• Journal of Haehwa Medicine
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• v.10 no.2
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• pp.1-10
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• 2002

In review of "invigorating spleen and supplementing qi" of clinical and experimental studies on malignant tumor, we obtained the conclusions as follows 1. Asthenic splenic qi is an important factor in mutation, occurrence and development of tumor. 2. The anti-tumor mechanism of "invigorating spleen and supplementing qi" is improvement of immune suveillance, controling cell proliferating period and enhancing body metabolism. 3. "Invigorating spleen and supplementing qi" is often used with "nourishing kidney" or "expelling pathogen" for treating cnacer. 4. In experimental studies, "invigorating spleen and supplementing qi" has effects on inhibiting occurrence and development of tumor, protecting mutation, inhibiting recurrence and metastasis, immune activity, enhancing metabolism, promoting bone marrow hemopoietic cell proliferation, increasing anti-tumor effect and protecting normal cells. 5. In clinical studies, "invigorating spleen and supplementing qi" has effects on prolonging the survival period of cancer patients, improving clinical symptoms and quality of life of cancer patients, degrading the side effects of western therapie(operation, chemotherapy and radiotherapy). 6. "Invigorating spleen and supplementing qi" is an extensive discipline of syndrome differentiation used to inhibit occurence, development, recurrence and metastasis.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.333-344
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• 2023

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high fatality. It has yet to be reported whether circ-SNX27 can affect the progression of HCC. This study attempted to analyze circ-SNX27's precise role and underlying mechanisms in HCC. HCC cell lines and tumor specimens from HCC patients were analyzed using quantitative real-time PCR and Western blotting to quantify the expressions of circ-SNX27, miR-375, and ribophorin I (RPN1). Cell invasion and cell counting kit 8 experiments were conducted for the evaluation of HCC cell invasion and proliferation. Caspase-3 Activity Assay Kit was utilized to gauge the caspase-3 activity. Luciferase reporter and RNA immunoprecipitation assays were executed to ascertain the relationships among miR-375, circ-SNX27, and RPN1. To determine how circ-SNX27 knockdown affects the growth of HCC xenografts in vivo, tumor-bearing mouse models were constructed. Elevated expressions of circ-SNX27 and RPN1 as well as a reduced miR-375 expression were observed among HCC cells and HCC patient tumor specimens. Knocking-down circ-SNX27 in HCC cells abated their proliferative and invasive abilities but raised their caspase-3 activity. Moreover, the poor levels of circ-SNX27 inhibited HCC tumor growth among the mice. Circ-SNX27 enhanced RPN1 by competitively binding with miR-375. Silencing miR-375 in HCC cells promoted their malignant phenotypes. Nonetheless, the promotive effect of miR375 silencing was reversible via the knockdown of circ-SNX27 or RPN1. This research demonstrated that circ-SNX27 accelerated the progression of HCC by modulating the miR-375/RPN1 axis. This is indicative of circ-SNX27's potential as a target for the treatment of HCC.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.129-141
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• 1994

Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cellls but not CCL-120 normal cells to radiation. Ouabain inhibits the $Na^+-K^+$-pump rapidly thus it increases intracellular Na concentration, Vanadate which is distributed extensively in almost all living organisms is known to be a $Na^+-K^+$-ATPase inhibitors, This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of $Na^+-K^+$ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMC cells and frypan blue dye exclusion test for L120, and spleen cells. Measurements of $Na^+-K^+$-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined $10^{-6}M$ vanadate and radiation treated cells were done. The results were summerized as fellows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Mininum or no cytotoxicity was seen with vanadate below concentration of $10^{-6}M$. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. e. 2- Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. $Na^+-K^+$-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiaiton itself inhibited $Na^+-K^+$-ATPase activity of tumor cell with high $Na^+-K^+$-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with orginal $Na^+-K^+$-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized tumor cells to radiation. Inhibitory effect of vanadate on $Na^+-K^+$-ATPase activity might be one of the contributing factors for radiosensitization to tumor cells which has greater enzyme activity than that of normal cell. It was suggested vanadate could be used as a potential radiosensitizer for tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3815-3819
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• 2012

The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

• Korean Journal of Pharmacognosy
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• v.26 no.3
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• pp.253-258
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• 1995

The purpose of this research was to investigate the effects of petroleum ether extract of Euonymus alatus (EAP) on the proliferation of human tumor cells. EAP inhibited the proliferation of HeLa, Hep G2, KHOS/NP and A431 cells. The cytotoxicity of doxorubicin on human tumor cells and Balb/c 3T3 cells were increased by the combination of EAP. EAP did not affect the proliferation of Balb/c 3T3 cells, mouse spleen cells and human lymphocytes. These results suggest that EAP has the cytotoxicity on human tumor cells without cytotoxicity on Balb/c 3T3 cells, mouse spleen cells and human lymphocytes, and increase the cytotoxicity of doxorubicin.

