International Journal of Radiation Research
Volume:17 Issue: 1, Jan 2019

Humans are exposed to ionizing radiation from different sources that include natural, occupational, medical, accidental exposures. Evaluation of the effect of low level of neutron exposure to human cells in vitro has important implications to human health. Attempts were made to measure genome damage, transcriptional profile of DNA damage response and repair genes in peripheral blood mono-nuclear cells (PBMCs) exposed to different doses of  neutron irradiation (241Am-9Be source) in vitro. Blood samples were collected from six random, healthy individuals with written informed consent. The frequency of micronuclei (MN), nucleoplasmic bridges (NPB), DNA strand breaks and gamma-H2AX foci intensity were measured in PBMCs exposed to low doses of neutron (3.0 to 12mGy). Transcription profile of ATM, P53, CDKN1A, GADD45A, TRF1, TRF2, PARP1, NEIL1, MUTYH, APE1, XRCC1, LIG3, FEN1 and LIG1 were analysed in PBMCs at 30 min and 4h post-irradiation using real time quantitative PCR. Our results revealed a significant increase (P≤0.05) in the frequency of MN at 9.0 and 12.0mGy as compared to control. A dose dependent increase in the percentage of DNA in tail and an increased intensity of gamma-H2AX foci were observed. CDKN1A and GADD45A showed marginal up-regulation at 30 min, whereas PARP1 showed increased expression at 4h post-irradiation across the doses studied. The present study revealed that GADD45A, CDKN1A and PARP1 can be used as early signatures for low-dose neutron exposure. However, further in vitro and in vivo studies are required to establish its implications in radiation protection science.

Accumulating reports suggest that the biological effects of low- and high- dose ionizing radiation (LDIR and HDIR) are qualitatively different and might cause different effects in human skin. To better understand the potential risks of LDIR, we analyzed three cDNA microarray datasets from the Gene Expression Omnibus database. A pathway analysis showed that genes in immune-associated pathways were upregulated while those in cancer-associated pathways were downregulated in skin exposed to LDIR as compared with non-irradiated control skin. Consistently, according to a comparative gene ontology analysis, “antigen presentation and processing” was the most different gene ontology between the LIDR and HDIR transcriptomes. To identify key molecules regulated by LDIR, we constructed a protein-protein interaction network analysis using topological metrics. One of the key molecules with a high network scores was E1A binding protein p300 (EP300), which is a potential target of a new therapeutic strategy to promote anti-tumor immunity. Our results showed that LDIR exposure mainly induced the upregulation of immune-related genes including chemokines (CXCL1, CXCL2, and CXCL5) and interleukins (IL1B, IL11, IL6, IL15, and IL7). Additionally, LDIR induced the upregulation of antigen processing and presentation-related genes including CIITA, HLA-DQB1, and KIF26A, but these genes were downregulated in HDIR-exposed skin. Our protein network interaction results indicated that EP300 is downregulated by the immune response in skin after LDIR exposure.

Cancer stem-like cells (CSCs) play a crucial role in the initiation, progression, and recurrence of cancer. Evidence indicates that the high linear energy transfer (LET) carbon ion beam is more effective against CSCs than the conventional X-ray beam. Carbon ion radiotherapy is considered as a promising cancer strategy, however, information about whether, or not, new CSCs are induced after carcinoma cells exposed to carbon ions is limited and incomplete. The selected A549 cells, derived from a single colony with low CD133 expression, were irradiated by high LET carbon ion beam or low LET X-ray, and then the cell clonal survival fraction, CD133+ expression subpopulations and soft agar colony formation potential were detected. The cell-killing ability of carbon ions was higher than that of X-rays. The fractions of CD133+ or Oct4+ high expression cells increased in a dose-dependent manner at 12 h after both X-ray and carbon ion exposure. Compared to that of carbon ion irradiation, the efficiency of transformation in a cell colony was higher in the X-ray irradiation group after 30 d; however, the amount of colonies with higher fractions of CD133+ expression cell subpopulation in the carbon ion irradiation group was more than that in X-ray irradiation treatment group after 30 and 50 d. Our results indicate that, although high-LET radiation kill more cells including cancer stem-like A549 cells, it may induce more stable stem cell-like colonies than low LET radiation.

