Large Number Of Lesions Research Articles

Melanoma progression

Tumours progress to fully malignant neoplasms through stages of development in a stepwise process. A carcinogenic stimulus such as UV light typically results in a large number of lesions, most of which are benign. Most such lesions will remain stable or regress, while a few will develop cytological and architectural atypia, placing them in a morphologically 'intermediate' category between wholly benign and fully malignant. It is important to categorise intermediate lesions, as they may be simulants, risk markers, and potential precursors of malignancy. Although many but not all malignancies arise in an evident precursor lesion, the vast majority of 'potential precursors' will not progress, as is evidenced by their vastly greater numbers in populations. Progression continues with the onset of malignancy including in metastatic disease. In melanoma as in other tumours, progression has been clearly related to the stepwise acquisition of genetic abnormalities. The first step is the activation of a single 'driver' oncogene, which is sufficient to induce a benign neoplasm whose growth is limited by oncogene-induced senescence driven by activated suppressors. In the intermediate lesions, additional genetic alterations occur such as additional driver mutations or heterozygous loss of suppressors due to copy number variation or other mechanisms. Fully malignant lesions are characterised by complete loss of relevant suppressors and by additional abnormalities, which together account for attributes of malignancy such as invasion and metastasis. Any of the steps of progression can be 'skipped', potentially due to telescoped progression or to alternative pathways. Although stages of progression might simply be viewed as markers of an individual's risk for developing subsequent stages, genetic associations that have been demonstrated among contiguous stages of progression in complex primary tumours and in their metastases would argue against this. For example, complex primary melanomas can be associated with remnants of earlier stage lesions both clinically and histologically. These include small symmetrical benign naevi and/or morphologically atypical dysplastic naevi ('precursor naevi'), and/or radial growth phase melanomas many of which may be inexorably progressive but lack competence for metastasis. Vertical growth phase is the stage of melanoma progression in which risk for metastasis may be acquired. This risk can be characterised statistically using prognostic attributes which at present are mostly clinicopathological, although in the future molecular profiling may contribute or even supplant these attributes. In metastatic disease, tumours can continue to progress, acquiring resistance to various therapeutic strategies which presents a considerable challenge to the efficacy of current promising therapeutic strategies.

Gingival proliferative lesions in children and adolescents in Brazil: A 15-year-period cross-sectional study.

Background:Studies assessing the prevalence of oral lesions in children and adolescents, particularly in gingiva are scarce in the literature. The aim of the study was to describe the distribution of gingival proliferative lesions based on clinical and histopathological diagnoses in children and adolescents.Materials and Methods:A review of clinical charts of children and adolescents aged between 0 and 18 years old, admitted to the Oral Medicine Outpatient Unit, of Universidade Federal do Paraná, for 15 years (1994–2009) was performed.Results:Six hundred and sixty-nine out of 5,129 patients treated during this period were aged between 0 and 18 years old, and 45 of these had gingival lesions. The largest number of lesions was observed between 11 and 16 years old. The majority of the patients were referred by Curitiba's public health system. Pyogenic granuloma was the most frequent lesion (19 = 42.2%), followed by peripheral giant cell lesion (11 = 24.4%), gingival fibromatosis (10 = 22.2%), and peripheral ossifying fibroma (5 = 11.1%).Conclusion:Gingival proliferative lesions can show similar clinical characteristics. Appropriate clinical and histopathological diagnoses are necessary to guide the healthcare professional to establish the adequate treatment and to estimate the risk of recurrence.

Tooth resorption in cats: pathophysiology and treatment options.

