Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of immunosuppression and head and neck cancer is supported by numerous reports demonstrating impaired cell-mediated immunity, depressed T-cell function, decreased lymphocyte responsiveness, and elevated circulating immune complexes. Fanconi's anemia (FA) is a rare autosomal recessive syndrome characterized by progressive pancytopenia, skeletal abnormalities, hyperpigmentation, and other congenital anomalies. Increased chromosomal instability and defective DNA repair have been uniform findings. Several reports suggest associated immune deficiencies. There is an increased frequency of leukemia, hepatocellular carcinoma, and squamous cell carcinoma (SCC), including six cases of head and neck SCC. We reported a young girl with FA who developed SCC of the tongue. Initial studies suggest low lymphocyte counts, but normal lymphocyte responsiveness. More precise characterization of the immune system defects in malignancy prone, genetically determined syndromes may provide clues for the diagnosis and treatment of patients with the more usual but more variable risk factors for SCC of the head and neck.
 ...
PMID:Squamous cell carcinoma in the immunosuppressed patient: Fanconi's anemia. 401 Apr 14

Retinoids regulate terminal differentiation of various cells and morphogenesis of various organs. Disorders of such regulations induce cellular and structural anomalies, and lead directly to carcinogenesis. According to these physiological roles of retinoids, many experimental studies have been conducted to test, and successfully demonstrate, the effect of retinoids for the treatment of cancers or the prevention of carcinogenesis. In clinical studies, however, retinoid therapy has not been established as a first choice treatment for solid tumors, although the effect of all-trans retinoic acid for acute promyelocytic leukemia is excellent. Primary cancer chemoprevention in general populations using beta-carotene has failed in all but one of four recently reported trials. In contrast, secondary chemoprevention by retinoids is promising for cancers such as head and neck cancer, uterine cervical cancer and hepatoma.
 ...
PMID:[Prevention and treatment of solid tumors with retinoids]. 888 31

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in lung and colorectal tumours, head and neck cancer, sarcoma, and hepatocellular carcinoma. It is found that the amount of FDG uptake strongly correlates with response to therapy: a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small numbers of patients, whereas the exact response mechanism is still unknown. Moreover, in these case series, the interval between tumour therapy and FDG-PET, as well as the method of quantification, SUV or tumour-to-non-tumour ratios, differ per study. Finally, dynamic imaging is a recommended technique by some authors, but it is not a standard technique in clinical practice to evaluate tumour therapy. Therefore, further study is required which has to deal with these major issues before it is possible to draw definite conclusions.
 ...
PMID:Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology. Part IIIb: Therapy response monitoring in colorectal and lung tumours, head and neck cancer, hepatocellular carcinoma and sarcoma. 1135 42

Chromosome 8p21-22 is a frequent site of loss of heterozygosity in many types of cancer, including hepatocellular carcinoma (HCC). Tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2/DR5), a member of tumor necrosis factor receptor family, is mapped to chromosome 8p21-22. Mutations of TRAIL-R2 have been detected in lung cancer, breast cancer, head and neck cancer, and non-Hodgkin's lymphoma. In this study, we analyzed the entire coding regions and all splicing sites of TRAIL-R2 in 40 HCCs and the death domain region in additional 60 HCCs. We could detect one point mutation in the death domain in only one HCC (1%). Our data suggest that somatic mutations of TRAIL-R2 gene do not play an important role in the carcinogenesis of HCC.
 ...
PMID:Mutation of the DR5/TRAIL receptor 2 gene is infrequent in hepatocellular carcinoma. 1217 36

Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges.
 ...
PMID:Chemoprevention of cancer--focusing on clinical trials. 1459 36

Proton beam therapy (PBT) makes it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to its identical biological characteristics with X-rays. PBT has a half-century history, and more than 35,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head and neck cancer, lung cancer, esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.
 ...
PMID:[Heavy charged particle radiotherapy--proton beam]. 1471 61

1. The prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) is activated by Escherichia coli nitroreductase (NTR) to a potent DNA-crosslinking agent. 2. Virus-mediated expression of NTR in tumour cells sensitizes them to CB1954 in vitro and in vivo, providing the basis for a strategy of cancer gene therapy. 3. A phase I trial of CB1954 in cancer patients has been completed, documenting the pharmacokinetics and establishing an acceptable dose. Subsequent trials of the replication-defective adenovirus CTL102 in patients with resectable tumours have documented expression of NTR in injected colorectal liver metastases, hepatocellular carcinoma, head and neck cancer and prostate cancer. Trials combining CTL102 and CB1954 are underway. 4. An oncolytic (replication-competent) adenovirus vector allowed increased expression of NTR in vitro and in a mouse tumour model, resulting in a greater reduction in tumour growth when combined with CB1954 treatment. 5. Alternative prodrugs may eventually prove superior to CB1954; a nitroaryl phosphoramide mustard prodrug activated by NTR shows a greater therapeutic index than CB1954 in a human ovarian carcinoma. 6. The crystal structure of NTR provided the basis for site-directed mutagenesis, which has identified a number of mutants with improved kinetics of CB1954 activation. These can provide improved cell sensitization to CB1954. Combinations of these are being tested. 7. The basis for a positive selection for improved NTR variants has been demonstrated.
 ...
PMID:Nitroreductase: a prodrug-activating enzyme for cancer gene therapy. 1556 99