Radiotherapy and adjuvant androgen deprivation therapy have historically been the first treatment choices for prostate cancer but treatment resistance often limits the capacity to effectively manage the disease. Therefore, alternative therapeutic approaches are needed. Here, the efficacies of radiotherapy and targeting the pro-survival cell signaling components epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and mammalian target of rapamycin (mTOR), with their respective inhibitors are compared. The cytotoxic effects of inhibitors of PI3K and mTOR (NVP-BEZ235) and EGFR (AG-1478), and X-rays, were evaluated in prostate cell lines (LNCaP: cancer; DU145: cancer; BPH-1: benign prostatic hyperplasia; 1542N: apparently “normal”) using a colony forming assay. The cells were exposed to a range of X-ray doses or varying concentrations of the inhibitors, to obtain cell survival curves from which relative sensitivities (RS) of the tumor cell lines were derived as the ratio of their sensitivities to that of the “normal” cell line. The LNCaP cells trended to be more sensitive to X-rays and AG-1478 exposure than 1542N cells, with RS-values of 1.65±0.48 (P=0.1644) and 1.37±0.22 (P=0.0822), respectively. NVP-BEZ235 emerged as very cytotoxic in all tumor cell lines, yielding RS-values of 3.69±0.83 (DU145; P=0.0025), 8.80±1.73 (LNCaP; P<0.0001), and 8.76±1.70 (BPH-1; P=0.0011). These findings demonstrated that targeted therapy, specifically that using NVP-BEZ235, might result in a more effective treatment modality for prostate cancer than conventional radiotherapy.

All To enhance the curative effect of radiotherapy, we established a radio-resistant cell line, CNE-2R from CNE-2, a radio-sensitive type of CNE, through repeated irradiation. The developed cell line provides a basis for further studies on the radio-resistance of CNE and the molecular mechanism of radiotherapy sensitization drugs. The CNE-2 cell line was selected and exposed repeatedly to high-dose X-ray intermittent irradiation (6 Gy/fraction for seven fractions and 20 Gy/fraction for three fractions). After the entire irradiation process, 20 Gy/time was administered to CNE irregularly. The cell growth curves of CNE-2 and CNE-2R were constructed based on MTT assays. Dose-survival curves were obtained through colony-forming tests and subjected to linear quadratic formulation matching. SF2 and correlation parameters of radiation biology were calculated. Changes in the cell cycle of CNE-2 and CNE-2R were also assessed by serum starvation. The doubling time of CNE-2 was 2.4 days, which is 0.4 days shorter than that of CNE-2R, indicating the faster growth rate of CNE-2. In the dose-survival equation of the survival clone test, the sensitization ratio of CNE-2R was enhanced relative to that of CNE-2. After synchronization and desynchronization for 24 h, G1 was arrested in CNE-2R. In the S phase, which is insensitive to radiation, the ratio of G1 increased, hence altering the cell cycle. We have established a radio-resistant nasopharyngeal carcinoma cell line by repeated exposure to radiation which is relevant to changes in the cell cycle.

People are exposed to more radiation than before with the application of radiation technology. Radiation is known to induce damage to cell structure, DNA, chromosomes and nucleus. In this study, we showed that CGJ extract can inhibit radiation-induced chromosomal damage in vivo and NLRP7 inflammasome activation in vitro, suggesting that the compound from CGJ can Be considered as a therapeutic materials to reduce adverse effect inflammation and chromosome aberration during radio-therapy. In this study the inhibitory effects of Cheonggukjang (CGJ) extract on the radiation-induced micronucleus formation in vivo and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in vitro. We observed the prolonged presence of radiation-induced inflammation and its onsecutive damage in hematopoietic tissues after irradiation by examining micronucleus formation in polychromatic erythrocytes. Mouse bone marrow-derived macrophages were used to investigate NLRP3 inflammasome activation. The micronucleus analysis with mouse peripheral polychromatic erythrocytes using acridine orange staining showed a significantly (p<0.05) reduced frequency of micronucleated bone marrow polychromatic erythrocytes (MnPCEs) in CGJ-treated mice. CGJ extract elevated the chance that mice would survive a potentially lethal dose of gamma-irradiation. Additionally, The CGJ extract attenuated IL-1β maturation by interrupting the inflammasome. The CGJ extract attenuates radiation-induced micronucleus formation possibly mediated by inhibiting inflammasome, which provides valuable information for the further study of the mechanism of action of CGJ extract.

