• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.11-18
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• 1995

Background: The natural history of bacillary tuberculosis was studied in India and results showed that at the end of the 5-year period, 49% of the patients were dead, 33% were cured and 18% remained sputum-positive. The aim of this survey is to observe the natural course of the patients with intractable tuberculosis disease who were incurable with all drug regimens of the national tuberculosis programme(NTP). Method: Of the patients who have been found as intractable cases in Kang-Weon Province by the supervisory medical officer during the period from January 1,1987 to December 31,1992, 179 were eligible for this study. Sputum examination was done for those who were survived until October in 1993 at the Kang-Weon provincial laboratory of KNTA. 49 out of 179 patients were transferred to the private sectors and retreated with the combination of prothionamide, cycloserine, ofloxacin, enviomycin, etc. They seemed to have been bacteriologically cured, and so they were excluded from the study. Finally 130 patients were analyzed by modified life table method to calculate the fatality rate and the survival rate during the period of 7 years. Results: 1) 80.8% of intractable cases were male and 19.2%, female. 2) More than 94% of intractable cases showed moderately or far advanced Tb findings on their X-rays at the time of registration at health centres. 3) The cumulative case-fatality rate was 19.74% at the end of 1-year period and has risen to 34.55% by the end of 4-year period(increasing by 4.9% a year on an average). The case-fatality rate has shown no appreciable rise since then until the end of 7-year period. 4) The case-survival rate was 80.26% at the end of 1-year period and has decreased to 65.45% by the end of 4-year period. And then there was no appreciable change in the survival rate until the end of 7-year observation. Conclusion: The case-survival rate of intractable cases was higher than that of untreated pulmonary tuberculosis patients and they may have risk of spreading multidrug resistant organisms. It is time we made an effort to improve case-management qualitatively.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.9-16
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• 2023

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of ⁶⁴Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that ⁶⁴Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

• Journal of Hospice and Palliative Care
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• v.16 no.3
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• pp.139-144
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• 2013

Advanced cancer patients tend to present multiple concurrent symptoms which are often moderate or severe in intensity. To date, the majority of studies have focused on either a single symptom, such as pain, fatigue, or depression or associated symptoms. While this approach has advanced understanding of some symptoms, it has offered clinicians not much guidance for treating several multiple concurrent symptoms in cancer patients. So in recent years, a few symptom management studies attempted a new approach of focusing on symptom clusters instead of individual symptoms. A symptom cluster is defined as two or more concurrent symptoms that are related to each other. If we better understand symptom clusters, interrelations of symptoms, and their common mechanisms in advanced cancer patients, clinicians can more effectively control multiple, concurrent symptoms and reduce drug side effects. And clinicians can also predict any other symptoms, functional performance, and the relationship between symptom clusters and survival in advanced cancer patients. At present, there is inconsistency in symptom clusters due to many unexplained mechanisms and various means to assess and analyze symptoms. Still, with further study, the approach to symptom clusters rather than individual symptoms could more effectively control symptoms and improve patients' quality of life.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.402-409
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• 2016

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

• Journal of Korean Neurosurgical Society
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• v.44 no.4
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• pp.222-227
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• 2008

Objective : Malignant gliomas are the most common primary cerebral neoplasms in adults. Despite multimodality treatments, the prognosis for patients with malignant glioma remains poor. However, recently, the effectiveness of concomitant chemoradiotherapy (CCRT) with temozolomide (TMZ) has been reported. We report for the first time preliminary results of the treatment with CCRT of newly diagnosed malignant gliomas in Korean people. Methods : Thirty-two patients over the age of 17 years with newly diagnosed and histologically confirmed high-grade gliomas (HGG), from June 2004 to August 2007 were the subjects of this study. There were 17 men and 15 women, with a median age of 53.5 years (range, 17-74). Pathologically, glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, and gliomatosis cerebri had been diagnosed in eighteen, eight, four, and two patients, respectively. These 32 patients were treated with CCRT with TMZ. Results : The median follow-up period was 12.5 months (range 3-48). At the time of this analysis, 13 patients died and three patients had been lost to follow-up. There was no mortality caused by drug toxicity. The median progression-free survival (PFS) of these patients was 9.0 months, and the six-month PFS rate was 72.4%. The median overall survival (OS) was 26 months, and the one-year OS rate was 83.6%. The 18 patients with glioblastoma were analyzed separately from the other patients with HGG, and the median OS was 18 months, and the one-year OS rates were 81.8%. The median PFS was seven months, and the six-month PFS rate was 75.0%. Conclusion : Our results are consistent with many other reports, confirming that CCRT with TMZ achieves good clinical outcomes in the treatment of HGG. Therefore, we suggest that CCRT with TMZ as adjuvant chemotherapy be considered as a standard therapy for patients with HGG.

