• cancer biomarker
• endothelial progenitor cells
• lung cancer
• prognosis

• ANGIOGENESIS
• BLOOD VESSELS
• CARCINOMA
• Neovascularization, Pathologic
• Parathyroid Diseases

• Humans
• Angiogenesis Inhibitors/therapeutic use
• Neovascularization, Pathologic/drug therapy
• Neoplasms/drug therapy
• Neoplasms/blood supply
• Vascular Endothelial Growth Factor A/antagonists & inhibitors
• Vascular Endothelial Growth Factor A/metabolism
• Bevacizumab/therapeutic use
• Signal Transduction/drug effects
• Angiogenesis

• colorectal cancer
• metastasis
• cell growth
• stem cells

• 11491 / 2018-1 KWF Kankerbestrijding (Dutch Cancer Society)
• OCENW.M.22.032 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)

• hypoxia
• hypoxia-inducible factors
• metastasis
• small G-proteins

• NRDIF-OTKA K147410 National Research, Development and Innovation Fund of Hungary
• 2022-2.1.1-NL-2022-00010 National Laboratories Excellence program, National Tumorbiology Laboratory project
• TKP2021-EGA-44 Hungarian Thematic Excellence Program
• 1018567 KDP-14-3/PALY-2021

• Humans
• Nasopharyngeal Carcinoma/diagnostic imaging
• Nasopharyngeal Carcinoma/pathology
• Lymphatic Metastasis/diagnostic imaging
• Lymphatic Metastasis/pathology
• Retrospective Studies
• Nasopharyngeal Neoplasms/pathology
• Perfusion Imaging
• Lymph Nodes/diagnostic imaging
• Lymph Nodes/pathology

• angiogenesis
• extracellular matrix
• immune checkpoint inhibitors
• proteoglycans
• tumor immunity
• tumor microenvironment
• tumor stroma
• tumor-associated fibroblasts

• Humans
• Tumor Microenvironment
• Ecosystem
• Neoplasms/metabolism
• Carcinogenesis
• Immunotherapy

• (under the National Tumor Biology Laboratory project NLP-17) National Laboratories Excellence program
• NKFI FK-138593; NKFI K-119283; NKFI ANN-128524 National Research, Development and Innovation Office (Hungary)

• intratumoural drug distribution
• laser ablation-inductively coupled plasma-mass spectrometry
• mass spectrometry imaging
• neoadjuvant chemotherapy
• platinum
• pleural mesothelioma

• Humans
• Mesothelioma/surgery
• Mesothelioma/drug therapy
• Platinum/therapeutic use
• Platinum/analysis
• Laser Therapy
• Mass Spectrometry/methods

• I 3977 Austrian Science Fund FWF
• Semmelweis 250 + Excellence PhD Scholarship
• Erasmus+ and Campus Mundi EFOP‐3.4.2‐VEKOP‐15‐2015‐00001 Traineeship program
• Austrian Science Fund
• Hungarian Respiratory Society
• Hungarian Academy of Sciences

• biomarkers
• fractals
• microvessel density
• prostate cancer
• vasculature

• Angiogenesis
• Cancer
• Gene expression
• Head and neck
• PTGS2
• VEGF

• CRLM
• cells
• tumor microenvironment

• VE-cadherin
• angiogenesis
• vasculogenic mimicry

• Humans
• Carcinoma, Renal Cell/drug therapy
• Kidney Neoplasms/drug therapy
• Kidney Neoplasms/pathology
• Vascular Endothelial Growth Factor A/therapeutic use
• Neoplasm Recurrence, Local
• Combined Modality Therapy

• P30 CA008748 NCI NIH HHS
• UL1 TR000457 NCATS NIH HHS
• UL1 TR002384 NCATS NIH HHS

• Cancer plasticity
• Epithelial mesenchymal transition
• Immunogenic mimicry
• Megakaryocytic mimicry
• Vasculogenic mimicry

• Angiogenesis
• canalization
• cancer
• colchicine
• isothermal calorimetry
• metastasis
• microtubules

• anti-angiogenic therapy resistance
• molecular mechanisms
• mouse models
• state-of-the-art analysis
• tumor vascularization
• vessel co-option

