Chemotherapy-mediated miR-29b expression inhibits the invasion and angiogenesis of cervical cancer.

Radiotherapy combined with platinum-based chemotherapy is the standard-of-care of locally advanced cervical cancer (CC) patients, while nearly 50% of patients do not respond to standard chemotherapy. Thus, identification of relative molecules participated in chemotherapy might provide new insights in the treatment of CC. In this study, we found a cohort of miRNAs were dysregulated upon treatment with cisplatin, among of which miR-29b was the most upregulated one. We further detected its expression in CC tissues, and found that miR-29b was significantly suppressed in CC and its precancerous lesions, HSIL tissues, and was negatively related with tumor invasion. However, upon treatment with cisplatin, the expression of miR-29b was significantly up-regulated. The biological function assays showed that overexpression of miR-29b suppressed the invasion, EMT procedure and angiogenesis of cervical cancer cells in vitro and inhibited tumor growth and neovascularization in vivo through targeting STAT3 signal pathway. While, inhibition of miR-29b could prevent the cisplatin-induced epithelial features, cell movement and angiogenesis of CC cells, which means miR-29b/STAT3 axis participates in the chemotherapy of cisplatin in CC. Collectively, our data suggest that chemotherapy-mediated miR-29b expression participates in the initiation and progression of cervical cancer through suppressing the proliferation, EMT procedure and angiogenesis of cervical cancer cells by targeting STAT3 signal pathway.

Speckle-variance optical coherence tomography: a novel approach to skin cancer characterization using vascular patterns.

Non-invasive imaging devices are currently being utilized in research and clinical settings to help visualize, characterize, anddiagnose cancers of the skin. Speckle-variance optical coherence tomography (svOCT) is one such technology that offers considerable promise for non-invasive, real time detection of skin cancers given its added ability to show changes in microvasculature. We present four early lesions of the face namely sebaceous hyperplasia, basal cell skin cancer, pigmented actinic keratosis, and malignant melanoma in situ that each display different important identification markers on svOCT. Up until now, svOCT has mainly been evaluated for lesion diagnosis using transversal (vertical) sections. Our preliminary svOCT findings use dynamic en face (horizontal) visualization to differentiate lesions based on their specific vascular organizations. These observed patterns further elucidate the potential of this imaging device to become a powerful tool in patient disease assessment.

Findings of the margin around lesions by magnifying endoscopy with narrow-band imaging in early gastric carcinoma and intestinal metaplasia.

OBJECTIVE: Many endoscopists have reported their own classifications of early gastric carcinoma (EGC) using magnifying narrow-band imaging (M-NBI). However, few reports on classifying the margin around lesions by M-NBI have been published. The aim of this study was to advocate the usefulness of the demarcation area classification for the diagnosis of EGC. METHODS: Altogether 197 lesions that could be investigated by M-NBI were included in this study, consisting of 115 EGC and 82 intestinal metaplasias (IM). We hypothesized that the changes in white zone (fusion and erasure signs) and blood vessel (extend and draw sign) were the indications of EGC and we retrospectively investigated this hypothesis. RESULTS: For the investigation of the white zone in the demarcation area, both fusion (P < 0.0001) and erasure signs (P < 0.0001) were observed more often in EGC than in IM, with an accuracy of 80.7%. For the investigation of blood vessel in the demarcation area, both the extend (P < 0.001) and the draw sign (P < 0.0001) were observed more often in EGC than in IM, with an accuracy of 59.9%. CONCLUSION: Estimations of the white zone and blood vessels in the demarcation area are useful for the diagnosis of EGC.

Hypovascular hepatic nodules at gadoxetic acid-enhanced MRI: whole-lesion hepatobiliary phase histogram metrics for prediction of progression to arterial-enhancing hepatocellular carcinoma.

