• CD68
• Catfish
• Histochemical
• Intestinal immune cells
• PCNA
• VEGF

• Animals
• Catfishes/parasitology
• Fish Diseases/parasitology
• Fish Diseases/immunology
• Intestinal Mucosa/parasitology
• Intestinal Mucosa/immunology
• Helminthiasis, Animal/parasitology
• Immunity, Cellular
• Vascular Endothelial Growth Factor A/metabolism
• Proliferating Cell Nuclear Antigen/metabolism
• Antigens, Differentiation, Myelomonocytic/metabolism
• Intestinal Diseases, Parasitic/veterinary
• Intestinal Diseases, Parasitic/parasitology
• Intestinal Diseases, Parasitic/immunology
• Antigens, CD/metabolism

• Assiut University

• genomic alterations in HNSCC
• oral squamous cell carcinoma
• prognostic signatures
• targeted therapy
• tumor microenvironment

• Humans
• Mast Cells
• Squamous Cell Carcinoma of Head and Neck/genetics
• Squamous Cell Carcinoma of Head and Neck/immunology
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/pathology
• Tumor Microenvironment/immunology
• Prognosis

• IL-1β
• NLRP3.
• endometrium
• inflammation
• lipopolysaccharide
• mast cells

• Animals
• Female
• Mice
• Acute Disease
• Annexin A1/metabolism
• Annexin A1/genetics
• Disease Models, Animal
• Endometritis/metabolism
• Endometritis/pathology
• Endometritis/chemically induced
• Inflammation/metabolism
• Inflammation/chemically induced
• Lipopolysaccharides/toxicity
• Mice, Inbred C57BL
• Mice, Knockout

• PD-1/PDL-1
• immune checkpoint inhibitors
• mast cells
• tumor growth
• tumor therapy

• Angiogenesis
• Cancer therapy
• Metabolic profile
• Signaling pathways
• Solid tumors
• Tumor microenvironment

• Dendritic Cells/pathology
• Humans
• Immune Checkpoint Inhibitors
• Immunotherapy
• Mast Cells/pathology
• Neoplasms/pathology
• Tumor Microenvironment

Prostate-specific membrane antigen (PSMA) expression is encountered in tumor-associated neovascularization.

PSMA-antibody was applied to the paraffin blocks of 51 patients who were diagnosed with squamous cell carcinoma of the larynx and underwent laryngectomy and one who underwent lymph node dissection. The percentage of vascular expression in tumoral and extratumoral stroma and lymph nodes and intensity score in tumoral epithelium were evaluated and divided into groups according to the level of PSMA expression. Final PSMA expression was determined by multiplying intensity and percentage scores.

The mean age was 61±10 years. Patients with perineural invasion, cartilage invasion, and local invasion exhibited higher PSMA expression scores. Age, tumor differentiation, tumor diameter, perineural invasion, tumor localization, capsular invasion, depth of invasion, surgical margin status, local invasion, nodal metastasis, TNM classification, and stage were similar in high and low PSMA expression groups. There was no PSMA expression in extratumoral vascular stroma. Significantly higher PSMA expression was observed in the vascular endothelium of metastatic lymph nodes compared with reactive lymph nodes. Patients with advanced-stage disease exhibited higher PSMA vascular expression scores compared to those with earlier stages (p<.001). PSMA expression was not correlated with overall survival, disease-specific survival, or disease-free survival (p>.05).

Our study suggests that higher PSMA expression is associated with cartilage invasion, local invasion, and advanced-stage of disease. PSMA expression can be utilized for detection of lymph node metastasis and has some predictive role in cases of neck metastasis.

• Organizer/organizational center
• cancer-associated fibroblast (CAF)
• differentiation
• extracellular matrix (ECM)
• stromal cells
• tumor microenvironment

• Cancer-Associated Fibroblasts
• Cell Differentiation
• Extracellular Matrix
• Humans
• Neoplasms/pathology
• Tumor Microenvironment

Metastasis is a key step in cancer progression, and was traditionally attributed to the accumulation of genetic and epigenetic changes within individual cancer cells. These changes promoted invasiveness, immune evasion and survival at distant sites. However, recent studies reveal that metastasis is not achieved by the cancer cell in isolation, but requires intervention from the immune system. The myeloid cell population in particular is now implicated in many aspects of metastasis. Here, we bring together the evidence for the importance of various myeloid cell sub-populations throughout the metastatic process, from initiation of cancer cell invasiveness, to priming the tissue site for colonization.