The development of methods to alleviate radiation-induced health effects is important for the practical use of radiation therapy and for understanding the molecular mechanisms mediating these effects. Here, we examined the protective capability of N-acetylcysteine (NAC) on life-shortening effects induced by continuous low dose-rate gamma-ray exposure in mice. Female B6C3F1 mice were exposed to gamma-rays for 400 days at a dose rate of 20 mGy/day beginning at 8 weeks of age. Control unexposed mice and exposed mice were divided into two groups; the first was provided with regular water, and the second was administered 40 mM NAC during the exposure period. Although NAC administration did not affect the life span of non-irradiated mice (p = 0.232), a 59-days life extension was observed in the exposed group (p = 0.0177). Moreover, radiation exposure and NAC treatment affected body weight. The reduction of body weight observed in NAC treated mice was associated with a reduction in water intake. Our data demonstrated that the life-shortening effects of chronic low dose-rate radiation exposure in mice were alleviated by NAC administration.

Electromagnetic radiation (EMR) is responsible for many hazardous impacts on living organisms. We aimed to investigate the effects of EMR on kidney tissue in rats in order to predict possible effects on human kidneys and to study the radioprotective effect of ferulic acid (FA). Six rats were used as controls, six rats were used as treated group with FA, six rats were used as irradiated group and six rats were given both FA and exposed to EMR.  Blood samples were taken from the heart forIL6, IL10 and TNF-α analysis in the sera, and a part of rat kidneys was homogenized for analysis of total antioxidant capacity (TAC) and lactate dehydrogenase (LDH).Another part of kidney tissue was used for histopathological studies. Irradiated rats showed a significant increase in the level of renal markers (urea and creatinine) and inflammatory markers (IL6, IL10 and TNFα) However, these effects were ameliorated in the group which was exposed to EMR and treated with ferulic acid (FA + EMR). TAC and LDH measured in kidney tissues were significantly decreased in irradiated rats and in FA+ EMR treated group, while significantly increased in FA treated group. According to our biochemical and histopathological findings, administration of FA reduced the renal injury effects of EMR.

To evaluate impact of spironolactone (S) on pulmonary toxicity of concomitant use of thoracic radiotherapy (RT) and trastuzumab (T).  Eighty rats were divided into eight groups: group (G) 1 was control group; G2, G3 and G4 were RT, S and T groups; G5, G6, G7 and G8 were RT+T, T+S, RT+S and RT+T+S groups respectively. Rats were sacrificed at 6 hour, 21 and 100 day after RT and lung samples were retrieved. By 100th days of RT inflammation score, lung fibrosis score and TGF- expression were significantly different within study groups (p values were 0.002, 0.001 and 0.043 respectively). Inflammation score of G8 was significantly lower than inflammation scores of G2 and G5 (p values: G2-G8= 0.004, and G5-G8=0.022). Inflammation score of G2 was significantly higher than G7 (p=0.028). There were significant differences regarding to fibrosis scores between G2-G8 (p=0.015), G2-G7 (p=0.017) and G5-G8 (p=0.011). TGF-β expression was higher in both G2 and G5 when compared to G8 (p = 0.038). Our results suggested that S is an effective treatment option for improving radiation-induced pulmonary fibrosis. These findings should be clarified with further preclinical and clinical studies.

Exposure to ionizing radiation is inevitable. Using of low-level laser therapy (LLLT) stimulates tissue repair and reduces inflammation. The objective of the present study aimed at evaluating the therapeutic efficacy of Helium-Neon (He-Ne) laser in stimulating the reparative processes in the liver of mice after whole body gamma-irradiation (WBγ-I). Two hundred and sixty four female mice were divided into 6 groups: Control, Laser irradiated,  One shot gamma irradiated group, One shot + laser irradiated, Cumulative gamma irradiated and Cumulative + laser irradiated. Ionizing radiation was performed using a Cesium-137 source. Two modes of exposure were used, 1- Mice were irradiated with a single shot sublethal dose of 5 Gy. 2- The same dose was given in fractionated mode daily installations of 1 Gy. Laser treatment was carried out using a computerized scanner emitting He-Ne (CW). The assessment of serum transferases (AST & ALT) was performed along with histopathological (HP) assessment of liver biopsies.  There was a significant increase in serum transaminases above the control levels in gamma irradiated groups. Laser therapy of these groups was accompanied by a significant decrease in the elevated levels of transaminases. HP changes in the liver of the shot gamma-irradiated group showed that the main brunt  of damage was on the liver cells. Meanwhile, in the cumulative gamma-irradiated group the main brunt was on the vascular system including the central veins and the portal blood vessels. It could be concluded that mice exposed to WBγ-I suffered from aggravated HP changes in the liver tissues accompanied by disturbances in the level of liver enzymes. These undesirable alterations were ameliorated by the treatment of the experimental mice by He-Ne laser before being irreversibly damaged.

