0000000000186024
AUTHOR
Klaus-michael Debatin
Abstract 3512: MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts
Abstract The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect …
Social outcomes of long-term survivors of adolescent cancer
Objectives: The study investigates psychosexual and family outcomes among German long-term survivors of adolescent cancer. Methods: Survivors of cancer during adolescence (n=820; age at onset of disease: M=15.8 years, SD=0.9, age at follow-up: M=30.4, SD=6.0 years) completed questionnaires on their family life and their psychosexual and autonomy development. Outcomes were compared to an age-matched sample (German Socio-Economic Panel, G-SOEP, n=820, age: M=30.4, SD=6.7 years) from the general population and to a control group of adults without cancer (n=1027, age: M=31.5, SD=7.0 years). Results: Compared to controls of the same sex, female survivors had achieved fewer developmental mileston…
Educational and vocational achievement among long-term survivors of adolescent cancer in Germany
Background Adolescence involves graduating from school and preparing one's professional career. The accomplishment of these tasks may be hampered by the experience of cancer. This study investigates the educational and professional achievements of German long-term survivors of adolescent cancer. Procedure Adult survivors of cancer during adolescence (n = 820, age at onset between 15 and 18 years; M = 15.8, SD = 0.9 years; age at follow-up: M = 30.4, SD = 6.0 years) were recruited through the German Childhood Cancer Registry. They completed self-reports with standard items on their educational and vocational level and their current occupational situation. Outcomes were compared to an age-mat…
Posttraumatic stress, depression and anxiety among adult long-term survivors of cancer in adolescence.
Abstract Background To determine the prevalence of posttraumatic stress, depression and anxiety in adults who have survived cancer (⩾5 years) diagnosed in adolescence, as compared to healthy controls. Patients and methods Survivors (n = 820) of cancer during adolescence (age M = 30.4 ± 6.0 years; M = 13.7 ± 6.0 years since diagnosis) and 1027 matched controls without history of cancer (age M = 31.5 ± 6.9 years) completed standardised questionnaires measuring posttraumatic stress, depression and anxiety. Additionally, sub-groups of 202 survivors and 140 controls with elevated scores received structured interviews to ascertain DSM-IV-diagnoses. Results A total of 22.4% of the survivors report…
Dexamethasone desensitizes hepatocellular and colorectal tumours toward cytotoxic therapy
The glucocorticoid dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and the supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact to cytotoxic treatment of colorectal and hepatocellular carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using 8 established cell lines, 18 surgical specimen and a xenograft on nude mice. In the presence of dexamethasone we found strong inhibition of apoptosis in response to 5-FU, cisplatin, gemcitabine or gamma-irradiation,…
Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.
Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review su…
MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts
The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect and a hyp…
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ?accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. "Regulated cell death" (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to…