Tooth resorption is common in the domestic cat and the incidence has been reported to increase with increasing age. Cats with clinically missing teeth have also been found to be more likely to have tooth resorption. All types of teeth in the feline dentition may be affected, but lesions seem to be more common in certain teeth. Tooth resorption can be difficult to detect, with cats often masking signs of oral discomfort or pain. Routine radiography is required for timely diagnosis, as clinical (visual and tactile) methods only detect late-stage lesions - that is, when they become evident in the crown. The aetiology of many tooth resorptions is not clear. A large number of lesions appear to be idiopathic and, to date, there is no known treatment that prevents the development and/or progression of this category of tooth resorption. Tooth extraction is the gold standard treatment but teeth with resorptive lesions are notoriously difficult to extract and coronal amputation is often indicated. Determining the best treatment option in an individual case again relies on radiography. This review is aimed at feline and general practitioners, as well as veterinarians with expertise in dentistry. The author draws on the published literature and her clinical experience and own research to review current thinking about the epidemiology, aetiology and pathogenesis of tooth resorptions, and to offer advice on diagnosis and treatment options.

BM-01 * DOSIMETRIC HOTSPOTS ARE THE MOST POWERFUL DOSIMETRIC PREDICTOR OF LOCAL CONTROL IN NSCLC BRAIN METASTASES

BACKGROUND: There is scant data on actionable parameters that may improve local control (LC) after SRS for brain metastases. We evaluated the impact of various patient, tumor, and dosimetric variables on LC of NSCLC brain metastases with SRS. METHODS: Patients with NSCLC brain metastases treated with single fraction SRS without prior metastasectomy or SRS to the same lesion were identified. Brain MRI imaging was reviewed from time of SRS until death or last follow up. LC was scored for each lesion as stability or decrease in the size of the treated metastasis. Dose volume histograms (DVH) were collected for each lesion and evaluated with a custom DVH tool. V18-V50Gy, D10, D50, D90, dose mean, maximum, minimum, and median were extracted as were dose gradient index and RTOG conformity index. Univariate and multivariate Cox Regression were used to identify factors predictive of LC, and LC was estimated using the Kaplan-Meier method. RESULTS: 612 brain metastases in 299 patients were identified, yielding 122 local failures. On univariate analysis, lack of prior whole brain, lack of whole brain < 2 months, Perfexion machine model, increasing dose, increasing isodose, fewer shots, increasing V18-V40, decreasing volume, and increasing conformity index were associated with increased LC (p < 0.05). On multivariate analysis (MVA), decreasing volume (HR 1.359, 95% CI 1.197-1.543), increasing V32Gy (HR 0.069 95% CI 0.018-0.264), and increasing isodose (HR 0.953, 95% CI 0.911-0.996. were associated with increased LC (p < 0.05). CONCLUSIONS: Significant plan quality variation exists for a given prescription dose for SRS, and prescription dose is not predictive of LC. Optimizing the volume of tumor receiving high dose (such as V32) for a given prescription dose represents an actionable variable to drive treatment planning during SRS for brain metastases. Analysis of a larger number of lesions within a multi-institutional registry (CONDR-IMD) will further clarify such parameters.

Avaliação macroscópica da exposição ao etanol e da desintoxicação alcoólica sobre lesões gástricas em ratos

AIMS: To investigate the effects of chronic ethanol consumption and alcohol detox on macroscopic gastric lesions in rats. METHODS: This is an experimental study in which 18 adult male rats (Rattus norvegicus) of the Wistar strain, with 40 days of life were divided into three randomized groups with six animals each: Control Group (CT), Detoxicated Group (DE) and Alcohol Group (AC). The AC animals have been subjected to an experimental model termed as chronic alcoholics, in which, after a period of adaptation, they received ethanol as the only liquid food available until completion of 13 weeks of the experiment. The DE was subjected to the same protocol as the AC, however, after six weeks of alcohol consumption, the animals were subjected to the alcohol detoxification process. At the end of the experiment, the stomach of the three groups of animals were collected in order to investigate the presence of gastric lesions. RESULTS: The animals in the CG showed no lesions. The animals in DE exhibited a larger number of lesions in comparison to the AC (44±3.7 and 21±0.3 respectively). Macroscopic examination of the animal’s stomachs indicates that the animals in the DE were those with the highest injury rate in the gastric mucosa. CONCLUSIONS: Ethanol consumed chronically or after alcohol detoxification triggered gastric lesions in AC and DE, but sharply in the group submitted to detoxification, which can characterize a possible synergism between ethanol consumption and alcohol detox post-stress in the pathogenesis of gastric ulcer.

