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At least 19 recordsLinked to original sources
PubMed2026

Epigenetic priming and locus-specific demethylation enhance cell-death susceptibility in liver cancer.

Liver cancer treatment with epigenetic drugs remains challenging because demethylating agents such as 5-azacytidine (5-AZA) induce genome-wide toxicity and may activate oncogenes. We hypothesized that a low, nontoxic dose of 5-AZA could prime liver cancer cells by partially relaxing chromatin at selected loci to restore silenced cell-death regulators. HepG2 cells treated with 2 μM 5-AZA underwent ATAC-seq and RNA-seq to identify genes with promoter opening and increased expression. Among ten candidates, BFL-1 and SQOR were prioritized for roles in cell death and redox control. Forced expression of either gene increased sensitivity to TNF-α/cycloheximide (CHX) and sorafenib, both of which elevated mitochondrial reactive oxygen species. To establish causality in a physiological context, we used CRISPR-dCas9-TET1 to demethylate CpG-rich promoter regions of BFL-1 or SQOR. Locus-specific editing sensitized cells to TNF-α/CHX more rapidly than conventional overexpression and reproduced the heightened death response elicited by low-dose 5-AZA without baseline toxicity. Analysis of the cancer cell line encyclopedia and The Cancer Genome Atlas datasets showed consistent BFL-1 downregulation in liver cancer, variable SQOR expression across cancers, and positive correlations of both genes with tumor-suppression markers and immune-cell infiltration. These results indicate that targeted reactivation of BFL-1 and SQOR increases cell-death susceptibility in liver cancer cells. Integrating low-dose pharmacologic priming with precise epigenetic editing may preserve genome-wide methylation while restoring cell-death competence, providing proof-of-concept for locus-specific epigenetic therapy in liver cancer.

Humans↗
PubMed1991

A worldwide perspective on the epidemiology and primary prevention of liver cancer.

Liver cancer is one of the ten most common cancers in the world with a pronounced geographic variation. The incidence of hepatocellular cancer is low in the Western countries compared to the high prevalence in South Africa, Asia, and the Pacific Islands. Risk factors, early signs and symptoms, and the strategies for early detection are discussed. Primary prevention involves conducting mass immunization for hepatitis B virus in endemic countries along with education programs to improve food hygiene, decreasing alcohol intake, using sterile implements for immunizations and injections, smoking cessation, avoiding unnecessary blood transfusions and screening of blood for transfusions.

Aflatoxins↗
PubMed1979

Radiocolloid imaging in primary liver cancer and amoebic liver abscess. Accuracy of differential diagnosis and extent of inter-observer variability.

Radiocolloid liver scans from 58 patients with primary liver cancer and 56 patients with amoebic liver abscess were examined 'blind' and independently by three nuclear physicians and one registrar in training in order to evaluate the accuracy of the differential diagnosis between the two conditions and to assess the extent of inter-observer variability in the interpretation of these scans. Each of the observers incorrectly interpreted about 12% of scintiphotographs and at least one observer was wrong in 25% of the scans. The difference in diagnostic accuracy between individual observers was not statistically significant. Observers disagreed in 21,6% of the scans. The main reasons for misdiagnosis were failure to realize that excessive extrahepatic uptake of radiocolloid can occur with liver abscesses, and the indistinguishable appearance of the defect or defects in some cases of primary liver cancer and amoebic liver abscess. This margin of error and of inter-observer variability must be borne in mind when interpreting liver scans of patients thought to have either primary liver cancer of amoebic liver abscess.

Colloids↗
PubMed1977

Mechanism of feminization in primary liver cancer.

Primary liver cancer occasionally presents with feminization. The mechanism is unknown. We studied a young man with primary liver cancer associated with feminization that disappeared after removal of the tumor. Before operation, the serum estrone level was markedly (1113 pg per milliliter) and estradiol and estriol levels were slightly elevated. Human placental lactogen was also increased (0.52 microng per milliliter). Luteinizing hormone, follicle-stimulating hormone and prolactin levels were normal, and testosterone reduced. Beta subunits of human chorionic gonadotropin were not detected in the serum. In vitro assay of tumor tissue showed estrogenic activity and high levels of these subunits. With a reversed isotope dilution technic with crystallization to constant specific activity, we showed the tumor tissue to convert dehydroepiandrosterone sulfate and dehydroepiandrosterone to estrone and estradiol. Production of beta subunits of chorionic gonadotropin and raised serum levels of placental lactogen provided further evidence that the tumor was functioning as trophoblastic tissue.

Adult↗
PubMed1991

[Targeting cancer chemotherapy for metastatic liver cancer--effects of DSM on hepatic hemodynamics and on clinical outcome].

