• Peptide Nucleic Acids
• Animals
• Bevacizumab/therapeutic use
• Bevacizumab/pharmacology
• Mice
• Tissue Distribution
• Cell Line, Tumor
• Humans
• Female
• Radioisotopes/therapeutic use

• U20A20384 Regional Joint Fund of the National Natural Science Foundation of China

• Disease response
• Pancreatic cancer
• Phase II
• RCT
• Survival

• Male
• Humans
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/etiology
• Double-Blind Method
• Vascular Endothelial Growth Factor A
• Neoplasm Recurrence, Local/drug therapy
• Adenocarcinoma/pathology

• P30 CA138292 NCI NIH HHS

• bevacizumab biosimilar
• intravitreal injection
• nonclinical
• ocular safety

• Animals
• Male
• Bevacizumab/pharmacology
• Macaca fascicularis
• Biosimilar Pharmaceuticals
• Vascular Endothelial Growth Factor A
• Intravitreal Injections
• Toxicokinetics
• Retina
• Angiogenesis Inhibitors

• apoptosis
• cell invasion
• cell migration
• cytotoxicity
• natural products
• prostate cancer

• Angiogenesis
• Cancer-associated acinar-to-ductal metaplasia
• Liver metastasis
• Macrophages
• Pancreatic cancer
• Prognosis

• NADPH Oxidase 4
• Pancreatic cancer
• Reactive oxygen species

• Animals
• Hydrogen Peroxide
• Mice
• NADPH Oxidase 4
• NADPH Oxidases
• Pancreatic Neoplasms
• Reactive Oxygen Species

• angiogenesis
• circular RNAs
• gastrointestinal cancers
• long non-coding RNAs
• microRNAs
• non-coding RNAs

Contrast-enhanced computed tomography (CT) contributes to the increasing detection of pancreatic neuroendocrine neoplasms (PNENs). Nevertheless, its value for differentiating pathological tumor grades is not well recognized. In this report, we have conducted a retrospective study on the relationship between the 2017 World Health Organization (WHO) classification and CT imaging features in 94 patients. Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2, including tumor size, shape, margin, heterogeneity, intratumoral blood vessels, vascular invasion, enhancement pattern in both contrast phases, enhancement degree in both phases, tumor-to-pancreas contrast ratio in both phases, common bile duct dilatation, lymph node metastases, and liver metastases. Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve (AUC) of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis. The portal enhancement ratio (PER) was shown the highest AUC of 0.855 in terms of quantitative features. Our data suggest that the traditional contrast-enhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.

• computed tomography
• heterogeneity analysis
• pancreatic neuroendocrine neoplasm
• tumor grade

Pancreatic cancer is characterized by a dense network of connective tissue surrounding clusters of cancer cells, the so-called stroma. This ubiquitous connective tissue impairs the delivery of oxygen to cancer cells. This results in hypoxia, which renders the cancer more aggressive and more resistant to treatment. In the present study, we investigated whether the extent of hypoxia in pancreatic cancer can be predicted by magnetic resonance imaging (MRI), a widely used medical imaging technique. More specifically, we used an MRI sequence which can quantitate the random motion (i.e., diffusion) of water molecules within the cancer tissue, namely diffusion-weighted (DW) MRI. We found that the random motion of water molecules is lower in cancer lesions with high hypoxia compared to those with low hypoxia. The findings from our study imply that DW-MRI can be used to identify pancreatic cancer lesions with high hypoxia which are at high risk for treatment failure.

Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.

• diffusion-weighted imaging
• hypoxia
• pancreatic ductal adenocarcinoma

• Phage ELISA
• Phage display-mediated immuno-PCR (PD-IPCR)
• Single-domain antibody
• VEGF

The microenvironment within solid malignant tumors, including feline mammary gland carcinomas (FMGCs), is commonly hypoxic, possibly due to the lack of functional blood vessels in rapidly proliferating neoplastic tissue. Malignant cells can undergo genetic and adaptive changes that prevent them from dying due to oxygen deprivation through expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Therefore, HIF-1α and VEGF are ideal biomarkers for cancer therapy and prognostic evaluation. The aims of this study were to evaluate the expression of HIF-1α and VEGF in feline mammary carcinomas and analyze their correlations with clinical and pathological factors, such as clinical stage, histologic grading, regional metastasis, and overall survival rate.