• Fonds Wetenschappelijk Onderzoek
• European Research Council
• Novo Nordisk Fonden
• HORIZON EUROPE Marie Sklodowska-Curie Actions

• Mesothelioma
• angiogenesis
• orthotopic mouse model of mesothelioma
• vascularization

• I 3977 Austrian Science Fund FWF

• Brain
• Brain Neoplasms/metabolism
• Breast Neoplasms/pathology
• Endothelial Cells
• Female
• Humans
• Pericytes/metabolism

• Colon cancer
• Esophageal adenocarcinoma
• Gastric cancer
• Gene sequencing, Gene expression profiling
• Molecular subtypes

Breast cancer is the most frequent malignancy in women worldwide. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. The vasculogenic mimicry (VM) process is associated with an invasive and metastatic cancer phenotype and a poor prognosis for human breast cancer patients. Our aim was to study the effect of WISP2, a matricellular protein, on VM. We found that WISP2 inhibits VM through inhibition of CYR61 protein expression and YAP-TAZ signaling. Our finding may open promising candidates for blocking VM in breast cancer.

Vasculogenic mimicry (VM) formed by aggressive tumor cells to create vascular networks connected with the endothelial cells, plays an important role in breast cancer progression. WISP2 has been considered as a tumor suppressor protein; however, the relationship between WISP2 and VM formation remains unclear. We used the in vitro tube formation assay and in vivo immunohistochemical analysis in a mouse model, and human breast tumors were used to evaluate the effect of WISP2 on VM formation. Here we report that WISP2 acts as a potent inhibitor of VM formation in breast cancer. Enforced expression of WISP2 decreased network formation while knockdown of WISP2 increased VM. Mechanistically, WISP2 increased retention of oncogenic activators YAP/TAZ in cytoplasm, leading to decreased expression of the angiogenic factor CYR61. Studies using an in vivo mouse model and human breast tumors confirmed the in vitro cell lines data. In conclusion, our results indicate that WISP2 may play a critical role in VM and highlight the critical role of WISP2 as a tumor suppressor.

• CYR61
• WISP2/CCN5
• YAP-TAZ signaling
• breast cancer
• vasculogenic mimicry

Metastatic lung tumors are relatively common, and their pathological diagnosis is crucial for determining the appropriate treatment strategy. Although bronchoscopy is one biopsy method, its role has not been established for peripheral metastatic lung tumors. The present study aimed to investigate the value of bronchoscopy, using radial endobronchial ultrasound for diagnosis. We analyzed 235 lesions consecutively, and the overall diagnostic yield was 76.6%, which was slightly higher than the reported cumulative sensitivity for general peripheral pulmonary lesions. There were no serious complications. The results demonstrated that bronchoscopy is a valuable technique for peripheral metastatic lung tumors that combines diagnostic accuracy and safety. Moreover, the higher diagnostic yield was associated with the large lesion size, inner location, and visibility on radiography. These findings should contribute to the selection of biopsy methods for metastatic lung tumors and improve the diagnostic yield.

Although lungs are one of the most frequent sites of metastasis for malignant tumors, little has been reported about the value of bronchoscopy for lung metastases presenting with peripheral pulmonary lesions (PPLs). This retrospective cohort study investigated the diagnostic value of bronchoscopy for peripheral metastatic lung tumors. Consecutive patients who underwent diagnostic bronchoscopy with radial endobronchial ultrasound for PPLs and were finally diagnosed with metastatic lung tumors from April 2012 to March 2019 were included. We analyzed 235 PPLs, with a median size of 18.8 mm. The overall diagnostic yield was 76.6%. In a multivariable analysis, large lesion size (>20.0 mm vs. <20.0 mm: 87.6% vs. 67.7%, p = 0.043, OR = 2.26), inner location (inner 2/3 vs. outer 1/3: 84.8% vs. 69.1%, p = 0.004, OR = 2.79), and visibility on radiography (visible vs. invisible: 83.2% vs. 56.1%, p = 0.015, OR = 3.29) significantly affected the diagnostic yield. Although a positive bronchus sign tended to have a higher yield, no significant difference was observed (81.8% vs. 70.6%, p = 0.063). Only one case of lung abscess was observed, with no serious complications. In conclusion, bronchoscopy is a valuable technique for peripheral metastatic lung tumors, with good diagnostic accuracy and safety.

