Cancer Research and Therapeutics

A comprehensive review of surgical margin in oral squamous cell carcinoma highlighting the significance of tumor-free surgical margins Mamata Kamat, Bhagawan Das Rai, Rudrayya S Puranik, Uma Vasant Datar Journal of Cancer Research and Therapeutics 2019 15(3):449-454 Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity, and surgery is the most accepted line of treatment. The surgical margins (SMs) or resection margins are boundaries of resection specimen excised by the surgeon. The status of these resected SMs is an important and valuable tool to predict the treatment outcome. It is necessary to attain optimal SM to avoid local recurrence and improve overall survival. However, the controversies exist regarding the concept of optimal SM. There are various factors that influence the assessment of the SMs. In addition, apart from routine histopathology, the molecular assessment of resected margins has recently gained value which has a promising role for margin surveillance. Furthermore, the histological and molecular appraisal of tumor-free margins is also necessary to standardize the treatment modalities. Hence, this review aims to summarize the above issues that influence the evaluation of SMs of OSCC along with recent updates. Furthermore, an attempt has been made to give an overview about future possible approaches for the tumor-free margins. An electronic search was performed for items related to the evaluation of SMs in OSCC, and the obtained articles were critically assessed and the relevant information was extracted and summarized.

Molecular characterization of metastasizing ameloblastoma: A comprehensive review Anjali P Ganjre, Gargi Sarode, Sachin Sarode Journal of Cancer Research and Therapeutics 2019 15(3):455-462 Metastasizing ameloblastoma (MA) is a very rare odontogenic tumor with 2% of incidence rate. It exhibits benign histopathological features and malignant intrinsic quality in the form of metastasis which makes it a little more than a pathological curiosity. Various molecular aspects related with malignant behavior have been discussed. Because of this, it provides a diagnostic challenge for clinicians and surgeons. It is an elusive lesion which should be more researched and studied so that definitive diagnostic features can be put forward. The objective of this paper is to review the molecular aspect involved in the pathogenesis of MA which will aid in differentiating non-MA from MA and thus helping in providing proper treatment at an early stage.

Oral submucous fibrosis: An enigmatic morpho-insight Alka Harish Hande, Minal S Chaudhary, Madhuri N Gawande, Amol R Gadbail, Prajakta R Zade, Shree Bajaj, Swati K Patil, Satyajit Tekade Journal of Cancer Research and Therapeutics 2019 15(3):463-469 Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disease affecting oral, oropharyngeal, and sometimes the esophageal mucosa. It is characterized by the progressive fibrosis of the submucosal tissue. The pathogenesis of OSMF has been directly related to the habit of chewing areca nut and its commercial preparation, which is widespread in Indian subcontinent and Southeast Asia. The areca nut has been classified as a “group one human carcinogen.” Oral squamous cell carcinoma in the background of OSMF is one of the most common malignancies in South and Southeast Asian countries. Malignant transformation has been reported in 7%–12% cases of OSMF. Histopathological spectrum of OSMF includes the apparent alterations observed in the epithelium and connective tissue. Epithelial atrophy and sometimes epithelial hyperplasia with or without dysplasia are the peculiar alterations seen in the epithelium. In the connective tissue, there is extracellular matrix remodeling which results in excessive collagenization. Further cross-linking of collagen leads to hyalinization which makes the collagen resistant to proteolysis. Owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu, that is, hypoxia. This tissue hypoxia elicits angiogenesis which may result in the malignant transformation of OSMF. Perpetual irritation of areca nut and its constituents to the oral mucosa leads to upregulation of pro-inflammatory cytokines and further juxtaepithelial inflammation. Thus, these coordinated reactions in epithelium and connective tissue leads the OSMF toward malignant transformation.