Paraffin-embedded tissue samples collected from 72 cats with FMGCs were retrospectively studied. Histologic pattern and histologic grading (Elston and Ellis grading system) of these FMGCs were determined. Our data indicated that grade II tubulopapillary carcinomas (43/72, 59.7%) prevailed in this study, and most FMCGs showed apparent necrosis, squamous metaplasia, and intratumoral stromal response. According to the results of immunohistochemical (IHC) stainings performed in tissue microarrays (TMAs), HIF-1α and VEGF overexpressions were respectively noted in 69.4% (50/72) and 77.8% (56/72) of FMGC cases. Chi-square test showed no correlation of HIF-1α overexpression with clinical and pathological factors. VEGF overexpression was significantly correlated with histologic pattern (p = 0.021), stromal response (p = 0.048), squamous metaplasia (p = 0.001), and lymphovascular invasion (p = 0.007). However, neither HIF-1α nor VEGF overexpression was correlated with histologic grading and metastasis. Of 38 cats with 1-year follow-up, IHC stainings of HIF-1α and VEGF were performed on whole tissue sections. The results showed that overexpression of HIF-1α was significantly correlated with the overall survival rate (p < 0.05) (log-rank test), whereas there was no significant correlation between VEGF overexpression and overall survival rate.

This study suggests that the overexpression of HIF-1α may indicate poor prognosis/overall survival rate in cats with FMGCs. Developing compounds that inhibit HIF-1α may be a potential approach to FMGC treatment.

• Feline
• Hypoxia-inducible factor 1 alpha (HIF-1α)
• Mammary gland carcinoma
• Vascular endothelial growth factor (VEGF)

• Angiocrine
• Angiogenesis
• Cancer
• Cancer microenvironment
• Endothelium

• Endothelial Cells
• Endothelium
• Humans
• Neoplasms/genetics
• Neovascularization, Pathologic
• Tumor Microenvironment

Vascularization influences tumor development by supporting the nutrition and dissemination of tumor cells. On the other hand, a low number of vascular vessels (VV^low) may induce hypoxia, accounting for selection of resistant clone(s) of tumor cells. This study aimed to evaluate the prognostic significance of vascular (VV) and lymphatic vessels (LV) in prostate cancer (PCa). Tumor samples from 400 PCa patients undergoing radical prostatectomy (RP) were prepared in duplex as tissue microarrays. Numbers of VV and LV were evaluated using immunohistochemistry detecting CD34 and podoplanin, respectively, and correlated to clinical data, biochemical recurrence (BR), and proteins analyzed in tumor cells. VV^low and LV were found in 32% and 43% of patients with informative PCa samples, respectively. VV^low correlated with a shorter time to BR 3, 5, and 10 years after RP in hormone-naïve patients (p = 0.028, p = 0.027 and p = 0.056, respectively). It was also shown to be an independent prognostic factor 5 years after surgery (multivariate analysis, p = 0.046). Tumors characterized by VV^low expressed the epithelial cell adhesion molecule, EpCAM, less frequently (p = 0.016) and revealed a borderline correlation to increased levels of tumor cell invasion marker Loxl-2 (p = 0.059). No correlations were found for LV. In summary, VV^low in hormone-naïve patients undergoing RP has prognostic potential and seems to be related to an aggressive phenotype of tumor cells.

• CD34
• heterogeneity
• hormone-naïve patients
• lymphatic vessels
• podoplanin
• prostate cancer
• tumor progression
• vascular vessels

To evaluate the role of blood vascular endothelial growth factor (VEGF) kinetics in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT).

A total of 97 locally advanced ESCC patients were enrolled. All the patients had their blood drawn at three time points to determine their levels of VEGF, including pre-chemotherapy (day 0), post-chemotherapy (day 5), and pre-cycle 2 chemotherapy (day 28). The VEGF levels were evaluated according to the day 0 value, day 5 value, day 28 value, day 5/day 0 ratio, day 28/day 0 ratio, and day 28/day 5 ratio. A VEGF cut-off level of 80 pg/mL was applied.