PURPOSE: To explore whole-lesion histogram analysis of the hepatobiliary phase (HBP) defect in indeterminate hypovascular liver lesions for predicting progression to arterial-enhancing hepatocellular carcinoma (HCC). METHODS: Twenty patients undergoing gadoxetic acid-enhanced MRI for HCC screening with 12° and 25° flip angle (FA) HBP acquisitions demonstrating an indeterminate lesion showing HBP hypointensity but no arterial enhancement were included. Volumes-of-interest were placed on HBP defects, from which histogram metrics were obtained. Associations between these metrics and progression to arterial-enhancing HCC on follow-up imaging were investigated. Lesions were also assessed for the presence of a signal abnormality on conventional sequences. RESULTS: 40% of lesions progressed to arterial-enhancing HCC; 60% were stable at ≥6 months follow-up. Neither T2-hyperintensity increased diffusion signal nor portal/equilibrium phase washout was different between progressing and nonprogressing lesions (p = 1.0). Among direct signal intensity-based measures (overall mean; mean of bottom 10th, 10-25th, and 25-50th percentiles), area-under-the-curve (AUC) for prediction of progression to arterial-enhancing HCC was consistently higher at 25° (range 0.619-0.657) than at 12° (range 0.512-0.548). However, at both FAs, the four measures with highest AUC were measures related to lesion texture and heterogeneity [standard deviation (SD), coefficient of variation (CV), skewness, and entropy], having AUC of 0.655-0.750 at 12° and 0.686-0.800 at 25. The metric with highest AUC at 12° was SD (AUC = 0.750) and at 25° was CV (AUC = 0.800). CONCLUSION: Whole-lesion histogram HBP measures of indeterminate hypovascular liver lesions may help predict progression to arterial-enhancing HCC by reflecting greater lesion heterogeneity, particularly at higher FA. Larger studies are therefore warranted.

Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long-term outcomes and risk factors for hypervascular transformation.

PURPOSE: To evaluate the long-term outcomes and imaging features associated with hypervascularization of hypovascular nodules that show T2 iso-/hypointensity and hypointensity on hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) images in patients with chronic liver disease. MATERIALS AND METHODS: Sixty patients and 114 nodules, which were hypovascular and iso-/hypointense on T2-weighted images and hypointense on HBP of gadoxetic acid-enhanced MRI, were included. We evaluated the effect of baseline clinical features, baseline MR features and growth rate on subsequent hypervascularization. RESULTS: Twenty-seven nodules in 21 patients transformed to hypervascular hepatocellular carcinoma (HCC). Using multivariate Cox analysis, T1 hyperintensity (hazard ratio [HR] = 2.69, P = 0.021), previous history of HCC (HR = 2.64, P = 0.021), and initial nodule size (HR = 1.09, P = 0.046) were identified to be associated with hypervascularization. The growth rate of nodules was a more powerful determinant of subsequent hypervascularization than baseline clinical and MR features. At long-term follow-up after >3 years, only one nodule with T1 isointensity showed hypervascularization. CONCLUSION: Careful follow-up or diagnostic procedures, such as biopsy, should be considered for up to 3 years after detection of hypointense nodules on HBP with T1 hyperintensity or a higher growth rate. KEY POINTS: • T1 hyperintensity is a baseline MR predictive factor for subsequent hypervascularization. • A higher growth rate is a more powerful determinant of subsequent hypervascularization. • Management of patients with these predictive factors requires more attention.

[Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions]. / Gefäßveränderungen der Stimmlippen - Teil 2: Perpendikuläre Gefäßveränderungen.

The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis.

Evaluation of Microvascularity by CD34 Expression in Esophagus and Oral Squamous Cell Carcinoma.

AIM: The present study was scheduled to evaluate microvascularity by CD34 expression in esophagus and oral squamous cell carcinoma. MATERIALS AND METHODS: This study was scheduled using 40 paraffin blocked samples including 20 of oral SCC and 20 of esophagus ones and Immunohistochemical staining was conducted using CD34 monoclonal antibody. Exact fisher test was used to evaluate frequency of expression between two studied groups. RESULTS: There was significant correlation between age and tumor size with CD34 expression in oral SCC samples (p < 0.05) and no significant correlation between sex and tumor differentiation level (grading) (p > 0.05). Also, there was no significant correlation between age, sex, tumor size and tumor differentiation level (grading) with CD34 expression in esophagus SCC samples (p > 0.05). There was no significant difference of CD34 expression frequency in oral and esophagus SCC (p = 0/583). Finally, CD34 expression was reported 'high' for major cases of esophagus and oral SCCs. CONCLUSION: It seems, other angiogenetic or nonangiogenetic factors except CD34 may play more important role and explain the different clinical behavior of SCC at recent different locations. CLINICAL SIGNIFICANCE: Other factors would be considered along with CD34 expression to interpret different clinical behavior of SCC at recent different locations.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

BACKGROUND: We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. MATERIAL AND METHODS: Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. RESULTS: Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. CONCLUSION: Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.

Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis.

