• Journal of Korean Neurosurgical Society
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• v.58 no.1
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• pp.1-8
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• 2015

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

• Molecules and Cells
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• v.25 no.1
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• pp.119-123
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• 2008

Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2000.04a
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• pp.8-9
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• 2000

Despite the advances made in the past few decades in cancer chemotherapy, many conventional anticancer drugs display relatively poor selectivity for cancer cells. The nonselectivity of anticancer drugs and the development of anticancer drug resistance have been recognized as serious limitations in their clinical usefulness. Therefore, a major challenge in cancer chemotherapy is the development of new anticancer agents with improved selectivity for tumor cells as well as the prevention of the host cell resistance, both of which result in the improvement of therapeutic effect against cancer cells. Cyclophosphamide (CP), a widely used anticancer agent, is a prodrug that is activated by hepatic microsomal mixed-function oxidase (MFO) catalyzed C$_4$- hydroxylation. The resulting 4-hydroxycyclophosphamide (4-OH-CP) is converted to the ring-opened tautomer to aldophosphamide (Aldo) which subsequently undergoes a base- catalyzed ${\beta}$-elimination to generate cytotoxic phosphoramide mustard (PDA) and acrolein. The cytotoxic activity of CP is attributed to the aziridinium ion species derived from PDA that cross-links interstrand DNA.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1058-1069
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• 2018

Neuropathic cancer pain (NCP) is caused by nerve damage attributable to the cancer per se, and/or treatments including chemotherapy, radiotherapy, and surgery; the prevalence is reported to be as high as 40%. The etiologies of NCP include direct nerve invasion or nerve compression by the cancer, neural toxicity, chemotherapy, and radiotherapy. NCP is subdivided into plexopathy, radiculopathy, and peripheral neuropathies, among several other categories. The clinical characteristics of NCP differ from those of nociceptive pain in terms of both the hypersensitivity symptoms (burning, tingling, and an electrical sensation) and the hyposensitivity symptoms (numbness and muscle weakness). Recovery requires several months to years, even after recovery from injury. Management is complex; NCP does not usually respond to opioids, although treatments may feature both opioids and adjuvant drugs including antidepressants, anticonvulsants, and anti-arrhythmic agents, all of which improve the quality-of-life. This review addresses the pathophysiology, clinical characteristics and management of NCP, and factors rendering pain control difficult.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.1-17
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• 1999

Large bowel cancer shows the 4-5th frequency in cancers that occurs in Korea. The western medicine cures the Large bowel cancer by radiation, surgery and chemotherapy. While, Oriental medicine cures the Large bowel cancer by Herb-drugs, acupuncture, moxa and et al. With just one way of treating Large bowel cancer can't be effective remedy. Because each medicine has a strength and weakness, it is effective treatment when two medicine combines and supplement each other. We got the following result about a trend of oriental and western combination treatment for Large bowel cancer through studding records. 1. In Large bowel cancer, colon cancer is referred hematochezia(腸風下血), rectal cancer is refereed enterotoxin(腸毒), and anal cancer is accumulation of pathogens in yin(結陰). 2. The western medicine treats Large bowel cancer patient with surgery first. They need on assembly treatment such as chemical, radiation and immune treatment. In oriental medicine, they treats Large bowel cancer patients with differentiation of symptom and signs and treatment(辨證施治) for example, insufficiency of spleen and stomach(脾胃虛弱), collapse of the spleen-ql(脾氣下陷), stagnation of blood stasis and toxic agent(瘀毒內結), reinforcing both qi and blood(脾血下陷), stagnation of damp-phlegm(痰濕凝結) and cure for them by acupuncture and moxa too. 3. In combination with oriental and western medical treatment princple of Large bowel cancer by each stage is as follows. First stage is cured with radical surgery and herb-drugs without chemotherapy. The intermediate and terminal stage patients is used radiation before surgery, or after palliative surgery cour with chemotherapy, radiation and Herb-drugs. In terminal stage patients, unable for surgery, is used combination between chemotherapy, palliative radiation and Herb-drugs. 4. After radiation surgery, the terminal stage patients who have extensively lymph node metastasis or local contraindication is able to undergo combination of Herb-durgs and chemotherapy. 5. The cure-effect with oriental and western medicine combination treatment was better than that just with oriental or western medical treatment. 6. The merits of oriental and western medicine combination treatment lengthen one's life and diminish the bad effect of chemotherapy and complete radiation treatment, prevent from relapsing, maintain the balance in their environment of body and improve immunity.

• Biomedical Science Letters
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• v.25 no.2
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• pp.159-169
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• 2019

Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

• Journal of Korean Neurosurgical Society
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• v.38 no.5
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• pp.366-374
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• 2005

Objective : Nitric oxide[NO] is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. Methods : U87MG and U373MG cells were treated with the NO donors sodium nitroprusside[SNP] and S-nitroso-N-acetylpenicillamine[SNAP], alone or in combination with the anticancer drugs 1,3-bis[2-chloroethyl]-1-nitrosourea[BCNU] and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. Results : NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. Conclusion : BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.149-153
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• 2014

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6831-6839
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• 2015

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.59-74
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• 2004

This report attempts to explain the (i) implications of comorbidity for research and practice in the fieldo of oncology, (ii) the approach for dosing of anti-cancer drugs in the presence of comorbidity, as an example of its clinical application, and finally (iii) the dosing guidelines for the anticancer drugs clinically active in gastric cancer in the presence of renal or liver dysfunction. This has resulted from the idea of approaching comorbidity in a systematic way and of integrating it with oncologic decisions. Various methods have been used to assess comorbidity. However, significant work remains to be done to analyze how various diseases combine to influence the oncologic outcome. The main end-point explored so far has been mortality, but a largely open challenge remains to correlate comorbidity with treatment tolerance and functional and quality of life, as well as to integrate it in clinical decision-making. Cancer chemotherapy in comorbidity should be considered as an example of the need for dose optimization in individual patients, and it should be determined by considering the basic principles of the pharmacokinetics and the pharmacodynamics of the agents. This review analyzes the available data on the pharmacokinetics and the toxicities of anti-cancer agents in the comorbidity population.