• Journal of Hospice and Palliative Care
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• v.13 no.4
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• pp.252-256
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• 2010

Breathlessness is a frequent and distressing symptom in terminal cancer patients. Refractory breathlessness is defined as a state that does not respond to conventional disease-specific therapy with an exclusion of reversible underlying causes, and the main classes of symptomatic drug treatments include opioids and benzodiazepines. Korean Family Medicine Palliative Medicine Research Group discussed two terminal cancer patients in whom severe breathlessness with different causes were treated with inhalation of nebulized furosemide, which is an emerging option of palliative treatment. It still remains unclear how it becomes effective or how much it is effective, therefore, its routine use seems to be somewhat early. Nevertherless, if a patient with intractable breathlessness does not have a marked obstructive airway lesion, its use should be considered. Based on the discussion in the seminar, we want to share our experience of the application of inhaled furosemide with other palliative care practitioners and strongly recommend further research on this topic in the future.

• Plant Resources
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• v.3 no.1
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• pp.1-45
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• 2000

To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for cancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids. lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically. Oridonin isolated from Rabdosia ssp. is now investigate for clinical trials in China. Moreover camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifotia. has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential Some efforts are continued in National Cancer Institute(NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin 111, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected In Japan, China, Korea. Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia In mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma(KB) cells in our laboratory, as primary screening. In this meeting, 1 will present on antitumor and cytotoxic substances of the higher plants(Rubis cordifolia, Ailanthus vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var. drupacea, etc.) selected from above screening tests.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• Proceedings of the Plant Resources Society of Korea Conference
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• 1999.10a
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• pp.1-45
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• 1999

To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for ncancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically Oridonin isolated from Rabdosia ssp.is now investigated for clinical trials in China. Moreover, camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity. This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifolia, has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential. Some efforts are continued in National Cancer Institute NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin III, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected in Japan, China, Korea, Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells in our laboratory, as primary screening. In this meeting, I will present on antitumor and cytotoxic substances of the higher plants (Rubia cordifolia, Ailanfhus Vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var drupacea, etc.) selected from above screening tests.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.381-392
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• 2004

Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.391-398
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• 2018

Mesenchymal stem cells (MSCs) are an attractive resource for refractory patients because of their anti-inflammatory/immunomodulatory capability and multi-lineage differentiation potential. The transplantation of MSCs has led to positive results in preclinical and clinical application to various diseases, including autoimmune disease, cardiovascular disease, cancer, liver cirrhosis, and ischemic stroke. On the other hand, studies have shown that paracrine factors, not direct cell replacement for damaged cells or tissue, are the main contributors in MSC-based therapy. More recently, evidence has indicated that MSC-derived exosomes play crucial roles in regulating the paracrine factors that can mediate tissue regeneration via transferring nucleic acids, proteins, and lipids to the local microenvironment and cell-to-cell communication. The use of these exosomes is likely to be beneficial for the therapeutic application of MSCs because their use can avoid harmful effects, such as tumor formation involved in cell transplantation. Therefore, therapeutic applications using MSC-derived exosomes might be safe and efficient strategies for regenerative medicine and tissue engineering. This review summarizes the recent advances and provides a comprehensive understanding of the role of MSC-derived exosomes as a therapeutic agent.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.