First reported cases of diffuse cutaneous leishmaniasis in human immunodeficiency virus positive patients in Jaipur District of Rajasthan, India

Diffuse cutaneous leishmaniasis (DCL) is characterized by the presence of a large number of lesions at several anatomic sites (head, limbs and trunk). The lesions include papules, nodules and areas of diffuse infiltration that do not ulcerate and reveal abundant parasites on histopathological examination. DCL and human immunodeficiency virus (HIV) co-infections are seldom reported. We report two cases of DCL in HIV positive patients without visceral involvement. DCL is emerging as a new opportunistic infection associated with HIV/acquired immunodeficiency syndrome.

Clinical applicability of magnetic resonance imaging in acute spinal cord trauma

To assess the clinical application of magnetic resonance imaging (MRI) in patients with acute spinal cord trauma (SCT) according to the type, extension, and severity of injury and the clinical-radiological correlation. Diagnostic imaging [computed tomography (CT) and MRI] tests of 98 patients with acute SCT were analyzed to assess their clinical diagnostic value. The following radiological findings of SCT were investigated: vertebral compression fractures, bursts and dislocations, posterior element fractures, C1 and C2 lesions, vertebral listhesis, bone swelling, spinal canal compression, disk herniation, extradural hematoma, spinal cord contusions, spinal cord swelling, and posterior ligamentous complex (PLC) injuries. The radiological findings were better visualized using MRI, except for the posterior elements (p = 0.001), which were better identified with CT. A total of 271 lesions were diagnosed as follows: 217 using MRI, 154 using CT, and 100 (36.9 %) using both MRI and CT. MRI detected 117 more lesions than CT. MRI was significantly superior to CT in the diagnosis of bone swelling, PLC injury, disk herniation, spinal canal compression, spinal cord contusion and swelling present in SCT. MRI detected a larger number of lesions than CT and is highly useful for the diagnosis of soft tissue and intrathecal injuries.

Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients

To document the type, location, extent, and complications of brain metastases in patients with breast cancer and identify associations with oestrogen receptor (ER) negative and human epidermal growth factor receptor 2 (HER-2) receptor expression. Breast cancer patients with known brain metastases were included in this retrospective study, if cross-sectional imaging of the brain [computed tomography (CT)] was available to review and HER-2 and ER status was known. Two neuroradiologists, who were blinded to the receptor status, separately and for each patient, documented on a proforma the location, number, and dimensions of the deposits and the presence or absence of hydrocephalus. Adjudication was sought where there was discrepancy between the two reports. ER status, HER-2 receptor status, and patient age were also documented. The results were analysed using two-sided Fisher's exact tests with Lancaster's mid-P correction and associations were sought between the tumour characteristics and the pattern of brain disease. Sixty patients were included in the study. There was an association between young age (<40 years) and HER-2 positivity [10 of 24 (41.7%) versus three of 36 (8.3%); p = 0.002]. In ER-negative women, HER-2 positivity was found to be associated with a larger number (six or more) of metastases [11 of 18 (61%) versus nine of 25 (36%); p = 0.049], more brain stem metastases [11 of 18 (61%) versus three of 26 (11.5%); p = 0.035], more frequent occurrence of hydrocephalus [7 of 12 (36.8%) versus three of 26 (11.5%); p = 0.049], and a higher incidence of occipital metastases [12 of 18 (66.7%) versus eight of 26 (30.8%); p = 0.029]. ER-negative HER-2-positive women are more likely to present with a larger number of lesions, more brain stem/occipital metastases, and hydrocephalus, which may predispose them to unfavourable outcomes following treatment.

