Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.
The respiratory gating radiation therapy which Irradiates only in the stable respiratory period with analyzing the periodic motion of a reflective marker on the patient's abdomen has been applied to the precise radiation treatment in order to minimize the effect of organ motion induced by the respiration. This respiratory gating system establishes irradiation region using the amplitude-based or phase-based method. Although phase-based method Is preferred because of the stability in the real treatment conditions, it has some limits to explain the exact correlation between the marker motion and organ motion. Even when the variation of amplitude which can introduce target motion considered as an error is produced, the phase-based method has the possibility to irradiate including the error positions. In this study, the error analysis program was developed for the verification of the tumor position's variation correlated with the variation of marker's amplitude which can be occurred during a phase-based respiratory sating treatment. The analysis program was tested with a virtual treatment record file and with a record file using moving phantom which were modified considering the irregular amplitude's variation simulating the real clinical situations. In both cases, accurate discrimination of error points and error calculation were produced. When the treatment record files of a real patient were analyzed with the program, the accurate recognition and calculation of the error points were also verified. The analysis program developed in this study will be applied as a useful tool for the analysis of errors due to the irregular variation of patients' respiration during the phase-base respiratory gating radiation treatment.
From October 1989 to March 1992, ten patients diagnosed as primary central nervous system (CNS) lymphoma were treated with radiation therapy at Asan Medical Center. To obtain pathologic diagnosis, five patients had stereotactic biopsy and the others underwent craniotomy & tumor removal. According to the classification by International Working Formulation, seven of 10 patients showed diffuse large cell types and the remaining 3 had diffuse mixed cell types. Computed tomographic scans of the brain disclosed solitary (6 cases) or multiple (4 cases) intracranial lesions. All patients received 4000 cGy/20 fx to the whole brain followed by an additional 2000 cGy/10 fx boost to the primary lesion. Six patients with initial cerebrospinal fluid (CSF involvement were treated with whole brain irradiation and intrathecal Methotrexate (IT-MTX) chemotherapy. One of them received an additional spinal irradiation after 3 cycles of IT-MTX chemotherapy because of MTX induced arachnoiditis. One patient received 3 cycles of systemic chemotherapy prior to rodiation therapy and one received 5 cycles of salvage chemotherapy for recurrence. With a median follow up time of 8 months, all patients were followed from 7 to 26 months. Radiologically seven patients showed complete remission and the remaining three showed partial remission at one month after radiotherapy. The 1 and 2 year survival rate was $86{\%}\;and\;69{\%}$ respectively. Until now, two patients expired at 7 and 14 months. These patients developed extensive CSF seeding followed by local failure. Considering initial good response to radiation therapy and low incidence of extraneural dissemination in primary CNS lymphoma, we propose to increase total tumor dose to the primary lesion by hyperfractionated radiotherapy or stereotactic radiosurgery. For the patients with CSF involvement at diagnosis, we propose craniospinal irradiation with IT MTX chemotherapy.
Berberine is an isoquinoline alkaloid used in traditional Chinese medicine and has been isolated from a variety of plants, such as Coptis chinensis and Phellodendron amurense. It has a wide spectrum of clinical applications such as in anti-tumor, anti-microbial, and anti-inflammatory activities. However, it is still unknown that berberine related with reactive oxygen species (ROS)-mediated apoptosis pathway in human hepatoma HepG2 cells. In the present study, we are examined the molecular mechanism of ROS- and p38 MAP kinase-mediated apoptosis by berberine in HepG2 cells. Berberine increased cytotoxicity effects by time- and does-dependent manner. $LD_{50}$ was detected 50 ${\mu}M$ at 48h of exposure to berberine. Nuclei cleavage and apoptotic DNA fragmentation were observed in cells treated with 50 ${\mu}M$ of berberine for 48h. Moreover, berberine induced the activating of caspase-3, p53, p38 and Bax expression, whereas the expression of anti-apoptotic signaling pathways, Bcl-2, was decreased. Additionally, berberine-treated cells had an increased level of generation of ROS and nitric oxide (NO). These results indicated that berberine induces apoptosis of HepG2 cells may be mediated oxidative injury acts as an early and upstream change, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, p38 and p53 activation, caspase-3 activation, and consequent leading to apoptosis.