Colorectal cancer (CRC) is the third most common cancer worldwide. Metastasis to secondary organs, such as the liver and lungs, is a key driver of CRC-related mortality. The tumor microenvironment, which consists of the primary cancer cells, as well as associated support and immune cells, significantly affects the behavior of CRC cells at the primary tumor site, as well as in metastatic lesions. In this paper, we review the role of the individual components of the tumor microenvironment on tumor progression, immune evasion, and metastasis, and we discuss the implications of these components on antitumor therapies.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

• colorectal cancer
• colorectal liver metastasis
• colorectal pulmonary metastasis
• immuno-oncology
• novel anticancer therapy
• tumor microenvironment

Glioblastomas (GBM) are the most aggressive tumors originating in the brain. Histopathologic features include circuitous, disorganized, and highly permeable blood vessels with intermittent blood flow. These features contribute to the inability to direct therapeutic agents to tumor cells. Known targets for anti-angiogenic therapies provide minimal or no effect in overall survival of 12–15 months following diagnosis. Identification of novel targets therefore remains an important goal for effective treatment of highly vascularized tumors such as GBM. We previously demonstrated in zebrafish that a balanced level of expression of the transmembrane protein TMEM230/C20ORF30 was required to maintain normal blood vessel structural integrity and promote proper vessel network formation. To investigate whether TMEM230 has a role in the pathogenesis of GBM, we analyzed its prognostic value in patient tumor gene expression datasets and performed cell functional analysis. TMEM230 was found necessary for growth of U87-MG cells, a model of human GBM. Downregulation of TMEM230 resulted in loss of U87 migration, substratum adhesion, and re-passaging capacity. Conditioned media from U87 expressing endogenous TMEM230 induced sprouting and tubule-like structure formation of HUVECs. Moreover, TMEM230 promoted vascular mimicry-like behavior of U87 cells. Gene expression analysis of 702 patients identified that TMEM230 expression levels distinguished high from low grade gliomas. Transcriptomic analysis of patients with gliomas revealed molecular pathways consistent with properties observed in U87 cell assays. Within low grade gliomas, elevated TMEM230 expression levels correlated with reduced overall survival independent from tumor subtype. Highest level of TMEM230 correlated with glioblastoma and ATP-dependent microtubule kinesin motor activity, providing a direction for future therapeutic intervention. Our studies support that TMEM230 has both glial tumor and endothelial cell intracellular and extracellular functions. Elevated levels of TMEM230 promote glial tumor cell migration, extracellular scaffold remodeling, and hypervascularization and abnormal formation of blood vessels. Downregulation of TMEM230 expression may inhibit both low grade glioma and glioblastoma tumor progression and promote normalization of abnormally formed blood vessels. TMEM230 therefore is both a promising anticancer and antiangiogenic therapeutic target for inhibiting GBM tumor cells and tumor-driven angiogenesis.

• angiogenesis and normalization of vascular network
• anticancer and antiangiogenic therapy
• cargo vesicle transport
• glioma
• kinesin motor proteins
• tumor cell migration and adhesion

MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional gene regulation. Over the past years, various studies have demonstrated the role of aberrant miRNA expression in the onset of cancer. The mechanisms by which miRNA exerts its cancer-promoting or inhibitory effects are apparent through the various cancer hallmarks, which include selective proliferative advantage, altered stress response, vascularization, invasion and metastasis, metabolic rewiring, the tumor microenvironment and immune modulation; therefore, this review aims to highlight the association between miRNAs and the various cancer hallmarks by dissecting the mechanisms of miRNA regulation in each hallmark separately. It is hoped that the information presented herein will provide further insights regarding the role of cancer and serve as a guideline to evaluate the potential of microRNAs to be utilized as biomarkers and therapeutic targets on a larger scale in cancer research.