Predictive Clinical Factors in the Diagnosis of Gastrointestinal Kaposi's Sarcoma and Its Endoscopic Severity

BackgroundThe diagnosis of gastrointestinal (GI) involvement in Kaposi's sarcoma (KS) is important to make because the need for treatment depends on the extent of the disease. Moreover, severe GI lesions can cause serious complications. Endoscopy with biopsy is an extremely useful method to diagnose GI-KS. However, determining the indications for endoscopy is difficult because KS can occur without GI symptoms or cutaneous KS. This study sought to clarify predictive clinical factors for GI-KS and its severity on endoscopy.Methodology/Principal FindingsA total of 1,027 HIV-infected patients who underwent endoscopy were analyzed. Sexual behavior, CD4 count, HIV RNA, history of highly active antiretroviral therapy (HAART), GI symptoms, and cutaneous KS were assessed. Endoscopic severity including bulky tumor, ulceration, and number of lesions were evaluated. Thirty-three patients had GI-KS and 46 patients cutaneous KS. Among the GI-KS patients, 78.8% (26/33) had no GI symptoms and 24.2% (8/33) had no cutaneous KS. Univariate analysis identified men who have sex with men (MSM), CD4 <100 cells/µL, HIV RNA ≥10,000 copies/mL, no history of HAART, and cutaneous KS were significantly associated with GI-KS. Among these factors, cutaneous KS was closely related to GI-KS on multivariable analysis. Among patients without cutaneous KS, MSM and CD4 count <100 cells/µL were the only independent clinical factors related to GI-KS. Bulky tumor was significantly associated with CD4 <100 cells/µL and large number of lesions was significantly associated with HIV-RNA ≥10,000 copies/mL.ConclusionsTo diagnose GI-KS, clinical factors need to be considered before endoscopy. The presence of GI symptoms is not useful in predicting GI-KS. MSM and CD4 count <100 cells/µL are predictive factors among patients without cutaneous KS. Caution should be exercised especially in patients with low CD4 counts or high HIV viral loads as they are more likely to develop severe GI-KS lesions.

Carbon Dioxide Laser Treatment of Cutaneous Neurofibromas

IntroductionNeurofibromatosis type 1 (NF1) is an autosomal dominant disorder, with multisystem involvement, including cutaneous manifestations of hyperpigmentation and neurofibromas. Multiple cutaneous lesions are often disfiguring and lead to emotional distress and social isolation. Treatment of NF1 is predominantly surgical but alternative treatments should be considered for patients with large numbers of lesions as cold steel excision of multiple lesions can be cumbersome and may not be practical. The authors report a series of patients with multiple neurofibromas successfully treated using a CO2 laser.MethodsData on CO2 laser treatments, follow-up, and recurrence following treatment was collected retrospectively. A post-treatment telephone survey was carried out to assess patient satisfaction using a standardized set of questions and a scoring tool.ResultsFive of seven patients who underwent CO2 laser treatment of their multiple neurofibromas responded to the post-treatment survey. All five patients (age range 36–56 years, mean age 45.2 years, three men:two women) had multiple variable-sized neurofibromas. The mean number of lesions per patient was 114 (range 20–200 lesions). The mean number of treatment sessions was 2.2 (range 1–4 sessions) and mean follow-up was 14.4 months (range 6–24 months). Three patients (60%) reported no recurrence up to 2 years post-laser treatment. Two patients (40%) had recurrences of a few lesions (≤10% of treated lesions per patient). The mean patient satisfaction score was 9.2 out of 10 (range 8–10). All patients mentioned that they would recommend CO2 laser treatment to others with multiple neurofibromas. Hypopigmentation or depigmentation at treatment sites were the only reported adverse effects.ConclusionBased on current results, the authors feel that CO2 laser treatment achieves a high level of patient satisfaction with a low recurrence of treated lesions.

