Pectin was dissolved in HCl, citric acid, and deionized distilled water (DW, 2%, v/v) and irradiated at different irradiation doses (2.5-50 kGy) by gamma ray to investigate its physicochemical characteristics and biological activity. Viscosity of pectin solution was significantly decreased by irradiation up to 10 kGy, then remained constant thereafter. Gamma-irradiation increased monosaccharide and polysaccharide levels up to 30-40 kDa. Electron donating ability of pectin solution was highest when DW was added and was increased by increasing irradiation dose (p<0.05). ${\beta}-Carotene$ bleaching assay revealed irradiation resulted in development of antioxidantive activity in pectin solution. Growth inhibition of cancer cell lines was observed in irradiated pectin solution in dose-dependent manner, with G36l showing the highest. Results suggested irradiation of pectin solution could be effective for preparation of functional pectin oligomer.
The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.
Actinomycin D is a natural antibiotic that is used in anti-cancer chemotherapy and is known as a transcription inhibitor. Interestingly, actinomycin D induces phosphorylation of signal transducers and activators of transcription 3 (STAT3) in renal cancer Caki cells. In this study, we examined the molecular mechanism of actinomycin D-induced STAT3 phosphorylation. Treatment with actinomycin D induced phosphorylation of STAT3 (Tyr705) in a dose- and time-dependent manner. However, actinomycin D did not induce phosphorylation of STAT3 (Ser727), STAT1 (Tyr701) and STAT1 (Ser727). Moreover, actinomycin D-induced STAT3 phosphorylation was caused by decreased protein and mRNA levels of SOCS3, but not by JAK2 and SHP-1. In addition, other transcription inhibitor (5,6-dichloro-1-b-D-ribofuranosyl benzimidazole; DRB) also induced phosphorylation of STAT3 (Tyr705). Taken together, the present study demonstrates that transcriptional inhibitors (actinomycin D and DRB) induce phosphorylation of STAT3 (Tyr705) in Caki cells by down-regulation of SOCS3.
Ji, Hae-Ri;Hwang, Deok-Sang;Lee, Chang-Hoon;Jang, Jun-Bok;Lee, Jin-Moo
The Journal of Korean Obstetrics and Gynecology
/
v.32
no.4
/
pp.1-13
/
2019
Objective: This study is aimed to investigate the anti-tumor metastasis by innate immunomodulating effects of crude polysaccharide isolated from Polygonati Rhizoma (CP-PR) on 4T1 breast cancer cells. Methods: CP-PR was isolated from Polygonati Rhizoma. Antimetastatic experiments were conducted in vivo mouse model by using 4T1 breast cancer cells. The cell viability of CP-PR was tested with normal spleen and 4T1 breast cancer cells. To observe the activation of macrophages with/without 4T1 breast cancer cells, production of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), IL-10 and IL-12 were measured with enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the lysis of YAC-1 cells and the production of granzymes were measured to observe the activation of natural killer (NK) cell. Results: Intravenous administration of CP-PR significantly inhibited metastasis of 4T1 breast cancer cells. In an in vitro cytotoxicity analysis, CP-PR affected the growth of normal spleen and 4T1 breast cancer cells above specific concentration. The production of $TNF-{\alpha}$, IL-6, IL-10 and IL-12 were significantly increased in macrophages with CP-PR. As compared with control, CP-PR showed significantly higher production of $TNF-{\alpha}$, IL-10 and IL-12 in macrophages co-cultured with 4T1 breast cancer cells. The lysis of YAC-1 cells and the production of granzymes were significantly up regulated by CP-PR. Conclusion: CP-PR appears to have considerable activity on the anti-metastasis by activation of innate immune system.
Breast cancer anti-estrogen resistance 3 (BCAR3) has been identified as one of the genes that induces anti-estrogen resistance in breast cancer. We have previously reported that BCAR3 activates promoters of c-Jun, activator protein-1, and the serum response element. In this study, we investigated the functional role of BCAR3 in the activation of the estrogen response element (ERE) in normal human breast MCF-12A cells. Transient expression of BCAR3 induced ERE activation, which was further increased by 17β-estradiol treatment but was not blocked by the anti-estrogen tamoxifen. Next, we studied the signaling pathway of BCAR3 leading to ERE activation. BCAR3-mediated ERE activation was inhibited by LY294002 and AZD5363, inhibitors of the phosphatidylinositol (PI) 3-kinase pathway, but not by PD98059 and U0126, inhibitors of the mitogen-activated protein kinase pathway. ERE activation was induced by the catalytic subunit p110α. of PI3-kinase or the active mutant of Akt, and this activation was not further increased by additional BCAR3 transfection. Based on these results, we propose that BCAR3 plays an important role in ERE activation through the PI3-kinase/Akt pathway in human breast MCF-12A cells.
