, smoking/tobacco chewing history in NMIBC andage in MIBC cohort. Higher values of CD105-MVD showed statistical relevance with tumor stage, grade, size, smoking/tobacco chewing history in NMIBC cohort. Kaplan Meier test identified high CD105-MVD as strong predictor of poor RFS in NMIBC patients. Conclusions Association of CD105 expression and MVD with the clinicohistopathological features as well as poor survival outcomes potentially identify it as a preferred marker of clinical significance in a given cohort of UCB patients. Clinical significance Strong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients. Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients. Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients. The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients.

Comment on “Diagnostic performance of computed tomography-digital subtraction angiography and conventional magnetic resonance imaging for evaluating the vascularity of osseous spinal tumors”

Comment on “Diagnostic performance of computed tomography-digital subtraction angiography and conventional magnetic resonance imaging for evaluating the vascularity of osseous spinal tumors”

An immunostimulatory liponanogel reveals immune activation-enhanced drug delivery and therapeutic efficacy in cancer

The clinical use of immunostimulatory polyinosinic:polycytidylic acid (pIC) for cancer therapy has been notably limited by its low tumor accumulation and poor cytosolic delivery to activate innate immune sensors. Here, we report a liponanogel (LNG)-based platform to address these challenges. The immunostimulatory LNG consists of an ionizable lipid shell coating a nanogel made of hyaluronic acid (HA), Mn2+ and pIC, which is denoted as LNG-Mn-pIC (LMP). The protonation of internal HA within acidic endosomes increases the endosomal membrane permeability and facilitates the cytosolic delivery of pIC. Moreover, Mn2+, previously reported to activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, synergizes with pIC to activate innate immune cells. Remarkably, intravenously injected LMP significantly induces tumor vasculature disruption and tumor cell apoptosis in an innate immune activation-dependent manner, facilitating the LMP delivery into tumors and leading to enhanced antitumor immunity that potently inhibits or even completely regresses the established tumors. In summary, this immunostimulatory LNG platform not only serves as a useful tool to uncover the immune activation-enhanced drug delivery profile but also represents a broadly applicable platform for effective cancer immunotherapy.

Prospective evaluation of quantitative response parameter in patients with Gastrointestinal Stroma Tumorundergoing tyrosine kinase inhibitor therapy-Impact on clinical outcome.

The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment(HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.

Clinical significance of tertiary lymphoid structure maturity in colorectal cancer patients.

To explore the clinical significance of the maturation of tertiary lymphoid structures (TLS) in colorectal cancer patients. A total of 230 surgical removed colorectal cancer specimens with detailed follow-up data were collected from Yinzhou Second Hospital. There were 128 cases of mature TLS and 108 cases of immature TLS according to immunohistochemical results. The patient age, gender, maximum tumor diameter, tumor location, differentiation degree, depth of invasion, lymph node metastasis, vascular tumor thrombus, liver metastasis, distant non-liver metastasis, mismatch repair status, expression of Ki-67, P53 and programmed cell death ligand 1 (PD-L1) were analyzed. The Kaplan-Meier method (Breslow test) was used to analyze the survival of patients, and multivariate Cox regression model was applied to analyze the prognostic factors. Compared to the immature TLS group, the mature TLS group showed a significantly lower rate of vascular tumor thrombus, lymph node metastasis, and liver metastasis. Additionally, the positive expression rate of Ki-67 was markedly reduced, while the rate of deficient mismatch repair and the positive expression rate of PD-L1 were significantly increased (all P<0.05). The overall survival rate of the mature TLS group was superior to that of the immature TLS group (Breslow=4.553, P<0.05). Cox regression analysis indicated that lymph node metastasis was an independent risk factor for the prognosis of colorectal cancer patients (P<0.01), while TLS maturation was a protective factor (P<0.05). The formation of TLS may play a significant role in inhibiting lymph node metastasis, liver metastasis, and vascular tumor thrombus in colorectal cancer, and patients with mature TLS have a favorable clinical prognosis, which can provide a reference for the immunotherapy and prognostic assessment of colorectal cancer patients.

A Case of Hepatic Epithelioid Hemangioendothelioma Treated with Radiofrequency Ablation

Epithelioid hemangioendothelioma is a rare, low to intermediate grade malignant vascular tumor. A 62-year-old woman visited our hospital with abdominal discomfort for 3 months. Abdominal ultrasound showed two homogeneous hypoechoic nodules with well-defined margin. Contrast-enhanced ultrasound showed rim enhancement in arterial phase and early and marked washout in portal phase. We decided to perform liver biopsy for histological confirmation. The lesions were diagnosed as hepatic epithelioid hemangioendothelioma. She was successfully treated with radiofrequency ablation.