The effects of intra-arterial infusion of degradable starch microsphere (DSM) on hepatic hemodynamics were studied in 22 patients with metastatic liver cancer and the clinical outcome with mitomycin C (MMC) combined with DSM was reported herein. Hepatic arterial blood flow, measured with a transit-time ultrasonic blood flow meter, changed 283 +/- 27 ml/min to 40 +/- 36 ml/min by an hepatic arterial infusion of DSM and, a mean occlusion time aS 24 +/- 11 min. Combined infusion with DSM and MMC reduced MMC levels in the peripheral blood at 0.0248 less than p less than 0.0421, compared with those by an infusion with MMC alone and consequently, these findings proved to result from intrahepatic accumulation of MMC. RI-angiography using 99mTc-macroaggregated albumin (99mTc-MAA) was performed to examine hemodynamic changes in the metastatic liver and, a tumor (T) to non-tumor (N) ratio of 99mTc-MAA accumulation increased 0.37 to 0.62 by combined use of DSM. Thus, an intra-arterial infusion combined DSM and MCC was performed for 22 patients with unresectable hepatic metastases. Tumor regression was observed in 16 patients (73%). Side effects possibly attributable to DSM was transient nausea and vomiting. These results show that combined use of DSM is effective for intra-arterial chemotherapy against metastatic hepatic cancer.

Aged↗
PubMed1991

Clustering of liver cancer deaths in Saitama Prefecture, Japan.

Cancer statistics in 1965 revealed that people in the eastern part of Saitama had a high risk of developing cancer of the liver. Clusters of liver cancer were also observed in 1975, though less for males than for females. In 1985, traces remained of clusters with higher death rates from liver cancer. A field survey revealed absence of correlation between geographical clustering of liver cancer and HBsAg positivity, geographical HBsAg positivity differences between sexes, and lack of correlation between geographical distribution of HBsAg positivity and death rates from liver diseases (cancer or cirrhosis). There was no geographical relationship of death rates from liver cancer to liver cirrhosis in Saitama. Statistics of the Saitama Cancer Center revealed lower averages than in the rest of Japan for the percentage of HBsAg positivity in HCC inpatients, the percentage of HCC inpatients with liver cirrhosis, and the ratio between the number of patients with HCC and those with cholangio carcinoma. A mail questionnaire revealed that farmers in the eastern part of Saitama had a strong positive association with death from liver cancer. These results suggest that HBV does not play an important role in the clustering of high death rates from liver cancer in Saitama.

Adenoma, Bile Duct↗
PubMed1990

[Evolution and prognosis in patients with primary liver cancer. I. The effect of individual factors on the survival of patients with primary liver cancer].

The data of the frequency, evolution and prognosis of 63 patients with primary liver carcinoma which had developed on the basis of liver cirrhosis are presented. An attempt is made to assess the importance of the etiologic factors, type of liver cirrhosis, macroscopic type of the tumor, histologic pattern of the cancer, sex and age for the evolution and prognosis of the disease. The patients with primary liver carcinoma without cirrhosis have a better prognosis. As high risk factors may be accepted: male sex, age over 50 years, toxic factors, hepatitis B virus infection and chronic alcoholism. The macroscopic type of the tumor also affects the prognosis. The histologic pattern of the cancer does not influence the survival of the patients with primary liver carcinoma.

Adolescent↗
PubMed1992

[Evaluation of US contrast medium (LEVOVIST) to experimental liver cancer].

Enhancement of liver cancer on ultrasonography (US) by injection of new contrast medium (LEVOVIST) was performed in rats with 3'-methyl-4-dimethylaminoazobenzene-induced hepatic carcinoma. Echosignals of cancer nodules increased remarkably after the intrahepatic arterial injection of LEVOVIST (200, 300 mg/ml), and contrast enhancement was observed for at least 15 minutes. Furthermore, US after the intrahepatic arterial injection of LEVOVIST (200 mg/ml) can visualize small nodule, which was not recognizable on plain US. As a result of increased echosignals of normal liver parenchyma after the intra-portal injection of LEVOVIST (300 mg/ml), the cancer nodules were demonstrated as hypoechoic. These results indicate that this new contrast medium for sonography is effective in the diagnosis of liver cancer.

Animals↗
PubMed1992

[Continuous intra-arterial infusion chemotherapy in colorectal cancer patients with nonresectable metastatic liver cancer].