Purpose: This study evaluated the pretreatment expression patterns of MDM2, p53, and pRb proteins to determine if the expression patterns could predict the outcome of concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma and aid in the decisions for the selection of treatment modalities. Materials and Methods: Fifty-one patients that were treated with definitive chemoradiotherapy for stage $I{\sim}IVa$ esophageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily $1.8{\sim}2\;Gy$ fractions up to a median dose of 54 Gy for primary tumors, and with four cycles of cisplatin/5-fluorouracil chemotherapy that was administered every 4 weeks, the first two cycles of which were administered concurrently with radiotherapy. Expression of MDM2, p53, and pRb was investigated by immunohistochemical analysis using pretreatment biopsy specimens. Results: MDM2, p53, and pRb were detected with high immunoreactivity in 19.6%, 27.5%, and 66.7% of the patients, respectively. However, there was no significant correlation between expression of these factors and clinical outcome. By the use of multivariate analysis with nine covariates-age, tumor location, tumor length, stage, pathological response, clinical response, MDM2 expression, p53 expression, and pRb expression, only pathological response and stage were significant factors for cause-specific survival. Conclusion: Expression of MDM2, p53, and pRb was not found to be clinically significant for predicting outcomes after CCRT in this study. Further studies with a larger patient population and longer follow-up periods are needed to re-evaluate the expression pattern and to identify new predictors for CCRT response.
Anticarcinogenic activity of Moutan radix for mouse ascites cancer induced by mouse Sarcoma 180 (S-180) cells was investigated. Methanol extract of Moutan radix including other folk medicinal plants (Taxus cuspidata, Curcuma longa, Artemisia capillaris, Ligrstri fructus, and Liriope platyphylla) used to remedy or cure many chronic human diseases like cancer was fractionated into hexane, chloroform ($CHCl_3$), ethylacetate (EtOAc), and butanol (BuOH) fractions. Anticarcinogenic activity of the fractions, exhibited a strong cytotoxicity for L1210 and S-180 cells, was examined for mouse ascites cancer induced by S-180 cells. Male ICR mice (7 mice/treatment, $5{\sim}6$ weeks of age, $23{\pm}1\;g$ were injected i.p. with S-180 cells ($1{\times}10^{7}\;cell/1\;ml$ PBS). One day later, each mouse was given 0.1 ml of 10% DMSO containing sample ($30\;{\mu}g/g$ body weight) every day for 10 consecutive days. Control mice were only given 0.1ml S-180 cells and 0.1 ml 10% DMSO. Mice treated with EtOAc fraction of Moutan radix showed 28.7 days of life, which is 167% of control mice's life. Based on the dose-dependant experiment mice treated with $30\;{\mu}g$ showed longer life relative to mice treated with ootherr doses (5, 15, $60\;{\mu}g$), and mice treated with $60\;{\mu}g$ exhibited toxic symptoms. Body weight of mice treated with Moutan radix was significantly reduced relative to that of control mice (p<0.05). GC-MS analysis in conjunction with silica-gel column chromatography revealed that the EtOAc fraction contained 2-methoxylphenol, benzoic acid, 1-(4-hydroxy-3-methoxyphenyl)ethanone, 8-methyl-2,4(1H,3H)pteridinedione and 2,5-furan-dicarboxylic dimethyl ester as regards to the anticarcinogenic property of the EtOAc fraction. These results suggest that Moutan radix might be included as an anticarcinogenic medicinal plant for treatment of ascites cancer.
Most terminally ill cancer patients experience various physical and psychological symptoms during their illness. In addition to pain, they commonly suffer from fatigue, anorexia-cachexia syndrome, nausea, vomiting and dyspnea. In this paper, I reviewed some of the common non-pain symptoms in terminally ill cancer patients, based on the National Comprehensive Cancer Network (NCCN) guidelines to better understand and treat cancer patients. Cancer-related fatigue (CRF) is a common symptom in terminally ill cancer patients. There are reversible causes of fatigue, which include anemia, sleep disturbance, malnutrition, pain, depression and anxiety, medical comorbidities, hyperthyroidism and hypogonadism. Energy conservation and education are recommended as central management for CRF. Corticosteroid and psychostimulants can be used as well. The anorexia and cachexia syndrome has reversible causes and should be managed. It includes stomatitis, constipation and uncontrolled severe symptoms such as pain or dyspnea, delirium, nausea/vomiting, depression and gastroparesis. To manage the syndrome, it is important to provide emotional support and inform the patient and family of the natural history of the disease. Megesteol acetate, dronabinol and corticosteroid can be helpful. Nausea and vomiting will occur by potentially reversible causes including drug consumption, uremia, infection, anxiety, constipation, gastric irritation and proximal gastrointestinal obstruction. Metoclopramide, haloperidol, olanzapine and ondansetron can be used to manage nausea and vomiting. Dyspnea is common even in terminally ill cancer patients without lung disease. Opioids are effective for symptomatic management of dyspnea. To improve the quality of life for terminally ill cancer patients, we should try to ameliorate these symptoms by paying more attention to patients and understanding of management principles.