• biomarkers
• cancer biology
• gene regulation
• microRNA (miRNA)
• therapeutic targets

• Antiangiogenic
• Anticancer
• Apoptosis
• Endothelial growth
• SC1
• Tumor angiogenesis

• angiogenesis
• cancer
• cancer stem cells
• co-option
• endothelial cells
• glioblastoma
• neovascularization
• vascular mimicry
• vasculogenesis
• vessel

• Animals
• Biomarkers
• Cell Communication
• Cell Differentiation
• Disease Susceptibility
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic
• Glioblastoma/etiology
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Glioblastoma/therapy
• Humans
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Neovascularization, Pathologic/metabolism
• Radiation Tolerance
• Signal Transduction
• Tumor Microenvironment

• PJA20171206146; PJA20191209477; PDF20191209822 Fondation ARC pour la Recherche sur le Cancer
• DEQ20180339184 Fondation pour la Recherche Médicale
• comités Loire-Atlantique, Maine et Loire, Vendée, Ille-et-Vilaine Ligue Contre le Cancer
• INCA-DGOS-Inserm_12558 Institut National Du Cancer

• anti-angiogenic therapy
• cancer cells
• endothelial cells
• macrophages
• metastasis
• pericytes
• resistance
• single-cell RNA sequencing
• tumor angiogenesis
• tumor vessel co-option

• Animals
• Cell Line, Tumor
• Endothelial Cells/pathology
• Female
• Kidney Neoplasms/pathology
• Lung Neoplasms/secondary
• Macrophages/pathology
• Mice, Inbred BALB C
• Myeloid Cells/pathology
• Neoplasms/blood supply
• Neoplasms/pathology
• Pericytes/pathology
• Single-Cell Analysis
• Mice

• NGR
• PET
• RGD
• SPECT
• VEGF
• angiogenesis
• fibronectin
• oncology

• Animals
• Biomarkers, Tumor/metabolism
• Cell Hypoxia
• Glucose/metabolism
• Humans
• Integrins/metabolism
• Matrix Metalloproteinases/metabolism
• Medical Oncology/instrumentation
• Medical Oncology/methods
• Molecular Imaging/methods
• Neoplasms/diagnostic imaging
• Neoplasms/pathology
• Neovascularization, Pathologic/diagnostic imaging
• Neovascularization, Pathologic/pathology
• Oligopeptides/metabolism
• Positron-Emission Tomography/methods
• Tomography, Emission-Computed, Single-Photon/methods
• Vascular Endothelial Growth Factor A/metabolism

• angiogenesis
• cancer
• hypoxia
• metabolism
• therapy

Tumors rely on blood vessels to grow and metastasize. Malignant tumors can employ different strategies to create a functional vascular network. Tumor cells can use normal processes of vessel formation but can also employ cancer-specific mechanisms, by co-opting normal vessels present in tissues or by turning themselves into vascular cells. These different types of tumor vessels have specific molecular and functional characteristics that profoundly affect tumor behavior and response to therapies, including drugs targeting the tumor vasculature (antiangiogenic therapies). In this review, we discuss how vessels formed by different mechanisms affect the intrinsic sensitivity of tumors to therapy and, on the other hand, how therapies can affect tumor vessel formation, leading to resistance to drugs, cancer recurrence, and treatment failure. Potential strategies to avoid vessel-mediated resistance to antineoplastic therapies will be discussed.

Blood vessels in tumors are formed through a variety of different mechanisms, each generating vessels with peculiar structural, molecular, and functional properties. This heterogeneity has a major impact on tumor response or resistance to antineoplastic therapies and is now emerging as a promising target for strategies to prevent drug resistance and improve the distribution and efficacy of antineoplastic treatments. This review presents evidence of how different mechanisms of tumor vessel formation (vasculogenesis, glomeruloid proliferation, intussusceptive angiogenesis, vasculogenic mimicry, and vessel co-option) affect tumor responses to antiangiogenic and antineoplastic therapies, but also how therapies can promote alternative mechanisms of vessel formation, contributing to tumor recurrence, malignant progression, and acquired drug resistance. We discuss the possibility of tailoring treatment strategies to overcome vasculature-mediated drug resistance or to improve drug distribution and efficacy.