Kilovoltage cone-beam computed tomography imaging dose estimation and optimization: Need of daily cone-beam computed tomography Gaurav Trivedi, Chandra K Dixit, Arun S Oinam, Rakesh Kapoor, Amit Bahl Journal of Cancer Research and Therapeutics 2019 15(3):470-474 Aim: The aim of the present study was to access the need of daily cone-beam computed tomography (CBCT) and the requirement of in-house protocols of image acquisition frequency to reduce unnecessary exposure to the patients undergoing radiotherapy treatment. Materials and Methods: The dose delivered during CBCT procedure (On-Board Imager, Trilogy, Varian medical system, Inc., Palo Alto, California) was assessed for pelvic and head and neck region. For dose estimation, cylindrical polymethyl methacrylate phantoms of 15 cm length, 16 cm, and 32 cm diameter were used to simulate the patient's head and neck and pelvic region thickness, respectively. More than 10 cm scatterer was added on either end of this phantom. Calibrated Ionization chamber DCT10 LEMO SN 1685 iba, dosimetry, Germany (10 cm active length) was used to measure the dose Index. The doses known as cone-beam dose index (CBDI100) were estimated for all the scanning protocols (kV and mAs setting) available on the machine. In this study, image acquisition frequency to correct the setup error was optimized. In-house protocol for image acquisition frequency during treatment has been suggested to reduce the dose. It was based on the principle of as low as reasonable achievable. Results: Optimized dose protocol observed was the “standard dose head” for which the CBDI100 was 2.43 mGy. Whereas for pelvic imaging, single protocol of 125 kV, 80 mA was available by which a dose of 7.61 mGy is likely to be received by the patient during scan. Maximum shift of 6 mm in lateral direction was observed to the patient of Pelvis region and 5 mm was observed in the longitudinal direction for the H and N patients. Angular shift measured in patient position was 3.8° and 3.1° for H and N and pelvic region, respectively. Conclusion: Three consecutive-day CBCT-imaging at the beginning of the treatment followed by once weekly CBCT and two-dimensional (2D) imaging in remaining days of treatment can be an optimized way of imaging for the patient having malignancy in the region of pelvic and abdomen. For H and N, once in a week, CBCT with standard dose head protocol, followed by 2D-imaging in remaining days can be an optimized way of imaging.

Optimization of low-energy electron beam production for superficial cancer treatments by Monte Carlo code Rana Akbarpoor, Navid Khaledi, Xufei Wang, Farhad Samiei Journal of Cancer Research and Therapeutics 2019 15(3):475-479 Context: Low energy electron beam has been being used widely for superficial cancer treatments. In the current study a design for production of very low energy electron beam, by different thickness of Perspex spoilers, is presented that may be used for skin cancer. Aims: MCNPX Monte Carlo code was used for modeling and simulations in the current study. An energy spoiler Perspex was modeled for degrading 4 MeV electron beam of Varian 2300 CD Linac. Materials and Methods: The thicknesses of 3, 7, and 10 mm were applied before electron applicator at a distance of 42 cm from phantom surface. Dosimetric properties of new electron beams including Rp, Dmax, E0, as well as the penumbra of the beam were investigated. Results: For the 3 mm spoiler, the superficial beam output decreased to 77%, and the Dmax, R90, R50, and RP were shifted to the depths of 4, 6, 9, and 12 mm, respectively. While for 10 mm filter the results were 5.2, 3.0 and 5.0 mm for R90, R50, and Rp, respectively. In addition, the surface dose was 93% and the Dmax was shifted to the depth of 1mm for the 10mm Perspex spoiler slab. Conclusions: The presented beam provides a novel surface dose, Dmax, and RP which can be applicable for treatment of skin cancers with minimum dose to the beyond normal tissues.