• Fibrosis
• Gastric cancer
• IL-17A
• Mast cell
• Peritoneal dissemination

• Animal model
• IL-8
• Intercellular space
• LPR
• VEGF
• pH

• CRR9
• apoptosis
• laryngeal squamous cell carcinoma
• miR-182
• proliferation

• 3' Untranslated Regions/genetics
• Animals
• Apoptosis/genetics
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/therapy
• Cell Line
• Cell Line, Tumor
• Cell Proliferation/genetics
• Female
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• Laryngeal Neoplasms/genetics
• Laryngeal Neoplasms/metabolism
• Laryngeal Neoplasms/therapy
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Mice, Nude
• Mice, SCID
• MicroRNAs/genetics
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• RNAi Therapeutics/methods
• Tumor Burden/genetics
• Xenograft Model Antitumor Assays/methods

• DIVAA™
• angiogenesis
• integrin
• mast cell
• proteases
• ubiquitin/proteasome

• Angiogenesis Inducing Agents/pharmacology
• Animals
• Cell Adhesion/drug effects
• Cell Differentiation/drug effects
• Cell Movement/drug effects
• Cells, Cultured
• Endothelial Cells/cytology
• Endothelial Cells/drug effects
• Endothelial Cells/metabolism
• Integrins/metabolism
• Male
• Mice
• Mice, Nude
• Morphogenesis/drug effects
• Neovascularization, Physiologic/drug effects
• Neovascularization, Physiologic/physiology
• Tryptases/metabolism
• Tryptases/pharmacology

Mast cells are being increasingly recognized as critical components in the tumor microenvironment. Protein Kinase D (PKD) is essential for the progression of prostate cancer, but its role in prostate cancer microenvironment remains poorly understood.

The expression of PKD, mast cells and microvessel density were examined by IHC. The clinical significance was determined by statistical analyses. The biological function of PKD and the underlying mechanisms were investigated using in vitro and in vivo models.

PKD2/3 contributed to MCs recruitment and tumor angiogenesis in the prostate cancer microenvironment. Clinical data showed that increased activation of PKD at Ser744/748 in prostate cancer was correlated with mast cell infiltration and microvascular density. PKD2/3 silencing of prostate cancer cells markedly decreased MCs migration and tube formation of HUVEC cells. Moreover, PKD2/3 depletion not only reduced SCF, CCL5 and CCL11 expression in prostate cancer cells but also inhibited angiogenic factors in MCs. Conversely, exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-κB signaling pathway, leading to AP-1 or NF-κB binding to the promoter of scf, ccl5 and ccl11. Finally, PKD-specific inhibitor significantly reduced tumor volume and tumor growth in mice bearing RM-1 prostate cancer cells, which was attributed to attenuation of mast cell recruitment and tumor angiogenesis.

These results demonstrate a novel PKDs function that contributes to tumor angiogenesis and progression through mast cells recruitment in prostate cancer microenvironment.

The online version of this article (10.1186/s13046-019-1118-y) contains supplementary material, which is available to authorized users.

• Angiogenesis
• Mast cells(MCs)
• Prostate cancer
• Protein kinase D(PKD)

• chemokines
• cytokines
• growth factors
• immunity
• inflammation
• mast cells

Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients.

Tissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median </≥7 vessels per visual field) was counted manually. Scores were correlated with N-stage, T-stage and 5-year overall survival rate.

A high expression of angiogenic biomarkers was not associated with poor overall survival in the overall cohort of patients. Instead high CD31 count was associated with early stage cancer (p = 0.004) and in this subgroup high VEGF expression correlated with poor survival (p = 0.032). Additionally, in early stage cancer a high vessel count was associated with an increased recurrence rate (p = 0.004).

Only in the early stage subgroup a high expression of angiogenic biomarkers was associated with reduced survival and an increased rate of recurrence. Thus, biomarkers of angiogenesis may be useful to identify high risk patients specifically in early stage LSCC.

