Osteonecrosis of the jaw related to the use of bisphosphonates

PURPOSE OF REVIEW: Osteonecrosis of the jaw associated with the use of potent nitrogen containing bisphosphonates is a new and challenging clinical entity with a high impact on quality of life. This review attempts to consolidate the rapidly expanding literature into practical guidelines and provides expert consensus for areas of uncertainty. RECENT FINDINGS: Diagnostic criteria and a staging system for osteonecrosis of the jaw have been proposed, and histomorphologic analysis has confirmed osteonecrosis of the jaw as a proper disease, distinctively different from osteoradionecrosis. Various guidelines for the management of osteonecrosis of the jaw have been suggested and further retrospective research has provided new insights into its epidemiology. SUMMARY: Osteonecrosis of the jaw is a distinct entity of uncertain origin that is increasingly being observed in patients treated with potent aminobisphosphonates, although the etiology is probably multifactorial. Recent data confirm the predisposition of multiple myeloma patients to develop osteonecrosis of the jaw. Although various treatment strategies have been reported, conservative management remains the mainstay of therapy.     

Understanding the mechanisms underlying the effects of negative age stereotypes and perceived age discrimination on older adults’ well-being

Abstract

Objectives: Although numerous studies have documented that negative age stereotypes and perceived age discrimination are related to older adults’ lower well-being, few studies have investigated the mechanisms underlying these relationships. In this study, we tested whether self-perceptions of aging and subjective age would help to account for the relation between stereotypes and discrimination and self-esteem. According to the internalization hypothesis, we expected that the effects of negative age stereotypes and greater perceived age discrimination would be driven by more negative self-perceptions of aging and older subjective age.

Method: A total of 151 older adults completed questions assessing their endorsement of negative age stereotypes, perceived age discrimination, self-perceptions of aging, subjective age, and self-esteem. Relationships among these variables were assessed using serial mediation analyses.

Results: Consistent with the internalization hypothesis, negative age stereotypes and perceived age discrimination indirectly predicted older subjective age and lower self-esteem through worsening self-perceptions of aging. However, we did not find a direct effect of negative age stereotypes or perceived discrimination on subjective age, nor an indirect effect of negative age stereotypes and perceived age discrimination on self-esteem through subjective age.

Conclusion: These results support the internalization hypothesis: among older adults, holding more negative age stereotypes and perceiving more age discrimination is associated with feeling older and with lower self-esteem through worsened perceptions of one’s own aging. Given the central role of self-perceptions of aging, these findings highlight the importance of promoting more positive self-perceptions in order to maintain or increase older adults’ well-being.     

Alcohol and Dietary Folate Intake and Promoter CpG Island Methylation in Clear-Cell Renal Cell Cancer

We investigated whether alcohol and dietary folate intakes were associated with promoter methylation in clear-cell renal cell carcinoma (ccRCC). The Netherlands Cohort Study with a case-cohort design included 120,852 subjects aged 55–69 yr in 1986. Diet was measured with a food-frequency questionnaire. After 20.3 yr of follow-up, paraffin-embedded tumor blocks were collected. Methylation-specific polymerase chain reaction (MSP) was used to analyze promoter methylation of 11 genes. ccRCC cases were classified into low (0–19% of the genes), intermediate (20–39%), and high (40%+) methylation. Multivariable Cox regression analyses were conducted, stratified according to methylation, including 3980 subcohort members and 297 ccRCC cases. Increasing alcohol intake was associated with decreased ccRCC risk, but was not statistically significant; multivariable adjusted hazard ratio (HR) for ≥30 g alcohol/day versus 0 g/day was 0.78 [95% confidence interval (CI): 0.48–1.24], and P-value for trend was 0.46. In strata according to methylation index, no significant heterogeneity was observed. Dietary folate intake was not associated with ccRCC risk. There was no significant heterogeneity between strata according to methylation index. There was no effect modification of alcohol and dietary folate intake on ccRCC risk, nor in strata according to methylation index. Our findings do not support the hypothesis that alcohol and dietary folate intakes are involved in ccRCC.     

RANK ligand inhibition in bone metastatic cancer and risk of osteonecrosis of the jaw (ONJ): non bis in idem?

Purpose  

The purpose of this study was to assess the necessity of post-marketing safety monitoring focused on osteonecrosis of the jaw (ONJ) in patients with bone metastatic cancer treated with denosumab (AMG162).     

Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer

ABSTRACT: BACKGROUND: Cell line models have proven to be effective tools to investigate a variety of ovarian cancer features. Due to the limited number of cell lines, particularly of the serous subtype, the heterogeneity of the disease, and the lack of cell lines that model disease progression, there is a need to further develop cell line resources available for research. This study describes nine cell lines derived from three ovarian cancer cases that were established at initial diagnosis and at subsequent relapse after chemotherapy. METHODS: The cell lines from three women diagnosed with high-grade serous ovarian cancer (1369, 2295 and 3133) were derived from solid tumor (TOV) and ascites (OV), at specific time points at diagnosis and relapse (R). Primary treatment was a combination of paclitaxel/carboplatin (1369, 3133), or cisplatin/topotecan (2295). Second line treatment included doxorubicin, gemcitabine and topotecan. In addition to molecular characterization (p53, HER2), the cell lines were characterized based on cell growth characteristics including spheroid growth, migration potential, and anchorage independence. The in vivo tumorigenicity potential of the cell lines was measured. Response to paclitaxel and carboplatin was assessed using a clonogenic assay. RESULTS: All cell lines had either a nonsense or missense TP53 mutations. The ability to form compact spheroids or aggregates was observed in six of nine cell lines. Limited ability for migration and anchorage independence was observed. The OV3133(R) cell line, formed tumors at subcutaneous sites in SCID mice. Based on IC50 values and dose response curves, there was clear evidence of acquired resistance to carboplatin for TOV2295(R) and OV2295(R2) cell lines. CONCLUSION: The study identified nine new high-grade serous ovarian cancer cell lines, derived before and after chemotherapy that provides a unique resource for investigating the evolution of this common histopathological subtype of ovarian cancer.