Browsing by Author "Çelik, ÖK"

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    Prognostic factors in definitive radiotherapy of uterine cervical cancer
    Yalman, D; Aras, AB; Özkök, S; Duransoy, A; Çelik, ÖK; Özsaran, Z; Haydaroglu, A
    Purpose: To determine the prognostic factors related to local control and survival in 257 patients with uterine cervical cancer treated with definitive radiotherapy (RT). Materials and Methods: The medical records of 257 patients treated with definitive RT from January 1987 to December 1998 were reviewed retrospectively. Pretreatment and treatment parameters were analyzed to determine their prognostic value on local control and survival. Survival analyses were performed using the Kaplan-Meier method. The log-rank test was used for univariate analyses and the Cox regression model was used for multivariate analyses. Results: Median age was 55 (range 25-82). Squamous cell carcinoma was the most common histologic type (89.1%). The distribution per FIGO Stage was IIA: 13.2%; IIB: 54.9%; IIIA: 3.9%; IIIB: 19.8%; IVA: 8.2%. Ninety-eight patients (38.1%) were treated with external RT alone; 134 (52.1%) received both external RT and intracavitary brachytherapy; 21 (8.2%) received external RT and chemotherapy and four (1.6%) received external RT, intracavitary brachytherapy and chemotherapy. Median follow-up duration was 50 months (range 24-155 months). The failure rate was 51.8% with 26.5% of patients having only local failure, 16.7% only distant failure and 8.6% both local and distant failure. Five-year local progression-free, disease-free and overall survival rates were 58.1%, 44% and 63.7%, respectively. In univariate analysis the prognostic factors identified for local progression-free survival were histology (p = 0.008), FIGO stage (p < 0.001), initial hemoglobin (Hgb) level (p = 0.001), total radiation dose (p = 0.039), use of brachytherapy (p = 0.001) and of chemotherapy (p = 0.037) and enlarged paraaortic nodes (p = 0.016). In multivariate analysis the prognostic factors were FIGO stage (p = 0.014), initial Hgb level (p = 0.040), and use of brachytherapy (p = 0.013). The prognostic factors identified for disease-free survival were histology (p = 0.011), FIGO stage (p < 0.001), initial Hgb level (p < 0.001), use of brachytherapy (p = 0.001) and of chemotherapy (p = 0.014) in univariate analysis; and FIGO stage (p < 0.001), initial Hgb level (p = 0.017), total tumor dose (p = 0.034), use of brachytherapy (p = 0.006) and of chemotherapy (p = 0.021) in multivariate analysis. Factors influencing overall survival were FIGO stage (p < 0.001), initial Hgb level (p = 0.006), overall treatment time (p = 0.028), total tumor dose (p = 0.007), use of brachytherapy (p < 0.001), enlarged paraaortic (p < 0.001) and pelvic nodes (p = 0.004) in univariate analysis; and FIGO stage (p < 0.001), overall treatment time (p = 0.031), enlarged paraaortic (p = 0.007) and pelvic lymph nodes (p = 0.043) in multivariate analysis. Conclusion: Definitive RT is an effective treatment for patients with uterine cervical cancer. There are many prognostic factors influencing treatment outcome. Brachytherapy and chemotherapy must be added in appropriate patients to improve the outcome. Future prospective trials should be undertaken to confirm the validity of these factors and to individualize the treatment strategy for every patient.
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    Current treatment approaches in locally advanced prostate cancer: a radiation oncologist perspective
    Çelik, ÖK
    Patients with locally advanced prostate cancer generally have a significant risk of disease progression and cancer-related death if left untreated. Curative RT combined with HT is the main treatment modality for these patients. Modern radiotherapy techniques, such as IMRT should be used in prostate cancers and this should combined with some form of image guided RT in order to visualize and correct the organ movement in real time. IMRT allows dose escalation for the target volume, produces sharp dose gradient around the target volume and enables radiation oncologists to increase radiation doses homogeneously within the target volume without exceeding the tolerance doses in organs at risk. A minimum dose of >= 74 Gy RT kombined with long-term HT is recommended for disease control.
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    Mitophagy in the A549 lung cancer cell line, radiation-induced damage, and the effect of ATM and PARKIN on the mitochondria
    Kurtman, C; Öztatlici, M; Üçöz, M; Çelik, ÖK; Sokur, I; Özbilgin, MK
    Background: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer, and radiotherapy (RT) is used for the cancer therapy. RT affects DNA and causes DNA double-strand breaks which are repaired by DNA repair protein ataxia telangiectasia mutated (ATM). RT also affects the mitochondria which is a key player in mediating the radiation response in tumors and removing damaged mitochondria through mitophagy. During mitophagy, PARKIN accumulates on defective mitochondria to mediate the clearance of damaged mitochondria. This study examines the effect of radiation on mitophagy using PARKIN and ATM antibodies on the human NSCLC A549 line. Materials and Methods: A549 cells were treated with 2, 4, 6 and 8 Gy of radiation were analyzed on days 1 and 3 after a single dose of radiotherapy. PARKIN and ATM expressions of A549 cells were examined by using immunohistochemical technique. Results: In the control groups, weak immunoreactivity of ATM and PARKIN was observed on both days 1 and 3. The most intense ATM expression was seen in the 6 and 8 Gy groups after day 1. The most intense PARKIN expression was seen after the days 1 and 3 in the 2 Gy groups. PARKIN immunoreactivity decreased due to increasing radiation dose. Conclusion: It must be considered that mitophagy mechanisms are activated in RT applications. It must be considered that the activation of mitophagy mechanisms in RT and A549 lung cancer cell lines may provide hemostasis in cancer cells. Molecules targeting mitophagy must be developed for use with radiotherapy.