Chronic alcohol consumption is associated with an increased risk for upper aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde production via alcohol dehydrogenase (ADH) has been implicated in the pathogenesis. The allele ADH1C*1 of ADH1C encodes for an enzyme with a high capacity to generate acetaldehyde. So far, the association between the ADH1C*1 allele and alcohol-related cancers among heavy drinkers is controversial. ADH1C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in a total of 818 patients with alcohol-associated esophageal (n=123), head and neck (n=84) and hepatocellular cancer (n=86) as well as in patients with alcoholic pancreatitis (n=117), alcoholic liver cirrhosis (n=217), combined liver cirrhosis and pancreatitis (n=17) and in alcoholics without gastrointestinal organ damage (n=174). The ADH1C*1 allele and genotype ADH1C*1/1 were significantly more frequent in patients with alcohol-related cancers than that in individuals with nonmalignant alcohol-related organ damage. Using multivariate analysis, ADH1C*1 allele frequency and rate of homozygosity were significantly associated with an increased risk for alcohol-related cancers (p<0.001 in all instances). The odds ratio for genotype ADH1C*1/1 regarding the development of esophageal, hepatocellular and head and neck cancer were 2.93 (CI, 1.84-4.67), 3.56 (CI, 1.33-9.53) and 2.2 (CI, 1.11-4.36), respectively. The data identify genotype ADH1C*1/1 as an independent risk factor for the development of alcohol-associated tumors among heavy drinkers, indicating a genetic predisposition of individuals carrying this genotype.
 ...
PMID:Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers. 1628 84

During the period of 1990-2005, 701 patients with the hepatocellular carcinoma were treated with intra-arterial infusion of 5-FU and epi-adriamycin with or without Lipiodol chemoembolization employing an implantable infusion port system. In 70% of the patients treated, an objective response was observed with marked regression of tumor and decrease in tumor marker (AFP and PIVKA-II). Also 1,091 patients with the metastatic liver cancer of colon, rectum, stomach and pancreas were treated with the same procedure employing 5-FU, mitomycin C, adriamycin, or epi-adriamycin. In more than 80% of the patients treated, an objective response was observed with marked regression of tumor and decrease in tumor marker (CEA, CA19-9, TPA, DUPAN-2, SPan-1). Intra-arterial infusion chemotherapy employing an implantable port system also proved to be a promising treatment modality for most of the intractable head and neck cancer, breast cancer and a few of the pancreas cancer.
 ...
PMID:[Intra-arterial infusion chemotherapy for advanced cancer--40 years of experience]. 1631 88

The strategy to prevent liver carcinogenesis consists of: (i) antiviral modalities such as vaccination, lamivudin, and interferon; (ii) anti-inflammatory modality; and (iii) chemoprevention using such compounds as retinoid analog and vitamin K. Cancer chemoprevention is defined as an approach where natural or synthetic chemical compound works to arrest or reverse premalignant cells by using physiological pathways. As a consequence, such a clone of premalignant cells is eradicated (clonal deletion) by differentiation induction or apoptosis, and thus the process toward the development of clinically detectable cancer is disrupted. A particularly effective candidate target of chemoprevention in liver diseases is an advanced stage of chronic hepatitis, that is supposed to contain transformed hepatocyte clone(s); that is, primary prevention from liver cirrhosis and prevention of recurrent and second primary hepatocellular carcinoma following the treatment of the initial cancer. Retinoid is a collective term of vitamin A analog that binds to nuclear retinoid receptors;retinoic acid receptors (RAR) and retinoid X receptors (RXR). After ligand coupling, these receptors form homo- or heterodimers, bind to the response element (RARE or RXRE) upstream of the target gene, and regulate the gene expression as a transcriptional factor. Biological phenotypes of such transcriptional regulation by retinoid include cellular differentiation, tissue morphogenesis, and programmed cell death (apoptosis). Due to these functions, retinoid analogs are clinically tried to prevent/treat carcinoma in a wide variety of organs including head and neck cancer, uterine cervical cancer, certain leukemia and liver cancer. In this article, clinical trials of retinoid analog to inhibit second primary hepatoma, supposed molecular mechanism of the action of the compound, and aberrant metabolism of RXR and its role in liver carcinogenesis are briefly reviewed.
 ...
PMID:Chemoprevention of liver carcinogenesis with retinoids: Basic and clinical aspects. 1787 99


1 2 3 4 Next >>