In the analysis of progression-free survival (PFS), the patients less than 60 years old had significantly superior PFS compared to those more than 60 years old. Patients who had VEGF < 80 pg/mL at day 28 and a day 28/day 5 ratio < 1 had better PFS than those with VEGF > 80 pg/mL and a day 28/day 5 ratio > 1, respectively. In the analysis of overall survival (OS), patients with N0–1 status had significantly superior OS compared to those with N2–3 status. Furthermore, patients who had VEGF < 80 pg/mL at day 28, a day 5/day 0 ratio < 1, and a day 28/day 5 ratio < 1 had superior OS compared to those patients with VEGF > 80 pg/mL, a day 5/day 0 ratio > 1, and a day 28/day 5 ratio > 1, respectively. In the multivariate analysis, only VEGF < 80 pg/mL at day 28 and a day 28/day 5 ratio < 1 represented independent prognostic factors of superior PFS and OS.

Our study suggests that VEGF kinetics is a prognostic factor for locally advanced ESCC patients receiving curative CCRT. For these patients, lower post-treatment VEGF levels and decreasing levels of VEGF during CCRT are significantly associated with better clinical outcomes.

• Concurrent chemoradiotherapy
• Esophageal cancer
• Squamous cell carcinoma
• VEGF

Tubeimoside-1 (TBMS1) possesses broad anticancer activities, including the cytostatic and anti-angiogenesis effects in lung cancer. However, the effect of TBMS1 on the metastasis of non-small cell lung cancer (NSCLC) cells and the potential underlying mechanism remain unclear. In the present study, a cell counting kit-8 assay revealed that TBMS1 suppressed the proliferation of NCI-H1299 cells significantly, particularly following 48 h of treatment. Further studies showed that TBMS1 notably enhanced the apoptosis, and inhibited the migration and invasion of NCI-H1299 cells upon treatment for 48 h. A total of 14 NSCLC tissues and 14 normal adjacent tissues were collected, reverse transcription-quantitative polymerase chain reaction revealed decreased expression of microRNA (miR)-126-5p in NSCLC tissues compared with adjacent NSCLC tissues, which was reversed following TBMS1 administration in NCI-H1299 cells. The overexpression of miR-126-5p induced by TBMS1 was demonstrated to target and downregulate vascular endothelial growth factor (VEGF)-A. Simultaneously, the expression of VEGF-R2 was reduced notably, along with a significant declined in the phosphorylation levels of dual specificity mitogen-activated protein kinase kinase 1 and extracellular signal-regulated kinase (ERK)1/2. Overall, the aforementioned results indicated that TBMS1 inhibited the proliferation and metastasis, and promoted the apoptosis of NCI-H1299 cells, which may be mediated by overexpressing miR-126-5p, which inactivates the VEGF-A/VEGFR2/ERK signaling pathway. Therefore, TBMS1 may be a promising drug for prevention and treatment of NSCLC.

• VEGF-A
• miR-126-5p
• non-small cell lung cancer
• tubeimoside-1

• attenuation value
• computed tomography
• pancreatic neuroendocrine neoplasm
• pathologic grade

• angiogenesis
• hypoxia
• interstitial fluid pressure
• metastasis
• pancreatic carcinoma

• Animals
• Biopsy
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/pathology
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Heterografts
• Humans
• Hypoxia/metabolism
• Lymphatic Metastasis
• Mice
• Neovascularization, Pathologic/metabolism
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Tumor Microenvironment
• Pancreatic Neoplasms

• pancreatic neoplasms
• molecular biology
• p53 protein
• prognosis
• microvessel

• Carcinoma, Pancreatic Ductal/blood supply
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/mortality
• Carcinoma, Pancreatic Ductal/pathology
• Female
• Humans
• Male
• Margins of Excision
• Microvessels/pathology
• Middle Aged
• Neoplasm Staging
• Pancreatic Neoplasms/blood supply
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Prognosis
• Survival Rate
• Tumor Suppressor Protein p53/metabolism

AIM: To develop a potent and safe gene therapy for esophageal cancer.