Thousands of Lesions in Disseminated Cysticercosis

Human cysticercosis is an important cause of seizures in the developing world. A small subset of patients acquires heavy infections with large numbers of lesions disseminated throughout the brain and skeletal muscle.1 Manifestations of heavy multiple cysticercotic syndromes include cysticercal encephalitis or signs and symptoms related to location. A 30-year-old man presented with intermittent partial complex seizures and headache for the previous 2 years. Examination revealed widespread small pea-sized nodules throughout the body, including the tongue (Figure 1). Calf hypertrophy was present (Figure 2). Higher mental function, cranial nerves, and motor, sensory, and reflexes were normal. An enzyme-linked immunsorbent assay for Taenia solium antibody was positive at high titers. A T2 sagittal magnetic resonance image of the brain showed numerous circumscribed lesions with visible scolices and involving adjacent soft tissues (Figure 3). Cysticercosis is caused by the cestode larvae of the pork tapeworm T. solium. Disseminated cysticercosis has the potential to cause severe clinical manifestations.2 Figure 1. Tongue of the patient demonstrating larval cyst. Figure 2. Photograph of the patient revealing calf hypertrophy. Figure 3. Magnetic resonance imaging of the cranium, T2 weighted sagittal image showing multiple well-circumscribed cysts with presence of scolex.

Thein situinflammatory profile of lymphocutaneous and fixed forms of human sporotrichosis

The most common clinical presentations of sporotrichosis are the lymphocutaneous (LC) and fixed cutaneous (F) forms, but little is known about the immunopathologic differences between them. The aim of this study was to evaluate through immunohistochemistry the composition of the in situ inflammatory reaction so as to correlate the results with the clinical presentation of the disease. The following two groups of patients were involved in the studies, i.e., LC (n=19) and F (n=11) patients. Those with the LC form, in contrast to F patients, were found to have a larger number of lesions (P=0.001), of longer duration (P=0.026) and require a more extended course of treatment (P=0.049). LC patients also presented a greater fungal burden (LC:0-6.5; F:0-1.5; P=0.021), a higher percentage of neutrophils (median LC:24.7%; F:6.7%, P=0.002), CD4(+) cells (median LC:40.9%; F:30.0%, P=0.0024), CD22(+) cells (median LC:15.3%; F:2.9%, P=0.048), and higher intensity of NOS2 expression (P=0.009). Thus, our data identified differences in cell profile and inflammatory activity in lesions of LC and F forms of human sporotrichosis.

Measurement of the field response of Musa genotypes to Radopholus Similis and Helicotylenchus Multicinctus and the implications for nematode resistance breeding

Crop growth and damage parameters (plant growth and yield, root damage and nematode population densities), believed to be associated with resistance of Musa genotypes to nematodes under field conditions, were evaluated in a field trial of 24 Musa genotypes inoculated at planting with a combination of Radopholus similis and Helicotylenchus multicinctus with the objective to identify parameters with strong association with nematode resistance and high heritability. Correlation and path analysis of the association between plant growth, yield, root damage and nematode population densities showed a strong negative association between percentage dead roots, percentage root necrosis, R. similis and H. multicinctus population densities and yield. The strongest negative association was observed between percentage dead roots and yield. Broad-sense genotype heritability estimates demonstrated that heritability estimates for percentage dead roots, number of large lesions and nematode population density were most affected by inoculation with nematodes. These results indicate therefore that effective selection for nematode resistance under field conditions could be obtained by using an index, that includes percentage dead roots, the number of large lesions, and nematode population density.

Reply to letter to the Editor re: Adrenal pheochromocytoma: correlation of MRI appearances with histology and function

