[Differentiation between hyperintense hepatocellular carcinoma and focal nodular hyperplasia in hepatobiliary phase with multimodal parameters of magnetic resonance imaging].

Objective: To differentiate hyperintense hepatocellular carcinoma (HCC) with focal nodular hyperplasia (FNH) in the hepatobiliary phase by MRI multimodal parameters. Methods: A retrospective cross-sectional study method was adopted. Clinical data on 15 cases with hyperintense HCC and 15 cases with FNH in the hepatobiliary phase admitted to the First Affiliated Hospital of the Army Medical University from January 2012 to December 2019 were collected. All patients with solitary lesions who underwent Gd-EOB-DTPA-enhanced MRI examinations were included. Surgically resected specimens were verified by pathological and immunohistochemical examination. HCC and FNH imaging features were analyzed by two radiologists. Results: (1) HCC and FNH apparent diffusion coefficient (ADC) values were 1 205.07±239.65×10-3 mm2/s and 1 434.73±217.6×10-3 mm2/s, respectively, and the SIADC difference was statistically significant (P<0.05) between the two groups. (2) In the dynamic contrast-enhanced MRI sequence, 15 cases of HCC were significantly enhanced in the arterial phase, of which 13 cases were characterized by continuous enhancement, and 2 cases were characterized by wash-in and wash-out enhancement. There was no statistically significant difference (P>0.05) between the two groups. SIenhancement rate between HCC and FNH (1.39±0.60 vs. 1.33±0.50, P>0.05) had no significant difference. (3) HCC and FNH morphological features in the hepatobiliary phase included: annular hypointensity: HCC (8 cases) vs. FNH (0 cases); contrast filling defects: HCC (8 cases) vs. FNH (0 cases); linear hyposignal separation: HCC (10 cases) vs. FNH (0 cases); and stellate scars: HCC (0) vs. FNH (5 cases), and there were statistically significant differences (P<0.05) between the two groups . Conclusion: Multimodal MRI have significant value for differentiating hyperintense HCC and FNH in the hepatobiliary phase.

Utilizing hydrogen sulfide as a novel anti-cancer agent by targeting cancer glycolysis and pH imbalance.

BACKGROUND AND PURPOSE: Many disparate studies have reported the ambiguous role of hydrogen sulfide (H2 S) in cell survival. The present study investigated the effect of H2 S on the viability of cancer and non-cancer cells. EXPERIMENTAL APPROACH: Cancer and non-cancer cells were exposed to H2 S [using sodium hydrosulfide (NaHS) and GYY4137] and cell viability was examined by crystal violet assay. We then examined cancer cellular glycolysis by in vitro enzymatic assays and pH regulator activity. Lastly, intracellular pH (pHi ) was determined by ratiometric pHi measurement using BCECF staining. KEY RESULTS: Continuous, but not a single, exposure to H2 S decreased cell survival more effectively in cancer cells, as compared to non-cancer cells. Slow H2 S-releasing donor, GYY4137, significantly increased glycolysis, leading to overproduction of lactate. H2 S also decreased anion exchanger and sodium/proton exchanger activity. The combination of increased metabolic acid production and defective pH regulation resulted in an uncontrolled intracellular acidification, leading to cancer cell death. In contrast, no significant intracellular acidification or cell death was observed in non-cancer cells. CONCLUSIONS AND IMPLICATIONS: Low and continuous exposure to H2 S targets metabolic processes and pH homeostasis in cancer cells, potentially serving as a novel and selective anti-cancer strategy.

Camptothecin-induced downregulation of MLL5 contributes to the activation of tumor suppressor p53.

Mixed lineage leukemia 5 (MLL5) has been implicated in multiple aspects of cell physiology, such as hematopoiesis, cell cycle control and chromatin regulatory network. In this study, we present evidence that MLL5 is involved in the camptothecin (CPT)-induced p53 activation. CPT promoted the degradation of MLL5 protein in a time- and dose-dependent manner in actively replicating cells. The downregulation of MLL5 led to phosphorylation of p53 at Ser392, which was abrogated by exogenous overexpression of MLL5. In MLL5-knockdown cells, p53 protein was stabilized and bound to DNA with higher affinity, leading to activation of downstream genes. Co-immunoprecipitation showed that MLL5 preferentially interacted with the tetramerized form of p53, and knockdown of MLL5 promoted chromatin accumulation of p53 tetramers, suggesting that the association of MLL5 with p53 may prevent the p53 tetramers from binding to the chromatin target sites. The role of MLL5 in CPT-induced p53 activation was conserved in developing zebrafish, where CPT downregulated zebrafish Mll5 protein, and the microinjection of zebrafish mll5 mRNA substantially blocked the CPT-induced apoptosis. In summary, our study proposed MLL5 as a novel component in the regulation of p53 homeostasis and a new cellular determinant of CPT.

[A nasopharyngeal carcinoma negatively related EST on 7q32].

To isolate and clone the tumor suppressor gene on chromosomal region 7q32 that corelated with the occurrence of human NPC, we detected the genotype of polymorphic microsatellite markers on 7q32 in 24 nasopharyngeal carcinoma biopsies and matched normal lymphocyte DNA. LOH was found in 30% biopsies. Using differential RT-PCR and Northern hybridization we compared the expression level of 20 EST on 7q32 between NPC cell line HNE1 and primary culture of normal nasopharyngeal epithelial cell, and found AA070437 EST expressed high in primary culture of normal nasopharyngeal epithelial cell, but very low in HNE1. Differential RT-PCR (dRT-PCR) analysis showed that the expression level of AA070437 was lower in 30.7% NPC biopses than in normal cell. Differential PCR (dPCR) showed that allelic loss of AA070437 was observed in 29.1% NPC biopses. This EST is a part of sequence of a new gene compared with GeneBank database. Our results showed that AA070437 EST negatively related with the occurrence of human NPC is a candidate of tumor suppressor gene of NPC on 7q32.

Interaction of the globular domains of pIII protein of filamentous bacteriophage fd with the F-pilus of Escherichia coli.

Gene 3 protein (pIII), a minor coat protein at one end of the filamentous bacteriophage fd, is involved in initiating the infection by the virus of Escherichia coli cells that display an F-pilus. Infection is thought to start with the adsorption of the D2 domain of pIII to the tip of the pilus, retraction of the pilus, and penetration of the E. coli cell membrane mediated by an interaction between the D1 domain of pIII and the Tol protein complex in the membrane. A subgene encoding the pIII-D1D2 di-domain was created, and the subgene was successfully overexpressed in E. coli cells. Domains D1 and D2 were separated after limited proteolysis of a modified pIII-D1D2 (designated pIII-D1D2.trp) into which two tryptic cleavage sites were introduced at appropriate points. The purified pIII-D1D2 di-domain and pIII-D2 domain were able to bind to the F-pilus, competing with the wild-type pIII and delaying infection by the intact filamentous phage. The pIII-D1 domain was unable to bind to the F-pilus by this criterion. This provides conclusive evidence that the pIII-D2 domain is responsible for the adsorption to the tip of the F-pilus and can achieve this in the absence of domain D1, opening the way to identifying the molecular basis of the interaction of pIII-D2 with the pilus.