McGlynn KA, Tarone RE, El Serag HBA comparison of trends in the incidence of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in the United States. Cancer Epidemiol Biomarkers Prev 15(6): 1198-1203
The incidence rates of liver cancers, both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are increasing in the U.S. It is possible that the increases are related to common exposures, and if so, similar trends in incidence by gender, age, ethnicity, and calendar period, might exist. To examine this hypothesis, age-specific trends in the incidence of HCC and ICC in the Surveillance, Epidemiology and End Results program (1976-2000) were examined by year of diagnosis and year of birth. Age-period-cohort models were also fit to the data. The incidence of HCC in the most recent time period was twice as high among Black men (8.8/100,000) and women (2.6/100,000) as among White men (4.6/100,000) and women (1.2/100,000). However, between 1976 and 2000, incidence among all four ethnic- and gender-specific groups increased by >90% (White males, 123.2%; White females, 96.8%; Black males, 97.9%; Black females, 91.9%) with young White men experiencing the greatest increases (432%). In contrast, ICC rates were similar for Black (0.93/100,000) and White men (0.92/100,000), but higher for White (0.57/100,000) than Black women (0.39/100,000). Although ICC incidence increased among all groups, the increase was greatest for Black men (138.5%), followed by White men (124.4%), White women (111.1%), and Black women (85.7%) Age-period-cohort analyses of HCC revealed a significant cohort effect among younger men (45-65 years old), but not older men (65-84 years old), suggesting possible differences in etiology. In conclusion, the rates of HCC and ICC approximately doubled between 1976 and 2000. Trends by age, gender, ethnicity, and birth cohort suggest that heterogeneity exists in the factors influencing these rates.
"In fact, up until the current 7th edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICCA) staging manual, there was no distinct internationally recognized staging system for iCCA . There are, however, important epidemiologic, etiologic, and biologic differences between iCCA and HCC  . As such, there has been an increasing realization of the importance of establishing a distinct staging system for iCCA . "
"A majority of these cases originates from developing countries and occurs more frequently in men than women. In the United States, the incidence of HCC has increased by more than 90% in the past three decades . Despite great advances have been achieved in HCC diagnosis and therapy, the morality rate remains high, especially for HCC in the advanced stage when the disease is usually diagnosed. "
[Show abstract][Hide abstract] ABSTRACT: The development of immunoliposomes for systemic siRNA (small interfering RNA) delivery is highly desired. We reported previously the development of targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab' (TLPD-FCC) for siRNA delivery, which showed superior gene silencing activity in EGFR-overexpressing breast cancers. However, TLPD-FCC did not achieve satisfactory gene silencing activity in EGFR-overexpressing hepatocellular carcinoma (HCC). In this study, some modifications including increased antibody conjugation efficiency and reduced PEGylation degree were made to TLPD-FCC to increase gene silencing activity in HCC. The resultant optimized liposomes denoted as TLPD-FP75 efficiently bound and delivered to EGFR-overexpressing HCC, resulting in enhanced gene silencing activity compared to untargeted LPD (NTLPD-FP75). Tissue distribution in vivo revealed that the accumulation of TLPD-FP75 was higher than NTLPD-FP75 in orthotopic HCC model of mice. The promoted uptake of TLPD-FP75 in HCC cells was confirmed by confocal microscopy. To investigate the in vivo gene silencing activity, we administered TLPD-FP75 by intravenous injections into mice bearing orthotopic HCC. The results showed TLPD-FP75 potently suppressed luciferase expression, while little silencing was observed in NTLPD-FP75. TLPD-FP75 was demonstrated to possess potent gene silencing activity in HCC and will potentially increase the feasibility of HCC gene therapy.
"Hepatocellular carcinoma (HCC) is the 5 th most common cancer and the third leading cause of cancer related deaths worldwide [El-Serag and Rudolph, 2007]. In the United States, the incidence of HCC and intrahepatic cholangiocarcinoma doubled in the last 30 years [McGlynn et al., 2006], with five-year survival rate for individuals with symptomatic HCC only 5% [El-Serag et al., 2001]. The current study examined the expression and potential role of the multifunctional protein disulfide isomerase (PDI) endoplasmic reticulum protein of 57 kDa (ERp57)/PDIA3/GRP58/1,25D 3 -MARRS in HepG2 cells, a model for HCC. "
[Show abstract][Hide abstract] ABSTRACT: ERp57/PDIA3/1,25-MARRS has diverse functions and multiple cellular locations in various cell types. While classically described as an endoplasmic reticulum (ER) resident protein, ERp57 has a nuclear location sequence (NLS) and can enter the nucleus from the cytosol to alter transcription of target genes. Dysregulation and variable expression of ERp57 is associated with a variety of cancers including hepatocellular carcinoma (HCC). We investigated the dynamic mobility of ERp57 in an HCC cell line, HepG2, to better understand the movement and function of the non-ER resident pool of ERp57. Subcellular fractionation indicated ERp57 is highly expressed in the ER with a smaller cytoplasmic pool in HepG2 cells. Utilizing an ERp57 green fluorescent protein fusion construct created with and without a secretory signal sequence, we found that cytoplasmic ERp57 translocated to the nucleus within 15 min after tumor necrosis factor-α (TNF-α) treatment. Protein kinase C activators including 1,25-dihydroxyvitamin D(3) and phorbol myristate acetate did not trigger nuclear translocation of ERp57, indicating translocation is PKC independent. To determine if an interaction between the rel homology binding domain in ERp57 and the nuclear factor-κB subunit, p65, occurred after TNF-α treatment and could account for nuclear movement, co-immunoprecipitation was performed under control and conditions that stabilized labile disulfide bonds. No support for a functional interaction between p65 and ERp57 after TNF-α treatment was found in either case. Immunostaining for both ERp57-GFP and p65 after TNF-α treatment indicated that nuclear translocation of these two proteins occurs independently in HepG2 cells.
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