Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

<p>Abstract</p> <p>Background</p> <p>Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC) but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs), has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE) treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence.</p> <p>Methods</p> <p>Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE). Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen.</p> <p>Results</p> <p>TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040). None of the other markers predicted recurrence.</p> <p>Conclusion</p> <p>High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of tumor cells with a CSC phenotype may be a critical factor in the likelihood of tumor recurrence in patients receiving liver transplantation after TACE.</p

Telomere maintenance and length regulation in Trypanosoma brucei

Transcription of telomere proximal variant surface glycoprotein genes is mono-allelic in bloodstream-form Trypanosoma brucei. The terminal DNA sequence at these telomeres consists of tandem T(2)AG(3) repeats, which increase in length by ∼8 bp per cell division balanced by occasional loss of large numbers of repeats. Here we have used targeted chromosome fragmentation to investigate the sequence requirements for telomere formation in T.brucei. Telomere formation is most efficient on tandem T(2)AG(3) repeats, but can also occur on specific templates found within ‘random’ sequence substrates and on G-rich motifs proximal to a double-strand break. Newly formed telomeres are extended faster than other native telomeres, but as the telomere becomes longer the rate of extension declines. Telomere length regulation in T.brucei is discussed in the context of recent results from other cell types

Complement C3a expression and tryptase degranulation as promising histopathological tests for diagnosing fatal amniotic fluid embolism

To date, the most recent specific diagnostic investigations for amniotic fluid embolism have been unable to conclusively identify any mechanism of disease other than a physical block to the circulation. We selected eight fatal cases in previously healthy women with uneventful singleton term pregnancies who presented to tertiary care centers in Italy for delivery. Pathologic features were assessed immu- nohistochemically using anti-fibrinogen, anti-tryptase, anti- C3a, and anti-cytokeratin antibodies. AE1/AE3 cytokeratin stains proved positive, and tryptase-positive material was documented outside pulmonary mast cells. In all studied cases, expression of complement C3a was twofold lower than in the control group, suggesting a possible complement activation in AFE, initiated by fetal antigen leaking into the maternal circulation