Radiation and Cancer Research

Thermal and nonthermal effects of radiofrequency on living state and applications as an adjuvant with radiation therapy Andras Szasz Journal of Radiation and Cancer Research 2019 10(1):1-17 One of the most frequently applied bioelectromagnetic effects is the deep heating of living species with electromotive force energy. Despite its long history, hyperthermia is a rarely applied oncotherapy because of controversial results and complicated control. The challenge in clinical studies of oncological hyperthermia is the disharmony of the local response and local control with overall survival. Both whole-body (complete isothermia for the body) and local (isothermia for the chosen target) heating show excellent local effects; however, this is not followed with the expected elongation of survival time. A possible solution could be nonisothermal heating to the heterogeneity of the malignancy itself. The distinguishing parameters to select the target are the electromagnetic properties of the malignant tissue together with the physiological differences between malignant cells and their healthy counterparts. Selection could allow for cellular targeting, generating natural reactions, such as programmed cell death (apoptosis) followed by immunogenic cell death involving extended immune reactions. This complex method is a new kind of hyperthermia, named modulated electrohyperthermia (tradename oncothermia). The selective, nonequilibrium energy absorption is well synergized with modern radiation therapies, presenting a solution of an active and controllable tumor-specific immune reaction and subsequent abscopal effects.

Retrospective analysis to assess the effect of hyperthermia along with radiotherapy on the outcomes of treatment in locally advanced carcinoma cervix Vibha Saluja, Rohit Dusane, Nagraj Huilgol Journal of Radiation and Cancer Research 2019 10(1):18-23 Aims: The present study was aimed to assess the impact of Hyperthermia along with Radiotherapy on the outcomes of treatment in locally advanced carcinoma cervix. Materials and Methods: Present study is a retrospective analysis of cancer cervix patients treated with radiotherapy and hyperthermia+/- chemotherapy from Jan 2012 to Jan 2018. Total twenty patients were included in this study. Among Twenty patients 12 patients received (HT+RT) while 8 patients received chemotherapy along with hyperthermia and Radiotherapy, (HT+RT+CT). All patients received EBRTdose 50 Gy in 25 fractions and 5 weeks. All patients were prescribed once a week or twice a week hypertermia for 5 weeks along with radiotherapy. Boost was given to primary disease either via brachytherapy or EBRT. Results: Complete response observed 75% of patients in RT+HT group. Similarly in RT+HT+CT group also 75% patients had complete response. Mean overall survival of 46.98 months with a median follow up time of 22 months. On univariate analysis significant impact of Hyperthermia fractions with (Hazard Ratio = 6.426 (95% CI 1.06 – 38.80), P value = 0.021) and radiation boost with (Hazard Ratio = 4.32 (95% CI 0.86 – 21.48), P value = 0.049) observed. On multivariate near about significance for Hyperthermia Fractions once a week as compared to twice a week (Hazard Ratio = 20.08 (95% CI 1.33 – 303.74), (P value = 0.030). Four patients developed pelvic recurrence. Mean recurrence free survival was 41.17 months. Kaplan Meier survival analysis was used as univariate analysis. P- value < 0.05 considered statistical significant. Conclusion: Combination of hyperthermia and radiotherapy shows better over all survival and hyperthermia is good option in patients with locally advanced carcinoma cervix who are not eligible for chemotherapy.

High-dose interstitial brachytherapy for accelerated partial-breast irradiation in clinical practice: Preliminary results from a tertiary cancer center in India Vijay Palwe, Prakash Pandit, Rajnish Nagarkar, Nishtha Paleja Journal of Radiation and Cancer Research 2019 10(1):24-26 Introduction: Over the past several years, there has been growing interest in the use of accelerated partial-breast irradiation (APBI) as an alternative to whole-breast radiation in properly selected patients. The use of multicatheter interstitial brachytherapy (MIB) for APBI is increasing due to better availability of expertise and experience than other forms of APBI. The use of APBI outside the framework of a clinical trial has markedly increased. We report the efficacy and safety of APBI through high-dose-rate (HDR) MIB for early-stage breast cancer. Materials and Methods: Between 2008 and 2017, 20 prospectively selected patients with early-stage breast cancer received APBI using MIB following breast-conserving surgery. The mean age was 62.85 years (range: 41–80). Mean size of the tumor was 2.04 cm. The dose of 34 Gy in 10 fractions given twice daily (3.4 Gy) over 5 days was delivered to the tumor bed plus a 2-cm margin. The mean follow-up was 57.75 months (range: 12–100). Ten (50%) patients received adjuvant chemotherapy. Thirteen (65%) patients received hormonal therapy. Results: A total of 18 (90%) patients reported having excellent-to-good cosmesis, while 2 (10%) had fair-to-poor cosmesis. All patients (100%) were clinically controlled at follow-up, i.e., no locoregional recurrence. Only three (15%) had distant metastasis on follow-up. Conclusion: APBI using HDR-MIB was associated with excellent local control, acceptable toxicity, and cosmesis for early-stage breast cancer patients.

