Heparan sulfate proteoglycans and their modification as promising anticancer targets in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer. Despite advancements in the treatment strategies of HCC, there is an urgent requirement to identify and develop novel therapeutic drugs that do not lead to resistance. These novel agents should have the potential to influence the primary mechanisms participating in the pathogenesis of HCC. Heparan sulfate proteoglycans (HSPGs) are major elements of the extracellular matrix that perform structural and signaling functions. HSPGs protect against invasion of tumor cells by preventing cell infiltration and intercellular adhesion. Several enzymes, such as heparanase, matrix metalloproteinase-9 and sulfatase-2, have been reported to affect HSPGs, leading to their degradation and thus enhancing tumor invasion. In addition, some compounds that are produced from the degradation of HSPGs, including glypican-3 and syndecan-1, enhance tumor progression. Thus, the identification of enzymes that affect HSPGs or their degradation products in HCC may lead to the development of novel therapeutic targets. The present review discusses the main enzymes and compounds associated with HSPGs, and their involvement with the pathogenicity of HCC.

Do spinal cord-injured individuals with stronger sense of coherence use different psychological defense styles?

OBJECTIVES: Although the importance of sense of coherence (SOC) and psychological defense mechanisms (PDMs) in the process of coping has been demonstrated, it has not yet been clarified whether individuals with stronger SOC use specific PDMs. STUDY DESIGN: Cross-sectional. SETTING: Iran. METHODS: Demographic and injury-related variables including injury level, time since injury, American Spinal Cord Association (ASIA) Scale and Spinal cord independence measure-III were collected among individuals with spinal cord injury (SCI). SOC was assessed by the Short-form Sense of Coherence Scale. PDMs were identified using 40-version of the Defense Style Questionnaire. RESULTS: Neurotic defense style was the most commonly used style especially. The overall most commonly used PDM was 'rationalization', which was used by 95%. Individuals with stronger SOC used more mature style (P=0.001, r=0.52), particularly 'humor' and 'suppression' mechanisms (P<0.0001 and 0.024, respectively). There was a negative correlation between stronger SOC and the use of immature defenses including passive aggression (P=0.001, r=-0.51), acting out (P=0.001, r=-0.48), isolation (P=0.009, r=-0.50), autistic fantasy (P=0.010, r=-0.30) and somatization (P<0.0001, r=-0.62). Married individuals had significantly stronger SOC (P=0.01). Age, gender, age at the time of injury incidence, time since injury, ASIA score and cause of injury were not determinants of SOC. CONCLUSION: In this study, PDMs, which are more probable to be used by individuals with stronger SOC, have been identified. Mature defenses including 'humor' and 'suppression' are used by stronger SOC more often, whereas immature mechanisms are less likely to be used.

Chorioretinitis after keratitis caused by Acanthamoeba: case report and review of the literature.

OBJECTIVE: A clinicopathologic study to evaluate the histopathologic features associated with Acanthamoeba keratitis and chorioretinitis. DESIGN: Retrospective observational case report. METHODS: On the basis of the clinical history and histologic appearance, the enucleated eye and native corneal button were examined using hematoxylin-eosin stains and special periodic acid-Schiff and Gomori methenamine silver stains. RESULTS: Results of histologic examination of the cornea and retina showed numerous Acanthamoeba cysts in the cornea stromal layers, the necrotic retina, and preretinal and subretinal spaces. CONCLUSIONS: To the authors' knowledge, this is the first proven histologic case of ipsilateral chorioretinitis secondary to primary chronic keratitis caused by Acanthamoeba. The patient had a 30-month history of recurrent keratitis requiring four penetrating keratoplasties. We believe the chorioretinitis resulted from direct spread of the corneal amebic infection. The spread of the Acanthamoeba may have been facilitated by a combined keratoplasty, extracapsular cataract extraction, and intraocular lens insertion. In both specimens, the native corneal button and the enucleated eye with a corneal transplant, the general pathologists overlooked the presence of Acanthamoeba.

Uveal melanoma: mean of the longest nucleoli measured on silver-stained sections.