The International Commission on Radiological Protection (ICRP) has attributed the same relative risk for X and gamma radiations of all energies. Several studies have proven that the biological effect of low energy photon is more than that of higher ones. The assessment of risks is important due to the wide use of low energy X-rays for mammography screening and other diagnostic applications.  Five X-ray beam qualities characteristics according to ISO-4037 and consultative committee of ionizing radiation (CCRI) were studied in details. In pilot study made to investigate the minimum dose that cause measurable biological effects, one hundred male albino rats were equally divided into five groups namely A, B, C, D and E. Group A was used as control while animals of other groups were whole body exposed to different radiation doses from 137Cs γ-rays. For studying the biological effect energy dependency, eighty male albino rats were equally divided into 8 groups namely F, G, H, I, J, K, L and M.  Group F was used as control and was not exposed to any type of radiation while animals of other groups were whole body exposed to the same dose of radiation but at different dose rates and different energies. Blood samples were collected and serum samples were separated for further biochemical investigations. Biochemical investigations for blood sera included alanine aminotransferase (SGPT), aspartate aminotransferase (SGOT), blood urea nitrogen (BUN), creatinine (CREA), calcium (Ca++) and Creatine phosphokinase (CPK) level.  The results showed remarkable variation of the measured biochemical parameters levels with different photon energies that reflect the energy dependency of the investigated parameters. It’s clear from the data that the same absorbed dose delivered to the exposed animals induces different effect according to the used photon energy. Low energy X-rays were found to be more biologically effective than higher ones.

Breast-conserving surgery (BCS) followed by radiotherapy (RT) is the standard of care for women with breast cancer. Evidence shows that RT dose to the heart can result in ischemic heart disease. In this study we compared 3 different RT techniques were for heart, left anterior descending coronary artery (LAD) and lung doses in left breast cancer patients after breast-conserving surgery. Three different plans were designed for each patient using conventional tangential fields, 6+18 MV combination beams, and field-in-field (FIF) technique. These were compared in terms of doses to the planning target volume (PTV), ipsilateral lung, heart and LAD. Forty left breast cancer patients were included in this study. Mean PTV V95% was 95.74% for conventional, 90.45% for FIF and 87.89% for 6+18 MV combination beams (p<0.05). Mean left lung dose was 11.22 Gy for FIF, 12.25 Gy for 6+18 MV and 12.95 Gy for conventional technique (p<0.05). Mean heart dose was 4.52 Gy for FIF, 4.85 Gy for 6+18 MV and 5.13 Gy for conventional technique (p<0.05), and mean D2% for LAD was 40.06, 43.43 and 45.25 Gy (p<0.01) in FIF, 6+18 MV and conventional techniques, respectively. These results indicated that FIF and 6+18 MV combination techniques significantly reduced the doses received by the heart, LAD and left lung compared to conventional tangential fields, while FIF was superior to 6+18 MV considering the above-mentioned variables. The lower doses to the organs at risk were achieved with a small but statistically significant loss in PTV coverage.