Ahn Yong Chan;Lim Do Hoon;Choi Dong Rak;Kim Moon Kyung;Kim Dae Yong;Huh Seung Jae;Kim Ho Joong;Chung Man Pyo;Kwon O Jung;Rhee Chong Heon
Radiation Oncology Journal
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v.14
no.4
/
pp.299-306
/
1996
Purpose : Respiratory symptoms related with malignant airway disease have been the main causes of lowered qualify of life and also sometimes may be life-threatening if not properly managed. The authors report the short-term experiences of endobronchial brachytherapy for symptomatic malignant airway obstruction using high dose rate after-loading brachytherapy unit. Materials and Methdos : Twenty-five Patients with symptomatic malignant airway obstruction were treated with endobronchial brachytherapy between the period of December 1994 and March 1996 at Department of Radiation Oncology of Samsung Medical Center Twenty-one ($84\%$) were patients with non-small cell lung cancer, three with tracheal malignancies, and one with recurrence of esophageal cancer. Twenty Patients were given elective external beam radiation therapy, while six were given endobronchial laser evaporation therapy on emergency bases in addition to endobronchial brachytherapy. Three procedures for each patient were planned and total of 70 procedures were completed. Results : Improvement rates of major respiratory symptoms after endobronchial brachytherapy procedures were $88\%$(22/25). $96\%$(22/23), $100\%$ (15/15), and $100\%$(9/9) for cough, dyspnea, hemoptysis and obstructive pneumonia, respectively. ECOG performance scores were improved in $56\%$ of total patients group, while there was no case with worsened ECOG score. Fifteen patients died and the median interval from the start of treatment to death was 4 months (range: $1\~17$ months), while that of ten survivors was 9 months (range $5\~19$ months). There were five patients with controlled intrathoracic disease, who have survived over one rear. All deaths were associated with uncontrolled local and/or distant disease. Four Patients died of massive fatal hemoptysis, three of who received emergency endobronchial laser evaporation therapy before the start of endobronchial brachytherapy. Conclusion : Endobronchial brachytherapy has been confirmed as an excellent palliative treatment modality improving respiratory symptoms as well as patients' general performance status. Based on the current observations, use of endobronchial brachytherapy in curative setting as a boost technique may be warranted.
Purpose : To evaluate the pathologic effects of preoperative radiotherapy o the resectable distal rectal cancer, we analyzed the results of postoperative pathologic findings for the patients with preoperative radiotherapy ant surgery Materials and Methods: From July 1995 to April 1996, we treated sixteen patients of resectable rectal cancer with preoperative radiation therapy and curative surgery At diagnosis, Thomas Jefferson (TJ) system was used for the clinical stage of the Patients. We treated the patients with conventional radiation therapy of 4500~5000cGy before surgery. The surgery was carried out 4 weeks after completion of radiation therapy. Modified Astler Coller (MAC) system was used for the postoperative pathologic stage. We analyzed the pathologic stages and findings according to preoperative clinical stage and compared with those of the control group in similar clinical stages. Result : All patients were treated with sphincter preservation surgery after Preoperative radiation therapy. Pathoiogic complete response (CR) was shown in 1 case $(6.3\%)$. We compared the results between preoperative radiation therapy group (Preop.RT group) and surgery only group (control group). In TJ stage II, among nine patients of Preop.RT group, 8 patients $(88.9\%)$ were in MAC stage 8 except 1 CR patient, but among 17 patients of control group. 11 patients$(64.7\%)$ were in MAC stage B and 6 Patients $(35.3\%)$ in MAC stage C. In TJ stage III, among 7 patients of Preop.RT group, 4 patients $(57.1\%)$ were in MAC stage B and 3 patients$(42.9\%)$ in MAC stage C. Among 14 Patients of control group, 4 patients $(28.6\%)$ were in MAC stage B and 10 Patients $(71.4\%)$ in MAC stage C. Above results showed that postoperative Pathologic stage was decreased in Preop.RT group with statistical significance (P=0.049). The postoperative Pathologic findings (blood vessel invasion. Iymphatic vessel invasion, perineural invasion) were decreased in the Preop.RT group compared with those of control group. But statistical significance was found only in Iymphatic vessel invasion (p=0.019). Conclusion : The Postoperative pathologic stages and adverse Prognostic pathologic findings were decreased in preoperative radiation therapy group. The Iymphatic vessel invasion and MAC stage C findings were abruptly decreased in Preoperative radiation therapy group. The preoperative radiation therapy was found to be effective in resectable rectal cancer. The patients group in our study was very small and long term follow up was not done. Therefore, further study about this issues is needed.
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