PURPOSE: To summarize and compare the various histologic methodologies for using nucleoli to assess the malignant potential of uveal melanoma. METHODS: This was an observational series of 100 samples of uveal melanoma in which histologic sections were studied. The cases were selected so that approximately half (n = 49) of the tumors were from patients who had died of metastatic malignant melanoma. The 51 remaining tumors were from patients who had survived at least 9 years without development of metastasis. Central sections from the uveal melanomas were stained using the colloidal silver nitrate stain for nucleolar organizing regions (AgNOR). These were compared with an adjacent hematoxylin and eosin (H&E)-stained section. A light microscope with a micrometer inset into the eyepiece (x10) was used at a final magnification of x1000 under oil immersion to measure the length of the nucleolus along the longest axis and the width perpendicular to that axis. From at least twenty cells selected from random fields throughout the tumor, the mean of the 10 longest and widest nucleoli (MLN) was calculated. Seven samples had to be discarded because the nucleoli were unmeasurable. RESULTS: T-tests and Cox proportional hazard regression analysis indicated that the MLN of nucleolar length as measured on AgNOR-stained slides was as significant as cell type but was more significant than other histopathologic prognosticating variables measured and evaluated in this study. These prognosticators included tumor size, calculated as the largest tumor dimension; MLN width; and MLN length, as measured on H&E-stained sections. CONCLUSIONS: It has previously been demonstrated that AgNOR-stained nucleoli, unlike H&E-stained nucleoli, can be captured and measured by an automated image analyzer with prognostically significant results. This new method of simple oil-immersion measurements of the longest AgNOR-stained nucleoli length in microscopic sections of uveal melanoma provides an inexpensive and highly significant method for predicting outcome in patients with uveal melanoma. Because of the high contrast with the background, the silver-stained nucleoli clearly define the nucleolar boundaries, rendering them readily discernible and allowing greater ease and speed of measurement when compared with H&E-stained nucleoli. The method of random sampling that was used was comparable with linear sampling in predicting outcome. Highly necrotic tumors, however, had to be excluded from the study because of loss of nucleolar morphology.

Ectopic chordoma with orbital invasion.

PURPOSE: To report a rare ectopic chordoma within the orbital wall. METHODS: Case report. RESULTS: A 63-year-old woman developed swelling of the eyelid, tearing, blurred vision, and progressive proptosis RE of 1 month's duration. Neuroimaging studies revealed an osteolytic mass with epicenter at the sphenozygomatic suture that eroded intracranially, invaded into the orbit, and compressed orbital soft tissues. Surgical debulking was done followed by radiation treatment. The pathologic findings of physaliphorous epithelial cells with multiple vacuoles containing mucin, prominent nuclei, and positive immunohistochemical staining for S-100, Vimentin, epithelial membrane antigen, and pancytokeratin were diagnostic for chordoma. CONCLUSION: Orbital wall ectopic localization of a chordoma distant from the clivus is a rare occurrence.

Totally necrotic choroidal and ciliary body melanomas: associations with prognosis, episcleritis, and scleritis.

PURPOSE: To report associations between prognosis, total tumor necrosis, scleritis, and episcleritis in choroidal and ciliary body melanomas. METHODS: In this retrospective observational histopathologic study, 157 totally necrotic melanomas and 177 melanomas that were not totally necrotic of choroidal and ciliary body were retrieved from the Registry of Ophthalmic Pathology. The eyes were examined for the histologic evidence of inflammatory cells within the sclera and episcleral tissues. Contingency table, Kaplan-Meier, and Cox proportional hazard regression analyses were performed. In the survival analyses, only deaths with metastatic melanoma were considered as events in the statistical analysis. RESULTS: Among the totally necrotic melanomas, 118 of 157 (75.1%) had both episcleritis and scleritis; two of 157 (1.3%) had scleritis only; 29 of 157 (18.5%) had episcleritis only; and eight of 157 (5.1%) had neither episcleritis nor scleritis. Among the non-necrotic melanomas, 23 of 177 (12.9%) had both episcleritis and scleritis; eight of 177 (4.5%) had scleritis only; 71 of 177 (40.1%) had episcleritis only; and 75 of 177 (42.3%) had neither episcleritis nor scleritis. Cox regression indicated that total necrosis and scleritis were prognostically significant (P <.05) when analyzed univariately but not significant when analyzed multivariately with tumor size. CONCLUSIONS: Scleritis and episcleritis were statistically significantly associated with total tumor necrosis. There was a higher incidence of episcleritis than scleritis in both the necrotic and non-necrotic tumor types. Associations with patient outcome were identified for necrosis and scleritis. However, these associations were statistically insignificant when the prognostic effect of tumor size was also considered in a multivariate model.