• antiangiogenic therapy
• drug resistance
• non-sprouting angiogenesis
• tumor microenvironment
• tumor vasculature

• FOXC2
• angiogenesis
• endothelial transdifferentiation
• epithelial-mesenchymal transition
• vasculogenic mimicry

Transforming Growth Factor-beta (TGF-β) is dysregulated in colorectal cancer and there is growing evidence that it is associated with a poor prognosis and chemo-resistance in several malignances, including CRC. In this study we have explored the therapeutic potential of targeting TGF-β using Tranilast in colon cancer. The anti-proliferative activity of Tranilast was evaluated in 2- and 3-dimensional cells. We used a xenograft model of colon cancer to investigate the activity of Tranilast alone or in combination with 5-FU on tumor growth using histological staining and biochemical studies, as well as gene expression analyses using RT-PCR and Western blotting. Tranilast alone or in combination with 5-FU inhibited tumor growth and was associated with a reduction of TGF-β expression and CD31 positive endothelial cells. Histological evaluation showed that Tranilast increased tumor necrosis and reduced tumor density and angiogenesis. Tranilast increased MDA and ROS production. It was also found that Tranilast reduced total thiol concentration and reduced SOD and catalase activity. Tranilast plus 5-FU was also found to attenuate collagen deposition, reducing tumor fibrosis in tumor xenografts. Our results show that Tranilast, a TGF inhibitor, in combination with 5-FU reduces tumor growth by inhibiting fibrosis and inducting ROS, thus supporting this therapeutic approach in CRC treatment.

• TGF pathway
• Tranilast
• angiogenesis
• colon cancer
• fibrosis

• angiogenesis peptide
• nanofibers
• self-assembly
• skin tissue regeneration

• Angiogenesis
• Cancer
• Cell adhesion
• EMT
• Sialyltransferases

• angiogenesis
• combinational therapy
• immunotherapy
• non-small cell lung cancer
• tumor endothelial cells
• tumor microenvironment
• vascular endothelial growth factor

During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth and metastasis. Additionally, the participation of oxidative stress and chronic inflammation in BC pathogenesis is indicated. The aim of the study was to evaluate the urinary levels of parameters of angiogenesis, stimulating angiogenin (ANG) and inhibiting angiostatin (ANGST), 8-iso-prostaglandin F2α (8-iso-PGF2α) as a marker of oxidative stress, ɣ-synuclein (SNCG) as a cancer progression parameter, and interleukin-13 (IL-13) as an anti-inflammatory immunomodulator. The levels of ANG, ANGST, 8-iso-PGF2α, SNCG, and IL-13 in the urine of BC patients and healthy controls were measured by the enzyme-linked immunosorbent assay. These parameters were examined in the whole group of BC patients and in subgroups depending on the clinical stage: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC); histopathologic malignancy: low grade (LG) and high grade (HG) and in primary and recurrent BC. Significantly, higher urinary parameters were found in BC patients in comparison to controls. Levels of all parameters increased with the development of cancer, with the exception of 8-iso-prostaglandin F2α, in which the level was higher in the early stages of the disease, but these differences were not statistically significant. Some correlations have been demonstrated between parameters in BC patients. Based on the receiver operating characteristic curves, ANG and ANGST had the best diagnostic value for BC. The obtained results indicate the important role of the examined parameters of angiogenesis, oxidative stress, and inflammation in the pathogenesis and development of BC. It is reasonable to continue research in order to thoroughly assess the impact of various associated processes on the course of BC. It is also important to carry out similar tests in patients with other urological diseases.

• CEUS
• cervical lymph nodes
• contrast-enhanced ultrasonography
• metastatic
• nasopharyngeal carcinoma

• Brain metastasis
• Connective tissue
• Growth pattern
• Pericytes
• Vascularization

• angiogenesis
• microenvironment
• multiple myeloma
• vascular endothelial growth factor
• vascular endothelial growth factor receptor

• IG20441 Associazione Italiana per la Ricerca sul Cancro
• 2009WCNS5C_004 Ministero dell'Istruzione, dell'Università e della Ricerca