Development of α-tocopherol surface-modified targeted delivery of 5-fluorouracil-loaded poly-D, L-lactic-co-glycolic acid nanoparticles against oral squamous cell carcinoma Saurabh Srivastava, Shalini Gupta, Shadab Mohammad, Irfan Ahmad Journal of Cancer Research and Therapeutics 2019 15(3):480-490 Objective: The aim of the study to develop surface modified targeted moiety α-tocopherol (α-t) encapsulated with 5-fluorouracil (5-FU)-poly-D, L-lactic-co-glycolic acid nanoparticles (PLGA NPs) toward the anticancer activity against oral squamous cell carcinoma (OSCC). Materials and Methods: 5-FU was conjugated with the polymer, PLGA by ionic cross-linking and α-tocopherol use as a functionalized surface moiety. Characterization, drug entrapment efficiency, and in-vitro drug release system were optimized at different pH 7.4 and pH 4.5. The in-vitro cell was performed to optimize the anticancer activity through MTT assay and apoptotic staining assay was also performed by flow cytometry to evaluate the cellular apoptotic activity and cellular uptake. Results: The particle size was distributed within an average range of 145–162 nm, the polydispersity index values lie 0.16–0.30, and the surface charge was at the negative side, –17mV to –23mV. The in vitro drug release system showed more sympathetic situation at pH 7.4 as compared to pH 4.5, for targeted NPs, approximately 86% and 69%, respectively. The non-targeted 5-FU-PLGA NPs showed drug release of 83% and 64% at pH 7.4 and 4.5 subsequently. In vitro anticancer activity confirmed the intense inhibition by α-t-FU-PLGA NPs of 79.98% after 96 h treatment of SCC15 cells and confirmed the steady-state inhibition of 83.74% after 160 h incubation in comparison to 5-FU-PLGA NPs. Subsequently, the early apoptosis, 27.98%, and 16.45%, and late apoptosis, 47.29%, and 32.57%, suggested the higher apoptosis rate in targeted NPs against OSCC. Conclusions: The surface modified α-t-FU-PLGA NP was treated over SCC15 cells, and the oral cancer cells have shown the high intensity of cellular uptake, which confirmed that the target moiety has successfully invaded over the surface of cancer cells and shown advanced targeted delivery against OSCC.

A Monte Carlo study on dose perturbation due to dental restorations in a 15 MV photon beam Mona Azizi, Ali Asghar Mowlavi, Mehdi Ghorbani, Courtney Knuap, Marziyeh Behmadi Journal of Cancer Research and Therapeutics 2019 15(3):491-497 Aim: The main purpose of this study is to evaluate the effect of dose perturbation due to common dental restoration materials in the head and neck radiotherapy with a 15 MV external photon beam. Setting and Design: Teeth with three dental restorations such as tooth filled with Amalgam, Ni-Cr alloy, and Ceramco were simulated by MCNPX Monte Carlo code. In this simulation, the dental materials were exposed by a 15 MV photon beam from a Siemens Primus linac, inside a water phantom. Materials and Methods: A Siemens Primus linear accelerator and a phantom including: tooth only, tooth with Amalgam, tooth with Ni-Cr alloy, and tooth with Ceramco were simulated by MCNPX Monte Carlo code, separately. The percentage dose change was evaluated relative to dose in water versus depth for these samples on the beam's central axis. The absolute dose by prescription of 100 cGy dose in water phantom at 3.0 cm depth was calculated for water, tooth, tooth with Amalgam, tooth with Ni-Cr alloy, and tooth with Ceramco. Results: The maximum percentage dose change is related to tooth with Ni-Cr alloy, tooth, tooth with Ceramco, and tooth with Amalgam with amounts of 7.73%, 6.95%, 4.7%, and 3.06% relative to water at 0.75 cm depth, respectively. When 100.0 cGy dose was prescribed at 3.1 cm, the maximum absolute dose was 201.0% in the presence of tooth with Ni-Cr alloy at 0.75 cm. Conclusion: Introduction of the compositions of dental restorations can improve the accuracy of dosimetric calculations in treatment planning and protect the healthy tissues surrounding teeth from a considerable overdose.

Analysis of induced error by susceptibility effect in low-density gel dosimeters Farideh Pak, Vahid Vaezzadeh, Ehsan Eqlimi, Mona Mirheydari Journal of Cancer Research and Therapeutics 2019 15(3):498-503 Purpose: In low-density (LD) gel dosimeter, diffusive spin–spin relaxation rate (R2)-dispersion caused by susceptibility-induced internal gradient leads to a significant deviation in the measured R2 from the real value. In this study, the effect of induced internal gradient on R2 was visualized and quantified algebraically as an important cause of inaccuracy in LD gel dosimeters. Materials and Methods: In this method, two sets of LD and unit-density (UD) gel dosimeters were prepared. The LD gel was made by mixing the UD gel with expanded polystyrene spheres. The R2 was used to determine the spatially resolved decay rates due to diffusion in internal magnetic field. The internal gradient was calculated for a multiple spin–echo sequence. Results: It is shown that in a LD gel, the internal gradient leads to overestimation of mean R2 value (R2mean). Pixel-by-pixel R2 measurements inside a LD gel showed significant deviation from R2 mapping in UD gel. Conclusion: It appears that significant differences between R2mean in a selected region of interest and pixel-by-pixel R2 values are the main source of inaccuracy in dose mapping of a LD gel.