Water-soluble version of SCR7-pyrazine inhibits DNA repair and abrogates tumor cell proliferation Monica Pandey, Vidya Gopalakrishnan, Hassan A Swarup, Sujeet Kumar, Radha Gudapureddy, Anjana Elizabeth Jose, Supriya V Vartak, Robin Sebastian, Mrinal Srivastava, Bibha Choudhary, Mantelingu Kempegowda, Subhas S Karki, Sathees C Raghavan Journal of Radiation and Cancer Research 2019 10(1):27-43 Aim: Mammalian DNA Ligases play pivotal role in processes such as DNA replication, recombination, and repair, which qualifies them as potent therapeutic targets to eradicate cancer cells. Recently, we have identified a small molecule inhibitor, SCR7 and its oxidized form SCR7-pyrazine (2-mercapto-6,7-diphenylpteridin-4-ol) (SCR7-P), which can inhibit nonhomologous end-joining (NHEJ) in a Ligase IV-dependent manner. In the present study, we describe a water-soluble version of ligase inhibitor, sodium salt of SCR7-P (Na-SCR7-P) and its anti-tumor effects. Materials and Methods: Water soluble version of SCR7-P was synthesised. To study the inhibitory effect of Na-SCR7-P on ligases, we did in vitro DNA end joining assays using double strand DNA substrates. For this, different concentrations of Na-SCR7-P was used along with purified ligases or cell-free extracts. Further, cytotoxicity induced by Na-SCR7-P was evaluated through trypan blue exclusion assay, JC-1 assay and cell cycle analysis. Anti-tumor activity of Na-SCR7-P was investigated in Swiss albino mice and its off-target effects were studied by conducting kidney and liver test and histological evaluation. Further, the anti-angiogenic effect of the compound was studied using in ovo chorioallantoic membrane assay. Results: Na-SCR7-P inhibited NHEJ in a Ligase IV-dependent manner. However, unlike SCR7 and SCR7-P, it blocked joining catalyzed by all three ligases in vitro, making it an ideal cancer therapeutic agent, as it may target multiple DNA transaction processes within the cancer cells. Na-SCR7-P decreased mitochondrial membrane potential (MMP) leading to cell death in cancer cells. Importantly, the administration of Na-SCR7-P led to a significant reduction in tumor growth from 12th day of treatment, and its impact was significantly higher than previously described SCR7, which targets Ligase IV within cells. Antitumor activity of Na-SCR7-P in mice resulted in enhanced lifespan, with minimal side effects. In addition, the in ovo chorioallantoic membrane assay revealed potent antiangiogenic property of Na-SCR7-P. Conclusion: Our results suggest that Na-SCR7-P can target NHEJ and other DNA repair pathways by disrupting Ligase mediated joining and can potentially be used as a strategy for cancer treatment, owing to its water solubility.

Early and late changes in radiation-induced gene expression arrays following radioprotection with amifostine Thomas M Seed, Vijay K Singh, Briana K Hanlon Journal of Radiation and Cancer Research 2019 10(1):44-57 Aims and Objectives: The study objective was to investigate differential gene expression in lymphohematopoietic tissues (spleens) of mice injected with amifostine and exposed to sublethal doses of 60Co γ-radiation. Materials and Methods: Differential cDNA gene expression arrays were used to examine early- (1 day) and late-occurring (63 days) changes in C3H/HeN mice that were administered either amifostine (100 mg/kg) or vehicle 30 min prior to exposure. Results: Sublethal irradiation initiated both early- and late-arising gene responses that were both specific and global in nature, with some significantly modified by amifostine. Of the early changes, ~15% of the genes were upregulated, whereas a comparable fraction was downregulated by irradiation. Notably, amifostine prophylaxis resulted in significant dampening of irradiation-related gene activity. Late-occurring changes were characterized by a reduction in fractional size (~11%) of upregulated genes, along with a corresponding increase of the downregulated fraction (~17%). Again, amifostine prophylaxis resulted in a significant dampening of gene activity, but only for downregulated genes. A cohort of pr oto-oncogenes responded comparably to the entire group of arrayed genes but with several notable exceptions. Differences in gene expression induced by sublethal whole-body radiation exposure were observed here within the splenic tissues of mice, and amifostine prophylaxis significantly altered patterns of gene expression within a sizable fraction of the arrayed genes. Conclusion: This study continues to illustrate the utility of differential cDNA array assays in identifying and dissecting critical gene events (e.g., hematopoietic growth factors and associated proto-oncogenes) altered by irradiation and by the radioprotective pharmacologic amifostine.