METHODS: An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo.

RESULTS: Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity.

CONCLUSION: The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.

• Esophageal cancer
• Suicide gene
• RNA interference
• Vascular endothelial growth factor
• Nanoparticles

• Animals
• Calcium Phosphates/chemistry
• Cell Line, Tumor
• Drug Carriers/chemistry
• Esophageal Neoplasms/therapy
• Female
• Flucytosine/administration & dosage
• Flucytosine/therapeutic use
• Genes, Transgenic, Suicide
• Genetic Vectors/administration & dosage
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles/chemistry
• Promoter Regions, Genetic
• RNA, Small Interfering/administration & dosage
• RNA, Small Interfering/metabolism
• RNA, Small Interfering/therapeutic use
• RNAi Therapeutics/methods
• Telomerase/genetics
• Transfection
• Treatment Outcome
• Vascular Endothelial Growth Factor A/metabolism
• Xenograft Model Antitumor Assays

• Angiogenesis
• Pancreatic cancer
• Vascular endothelial growth factor (VEGF)

• STAT3
• TGF-β
• angiogenesis
• mouse model
• pancreatic cancer

• Adenocarcinoma/genetics
• Adenocarcinoma/mortality
• Animals
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/mortality
• Cell Proliferation
• Disease Models, Animal
• Humans
• Mice
• Neovascularization, Pathologic/metabolism
• STAT3 Transcription Factor/metabolism
• Signal Transduction
• Xenograft Model Antitumor Assays

• R37 CA075059 NCI NIH HHS
• P30 CA082709 NCI NIH HHS
• UL1 TR001108 NCATS NIH HHS
• T32 GM077229 NIGMS NIH HHS
• CA-075059 NCI NIH HHS
• R01 CA075059 NCI NIH HHS

• Adult
• Aged
• Carcinoma, Neuroendocrine/diagnostic imaging
• Carcinoma, Neuroendocrine/pathology
• Contrast Media
• Female
• Humans
• Iohexol/analogs & derivatives
• Male
• Middle Aged
• Neoplasm Grading
• Pancreas/diagnostic imaging
• Pancreas/pathology
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/pathology
• Radiographic Image Enhancement/methods
• Reproducibility of Results
• Retrospective Studies
• Sensitivity and Specificity
• Tomography, X-Ray Computed/methods

The aim of this pilot study was to determine the plasma levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) and find possible association between them and main clinical features and parameters of tumor burden in patient with multiple myeloma (MM). Plasma levels of OPN and VEGF were determined in 44 newly diagnosed MM patients and 24 healthy persons by ELISA method. These values were compared with the presence of anemia, renal dysfunction, and bone lesions as myeloma related clinical manifestations and with serum beta-2 microglobulin and Durie-Salmon clinical stage as prognosticators related to tumor mass. The value of OPN was significantly higher in MM patients with evident bone lesions (P = 0.03) and there was also a positive correlation with serum beta-2 microglobulin (r = 0.366; P = 0.04). Furthermore, patients with lower Durie-Salmon stage had significantly lower OPN and VEGF levels (P = 0.05; P = 0.04, resp.). Our preliminary results found positive association between plasma level of OPN, tumor burden, and bone destruction. Further analysis should provide information about the possible use of OPN as useful clinical biomarker for monitoring bone disease and tumor mass, as well as a prognostic factor, or a possible target for pharmacological intervention.

The complex signaling networks between cancer cells and adjacent endothelial cells make it challenging to unravel how cancer cells send extracellular messages to promote aberrant vascularization or tumor angiogenesis. Here, in vitro and in vivo models show that pancreatic cancer cell generated unique microenvironments can underlie endothelial cell migration and tumor angiogenesis. Mechanistically, we find that pancreatic cancer cell secreted CCN1/Cyr61 matricellular protein rewires the microenvironment to promote endothelial cell migration and tumor angiogenesis. This event can be overcome by Sonic Hedgehog (SHh) antibody treatment. Collectively, these studies identify a novel CCN1 signaling program in pancreatic cancer cells which activates SHh through autocrine-paracrine circuits to promote endothelial cell migration and tumor angiogenesis and suggests that CCN1 signaling of pancreatic cancer cells is vital for the regulation of tumor angiogenesis. Thus CCN1 signaling could be an ideal target for tumor vascular disruption in pancreatic cancer.