PURPOSE: To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. MATERIALS AND METHODS: Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and fetuses were used. Traditional histological as well as immunohistochemical methods have been used. RESULTS: The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. Glandular epithelial coverings, as well as transitional epithelium, do not contain blood vessels. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus, the cells of squamous epithelium are more vulnerable to blood deficiency, since for instance in the pseudo-multilayered respiratory epithelium each cell is attached directly to the basal membrane and has more ample access to the blood supply. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels. CONCLUSION: The process of redistribution of vascular network occurring at the interface of epithelial-stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations.

Social determinants of hospitalizations for ambulatory care sensitive conditions in Guarulhos, São Paulo / Los determinantes sociales de las hospitalizaciones por condiciones sensibles a la atención primaria en guarulhos, são paulo / Determinantes sociais das Internações por Condições Sensíveis à Atenção Primária em Guarulhos, São Paulo

The study goals present an overview of Hospitalizations for Ambulatory Care Sensitive Conditions (ACSC) in Guarulhos, SP, from 2008 to 2012. This is an ecological study based on secondary data obtained from the Brazilian Hospital Information System, and supported by the Praxical Theory of Intervention of Collective Health Nursing. Applied descriptive statistics for analysis. It was observed that Guarulhos shows an upward trend in hospitalizations by ACSC (20% increase), the most frequent causes of heart failure (11.8%), cerebrovascular disease (10.6%) and angina (9.7%), most frequently in the age group ≥ 65years old, for both sexes. The results are similar to other Brazilian studies, but their analysis should extrapolate the biological limits and the supply of healthcare resources, focusing on the social determinants of the health-disease process.


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El estudio tuvo como objetivo proporcionar una visión general de las Hospitalizaciones por Condiciones Sensibles a la Atención Primaria (ICSAP) en Guarulhos, SP, en el período 2008-2012. Se trata de un estudio ecológico a partir de datos secundarios obtenidos a través del Sistema de Información Hospitalaria, y apoyado por la Teoría de Intervención Práxica de la Enfermería en Salud Colectiva. Se aplicó la estadística descriptiva para el análisis. Se observó que Guarulhos muestra una tendencia al alza en las hospitalizaciones por ICSAP (aumento del 20%), las causas más frecuentes de insuficiencia cardiaca (11,8%), enfermedad cerebrovascular (10,6%) y la angina (9,7% ), con mayor frecuencia en el grupo de edad ≥ 65 años para ambos sexos. Los resultados son similares a otros estudios brasileños, pero su análisis debe extrapolar los límites biológicos y el suministro de los recursos sanitarios, centrándose en los determinantes sociales del proceso salud-enfermedad.
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Objetivo Apresentar o panorama das Internações por Condições Sensíveis à Atenção Primária (ICSAP) no município de Guarulhos, SP, no período de 2008 a 2012. Método Estudo ecológico, com dados secundários obtidos via Sistema de Informações Hospitalares, sustentado pela Teoria de Intervenção Práxica da Enfermagem em Saúde Coletiva. Empregou-se estatística descritiva para análise. Resultados Observou-se que Guarulhos apresenta trajetória crescente nas internações por ICSAP (aumento de 20%), sendo as causas mais frequentes a insuficiência cardíaca (11,8%), as doenças cerebrovasculares (10,6%) e a angina (9,7%), com maior frequência na faixa etária ≥ 65 anos, para ambos os sexos. Conclusão Os resultados encontrados assemelham-se a outros estudos brasileiros, porém sua análise deve extrapolar os limites biológicos e a oferta de recursos assistenciais, atentando para as determinações sociais do processo saúde-doença. .

The clinical effectiveness of reflectance optical spectroscopy for the in vivo diagnosis of oral lesions.

Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green-amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the Identafi(®) system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using Identafi(®) device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker (CD34) were performed on these tissue samples. The clinical vascular grading using the green-amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to 3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.

Narrow-band imaging system with magnifying endoscopy for early oral cancer.

It is often difficult to detect early oral cancer due to the specificity of the oral mucosa structure. The aim of this study was to investigate the potential of narrow band imaging (NBI) as an effective and non-invasive diagnostic tool in early oral cancer and other oral diseases. A magnifying endoscopy system manufactured by Olympus Corporation was used. A total of 121 subjects were included in the study. Subepithelial capillary loops were identified and categorized according to the classification of Inoue, with healthy mucosa graded as Type I or II, and that showing evidence of cancer-induced morphological change as Type III or IV. Sensitivity and specificity for the identification of oral cancer were estimated at 92.3% and 88.2%, respectively. Examination under a microscope with H&E staining and immunostaining for CD34 revealed dilation and extension of the capillaries in epithelial dysplasia, in addition to thickening of the epithelial layer. The present results indicate that use of NBI in conjunction with conventional magnifying endoscopy has great potential as an effective and non-invasive diagnostic tool in the early detection of oral cancer.