This paper presents a method to reduce radiation exposure during mammography by analysing the doses to ipsilateral and contralateral breasts and to adjacent organs by evaluating material-dependent shielding performance.  Six target-filter combinations (Mo-Mo, Mo-Rh, Rh-Rh, Rh-Mo, W-Mo, W-Rh) were tested by measuring the doses delivered to the breasts and adjacent organs, with the contralateral (opposite side) breast shielded. The shield was designed to have a simple (┓,┎) shape for ease of use in actual clinical settings, using lead, copper, bismuth, and barium sulphate (BaSO4) as materials for shield configuration. The dosimetric data revealed that the highest absorbed dose was exhibited by the target filter combination of Rh/Rh, followed by W/Rh, W/Mo, Rh/Mo, Mo/Rh, and Mo/Mo. Additionally, the radiation dose was reduced by 54–55%, with the average absorbed dose on the contralateral breast reduced from 0.655 to 0.359 mGy. All four shielding materials used in the experiments were analysed for the shielding effect.   This Using a shield during screening mammography would alleviate concerns about the mammography-induced risk of breast cancer and secondary effects.

During intensity modulated radiation therapy (IMRT) technique, theoretically, presence of flattening filter (FF) across the beamline of clinical linear accelerator (linac) is not essential to obtain uniform lateral profiles due to intensity modulation of photon beams by multileaf collimators (MLCs). The aim of this study was to investigate the dosimetrical properties of 18 MV photon beam-Varian linac with and without FF. All dose measurements were performed on 18 MV, FF mode-Varian 2100C/D linac. The FF and flattening filter free (FFF) modes of linac were modeled by MCNPX 2.4. code. The photon and contaminant electrons spectra, dose rate, present depth doses (PDD), lateral dose profiles, total and collimator scatter factors and out of field doses were calculated and compared with and without FF. Removing the FF increased the photon and contaminant electron fluences by factors of 5.48 and 3.94 for a 5 × 5 cm2 field size, respectively. The surface dose increased up to 155%. The flatness of dose profile was disturbed and deteriorated with increase of field size. Despite the dependence of the total scattering factor on field size, the variation of collimator scattering factors was neglected. The out-of-field dose decreased about 81.5 % for a 5 × 5 cm2 field size. Removing FF from the linac head increases the dose rate and decreases the out-of-field dose, but the increased skin dose and deteriorated flatness of lateral dose profile are the main disadvantages of the FFF mode.

The aim of this study was to measure and determine diagnostic reference levels (DRLs) of programs used at intraoral and dent panoramic examinations in Kosovo. To determine DRL, were performed measurements for dose area product (DAP) at intraoral and dental panoramic radiology systems. This study has covered over 47% of X-ray units, which are in use for intraoral and panoramic imaging examinations on the country.  From results, we conclude that, the mean of DAP (mGy cm2) for single intraoral examination is 26.8, 29.6 and 39.7 for incisor, premolar and molar, respectively. Therefore the mean of DAP (mGy cm2) value for panoramic dental radiology is 62.7, 74.1 and 90.3 for child, adult and large adult, respectively. For each modality mention above are proposed specific DRLs. Recommended DRLs value for intraoral radiography for incisor, premolar and molar programs are: 28.5, 36.5 and 50.3 mGy cm2, respectively. Also, DRLs for dental panoramic radiography for child, adult and large adult programs are: 73.0, 81.0 and 93.0 mGy cm2, respectively. A better quality assurance (QA) and quality control (QC) should be enforcement. For strengthening of QA and QC engagement of radiographers and Medical Physicist is mandatory.

All human beings and living organisms are exposed to natural radiations on daily basis, which is mainly due to the activity concentration of primordial radionuclides 232Th, 238U and their products of decay together with the natural radionuclide 40K present in the earth’s crust. A total of 59 soil samples were collected around the banks and surroundings of the Lancaster dam using an auger at a depth of about 0.75 meters from the top surface. The samples were analysed using low background co-axial n-type High Purity Germanium (HPGe) detector of high-resolution and the resulting spectrum were analysed using Canberra Genie software. This study revealed that the activity concentration values are in the order of 232Th <40K<238U in all sampling sites. A statistical analysis based on Pearson correlation showed a positive correlation between the radiological parameters and the two primordial radionuclides 232Th, 238U and the natural radionuclide 40K. This implied that the two primordial radionuclides 232Th, 238U and their products of decay including the natural radionuclide 40K contribute to the emission of gamma radiation in all the locations of the study area. The calculated 238U/232Th concentration ratio in soils of present study was almost six times higher compared with different countries of the world.