• Angiogenesis
• Biomarkers
• CD31
• Laryngeal squamous cell carcinoma
• VEGF

• basal cell carcinoma
• inflammation
• neurohormones
• neuromediators
• neuropeptides
• photo-carcinogenesis
• squamous cell carcinoma
• penile neoplasms

• Carcinogenesis/genetics
• Carcinoma, Basal Cell/epidemiology
• Carcinoma, Basal Cell/pathology
• Carcinoma, Neuroendocrine/classification
• Carcinoma, Neuroendocrine/epidemiology
• Carcinoma, Neuroendocrine/pathology
• Carcinoma, Squamous Cell/epidemiology
• Humans
• Skin Neoplasms/classification
• Skin Neoplasms/epidemiology
• Skin Neoplasms/pathology
• Solar System
• Ultraviolet Rays/adverse effects

• breast cancer
• colon cancer
• gene expression
• lung cancer
• mast cell

The imbalance of angiogenic regulators in tumors drives tumor angiogenesis and causes the vasculature to develop much differently in tumors than in normal tissue. There are several cancer therapy techniques currently being used and developed that target the tumor vasculature for the treatment of solid tumors. This article reviews the aspects of the tumor vasculature that are relevant to most cancer therapies but particularly to vascular targeting techniques.

We conducted a review of identified experiments in which tumors were transplanted into animals to study the development of the tumor vasculature with tumor growth. Quantitative vasculature morphology data for spontaneous human head and neck cancers are reviewed. Parameters assessed include the highest microvascular density (h-MVD) and the relative vascular volume (RVV). The effects of the vasculature on the tumor microenvironment are discussed, including the distributions of hypoxia and proliferation.

Data for the h-MVD and RVV in head and neck cancers are highly varied, partly due to methodological differences. However, it is clear that the cancers are typically more vascularized than the corresponding normal tissue. The commonly observed chronic hypoxia and acute hypoxia in these tumors are due to high intratumor heterogeneity in MVD and lower than normal blood oxygenation levels through the abnormally developed tumor vasculature. Hypoxic regions are associated with decreased cell proliferation.

The morphology of the vasculature strongly influences the tumor microenvironment, with important implications for tumor response to medical intervention such as radiotherapy. Quantitative vasculature morphology data herein may be used to inform computational models that simulate the spatial tumor vasculature. Such models may play an important role in exploring and optimizing vascular targeting cancer therapies.

• cancer
• head and neck
• hypoxia
• radiotherapy response
• vasculature morphology

To explore angiogenesis in osteosarcoma under the condition of hypoxia-inducible factor (HIF)-1α gene silenced by small interference RNA (siRNA).

The SaOS-2 osteosarcoma cells, transfected with the recombinant plasmid pSilencer2.1-HIF-1α or pSilencer2.1-SCR, were classified as HIF-1α/siRNA group or SCR/siRNA group, respectively. In which, vascular endothelial growth factor (VEGF) immunohistochemistry were performed. HIF-1α and VEGF protein contents were detected by western blot. Gene expressions of HIF-1α and VEGF were quantified by qPCR. Then the transfected SaOS-2 cells were inoculated in nude mice and transplantation tumor were checked via HE staining, VEGF and CD34 immunohistochemistry, and calculation of microvascular density (MVD).

In vitro, VEGF immunohistochemistry stains, HIF-1α and VEGF protein contents, and the relative expressions of HIF-1α mRNA and VEGF mRNA in HIF-1α/siRNA group were obviously reduced. In vivo, morphological observation illustrated that heteromorphism were not obvious in the cells of HIF-1α/siRNA group and vascular systems were sparse in its transplantation tumor tissue, and immunohistochemistry revealed that both VEGF and CD34 stains were significantly decreased in HIF-1α/siRNA group, and MVD in HIF-1α/siRNA group (7.3±1.1) were obviously less than that in SCR/siRNA group (17.2±3.2) (P<0.05).

Angiogenesis in osteosarcoma can be inhibited by siRNA-mediated HIF-1α gene silencing, which is expected to provide a novel and attractive target of therapeutic strategies of osteosarcoma.

• Angiogenesis
• CD34
• Gene silencing
• Hypoxia-inducible factor-1α
• Osteosarcoma
• Small interference RNA
• Vascular endothelial growth factor

• Angiogenesis
• CD24
• Cancer stem cells
• Head and neck cancer
• Oral cancer
• Oral squamous cell carcinoma

• Breast carcinoma
• Lymph node metastasis
• Lymphangiogenesis
• Mast cell density