Mechanistic insights into self-reinforcing processes driving abnormal histogenesis during the development of pancreatic cancer.

Pancreatic ductal adenocarcinoma, one of the most feared lethal and painful diseases, is increasing in incidence. The poor prognosis of pancreatic ductal adenocarcinoma-affected patients primarily is owing to our inability to develop effective therapies. Mechanistic studies of genetic, epigenetic, and cell-to-cell signaling events are providing clues to molecular pathways that can be targeted in an attempt to cure this disease. The current review article seeks to draw inferences from available mechanistic knowledge to build a theoretical framework that can facilitate these approaches. This conceptual model considers pancreatic cancer as a tissue disease rather than an isolated epithelial cell problem, which develops and progresses in large part as a result of three positive feedback loops: i) genetic and epigenetic changes in epithelial cells modulate their interaction with mesenchymal cells to generate a dynamically changing process of abnormal histogenesis, which drives more changes; ii) the faulty tissue architecture of neoplastic lesions results in unsynchronized secretion of signaling molecules by cells, which generates an environment that is poor in oxygen and nutrients; and iii) the increased metabolic needs of rapidly dividing cells serve as an evolutionary pressure for them to adapt to this adverse microenvironment, leading to the emergence of resistant clones. We discuss how these concepts can guide mechanistic studies, as well as aid in the design of novel experimental therapeutics.

Detection and characterization of early gastric cancer for curative endoscopic submucosal dissection.

Because endoscopic submucosal dissection (ESD) of gastric cancer can only be curative if the cancer is detected at an early stage and a precise preoperative diagnosis is made, we reviewed the detection and characterization of early gastric cancer (EGC) using both conventional endoscopy with white-light imaging (C-WLI) and image-enhanced endoscopy (chromoendoscopy [CE] and magnifying narrow-band imaging [M-NBI]). Systematic screening of the stomach by C-WLI after ideal preparation of the patient is important for detecting a mucosal lesion, which can then be characterized using CE. However, a limitation of C-WLI with CE is the diagnosis of flat or small gastric cancers. To overcome this, M-NBI together with a comprehensive diagnostic system, termed the 'vessel plus surface classification' system, was developed and has proven very useful. Preoperative assessment for ESD involves determining: (i) histological type; (ii) size; (iii) depth of invasion; (iv) presence or absence of associated ulceration; and (v) horizontal extent of the cancer. A limitation of endoscopic diagnosis using M-NBI is the histologically undifferentiated type of carcinoma, in which case the biopsy specimen is used to make a histopathological diagnosis.

[Effect of huazhuo jiedu hewei recipe on the mechanism of angiogenesis in precancerous lesions of gastric cancer rats].

OBJECTIVE: To explore the possible angiogenesis mechanism of Huazhuo Jiedu Hewei Recipe (HJHR) in preventing and treating precancerous lesions of gastric cancer (PLGC). METHODS: Totally 66 Wistar rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the retinoic acid (RA) group, the high dose HJHR group, the middle dose HJHR group, the low dose HJHR group, 11 in each group. PLGC model was duplicated by inserting a spring with Helicobacter. Corresponding medicines were administered to rats in each medicated group once daily by gastrogavage, 2 mL each time for 12 successive weeks. The effect of HJHR on hypoxia induced factor (HIF-1alpha) and vascular endothelial growth factor (VEGF) of PLGC in chronic atrophic gastritis (CAG) rats' gastric mucosa was observed by immunohistochemical assay and Western blot method. RESULTS: Compared with the normal control group, the expression of VEGF and HIF-1alpha increased in the model group (P < 0.05). Compared with the model group, the expression of VEGF and HIF-1alpha decreased in each medicated group (P < 0.05). Besides, they were lower in the high and middle dose HJHR groups than in the RA group and the low dose HJHR group (P < 0. 05). There was no statistical difference between the low dose HJHR group and the RA group (P > 0.05). CONCLUSION: HJHR could prevent and treat PLGC of CAG rats possibly through decreasing the expression of HIF-1alpha and VEGF in a dose-dependent manner.

Evaluation of microvascular density in Barrett's associated neoplasia.

