Biomedical subjects

H Garewal

Publications and source records attributed to H Garewal.

At least 19 recordsLinked to original sources

PubMed2006

Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells.

Nuclear factor kappa B (NF-kappaB) is a redox-associated transcription factor that is involved in the activation of survival pathways. We have previously shown that deoxycholate (DOC) activates NF-kappaB in hepatocytes and colon epithelial cells and that persistent exposure of HCT-116 cells to increasing concentrations of DOC results in the constitutive activation of NF-kappaB, which is associated with the development of apoptosis resistance. The mechanisms by which DOC activates NF-kappaB in colon epithelial cells, and whether natural antioxidants can reduce DOC-induced NF-kappaB activation, however, are not known. Also, it is not known if DOC can generate reactive oxygen species within mitochondria as a possible pathway of stress-related NF-kappaB activation. Since we have previously shown that DOC activates the NF-kappaB stress-response pathway in HCT-116 cells, we used this cell line to further explore the mechanisms of NF-kappaB activation. We found that DOC induces mitochondrial oxidative stress and activates NF-kappaB in HCT-116 cells through multiple mechanisms involving NAD(P)H oxidase, Na+/K+-ATPase, cytochrome P450, Ca++ and the terminal mitochondrial respiratory complex IV. DOC-induced NF-kappaB activation was significantly (P < 0.05) inhibited by pre-treatment of cells with CAPE, EGCG, TMS, DPI, NaN3, EGTA, Ouabain and RuR. The NF-kappaB-activating pathways, induced by the dietary-related endogenous detergent DOC, provide mechanisms for promotion of colon cancer and identify possible new targets for chemoprevention.

Antioxidants↗

PubMed2006

Esophageal acid exposure at pH < or = 2 is more common in Barrett's esophagus patients and is associated with oxidative stress.

Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid exposure profile than other gastroesophageal reflux disease patients. Cellular oxidative stress has been proposed to contribute to the development of BE and esophageal adenocarcinoma. However, a relationship between low esophageal pH and oxidative stress has yet to be elucidated. The aim of this study was to determine the duration of low pH exposure in the esophagus of BE patients compared to those with erosive esophagitis (EE) and to test if brief exposure to low pH leads to the induction of reactive oxygen species (ROS). Seventy-three patients with BE or EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2 by flow cytometry and fluorescent microscopy for the production of ROS. BE patients demonstrated a significantly higher exposure to low pH values (pH < or = 2) than EE patients. The mean percent total time, duration and mean number of reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/- 11.4 episodes in BE patients, whereas in EE patients they were significantly less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically relevant to the clinical situation. Our studies indicate that such exposure induces oxidative stress. This stress may cause DNA damage, mutations and progression to cancer.

Adenocarcinoma↗

PubMed2005

Bile acids as carcinogens in human gastrointestinal cancers.

Bile acids were first proposed to be carcinogens in 1939 and 1940. On the basis of later work with rodent models, bile acids came to be regarded as cancer promoters rather than carcinogens. However, considerable indirect evidence, obtained more recently, supports the view that bile acids are carcinogens in humans. At least 15 reports, from 1980 through 2003, indicate that bile acids cause DNA damage. The mechanism is probably indirect, involving induction of oxidative stress and production of reactive oxygen species that then damage DNA. Repeated DNA damage likely increases the mutation rate, including the mutation rate of tumor suppressor genes and oncogenes. Additional reports, from 1994 through 2002, indicate that bile acids, at the increased concentrations accompanying a high fat diet, induce frequent apoptosis. Those cells within the exposed population with reduced apoptosis capability tend to survive and selectively proliferate. That bile acids cause DNA damage and may select for apoptosis-resistant cells (both leading to increased mutation), indicates that bile acids are likely carcinogens. In humans, an increased incidence of cancer of the laryngopharyngeal tract, esophagus, stomach, pancreas, the small intestine (near the Ampulla of Vater) and the colon are associated with high levels of bile acids. The much larger number of cell generations in the colonic (and, likely, other gastrointestinal) epithelia of humans compared to rodents may allow time for induction and selection of mutations leading to cancer in humans, although not in rodents.

Animals↗

PubMed2003

Caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis: protective role of the nitric oxide signaling module.

