Evaluation of Predictive and Prognostic Importance of Lung Immune Prognostic Index in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The systemic inflammatory response (SIR) is known as an important factor associated with tumorigenesis and tumor progression, and can be reflected by inflammatory markers. One of the markers that reflect this is the lung immune prognostic index (LIPI). It is based on a derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level. We aimed to investigate the significance of LIPI in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (NACRT). METHODS: In this retrospective study, we stratified the patients according to LIPI score as good LIPI and intermediate (int)/poor LIPI. According to pathological response to NACRT, we divided the patients into two groups as those with complete response (CR) or near-CR, and those with partial response (PR) or poor/no response. We classified CR and near-CR as good response. We evaluated the predictive and prognostic significance of LIPI for NACRT response, disease-free survival (DFS), and overall survival (OS) by univariate and multivariate analyses. RESULTS: We included 137 patients in the results, with 72 (52.6%) having good LIPI and 65 (47.4%) having int/poor LIPI. The median follow-up period was 44.7 months (range: 10-105 months). Thirteen patients (18.0%) in the good LIPI group and 22 patients (34.0%) in the int/poor LIPI group achieved good response. In multivariate analysis, we found only the LIPI score as an independent risk factor (hazard ratio (HR): 2.4, p = 0.04) for NACRT response. Median DFS was 89.2 months (95% CI: 11.4-167.0) in the int/poor LIPI group; however, the DFS of all study populations and patients in the good LIPI group did not reach the median value. In multivariate analysis for DFS, we identified abdominoperineal resection (APR) (HR: 2.21, p = 0.02), presence of tumor deposit (HR: 2.96, p = 0.003), and int/poor LIPI score (HR: 2.07, p = 0.02) as separate risk variables. OS of all study populations and the patients in the LIPI groups did not reach the median value. In multivariate analysis for OS, we identified APR (HR: 2.74, p = 0.02), surgical margin positivity (HR: 12.94, p < 0.001), and adjuvant CT (HR: 0.20, p = 0.002) as separate risk variables for OS. CONCLUSION: This is the first study investigating the predictive and prognostic significance of LIPI in LARC patients treated with NACRT. The results revealed that int/poor LIPI was associated with a higher rate of good response but shorter DFS compared to good LIPI. The baseline LIPI score serves as an easily accessible and useful prognostic index, and it has significant potential for making appropriate treatment decisions in LARC.

Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in kidney tissue of rats.

Ionizing radiation leads to release of free radicals into the systemic circulation from irradiated tissues. These free radicals cause oxidative stress in distant organs. Oxidative status may be reversed by naturally occurring antioxidant agents. The aim of this study was to investigate protective and antioxidant effects of Nigella sativa oil (NSO) and thymoquinone (TQ) in kidney tissue of rats exposed to cranial irradiation. Forty-eight Sprague-Dawley rats were divided into six groups: IR group received irradiation (IR) to total cranium plus saline; IR plus NSO group received IR and NSO; IR plus TQ group received IR and TQ; sham group did not receive NSO, TQ or IR; control group of TQ received dimethyl sulfoxide; control group of NSO received saline. Total oxidant status (TOS), oxidative stress index (OSI) and lipid hydroperoxide (LOOH) levels were studied as oxidative parameters, and total antioxidant status (TAS), total sulfhydryl levels, paraoxonase (PON), ceruloplasmin (Cp) and arylesterase activities were determined as antioxidative parameters in the kidney tissue of rats. Kidney TOS, OSI and LOOH levels were significantly lower in IR plus TQ, IR plus NSO and sham groups compared to IR group (p < 0.001). TAS, PON and Cp activities in IR group were significantly lower compared to the control group (p < 0.001). PON and Cp activities were significantly higher in IR plus NSO and IR plus TQ groups compared to IR group (p < 0.001). In conclusion, free radicals generated by cranial ionizing radiation exposure cause oxidative stress in kidney. NSO and TQ exhibit protective and antioxidant effects against oxidative damage in rats.

Radioprotective effect of thymoquinone on salivary gland of rats exposed to total cranial irradiation.

BACKGROUND: The purpose of this study was to investigate the radioprotective effects of thymoquinone against radiation-induced damage in the salivary glands of rats exposed to total cranial gamma irradiation. METHODS: Thirty-two Sprague-Dawley rats were divided into 4 groups to test the radioprotective effectiveness of thymoquinone by intraperitoneal injection. An appropriate control group was also studied. Biochemical parameters in liver tissue of rats were determined by spectrophotometer. RESULTS: Glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), total (enzymatic plus nonenzymatic) superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), and superoxide dismutase (SOD) activities were significantly decreased, whereas xanthine oxidase, nitric oxide synthase activities, malondialdehyde, nitric oxide, and peroxynitrite levels were significantly increased in the irradiation group when compared to the control and sham control groups. CONCLUSION: Results showed that thymoquinone reduces oxidative and nitrosative stress parameters and has antioxidant effects and a free radical scavenging activity.