Mast cells have been shown to express vascular endothelial growth factor (VEGF), thereby implicating mast cells in pro-angiogenic processes. However, the mechanism of VEGF induction in mast cells and the possible expression of VEGF in fully mature mast cells have not been extensively studied. Here, we report that terminally differentiated peritoneal cell-derived mast cells can be induced to express VEGF in response to challenge with Staphylococcus aureus, thus identifying a mast cell–bacteria axis as a novel mechanism leading to VEGF release. Whereas live bacteria produced a robust upregulation of VEGF in mast cells, heat-inactivated bacteria failed to do so, and bacteria-conditioned media did not induce VEGF expression. The induction of VEGF was not critically dependent on direct cell–cell contact between bacteria and mast cells. Hence, these findings suggest that VEGF can be induced by soluble factors released during the co-culture conditions. Neither of a panel of bacterial cell-wall products known to activate toll-like receptor (TLR) signaling promoted VEGF expression in mast cells. In agreement with the latter, VEGF induction occurred independently of Myd88, an adaptor molecule that mediates the downstream events following TLR engagement. The VEGF induction was insensitive to nuclear factor of activated T-cells inhibition but was partly dependent on the nuclear factor kappa light-chain enhancer of activated B cells signaling pathway. Together, these findings identify bacterial challenge as a novel mechanism by which VEGF is induced in mast cells.

• NF-κB
• Staphylococcus aureus
• VEGF family
• mast cells
• peritoneal cavity

• immunohistochemistry
• oral cancer
• real-time polymerase chain reaction
• vascular endothelial growth factor

An association between mast cells and tumor angiogenesis is known to exist, but the exact role that mast cells play in this process is still unclear. It is thought that the mediators released by mast cells are important in neovascularization. However, it is not known how individual mediators are involved in this process. The major constituents of mast cell secretory granules are the mast cell specific proteases chymase, tryptase, and carboxypeptidase A3. Several previous studies aimed to understand the way in which specific mast cell granule constituents act to induce tumor angiogenesis. A body of evidence indicates that mast cell proteases are the pivotal players in inducing tumor angiogenesis. In this review, the likely mechanisms by which tryptase and chymase can act directly or indirectly to induce tumor angiogenesis are discussed. Finally, information presented here in this review indicates that mast cell proteases significantly influence angiogenesis thus affecting tumor growth and progression. This also suggests that these proteases could serve as novel therapeutic targets for the treatment of various types of cancer.

• U54 GM104942 NIGMS NIH HHS

• Alleles
• Animals
• Cost of Illness
• Dog Diseases/pathology
• Dogs
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Mast Cells/metabolism
• Mast Cells/pathology
• Mastocytosis/genetics
• Mastocytosis/pathology
• Prognosis
• Proto-Oncogene Proteins c-kit/biosynthesis
• Uterine Neoplasms/genetics

The anti-inflammatory protein annexin A1 (ANXA1) has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX) in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1_2–26 (annexin A1 N-terminal-derived peptide), Boc2 (antagonist of FPR) and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA1_2–26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1_2–26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth and metastasis through paracrine mechanisms that are mediated by FPR2/ALX. These data may lead to new biological targets for therapeutic intervention in human laryngeal cancer.

• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Annexin A1/chemistry
• Annexin A1/metabolism
• Carcinoma, Squamous Cell/immunology
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cell Degranulation/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Humans
• Inflammation/immunology
• Inflammation/metabolism
• Inflammation/pathology
• Laryngeal Neoplasms/immunology
• Laryngeal Neoplasms/metabolism
• Laryngeal Neoplasms/pathology
• Male
• Mast Cells/cytology
• Mast Cells/drug effects
• Metalloproteases/metabolism
• Middle Aged
• Molecular Sequence Data
• Neoplasm Metastasis
• Neutrophils/drug effects
• Neutrophils/immunology
• Peptide Fragments/chemistry
• Peptide Fragments/pharmacology
• Prostaglandins/metabolism
• Receptors, Formyl Peptide/metabolism
• Receptors, Lipoxin/metabolism
• Receptors, Prostaglandin E, EP3 Subtype/metabolism
• Receptors, Prostaglandin E, EP4 Subtype/metabolism
• Signal Transduction/drug effects
• Tumor Microenvironment/drug effects
• Up-Regulation/drug effects

• Mast cells
• activation
• function
• immunity
• mdiators
• origin

• Animals
• Disease
• Humans
• Mast Cells/cytology
• Mast Cells/immunology
• Mast Cells/metabolism
• Phenotype

Angiogenesis, the formation of new blood vessels, as well as inflammation with massive infiltration of leukocytes are hallmarks of various tumor entities. Various epidemiological, clinical, and experimental studies have not only demonstrated a link between chronic inflammation and cancer onset but also shown that immune cells from the bone marrow such as tumor-infiltrating macrophages significantly influence tumor progression. Tumor angiogenesis is critical for tumor development as tumors have to establish a blood supply in order to progress. Although tumor cells were first believed to fuel tumor angiogenesis, numerous studies have shown that the tumor microenvironment and infiltrating immune cell subsets are important for regulating the process of tumor angiogenesis. These infiltrates involve the adaptive immune system including several types of lymphocytes as well as cells of the innate immunity such as macrophages, neutrophils, eosinophils, mast cells, dendritic cells, and natural killer cells. Besides their known immune function, these cells are now recognized for their crucial role in regulating the formation and the remodeling of blood vessels in the tumor. In this review, we will discuss for each cell type the mechanisms that regulate the vascular phenotype and its impact on tumor growth and metastasis.