Recently, there are many considerations and studies on biological effects of radiations in radiation workers, as well as in accidentally or therapeutically irradiated persons. The most practical and reliable method of dosimetry for radiation accidents is the scoring of gross chromosomal aberrations in human lymphocytes (Ydr) as a biological dosimetry. By the way, although usual doses of $^{131}I$ administered therapeutically for thyroid cancer are ranging from 100 mCi to 200 mCi, there are differences of absorbed doses and Ydr, ranging from 0.004 to 0.04, on equally administered $^{131}I$ due to variations in metabolic characteristics, stage of tumors and physical status of subjects. In this study, We exert to obtain the dose-response relationships of $^{131}I$, as a good guide to evaluating acute effects of accidental irradiations and radiation induced leukemia or solid tumor, by in vitro induction of chromosomal aberrations. we studied the relationship between radiation dose (D) and the frequency of chromosomal aberrations (Ydr) obserbed in peripheral lymphocytes that were irradiated in vitro with $^{131}I$ at doses ranging from 0.05 to 6.00 Gy. By scoring cells with unstable chromosomal aberrations (dicentric chromosomes and ring chromosomes) we obtained this linear-quadratic dose response equation Ydr=0.064351 $D^2$-0.13143 D+0.045684 This dose-response relationship may be useful for evaluating acute and chronic $^{131}I$ induced biological effects.
Some natural products are able to inhibit radiation effects and exert an antitumor effect with fewer adverse reactions; however, their antitumor effects are less than those of widely-used synthetic drugs. Propolis is a natural material that has been attracting attention, and we extracted this material with water and investigated the effect of continuous propolis administration on radioactivity-induced reduction of hemocytes, in addition to the antioxidant and antitumor effects of propolis. Following a 1-week adjustment period, water-soluble propolis was administered intraperitoneally to male ICR mice at a dose of 100 mg/kg every other day for 2 weeks. Following administration, 2 Gy whole-body irradiation was performed and the counts of leukocytes, lymphocytes, and granulocytes and monocytes in the peripheral blood were determined 1, 3, 7, 15 and 30 days after irradiation. These cells were considered since they are closely associated with immunity to radioactivity. In a second experiment, water-soluble propolis was similarly administered to the mice for 2 weeks after a 1-week adjustment period, and 2 Gy whole-body irradiation was performed. The antioxidant effects in hemocytes were then investigated using 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), a radical generator. In a third experiment, $1\;{\times}\;10^6$ Sarcoma-180 cells were inoculated into the right thigh of mice, which were divided into four groups: control, water-soluble propolis-treated, 6 Gy irradiated and water-soluble propolis-treated + 6 Gy irradiated groups, and changes in tumor size were measured for 20 days. Statistical analysis was conducted using ANOVA for multiple groups. In the three experiments, administration of water-soluble propolis inhibited the reduction of hemocytes caused by whole-body irradiation, showed antioxidant effects against radioactivity, and inhibited tumor growth, respectively. In conclusion, our data suggest that the antioxidant effect of watersoluble propolis inhibits hemocyte reduction caused by whole-body irradiation and enhances immunological inhibition of tumor growth.
Su, Meng;Yin, Zhi-Hua;Wu, Wei;Li, Xue-Lian;Zhou, Bao-Sen
Asian Pacific Journal of Cancer Prevention
/
v.15
no.24
/
pp.10675-10681
/
2015
Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. Results: A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Conclusions: The TP53 Arg72Pro C allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted.