Dear Editor, We thank Dr. Park for his interest in our article [1]. We would like to expand on and clarify a number of points raised. The wide size range of phaemochromocytoma in our study reflects the large number of lesions in this series and is comparable with other previously reported large series [2, 3]. Lesion size was considered when we analysed the MR imaging features of phaeochromocytoma and was included in the publication. We agree that increasing amounts of haemorrhage, necrosis and fibrosis are seen in larger lesions which tend to be more heterogeneous. The lesions which appeared homogenous were smaller (mean size 4.5 cm; range 1.2– 7.4 cm) compared with the heterogeneous lesions (mean size 6.3 cm; range 2.3–15 cm). This just reached statistical significance (P=0.046) although a considerable overlap of size between the two groups was observed (Fig. 1). If the lesions are stratified according to size as suggested, the smaller lesions ( 6 cm), which were homogeneous in only 3/13 (23%) and heterogeneous in the remainder. The majority of lesions in the midrange group (3.1–6 cm) however were almost equally distributed between the homogeneous (13/23) and heterogeneous (12/23). Detailed lesion-by-lesion radiological-pathological correlation was not possible in this retrospective study. However, the pathological reports were very detailed with macroscopic and microscopic descriptions of the tumours. This allowed us to match the MRI appearances with the pathological description, particularly the presence of haemorrhage, necrosis and calcification. Time-interval data are available for 37 out of the 44 phaeochromocytomas included in our study. The time between the MRI scan and surgery ranged from 5 to 115 days (mean 40.4 days, median 45 days). In our institution it is usual practice to allow at least 6 weeks between surgery and the diagnosis of a phaeochromocytoma to allow complete alpha blockade prior to surgery. We do not believe the time intervals in our study conferred a significant time delay and they are believed to be less than the presumed doubling-time of these slow-growing tumours. Overall, we set out in our study to describe the MRI appearance of adrenal phaeochromocytoma and to quantify the frequency with which the previously described ‘classical’ hyperintense ‘light-bulb’ appearance on T2-weighted MRI actually occurs. We have described a wide range of appearances which we feel are important for the diagnostic radiologist to be aware of. In particular, size, heterogeneity and T2 signal intensity should not dissuade the radiologist of the correct diagnosis, and appropriate biochemical evaluation should be made. This is the authors’ reply to a letter that can be found at doi 10.1007/s00330-0091387-5.

Simulação numérica tridimensional da mecânica do joelho humano

OBJETIVO: Por ser a articulação mecanicamente mais solicitada de nossa estrutura e pelo grande número de lesões associadas, motivaram a construção de um modelo tridimensional da articulação do joelho humano para simular a cinemática da articulação e obter as solicitações mecânicas nos principais ligamentos durante o movimento de flexão do joelho. Essas informações podem futuramente ser empregada como ferramenta de apoio à decisão médica em ortopedia, fornecendo subsídios na escolha do procedimento cirúrgico. MÉTODOS: Método dos Elementos Finitos foi utilizado para construir um modelo biomecânico, tridimensional, da articulação do joelho. Nesse modelo com seis graus de liberdade é aplicado movimento de flexão/extensão sendo os demais cinco graus de liberdade governados pelas interações entre os componentes da articulares. RESULTADOS: Foram obtidas informações dos movimentos, das rotações interna/externa e adução/abdução, das translações anterior/posterior, lateral/medial e superior/inferior e dos esforços nos quatro principais ligamentos articulares, no decorrer de um amplo movimento de flexão/extensão. Estes valores foram comparados, de forma qualitativa, com valores equivalentes obtidos na literatura. CONCLUSÃO: A análise de resultados permitiu observar que vários aspectos cinemáticos são satisfatoriamente reproduzidos. A pré-carga inicial dos ligamentos e o posicionamento das inserções ligamentares no modelo mostraram-se variáveis relevantes nos resultados.

Denture-related hyperplasia: a clinical study of a turkish population group

Inflammatory fibrous hyperplasia (epulis fissuratum) (IFH) and inflammatory papillary hyperplasia (IPH) are oral mucosal diseases caused by ill-fitting denture wearing. A study was carried out on a group of Turkish people consisted of 131 female and 39 male complete denture wearers (n= 170) distributed in two age groups (30-60 and 60-80 years old). The analysis of data collected from patients showed that while the incidence of IFH was higher in women than in men, the incidence of IPH was similar. Most lesions were found in the 30-60 year-old group. The incidence of lesions increased as the denture wearing period increased. Soft tissue growth was the main complaint of the patients with IFH and IPH. In the maxilla, the incidence of IFH was higher than IPH. There was also a significant difference between the distribution of the lesion types in the jaws. There were a larger number of lesions in the maxilla compared to the mandible and most IFH lesions were located in the anterior region of the jaws.

