Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antineoplaston A3 is an oxidated mixture of small peptides and amino acid derivatives isolated from human urine which have shown antineoplastic activity in tissue culture and low toxicity in mice. Twenty-four patients diagnosed with 25 cases of neoplastic diseases were involved in the studies. The patients' diagnoses included: adenocarcinoma of the prostate, stage IV (7 cases); adenocarcinoma of the breast, stage IV (3); adenocarcinoma of the colon and rectum, stage IV (3); adenocarcinoma of the colon, status post resection (1); adenocarcinoma of the lung, stage III (2); squamous cell carcinoma of the lung, stage III (2); adenocarcinoma of the pancreas, stages II and IV (2); and single cases of adenocarcinoma of the kidney, stage IV; malignant fibrohistiocytoma, stage IV; glioblastoma multiforme, stage IV; basal cell epithelioma; and transitional cell carcinoma of the bladder, grade II. Only patients who had over six weeks' anticipated survival and who continued the treatment for over six weeks were eligible. In 23 patients, Antineoplaston A3 was administered in divided doses daily i.v. through a subclavian vein catheter. In one patient, the injections were given i.m. The length of treatment was from 44 to 478 days and the highest dosage was 76 mg/kg/24 h. Side-effects associated with treatment included febrile reaction (4 patients), vertigo (2), headache (2), flushing of the face, nausea and tachycardia (1 each). Adverse reactions were mild and occurred only once during the entire course of treatment. Desirable side-effects included increase of platelet count, increase of white blood cell count and increase of reticulocyte count. At the end of the study, there were 5 cases of complete remission, 5 of partial remission, nine of stable disease and six of increasing disease. The patients who obtained complete remission were diagnosed with cancers of the bladder, prostate, colon, and basal cell epithelioma. In view of its very limited toxicity and the interesting responses obtained, Antineoplaston A3 was submitted for Phase II clinical trials to establish its usefulness in cancer treatment.
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PMID:Phase I clinical studies of antineoplaston A3 injections. 356 12

Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
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PMID:[Alcohol and oropharyngolaryngeal and digestive tract cancer]. 1182 13

Early esophageal squamous cell carcinoma detected by esophageal iodine staining can be easily treated by endoscopic mucosectomy, and identifying its predictors is important in better selecting candidates to screen for this high-mortality cancer. The common etiologies of elevated mean corpuscular volume (MCV) and esophageal cancer, including folate deficiency, smoking, drinking and high acetaldehyde exposure, suggest testing MCV as such a predictor. Japanese alcoholic men with (n = 65) and without (n = 206) esophageal squamous cell carcinomas, excluding those with liver cirrhosis, were assessed for MCV within 7 days of their last drink, alone or in combination with findings from either the alcohol flushing questionnaire or genotyping to identify inactive aldehyde dehydrogenase-2 (ALDH2*1/2*2) and the less-active form of alcohol dehydrogenase-2 (ADH2*1/2*1), which pose risks for esophageal squamous cell carcinoma. MCV was higher in cancer patients than in the control group. MCV was higher in both groups in those who were heavier smokers, had lower body mass index (BMI), experienced alcohol flushing, and had ALDH2*1/2*2. After adjusting for age, drinking and smoking habits, BMI and ALDH2/ADH2 genotypes, macrocytosis of MCV > or =106 fl was associated with increased risk for esophageal cancer (OR = 2.75). Men with both MCV > or =106 fl and alcohol flushing had an even higher cancer risk (OR = 5.51). The combinations of MCV > or =106 fl with ALDH2*1/2*2 or ADH2*1/2*1 alone, and both ALDH2*1/2*2 and ADH2*1/2*1 (ORs = 11.44, 21.22 and 319.7, respectively) showed consistently higher risk than the corresponding group with MCV <106 fl (ORs = 7.24, 4.71 and 27.01, respectively). In conclusion, MCV measurement, alone or in combination with the markers of alcohol sensitivity, provides a new means of predicting risk for esophageal squamous cell carcinoma in Japanese alcoholic men.
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PMID:Macrocytosis, a new predictor for esophageal squamous cell carcinoma in Japanese alcoholic men. 1294 54

