Modelling the potential impact of global hepatitis B vaccination on the burden of chronic hepatitis B in the United States.

About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non-US-born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals.

Rational design, synthesis and structural characterization of peptides and peptidomimetics to target Hsp90/Cdc37 interaction for treating hepatocellular carcinoma.

Heat shock protein 90 (Hsp90) and cell division cycle 37 (Cdc37) work together as a molecular chaperone complex to regulate the activity of a multitude of client protein kinases. These kinases belong to a wide array of intracellular signaling networks that mediate multiple cellular processes including proliferation. As a result, Hsp90 and Cdc37 represent innovative therapeutic targets in various cancers (such as leukemia, multiple myeloma, and hepatocellular carcinoma (HCC)) in which their expression levels are elevated.

Exploring Biomolecular Interaction Between the Molecular Chaperone Hsp90 and Its Client Protein Kinase Cdc37 using Field-Effect Biosensing Technology.

Biomolecular interactions play versatile roles in numerous cellular processes by regulating and coordinating functionally relevant biological events. Biomolecules such as proteins, carbohydrates, vitamins, fatty acids, nucleic acids, and enzymes are fundamental building blocks of living beings; they assemble into complex networks in biosystems to synchronize a myriad of life events. Proteins typically utilize complex interactome networks to carry out their functions; hence it is mandatory to evaluate such interactions to unravel their importance in cells at both cellular and organism levels.

A Humanized Anti-GPC3 Antibody for Immuno-Positron Emission Tomography Imaging of Orthotopic Mouse Model of Patient-Derived Hepatocellular Carcinoma Xenografts.

Glypican-3 (GPC3) is an attractive diagnostic marker for hepatocellular carcinoma (HCC). We previously reported the potential of an Zr-labeled murine anti-GPC3 antibody (clone 1G12) for immunoPET imaging of HCC in orthotopic patient-derived xenograft (PDX) mouse models. We now humanized the murine antibody by complementarity determining region (CDR) grafting, to allow its clinical translation for human use.

An NIR-II/MR dual modal nanoprobe for liver cancer imaging.

Hepatocellular carcinoma (HCC) is a malignancy of the liver worldwide and surgical resection remains the most effective treatment. However, it is still a great challenge to locate small lesions and define the border of diffused HCC even with the help of preoperative imaging examination. Here, we reported a rare-earth-doped nanoparticle NaGdF4:Nd 5%@NaGdF4@Lips (named Gd-REs@Lips), which simultaneously performed powerful functions in both magnetic resonance imaging (MRI) and second near-infrared fluorescence window imaging (NIR-II, 1000-1700 nm).

Racial/ethnic- and county-specific prevalence of chronic hepatitis B and its burden in California.

Background: In the United States, the highest burden of chronic hepatitis B (CHB) and CHB-related liver cancer is in the state of California, primarily in the San Francisco (SF) Bay and Los Angeles (LA) areas. The aim of this study was to estimate county-specific hepatitis B surface antigen (HBsAg) prevalence and quantify CHB cases by age, race/ethnicity, nativity, and disease activity status.

Methods: Twelve counties in SF Bay Area and three large counties in LA area were included for this analysis.

Disparities in hepatocellular carcinoma incidence by race/ethnicity and geographic area in California: Implications for prevention.

Background: The incidence of hepatocellular carcinoma (HCC) has been rising rapidly in the United States. California is an ethnically diverse state with the largest number of incident HCC cases in the country. Characterizing HCC disparities in California may inform priorities for HCC prevention.

Cost-Effectiveness and Cost Thresholds of Generic and Brand Drugs in a National Chronic Hepatitis B Treatment Program in China.

Chronic liver disease and liver cancer associated with chronic hepatitis B (CHB) are leading causes of death among adults in China. Although newborn hepatitis B immunization has successfully reduced the prevalence of CHB in children, about 100 million Chinese adults remain chronically infected. If left unmanaged, 15-25% will die from liver cancer or liver cirrhosis.

Suppression of ATAD2 inhibits hepatocellular carcinoma progression through activation of p53- and p38-mediated apoptotic signaling.

The ATPase family, AAA domain containing 2 (ATAD2) is highly expressed in multiple cancers. We aim to understand the clinical and biological significance of ATAD2 over-expression in hepatocellular carcinoma (HCC), as a means to validate it as a therapeutic target in HCC. We demonstrated that ATAD2 was over-expressed in HCC patients, where high ATAD2 levels were significantly correlated with aggressive phenotypes such as high AFP levels, advanced tumor stages, and vascular invasion.

NDRG1 promotes growth of hepatocellular carcinoma cells by directly interacting with GSK-3β and Nur77 to prevent β-catenin degradation.

The N-myc downstream regulated gene 1 (NDRG1) is significantly associated with advanced tumor stages and poor survival of hepatocellular carcinoma (HCC), thereby implicating it as a potential target for HCC treatment. We aim to further understand its biological roles in hepatocarcinogenesis, as a means to exploit it for therapeutic purposes. By screening using the ProtoArray® Human Protein Microarrays, we identified glycogen synthase kinase 3β (GSK-3β) and the orphan nuclear receptor (Nur77) as potential interaction partners of NDRG1.

Medical training fails to prepare providers to care for patients with chronic hepatitis B infection.

Aim: To investigate physicians' knowledge including chronic hepatitis B (CHB) diagnosis, screening, and management in various stages of their training.

