Objectives : It is the objective of this study to compare hepatotoxicity of nickel chloride and cadmium chloride with each other through IPRL(Isolated Perfused Rat Liver) method. Methods : Biochemical indicator of hepatic function such as AST(aspartate aminotransferase), ALT(alanine aminotransferase), LDH(lactate dehydrogenase) and perfusion flow rate were used as the indicator of hepatotoxicity. Oxygen consumption rate were used as vability indicator. $300({\pm}50)g$ - weighted rats were allocated randomly to each group($0{\mu}M,\;50{\mu}M,\;200{\mu}M\;NiCl_2\;and\;CdCl_2$ exposure) by 5, totally 25. After Krebs-Ringer bicarbonate butler solution flowed into the penal vein and passed the liver cell, it flowed out of vena cava. Liver was administered with each $NiCl_2\;and\;CdCl_2$ of each concentration and observed with buffer solution sampling time. Butler which got out of liver was sampled and then biochemical indicator of hepatotoxicity was measured. Results : AST, ALT, and LDH in buffer increased with sampling time much more in $CdCl_2$ exposure group than $NiCl_2$ exposure group in both 50 and $200{\mu}M$ and statistical significance w3s verified with 2-way repeated ANOVA. Viability was decreased more and more in all substances during passed time. Conclusions : It is inferred that $CdCl_2$ has stronger hepatotoxicity than $NiCl_2$. IPRL method would be used widely for acute hepatotoxicity when considerating the benefit of it.
Background: Metastatic cancer with invasion of skin, soft tissue and skeletal muscle is not common. Examples presenting as soft tissue masses could sometimes lead to misdiagnosis with delayed or inappropriate management. The purpose of current study was to investigate clinical characteristics in the involvement of metastatic cancer. Materials and Methods: A total of 1,097 patients complaining of skin or soft tissue masses and/or lesions were retrospectively reviewed from January 2012 to June 2013. Tumors involving skin, soft tissue and skeletal muscle of head and neck, chest wall, abdominal wall, pelvic region, back, upper and lower extremities were included in the study. Results: Fifty-seven (5.2%) patients were recognized as having malignancies on histopathological examination. The most common involvement of malignancy was basal cell carcinoma, followed by cutaneous squamous cell carcinoma, sarcoma and melanoma. The most common anatomical location in skin and soft tissue malignancies was head and neck (52.6% of the malignancies). Four (0.36%) of the malignant group were identified as metastatic cancer with the primary cancer source from lung, liver and tonsil and the most common site was upper extremities. One of them unexpectedly expired during the operation of metastatic tumor excision at the scalp. Conclusions: Discrimination between benign and malignant soft tissue tumors is crucial. Performance of imaging study could assist in the differential diagnosis and the pre-operative risk evaluation of metastatic tumors involving skin, soft tissue and skeletal muscle.
Objectives : This study was performed for the investigation of anticancer effects of methanol extract of Rheum Rhizoma (MeOH-RR) on a human liver cancer cell line (HepG2). Methods : To study the cytotoxic effect of MeOH-RR on HepG2 cells, the cell viability was determined by XTT reduction method and trypan blue exclusion assay. The cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, MeOH-RR-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome c from mitochondria to cytosol, the level of Bcl-2 and Bax were examined by western blot analysis. Results : MeOH-RR reduced proliferation of HepG2 cells in a dose-dependent manner at 24 h and 48 h treatment. MeOH-RR induced the activation of caspase-3, -8, and -9 and the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3. Furthermore, treatment with MeOH-RR resulted in internucleosomal DNA fragmentation, evidenced by the formation of a DNA ladder on agarose gel, a hallmark of cells undergoing apoptosis. MeOH-RR downregulated Bcl-2, upregulated Bax, and increased the release of cytochrome c from the mitochondria into cytosol in a dose-dependent manner. Moreover, MeOH-RP increased caspase-3 activity. Conclusion : There results suggest that MeOH-RR induce apoptosis via mitochondrial pathway and caspase-3-dependent pathway in HepG2 cells. There results suggest that MeOH-RR is potentially useful as a chemotherapeutic agent in human liver cancer.
Kim Myung-jin;Lee Jae-il;Kim Young-suk;Son Hwa-young;Jun Moo-hyung;Park Chang-sik;Kim Myung-cheol
Journal of Veterinary Clinics
/
v.22
no.3
/
pp.264-267
/
2005
A 12-year-old, 8.0 kg, spayed female, mixed-breed dog was presented to the Veterinary Medical Teaching Hospital of Chungnam National University (VMTH, CNU). That case has been growing up mass in her left upper hindlimb about for 2 years and has showed vomiting and anorexia for 3 days. The patient was diagnosed with mast cell tumor on the basis of fine-needle aspiration (FNA) cytology techniques. According to World Health Organization clinical staging system for diagnosing mast cell tumors, it was classified into stage IIIa. The patient was treated by adjuvant corticosteroid therapy, but complete surgical excision was not achieved by owner's request. In the early stage of therapy, the size of the mass was gradually reduced with only adjuvant glucocorticoid therapy, so the patient's general condition was maintained well. But after 53 days later, the treatmant was not effective anymore and mass size was increased. Two months later, she was euthanized because of intermittent vomiting and severe respiratory distress. Splenic mass, duodenal ulceration, liver mass and infiltrated mast cell tumor in upper hindlimb muscle region were found in necropsy examination.
