Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference

The p53 tumor suppressor gene has come to the forefront of cancer research because it is commonly mutated in human cancer and the spectrum of p53 mutations in these cancers is providing clues to the etiology and molecular pathogenesis of neoplasia (1â€”3). Detection of p53 abnormalities may have diagnostic, prognostic, and therapeutic implications (4). The 15-year history of p53 investigations is a paradigm in cancer research, illustrating the convergence of previously parallel lines of basic, clinical, and epidemiological investigation and the rapid trans fer of research findings from the laboratory to the clinic. p53 is clearly a component in biochemical pathways central to human carcinogen esis; p53 protein alterations due to missense mutations and loss of p53 protein by nonsense or frameshift mutations provide a selective ad vantage for clonal expansion of preneoplastic and neoplastic cells (5). The potential for a missense mutation to cause loss of tumor suppres sor function and gain of oncogenic activity, i.e., to transform cells by two mechanisms, is one explanation for the commonality of p53 mutations in human cancer. Recent studies investigating the mecha nisms underlying the biological activity of p53 indicate that the protein is involved in gene transcription, DNA synthesis and repair, genomic plasticity, and programmed cell death (1â€”6).These complex biochemical processes are performed by multicomponent protein ma chines; therefore, it is not surprising that the p53 protein forms complexes with other cellular proteins (Fig. 1) and that some viral oncoproteins alter the functions of these machines by binding to p53 and perturbing its interaction with other cellular protein components. In this Perspective, we will focus on the origin of p.53 mutations, the mutational spectrum of p.53 in human cancers, and the hypotheses generated by the analysis of p53 mutations in premalignant and malignant cells. The interpretation ofp53 mutations in human cancers is based on observations of the patterns of DNA damage induced by chemical and physical mutagens in model systems. In this Introduc tion, we will review these data, which provide the background for many of the inferences drawn from p53 mutational analysis.

https://cancerres.aacrjournals.org/content/canres/54/18/4855.full.pdf

Mutations in the p53 Tumor Suppressor Gene: Clues to Cancer Etiology and Molecular Pathogenesis

Epidemiological evidence indicates that avoidance of smoking, increased consumption of fruits and vegetables, and control of infections will have a major effect on reducing rates of cancer. Other factors include avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. A substantial reduction in breast cancer is likely to require modification of sex hormone levels, and development of practical methods for doing so is a high research priority. Resolution of the potential protective roles of specific antioxidants and other constituents of fruits and vegetables deserves major attention. Mechanistic studies of carcinogenesis indicate an important role of endogenous oxidative damage to DNA that is balanced by elaborate defense and repair processes. Also key is the rate of cell division, which is influenced by hormones, growth, cytotoxicity, and inflammation, as this determines the probability of converting DNA lesions to mutations. These mechanisms may underlie many epidemiologic observations.

/pdf/the-causes-and-prevention-of-cancer-2uy0kk9grj.pdf

The causes and prevention of cancer.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.23527

The Incidence and Risk Factors of Hepatocellular Carcinoma in Patients with Nonalcoholic Steatohepatitis

https://www.liver.theclinics.com/article/S1089-3261(04)00130-8/pdf

Epidemiology of hepatocellular carcinoma.

Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in Southern Guangxi, China

Guangxi is a very high-risk area for primary hepatocellular carcinoma (PHC); the age-standardized (world population) rates for males and females in that Chinese Autonomous Region were 32.5 and 8.5, respectively. Blood specimens from 50 PHC patients and 50 age- and sex-matched controls in Guangxi were analyzed for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen. Eighty-six % of cases were hepatitis B surface antigen positive, compared to 22% of controls (relative risk, 17.0). We estimate from the data that persistent hepatitis B virus infection can account for at least 80% of all PHC cases occurring in Guangxi. The consistency of our findings with those from Hong Kong and Taiwan strongly suggests that hepatitis B virus infection is also an important risk factor for PHC in other parts of southern China.

https://cancerres.aacrjournals.org/content/canres/45/2/872.full.pdf

A Serological Case-Control Study of Primary Hepatocellular Carcinoma in Guangxi, China

The effect of BCG vaccination and risk factors for latent tuberculosis infection among college freshmen in China.

ESAT6-CFP10 (EC) skin test has been reported accurate and safe in identifying tuberculosis infection. We aimed to demonstrate the safety of EC skin test compared with tuberculin skin test (TST) in university freshmen.We conducted a double-blind, randomized, controlled clinical study in a university freshmen population with 16,680 participates in China, and finally 14,579 completed the study. About a half received an EC skin test and the others received TST. Adverse reactions were evaluated.Out of the 14,579 participants, 48.2% (7029/14,579) were males. The average age was 18.1 ± 0.8 years and the average BMI was 20.9 ± 3.1 kg/m2. 50.4% (7351/14,579) participants received EC skin test and 49.6% (7228/14,579) received TST. The EC group had significantly less adverse reactions compared with the TST group (21.3%, 1565/7351 vs. 34.6%, 2499/7228, P = 0.000). The most common adverse reactions for EC were bleeding (5.63%, 414), dermatodyschroia (4.27%, 314), induration (3.90%, 287), swelling (2.49%, 183), pain (1.59%, 117) and pruritus (1.48%, 109). Bleeding, dermatodyschroia, swelling and erythema were significantly less in EC group (P < 0.05), while others were similar to those of TST.the EC skin test was safe in our cohort. And its incidence of total adverse drug reactions (ADRs) is less than that of TST. Most adverse reactions were mild or moderate, lasting less than 48 h and self-limiting. Considering the satisfactory diagnostic accuracy in identifying tuberculosis infection, the cost and safety, the EC skin test might be a potential candidate for replacing TST in high burden countries or those with routine BCG vaccination.ChiCTR2000038622, Safety of the EC skin test to screen tuberculosis infection in two universities, compared with the tuberculin skin test: a double-blind, randomized, controlled trial. registered on 26/09/2020 at http://www.chictr.org.cn . 

https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07765-w

Safety of a Novel ESAT6-CFP10 skin test compared with tuberculin skin test in a double-blind, randomized, controlled study

China has made substantial efforts aimed to promote the uptake of antiviral treatment of hepatitis B (HB). It is unclear whether these policies achieved the desired impact. This study adopted medicines procurement data from 31 provinces to generate the first evidence about the number of standard antiviral treatment of HB overtime at both national and provincial levels in China.

Uptake of hepatitis B antiviral treatment: A panel data analysis of 31 provinces in China (2013–2020)

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