Protective action of picroliv isolated from Picrorhiza kurroa against radiation clastogenecity on mice and cyclophosphamide-induced cytotoxicity in Allium cepa Root Papiya Bigoniya, Ankita Warathe, Chandra Shekar Singh Journal of Radiation and Cancer Research 2019 10(1):58-65 Objective: Wide-scale cell death, following chemo and radiation therapy, is a major concern in clinical therapy of cancer. The need to identify agents with a potential for chemo and radioprotective potential has assumed great importance. The study aims at the evaluation of the efficacy of picroliv, a potent antioxidant derived from the plant Picrorhiza kurroa, as cyto- and radioprotector. Materials and Methods: Picroliv was fed to mice in a dose of 20 and 30 mg/kg, i.p. daily for 15 days following 4 Gy gamma rays exposure. Body weight, mortality, and hematology were assessed along with endogenous spleen colony-forming unit (CFU) and micronucleus (MN) scoring. In vitro cytoprotective activity was assessed on Allium cepa root meristem growth parameters against cyclophosphamide-induced genotoxicity by determination of mitotic index (MI) and chromosome aberrations (CA). Results: Picroliv treatment resulted in reduced body weight loss, recovery of hematological parameters, increased CFU preservation, and reduced MN expression. Picroliv caused an increase in root length and number of A. cepa simultaneously exposed with cyclophosphamide. Cyclophosphamide-induced cellular damage as measured by MI, and CA was significantly less. Picroliv at 10 mg/ml concentration showed normal dividing cells with few fragments, and sticky chromosome reversing the severe cytotoxicity of cyclophosphamide expressed with chromosome fragmentation, vagrant, sticky, and C-anaphase chromosomes. Conclusion: The results of this study strongly suggest picroliv to be a promising agent for ameliorating injury, following radiation and chemotherapy. The potent antioxidant, hepatoprotective, and immune-modulatory properties of picroliv may be responsible for the apparent cyto- and radioprotective activity.

Investigation of radon concentrations and effective radium content in soils and dwellings of Wolaita Sodo Town, Ethiopia Nigus Maregu, Lingerew Nebere, Natnael Abeje, Belachew Dessalegn, Tamirat Yibka Journal of Radiation and Cancer Research 2019 10(1):66-71 Background: People in the world have always been exposed continuously to natural radionuclides originated from the Earth's crust. Radionuclide of terrestrial origin like radon is the most abundant in the environment and the second leading cancer risk next to cigarette. Objectives: The purpose of this study was to investigate the radon concentration and effective radium content in soil samples and dwellings of Wolaita Sodo town, Ethiopia. Materials and Methods: A total of 35 soil samples and 24 records in dwellings were collected. The radon concentrations and effective radium content in soil samples and dwellings were estimated using LR-115 plastic track detector and alpha spectroscopy, respectively. Results: The result shows the concentrations of radon gas and effective radium content in soil samples ranges from 74.74 to 436.97 Bq/m3 with an average value of 221.4 Bq/m3 and 89.30–522.07 Bq/kg with an average value of 264.54 Bq/kg respectively. While radon in dwellings ranges from 30.78 to 708.12 Bq/m3 with an average value of 236.72 Bq/m3. Conclusion: Generally, the average radon concentration both in soil samples and dwellings of the area was higher than the recommended level by the International Commission on Radiation Protection.

A survey on urban adult addiction pattern Shradha G Jaiswal, Digpal Dharkar, Rajeev Shrivastav Journal of Radiation and Cancer Research 2019 10(1):72-76 Introduction: Oral cancer is a multifactorial disease, which is largely preventable. Awareness about cancer and its risk factors and symptoms can lead to prevention and early clinical diagnosis. Proper monitoring of the high-risk population along with periodic follow-up and deaddiction protocol can help reduce the incidence of oral cancer and lead to an early clinical diagnosis. Materials and Methods: A pretested questionnaire was the primary tool of the study. It had a total of 24 questions which were divided into three categories which would analyze the awareness, habits, and symptoms. Results: We found a statistically significant correlation between habits and symptoms and also between habit, age, and awareness. Conclusion: The study emphasizes the need for improving awareness and self-assessment of oral symptoms for early detection of precancerous lesions.

Harnessing heat for diagnosis and therapy Nagraj Gururaj Huilgol Journal of Radiation and Cancer Research 2019 10(1):77-78 Hyperthermia is an important adjunct to radiation therapy and chemotherapy. Heat includes in cellular organelle, cell membrane and vasculature. The changes can't be measured and imaged using magnetic resonance imaging. Currently, MRI thermometry is available while cellular and structural changes following heat for the purpose of diagnostics and prognostication needs further exploration. MRI- can be developed for theranostics.

Comments on "Thyroid nodule prevalence among young residents in the evacuation area after fukushima daichi nuclear accident: Results of preliminary analysis using the official data" Christoph Reiners, Ausrele Kesminiene, Joachim Schüz Journal of Radiation and Cancer Research 2019 10(1):79-80