• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.77-89
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• 1999

Background: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. Methods: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. Results: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, and cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/$m^2$ and that of cyclophosphsmide was 6,000 mg/$m^2$. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. Conclusion: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be bel1eficial in some cases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.605-610
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• 2003

According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.

• Radiation Oncology Journal
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• v.36 no.1
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• pp.17-24
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• 2018

Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

• Journal of Veterinary Clinics
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• v.28 no.6
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• pp.549-554
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• 2011

FK506 is a widespread immunosuppressive drug after liver transplantion in patients with advanced-stage hepatocellular carcinoma. Dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. Our aim was to investigate antitumor effects of FK506 in Hep3B cells, one of differentiated human hepatocellular carcinoma cell lines and inhibitory effects of dexamethsone on FK506- induced antitumor effects. Cell injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in Hep3B cells. Intracellular calcium concentration ([$Ca^{2+}$]i) and the level of activation of the c-Jun-N-terminal kinase (JNK) and the Bax protein in cultured Hep3B cells was measured. Exposure of 0.1 ${\mu}M$ FK506 to Hep3B cells led to cell death accompanied by a decrease in cell viability and an increase in LDH, ROS and [$Ca^{2+}$]i. FK506 induced an increase in activity of Bax and JNK protein but inhibited the activity of Bcl-2 protein. Treatment of dexamethsone, per se, had no effects on cell viability, LDH and ROS. However, co-treatment of FK506 and dexamethasone diminished the FK506-induced LDH release, ROS generation and JNK activation. These results demonstrate that FK506 has antitumor effect in Hep3B cells but the combination of FK506 and dexamethasone antagonizes the FK506-induced antitumor effects.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.2
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• pp.57-67
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• 2011

In this study, we investigated the correlation between the administration of various antiviral agents and the alternation of specific biomarkers induced by the hepatitis B virus (HBV). Eligible subjects diagnosed with chronic hepatitis B were prescribed with antiviral drugs at the Gastroenterology Internal Medicine Department of E University Hospital in Daejeon between May 2004 and September 2009. Lamivudine was prescribed to 66 out of 100 patients. Of the 12 patients, 6 (50.0%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative. Of the 39 patients, 23 (59.0%) showed higher than 40 IU/L alanine aminotransferase (ALT). Of the 65 patients, 41 (63.1%) showed HBV DNA decrease of 1 log, and were prescribed with Lamivudine. Adefovir was prescribed to 3 out of 100 patients. Of the 12 patients, 1 (8.3%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative, and was prescribed with Adefovir. Entecavir was prescribed to 19 (19.0%) out of 100 patients. Of the 12 patients, 3 (25.0%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative. Of the 12 patients, 3 (125.8%) showed higher than 40 IU/L ALT. Of the 65 patients, 14 (21.5%) showed HBV DNA decrease of 1 log, and were prescribed with Entecavir. Clavudine was prescribed to 7 out of 100 patients. Of the 12 patients, 1 (8.3%) showed a change from positive HBe antigen to negative HBe antigen. Of the 39 patients, 5 (12.8%) showed higher than 40 IU/L ALT. Of the 65 patients, 6 (9.2%) showed HBV decrease of 1 log, and were prescribed with Clavudine. These results do not show a statistically significant correlation between drugs and biomarkers. Data on combination therapy using Lamivudine and Adefovir show no statistically significant difference between drugs and biomarkers. Medications for periodic inspection was not correlated to HBe-antigen-negative conversion, ALT, and HBV DNA. HBV DNA was significantly reduced in patients with high levels of AST(aspartic acid aminotransferase) and ALT before treatment. In addition, the decrease of HBV DNA after 12 months of treatment was less frequently observed in patients treated with Lamivudine compared with other drugs. This result is associated with Lamivudine resistance. Although the association of drugs with diagnostic markers and the correct choice of treatment is difficult to determine, these results may be useful for further research on diagnosis and treatment of the hepatitis B virus.

• The Journal of Internal Korean Medicine
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• v.37 no.1
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• pp.90-108
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• 2016

