Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics.

The implication of the let-7 family in cancer development is multifaceted. The family acts as tumor suppressor miRNA although overexpression of let-7 has also been described in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). The aim of this study includes whether different expression levels of let-7d has an influence on chemo- and radiosensitivity. FaDu cell line models with a gradually increased level of let-7d (models from A to E) were generated with the lentiviral system. Expression levels of pluripotency, chemo-radioresistance/apoptosis, and targets of mRNAs were analyzed by real-time reverse transcription-PCR (qRT-PCR). Radiosensitivity was analyzed using a clonogenic assay after irradiation. Response to cisplatin, 5-FU, doxorubicin, and paclitaxel was done with MTT assay. Statistically significant decrease of K-RAS (p = 0.0369) and CASPASE3 (p = 0.0342) were observed with the growing expression level of let-7d. Cisplatin, 5-FU and doxorubicin caused similar decreased of cell survival with the increase of let-7d level (p = 0.004, post-trend p = 0.046; p = 0.004, post trend p = 0.0005 and p<0.0001, post trend p = 0.0001, respectively). All models were resistant to paclitaxel, irrespective of let-7d expression levels. Only two of the generated models (A and C) were radiosensitive (p = 0.0002). CONCLUSION: the above results indicated that the level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics.

Carcinogenesis Induced by Low-dose Radiation.

BACKGROUND: Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure. CONCLUSIONS: Understanding the molecular mechanisms of response to low dose radiation is crucial for the proper evaluation of risks and benefits that stem from these exposures and should be considered in the radiotherapy treatment planning and in determining the allowed occupational exposures.

Influence of the type of imaging on the delineation process during the treatment planning.

AIM: The aim of this study was to compare the intra- and interobserver contouring variability for structures with density of organ at risk in two types of tomography: kilovoltage computed tomography (KVCT) versus megavoltage computed tomography (MVCT). The intra- and interobserver differences were examined on both types of tomography for structures which simulate human tissue or organs. MATERIALS AND METHODS: Six structures with density of the liver, bone, trachea, lung, soft tissue and muscle were created and used. For the measurements, the special water phantom with all structures was designed. To evaluate interobserver variability, five observers delineated the structures in both types of computed tomography (CT). RESULTS: Intraobserver variability was in the range of 1-14% and was the largest for the liver. The observers segmented larger volumes on MVCT compared with KVCT for the trachea (79.56 ccm vs.74.91 ccm), lung (87.61 vs. 82.50), soft tissue (154.24 vs. 145.47) and muscle (164.01 vs. 157.89). For the liver (98.13 vs. 99.38) and bone (51.86 vs. 67.97), the volume on MVCT was smaller than KVCT. The statistically significant differences between observers were observed for structures with density of the liver, bone and soft tissue on KVCT and for the liver, lung and soft tissue on MVCT. For the structures with density of the trachea and muscles, there were no significant differences for both types of tomography. CONCLUSIONS: During the contouring process the interobserver and intraobserver contouring uncertainty was larger on MVCT, especially for structures with HU near 80, compared with KVCT.