BackgroundDespite progress in adjuvant chemotherapy in the recent decades, pancreatic and colon cancers remain common causes of death worldwide. Bacterial toxins, which specifically bind to cell surface-exposed glycosphingolipids, are a potential novel therapy. We determined the expression of globotriaosylceramide (Gb3Cer/CD77), the Shiga toxin receptor, in human pancreatic and colon adenocarcinomas.Methodology/Principal FindingsTissue lipid extracts of matched pairs of cancerous and adjacent normal tissue from 21 pancreatic and 16 colon cancer patients were investigated with thin-layer chromatography overlay assay combined with a novel mass spectrometry approach. Gb3Cer/CD77 was localized by immunofluorescence microscopy of cryosections from malignant and corresponding healthy tissue samples. 62% of pancreatic and 81% of colon adenocarcinomas showed increased Gb3Cer/CD77 expression, whereas 38% and 19% of malignant pancreas and colon tissue, respectively, did not, indicating an association of this marker with neoplastic transformation. Also, Gb3Cer/CD77 was associated with poor differentiation (G>2) in pancreatic cancer (P = 0.039). Mass spectrometric analysis evidenced enhanced expression of Gb3Cer/CD77 with long (C24) and short chain fatty acids (C16) in malignant tissues and pointed to the presence of hydroxylated fatty acid lipoforms, which are proposed to be important for receptor targeting. They could be detected in 86% of pancreatic and about 19% of colon adenocarcinomas. Immunohistology of tissue cryosections indicated tumor-association of these receptors.Conclusions/SignificanceEnhanced expression of Gb3Cer/CD77 in most pancreatic and colon adenocarcinomas prompts consideration of Shiga toxin, its B-subunit or B-subunit-derivatives as novel therapeutic strategies for the treatment of these challenging malignancies.

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BackgroundThis is the first report of anisakiasis in a Croatian patient, evidenced from an archival paraffin-embedded and hematoxylin-eosin stained tissue section. Anisakiasis has been only suspected in the country based on previously detected anti-Anisakis IgE seroprevalence in the healthy coastal population, as well as an acute case where pathohistological and serological findings suggested the diseases, but the migrating larva has not been retrieved.Case presentationSeventy years-old female, operated in 1998 for pulmonary carcinoma, was admitted to the General hospital Šibenik, Croatia in 2003, because of gastric pain and nausea that lasted for couple of days. She was showing good general condition, full mobility and lucidity, subfebrile status. Abdominal palpation inferred acute pain in paraumbilical and ileocecal region. Exploratory right pararectal laparotomy revealed a hardened, 5 cm-long structure, located intraluminally in the sigmoid colon, not perforating colon serosa. The process has been dissected and sent for patohistological diagnosis. Results showed a 2 mm-long whitish nematode spiralised in muscular layer of colon mucosa surrounded by granulomatous inflammation.ConclusionAfter genomic DNA isolation of the nematode from the histological section, and amplification at the mitochondrial cytochrome oxidase 2 locus, etiological agent has been identified as Anisakis pegreffii. Used methodology suggests that screening of archival suspicious sections is feasible in order to study epidemiology of this zoonotic disease poorly recognised in Croatia.

Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Because as yet no treatments are available that produce a substantial survival benefit for this fatal neoplasia, new therapeutic concepts are urgently required to support cancer standard treatment. In search of tumorassociated gangliosides with therapeutic background, we probed a random collection of cancerous and adjacent normal postoperative tissue samples from 38 patients for the expression of CD75s-and iso-CD75s-gangliosides. We exhaustively analyzed the expression of CD75s-1-ganglioside (IV 6 Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1-ganglioside (IV 3 Neu5Ac-nLc4Cer) by means of immunohistology of cryosections and semiquantitative TLC of tissue lipid extracts combined with mass spectrometry. CD75s-1-and iso-CD75s-1-ganglioside showed an elevated expression in 42% and 66% of the tumors, respectively, indicating a significant association with neoplastic transformation (P = 0.001). Thus, increased expression of CD75s-1-and iso-CD75s-1-gangliosides renders these cell surface molecules promising candidates for oncologic applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (grade >2) suggesting this ganglioside as a potential marker for poor differentiation. The CD75s-specific antitumor drug rViscumin, which represents the recombinant counterpart of the ribosome-inactivating lectin viscumin, has successfully passed clinical phase I trials and provides an opportunity for treating pancreatic cancer. Consequently, if an enhanced expression is existent in malignant tissues, we propose the targeting of CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant treatment of pancreatic malignancies. [Mol Cancer Ther 2008;7(8):2464 -75]

The administration of urapidil before detorsion prevents ischemia/reperfusion cellular damage in testicular tissue. LMWH was not found to have a beneficial effect on testicular T/D injury in rats.

Meningiomas are one of the most common CNS tumors whose appearance is closely linked to NF2 gene product merlin. Tumor markers Ki-67 and p53 play established role in tumor progression which should be analyzed in close association with merlin expression. The aim of this study was to investigate the immunohistochemical expression of merlin in meningiomas, correlation with Ki-67 and p53, and to determine the association of these results with histologic grade and subtype. The histologic sections of 170 patients with totally resected meningiomas, between January 2000 and December 2010, were classified according to WHO, immunohistochemically stained for Ki-67, p53, and merlin, and analyzed using light microscope. Ki-67 median was 5.6 times higher in group of patients with negative merlin than in those with positive merlin (P=0.05). Statistically significant correlation of merlin with p53 was found (P<0.001). Merlin expression between 2 combined groups (meningothelial/secretory and fibroblastic/transitional) was statistically significant (P=0.002). By comparing merlin expression and p53 levels, statistically significant difference was found (P=0.017). In the group with positive merlin and negative p53 as well as positive merlin and low p53, meningothelial/secretory subtypes of meningiomas were more common. In combination of negative merlin and negative p53 as well as negative merlin and high p53, there were more meningiomas of fibroblastic/transitional subtype. There was no statistically significant correlation between merlin and tumor grade (P=0.420). There is undeniable influence of merlin on the development and the proliferative ability of meningioma subtypes. Significant role of p53 pathway was confirmed.

Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.

There is ample evidence that environmental stressors such as extreme weather conditions affect animal behavior and that this process is in part mediated through the elevated activity of the hypothalamic pituitary adrenal axis which results in an increase in cortisol secretion. This relationship has not been extensively researched in humans, and weather conditions have not been analyzed as a potential confounder in human studies of stress. Consequently, the goal of this paper was to assess the relationship between salivary cortisol and weather conditions in the course of everyday life and to test a possible moderating effect of two weather-related variables, the climate region and timing of exposure to outdoors conditions. The sample consisted of 903 secondary school students aged 18 to 21 years from Mediterranean and Continental regions. Cortisol from saliva was sampled in naturalistic settings at three time points over the course of a single day. We found that weather conditions are related to salivary cortisol concentration and that this relationship may be moderated by both the specific climate and the anticipation of immediate exposure to outdoors conditions. Unpleasant weather conditions are predictive for the level of salivary cortisol, but only among individuals who anticipate being exposed to it in the immediate future (e.g., in students attending school in the morning shift). We also demonstrated that isolated weather conditions or their patterns may be relevant in one climate area (e.g., Continental) while less relevant in the other (e.g., Mediterranean). Results of this study draw attention to the importance of controlling weather conditions in human salivary cortisol research.