Objectives: This study aimed to learn what should be considered in the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) by analyzing the existing guidelines and clinical trials.Methods: The development committee searched the existing guidelines for herbal medicinal products or GERD. Then, clinical trials related to GERD using herbal medicine were selected. The chosen trials were analyzed in terms of their inclusion and exclusion of participants, intervention, comparators, outcome, and trial design. Then, we compared the results of the analysis according to the regulations and guidelines of the Ministry of Food and Drug Safety to suggest the issues that we will have to consider when developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).Results: As a result, few guidelines for GERD and clinical trials with herbal medicinal products were located in the national institution homepage. In addition, 8 articles were found using the following combination of search terms: “Gastroesophageal reflux disease”, “GERD”, “herbal medicine”, “herbal therapy”, “Korean Medicine”, “Traditional Chinese Medicine”, and “TCM”. Even though all trials had their own unique research questions, all studies were performed using a randomization method. Most trials included participants with reflux esophagitis, but two trials targeted proton pump inhibitor-refractory GERD. The type of intervention varied, such as decoction, granules, and capsules. Additionally, individualized herbal medicines were used in two studies. Comparators were diverse, such as placebo, Western medicine, and electro-acupuncture. The most frequently used outcome for efficacy was the effectiveness rate. In addition, the outcome for evaluating quality of life, esophageal mucosa and pressure, esophageal acid reflux, and recurrence rates were used. Safety was investigated by recording adverse events and carrying out laboratory tests.Conclusions: We identified some issues by reviewing the existing guidelines and comparing them with clinical trials for GERD and herbal medicinal products. These results will be utilized for developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1693-1697
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• 2012

Objective: To explore the effect on radiosensitivity of arsenic trioxide ($As_20_3$) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of $As_20_3$ was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of $IC_{50}$ value and choice of 20% of the $IC_{50}$ as the experimental drug concentration. Blank control, $As_20_3$, hyperthermia, radiotherapy group, $As_20_3$ + hyperthermia, $As_20_3$ + radiotherapy, hyperthermia + radiotherapy and $As_20_3$ + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: $As_20_3$ exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an $IC_{50}$ of 18.7 ${\mu}mol/L$. After joint therapy of $As_20_3$ + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the $G_2$/M phase, and as the ratio of cells in $G_0/G_1$ and S phases decreased, cell death became more pronounced. Conclusion: $As_20_3$ and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, $As_20_3$ and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

• Journal of Hospice and Palliative Care
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• v.19 no.4
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• pp.296-302
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• 2016

Purpose: This study examined the effectiveness of a hand massage combined with analgesics on pain control in hospice patients with terminal cancer. Methods: This study is a quasi-experimental study with a single group time series design. The study included 25 terminal cancer patients who were admitted to a hospice ward. Each patient's pain level was measured after analgesics use only (control group). When patients complained of pain again, the pain level was assessed after administering a combination of hand massage and analgesics (experimental group). As for the experimental treatment, the participants were provided with oil hand massage on each hand for 5 minutes. Results: The experimental group and the control group showed no significant differences in the changes of pain score (F=0.74, P=0.3939). Conclusion: Although the pain level of the experimental group did not significantly improve compared with the control group, their pain levels tended to be low to begin with. Thus, a complementary utility value of hand massage cannot be completely excluded in terminal cancer patients. Since the pain level significantly changed according to the dosage of analgesic, nurses need more education and research on analgesic drug therapy for terminal cancer patients.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.274-283
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• 2022

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2003.09a
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• pp.44-44
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• 2003

As a basic measurement tool in the areas of animal models of human disease, gene expression and therapy, and drug discovery and development, small animal PET imaging is being used increasingly. An ideal small animal PET should have high sensitivity and high and uniform resolution across the field of view to achieve high image quality. However, the combination of long narrow pixellated crystal array and small ring diameter of small animal PET leads to the degradation of spatial resolution for the source located at off center. This degradation of resolution can be improved by determining the depth of interaction (DOI) in the crystal and by taking into account the information in sorting the coincident events. Among a number of 001 identification schemes, dual layer phsowich detector has been widely investigated by many research groups due to its practicability and effectiveness on extracting DOI information. However, the effects of each crystal length composing dual layer phoswich detector on DOI measurements and image qualities were not fully characterized. In order to minimize the DOI effect, the length of each layer of phoswich detector should be optimized. The aim of this study was to perform simulations using a simulation tool, GATE to design the optimum lengths of crystals composing a dual layer phoswich detector. The simulated small PET system employed LSO front layer LuYAP back layer phoswich detector modules and the module consisted of 8${\times}$8 arrays of dual layer crystals with 2 mm ${\times}$ 2 mm sensitive area coupled to a Hamamatsu R7600 00 M64 PSPMT. Sensitivities and variation of radial resolutions were simulated by varying the length of LSO front layer from 0 to 10 mm while the total length (LSO + LuYAP) was fixed to 20 mm for 10 cm diameter ring scanner. The radial resolution uniformity was markedly improved by using DOI information. There existed the optimal lengths of crystal layers to minimize the variation of radial resolutions. In 10 cm ring scanner configuration, the radial resolution was kept below 3.4 mm over 8 cm FOV while the sensitivity was higher than 7.4% for LSO 5 mm : LuYAP 15 mm phoswich detector. In this study, the optimal length of dual layer phoswich detector was derived to achieve high and uniform radial resolution.