The 2001 Harvard School of Public Health College Alcohol Study surveyed students at 119 4-year colleges that participated in the 1993, 1997, and 1999 studies. Responses in the 4 survey years were compared to determine trends in heavy alcohol use, alcohol-related problems, and encounters with college and community prevention efforts. In 2001, approximately 2 in 5 (44.4%) college students reported binge drinking, a rate almost identical to rates in the previous 3 surveys. Very little change in overall binge drinking occurred at the individual college level. The percentages of abstainers and frequent binge drinkers increased, a polarization of drinking behavior first noted in 1997. A sharp rise in frequent binge drinking was noted among students attending all-women's colleges. Other significant changes included increases in immoderate drinking and harm among drinkers. More students lived in substance-free housing and encountered college educational efforts and sanctions resulting from their alcohol use.

In 1999, the Harvard School of Public Health College Alcohol Study resurveyed colleges that participated in the 1993 and 1997 surveys. Responses to mail questionnaires from more than 14,000 students at 119 nationally representative 4-year colleges in 39 states were compared with responses received in 1997 and 1993. Two of 5 students (44%) were binge drinkers in 1999, the same rate as in 1993. However, both abstention and frequent binge-drinking rates increased significantly. In 1999, 19% were abstainers, and 23% were frequent binge drinkers. As before, binge drinkers, and particularly frequent binge drinkers, were more likely than other students to experience alcohol-related problems. At colleges with high binge-drinking rates, students who did not binge drink continued to be at higher risk of encountering the second-hand effects of others' heavy drinking. The continuing high level of binge drinking is discussed in the context of the heightened attention and increased actions at colleges. Although it may take more time for interventions to take effect, the actions college health providers have undertaken thus far may not be a sufficient response.

Our study indicates that tobacco use is common among college students and is not limited to cigarettes. College appears to be a time when many students are trying a range of tobacco products and are in danger of developing lifelong nicotine dependence. National efforts to monitor and reduce tobacco use of all types should expand to focus on college students and other young adults. JAMA. 2000;284:699-705

There is a recently proposed subtype of hepatocellular carcinoma (HCC) that is histologically similar to usual HCC, but characterized by the expression of ''stemness''-related markers. A large-scale study on two different cohorts of HCCs was performed to investigate the clinicopathologic features and epithelial-mesenchymal transition (EMT)-related protein expression status of this subtype of HCCs. The expression status of stemnessrelated (e.g., keratin 19 [K19], cluster of differentiation [CD]133, epithelial cell adhesion molecule [EpCAM], and c-kit) and EMT-related markers (e.g., snail, S100A4, urokinase plasminogen activator receptor [uPAR], ezrin, vimentin, E-cadherin, and matrix metalloproteinase [MMP]2) were examined using tissue microarrays from cohort 1 HCCs (n 5 137). K19 protein expression in cohort 2 HCCs (n 5 237) was correlated with the clinicopathologic parameters and messenger RNA (mRNA) levels of K19, uPAR, VIL2, Snail, Slug, and Twist. K19, EpCAM, c-kit, and CD133 positivity were observed in 18.2%, 35.0%, 34.3%, and 24.8%, respectively. K19 was most frequently expressed in combination with at least one other stemness-related marker (92.0%). K19-positive HCCs demonstrated more frequent major vessel invasion and increased tumor size, compared to K19-negative HCCs (P < 0.05). K19 was most significantly associated with EMT-related protein expression (e.g., vimentin, S100A4, uPAR, and ezrin) (P < 0.05) and a poor prognosis (overall survival: P 5 0.018; disease-free survival: P 5 0.007) in cohort 1. In cohort 2, HCCs with high K19 mRNA levels demonstrated higher mRNA levels of Snail, uPAR, and MMP2 (P < 0.05). K19-positive HCCs demonstrated more frequent microvascular invasion, fibrous stroma, and less tumor-capsule formation, compared to K19-negative HCCs (P < 0.05). K19 expression was a significant independent predictive factor of poor disease-free survival (P 5 0.032). Conclusion: K19 was well correlated with clinicopathologic features of tumor aggressiveness, compared to other stemnessrelated proteins. K19-positive HCCs showed significantly increased EMT-related protein and mRNA expression, suggesting that they may acquire more invasive characteristics, compared to K19-negative HCCs through the up-regulation of EMT-associated genes.

Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.

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Underage drinking is a major problem at American colleges, but little is known about the extent of alcohol use in different student groups, in different colleges, and in states with different control policies. We used data from the 2001 and 3 previous Harvard School of Public Health College Alcohol Studies that compared responses of underage students with those of their 21-23-year-old peers. Underage students drank alcohol less frequently but were more likely to drink to excess when they drank. College educational efforts and deterrent policies were limited in their outreach, and half of underage students obtained alcohol very easily. Underage students in states with extensive laws restricting underage and high-volume drinking were less likely to drink and to binge drink. A majority of underage students supported increasing efforts to control underage drinking. The results suggest that additional policy efforts to control underage drinking may be effective and feasible.

The authors examined changes in college students' illicit drug use, patterns of polydrug use, and the relationship between students' ages of initiation of substance use and later use of marijuana and other illicit drugs between 1993 and 2001. Data from 119 US colleges and universities in the Harvard School of Public Health College Alcohol Study were used in the study. They found significant increases in percentages of students' use of marijuana in the past 30 days (from 13% to 17%), past year (from 23% to 30%), and lifetime (from 41% to 47%) between 1993 and 2001, with most of the increase occurring between 1993 and 1997. Past 30-day use of other illicit drugs increased from 4% to 7% and past year use increased from 11% to 14%. More than 98% of marijuana and other illicit drug users used another substance. They also either smoked, were binge drinkers, and/or were users of another illicit drug. Drug prevention programs should emphasize heavy alcohol use and smoking and should start when students are in high school or earlier.