Alcohol flushing after light drinking is triggered mainly by severe acetaldehydemia in individuals possessing inactive aldehyde dehydrogenase (ALDH)-2. Inactive ALDH2 encoded by ALDH2*1/2*2 and the low-activity form of alcohol dehydrogenase (ADH)-2 encoded by ADH2*1/2*1 enhance the risk for esophageal cancer in Japanese light to heavy drinkers, a significant association that emphasizes the importance of screening tests for inactive ALDH2 based on alcohol flushing. The objectives of the present report were (a). to evaluate the reliability of a simple questionnaire that asks about both current and past flushing for detecting inactive ALDH2 and (b). to predict cancer risk based on flushing in a case-control manner. The study subjects consisted of 233 Japanese men with esophageal squamous cell carcinoma and 610 cancer-free Japanese men. When current or former flushing individuals were considered to have inactive ALDH2, the sensitivity and specificity of the test were 84.8% and 82.3%, respectively, for the cases and 90.1% and 88.0%, respectively, for the controls. To clarify the characteristics of men who had genetically inactive ALDH2 but did not report alcohol flushing, we analyzed individuals possessing the ALDH2*1/2*2 genotype and found that those who also had ADH2*1/2*1 (both cases and controls) tended not to report current flushing, and those who did not report current flushing (controls only) tended to be heavier drinkers. As compared with overall never or rare drinking, the cancer risks for light (1-8.9 units/week; 1 unit = 22 g of ethanol), moderate (9-17.9 units/week), and heavy (18+ units/week) drinkers with current or former flushing (odds ratio = 6.69, 42.66, and 72.86, respectively) significantly exceeded the risks for those who had never flushed (odds ratio = 1.27, 10.12, and 15.61, respectively), even after adjustment for age, smoking, and diet. The flushing questionnaire may be used in large-scale epidemiological studies as a surrogate marker of ALDH2 genotype to predict individual cancer risk.
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PMID:Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes, and risk for esophageal squamous cell carcinoma in Japanese men. 1465 86

A 55-year-old Caucasian man presented to a plastic surgeon for the treatment of two lesions on his nose, first a chronic indented area with some telangiectasia on the proximal nasal bridge (Figure 1) and second a hyperkeratotic nodule with central crusting on the ala nasi that developed rapidly over several weeks (Figure 2). The surgeon appropriately diagnosed the ala nasi nodule as a squamous cell carcinoma, keratoacanthoma type, but requested an opinion from dermatology for the proximal nasal bridge indentation that he suspected to be a morpheaform or erosive basal cell carcinoma possibly requiring Mohs micrographic surgery. Upon further questioning, the patient revealed that he has had persistent erythema and problems with facial flushing for many years, particularly with alcohol, coffee, and moderate exercise. He infrequently develops papulopustular lesions. Closer clinical inspection revealed a mild erythema, telangiectases, and a hypertrophied nose. He noted that he wore an old heavy pair of glasses every day. He was notified of a coexisting diagnosis of rosacea, and various treatment options were discussed. He was pleased that he would not need any further surgery to his nose.
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PMID:A basal cell carcinoma mimicking a sign of rosacea. 1601 77

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously called ADH2), and ADH1C (previously called ADH3) affect the metabolism of alcohol. The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase the risk of esophageal squamous cell carcinoma in East Asian drinkers. This case-control study involved 96 Japanese men with oral and pharyngeal squamous cell carcinoma (hypopharyngeal cancer in 43 patients and oral/oropharyngeal cancer in 53) and 642 cancer-free Japanese men. The risk of the cancers overall and of hypopharyngeal cancer was increased 3.61- and 10.08-fold, respectively, by ALDH2*1/*2 among moderate-to-heavy drinkers (9+ units/week; one unit = 22 g of ethanol), but the risk of oral/oropharyngeal cancer was not significantly affected by the ALDH2 genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping. Among moderate-to-heavy drinkers, men with the less-active ADH1B*1/*1 had a significantly higher risk of the cancers overall, of hypopharyngeal cancer, and of oral/oropharyngeal cancer (OR = 5.56, 7.21 and 4.24, respectively). In view of the linkage disequilibrium between ADH1B and ADH1C, the ADH1C genotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactive ALDH2*1/*2, less-active ADH1B*1/*1, frequent drinking of strong alcohol beverages straight, smoking, and lower intake of green-yellow vegetables. Educating these risks for cancer of the upper aerodigestive tract could be a useful new strategic approach to the prevention of these cancers in Japanese.
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PMID:Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma. 1707 28