Angiogenesis has an important role in the carcinogenesis of esophageal adenocarcinoma, however, the diagnostic and prognostic utility of microvascular density counts have not been clinically established. The aim of this study is to assess the correlation between microvascular density and disease progression of non-dysplastic Barrett's esophagus, low-grade dysplasia, high-grade dysplasia and invasive carcinoma in the superficial aspects of the tissue. Archival histological specimens from two referral centers for Barrett's esophagus and esophageal cancer were selected for review. A total of 160 regions marked according to histological grade were assessed with digitally interactive software to measure microvascular density. This was quantified in three levels: 0-50, 50-100 and 100-150 µm. In the areas of gastric cardia, Barrett's esophagus, low-grade dysplasia, high-grade dysplasia and cancer, microvascular density was significantly different (P<0.0001) among the five groups in the most superficial 150 µm of the mucosa. Furthermore, when examining the pairwise difference between the groups, there was a significant difference between cancer and each of the lower grades of histology (P<0.05) and between high-grade dysplasia and each of the lower grades of histology (P<0.05). These statistically significant differences were preserved in examining the depth at the most superficial 50 µm. We have used digital pathology to demonstrate a significant and stepwise increase in microvascular density, which supports the hypothesis that angiogenesis has a key role in Barrett's carcinogenesis. Furthermore, the differences in the most superficial mucosal layers are consistent with findings of increased vascularity by depth-restricted imaging modalities.

VEGF and CD105 immunoexpression in squamous cervical carcinomas and associated precancerous lesions.

In this study, we analyzed the VEGF and CD105 immunoexpression in 24 cervical squamous cell carcinomas and CIN associated lesions with different degrees. For both lesions, MVD values were higher in patients who had associated risk factors. VEGF and MVD expression increased in both categories for high-grade lesions, respectively CIN III lesions compared with CIN I/II and poorly differentiated carcinomas compared with well-differentiated ones. Also, there was a statistically significant association between VEGF and MVD in poorly differentiated carcinoma and CIN III. The study indicated that analyzed markers were specific for both early and advanced stages of cervical angiogenesis. Maximum values of VEGF and MVD in CIN III designate this lesion as critical to the progression of neoplasia.

Blood vessel normalization in the hamster oral cancer model for experimental cancer therapy studies.

BACKGROUND: Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. MATERIALS AND METHODS: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. RESULTS: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. CONCLUSION: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

VEGF expression from human dysplastic or malignant oral epithelium may be related to mast cell density and the subsequent angiogenetic phenomena.

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine and mast cells play a role in neoangiogenesis in various malignancies. The aim of the present study was to elucidate the role of VEGF and mast cells in the early stages of tumorigenesis in oral squamous cell carcinoma (OSCC). Immunohistochemistry was conducted to study VEGF expression and microvessel density (MVD) in 49 tissue samples, 31 OSCCs, 13 leukoplakias (8 with and 5 without dysplasia) and 5 samples from normal oral tissue. Counterstaining with tolouidine blue was conducted to reveal mast cells. The number of microvessels and mast cells were counted at the same optical field. A gradually increased VEGF expression was observed from normal oral epithelium to leukoplakia and OSCC. MVD was found to increase significantly between normal oral tissue and OSCC (p=0.000). The number of mast cells was found to increase significantly between normal oral tissue, dysplasia (p=0.012) and OSCC (p=0.000). In the early stages of tumorigenesis in OSCC, VEGF, which is secreted by the epithelium, is gradually increased immediately affecting the population of mast cells, which are then related to the increase of microvessels.

Clinical appraisal of endoscopy with narrow-band imaging system in the evaluation and management of homogeneous oral leukoplakia.

PURPOSE: To evaluate the clinical usefulness of endoscopy with a narrow-band imaging (NBI) system for the evaluation and management of homogeneous oral leukoplakia. METHODS: The chart records, morphology of vascular architecture of NBI, and histopathology of patients with homogeneous leukoplakia were retrospectively reviewed and analyzed. RESULTS: A total of 160 patients, with an average age of 50.96 ± 10.25 years, were enrolled. In 35 cases of thin leukoplakia, only intraepithelium papillary capillary loop (IPCL) type I was shown by NBI, and only squamous hyperplasia was revealed pathologically. In 125 cases of thick leukoplakia, IPCL type I was found in 94, IPCL type II in 29, and IPCL type III in 2. The Kendall rank correlation between pathology and NBI images was significant (p < 0.0001). CONCLUSIONS: The dichotomous classification of homogeneous leukoplakia by NBI is meaningful, and endoscopy with the NBI system is a promising tool for the evaluation and management of homogeneous oral leukoplakia.