Yoon Sei Chul;Oho Yoon Kyung;Gil Hak Jun;Chung Su Mi;Shinn Kyung Sub;Bahk Yong Whee
Radiation Oncology Journal
/
v.5
no.1
/
pp.31-36
/
1987
Radiobiological and clinical evidences indicate that hyperthermia combined with ionizing radiation produces a significant improvement in therapeutic effect of cancer. In general, malignant cells are more sensitive to heat than normal cells in the heat range of $41\~45^{\circ}C$. We report the experiences obtained from 42 patients with advanced malignant neoplasms managed with 2,450MHz microwave-induced local hyperthermia and ionizing radiation at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. A clinical analysis of 42 thermoirradiated patients showed result of 11(26\%),\;15(36\%),\;11(26\%)\;and\;5(12\%)$ patients with complete response (CR), partial response (PR), minor response (MR) and no response (NR), respectively. Histologically there were $17(40.2\%)$ squamous cell carcinomas, $12(28.6\%)$ adenocarcinomas and $6(14.3\%)$ miscellaneous cancers. Eleven patients with CR consisted of five squamous cell carcinomas, five adenocarcinomas, and one chloroma. Among 15 patients with PR were five squamous cell carcinomas, five adenocarcinomas, three unknown primary tumors, and one poorly differentiated, and miscellaneous tumor each.
Background: Panax ginseng is a marvelous herbal remedy for all ailments of body. That may be why it is called Panax, which means "cure for all". Melanin is a pigment that gives color to our skin; however, increased melanin production can lead to tumor formation. Human exposure to ultraviolet B radiation has increased extensively owing to the increased sunlight due to global warming. Consequently, a phenomenon called photoaging has been observed for all skin colors and types. As a result of this phenomenon, a set of enzymes called matrix metalloproteinases, which serve as degradation enzymes for extracellular matrix proteins, mainly collagen, is increased, causing depletion of collagen and resulting in early wrinkle formation. Methods: Therefore, in our study, we used the murine melanoma cell line B16/F10 to study the inhibition of melanogenesis by Korean Red Ginseng (KRG) extract in vitro and HRM-2 hairless mice exposed to artificial ultraviolet B to examine the efficacy of KRG in vivo. We prepared a 3% red ginseng extract cream and evaluated its effects on human skin. Results: Our results demonstrated that KRG induced potent suppression of tyrosinase activity and melanin production in B16/F10 cells; moreover, it reduced the transcription and translation of components involved in the melanin production pathway. In the in vivo experiments, KRG potently suppressed the expression of matrix metalloproteinases, reduced wrinkle formation, and inhibited collagen degradation. On human skin, ginseng cream increased skin resilience and skin moisture and enhanced skin tone. Conclusion: Therefore, we conclude that KRG is an excellent skin whitening and antiaging product.
Bae, Won-Young;Jung, Woo-Hyun;Shin, So Lim;Kwon, Seulgi;Sohn, Minn;Kim, Tae-Rahk
Food Science of Animal Resources
/
v.42
no.6
/
pp.1031-1045
/
2022
Postbiotics are defined as probiotics inactivated by heat, ultraviolet radiation, sonication, and other physical or chemical stresses. Postbiotics are more stable than probiotics, and these properties are advantageous for food additives and pharmacological agents. This study investigated the immunostimulatory effects of heat-treated Lactiplantibacillus plantarum LM1004 (HT-LM1004). Cellular fatty acid composition of L. plantarum LM1004 isolated form kimchi was analyzed by gas chromatography-mass spectrometry detection system. The nitric oxide (NO) content was estimated using Griess reagent. Immunostimulatory cytokines were evaluated using enzyme-linked immunosorbent assay. Relative protein expressions were evaluated by western blotting. Phagocytosis was measured using enzyme-labelled Escherichia coli particles. L. plantarum LM1004 showed 7 kinds of cellular fatty acids including palmitic acid (C16:0). The HT-LM1004 induced release of NO and upregulated the inducible NO synthase in RAW 264.7 macrophage cells. Tumor necrosis factor-α and interleukin-6 levels were also increased compared to control (non-treated macrophages). Furthermore, HT-LM1004 modulated mitogen-activated protein kinase (MAPK) subfamilies including p38 MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase. Therefore, these immunostimulatory effects were attributed to the production of transcriptional factors, such as nuclear factor kappa B (NF-κB) and the activator protein 1 family (AP-1). However, HT-LM1004 did not showed significant phagocytosis of RAW 264.7 macrophage cells. Overall, HT-LM1004 stimulated MAPK/AP-1 and NF-κB expression, resulting in the release of NO and cytokines. These results will contribute to the development of diverse types of food and pharmacological products for immunostimulatory agents with postbiotics.
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