Adrenomedullin expression in the developing human fetal lung.

BACKGROUND: Adrenomedullin (AM) is a vasodilator peptide produced by endothelial and smooth muscle cells in the systemic and pulmonary circulation. It promotes angiogenesis and alveolar growth and has protective effects in the cardiovascular and respiratory systems. Adrenomedullin's role in human pulmonary vascular and alveolar development is unknown. OBJECTIVE: To test the hypothesis that AM is expressed during normal human lung development and that its expression changes with advancing gestational age by investigating the messenger RNA and protein expression of AM and its receptor components, calcitonin-receptorlike receptor (CRLR), receptor activity-modifying protein (RAMP)2, and RAMP3 in human fetal lung from 10 to 24 weeks of gestation. METHODS: The gene expression of AM, CRLR, RAMP2, and RAMP3 was measured with real-time reverse-transcription polymerase chain reaction. Adrenomedullin protein expression was measured with Western blot. Immunohistochemical analyses of sections of lung tissue were performed. Statistical analysis was performed using linear regression and one-way analysis of variance followed by the Tukey range test. RESULTS: Adrenomedullin, CRLR, RAMP2, and RAMP3 transcripts were expressed in the midgestation human fetal lung. The gene expression of AM, CRLR, and RAMP2 increased with increasing gestational age, whereas the gene expression of RAMP3 decreased. Adrenomedullin protein expression increased with increasing gestational age. CONCLUSION: Adrenomedullin is expressed in the midgestation human fetal lung and its gene and protein expression increased with increasing gestational age, suggesting a role for AM in human lung development. Supporting this conclusion, the AM1 receptor components CRLR and RAMP2 gene expression also increased with increasing gestational age. Conversely, the expression of RAMP3, a structural component of the AM2 receptor, decreased with increasing gestational age, suggesting different functions for the AM receptors in human fetal lung, as it has been demonstrated in animal models. This speculation requires further investigation.

Endometrial cancer and a family history of cancer.

OBJECTIVE: Lynch Syndrome (LS), an inherited genetic syndrome, predisposes to cancers such as colorectal and endometrial. However, the risk for endometrial cancer (EC) in women not affected by LS, but with a family history of cancer, is currently unknown. We examined the association between a family history of cancer and the risk for EC in non-LS patients. METHODS: This population-based case-control study included 519 EC cases and 1015 age-matched controls and took place in Alberta, Canada between 2002 and 2006. Information about risk factors, including family history of cancer in first and second degree relatives, was ascertained via in-person interviews. Microsatellite instability (MSI) status of tumor tissue was assessed to determine involvement of DNA mismatch repair (MMR) genes. RESULTS: A first or second degree family history of uterine cancer was modestly associated with the risk for overall EC [odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9, 1.9], and the risks were similar for MSI+cancer (OR=1.5, 95%CI=0.7, 3.3) and MSI- cancer (OR=1.3, 95%CI=0.8, 2.4). Although consistent, these associations were modest and not significant. In contrast, the risk for MSI+cancer was elevated with a reported family history of colorectal cancer (OR=1.4, 95%CI=1.0, 2.2), but not for MSI- cancer. CONCLUSIONS: A family history of uterine cancer may be modestly associated with EC risk in non-LS patients regardless of MSI status, suggesting that risk was not related to inherited defects in the MMR gene pathway. These results provide preliminary support for an EC-specific genetic syndrome.

Comorbidities and endometrial cancer survival in Hispanics and non-Hispanic whites.