Five colorectal cancer patients with nonresectable metastatic liver cancer underwent continuous intraarterial chemotherapy in our institute from January to December 1991. Patients included four rectal cancers and one colonic cancer. 5-fluorouracil (5-FU) was infused continuously through an Infuse-A-Port; 360 mg/m2/day for one week after operation, and 180 mg/m2/day for the following three weeks. Since the fifth week after operation, two weeks without infusion and two weeks of infusion (180 mg/m2/day) were alternated as long as possible. Total periods of 5-FU infusion therapy were from one to 11 months and total doses of 5-FU ranged from 8,750 mg to 25,650 mg. Three patients showed partial response (PR) and two patients progressive disease (PD) (response rate; 60%). In three cases of PR, lengths of infusion therapy and total doses of 5-FU before PR was first observed was 8 weeks, 10,750 mg, 6 weeks, 9,250 mg, and 4 weeks, 8,750 mg, respectively. Four patients presented nausea, appetite loss or abdominal pain, which were considered to be side effects of 5-FU. In one of these four patients, infusion could not be continued because symptoms were so severe. However, catheter troubles were not noticed among all cases.

Colonic Neoplasms↗
PubMed1992

The risk and predictive factors for developing liver cancer among patients with decompensated liver cirrhosis.

Patients with decompensated liver cirrhosis (n 1441) and those with post-transfusion hepatitis (n 343), whose medical expenses were subsidized by the Aichi Prefectural Government, were followed up for three years by record linkage with the Aichi Cancer Registry. During the follow-up period, 122 incident cases of liver cancer were identified. Compared with the general population, patients with decompensated liver cirrhosis were at a 64.9 times greater risk (50.5 times in males and 100.4 times in females) and those with post-transfusion hepatitis were at a 9.4 times greater risk (8.9 times in males and 13.7 times in females) of developing liver cancer. Information on prognostic factors for 1,068 patients with decompensated liver cirrhosis was also collected in a questionnaire survey by the physicians in charge. Patients positive to hepatitis B surface antigen (HBs Ag) and those positive to HBe Ag had a significantly increased risk of subsequent liver cancer. The risk of developing liver cancer was positively associated with base-line levels of GPT and AFP and age and, inversely associated with total alcohol intake and female sex. In multivariate analyses, the associations with HBe Ag, AFP, sex and age remained statistically significant, whereas the associations with GPT, total alcohol intake and HBs Ag were of borderline significance.

Age Factors↗
PubMedDate not supplied

Etiology of human liver cancer: controlled prospective study in liver cirrhosis.

The incidence of primary liver cell carcinoma was investigated in a prospective study over 6 yr and 5 mo in 403 clinically unselected patients derived from a homogeneous population by means of serial determination of alpha 1-fetoprotein (AFP) by radioimmunoassay. The diagnosis of liver cirrhosis was proved in 90% by laparoscopy and/or histology and/or autopsy. The incidence of primary liver cell carcinoma in liver cirrhosis in the clinically studied patients was 4.47%, significantly lower than in the autopsy material (11.03%; p less than or equal to 0.025). In the follow-up study, all patients with increasing AFP concentrations exhibited a primary liver cell carcinoma. A transitory rise of AFP (higher than 50 ng/ml) was observed in 15.1% of patients with liver cirrhosis without primary liver cell cancer. In contrast to the results of animal experiments, this transitory rise of AFP was not followed by malignant transformation of the cirrhotic tissue. Posthepatitic liver cirrhosis was observed in 21.57%, postalcoholic liver cirrhosis in 42.93%, and cryptogenic liver cirrhosis in 27.30%. Liver cirrhosis of other etiology occurred in 8.19%. The incidences of primary liver cell cancer in these 4 groups were 4.94, 4.62, 5.45, and 0%, respectively. These differences are not statistically significant, although in absolute figures postalcoholic liver cirrhosis is the main cause of primary liver cell carcinoma in this sample from West Germany. HBs antigen-positive liver cirrhosis was more often associated with primary liver cell cancer than HBs antigen-negative liver cirrhosis (6.58 versus 3.96%); this difference also is not statistically significant. Observations of larger groups of patients may show a higher risk of developing primary liver cell carcinoma in those with a combination of alcohol abuse and HBs antigenemia and/or acute hepatitis in the history. Patients without these 2 risk factors had an incidence of primary liver cell carcinoma of 2.61%; those with 1 risk factor, 5.77%; and those with both risk factors, 10.71%.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

The accuracy of liver cancer as the underlying cause of death on death certificates.

Studies of liver cancer mortality are subject to confusion attributable to the changes in categories by which liver cancer is identified in successive revisions of the International Classification of Diseases. To determine the effects of these changes, diagnoses of 2,388 cases of primary liver cancer in the years 1973-80 were compared to the underlying causes of death recorded on the death certificates, using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Results showed that only 53 percent of the deaths were attributed on death certificates to primary liver cancer. In a reverse comparison of 2,977 death certificates from the years 1973-85 with an underlying cause of death of primary liver cancer, 83 percent had been diagnosed as liver cancer. However, among the certificates that specified cancer of the liver, not specified as primary or secondary, as the cause of death, only 40 percent had been diagnosed originally as liver cancer. The mortality of liver cancer can be either underestimated or overestimated depending on which disease classification categories are used.