Lee, H. G;Lee, P. Y.;Lee, Y. K.;Kim, S. J.;H. K. Chung;M. K. Seo;Park, J. K.;K. S. Min;W. K. Chang
Korean Journal of Animal Reproduction
/
v.27
no.4
/
pp.299-307
/
2003
The effects of additions/deletions in glycosylated residues of recombinant human EPO (rhEPO) produced in CHO-K1 on their secretion were examined. hEPO cDNA was amplified from human liver mRNA and cloned into the pCR2.1 TOPO. Using overlapping-extension site-directed mutagenesis method, glycosylation sites at 24th, 38th, 83rd, and 126th were respectively or accumulatively removed by substituting its asparagine (or serine) with glutamine. To add novel glycosylation sites, 69 and 105th leucine was mutated to asparagine. Mutant and wild type rhEPO constructs were cloned into the pcDNA3 expression vector with CMV promoter and transfected into CHO cell line, CHO-K1, to produce mutant rhEPO mutant rhEPO proteins. Enzyme-linked immunosorbant assay (ELISA) and Western analysis with monoclonal anti-EPO antibody were performed using supernatants of the cultures showing transient and stable expressions respectively. Addition of novel glycosylation reduced rhEPO secretion dramatically while deletion mutants had little effect except some double deletion mutants ($\Delta$24/83 and $\Delta$38/83) and triple mutant ($\Delta$24/38/83). This fact suggests that not single but combination of changes in glycosyl groups affect secretion of rhEPO in cell culture, possibly via changes in their conformations.
Kim, Yoon-Tae;Lee, Heon-Jae;Kim, Gil-Whon;Shin, Heung-Mook
Journal of Physiology & Pathology in Korean Medicine
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v.19
no.3
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pp.640-646
/
2005
This study was performed for the investigation of anticancer effects of Siegesbeckia glabrescens(SG) on HepG2 cells, a human hepatoma cell line. In the previous study, we examined the involvement of nitric oxide (NO) on anti-proliferative and apoptotic efficacy of SG in vascular smooth muscle cells. The possible mechanism of the apoptotic effects of SG was investigated in HepG2 cells. SG showed potent cytotoxic activity in HepG2 but not chang cells, liver normal cells. SG treatment caused morphological change such as cell shrinkage, nuclei condensation and cell blebbing in HepG2 cells. SG also increased the nitrite production of HepG2 cells in a dose-dependent manner. Furthermore, L-NNA treatment inhibited the anti-proliferative effect of SG. From RT-PCR, SG decreased Bcl-2 but no affected on Bax. Western blot for procaspase-3 and COX-2 showed that degradation of procaspase-3 protein level or inhibition of COX-2 protein expression by SG treatment. In addition, the apoptotic effect of SG was also demonstrated by DNA laddering. In conclusion, SG-induced HepG2 cells death can occur via apoptosis which was dose-dependent, and associated with apoptosis-related Bcl-2/Bax gene expressions, COX-2 inhibition, caspase-3 activation and NO pathway. These results suggest that SG is potentially useful as a chemotherapeutic/chemopreventive agent in hepatocellular carcinoma.
Park, Chan-ran;Kim, Eun-ji;Son, Chang-gue;Cho, Jung-hyo;Lee, Nam-hun
The Journal of Internal Korean Medicine
/
v.42
no.3
/
pp.444-454
/
2021
Objectives: High natural killer cell activity (NKA) is associated with a clinically favorable status in patients with cancer. This study explores whether traditional Korean medicine (TKM) improves NKA in patients with cancer. Methods: We report three clinical cases involving patients with cancer who underwent NKA tests while they received TKM treatment, including acupuncture, moxibustion, wild ginseng pharmacopuncture, and Korean herbal medicines. We analyzed the treatment process and NKA test results of each patient. Results: The NKA of all three patients presented with an increasing tendency during the treatment process. Patient 1, who had been diagnosed with breast cancer, received inpatient treatment 3 times between September 16, 2017 and February 27, 2019. The NKA increased from 7.2 pg/mL to 571.7 pg/mL. Patient 2, who had thyroid cancer, was hospitalized 4 times between July 23, 2019 and August 27, 2020. The NKA improved from 317.4 pg/mL to 2000 pg/mL. Patient 3, who had liver cancer, received inpatient treatment 4 times between May 27, 2016 and January 10, 2017. The NKA increased from 22.2 pg/mL to 459.5 pg/mL. The chief complaints of these patients also were alleviated. Conclusions: TKM may be an effective treatment for accelerating NKA. Further research is needed to establish evidence that TKM stimulates NKA.