• Hypoxia inducible factor-1α
• Microvessel count
• Pancreatic cancer
• Thymidine phosphorylase
• Vascular endothelial growth factor

• Angiogenesis Inducing Agents/metabolism
• Animals
• Arterioles/physiology
• Disease Models, Animal
• Gene Expression Regulation, Neoplastic
• Islets of Langerhans/blood supply
• Islets of Langerhans/metabolism
• Mice
• Mice, Knockout
• Microvessels/pathology
• Multiple Endocrine Neoplasia Type 1/blood supply
• Multiple Endocrine Neoplasia Type 1/metabolism
• Multiple Endocrine Neoplasia Type 1/pathology
• Neoplasm Proteins/metabolism
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/metabolism
• Neovascularization, Pathologic/pathology
• Pancreatic Neoplasms/blood supply
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Pericytes/pathology
• Proto-Oncogene Proteins/metabolism
• RNA, Messenger/genetics

Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The present study was designed to determine the role of VEGF in tumor growth and metastasis. The sequences for the VEGF gene were cloned into expression plasmids and then transfected into melanoma B16 cells. Overexpression of VEGF transfected with expression plasmids or given exogenous VEGF and epidermal growth factor (EGF) significantly enhanced tumor cell proliferation, migration, and invasion. Tumor growth and metastasis of melanoma B16 cells transfected with VEGF plasmid were significantly promoted compared with those of cells administered with exogenous VEGF or EGF. These results indicated that VEGF can be an effective antiangiogenic strategy for melanoma.

• B16 cells
• EGF
• VEGF

Tumor angiogenesis is known to be regulated by growth factors secreted by host and tumor cells. Despite the importance of tumor vasculature and angiogenic heterogeneity in solid tumors, few studies have compared the vasculature in different regions of human cancer. Blood vessels from different regions of carcinomas might have morphofunctional implications in tumor angiogenesis. In the present study, therefore, we have examined the relationship between microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression and alpha smooth muscle actin (α-SMA) expression in the center of the tumor (CT), periphery (P) and metastasis (M) regions from gastrointestinal carcinomas (GITC), as well as the association of MVD with clinicopathological factors. Surgically resected specimens corresponding to the CT, P and M from 27 patients were examined for FVIII, VEGF and α-SMA by immunohistochemistry. The MVD was not significantly different in the CT, P and M regions from GITC. The MVD in the VEGF positive group was significantly higher than in the VEGF negative group (CT, p = 0.034; P, p = 0.030; M, p = 0.032). The MVD as a function of α-SMA expression was also significantly higher in the CT and P region compared to the M region (p = 0.0008). In conclusion, the MVD association with VEGF and α-SMA expression, might indicate an increase of the number of neoformed and preexisting blood vessels uniformly or partially covered by pericytes in different regions of GITC, suggesting that not only MVD and VEGF are important parameters to the tumor vasculature, but also blood vessels maturation is a crucial factor for gastrointestinal tumor angiogenesis regulation and possible target of vascular therapy.

• Biomarkers, Tumor/metabolism
• Carcinoma, Pancreatic Ductal/diagnosis
• Carcinoma, Pancreatic Ductal/mortality
• Humans
• Immunohistochemistry/methods
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/mortality
• Prognosis

