Radiation and Cancer Research

DNA-Dependent protein kinase in DNA damage response: Three decades and beyond Yoshihisa Matsumoto, Mukesh Kumar Sharma Journal of Radiation and Cancer Research 2020 11(4):123-134 Ionizing radiation exerts various biological effects, including cell killing and carcinogenesis, mainly through generating damage on DNA. Among various types of DNA damage, DNA double-strand break (DSB) is considered the most deleterious and most intimately related to biolog?ical effects of radiation. DNA-dependent protein kinase (DNA-PK), consisting of DNA-PK catalytic subunit and Ku80-Ku70 heterodimer (Ku), is activated upon binding to the end of double-stranded DNA and acts as the molecular sensor for DSB. While DSB is repaired mainly through homologous recombination and nonhomologous end joining in eukaryotes, DNA-PK is shown to be essential in the latter pathway. Moreover, DNA-PK is reported to be capable of phosphorylating a number of proteins, suggesting versatile functions of DNA-PK in cellular response to DSB. Here, we review the advance in our understanding on DNA-PK in three decades and remaining problems.

An approach to cancer amid COVID-19 pandemic – Radiation oncologists perspective Shaqul Qamar Wani, Talib Khan, Fir Afroz Journal of Radiation and Cancer Research 2020 11(4):135-139 The background of this article is to provide a general information regarding the safety of the patients and health-care workers besides providing management guidelines for cancer patients in the current context of COVID 19 (SARS CoV-2) crisis. The treatment recommendations are prioritized as per the risk stratification till the current crisis is mitigated. The recommendations not only provides information in dealing with different malignancies treated either with curative or palliative intent but also ascertains the role of electronic media as an effective source of communication with patients whether on active or pending treatment or on follow-up, so that their anxiety levels and mental fears regarding their disease and future management plans amid COVID-19 pandemic are minimised.

The tubarial glands: Discovered but not defined – A narrative review Tarun Kumar Suvvari, Nithya Arigapudi Journal of Radiation and Cancer Research 2020 11(4):140-141 A pair of salivary glands, named as tubarial glands, was found between the nasal cavity and throat, i.e., at the nasopharynx's lateral walls, overlaying the torus tubarius by the Netherlands Cancer Institute while working on radiation toxicity among prostate cancer patients. The tubarial glands were identified using prostate-specific membrane antigen imaging using positron emission tomography coupled with computed tomography, which is used to detect the spread of prostate cancer. The anatomy, physiology, oncological study of the glands, and data's interpretation and limitations from the research to date have been discussed.

Complexity of chromosomal aberrations and gene expression changes in human blood lymphocytes after exposure to alpha particle radiation Karthik Kanagaraj, Vasumathy Rajan, Badri N Pandey, Perumal Venkatachalam Journal of Radiation and Cancer Research 2020 11(4):142-149 Background: Targeted alpha therapy (TAT) is emerging as an effective treatment modality of cancer especially for micrometastasis, lymphoproliferative malignancies, and palliative approaches of bone cancer. Human blood lymphocytes may encounter alpha (a) exposure while traversal of targeted a particle emitting radio isotopes to the tumor site, due to their nonspecificity and release of radio isotopes from the legends used for targeting. Such radiation effects to lymphocytes may be implicated in short and long term health effects during TAT. Aims and Objectives: To see the effects of a-particle in blood lymphocytes and to compare their complexity of aberration with both and X-rays. Materials and Methods: Chromosomal aberrations such as dicentric chromosome, micronuclei, nucleoplasmic bridge (NPB) in the peripheral blood lymphocytes were scored for both a alpha particle and X rays. Then, the chromosome aberrations (CA) frequency was correlated with the gene expression (FDXR, CDKN1A and GADD45A) to both the type of radiations. Results: CA induced by a radiation was complex and highly dispersed when compared to low LET radiation. Moreover, magnitude of NPB was significantly higher in case of a radiation than radiation. A dose dependent increase in gene expression (FDXR, CDKN1A and GADD45) was observed after a radiation, which however, was higher in case of a radiation than X rays. Conclusion: These results provide better understanding about effects of a radiation on human lymphocytes, which may be significant implications in developing better TAT strategies for cancer.

Activation of epidermal growth factor receptor/insulin-like growth factor 1 receptor-β-Catenin-CD44 pathway in periampullary cancer Biswabandhu Bankura, Suvendu Maji, Balarko Chakraborty, Neyaz Alam, Chinmay Kumar Panda Journal of Radiation and Cancer Research 2020 11(4):150-156 Background: Periampullary cancer (PC) is a global medical burden. Less than 5% of patients experience an overall survival of 5 years or more. The study aims to analyze the importance of epidermal growth factor receptor (EGFR)/insulin-like growth factor 1 receptor (IGF1R)–beta-catenin (β-catenin)–CD44 pathway in the development of periampullary cancer of Indian patients. Subjects and Methods: Expression profile of EGFR, IGF1R, β-catenin, and CD44 was verified by immunohistochemical analysis in primary tumor samples (N = 14) and respective adjacent normal tissues. Results: In periampullary carcinoma patients, a high level of EGFR expression was seen in 64% of the samples along with co-expression of IGF1R in 77.8% of samples. Furthermore, the high expression of EGFR and IGF1R significantly correlated with the increased expression of β-catenin along with CD44 expression of the tumors. Conclusion: The EGFR/IGF1R–β-catenin–CD44 pathway seems to be important in the development of PC with clinical importance.