Characterization of lesions induced in linear-formed plasmid DNA by valence ionization and Auger decay at carbon, nitrogen and oxygen

Purpose: To study the DNA lesions induced by the Auger decay of carbon, nitrogen, and oxygen using ultrasoft X-rays (USX) that are expected to be important with the DNA repair system of living cells.Materials and methods: pUC19 plasmid DNA dry samples were irradiated with USX photons at 270 and 560 eV and 60Co γ-rays in vacuum at room temperature. The amounts of unaltered base release by the direct radiation effects were quantified using high-performance liquid chromatography. To quantify and characterize the strand break termini the rate at which snake venom phosphodiesterase (SVPD) digested irradiated DNA pretreated with and without calf intestine alkaline phosphatase was measured. Moreover, the piperidine-labile base lesions and abasic sites of the irradiated DNA were estimated using the SVPD method.Results: The yields of unaltered base release for 270, 560 eV photons and 60Co γ-rays were 0.016, 0.014, and 0.018 μmol/J, respectively. The total 3′ termini for the three kinds of photons were around 0.1 μmol/J. The production of 3′ termini with phosphate was found to be predominant with respect to that of 3′OH termini for the three kinds of radiation. The yield of piperidine-labile sites for 270 eV (∼0.1 μmol/J) was slightly larger than that for 560 eV (∼0.07 μmol/J) and also for γ-rays (∼0.082 μmol/J).Conclusion: Although the Auger process in DNA-constituent atoms was expected to induce Auger-specific lesions in the molecule the chemical endpoints would have been covered with a large number of lesions produced from secondary electrons in the surrounding bulk DNA molecules. The present results, however, suggest that a low-energy electron field produced by the USX photons in the bulk DNA is basically not at all specific to DNA damage being produced when compared with the high-energy electron field produced by 60Co γ-rays.

Inhibiting vascular endothelial growth factor receptor-2 signaling reduces tumor burden in the ApcMin/+ mouse model of early intestinal cancer

The Apc(Min/+) mouse model is a clinically relevant model of early intestinal cancer. We used AZD2171, an oral, highly potent and selective vascular endothelial growth factor (VEGF) signaling inhibitor, to investigate the role of VEGF receptor-2 (VEGFR-2) signaling in adenoma development and growth in Apc(Min/+) mice. AZD2171 (5 mg/kg body wt/day) was administered once daily for 28 days to 6-week-old (early-intervention) or 10-week-old (late intervention) mice. In the early-intervention study, AZD2171 reduced the number of macroscopic polyps in the small bowel and colon. Macropolyp diameter was lower in the small bowel, but remained unchanged in the colon. In animals receiving AZD2171, microscopic evaluation of the small intestine showed a significant reduction in the number of larger lesions. In the late-intervention study, AZD2171 treatment reduced macropolyp diameter (but not number) in the small intestine. Microscopic analysis revealed that AZD2171 significantly reduced the number of larger micropolyps in the small bowel, with no large micropolyps present in the colon. AZD2171 treatment had no effect on microvessel density or localization of beta-catenin staining in adenomas or non-tumor intestinal tissue, but significantly reduced the number of cells expressing VEGFR-2 mRNA. In conclusion, the effects of AZD2171 in the small intestine of Apc(Min/+) mice are consistent with an antiangiogenic mechanism of action, limiting growth of adenomas to < or =1 mm. These data also suggest that an early step in adenoma development may depend on VEGFR-2 signaling. Together, these results indicate that VEGFR-2 signaling may play key roles in the development and progression of intestinal adenomas.

The Pitfalls of Treating All Actinic Keratoses as Squamous Cell Carcinomas

The greatest difficulties in managing a patient with numerous actinic keratoses is deciding the order in which to treat the specific lesions and what modality to use. The patient with a small number of lesions is probably most conveniently and cost effectively treated using destructive techniques like cryosurgery, electrodesiccation or photodynamic therapy with lasers. However, patients with large numbers of lesions are probably best managed using a topical chemotherapy agent, like 5-florouracil or imiquimod. If the patient's health insurance company limits coverage for the treatment of a specific number AK's per visit, it may be most prudent and logical to begin treatment of the largest or most rapidly growing AK's first and continue treatment of remaining lesions at subsequent visits until all lesions have been eradicated.

Thermodetection of Lung Cancer-Hot Stuff?

Thermodetection of Lung Cancer-Hot Stuff?