Hydrophobic bile acids such as deoxycholate are known tumor promoters in the gastrointestinal tract. We have previously shown that deoxycholate induces apoptosis in colon epithelial cells and that these cells can be made resistant to deoxycholate-induced apoptosis. We now show that the nitric oxide synthase/nitric oxide/guanylate cyclase/cyclic guanosine monophosphate/cGMP-activated protein kinase (NOS/NO/GC/cGMP/PKG) signaling module contributes, in part, to the observed resistance of the cultured DOC-resistant colon epithelial cells (HCT-116R) using pharmacological inhibitors/antagonists (NS2028, Rp-8pCPT-cGMP, KT5823) of members of this signaling module. A novel finding from this study is the caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis of deoxycholate-sensitive HCT-116SA cells and the absence of guanylate cyclase alpha 1 cleavage in deoxycholate-treated HCT-116R resistant cells using Western blot analyses. This cleavage was specific to caspases as lysosomal, proteasomal, serine protease, cathepsin and calpain inhibitors failed to prevent the cleavage, whereas a general caspase inhibitor and a specific caspase-6 inhibitor did prevent guanylate cyclase alpha 1 cleavage.

Animals↗

PubMed2002

Activation of the metallothionein IIA promoter and other key stress response elements by ursodeoxycholate in HepG2 cells: relevance to the cytoprotective function of ursodeoxycholate.

Ursodeoxycholate, used to treat a variety of pathologies, has the ability to reverse cytotoxic and hepatotoxic conditions. We examined HepG2, a hepatic cell line, treated with increasing levels of ursodeoxycholate, for responses of a range of promoters/response elements responsive to DNA damage, heavy metal ions, protein denaturants, aromatic hydrocarbons, retinoids, changes in intracellular AMP levels, end endoplasmic reticulum stress. The metallothionein IIA promoter was the most highly activated by ursodeoxycholate. Since ursodeoxycholate protects against the cytotoxic effects of deoxycholate, our data, combined with observations made by others, implicate metallothionein IIA as being important in this protective pathway.

Cell Survival↗

PubMed2001

The specific NOS2 inhibitor, 1400W, sensitizes HepG2 cells to genotoxic, oxidative, xenobiotic, and endoplasmic reticulum stresses.

We tested the hypothesis that the constitutive activity of the inducible form of nitric oxide synthase (NOS2) serves to protect cells against numerous endogenous stresses. To accomplish this, we treated HepG2 cell lines that were individually transfected with 13 different promoter/response element (RE) chloramphenicol acetyl transferase (CAT) reporter constructs, with a highly selective NOS2 inhibitor, 1400W [N-(3-(aminomethyl)benzyl) acetamidine)]. HepG2 cells were incubated for 6 h with 0, 1, 10, 50, 100, and 200 microM 1400W, and the activation of the promoter/RE CAT reporter constructs was simultaneously determined. The highest fold inductions occurred at 200 microM 1400W, a concentration that had no effect on overall cell viability, as determined by the MTT assay. Twelve of the 13 promoter/RE CAT reporter constructs were significantly activated by 200 microM 1400W. These results indicate the extensive protective role of constitutive NOS2 against genotoxic, oxidative, and endoplasmic reticulum stresses. The mechanism of this protection may involve the complexing of iron by nitric oxide (NO) to reduce hydroxyl radical formation, NO inhibition of electron transport and the generation of reactive oxygen species within mitochondria, NO inhibition of cyclooxygenase, lipoxygenase, and cytochrome P450 enzyme activity, and the scavenging of superoxide anions by NO to form peroxynitrite.

Amidines↗

PubMed2000

Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380.

BACKGROUND AND METHODS: The role of colonoscopy in screening for colorectal cancer is uncertain. At 13 Veterans Affairs Medical Centers, we performed colonoscopy to determine the prevalence and location of advanced colonic neoplasms and the risk of advanced proximal neoplasia in asymptomatic patients (age range, 50 to 75 years) with or without distal neoplasia. Advanced colonic neoplasia was defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. In patients with more than one neoplastic lesion, classification was based on the most advanced lesion. RESULTS: Of 17,732 patients screened for enrollment, 3196 were enrolled; 3121 of the enrolled patients (97.7 percent) underwent complete examination of the colon. The mean age of the patients was 62.9 years, and 96.8 percent were men. Colonoscopic examination showed one or more neoplastic lesions in 37.5 percent of the patients, an adenoma with a diameter of at least 10 mm or a villous adenoma in 7.9 percent, an adenoma with high-grade dysplasia in 1.6 percent, and invasive cancer in 1.0 percent. Of the 1765 patients with no polyps in the portion of the colon that was distal to the splenic flexure, 48 (2.7 percent) had advanced proximal neoplasms. Patients with large adenomas (> or = 10 mm) or small adenomas (< 10 mm) in the distal colon were more likely to have advanced proximal neoplasia than were patients with no distal adenomas (odds ratios, 3.4 [95 percent confidence interval, 1.8 to 6.5] and 2.6 (95 percent confidence interval, 1.7 to 4.1], respectively). However, 52 percent of the 128 patients with advanced proximal neoplasia had no distal adenomas. CONCLUSIONS: Colonoscopic screening can detect advanced colonic neoplasms in asymptomatic adults. Many of these neoplasms would not be detected with sigmoidoscopy.