Clinical and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status correlation study in breast cancer patients: An experience from a tertiary care center Rashmi Singh, Anup Kumar, Rajanigandha Tudu, Praveer Kumar Singh Munda Journal of Radiation and Cancer Research 2020 11(4):157-160 Background: Breast cancer is usually a systemic disease with outcomes dependent on various factors. We present here our departmental retrospective data of 74 breast cancer patients treated between January 2016 and October 2017, with a focus on various prognostic and predictive factors. Materials and Methods: Patients' details were retrieved from departmental case records regarding age, menopausal status, tumor size (T), axillary lymph node status (N), grade, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her2) status. Using SPSS software version 20.0, cross-tabulation, the Chi-square test, and Spearman correlation were applied where appropriate. Results: The median age of patients was 48.75 ± 11.08 years with more patients in premenopausal age (54.1%). Stage III was the most common presentation (66.2%). In addition, Grade 3 in tumor was most common (51.4%). ER(+), PR(+), and Her2(+) cases were 58.1%, 52.7%, and 28.4%, respectively. Nearly 29.7% of patients were triple negative. Grade of the tumor correlated significantly with tumor size and lymph node staging (P = 0.002). In addition, ER and PR expression was correlated with each other (P = 0.000). Conclusions: Advanced stage, higher tumor grade, and high prevalence of Triple-negative breast cancer in our patients are poor prognostic and predictive factors. Higher tumor grade is correlated with increased T and N staging, and tumor ER and PR expressions were correlated with each other.

DNA damage and survival in bystander human intestinal cells treated with conditioned medium from tritium-labeled cells Manjoor Ali, Vasumathy Rajan, Badri Narain Pandey Journal of Radiation and Cancer Research 2020 11(4):161-166 Background: Tritium exposure could be one of the radiation hazards in case of accidental exposure with intestine as one of the major target organs. In the cells, low-energy beta emitted from tritium would traverse a very short distance (a few microns). Hence, the intestinal epithelial cells with nuclear localization of tritium would exert its radiobiological effect also through bystander mechanism. In the present study, the effect of conditioned medium obtained from tritiated thymidine-labeled human normal intestinal epithelial (INT407) cells was studied on respective bystander cells in terms of magnitude of survival and induction of DNA damage. Materials and Methods: The survival and proliferation of bystander INT407 cells treated with control/irradiated conditioned medium were studied using clonogenic and 5-bromo-2-deoxyuridine (BrdU)-labeling assays. The magnitude of DNA double-strand break was measured by immunofluorescence of η-H2AX by confocal microscopy. Intracellular nitric oxide (NO) in these cells was measured using 4,5-diaminofluorescein diacetate fluorescent dye. Results: Bystander cells treated with conditioned medium from tritiated thymidine-labeled cells showed increased clonogenic survival and BrdU labeling. Cells labeled with tritiated thymidine showed attenuation of η-H2AX foci at longer period (24 and 48 h) of labeling than at 15 h. Moreover, the bystander cells treated with irradiated conditioned medium showed a higher magnitude of η-H2AX foci at 24 h. However, compared to 24 h, 48-h treatment of irradiated conditioned medium resulted in a decrease in η-H2AX foci in the bystander cells. Increased level of intracellular NO was observed in the bystander cells treated with irradiated conditioned medium. Conclusions: Bystander cells treated with conditioned medium obtained from tritiated thymidine-labeled cells showed increased clonogenic survival and proliferation, which was correlated with an increase in DNA double-strand break and NO production in these cells.