• The Journal of Korean Obstetrics and Gynecology
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• v.25 no.3
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• pp.40-60
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• 2012

Objectives: The object of this study was to observe antitumor, anticachexia and immunomodulatory effects of Shipyeukmiyeugi-eum(SYM) on human breast cancer cell, MCF-7, xenograft Balb/c nu-nu nude mice. Methods: Three different dosages of SYM-125, 250 and 500 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation, and the changes on the body weights, tumor volume and weights, weights of spleen and popliteal lymph node and epididymal fat, serum IL-6 and IFN-${\gamma}$ levels, NK cell and peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were observed. In addition, histopathological observations of apoptotic cell, spleen, popliteal lymph node and cervical brown adipose were also detected. The results were compared with a potent cytotoxic estrogen receptor antagonist, Tamoxifen 20 mg/kg treated mice. Results: Tumor volumes and weights were decreased without cytotoxic effects on the both MCF-7 and MCF-10A cells as results of all three different dosages of SYM treatment. And weights of body, spleen, popliteal lymph node, epididymal fat, serum IFN-${\gamma}$, NK cell, peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were increased with decrease of serum IL-6. At histopathological observations, apoptotic tumor cells, spleen, popliteal lymph node and cervical brown adipose tissue were increased. That means tumor-related immunosuppress and cachexia were markedly inhibited by SYM treatment as compared with tumor-bearing mice. On the other hand, Tamoxifen showed marked cytotoxic effects against MCF-7 and MCF-10A, decreases of tumor volume and weights, and increases of apoptotic tumor cells and related decreases of tumor cell volumes, but tamoxifen markedly deteriorated the tumor-related immune-suppress and cachexia. Conclusions: The results obtained in this study suggest that SYM showed favorable anticancer effects and anticachexic effects on the MCF-7 cell xenograft through immunomodulatory effects. SYM did not induce any cytotoxic effects against both normal and cancer cells.

• Journal of Chest Surgery
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• v.36 no.10
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• pp.711-720
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• 2003

Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

• Toxicological Research
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• v.6 no.1
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• pp.21-28
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• 1990

This study was undertaken to evaluate the immune responses to sheep red blood cell (SRBC) and potential anti-tumor effect of Bacillus Calmette-Guerin (BCG) in the mice bearing rumor induced by DMBA. The frequencies of tumor appearances were 62% in DMBA-treated mice and 14% in DMBA and BCG-treated group, respectively. Cellular immune response such as delayed-type hypersensitivity (DTH) to SRBCs, natural killer (NK) cell activity and antigen-binding cell (ABC) assay were decreased apparently in the tumor bearing mice compared to the normal controls. Humoral immune responses such as hemagglutinin (HA) and hemolysin (HE) were noted to be reduced in the tumor bearing mice, but the spleen index increased in tumor bearing mice. All the immunological parameters in the DMBA and BCG-group appeared to be higher than those of only DMBA-treated group. These results indicated that DMBA-induced tumor suppressed host immune responses. Also, they imply the idea that BCG enhanced the immune responses of tumor-bearing host and antitumor effects.

• Journal of Society of Preventive Korean Medicine
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• v.5 no.1
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• pp.103-115
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• 2001

Background : Gamisamryungbaekchul-san(加味蔘?白朮散) is a herbal medicine which has been used for the traditional therapeutic agent of augmentation of the spleen and reinforcement of the Qi. Objective : This Study was performed to investigate the effect of Gamisamryungbaekchul-san on the tumor and immune response in the moose B16 melanoma tumor model. Materials and Methods : The tumor was induced by subcutaneous inoculation of B16BL6 melanoma cells in the shaved dorsal region of mice. Mice were orally administered with Gamisamryungbaekchul-san extract(26.3mg/mouse) for 14days after inoculation. For making examination of antitumor effect, the Increase of life span, Tumor growth inhibition rate, change of body weight were measured and evaluated. For the immune response increasing effect, the percentage of T lymphocyte and B Lymphocyte in the peripheral blood, the percentage of CD4+ T-cell, CD8+ T-cell and CD4+/CD8+ ratio in the peripheral blood and spleen, interleukin-2 productivity were measured and evaluated. Results : Gamisamryungbaekchul-san showed 16.59% increase of life span, 31.64% tumor growth inhibition rate and increase of body weight. Gamisamryungbaekchul-san increased the percentage of T lymphocyte in the peripheral blood, CD4+ T cell percentage of peripheral blood and spleen, and Interleukin-2 productivity as compared with the Control group. Whereas Gamisamryungbaekchul-san had no effect on the percentage of B lymphocyte in the peripheral blood, the percentage of CD8+ T cell, CD4+/CD8+ T-cell ratio in both of peripheral blood and spleen as compared with the Control group. Conclusion : This study shows that Gamisamryungbaekchul-san has anti-tumor effects and immunoregulatory effects on the B16 melanoma tumor model. It is suggested that Gamisarmyungbaekchul-san could be a useful immunomodulator and anti-tumor agent.

• Journal of Veterinary Clinics
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• v.19 no.4
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• pp.443-446
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• 2002

A primary metastatic malignant plasma cell tumor was presented in a 7-year-old, female, mixed breed dog. The dog was admitted to Veterinary Teaching Hospital at College of Veterinary Medicine, Seoul National University after suffering from depression, anorexia, and dyspnea. The dog was euthanized due to poor prognosis. At necropsy, numerous, firm and tan round nodules, 1 to 2 cm in diameter were noted in the ribs. The nodules formed chain or were occasionally coalescing, causing osteolysis of the ribs. A large amount of clear fluid was present in the thoracic cavity. The spleen and liver were markedly enlarged and congested. Histologically, the nodular masses were diagnosed as plasma cell tumor which was believed to be originated from the rib. Evidence of metastasis was observed in the spleen, liver, and kidney.