Adenoma↗

PubMed1999

A bile acid-induced apoptosis assay for colon cancer risk and associated quality control studies.

Bile acids are important in the etiology of colorectal cancer. Bile acids induce apoptosis in colonic goblet cells at concentrations comparable to those found in fecal water after high-fat meals. Preliminary evidence indicated that cells of the normal-appearing (nontumorous) portion of the colon epithelium of colon cancer patients are more resistant to bile salt-induced apoptosis than are cells from normal individuals. In the present study, 68 patients were examined, and biopsies were taken at 20 cm from the anal verge, cecum, and descending colon. The patients included 17 individuals with a history of colorectal cancer, 37 individuals with adenomas, and 14 individuals who were neoplasia free. The mean bile salt-induced apoptotic index among normal individuals was 57.6 +/- 3.47 (SE), which differed significantly (P < 0.05) from the mean value of 36.41 +/- 3.12 in individuals with a history of colon cancer. The correlation between independent observers was 0.89 (P < 0.001), indicating good interobserver reliability. Components of variance comparing interindividual versus intraindividual sources of variation suggested that site-to-site variability, both between regions of the colon and for adjacent biopsies, was larger than the interpatient variability for individuals with a history of neoplasia. Therefore, there was "patchiness" of the susceptibility of regions of the colon to bile acid-induced apoptosis in individuals with a history of neoplasia (a patchy field effect). There was no obvious correlation of low-apoptotic index regions with regions in which previous neoplasias had been found and removed. On the other hand, for normal, i.e., neoplasia-free, individuals, there was relatively less intraindividual variation compared to interindividual variation. Our assay shows an association between resistance to bile acid-induced apoptosis, measured at 20 cm from the anal verge, and colon cancer risk. Thus, this assay may prove useful as a biomarker of colon cancer risk.

Adenoma↗

PubMed1999

Reactive nitrogen species in colon carcinogenesis.

The role of reactive nitrogen species (RNS) in colon carcinogenesis is multifactorial and affects diverse processes, such as proliferation, apoptosis, differentiation, tumorigenesis, and metastases. This review describes the stages in colon carcinogenesis where nitric oxide (NO) and inducible NO synthase (NOS2) may influence the progression of a normal mucosa to overt metastatic cancer. Overexpression of NOS2 and an increase in the generation of NO and other RNS may lead to apoptosis resistance, DNA damage, mutation, up-regulation of COX-2, increased proliferation, an increase in oxidative stress and an increase in tumor vascularity and metastatic potential. Therefore, future goals are to establish mechanistically based biomarkers to assess individuals at risk for colon cancer and to implement chemopreventive and dietary strategies that reduce colon cancer risk. An understanding of NO signaling pathways in colon epithelial cells should provide the basis for novel biomarker development. Colon cancer prevention may be achieved effectively by chemically interfering with key components of the NO signaling pathways, changing dietary habits to reduce fat and increase antioxidant-containing vegetables, and dietary supplementation to increase DNA repair.

Animals↗

PubMed1999

Biomarker studies in reversed Barrett's esophagus.

OBJECTIVE: The purpose of this study was to use biomarkers to assess for cancer risk in Barrett's esophagus patients with either squamous islands or complete reversal of their intestinal metaplasia to squamous epithelium. METHODS: The biomarkers included proliferation characteristic using Ki-67, p53 abnormalities using immunohistochemical methods with two antibodies, DO-1 and DO-7, and ornithine decarboxylase (ODC) activity. RESULTS: Eleven patients had complete reversal produced by a combination of acid suppression and thermal injury (multipolar electrocoagulation). Ki-67 staining was indistinguishable from that of normal squamous esophageal epithelium, i.e., basal layer staining only. All 11 cases were negative for p53. ODC activity was low and in the range for normal squamous epithelium. Fourteen patients had squamous islands (partial reversal) after prolonged proton pump inhibitor therapy. Multilayer Ki-67 staining occurred in nine cases (64%), and six (43%) had areas of positive p53 staining. CONCLUSIONS: Initial biomarker studies suggest that completely reversed squamous epithelium is biologically similar to normal squamous epithelium and of low cancer risk. In contrast, partial reversal, manifest as squamous islands, is accompanied by biomarker abnormalities.