Cause of Death↗
PubMed1992

[Preliminary observations on effect of selenium yeast on high risk populations with primary liver cancer].

Two populations with high risk primary liver cancer (PLC), one of 226 cases with HBsAg carriers and another of 3849 first-relatives in the pedigree with high incidence of PLC, were randomly divided into the supplementing selenium group (selenium yeast 200 g Se1Tab/day) and the control group (common yeast 1 Tab/day), and were followed-up for four years and two years respectively. In the population with HBsAg carriers, no liver cancer occurred in the supplementing selenium group; where as the liver cancer incidence rate was 1573.03/10(5) in the control group. Among the first relatives. The liver cancer incidence rate in the supplementing selenium group was 219.37/10(5); and 553.15/10(5) in the control group. The results showed that the incidence of PLC in the supplementing selenium group was significantly lower than in the control group. This study indicates that selenium has distinct anti-PLC effect.

Adolescent↗
PubMed1991

Increase in incidence of disease due to diagnostic drift: primary liver cancer in Denmark, 1943-85.

OBJECTIVE: To examine the extent to which changes in diagnostic methods and classification are responsible for the striking increase in incidence of primary liver cancer in Denmark since 1943. DESIGN: Analysis of the time trends in sex specific, age standardised incidence of primary liver cancer and unspecified liver cancer (either secondary without known primary cancer or not specified as primary cancer) in the entire population from 1943 to 1985. By review of the 727 notifications from three periods of 5 years (1948-52, 1963-7, and 1978-82) the changes in histological diagnosis and classification were assessed. SETTING: Denmark. SUBJECTS: Notifications of liver cancer to the Danish cancer registry. RESULTS: Concomitant with the increase in primary liver cancer, the incidence of the unspecified liver cancer declined. The proportion of histologically diagnosed primary liver cancer rose from 85% to 98%, whereas the proportion for unspecified liver cancer rose from 12% to 51%. When the proportion of primary versus unspecified liver cancer obtained by histological diagnosis was extrapolated to all cases, the annual incidence of primary liver cancer was 4.4 rather than 1.6 per 100,000 population in 1948-52 and 6.0 rather than 5.5 per 100,000 in 1978-82. CONCLUSION: The increase in the incidence of primary liver cancer may be much smaller than the numbers of registered cases indicate. This example emphasises the need to consider diagnostic drift in time trend studies of disease incidence.

Denmark↗
PubMed2026

Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review.

Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype-resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi-omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation-stage tools. Their clinical value remains constrained by sampling bias, biospecimen-dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi-omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question-specific, stage-aware, and specimen-aware rather than universal multi-analyte panels.

Humans↗
PubMed1992

[Liver cancer and hepatitis B and C virus].

Chronic infection by hepatitis B and C viruses is frequently associated to the development of primary liver cancer. Liver cirrhosis, induced by these viral infection, plays an important role in the liver carcinogenesis. In addition, HBV has a direct role in liver cell transformation by a transactivating effect of some viral proteins as well as insertional mutagenesis. The role of hepatitis C virus is not known. The strong association, even in France, of primary liver cancer to these viral infections underline the importance of their prevention by vaccination.

Hepatitis B Antigens↗
PubMed1991

Subrenal capsule assay using liver cancer specimens obtained by fine needle biopsy.

Twenty-seven liver cancer biopsies (20 hepatocellular carcinomas, 4 metastatic liver cancers and 3 cholangiocellular carcinomas) were obtained using a 21-gauge fine needle biopsy guided by ultrasonography. These cancers were subcutaneously transplanted to the subrenal capsular region of BDF1 mice premedicated with immunosuppressive agents to modulate the host immune reaction. The SRCA was based on the change in tumor size (delta TS) and the tumor growth inhibition rate (TGIR). The transplantation rate of the 27 liver cancer specimens was 85% by delta TS and 67% by TGIR. The efficacy rates of Adriamycin, cis-platinum, and mitomycin were respectively 71%, 58%, and 43% by delta TS, and 73%, 56% and 50% by TGIR. Thus, liver cancer specimens obtained by fine needle biopsy and examined by SRCA had a fairly high transplantation rate, and this method can be useful for patients with inoperable liver cancer, as a general chemosensitivity test for anticancer drugs.

Adenoma, Bile Duct↗