Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor

In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease.     

Cancer statistics for African Americans

The American Cancer Society provides estimates on the number of new cancer cases and deaths, and compiles health statistics on African Americans in a biennial publication, Cancer Facts and Figures for African Americans. The compiled statistics include cancer incidence, mortality, survival, and lifestyle behaviors using the most recent data on incidence and survival from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program, mortality data from the National Center for Health Statistics (NCHS), and behavioral information from the Behavior Risk Factor Surveillance System (BRFSS), Youth Risk Behavior Surveillance System (YRBSS), and National Health Interview Survey (NHIS). It is estimated that 132,700 new cases of cancer and 63,100 deaths will occur among African Americans in the year 2003. Although African Americans have experienced higher incidence and mortality rates of cancer than whites for many years, incidence rates have declined by 2.7 percent per year in African-American males since 1992, while stabilizing in African-American females. During the same period, death rates declined by 2.1 percent and 0.4 percent per year among African-American males and females, respectively. The decrease in both incidence and death rates from cancer among African-American males was the largest of any racial or ethnic group. Nonetheless, African Americans still carry the highest cancer burden among US racial and ethnic groups. Most cancers detectable by screening are diagnosed at a later stage and survival rates are lower within each stage of disease in African Americans than in whites. The extent to which these disparities reflect unequal access to health care versus other factors is an active area of research.     

A comparison of normative and subjective assessment of the child prevalence of developmental defects of enamel amongst 12-year-olds living in the North West Region, UK

Analysis of data from a 1996-97 cross sectional epidemiological study of the dental health of a sample of 12-y-old children living in Crewe, in north west England was used to compare normative and subjective assessment of developmental defects of enamel. Five hundred and twenty two 12-y-old children from secondary schools in Crewe were examined. One hundred and eighty two children (34.8%), had home post codes within the optimally fluoridated part of Crewe. Using the Developmental Defects of Enamel Index, 178 children (34%) in Crewe were normatively identified as having enamel defects present on their upper incisors. Thirty five children (6.7%), were unhappy with the appearance of their upper incisors because of marks that would not brush off. Neither the normative nor the subjective assessment of enamel defects demonstrated any difference in prevalence between the fluoridated and non-fluoridated areas. In Crewe, one in 20 children normatively diagnosed as being free from enamel defects were unhappy with the appearance of their upper incisors because of marks that would not brush off. There are differences in perception between dental professionals and 12-y-old children over the presence and relevance of developmental defects of enamel. Further research is required if we are to understand the difference in professional and lay perceptions of developmental defects affecting upper incisor teeth.     

Sun protective behaviors and sunburn experiences in parents of youth ages 11 to 18

BACKGROUND: Recent studies suggest that parental sun protective behaviors and communication influence their adolescents. However, there is limited information on sun protection for parents of adolescents. METHODS: A telephone-based, nationally representative prevalence study of sun exposure among youth, aged 11-18, and their parents living in households was conducted in 1998. Separate, independent responses were collected. Weighted prevalence estimates and 95% confidence intervals were estimated and presented for parents only (n = 1187). RESULTS: Approximately one-third of parents planned activities to avoid the sun and used sunscreen. Among parents who used sunscreen, 70% applied it while at the beach or pool, but not as often during other outdoor activities. Almost one-third of parents were participating in water or non-water recreational activities during their most serious sunburn. Differences in sun protection and sunburn experiences were observed by age, gender, sun sensitivity, race and ethnicity, and educational attainment. CONCLUSIONS: Parents have adopted sun protection habits, but have not surpassed national sun-protection goals. Combined use of sun protection behaviors may reduce sunburn prevalence and number of incident skin cancers. These data may be useful for developing or enhancing current sun protection programs for effective sun protection that include parents and their adolescents.     

The prescription and relative outcomes of different materials used in general dental practice in the north west region of England to restore the primary dentition

OBJECTIVE: To identify the type of restorative materials used in general dental practice and their effects on the outcomes of restorative treatment of primary teeth. METHOD: The study involved a retrospective investigation of case notes of 677 child patients of 50 general dental practitioners (GDPs) in the northwest of England. The history of dental care received by each child during the primary dentition period was recorded. The type of restorative material used and the number of times that each tooth was restored were recorded. The proportion of primary teeth that were extracted due to pain or sepsis was calculated according to whether they were filled by amalgam or glass ionomer, or were left unfilled. RESULTS: Of the treated teeth, 61% of first and 55% of second primary molars were restored with glass ionomer. Some 27.4% of first molars restored with amalgam required repeat restorations, compared with 42.5% of those filled with glass ionomer. The difference was highly significant (p<0.001). For all primary molar teeth, there was no difference in the proportion of extractions, according to the type of restorative material used or if carious teeth were left unrestored. CONCLUSIONS: In the hands of GDPs, glass ionomer restorations are used most commonly and are significantly more likely to require replacement than amalgam restorations. The type of restorative material used had no influence on outcomes.     

Socioeconomic and geographical influences on primary dental care preferences in a population of young children

OBJECTIVE: To compare the socioeconomic profiles of children registered in the GDS, with those using the CDS services and unregistered children. Secondly to examine the effects of socioeconomic status on travelling to access primary dental care, and finally to map out the location of unregistered children in relation to primary dental care services. SETTING: The study was carried out in 1998 in Ellesmere Port in the North West of England. SUBJECTS AND MATERIALS: The study population was all children younger than 6 years who used primary dental care services in, or were residents of, Ellesmere Port. The study population was categorized into those registered with a GDS dentist, those using CDS services and those unregistered by matching GDS and CDS data to the HA population register. Socioeconomic status was measured using the Super Profiles geodemographic classification. The relationship between service preferences and travelling to access primary dental care with socioeconomic status were compared using cross-tabulations and chi square tests. RESULTS: There was a significant socioeconomic trend evident in the use of dental services. Two thirds of those using CDS services came from the most deprived area types. Of those who were unregistered half lived in the most deprived area types compared with one third of those registered with the GDS. Those who travelled into Ellesmere Port to access primary dental care were significantly more likely to live in an affluent area. Unregistered patients were homogeneously spread across the town. CONCLUSIONS: The ability to match GDS and CDS data to the HA population register is essential to understand how dental services are used by the local population. Children from deprived areas are more likely to use the CDS and a service local to their homes, therefore primary dental care services for deprived communities have to be provided locally.