Methods: A voluntary 20-question survey was administered in Santa Clara County, CA where Asian and Pacific Islanders (API) account for a third of the population. Among the 219 physician participants, there were 63 interns, 60 second-year residents, 26 chief residents and 70 attending physicians.

Imaging of hepatocellular carcinoma patient-derived xenografts using ⁸⁹Zr-labeled anti-glypican-3 monoclonal antibody.

Imaging probes for early detection of hepatocellular carcinoma (HCC) are highly desired to overcome current diagnostic limitations which lead to poor prognosis. The membrane protein glypican-3 (GPC3) is a potential molecular target for early HCC detection as it is over-expressed in >50% of HCCs, and is associated with early hepatocarcinogenesis. We synthesized the positron emission tomography (PET) probe (89)Zr-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with (89)Zr, and evaluated its tumor-targeting capacity.

Suppressing N-Myc downstream regulated gene 1 reactivates senescence signaling and inhibits tumor growth in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most lethal malignancy worldwide with no curative therapies. To discover potentially novel therapeutic targets for HCC, we previously studied the gene expression profiles of HCC patients and identified that significant upregulation of N-Myc downstream regulated gene 1 (NDRG1) is associated with more aggressive phenotypes and poorer overall survival of HCC patients. In this study, we further used a loss-of-function approach (RNA interference) to understand the role of NDRG1 in hepatocarcinogenesis.

Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes.

Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%-20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates.

Education and counseling of pregnant patients with chronic hepatitis B: perspectives from obstetricians and perinatal nurses in Santa Clara County, California.

Background: This study aimed to better understand the barriers to perinatal hepatitis B prevention and to identify the reasons for poor hepatitis B knowledge and delivery of education to hepatitis B surface-antigen- positive pregnant women among healthcare providers in Santa Clara County, California.

Materials And Methods: Qualitative interviews were conducted with 16 obstetricians and 17 perinatal nurses in Santa Clara County, California, which has one of the largest populations in the United States at high risk for perinatal hepatitis B transmission.

Results: Most providers displayed a lack of self-efficacy attributed to insufficient hepatitis B training and education.

Low levels of knowledge and preventive practices regarding vertical hepatitis B transmission among perinatal nurses.

Objective: To evaluate current levels of hepatitis-B-related knowledge and clinical practice among perinatal nurses.

Design: Cross-sectional study.

Setting: Santa Clara County, California, home to one of the largest U.

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer.

Suppression of glypican 3 inhibits growth of hepatocellular carcinoma cells through up-regulation of TGF-β2.

Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). To evaluate the efficacy of targeting GPC3 at the translational level, we used RNA interference to examine the biologic and molecular effects of GPC3 suppression in HCC cells in vitro and in vivo. Transfection of Huh7 and HepG2 cells with GPC3-specific small interfering RNA (siRNA) inhibited cell proliferation (P < .

A model program for hepatitis B vaccination and education of schoolchildren in rural China.

Objectives: Incomplete hepatitis B virus (HBV) vaccine coverage and poor HBV-related knowledge in China leave millions of children unprotected from this life-threatening infection. To address these gaps, a pilot program for HBV education and vaccination was launched in rural China.

Methods: In 2006, public and private organizations in the US and China collaborated to provide HBV education and vaccination to 55,000 school-age children in the remote, highly HBV-endemic area of Qinghai Province.

Doing Good with Good OR: Supporting Cost-effective Hepatitis B Interventions.

In an era of limited healthcare budgets, mathematical models can be useful tools to identify cost-effective programs and to support policymakers in informed decision making. This paper reports results of our work carried out over several years with the Asian Liver Center at Stanford University, a nonprofit outreach and advocacy organization that is an international leader in the fight against hepatitis B and liver cancer. Hepatitis B is a vaccine-preventable viral disease that, if untreated, can lead to death from cirrhosis and liver cancer.

Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker.

Purpose: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC).

Patients And Methods: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC.

Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin.

Background: There are limited therapeutic options for hepatocellular carcinoma (HCC), the most common liver malignancy worldwide. Recent studies have identified the Frizzled-7 receptor (FZD7), important for activation of Wnt-mediated signaling, as a potential therapeutic target for HCC and other cancers.

Methods: We hypothesized that the extracellular domain of FZD7 (sFZD7) would be a clinically more relevant therapeutic modality than previously studied approaches to target FZD7.

San Francisco hep B free: a grassroots community coalition to prevent hepatitis B and liver cancer.

Chronic hepatitis B is the leading cause of liver cancer and the largest health disparity between Asian/Pacific Islanders (APIs) and the general US population. The Hep B Free model was launched to eliminate hepatitis B infection by increasing hepatitis B awareness, testing, vaccination, and treatment among APIs by building a broad, community-wide coalition. The San Francisco Hep B Free campaign is a diverse public/private collaboration unifying the API community, health care system, policy makers, businesses, and the general public in San Francisco, California.

Disparities in liver cancer incidence by nativity, acculturation, and socioeconomic status in California Hispanics and Asians.

Background: Asians and Hispanics have the highest incidence rates of liver cancer in the United States, but little is known about how incidence patterns in these largely immigrant populations vary by nativity, acculturation, and socioeconomic status (SES). Such variations can identify high-priority subgroups for prevention and monitoring.

Methods: Incidence rates and rate ratios (IRR) by nativity among 5,400 Hispanics and 5,809 Asians diagnosed with liver cancer in 1988-2004 were calculated in the California Cancer Registry.