A bulbo medullary hemangioblastoma revealed by hemorrhage: A case report

Introduction: Hemangioblastomas are highly vascularized tumors of unclear origin. Most hemangioblastomas arise in the posterior fossa. Although spontaneous hemorrhage from these tumors is extremely rare, despite their vascular nature, we describe a case of a bulbo- medullary hemangioblastoma revealed by hemorrhage. Case report: This is a 12-year-old child, with no past-history, presented with a picture of subarachnoid hemorrhage (sudden, intense, thunderclap headaches associated with vomiting and stiff neck, for which the Neuroradiological investigation was in favor of a bulbo-medullary lesion which infracentimetric lesion was found, with anapath was in favor of a hemangioblastoma. Conclusion: Hemangioblastomas are rare tumors that can be revealed by hemorrhage. Imagery can be misleading. In the case with very small lesion, careful neurovascular appraoch is recommended.

Current Operating Procedure (COP) for Bleomycin ElectroScleroTherapy (BEST) of low-flow vascular malformations.

Bleomycin ElectroScleroTherapy (BEST) is a new approach in the treatment of vascular malformations. After bleomycin is administered to the malformation, electric pulses are applied to the target area to enhance the effectiveness of bleomycin. The mode of action is comparable to the effect of electrochemotherapy on tumour vasculature. For the wider and safer use of BEST in the clinical treatment of low-flow vascular malformations, this Current Operating Procedure (COP) is being prepared. It is a proposal for the clinical standardisation of BEST using the Cliniporator® as the electrical pulse generator with its associated electrodes. The electrical parameters considered in this protocol are those validated by the European Standard Operating Procedures for Electrochemotherapy (ESOPE) with the Cliniporator®. General requirements are proposed, and, depending on the type of lesion, local skills and the availability of radiological equipment, two technical approaches of BEST are described based on ultrasound guided intervention or combined ultrasound and fluoroscopic guided intervention.

Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition.

Cancer cells often experience nutrient-limiting conditions because of their robust proliferation and inadequate tumour vasculature, which results in metabolic adaptation to sustain proliferation. Most cancer cells rapidly consume glucose, which is severely reduced in the nutrient-scarce tumour microenvironment. In CRISPR-based genetic screens to identify metabolic pathways influenced by glucose restriction, we find that tumour-relevant glucose concentrations (low glucose) protect cancer cells from inhibition of de novo pyrimidine biosynthesis, a pathway that is frequently targeted by chemotherapy. We identify two mechanisms to explain this result, which is observed broadly across cancer types. First, low glucose limits uridine-5-diphosphate-glucose synthesis, preserving pyrimidine nucleotide availability and thereby prolonging the time to replication fork stalling. Second, low glucose directly modulates apoptosis downstream of replication fork stalling by suppressing BAK activation and subsequent cytochrome c release, key events that activate caspase-9-dependent mitochondrial apoptosis. These results indicate that the low glucose levels frequently observed in tumours may limit the efficacy of specific chemotherapeutic agents, highlighting the importance of considering the effects of the tumour nutrient environment on cancer therapy.

Dual-phase nanoscissors disrupt vasculature-breast cancer stem cell crosstalk for breast cancer treatment

Clinical treatment effects of breast cancer are heavily frustrated by the malignant crosstalk between tumor vasculature and breast cancer stem cells (BCSCs). This study introduces a two-phase therapeutic strategy targeting the interplay between tumor vasculature and BCSCs to overcome this challenge. Here, we designed an FLG/ZnPc nanoscissor, which combines mild photodynamic therapy (PDT) to generate reactive oxygen species (ROS) with vascular normalization therapy (VNT) to break the crosstalk between tumor vessels and BCSCs. In the first phase, our approach breaks the vascular niche that supports BCSCs by restoring tumor vascular function and promoting ROS-induced BCSCs differentiation into less malignant forms, enhancing treatment sensitivity. The second phase employs high-impact photothermal therapy (PTT) to ablate tumor masses. This integrated “mild PDT-PTT” approach aims to reduce tumor growth and metastasis, offering a comprehensive strategy for effective breast cancer management.

Hemostasis and thrombosis risks and management in vascular anomalies.

The role of the hematologist in the management of vascular anomalies is evolving. Several vascular tumors and malformations are associated with complex coagulation derangements. Kaposiform hemangioendothelioma or tufted angiomas may present with a consumptive coagulopathy known as the Kasabach-Merritt phenomenon (KMP). The management of KMP is essential to reduce morbidity and mortality from this condition. Slow-flow vascular malformations (SFVM) are also frequently complicated by a coagulopathy requiring anticoagulation, especially during and after surgical procedures, and some of these conditions pose a high risk of venous thromboembolism. Pain in SFVM is also frequently responsive to anticoagulation as well. It is essential for a hematologist with expertise in vascular anomalies to assist in the management of these complex conditions as part of a multidisciplinary team to reduce morbidity and mortality. Through case-based discussions, we attempt to highlight the critical role of the hematologist in managing these anomalies.