Ye Lim Kim;Hyo Jeong Jin;Sang Mi Park;Kyung Hwan Jegal;Chang Hyun Song;Kyung Soon Kim;Sung Hui Byun;Sang Chan Kim
Herbal Formula Science
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v.31
no.4
/
pp.265-281
/
2023
Objectives : Ukgan-san plus Citri Pericarpium and Pinelliae Rhizoma (UCP) is used as a traditional herbal formula in Korea and Japan for treatment of fever, fever-induced convulsions, and liver dysfunction and so on. In this study, we investigated the cytoprotective effect and underlying mechanism of UCP against oxidative stress induced by cotreatment of arachidonic acid (AA) and iron. Methods : To evaluate the hepatoprotective effects of UCP against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The changes in intracellular reactive oxygen species (ROS), glutathione (GSH), and mitochondrial membrane permeability (MMP) were investigated against to the oxidative stress. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) and its downstream target genes were examined by immunoblot analysis. Results : Treatment of UCP increased the cell viability and altered the expression levels of apoptosis-related proteins such as PARP, caspase-9, caspase-3, Bcl-2. UCP also inhibited the GSH depletion, excessive ROS production and mitochondrial dysfunction induced by AA + iron. In addition, the Nrf2 and the Nrf2 target genes activation were increased by UCP. Conclusions : These results indicated that UCP has the ability to protect against oxidative stress-induced hepatocyte damage, which may be mediated with Nrf2 pathway.
This experiment was conducted to investigate antitumor and immunomodulatory effects of Artemisia capillaris extracts against Hepa-lc1c7 and Sarcoma 180 cancer cells. In in vivo experimental tests using 210 ICR mice, on the $28^{th}$ day and the $42^{nd}$ day, all animals in vehicle controled HP (Hepa-lclc7 tumor cell inoculated vehicle control) and SP (Sarcoma 180 tumor cell inoculated vehicle control) showed tumor cells in the liver and spleen based on the histopathology. However, the incidences and the percentages of regions occupied by tumor cells were dramatically and dose-dependently decreased by mACH (Artemisia capillaris methanol extracts) treatment on the histomorphometry. Although the exact mechanism of inhibition of the incidences of tumor cells in the parenchyma whether inhibition of metastasis or proliferation is unclear, mACH dramatically reduce the percentages of regions occupied by tumor cells in the liver and spleen apart from the inoculation sites of Hepa-lclc7 and Sarcoma 180. In addition, they also effectively inhibit the abnormal changes on the kidney detected in the present study. The results suggest that Artemisia capillaris methanol extracts have prominent antitumor effects on the cancer cell lines Hepa-lclc7 and Sarcoma 180 m mice.
We investigated a method to improve anticancer activities of Acer mono wood extracts by ultra high pressure extraction process. The A. mono was extracted by water at $40^{\circ}C$ and 300 MPa for 15 min (High Pressure Extraction, HPE). The extraction yield by ultra high pressure extraction process was 5.42%. The cytotoxicity on human normal lung cell (HEL299) of the extracts from HPE showed 21.54% lower than that from conventional water extraction at $100^{\circ}C$ in adding the maximum concentration of 1.0 mg/$m{\ell}$. Ultra high pressure extracts process for 15 minutes extracts (HPE15) showed more potent scavenging effect than the control, BHA. On SOD-like test, the HPE15 showed highest activity as 32.4% at 1.0 mg/$m{\ell}$ concentration. Human stomach adenocarcinoma, liver adenocarcinoma, breast adenocarcinoma and lung adenocarcinoma cell growth were inhibited up to about 67~79%, in adding 1.0 mg/$m{\ell}$ of extracts from HPE. HPE was 20~25% higher than conventional water extraction. It was interesting that, among several cancer cell lines (stomach adenocarcinoma, liver adenocarcinoma), the growth of digestive related cancer cells were most effectively inhibited as about 75~79%. On in vivo experiment using ICR mice, the variation of body weight of mice group treated A. mono wood extracts from HPE of 100 mg/kg/day concentration was very lower than control and other group. The survival times of group treated this extracts was 61.96% longer than that of the control group and this extracts showed the lower tumor weight, which were 10.49 g than positive control as 16.17 g. Based on these results, we could tell that the HPE wood extracts of A. mono had higher anticancer activity than conventional water extraction. The results of HPE showed obvious advantages in higher efficiency, shorter extraction time, at lower energy costs.
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