Asian case-control studies have shown a strong relationship between the development of squamous cell carcinoma (SCC) of the esophagus and alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2*1/*2), less-active alcohol dehydrogenase-1B (ADH1B*1/*1), high mean corpuscular volume (MCV), and self-reported facial flushing in response to alcohol. However, little is known about whether these risk factors prospectively influence cancer development in cancer-free alcoholics. Between 1993 and 2005, 808 Japanese alcoholic men diagnosed as cancer-free by an initial endoscopic screening examination received follow-up examinations ranging from 1 to 148 months (median, 31 months) later, and SCC of the upper aerodigestive tract was diagnosed in 53 of them (esophagus in 33 and oropharyngolarynx in 30). Cox proportional hazards analysis showed that the age-adjusted relative hazard for SCC was 11.55 [95% confidence interval (95% CI), 5.73-23.3] in ALDH2*1/*2 heterozygotes compared with ALDH2*1/*1 homozygotes, 2.02 (95% CI, 1.02-4.02) in ADH1B*1/*1 homozygotes compared with ADH1B*1/*2 heterozygotes or *2/*2 homozygotes, 2.64 (95% CI, 1.49-4.67) in patients with flushing compared with those who had never experienced flushing, 2.91 (95% CI, 1.63-5.20) in those with an MCV >or= 106 compared with those with an MCV < 106, 2.52 (95% CI, 1.22-5.22) in those who smoked >or=30 cigarettes per day compared with those who smoked 0 to 19 cigarettes per day, 7.26 (95% CI, 3.99-13.23) in those with esophageal dysplasia compared with those without distinct iodine-unstained lesions >or=5 mm, and 0.28 (95% CI, 0.09-0.85) in those with body mass index >or= 23.2 (highest quartile) compared with those with body mass index < 19.0 (lowest quartile). These predictors are useful for selecting appropriately patients for careful follow-up examinations.
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PMID:Risk of squamous cell carcinoma of the upper aerodigestive tract in cancer-free alcoholic Japanese men: an endoscopic follow-up study. 1711 48

We examined the effect of alcohol consumption, cigarette smoking and flushing response on esophageal squamous cell carcinoma (ESCC) in a large-scale population-based cohort study. 44,970 middle-aged and older Japanese men were followed. A total of 215 cases of ESCC were newly diagnosed. Alcohol consumption and cigarette smoking are strongly associated with the incidence of ESCC. Heavy alcohol consumption increased the risk of ESCC especially among heavy smokers with the flushing response (HR = 3.41, 95% CI = 2.10-5.51). Strong effect modification was detected in heavy smokers. Our results suggest that heavy alcohol consumption together with heavy smoking may increase the risk of ESCC particularly in individuals with the flushing response.
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PMID:Effect of alcohol consumption, cigarette smoking and flushing response on esophageal cancer risk: a population-based cohort study (JPHC study). 1903

Both cigarette smoking and alcohol drinking are well-established risk factors for esophageal squamous cell carcinoma (ESCC), and the relationship of dose to cancer risk has already been described. Furthermore, the synergistic effect of these two factors has been reported. Our case-control study revealed the odds ratio of ESCC to be 50.1 for those who were both heavy smokers and heavy drinkers in comparison to people who neither drank nor smoked. In patients with ESCC, head and neck cancers as well as dysplastic lesions are frequently observed. Heavy smoking and heavy drinking are closely related to such multicentric carcinogenesis events in the upper aerodigestive tract (UADT), including the esophagus and head andneck region. Polymorphisms in acetaldehyde dehydrogenase 2 (ALDH2) are reported to be a key event in deciding individual susceptibility to UADT cancer. Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers. For the early detection of the disease, effective follow up using endoscopy with Lugol staining or narrow band imaging endoscopy is strongly recommended for high-risk populations, such as smokers, heavy drinkers, people with experience of flushing after the drinking of alcohol, and patients with UADT cancer.
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PMID:Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention. 2022 84

The ethanol in alcoholic beverages and the acetaldehyde associated with alcohol consumption are Group 1 human carcinogens (WHO, International Agency for Research on Cancer). The combination of alcohol consumption, tobacco smoking, the inactive heterozygous aldehyde dehydrogenase-2 genotype (ALDH2*1/*2) and the less-active homozygous alcohol dehydrogenase-1B genotype (ADH1B*1/*1) increases the risk of squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) in a multiplicative fashion in East Asians. In addition to being exposed to locally high levels of ethanol, the UADT is exposed to a very high concentration of acetaldehyde from a variety of sources, including that as an ingredient of alcoholic beverages per se and that found in tobacco smoke; acetaldehyde is also produced by salivary microorganisms and mucosal enzymes and is present as blood acetaldehyde. The inefficient degradation of acetaldehyde by weakly expressed ALDH2 in the UADT may be cri! tical to the local accumulation of acetaldehyde, especially in ALDH2*1/*2 carriers. ADH1B*1/*1 carriers tend to experience less intense alcohol flushing and are highly susceptible to heavy drinking and alcoholism. Heavy drinking by persons with the less-active ADH1B*1/*1 leads to longer exposure of the UADT to salivary ethanol and acetaldehyde. The ALDH2*1/*2 genotype is a very strong predictor of synchronous and metachronous multiple SCCs in the UADT. High red cell mean corpuscular volume (MCV), esophageal dysplasia, and melanosis in the UADT, all of which are frequently found in ALDH2*1/*2 drinkers, are useful for identifying high-risk individuals. We invented a simple flushing questionnaire that enables prediction of the ALDH2 phenotype. New health appraisal models that include ALDH2 genotype, the simple flushing questionnaire, or MCV are powerful tools for devising a new strategy for prevention and screening for UADT cancer in East Asians.
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PMID:Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for prevention and screening for cancer in the upper aerodigestive tract in East Asians. 2118 98


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