Outcome After Therapeutic Lymph Node Dissection in Patients with Unknown Primary Melanoma Site

Purpose: The aim of this study was to evaluate the incidence and outcome of melanoma of unknown primary site (MUP) after therapeutic lymph node dissection (TLND) of palpable nodal melanoma metastases. Disease-free (DFS) and overall survival (OS) time of MUP patients were analyzed and compared to patients undergoing a TLND for known primary melanomas (MKP). Methods: This single institution retrospective study analyzed 342 consecutive patients who were treated with 415 TLNDs for palpable nodal disease from 1982 to 2009. Univariate and multivariate analyses included: MUP versus MKP, gender, Breslow thickness, ulceration of primary tumor, site of prima

Teacher Wellbeing: The Importance of Teacher–Student Relationships

Many studies have examined the importance of teacher-student relationships for the development of children. Much less is known, however, about how these relationships impact the professional and personal lives of teachers. This review considers the importance of teacher-student relationships for the wellbeing of teachers guided by the Transactional Model of Stress and Coping of Lazarus (1991). Based on theories on interpersonal relationships, it is postulated that teachers have a basic need for relatedness with the students in their class that originates from the close proximity between teacher and student. It is discussed that teachers internalize experiences with students in representational models of relationships that guide emotional responses in daily interactions with students, and changes teacher wellbeing in the long run. In addition, the notion of mental representations of relationships at different levels of generalization could offer a window to understand how individual teacher-student relationships may affect the professional and personal self-esteem of teachers. Lastly, it is argued that the influence of student misbehavior on teacher stress may be more fully understood from a relationship perspective. The review shows that few studies have directly tested these propositions and offers suggestions for future research

Upregulation of p27 and its inhibition of CDK2/cyclin E activity following DNA damage by a novel platinum agent are dependent on the expression of p21

The cisplatin analogue 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinumIV (DAP) is a DNA-damaging agent that will be entering clinical trials for its potent cytotoxic effects against cisplatin-resistant tumour cells. This cytotoxicity may reside in its ability to selectively activate G1-phase checkpoint response by inhibiting CDKs via the p53/p21 pathway. We have now evaluated the role of another CDK inhibitor p27 as a contributor to DAP-mediated inhibition of G1-phase CDK2 activity. Our studies in ovarian A2780 tumour cells demonstrate that p27 levels induced by DAP are comparable to or greater than those seen for p21. The induction of p27 is not through a transcriptional mechanism, but rather is due to a four-fold increase in protein stabilisation through a mechanism dependent on p21. Moreover, DAP-induced p21 promoted the selective increase of p27 in the CDK2 complex, but not in CDK4 complex, and this selective increase contributed to inhibition of the CDK2 kinase activity. The inhibited complex contained either p27 or p21, but not both, with the relative levels of cyclin E associated with p27 and p21 indicating that about 25% of the inhibition of CDK2 activity was due to p27 and 75% due to p21. This study provides the first evidence that p27 upregulation is directly attributable to activation of the p53/p21 pathway by a DNA-damaging agent, and promulgates p53/p21/p27 axis as a significant component of checkpoint response

Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study

Background: Multiple studies showed conflicting results on the association between oral contraceptive (OC) use and the development of cutaneous melanoma (CM). We investigated the association between estrogen use and CM incidence. Patients and methods: Data from PHARMO Pharmacy database and PALGA, the pathology database in The Netherlands, were linked. Women, >= 18 years, with a pathology report of a primary CM from 1 January 1991 to 14 December 2004 and >= 3 years of follow-up before CM diagnosis were eligible cases. Controls were matched for age and geographic region. Multivariate logistic regression was used to calculate adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between CM incidence and estrogen use, OCs and hormonal replacement therapy (HRT), separately. Results: In total, 778 cases and 4072 controls were included. CM risk was significantly associated with estrogen use (>= 0.5 year; adjusted OR = 1.42, 95% CI 1.19-1.69). This effect was cumulative dose dependent (P trend = 0.5 year: OR = 2.08; 95% CI 1.37-3.14) and OC (>= 0.5 year: OR = 1.28; 95% CI 1.06-1.54). Conclusion: Our study suggests a cumulative dose-dependent increased risk of CM with the use of estrogens

Non-Steroidal Anti-Inflammatory Drugs and Melanoma Risk: Large Dutch Population-Based Case-Control Study

This case-control study investigates the potential chemoprophylactic properties of non-steroidal anti-inflammatory drugs (NSAIDs) on the incidence of cutaneous melanoma (CM). Data were extracted from the Dutch PHARMO pharmacy database and the PALGA pathology database. Cases had a primary CM between 1991 and 2004, were >= 18 years, and were observed for 3 years in PHARMO before diagnosis. Controls were matched for date of birth, gender, and geographical region. NSAIDs and acetylsalicylic acids (ASAs) were analyzed separately. Adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariable logistic regression, and the results were stratified across gender. A total of 1,318 CM cases and 6,786 controls were eligible to enter the study. CM incidence was not significantly associated with ever ASA use (adjusted OR: 0.92, 95% CI: 0.76-1.12) or ever non-ASA NSAID use (adjusted OR: 1.10, 95% CI: 0.97-1.24). However, continuous use of low-dose ASAs was associated with a significant reduction of CM risk in women (adjusted OR: 0.54, 95% CI: 0.30-0.99) but not in men (OR: 1.01, 95% CI: 0.69-1.47). A significant trend (P = 0.04) from no use, non-continuous use to continuous use was observed in women. Continuous use of low-dose ASAs may be associated with a reduced incidence of CM in women, but not in men

Epidemiology of Extracutaneous Melanoma in the Netherlands

Background: Reliable population-based incidence and survival data on extracutaneous melanoma (ECM) are sparse. Methods: Incidence data (1989-2006) from the Netherlands Cancer Registry were combined with vital status on January 1, 2008. Age-adjusted annual incidence rates were calculated by direct standardization, and the estimated annual percentage change was estimated to detect changing trends in incidence. Additionally, we carried out cohort-based relative survival analysis. Results: Ocular melanomas were the most common ECM subsite with European standardized incidence rates (ESR) of 10.7 and 8.2 per 1,000,000 person-years for males and females, respectively. In comparison, for cutaneous melanoma (CM), the ESRs for men and women were 122 and 155 per million person-years, respectively. No statistically significant trends in the incidence of ECM were detected, whereas an annual increase of 4.4% for men and 3.6% for women was detected in the incidence of CM. Relative survival for ECM was poor, but differed largely between anatomic subtypes ranging from a 5-year relative survival of 74% for ocular melanomas to 15% for certain subsites of mucosal melanomas. Conclusions: Of all ECM subsites, ocular melanomas had the highest incidence and the best survival. Mucosal melanomas were the second most frequent subsite of ECM. Five-year relative survival for all ECM subtypes was worse if compared with CM. No statistically significant trends in the incidence of (subsites of) ECM were determined. Impact: This study gives insight into the relative sizes of the different subgroups of ECM as well as an estimate of 5-year survival, which varies substantially by subsite. Cancer Epidemiol Biomarkers Prev; 19(6); 1453-9. (C) 2010 AACR