• Parasites, Hosts and Diseases
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• v.27 no.2
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• pp.79-86
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• 1989

A pathogenic free-living amoeba, Naegleria fowleri, causes primary amoebic meningoencephalitis to human and experimental animals. This infection is rare, but the mortality is very high. Nowadays, drug treatment or active immunization of human or mice are being tried with partial effectiveness. This study shows passive immunization effect by transfer of immunized spleen cells, serum, or milk from immunized mother in mouse experimental model. Young BALB/c mice were immunized intraperitoneally with $2~3{\times}10^{6}$ trophozoites of N. fowleri, and spleen cells and sera were collected for injection to recipient mice. There were seven transfer groups, i.e., immunized mouse serum, spleen cells, serum and spleen cells, normal mouse serum, spleen cells, serum and spleen cells, and control group. Three days later, BALB/c mice were inoculated with $1{\times}10^{4}$ trophozoites of N. fowleri intranasally. After infection, decreased mortality ana prolonged survival time of mice were noted in immunized Bloops compared with non.immuniBed control group. The groups Injected with immunized spleen cells or normal serum shewed lower moltality than that of controls bult showed no changes of Serum IgG level. The groups injected with immunized serum or normal spleen cells showed increased serum IgG level after immunization but hundred percent mortality was observed. Mother mice were ifnfnunised increperitqneeliy with $2~3{\times}10^{6}$ trephozoites of N. fowleri at the end of pregnancy and weaning Period. Soon after the delivery, Jitters born of non-immunszed mother were matched with immunized mother for feeding immune milk. After three weeks, the litters were infected with $1{\times}10^{4}$ trophozeites of N. fowleri or sacrificed for serum collection to measure the IgG levels. The results show that anti-JV. fowleri IgG from mother was transferred to litter through milk but this IgG did not inauence the mortality or survival time of the infected mice.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2131-2135
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• 2013

Background: To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. Materials and Methods: A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. Conclusions: DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

• Radiation Oncology Journal
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• v.4 no.1
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• pp.1-13
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• 1986

In order to clarify the effect of radiation on the mouse jejunal crypt cells by combined administration of administration and radiation and also to evaluate the enhancing effect of adriamycin, the authors performed this study by delivering single irradiation of 1,000 to 1,600 rad to the whole abdomen of mice by cobalt-60 teletherapy unit. In combination with adriyamycin treatment groups, the drug was administered as single dose of 10 mg/kg either 2 hours before or 4 hours after graded single dose,900 to 1,400 rad, of irradiation. The authors studied the quantitative changes of intestinal crypt cells by microcolony survival assay technique and the morphological changes of small intestinal villi by scanning electron microscope in mice following to combined therapy with adriamycin and irradiation, The average number of jejunal crypts per circumference was $130{\pm}16$ in control group. The mean lethal dose(Do) of each irradiation alone and combined therapy groups 2 hours before and 4 hours after irradiation, were 160, 170, and 170 rad in cell survival curves, respectively. The dose effect factor(DEF) of adriamycin in each groups of pre-irradiation and post-irradiation were 1.19 and 1.26, respectively. The conical shaped villi were noted on 1,200 rad in irradiation alone group and 1,000 rad in combined groups. For the proper clinical application we must be careful of the radiation injury to small bowel when the anticancer chemotherapy and radiation therapy to the abdomen and pelvic area are used as combined therapeutic modality.

• The Korean Society of Law and Medicine
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• v.12 no.1
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• pp.177-225
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• 2011

Verdicts related to major medical litigation given by the Seoul Central District Court, the Seoul High Court and the Supreme Court in 2010 were analyzed. It's shown that in cases of the medical negligence regarding the occurrence of neonatal cerebral palsy, the plaintiff claims were dismissed using criteria proposed by associations of Obstetrics and Gynecology and Pediatrics in US, and thereof the burden of plaintiffs to prove the medical negligence has increased. In addition, in case of that the expected survival period of infants gets longer, payments for treatment and nursing after survival period determined by judges are made and it was judged to compensate it as a periodical indemnity. In case for the explanation obligation the most frequently mentioned in the medical litigation, in addition to cases of invoking the existing theory of explanation obligation, verdicts to mention the instructions of theory regarding instruction explanation obligation and the possibility of compensation for damages on property are given. Particularly, in cases for a liability of reparation by exaggerating the effects and not disclosing the risks related to treatment with stem cells, even if the treatment not approved by Food and Drug Administration is in violation of the Pharmaceutical Affairs Law, it's not illegal as violation in Pharmaceutical Affairs Law itself. But there is a certain verdict to present the possibility of an extension of the theory of explanation obligation by acknowledging the liability of reparation caused by illegal acts with no explanations of effects and risks of treatment with stem cell by doctors and pharmaceutical companies. In an incident in which a mental patient fell and died through the opened door of the roof at the hospital, a liability of reparation was acknowledged due to defects in structure installation management and this verdict drew an attention since the overall management responsibility about patients including structures was acknowledged to the hospital besides the obligations on medical practice. In case of the verdict without giving the opportunity to state the opinion with respect to the main legal issues, the responsibility of the court was emphasized since the court did not fulfill the explanation obligations. There were some cases in which payments for nursing and caring to a patient in vegetative state during the plastic surgery was admitted. However, in dental-related incidents, the proportion of cases in which plaintiff won was low since the difficulty of proving may be reflected. In the area of administrative litigation, unlike the existing position regarding arbitrary medical charge cover collected from patients in hospital, the verdict to admit the legitimacy of collection of medical treatment was given and attracted the attention of people. Verdict in which the expression related to medical advertisement was not exaggerated disposed the original verdict and pointed out the problem of excessive regulations on medical advertisement. The effort to analyze the trend of verdicts of court through reviewing the decisions and to organize should be continued, but the full decision should be disclosed as a base, and people and systems to enable the all time monitoring should be prepared.

• Journal of Gastric Cancer
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• v.15 no.4
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• pp.223-230
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• 2015

Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.