One of the most significant radionuclides in natural drinking waters is 226Ra and its decay products. It is potential of health problems, including cancer risk. In this study, the effect of 226Ra concentration in 28 drinking water samples collected from the North Guilan province was investigated. The activity concentrations of 226Ra were measured by using of radon emanation method and Pylon AB-5 radon scintillation detector. The annual effective dose distribution by age groups, radiological risk and chemical toxicity risk were calculated in drinking water.   The activity concentration results range from a low limit of detection (LLD) 2.0±0.1 mBq l-1 to 38.2±2.4 mBq l-1. Also, the annual effective dose distribution by age groups estimated results were from 1.8×10-6 Sv y-1 for adults to 1.5×10-5 Sv y-1 for infants.  The radiological risk assessment results were 1.06×10-6 to 2.03×10-5 for morbidity risk, 7.32×10-7 to 1.40×10-5 for mortality risk. The chemical toxicity risk results obtained from 1.08×10-1 to 5.63×10-3. The activity concentration level of 226Ra in all drinking water samples were less than the recommended level WHO for drinking water 1000 mBq l-1. Meanwhile, annual effective dose level, cancer morbidity, mortality risk and life annual daily dose due to consumption of selected drink water samples were less than the standard limit.

Man-made  radionuclides, which are present in environment, have been created by human activities and added to the inventory of natural radionuclides for example 3H, 131I, 129I, 137Cs, 90Sr and 239Pu, in spite of the amount added is little compared to natural quantities. The aim of this study is to estimate the levels of radiological doses in the soil samples collected from different locations in Kerbala city, Iraq. Thirty soil samples were collected from different sites of Karbala city and gamma-ray spectroscopy system with NaI (Tl) "1.5×2" detector in low-background and 24 hours used to achieve the results.  The average values of absorbed gamma-ray dose rate, annual effective dose equivalent and annual gonadal dose equivalent were found to be 14.09±0.32, 19.59±0.39 and 112.81±2.25 respectively. The average values of gamma representative level index and external hazard index resulting from natural radionuclides for all samples in the study area were 0.25±0.005  and 0.09±0.002 respectively. The obtained results in current work were compared with some results of soil samples in literature over the world. They do not exceed the upper limit calculated by UNSCEAR reports.

To investigate a method for standardizing intensity modulated radiation therapy (IMRT) optimization for nasopharyngeal carcinoma (NPC), in order to reduce the influence of subjective factors. This study is based on example IMRT plans for NPC, which were randomly divided into data acquisition and data verification groups. Organs at risk (OARs) were analyzed for various sub-organs. The data acquisition group was used for statistical evaluations of the mean value of the normalized mean doses of sub-organs. The data validation group was used to validate the findings. Significant negative correlations were observed between the normalized mean doses of sub-organs for each OAR and the shortest distance between sub-organs and the target region surface. For each OAR, there was no statistically significant difference in the normalized mean doses of sub-organs between the data acquisition and verification groups (p > 0.05). The influence of subjective factors can be reduced by using the normalized mean doses of sub-organs for each OAR as the evaluation parameter for standardizing. This method is relatively simple; a majority of radiotherapy centers can apply the model for standardizing IMRT planning optimization based on the existing planning system.

Malignant pleural effusion is common in patients with advanced malignant tumor. The aim of this study is to analyze the characteristics of pleural metastasis of renal clear cell carcinoma, pleural effusion under medical thoracoscopy and the diagnostic value of interventional thoracoscopy-guided biopsy, and to improve the understanding of pleural metastasis of renal clear cell carcinoma. 3 cases with pleural metastasis of renal clear cell carcinoma in our hospital were reported. The clinical characteristics and performs were retrospectively analyzed. In addition, a complete resection of tumor nodules was conducted by applying interventional electric knife and cryotechnique with thoracoscopy. Three cases were all male and presented as dyspnea. By thoracoscopy testing, main lesions showed different size and amount nodules, and pleural thickening and congestion. Tumor tissues had abundant blood supplying and were crisp. Bleeding was easily caused in forcep biopsy, while complete resection of nodules could be achieved by an electric knife, and a larger number of samples were obtained. To our knowledge, pleural metastasis of renal clear cell carcinoma and formation of pleural effusion are rarely in clinic, most of whom are in male and presented as dyspnea. Medical thoracoscopy can directly displaying thoracic lesions and biopsy of adequate tissue through interventional techniques, which is important in the diagnosis pleural metastasis of renal clear cell carcinoma.