Improvement of dose distribution in ocular brachytherapy with 125I seeds 20-mm COMS plaque followed to loading of choroidal tumor by gold nanoparticles Mansour Zabihzadeh, Hadi Rezaee, Seyed Mohammad Hosseini, Mostafa Feghhi, Amir Danyaei, Mojtaba Hoseini-Ghahfarokhi Journal of Cancer Research and Therapeutics 2019 15(3):504-511 Aims and Objectives: Brachytherapy using removable ophthalmic plaques loaded with suitable small sealed radioactive seeds adjacent to the ocular's tumor has been widely used as an effective treatment. The aim of this study was to investigate the dose distribution in a modeled eyeball followed to loading of an ocular melanoma tumor with different concentrations of gold nanoparticles (GNPs) as dose enhancement agent by Monte Carlo (MC) calculations. Materials and Methods: The MC code of MCNPX 2.6.0 was used to modeling of COMS standard eye plaque loaded with 24 125I sources (6711 model) located on the sclera of modeled eyeball with detailed structures and materials. A choroidal melanoma tumor was simulated and loaded with different concentrations of spherical gold GNPs (50 nm in diameter). Dose enhancement factors (DEFs) of ocular components were calculated. Results: The dosimetric properties of 125I source (6711 model) and dose distribution of COMS standard eye plaque were calculated successfully as recommended by TG-43U1; AAPM. Loading of tumor with GNPs increased dose to the tumor and decreased dose to the normal tissues; the DEF was increased up to 2.280 and 2.030 for tumor apex, while it was decreased to 0.760 and 0.892 for macula and for gold-tumor mixture and nanolattice distributions, respectively. Conclusion: Loading the choroidal tumor volume with GNPs improves the dose distribution by increasing dose to the tumor and decreasing dose to the health components in ocular brachytherapy with 125I seeds 20-mm COMS plaque.

Radioprotective effect of grape seed extract against gamma irradiation in mouse bone marrow cells Reza Ghasemnezhad Targhi, Amin Banaei, Valiallah Saba Journal of Cancer Research and Therapeutics 2019 15(3):512-516 Introduction: Ionizing radiations produce free radicals which are often responsible for DNA damage or cell death. Grape seed extract (GSE) is a natural compound having an antioxidant that protects DNA, lipids, and proteins from free radical damages. In this study, radioprotective effect of the GSE has been investigated in mouse bone marrow cells using micronucleus test. Materials and Methods: Four groups of mice were investigated in this study: Mice in Group 1 were subjected to injection of distilled water with no irradiation. Mice in Group 2 were exposed to 3 Gy gamma radiation after the injection of distillated water. Mice in Group 3 were injected with 200 mg/kg of the GSE without any irradiation. In another group, mice were exposed to three gray gamma irradiation after the injection of GSE. Animals were killed, and slides were prepared from the bone marrow cells 24 h after irradiation. The slides were stained with May Grunwald–Giemsa method and analyzed microscopically. The frequency of the micronucleated polychromatic erythrocytes (MnPCEs), micronucleated normochromatic erythrocyte (MnNCEs), and polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte (PCE/PCE + NCE) ratios was calculated. Results: Injection of GSE significantly decreased the frequency of MnPCEs (P < 0.0001) and MnNCEs (P < 0.05) and increased the ratio of PCE/PCE + NCE (P < 0.0001) compared to the irradiated control group. Discussion and Conclusions: GSE could reduce clastogenic and cytotoxic effects of gamma irradiation in mice bone marrow cells; therefore, it can be concluded that the GSE is a herbal compound with radioprotective effects against gamma irradiation. Free radical scavenging and the antioxidant effects of the GSE probably are responsible mechanisms for the GSE radioprotective effects.