• angiogenesis
• endothelial cells
• immune cells
• leukocytes
• microenvironment

Neoangiogenesis is essential for tumor development, invasion, and dissemination. The most potent of the cytokines associated with angiogenesis is vascular endothelial growth factor (VEGF). The aim of the present study was to determine VEGF serum level in patients with salivary gland tumor. Using an ELISA kit, the circulating levels of VEGF in sera from 58 patients with salivary gland tumor and 30 healthy controls were assessed. Mean VEGF levels in sera of patients with salivary gland tumors (574.9 ± 414.3) were significantly higher than those in controls (263.9 ± 310.0) (P = 0.009). Within the salivary gland tumor group, mean serum VEGF concentration in malignant tumors (n = 27) was 727.3 ± 441.8 pg/mL, and that in benign tumors (n = 31) was 442.2 ± 343.3 pg/mL. Mean serum VEGF concentration was significantly higher in malignant tumors than in benign tumors (P = 0.008) and was higher in benign tumors than in controls (P = 0.03). The data in the present study clearly show that VEGF level was consistently upregulated in benign and malignant tumors in comparison to healthy controls. However, the role of VEGF as a prognostic factor in salivary gland tumor and its application in antiangiogenic therapy require further clinical research.

• Angiogenesis
• Macrophages
• Mast cells
• Tumor progression

• Cell Proliferation
• Disease Progression
• Humans
• Inflammation/immunology
• Intercellular Signaling Peptides and Proteins/metabolism
• Macrophages/immunology
• Macrophages/metabolism
• Mast Cells/immunology
• Mast Cells/metabolism
• Neoplasms/blood supply
• Neoplasms/pathology
• Neovascularization, Pathologic/immunology
• Tumor Microenvironment/immunology

Head and neck squamous cell carcinoma (HNSCC) is a complex tissue that contains tumor cells and the surrounding stroma, which is populated by different types of mesenchymal cells and the extracellular matrix (ECM). Collectively, they are referred to as the tumor microenvironment (TME). Recent studies have shown that TME has a more profound influence on the growth and metastasis of HNSCC than was previously appreciated. Because carcinoma-associated fibroblasts (CAFs) are frequently observed in the stroma of the tumor, this review focuses on the potential role of tumor-CAFs interactions in progression of HNSCC. Tumor-CAFs crosstalk enhances the production of growth factors, cytokines, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, which eventually facilitates tumor growth. In fact, factors and cells that do not support tumor growth are usually down regulated or mitigated in TME. Therefore TME may determine the fate of the tumors at the site of invasion and metastasis. For tumor cells that survive at these sites, stromal activation may serve to establish a supportive tumor stroma, fostering the outgrowth of the metastatic cells. The concept of tumor-stromal interactions and microenvironmental niche has profound consequences in tumor growth and metastasis and therefore, it's understanding will open up new strategies for the diagnosis, prognosis and therapy of HNSCC.

• CCL12.
• CXCR4
• Cancer associated fibroblasts (CAFs)
• Cycloxygenase-2 (COX-2)
• Head and neck cancer
• Matrix metalloproteinases (MMPs)

• Antigens, CD34/analysis
• Carcinoma, Squamous Cell/blood supply
• Carcinoma, Squamous Cell/pathology
• Cell Count
• Cell Transformation, Neoplastic/pathology
• Disease Progression
• Epithelium/blood supply
• Epithelium/pathology
• Female
• Histocytological Preparation Techniques
• Humans
• Immunohistochemistry
• Male
• Mast Cells/pathology
• Microvessels/pathology
• Mouth Mucosa/blood supply
• Mouth Mucosa/pathology
• Mouth Neoplasms/blood supply
• Mouth Neoplasms/pathology
• Neovascularization, Pathologic/pathology
• Precancerous Conditions/blood supply
• Precancerous Conditions/pathology
• Tryptases/analysis