Radioprotective effects of Nigella sativa oil against oxidative stress in liver tissue of rats exposed to total head irradiation.

OBJECTIVE: Many cancer patients treated with radiotherapy suffer severe side effects during and after their treatment. The aim of this study was to investigate the effects of irradiation and the addition of Nigella sativa oil (NSO) on the oxidant/antioxidant system in the liver tissue of irradiated rats. METHODS: A total of 24 Sprague-Dawley rats were randomly distributed into three groups of equal numbers. The control group received neither NSO nor irradiation but received 1-ml saline orally. The irradiation group (IR) received total head 5 gray (Gy) of gamma irradiation as a single dose, plus 1-ml saline orally. The IR plus NSO group received both total head 5 Gy of gamma irradiation as a single dose and 1 g/kg/day NSO orally through an orogastric tube starting one hour before irradiation and continuing for 10 days. RESULTS: While liver tissue total oxidant status (TOS), lipid hydroperoxide (LOOH) level, and oxidative stress index (OSI) were significantly increased in the IR group compared to the control group, total antioxidant status (TAS), sulfhydryl (-SH) levels, and PON activity were significantly decreased. Cp activity in the IR plus NSO and IR groups was higher than in the control group. ARYL activity in the IR plus NSO supplemented group was higher than that in other groups. CONCLUSIONS: NSO reduces oxidative stress markers and has antioxidant effects, which also augments the antioxidant capacity in the liver tissue of rats.

Radiation-modifying abilities of Nigella sativa and thymoquinone on radiation-induced nitrosative stress in the brain tissue.

To investigate Nigella sativa oil (NSO) and Thymoquinone (TQ) for their antioxidant effects on the brain tissue of rats exposed to ionizing radiation. Fifty-four male albino Wistar rats, divided into six groups, were designed as group I (normal control group) did not receive NSO, TQ or irradiation; group II (control group of TQ) received dimethyl sulfoxide and sham irradiation; group III (control group of NSO) received saline and sham irradiation; group IV (irradiation plus NSO group) received both 5 Gray of gamma irradiation to total cranium and NSO; group V (irradiation plus TQ group) received both irradiation and TQ; group VI (irradiation alone group) received irradiation plus saline. Alterations in nitric oxide (NO·) and peroxynitrite (ONOO(-)) levels, and nitric oxide synthase (NOS) enzyme activity were measured by biochemical methods in homogenized brain tissue of rats. Levels of NO· and ONOO(-), and enzyme activity of NOS in brain tissue of the rats treated with NSO or TQ were found to be lower than in received IR alone (p<0.002) Nigella sativa oil (NSO) and its active component, TQ, clearly protect brain tissue from radiation-induced nitrosative stress.

FDG PET uptake as a predictor of pain response in palliative radiation therapy in patients with bone metastasis.

PURPOSE: To evaluate the relationship between fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) maximum standardized uptake value (SUV(max)) and pain response to radiation therapy (RT) in patients with bone metastasis. MATERIALS AND METHODS: Institutional ethical board approval for the study was obtained, with informed consent, for this prospective study. Thirty-one patients with metastatic bone pain who underwent FDG PET/computed tomography before RT were included. Patients were diagnosed with lung (n = 16), breast (n = 7), stomach (n = 2), and head and neck cancers (n = 3), as well as unknown primary tumor (n = 3). Eighty-five painful metastatic locations with FDG PET scans geographically corresponding to 40 treatment fields were evaluated. Pain scores using visual analog scale or faces pain rating scale and SUV(max) at each location were recorded. All patients were treated with a single fraction 8 Gy RT. Pain scores after RT were assessed at weeks 2, 4, 8, 12, 16, 20, and 24. The pretreatment pain scores and pain response to RT were compared with FDG PET SUV(max) of each location. Pearson correlation, independent t test, one-way analysis of variance, and χ(2) tests were used for statistical analysis. RESULTS: Median SUV(max) and initial pain scores for all locations were 7.2 (range, 1.5-22.5) and 6 (range, 2-8), respectively. Median follow-up time was 24 (range, 3-112) weeks. Median SUV(max) was 4.5 (range, 3.1-7.3), 4.75 (range, 1.5-10.3), 8.8 (range, 5.2-11.9), and 12.1 (range, 7-22.5) for pretreatment pain scores of 2, 4, 6, and 8, respectively. SUV(max) was correlated with pretreatment pain scores (P < .0001). SUV(max) and pretreatment pain scores were also significantly associated with pain response to RT. Median SUV(max) for locations with complete response, partial response, pain progression, and indeterminate response was 5.2, 9.75, 10.8, and 6.4, respectively (P ≤ .001). CONCLUSION: FDG PET SUV(max) correlated with initial pain severity and pain response to RT and can be used as a predictive factor for treatment response in patients with painful bone metastasis treated with palliative RT.