Aged↗

PubMed1997

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy.

BACKGROUND: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy. PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1-3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery. RESULTS: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment. CONCLUSION: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.

Adult↗

PubMed1997

Reduced chemoreceptor sensitivity in patients with Barrett's esophagus may be related to age and not to the presence of Barrett's epithelium.

BACKGROUND: Patients with Barrett's esophagus have demonstrated reduced chemo- and mechanoreceptor sensitivity to acid infusion and balloon distension, respectively. However, Barrett's esophagus is mainly a disease of the elderly, making age the possible underlying mechanism for altered pain perception in this patient population. OBJECTIVES: To determine perception thresholds to acid infusion in elderly (>65 yr) versus younger (< or =50 yr) patients with Barrett's esophagus. METHODS: Twelve elderly and 10 younger patients, matched by length of Barrett's mucosa, were recruited into the study. All patients participated in our Barrett's esophagus surveillance program. The patients were treated with omeprazole 20 to 60 mg/day and were symptom free. Chemosensitivity was determined by a modified acid perfusion test, in which acid perception thresholds were quantified by the lag time to initial typical symptom perception, sensory intensity rating, and an acid perfusion sensory score. RESULTS: Five of the elderly patients with Barrett's esophagus had a negative test, whereas all younger patients with Barrett's esophagus experienced typical symptom perception during acid infusion. Elderly patients with Barrett's esophagus had significantly longer lag time to initial perception, lower acid perfusion sensory score, and sensory intensity rating in comparison with the younger patients. CONCLUSIONS: Reduced chemoreceptor sensitivity to acid perfusion that has previously been demonstrated in patients with Barrett's esophagus may be related to age and not to the presence of Barrett's epithelium.

Adult↗

PubMed1996

Reduced bile acid-induced apoptosis in "normal" colorectal mucosa: a potential biological marker for cancer risk.

Dietary factors, including bile acids, are important in the causation of colorectal cancer (CRC). We have previously shown that in vitro exposure of colorectal mucosal biopsies to low concentrations of bile acids produces apoptosis selectively in goblet cells. Apoptosis is an important mechanism for clearing DNA-damaged cells. Inhibition of apoptosis would result in increasing accumulation of DNA-damaged cells, resulting in increased cancer risk. We compared the percentage of apoptosis induced by bile acids in mucosal biopsies from CRC patients with that of noncancer subjects. Mucosal biopsies from 15 to 20 cm from the anal verge were incubated in 1 mM sodium deoxycholate, and the percentage of goblet cells undergoing apoptosis was quantitated. Seven patients with a history of CRC within the previous 5 years were compared with 18 noncancer subjects [4 neoplasia free and 14 with small (< or = 9 mm) polyps only]. The CRC patients had a significantly lower percentage of apoptosis than noncancer subjects; the mean for CRC was 10.7% (range, 0.9-26%) and for noncancer subjects was 55.9% (range, 20.3-71%; P < or = 0.001). Two other noncancer patients had very high-risk lesions, i.e., large villous adenomas and multiple large polyps during several colonoscopies over the previous 6 years. Their percentage of apoptosis was in the cancer range, i.e., 6.2 and 10.7%. Reduced apoptotic ability may imply increased cancer risk. By applying a quantitative bile acid-induced apoptosis assay to colorectal mucosal biopsies, the percentage of apoptosis was found to be significantly reduced in CRC patients. This assay may prove to be a useful intermediate biological marker for identifying subjects at increased risk of cancer.

Aged↗

PubMed1995

Antioxidants in oral cancer prevention.

