がんの科学と治療

1.1 Objective: To study the impact of changes in national healthcare legislation and financial cuts by insurance companies on inflow of clients and their evaluation in psycho-oncological aftercare. These legislation changes and financial cuts did lead to a more complex in-take processes and less free-of-charge psycho-oncological care against higher costs. The psychosocial care concerns individual, cognitive behavioural, and art therapy. 1.2 Method: Two groups of clients were formed, based on financial policy cuts in 2012/2013 (N=334) and 2014/2015 (N=360). Data was part of the annual evaluation by De Vruchtenburg (Psycho-oncological Centre, Rotterdam, the Netherlands). The questionnaire was filled at home after the therapy, returned postage free. Analyses applied ANOVA, Mann-Whitney and MANOVA tests. 1.3 Results: Results showed that due legislation changes and financial cuts fewer cancer clients visited the centre in 2014/2015 as compared to 2012/2013. In 2014/2015, clients were more frequently women, relatives and older patients, got therapy longer time after medical diagnoses, with more unknown prognosis. The measures led to delay in seeking psycho-oncological care. Clients in 2014/2015 evaluated more negatively their treatment compared to 2012/2013, regarding information about therapy, participation in choosing fitting therapy, and the counselling in general. Separately evaluation of the individual, cognitive behavioural and therapy gave identical results. 1.4 Conclusions: Psycho-oncological care became less accessible due to higher cost, as a result of national legislation policy and financial cuts in healthcare insurance. European studies should be promoted to increase insight into changing national financially thresholds for seeking psycho-oncological care.

Objective: Ovarian cancer is the fifth-most common cause of cancer-related death in women. As a result of these high mortality rates, ovarian cancer fulfils some of the criteria necessary for early detection and for introduction of population screening: It is an important health problem, and early detection is associated with improved outcomes. However, there are no safe methods for early diagnosis nor any accepted screening programmed for ovarian cancer. Experimental data indicated that the detection of volatile organic compounds released by various cancer cells may be useful in diagnosing cancer.
Methods: We constructed an electronic nose that is adapted in a number of ways to analyses volatile organic compounds (VOCs) from blood.
Results: A statistical analysis of the detected signals from 165 patients showed an AUC 95% with CI of 0.9559- 0.9929. The sensitivity was 92% and the specificity was 93%.
Conclusion: This device is the first clinically useful tool for the early diagnosis of ovarian carcinoma. The operation of the instrument is based on the accurate detection of specific VOC: s from blood that are characteristic of ovarian carcinoma.

To determine whether mitochondria are involved in cross-resistance to docetaxel and X-rays in radioresistant cancer cells, ρ0 cell lines were established. As with radioresistant cells, a reduction in mitochondrial membrane potential in ρ0 cell lines compared with the corresponding ρ+ cell lines was confirmed. As expected, ρ0 cells were resistant to single-dose X-rays and docetaxel, as compared with the corresponding ρ+ cells. However, at 2 Gy/ day, all ρ0 cells died out after exposure to fractionated X-rays. Therefore, mitochondria may not be involved in the radioresistance of cancer cells against fractionated radiation therapy.

Objective: Osteosarcoma (OS) is highly metastatic and the most common primary malignant bone tumor. Hypoxia and CXCR4-overexpression in OS may play a role in resistance to radiotherapy. Using a metastatic OS mouse model, we investigated whether combining radiotherapy with a stroma-modifying drug (the angiotensin receptor 1 blocker losartan) and an anti-metastatic agent (the CXCR4 inhibitor AMD3100) is an effective OS treatment strategy.
Material and Methods: A highly metastatic, CXCR4-overexpressing Os-P0107 cell line was used to generate subcutaneous isografts in syngeneic C3Hf/Sed mice. When the tumors reached 6 mm in diameter, we treated the mice with either losartan (40 mg/kg body weight, gavage), AMD3100 (AMD, 5 mg/kg body weight, i.p.), or a combination of both drugs daily for 14 days, with 20 Gy local irradiation (IR) on day 7. We evaluated the tumorgrowth delay (TGD), distant metastases and host survival, as well as tumor vascular perfusion and tumor hypoxia.
Results: Treatment with IR, Losartan+IR, or AMD+IR resulted in a significant and comparable TGD (12 to 20 days) in Os-P0107 tumors versus the controls (all p<0.01). However, only the combination of Losartan+AMD+IR significantly enhanced tumor response to radiation by increasing TGD (additional 12 days, Losartan+AMD+IR vs. IR p=0.0215), decreasing distant metastasis (p=0.008), and increasing survival (p=0.025). Losartan treatment significantly increased CD31 positive tumor vascular density and decreased pimonidazole positive (hypoxic) areas (Percentage of CD31 and Pimo positive area; Losartan vs. Control, both p<0.01).
Conclusion: The combination of Losartan+AMD+IR significantly increases the efficacy of radiotherapy in a highly metastatic OS mouse model. The therapeutic effects are most likely due to the targeting both of tumor hypoxia and CXCR4 by losartan and AMD3100 with local irradiation. Our finding strongly suggests that losartan and AMD3100 with radiotherapy could be a potential new strategy for clinical metastatic OS treatment.