• Korean Journal of Clinical Pharmacy
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• v.19 no.2
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• pp.89-95
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• 2009

Gemtuzumab ozogamicin (GO) is an antibody-targeted chemotherapeutic agent consisting of calicheamicin, a potent cytotoxic antibiotic linked to a recombinant humanized anti CD33 monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). GO is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. GO has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.385-392
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• 2006

Paclitaxel is an important chemotherapeutic agent for the treatment of human solid tumors. Multicellular resistance(MCR) is considered to be a major mechanism of resistance of human solid tumors to chemotherapeutic agent such as paclitaxel, which includes barriers to drug penetration through tumor tissues. Multicellular layers(MCL) cultures resemble in vivo tumor condition in terms of MCR and has been used successfully to produce clinically relevant data. In the present study, we evaluated the penetration characteristics and post-penetration anti-proliferative activity of paclitaxel using MCL of human colorectal cancer cells(DLD-1 and HT-29) grown in Transwell inserts. The penetration of $[^{14}C]-paclitaxel$ was slower than that of mannitol which penetrates via paracellular pathway in DLD-1 MCL. The penetration of $[^{14}C]-paclitaxel$ was faster in HT-29 MCL compared to DLD-1 MCL, i.e., at 10 ${\mu}M$ 100% and 40% penetration were observed after 48 hr incubation for HT-29 and DLD-1 cells, respectively. When calculated using anti-proliferative activity in the conditioned media of bottom chamber, the penetration after 24 hr was very limited(less than 50%) and concentration-dependent at the concentrations tested in both MCL's. These results suggest that limited and differential penetration of paclitaxel in tumor tissues may contribute to lower and differential efficacy against human solid tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1637-1641
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• 2016

Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

• The Korean Journal of Oral and Maxillofacial Pathology
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• v.42 no.6
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• pp.167-174
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• 2018

Natural products are vastly utilized as a source of chemotherapeutic agents for human cancers. Kochia scopraia is traditionally used for the cure of urological and dermatological diseases. Recently, methanol extract of Kochia scoparia (MEKS) has been shown to have anti-cancer activity to various human cancers. However, there is no report demonstrating the anti-cancer activity of MEKS in human mucoepidermoid carcinoma (MEC) cells. In this study, the authors studied the effects of MEKS on the cell proliferation and underlying mechanism in YD15 human MEC cells. MEKS decreased YD15 cell proliferation proven by trypan blue exclusion assay and induced apoptosis, evidenced by cell cycle analysis and western blotting. Autophagy induction by MEKS was verified by western blotting. In addition, MEKS regulated the expression of phosphorylated Akt, phosphorylated p38 and Nrf2 protein. This results can imply that MEKS might be a potential candidate for the treatment of human MEC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• Development and Reproduction
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• v.18 no.4
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• pp.225-231
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• 2014

Autophagy is a homeostatic degradation process that is involved in tumor development and normal development. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagy results in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and is currently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of these dual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in dose- and time-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of CQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor or LMP inducer, in concentration-dependent manner.

• Bulletin of the Korean Chemical Society
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• v.29 no.3
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• pp.595-598
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• 2008

Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is a natural chemotherapeutic compound with diverse biological properties including an antitumor activity. Emodin, a specific inhibitor of the protein tyrosine kinase, has a number of cellular targets in related to it. Its inhibition activity affects the mammalian cell cycle regulation in specific oncogene. Practically, it has been proven to inhibit HER-2/neu tyrosine kinase expressing breast cancer cells as an anticancer agent. 2-[123I]iodoemodin has been synthesized and evaluated human breast cancer cells (MDA-MB-231, MCF-7, fibroblast as a control) which express basal levels of HER-2/neu tyrosine kinase to investigate its suitability as a breast cancer imaging agent and 2-iodoemodin has been synthesized as a standard compound. The radiochemical yield of the 2-[123I]iodoemodin was about 72% and its radiochemical purity was over 97% after purification. The radioactivity of the 2-[123I]iodoemodin was increased in a time dependent manner in both cell lines and the ratio of MDA-MB-231 and MCF7 to fibroblast was 2.9 and 1.7, respectively.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.302-313
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• 1995

Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

• Journal of Oral Medicine and Pain
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• v.40 no.2
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• pp.82-87
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• 2015

Methotrexate (MTX) is a chemotherapeutic agent that is used to treat a host of malignancies. But recently, MTX has also been used as a therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, and systemic lupus erythematosus. However, MTX is an antimetabolite that affects rapidly dividing normal cells such as oral mucosal epithelial cells, gastrointestinal epithelial cells, and bone marrow cells-which explains why oral mucositis is often an initial manifestation of MTX toxicity. Because oral lesions are frequently initially presented in dental clinics, dentists should consider the possibility of adverse drug reactions in the differential diagnoses of oral lesions through a meticulous collection of patients' medical histories. In this report, we examine patients who suffered from oral ulcerative lesions upon diagnosis of MTX-induced oral mucositis. Then, we suggest approaches for the diagnosis and treatment of MTX-induced oral mucositis through a review of literature.

• Journal of Chest Surgery
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• v.13 no.4
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• pp.507-511
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• 1980

Most cases of plasma-cell granuloma occur in adult skeleton system. They usually present as a single lesion, but multiple lesions are not uncommon. Roentgenographically, the lesions are lytic, sclerotic or mixed, but in the majority there is some degree of sclerosis. No specific etiologic agent is known, but it is postulated that the reaction may be associated with a variety of organisms of low-grade virulence. Certain organisms have long been known to produce predominantly plasmacytic infiltrate, notably spirochetes, mycobacteria and some exotic viruses. It is most important, however, that this entity, plasma-cell granuloma, be distinguished from multiple myeloma so those potentially life-threatening chemotherapeutic agents are not prescribed. Histologically, aggregates of chronic inflammatory cells are intermingled with the meets of plasma cells, and note the markedly thickened bone trabeculae in surrounding bone. We experienced a case of plasma-cell granuloma of right 7th. rib, occurring in 32 year old male and reported it with review of literatures.