• sp1
• angiogenesis
• vegf
• betulinic acid
• mithramycin a

• Adenocarcinoma/blood supply
• Adenocarcinoma/drug therapy
• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Animals
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Cell Division/drug effects
• Cell Line, Tumor/drug effects
• Collagen
• Drug Combinations
• Drug Screening Assays, Antitumor
• Drug Synergism
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Laminin
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Neovascularization, Pathologic/drug therapy
• Pancreatic Neoplasms/blood supply
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Pentacyclic Triterpenes
• Plicamycin/administration & dosage
• Plicamycin/pharmacology
• Promoter Regions, Genetic/genetics
• Proteoglycans
• Recombinant Fusion Proteins/biosynthesis
• Sp1 Transcription Factor/genetics
• Triterpenes/administration & dosage
• Triterpenes/pharmacology
• Vascular Endothelial Growth Factor A/genetics
• Xenograft Model Antitumor Assays
• Betulinic Acid

• P20 CA101936 NCI NIH HHS
• R01 CA129956 NCI NIH HHS
• R01 CA148954 NCI NIH HHS
• R01 CA152309 NCI NIH HHS

• immunohistochemistry
• molecular
• pancreatic cancer
• meta-analysis
• prognosis

• Adenocarcinoma/chemistry
• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/immunology
• Cyclin-Dependent Kinase Inhibitor p16
• ErbB Receptors/analysis
• Humans
• Immunohistochemistry
• Neoplasm Proteins/analysis
• Pancreatic Neoplasms/chemistry
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/surgery
• Predictive Value of Tests
• Prognosis
• Proto-Oncogene Proteins c-bcl-2/analysis
• Smad4 Protein/analysis
• Tumor Suppressor Protein p53/analysis
• Vascular Endothelial Growth Factor A/analysis
• bcl-2-Associated X Protein/analysis

• 08/29/02 Department of Health
• 11883 Cancer Research UK
• 8968 Cancer Research UK

• pancreatic ductal adenocarcinoma
• vascular endothelial growth factor receptor
• epidermal growth factor receptor
• p53

• adhesion
• angiogenic potential
• invasion
• migration
• pancreatic adenocarcinoma cell lines
• tumorigenicity

• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p16/genetics
• Genotype
• Humans
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Phenotype
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins p21(ras)
• Smad4 Protein/genetics
• Tumor Suppressor Protein p53/genetics
• ras Proteins/genetics

• T35 HL007744 NHLBI NIH HHS
• T35HL07744 NHLBI NIH HHS

• confocal laser scanning imaging
• magnetic resonance imaging
• dorsal window chamber
• permeability
• vasculature

• Animals
• Bone Neoplasms/blood supply
• Capillary Permeability
• Contrast Media
• Disease Models, Animal
• Female
• Humans
• Linear Models
• Magnetic Resonance Imaging/methods
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Confocal/methods
• Microvessels/metabolism
• Microvessels/pathology
• Neovascularization, Pathologic/pathology
• Osteosarcoma/blood supply
• Structure-Activity Relationship
• Transplantation, Heterologous

• Animals
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Blotting, Western
• Body Weight/drug effects
• Cell Line, Tumor
• Chromatin Immunoprecipitation
• Dose-Response Relationship, Drug
• Drug Synergism
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Plicamycin/administration & dosage
• Plicamycin/analogs & derivatives
• Promoter Regions, Genetic/genetics
• Protein Binding
• Sp1 Transcription Factor/genetics
• Sp1 Transcription Factor/metabolism
• Tumor Burden/drug effects
• Vascular Endothelial Growth Factor A/genetics
• Vascular Endothelial Growth Factor A/metabolism
• Xenograft Model Antitumor Assays
• ortho-Aminobenzoates/administration & dosage

• 1P20-CA101936-01-PP4 NCI NIH HHS
• R01 CA129956 NCI NIH HHS
• R01 CA148954 NCI NIH HHS
• P20 CA101936-010004 NCI NIH HHS
• 5R01-CA129956 NCI NIH HHS
• P20 CA101936 NCI NIH HHS
• R01 CA129956-02 NCI NIH HHS
• R01 CA129956-01A1 NCI NIH HHS
• R01 CA152309 NCI NIH HHS

• Angiogenesis Inhibitors/therapeutic use
• Humans
• Neoplasms/blood supply
• Neoplasms/drug therapy
• Neoplasms/physiopathology
• Neovascularization, Pathologic/drug therapy
• Neovascularization, Pathologic/physiopathology