A huge malignant perivascular epithelioid cell tumor (PEComa) of the uterine cervix and vagina

Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal neoplasms, including angiomyolipoma, clear-cell “sugar” tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear-cell tumors at various other anatomic sites.     

Methylene chloride and brain cancer: Interpreting a new study in light of existing literature

(This article is a US Government work and, as such, is in the public domain in the United States of America.)     

Effect of peri-operative blood transfusions on long-term prognosis of patients with colorectal cancer

BackgroundPatients with colorectal cancer often present with anaemia and require red blood cell transfusions (RBCT) during their peri-operative course. Evidence suggests a significant association between RBCT and poor long-term outcomes in surgical patients, but the findings in colorectal cancer are contradictory.Material and methodsThe aim of this retrospective, single-centre, cohort study was to investigate the prognostic role of peri-operative RBCT in a large cohort of patients with stage I–III colorectal cancer submitted to curative surgery between 2005 and 2017. The propensity score matching technique was applied to adjust for potential confounding factors.ResultsAmong 1,414 patients operated within the study period, 895 fulfilled the inclusion criteria: 29.6% (n=265) received peri-operative RBCT. The group that received peri-operative RBCT was significantly older (p<0.001), had more comorbidities (p<0.001), more advanced tumours (p<0.001) and more colon tumours (p=0.002) and stayed in hospital longer (p<0.001). Post-operative mortality was 7-fold higher (2.3 vs 0.3%, p=0.01) in this group. Survival outcomes were significantly worse in the group receiving RBCT than in the group not receiving RBCT for both overall (64.5 vs 80.1%, p<0.001) and cancer-specific survival (74.3 vs 85.1%, p<0.001). On multivariable analysis, peri-operative RBCT was significantly associated with poorer overall survival (hazard ratio 1.51, p=0.009). When transfused and non-transfused cases were paired through the propensity score matching technique considering main clinico-pathological features, no differences in overall and cancer-specific survival were found.DiscussionOur data suggest that, after adjustment for potential confounding factors, no significant association exists between RBCT and prognosis in colorectal cancer.     

Loss of CB1 receptors leads to decreased cathepsin D levels and accelerated lipofuscin accumulation in the hippocampus

Early onset of age-related changes in the brain of cannabinoid 1 receptor knockout (Cnr1^−/−) mice suggests that cannabinoid 1 (CB1) receptor activity significantly influences the progression of brain aging. In the present study we show that lack of CB1 receptors leads to a significant increase in lipofuscin accumulation and a reduced expression and activity of cathepsin D, lysosomal protease implicated in the degradation of damaged macromolecules, in the hippocampus of 12-month-old mice. The impaired clearance of damaged macromolecules due to the low cathepsin D levels and not enhanced oxidative stress may be responsible for the lipofuscin accumulation because macromolecule oxidation levels were comparable between the genotypes within the same age group. The altered levels of autophagy markers p62 and LC3-II suggest that autophagy is upregulated in CB1 knockout mice. Increased autophagic flux in the absence of CB1 receptors is probably a compensatory mechanism to partially counteract decreased lysosomal degradation capacity. Together, these results suggest that CB1 receptor activity affects lysosomal activity, degradation of damaged macromolecules and thus it may influence the course and onset of brain aging.     

Antibodies to the neuronal cytoskeleton are elicited by Alzheimer paired helical filament fractions

Antibodies were raised to paired helical filament (PHF) enriched fractions obtained from brains of individuals with Alzheimer disease by extraction with ionic detergent followed by sucrose gradient centrifugation. Electron microscopic examination showed that the fractions were enriched in Alzheimer PHF but contained also lipofuscin, amyloid, granular material and membranous elements. Analysis of these fractions with SDS-PAGE stained with Coomassie blue showed only a faint band at approximately 60 kDa while most of the material was excluded from the stacking gel. BALB/c mice were injected weekly with 100 or 200 μg of these fractions or corresponding fractions from age-matched control brains. The 3 mice injected with Alzheimer brain, but not the 5 mice injected with control brain fractions, produced antibodies that reacted with central and peripheral nervous system axons, Alzheimer neurofibrillary tangles in intact tissue as well as with isolated, SDS-treated paired helical filaments. In gel strips antibodies from all 3 mice injected with Alzheimer brain fractions reacted with the 200-kDa and 168-kDa but not the 68-kDa neurofilament subunits. The 3 antisera reacted also with some forms of the microtubule-associated protein τ. Adsorptions with the insoluble fraction from Alzheimer but not from control brains blocked staining of axons and NFT by all 3 antisera. Adsorption with highly purified neurofilament proteins or with a preparation containing the 200-kDa 168-kDa neurofilament subunits blocked axon and NFT immunostaining only in one antiserum. Adsorptions with microtubule protein, heat-stable microtubule-associated protein, or a preparation of τ did not completely block immunostaining by any of the 3 antisera. These results demonstrate that fractions enriched with Alzheimer paired helical filaments contain insoluble neurofilament, τ and other yet unidentified antigens.     

Prognostic value of persistent thallium-201 defects that become reversible after reinjection in patients with chronic myocardial infarction

Background

The presence of defects at stress-redistribution thallium-201 scintigraphy is related to a higher risk of cardiac events. However, the prognostic value of defects that become reversible after reinjection is not known. In this study we evaluated the prognostic contribution of stress-redistribution-reinjection with special regard to 3-hour fixed defects that become reversible after reinjection.

Methods and Results

We studied 122 patients with chronic myocardial infarction (>2 months) and suspected or known residual ischemia, with stress-redistribution-reinjection planar scintigraphy. Thallium scans were analyzed by three observers (three segments per view, 5-point score) and classified as normal, fixed, and reversible. The lung/heart ratio was also calculated. At a median follow-up of 47 months, 10 patients had hard events (four deaths and six myocardial infarctions) (group I), 12 patients had unstable angina (group II), 12 patients underwent planned coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (group III), and 86 patients had no events (group IV). The presence of fixed defects that became reversible after reinjection did not identify patients at higher risk. The number of reversible defects at 3 hours was significantly higher only in patients who underwent revascularization. Unstable angina was not predicted by any scintigraphic pattern. The variables that were statistically related to hard events by univariate analysis were increased lung uptake, reversible cavity dilation, and the number of fixed defects that remained fixed after reinjection. By Cox multivariate analysis, the strongest predictor of hard events was the presence of more than three fixed defects that remained fixed after reinjection as a marker of irreversible myocardial damage.

Conclusions

²⁰¹TI reinjection is a useful approach for not only detecting viable myocardium but also risk stratification in patients with chronic myocardial infarction.     

Desmoplastic Reaction Influences Pancreatic Cancer Growth Behavior

Connective tissue growth factor (CTGF), which is regulated by transforming growth factor-ß (TGFß), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46-fold increase in CTGF mRNA expression (p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFß-induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation (p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) (p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFß, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.