I present evidence in support of a chemopreventive role for the so-called antioxidant nutrients, beta-carotene and vitamin E, against oral cavity cancer. This evidence is from laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and prevention of malignancies in particularly high-risk subjects. Because agents proposed for disease prevention are meant to be used widely without close medical supervision, almost any toxicity is unacceptable. beta-Carotene and vitamin E fulfill this criterion for a suitable chemopreventive agent. In several epidemiologic studies, low intakes of vitamin E, carotenoids, or both have been associated with a higher cancer risk. Smoking, a major risk factor, results in lower beta-carotene concentrations in plasma and oral mucosal cells. In several laboratory and animal model systems, beta-carotene and other antioxidant nutrients are inhibitors of oral cavity carcinogenesis. beta-Carotene and vitamin E can produce clinical regression of oral leukoplakia, a premalignant lesion for oral cancer. The design and limitations of such studies in oral leukoplakia are discussed. Cancer incidence reduction trials in high-risk groups have targeted prevention of second malignancies in patients cured of a primary oral cancer. These trials are in progress. The data thus far are supportive of a significant preventive role for these nutrients in oral cancer.

Animals↗

PubMed1995

Analysis of K-ras gene mutations in malignant and nonmalignant endobronchial tissue obtained by fiberoptic bronchoscopy.

Using polymerase chain reaction DNA amplification, we identified K-ras oncogene mutations in bronchial biopsies obtained from patients undergoing bronchoscopy for clinical indications. We hypothesized that these mutations would be found in a field encompassing malignant and nonmalignant tissues in patients with pulmonary carcinomas, and also possibly in tissue from some patients who smoked but did not have pulmonary malignancy. We found K-ras mutations in endobronchial biopsies from nine of 22 patients (41%) with carcinoma of the lung. In five of these patients, mutations were found in both malignant and nonmalignant specimens. In two instances, mutations were found only in the neoplastic tissue, and in two cases mutations were present only in the nonmalignant tissue. Furthermore, we identified two patients with K-ras mutations among seven patients in whom no clinical malignancy was apparent. Our data suggest that some oncogene activations may occur over a broad area in smokers with and without malignancy, and they imply that K-ras mutations may serve as surrogate markers for malignant potential.

Aged↗

PubMed1995

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo.

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.

Administration, Oral↗

PubMed1995

Risk factors for Barrett's oesophagus: a life history approach to behavioural assessment in the distant past.

Little is known about the aetiology of Barrett's oesophagus, a condition in which columnar epithelium replaces normal squamous epithelium above the juncture of the oesophagus with the stomach. An exploratory retrospective study of males from the Tucson Veteran's Affairs Medical Center (Tucson, AZ, USA), looking at 22 Barrett's cases and 22 controls, was undertaken to: (1) determine whether risk factors previously reported for squamous oesophageal cancer were also potential risk factors for Barrett's oesophagus; and (2) explore which of several retrospectively determined dietary factors would permit maximum discrimination of Barrett's cases from controls. Because of the recognized difficulty with retrospective dietary assessment, an intensive interview-based life history approach was developed to assess behavioural factors throughout adulthood. We examined the dose-response relationship involving questions (1) and (2) separately for subjects with lesions less than or greater than 7 cm in length. A literature-based oesophageal cancer risk factor score (including use of tobacco and intakes of alcohol, fat, vitamin A, linoleic acid and protein) discriminated cases from controls. Alcohol consumption alone discriminated patients with lesions < 7 cm in length from controls, and a more complex risk factor score (including tobacco use, alcohol, fat, fruits and vegetables) discriminated patients with lesions > 7 cm in length from controls.

Adult↗

PubMed1994

Chemoprevention of oral cancer: beta-carotene and vitamin E in leukoplakia.

The most definitive and direct way to show that a putative chemoprevention agent actually prevents cancer would be to demonstrate a reduction in cancer incidence in a clinical trial. From a practical standpoint this approach is not feasible for most cancers. Therefore, it becomes necessary to draw conclusions on chemopreventive activity through consideration of indirect lines of evidence, one of which is activity in premalignant lesions such as leukoplakia. As a corollary, it must be emphasized that the goal of undertaking chemoprevention trials in oral leukoplakia is to develop approaches for the prevention of oral cancer. Because the risk of cancer in the usual leukoplakia lesion is low, only non-toxic agents should be tested in this setting and they should be suited for eventual use in a prevention setting. Beta-carotene and vitamin E, unlike the retinoids, fulfill the criteria for a suitable chemopreventive agent and several lines of evidence point to a preventive role for them against oral cancer. These include laboratory in vitro and animal model findings, but the strongest evidence comes from epidemiologic studies which uniformly suggest protection by beta-carotene against head and neck cancer. Much like the retinoids, but without toxicity, beta-carotene and vitamin E can produce regression of oral leukoplakia, a premalignant lesion for oral cancer, as has now been shown in eight clinical trials, five with beta-carotene alone, one with vitamin E alone and two that used these agents as part of combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