The deregulated nonoxidative pentose phosphate pathway (PPP) is known to promote oncogenesis, but the molecular mechanism remains unknown. Here, we report that human ribose-5-phosphate isomerase A (RPIA) plays a role in human hepatocellular carcinoma (HCC). A significant increase in RPIA expression was detected both in tumor biopsies of HCC patients and in a liver cancer tissue array. Importantly, the clinicopathological analysis indicated that RPIA mRNA levels were highly correlated with clinical stage, grade, tumor size, types, invasion and alpha-fetoprotein levels in the HCC patients. In addition, we demonstrated that the ability of RPIA to regulate cell proliferation and colony formation in different liver cancer cell lines required ERK signaling as well as the negative modulation of PP2A activity and that the effects of RPIA could be modulated by the addition of either a PP2A inhibitor or activator. Furthermore, the xenograft studies in nude mice revealed that the modulation of RPIA in liver cancer cells regulated tumor growth and that NIH3T3 cells overexpressing RPIA exhibited increased proliferation, enhanced colony formation, elevated levels of p-ERK1/2 and accelerated tumor growth. This study provides new insight into the molecular mechanisms by which RPIA overexpression can induce oncogenesis in HCC. Furthermore, it suggests that RPIA can be a good prognosis biomarker and a potential target for HCC therapy.

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare, and its surgical management is difficult because of its unique anatomic location. We have seen six such cases at our hospital. For patients with fair to excellent liver reserve, we advocated caudate lobectomy combining other types of hepatic resection. For patients with marked liver cirrhosis and poor liver reserve or a small HCC, we advocated simple partial caudate lobectomy (limited hepatic resection). There was no operative mortality or major operative morbidity. We conclude that such approaches are safer, less time-consuming, and less technique-demanding, and they produce a fair survival result compared with the approaches of other procedures. With such approaches, it is our experience that patients with HCC from the caudate lobe have a prognosis comparable to that of patients with HCC in other parts of the liver.

hBUB1 gene is a component of the mitotic checkpoint that monitors proper assembly of the mitotic spindles and the alteration of the hBUB1 gene has been found to be associated with chromosomal instability in some tumor cell lines. We analyzed the coding region of the hBUB1 gene for mutations and its expression in 92 acute myeloid leukemia (AML) specimens and five hematopoietic cell lines. We also used Southern hybridization to analyze the genomic DNA of those cases, which had aberrant transcription to confirm the lesion. A thymine/cytosine polymorphism at 8 bp upstream of the 5' splice acceptor site of exon 10 was observed in Raji cell line and two AML specimens without a resultant change in the expression of hBUB1. Reduced expression and aberrant transcription of the hBUB1 gene, which may affect the control of mitotic checkpoint, were detected in AML specimens by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Our study suggests that the mutation of the hBUB1 gene is a rare event in AML, and further studies are necessary to clarify its role in leukemia.

ST50, an outer-membrane component of the multi-drug efflux system from Salmonella enterica serovar Typhi, is an obligatory diagnostic antigen for typhoid fever. ST50 is an excellent and unique diagnostic antigen with 95% specificity and 90% sensitivity and is used in the commercial diagnosis test kit (TYPHIDOTTM). The crystal structure of ST50 at a resolution of 2.98 Å reveals a trimer that forms an α-helical tunnel and a β-barrel transmembrane channel traversing the periplasmic space and outer membrane. Structural investigations suggest significant conformational variations in the extracellular loop regions, especially extracellular loop 2. This is the location of the most plausible antibody-binding domain that could be used to target the design of new antigenic epitopes for the development of better diagnostics or drugs for the treatment of typhoid fever. A molecule of the detergent n-octyl-β-D-glucoside is observed in the D-cage, which comprises three sets of Asp361 and Asp371 residues at the periplasmic entrance. These structural insights suggest a possible substrate transport mechanism in which the substrate first binds at the periplasmic entrance of ST50 and subsequently, via iris-like structural movements to open the periplasmic end, penetrates the periplasmic domain for efflux pumping of molecules, including poisonous metabolites or xenobiotics, for excretion outside the pathogen.