Prospective evaluation of the impact of [18F]fluoro-2-deoxy-D-glucose positron emission tomography of resectable colorectal liver metastases

BACKGROUND: The aim of this study was to assess the additional value of information provided by positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-D-glucose (FDG) over that provided by computed tomography (CT) in patients with resectable liver metastases from colorectal cancer. METHODS: Between October 2001 and November 2002, a prospective double-blind comparison of preoperative FDG-PET and thoracoabdominal CT was performed in 53 patients with potentially resectable liver metastases from colorectal cancer. All resected metastases were subjected to histological examination. RESULTS: Histological examination confirmed the presence of malignant or benign lesions detected by PET and/or CT in 95 per cent of instances. Overall sensitivity (78 per cent) and accuracy (88 per cent) of PET were equivalent to those of CT (76 and 86 per cent respectively). The sensitivity of PET was equivalent to that of CT for hepatic sites (both 79 per cent), but was superior for extrahepatic abdominal sites (63 and 25 per cent respectively). PET provided additional information in five patients, mainly by revealing abdominal extrahepatic metastases, but falsely upstaged three patients. CONCLUSION: Whole-body FDG-PET may identify unrecognized extrahepatic metastases in patients with potentially resectable liver metastases imaged by CT. However, additional information provided by PET is not as reliable as suggested by earlier retrospective studies.     

Fatal case of Naegleria fowleri meningo-encephalitis in an infant: case report

Primary amoebic meningo-encephalitis (PAM) is extremely rare and is caused by Naegleria fowleri. It is ?commonly seen in older children who swim in water contaminated with Naegleria species. It is very rare to contract the illness by any other means. We report a case of PAM in an infant aged 6 months. To the best of our knowledge, only one other case of PAM in an infant has been reported from India. A high index of suspicion is required in infants who manifest similarly to pyogenic meningitis but whose CSF shows no bacterial organisms so that a wet mount of a CSF sample can be done for early detection of Naegleria fowleri infection and appropriate intervention.     

Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells

Epigallocatechin-3-gallate (EGCG), a major component in green tea polyphenols, has been proven to suppress colonic tumorigenesis in animal models and epidemiological studies. As EGCG is retained in the gastrointestinal tract after oral administration, this pharmacokinetics property gives it the potential to function as a chemopreventive agent against colon cancer. In this study, human colorectal carcinoma HT-29 cells were treated with EGCG to examine the anti-proliferative and pro-apoptotic effects of EGCG, as well as the molecular mechanism underlying these effects. Cell viability assay, nuclear staining, DNA fragmentation, caspase assay, cytochrome c release, DiOC6(3) staining, mitogen-activated protein kinases (MAPK) phosphorylation and trypan blue exclusion assays, were utilized to dissect the signaling pathways induced by EGCG. After 36 h treatment, EGCG inhibited HT-29 cell growth with an IC50 of approximately 100 microM. HT-29 cells treated with doses higher than 100 microM showed apparent nuclear condensation and fragmentation, which was confirmed by DNA laddering. Caspase-3 and -9 activation was detected after 12 h treatment, accompanied by mitochondrial transmembrane potential transition and cytochrome c release. Activation of MAPKs was detected as early signaling event elicited by EGCG. Inhibition of c-Jun N-terminal kinase (JNK) pathway showed the involvement of JNK in EGCG-induced cytochrome c release and cell death. EGCG-induced JNK activation was blocked by the antioxidants glutathione and N-acetyl-l-cysteine, suggesting that the cell death signaling was potentially triggered by oxidative stress. In summary, our results from this study suggest that in HT-29 human colon cancer cells (i) EGCG treatment causes damage to mitochondria, and (ii) JNK mediates EGCG-induced apoptotic cell death.     

N6-substituted D-4'-thioadenosine-5'-methyluronamides: potent and selective agonists at the human A3 adenosine receptor

4'-Thio analogues 3-5 of Cl-IB-MECA (2) (K(i) = 1.0 +/- 0.2 nM at the human A(3) adenosine receptor) were synthesized from d-gulono-gamma-lactone via 4-thioribosyl acetate 14 as the key intermediate. All synthesized 4'-thionucleosides exhibited higher binding affinity to the human A(3) adenosine receptor than Cl-IB-MECA, among which 4 showed the most potent binding affinity (K(i) = 0.28 +/- 0.09 nM). 4 was also selective for A(3) vs human A(1) and human A(2A) receptors by 4800- and 36000-fold, respectively.     

Prognostic value of circulating soluble E-selectin concentrations in node-negative breast cancer patients.

Several studies have suggested that endothelial cells participate in tumor development. Soluble E-selectin (sE-selectin) is specifically released by activated endothelial cells, and its serum concentration can be considered a marker of endothelial activation. In this study, we assessed the prognostic value of sE-selectin concentrations in node-negative breast cancer patients. Serum sE-selectin concentrations were measured by an ELISA method prior to surgery in 456 node-negative breast cancer patients. We analyzed also tumor size (TS), histoprognostic grading, and steroid hormone receptor status. The mean sE-selectin concentration was 24.9 +/- 15.0 ng/ml. The sE-selectin concentrations were mildly correlated with the TS but not with the other factors. For prognostic analyses, the median follow-up duration was 7.5 years. The cutoff sE-selectin concentration used was 40 ng/ml. In overall survival studies, univariate analyses demonstrated a prognostic value of sE-selectin, TS, and histoprognostic grading, and multivariate analyses demonstrated a prognostic value of sE-selectin and TS. For disease-free survival, univariate and multivariate analyses demonstrated a prognostic value of sE-selectin and TS. sE-selectin concentration is an easily measurable and strong prognostic factor in node-negative breast cancer patients. These results provide further evidence for the role of adhesion molecules expression by endothelial cells in tumor progression.     

A neurodegenerative mitochondrial disease phenotype due to biallelic loss‐of‐function variants in PNPLA8 encoding calcium‐independent phospholipase A2γ

Animal studies have demonstrated the critical roles of the patatin‐like protein family plays in cellular growth, lipid homeostasis, and second messenger signaling the nervous system. Of the nine known calcium‐independent phospholipase A2γ, only PNPLA2, PNLPA6, PNPLA9 and most recently a single patient with PNPLA8 are associated with mitochondrial‐related neurodegeneration. Using whole exome sequencing, we report two unrelated individuals with variable but similar clinical features of microcephaly, severe global developmental delay, spasticity, lactic acidosis, and progressive cerebellar atrophy with biallelic loss‐of‐function variants in PNPLA8.