PURPOSE: We investigated comorbidities and endometrial cancer survival by ethnicity because Hispanic whites (HWs) have worse survival than non-Hispanic whites (NHWs). METHODS: An endometrial cancer cohort (1992-2004) established with the Surveillance, Epidemiology and End Results-Medicare-linked database (n = 3,286) was followed through 2007. Endometrial cancer-specific and other cause mortality were evaluated with multivariate hazard ratios (mHRs). RESULTS: HWs were more likely than NHWs to have regional/distant disease (31.7 vs. 24.8 %), diabetes (31.7 vs. 11.0 %), and hypertension (49.4 vs. 37.6 %). HWs had poorer endometrial cancer-specific survival than NHWs (age-adjusted HR = 1.28; 95% CI 1.01-1.61), but not after adjustment for tumor characteristics and treatment (mHR = 1.02; 95% CI 0.81-1.29). In contrast, even after adjustment for cancer-related factors, other cause mortality in HWs was elevated (mHR = 1.27; 95% CI 1.01-1.59), but not after further adjustment for comorbid conditions (mHR = 1.07; 95% CI 0.85-1.35). CONCLUSIONS: Comorbidities, particularly diabetes, were more common in HWs than in NHWs and impacted other cause mortality. Improving diabetes management may be an effective means of improving other cause mortality. This may be particularly true for HWs, given their particularly high prevalence of diabetes.

Age disparity in the dissemination of imatinib for treating chronic myeloid leukemia.

BACKGROUND: Imatinib is a highly effective treatment for chronic myeloid leukemia. It was approved by the Food and Drug Administration in 2001 and thereafter rapidly became front-line therapy. This study characterized the prevailing chronic myeloid leukemia therapies in the United States and assessed the impact of imatinib on chronic myeloid leukemia survival and mortality rates in the general population. METHODS: Investigators with the National Cancer Institute's Patterns of Care study reviewed medical records and queried physicians regarding therapy for 423 patients with chronic myeloid leukemia diagnosed in 2003 who were randomly selected from cancer registries in the Surveillance, Epidemiology, and End Results Program. Characteristics associated with the receipt of imatinib were documented, as were survival differences between those who received imatinib and those who did not. Population-based data were used to assess chronic myeloid leukemia survival and mortality rates in time periods before and after the introduction of imatinib. RESULTS: Imatinib was administered to 76% of patients in the Patterns of Care study. Imatinib use was inversely associated with age: 90%, 75%, and 46% for patients ages 20 to 59 years, 60 to 79 years, and 80 or more years, respectively. Elderly patients who received imatinib survived significantly longer than those who did not. After adjusting for age, imatinib use did not vary significantly by race/ethnicity, socioeconomic status, urban/rural residence, presence of comorbid conditions, or insurance status. Overall, chronic myeloid leukemia survival in the Surveillance, Epidemiology, and End Results population improved, and mortality in the United States declined dramatically during the period when imatinib became widely available; these improvements diminished with increasing age. CONCLUSION: Age disparities in treatment with imatinib likely contributed to worse survival for many elderly patients with chronic myeloid leukemia.

Site of oncologic specialty care for older adolescents in Utah.

PURPOSE: Adolescents with cancer may access oncologic care from pediatric or adult medical centers, given overlapping age eligibility. However, some recent data suggest a benefit to adolescents with certain cancers when treated at pediatric centers or on pediatric protocols. We used a population-based registry to determine the site of care of children, adolescents, and young adults (age 0 to 24 years) with newly diagnosed cancer. PATIENTS AND METHODS: From the Utah Cancer Registry 1994 to 2000, new malignant cases in patients aged 0 to 24 years were chosen; data including diagnosis, home ZIP code and sites of oncologic care were abstracted. Distance between home ZIP code and Primary Children's Medical Center (PCMC; Salt Lake City, Utah), the state's sole site of pediatric oncology care, was determined. RESULTS: Sixty-six percent of Utah 15- to 19-year-olds with cancer were never seen by a PCMC oncologist. Even among this narrow age range, utilization of the pediatric center dropped with each additional year of age. Not unexpectedly, few of those with epithelial malignancies in this age group were seen at PCMC. But surprisingly, 47% of the older adolescents with leukemia, 66% with brain tumors, and 71% with lymphoma never saw a pediatric oncologist. After consideration of age and diagnosis, distance the patient lived from PCMC had a negligible effect on the likelihood of an adolescent being seen there. CONCLUSION: The referral of adolescents with cancer to a pediatric oncology center diminishes greatly with age, and is moderately influenced by diagnosis and minimally by distance from center. Further study should investigate reasons for referral patterns, and impact on outcomes.