Management and outcome of extraosseous ewing's sarcoma family tumors treated at a tertiary care center in North East India: A retrospective analysis Mouchumee Bhattacharyya, Partha Pratim Medhi, Apurba K Kalita, Faridha Jane R M Momin, Subhalakshmi Saikia, Manoj Kalita, Rakesh Mishra, Ghritashee Bora, Shashank Bansal Journal of Radiation and Cancer Research 2020 11(4):167-173 Introduction: Extraosseous Ewing's Sarcoma is rare, aggressive malignant soft-tissue tumors treated similar to Ewing's sarcoma of bone. This study evaluates the clinicopathological pattern, treatment and outcomes of localized extraosseous Ewing's sarcoma family tumors (ESFTs) treated with an uniform treatment regimen. Materials and Methods: This is a retrospective single institution study where we evaluated the hospital records of localized extraosseous ESFT treated between January 2011 and December 2018. Fifteen patients were found eligible for analysis. Patient demographics, management details, and outcomes were analyzed statistically. Time to event was measured from the date of diagnosis and survival curves were estimated by Kaplan–Meier method with Log-rank test for comparison. Results: The median follow-up of the cohort was 17 months (range: 3–81 months). The mean age of patients was 14.4 years and the average tumor size was 9.92 cm. Two-thirds of the patients received definitive radiotherapy as the local treatment with 93.3% patients receiving induction chemotherapy. The 5-year local control rate, progression-free survival, and overall survival (OS) were 80%, 53.3%, and 46.7%, respectively. On univariate analysis, tumor size <8 cm and good response to chemotherapy were associated with significantly improved OS (P = 0.049 and 0.04, respectively), while local control rates were better for patients receiving radiotherapy dose 54 Gray and above (P = 0.044). Conclusion: The optimum management of extraosseous ESFT consists of multimodality therapy with multidrug chemotherapy, surgery, and radiotherapy. Localized tumors of <8 cm size with favorable response to induction chemotherapy have the best prognosis.

Carcinoma glottis with parotid metastasis U Suryanarayan, Shah Aastha Ashokkumar, Isha Shah, Rajal Shah Journal of Radiation and Cancer Research 2020 11(4):174-177 Introduction: Glottic carcinomas represent approximately one third of the laryngeal cancers. True glottis includes both true vocal cords including anterior and posterior commissures. True vocal cord are as such devoid of lymphatics, so the chances of lymph node metastasis as such is very low. The chances of distant metastasis is also very rare. Herein we report a case of glottic cancer metastasising to parotid gland. Case report: A sixty eight year old male non smoker reported to our department with complaint of change of voice since three months. On computed tomography scan of head and neck, soft tissue thickness of about seven millimeter was seen over right true and false vocal cord and 2.3 * 1.9 cm lesion was seen involving the left lobe of the parotid gland. MRI of neck and paranasal sinuses was performed immediately following tomography which showed 2.6*1.9*3.1 cm lesion was seen involving deep lobe of left parotid gland which appeared isointense on T1w, hyperintense on T2w, not suppressed on STIR. There was no any evidence of capsular breach. Seven millimeter thickness was seen over right true and false vocal cord. These findings were further confirmed by direct laryngoscopic examination which showed mucosal irregularity over right true and false vocal cord with normal mobility of both vocal cords and punch biopsy was taken from it which came out to be well differentiated squamous cell carcinoma. Ultrasonography guided biopsy was taken from the deep lobe of the left parotid gland which came out to be metastatic squamous cell carcinoma. Patient was offered curative radiotherapy to a dose of 55 Gy in 20 fractions and the parotid lesion was addressed by parotidectomy, which showed no evidence of malignancy which might be considered to be an abscopal effect. Conclusion: The involvement of the parotid gland in case of glottic cancer is a very rare occurrence.

Dosimetric evaluation of hippocampus incidental radiation dose in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy Tony Jacob, Donald Fernandes, MS Athiyamaan, B Sandesh Rao, Sharaschandra Shankar, MS Vidyasagar, V Mohsina Journal of Radiation and Cancer Research 2020 11(4):178-182 Background: The incidental radiation exposure to hippocampus during radiation therapy for nasopharyngeal cancers may contribute to short-term toxicity like disequilibrium and lack of inhibition and also to long-term memory loss. Objective: To diametrically evaluate the dose received by hippocampus in patients with nasopharyngeal cancer undergoing intensity-modulated radiotherapy (IMRT). Materials and Methods: Eleven patients with histologically proven locally advanced nasopharyngeal squamous cell carcinoma were retrospectively analyzed in this study. The total prescribed dose to the planning target volume was 70 Gy (D95%) delivered in 2 Gy daily fractions using IMRT technique. Employing the anatomical guidelines and magnetic resonance imaging coregistration, the hippocampi were delineated on axial imaging from the simulation computed tomography scan for each patient. IMRT treatment plans were generated without applying dose–volume constraints to the hippocampus. Maximum hippocampus dose, mean hippocampus dose, minimum hippocampus dose, and hippocampus volume receiving 3 Gray dose (V3Gy) were analyzed. Results: The mean hippocampus volume was 4.7 cm3. The average minimum dose to the entire hippocampus was 5.276 Gy (range, 0.072–18.609 Gy); the average maximum point dose to the hippocampus was 21.405 Gy (range, 0.595–59.832 Gy); and the average mean dose to the entire hippocampus volume was 10.922 Gy (range, 0.194–34.706 Gy) and V3Gy was 79.15 Gy (range, 0%–100%). Conclusion: The dosimetric analysis suggests that patients who underwent IMRT for nasopharyngeal cancer received significantly high incidental dose to the hippocampus. The study creates awareness regarding the need to routinely delineate hippocampus as an organ at risk in the radiotherapy for nasopharyngeal cancers.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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