• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.925-928
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• 2014

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD=13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

• Genomics & Informatics
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• v.16 no.4
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• pp.26.1-26.12
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• 2018

Shigella spp. constitutes some of the key pathogens responsible for the global burden of diarrhoeal disease. With over 164 million reported cases per annum, shigellosis accounts for 1.1 million deaths each year. Majority of these cases occur among the children of the developing nations and the emergence of multi-drug resistance Shigella strains in clinical isolates demands the development of better/new drugs against this pathogen. The genome of Shigella flexneri was extensively analyzed and found 4,362 proteins among which the functions of 674 proteins, termed as hypothetical proteins (HPs) had not been previously elucidated. Amino acid sequences of all these 674 HPs were studied and the functions of a total of 39 HPs have been assigned with high level of confidence. Here we have utilized a combination of the latest versions of databases to assign the precise function of HPs for which no experimental information is available. These HPs were found to belong to various classes of proteins such as enzymes, binding proteins, signal transducers, lipoprotein, transporters, virulence and other proteins. Evaluation of the performance of the various computational tools conducted using receiver operating characteristic curve analysis and a resoundingly high average accuracy of 93.6% were obtained. Our comprehensive analysis will help to gain greater understanding for the development of many novel potential therapeutic interventions to defeat Shigella infection.

• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.297-308
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• 2006

Fowl typhoid (FT) is a septicemic disease caused by Salmonella gallinarum. The purpose of this study was to investigate the antimicrobial resistance and pulsed -field gel electrophoresis (PFGE) patterns of S gallinarum isolated from broiler. During 1999 to 2004, there was isolated a total of 26 strains in liver and spleen. The biochemical characteristics of S gallinarum isolates was nonmotile, no production of $H_2S$, glucose gas, non-fermented rhamnose, indole-negative, fermentation of dulcitol, mannitol, maltose, and ornithine decarboxylase. At antimicrobial susceptibility, all of isolates were susceptible to amoxicillin/clavulanic acid, amikacin, neomycin, kanamycin, and cephalothin. Twenty-six isolates were divided into 19 resistant patterns and 6 strains was 8-multi-drug resistance. PFGE of Xba I restriction fragments of S gallinarum isolates was 22 patterns.

• Korean Journal of Veterinary Service
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• v.32 no.2
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• pp.155-163
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• 2009

Fowl typhoid (FT) is a septicemic disease caused by Salmonella Gallinarum. The purpose of this study was to investigate the antimicrobial resistance and pulsed-field gel electrophoresis (PFGE) patterns of S. Gallinarum isolated from chicken. During 1999 to 2004, there was isolated a total of 100 strains in liver and spleen. The biochemical characteristics of S. Gallinarum isolates was nonmotile, no production of H$_2$S, glucose gas, non-fermented rhamnose, indole-negative, fermentation of dulcitol, mannitol, maltose, and ornithine decarboxylase. At antimicrobial susceptibility, all of isolates were susceptible to amoxicillin/clavulanic acid, amikacin, neomycin, kanamycin, norfloxacin and enrofloxacin. One hundred isolates were divided into 54 resistant patterns and 37 strains was 6-multi drug resistance. PFGE of Xba I restriction fragments of S. Gallinarum isolates was 20 patterns.

• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.489-498
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• 2018

Objective: Foot and mouth disease (FMD) and porcine reproductive and respiratory syndrome (PRRS) are major diseases that interrupt porcine production. Because they are viral diseases, vaccinations are of only limited effectiveness in preventing outbreaks. To establish an alternative multi-resistant strategy against FMD virus (FMDV) and PRRS virus (PRRSV), the present study introduced two genetic modification techniques to porcine cells. Methods: First, cluster of differentiation 163 (CD163), the PRRSV viral receptor, was edited with the clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 technique. The CD163 gene sequences of edited cells and control cells differed. Second, short hairpin RNA (shRNAs) were integrated into the cells. The shRNAs, targeting the 3D gene of FMDV and the open reading frame 7 (ORF7) gene of PRRSV, were transferred into fibroblasts. We also developed an in vitro shRNA verification method with a target gene expression vector. Results: shRNA activity was confirmed in vitro with vectors that expressed the 3D and ORF7 genes in the cells. Cells containing shRNAs showed lower transcript levels than cells with only the expression vectors. The shRNAs were integrated into CD163-edited cells to combine the two techniques, and the viral genes were suppressed in these cells. Conclusion: We established a multi-resistant strategy against viral diseases and an in vitro shRNA verification method.

• The Plant Pathology Journal
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• v.25 no.4
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• pp.408-416
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• 2009

A molecular survey was conducted to identify the presence of the bacterial blight resistance genes (Xa1, Xa4, xa5, xa13 and Xa21) in 86 accessions of aromatic rice obtained from germplasm. The results revealed that the resistance gene Xa4 (32.5%), Xa21 (17%), and xa5 (16%) were widely observed in tested rice germplasm. Among tested rice germplasm, 49 accessions showed the presence of more than one of five R genes, and 37 accessions possessed none of the R gene. TALLi and 05-IRRi-M-46 showed the presence of Xa4, xa5, xa13 and Xa21. Rice race $415{\times}Ir352$ exhibited positive amplicon for the Xa1, Xa4, xa5 and Xa21. Hyangmibyeo1hos, Ir841-85-1-1-2 and Jasmine85 showed the positive amplicon for the Xa1, Xa4 and xa5 genes. Yekywin Yinkya Hmwe and Khao Dawk Mali105 showed the presence of Xa1, Xa4 and Xa21 gene. Masino Basmati showed the presence of xa5, xa13, Xa21 genes. Xa1 and Xa21 genes were noticed in Mihayngbyeo, Tarana Deshi, Mayataung and AZUCENA. Hyangmibyeo2ho, Basmati 6311 and Basmati405 possessed only two R genes such as Xa4 and xa5, and xa5 and xa13, respectively. The evaluation results of bacterial blight resistance genes in aromatic rice germplasm will help in breeding of multi disease resistant varieties.

• Journal of Chest Surgery
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• v.36 no.11
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• pp.839-845
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• 2003

Background: Even today when chemotherapy has been established as a treatment for tuberculosis and the prevalence of tuberculosis is gradually decreasing, multi-drug resistance tuberculosis still results in poor treatment performance and lowered survival periods. This research sought to analyze the surgery of multi-drug resistance tuberculosis, and determine the usefulness and danger of surgery in connection with this disease. Material and Method: Starting from February 1990 to February 2002, retrospective surveys were conducted targeted at 21 cases involving 20 patients who underwent surgery due to multi-drug resistance tuberculosis. The survey included 14 males cases and 6 females cases with the age averaging 42.8$\pm$12.1 years. 10.3$\pm$7.6 years on average passed after patients were initially diagnosed with tuberculosis. 13 patients (65%) tested positive in the pre-operative sputum AFB test, and all showed resistance against an average of 3.5 anti-tuberculosis agents including INH and RFP. Pre-operative radiologic examinations revealed cavitary lesions in 15 patients (75%), and three patients had lesions in the both lung fields, with the major lesions existing in the unilateral area. 13 patients (75%) failed negative conversion with medical treatment, while two patients (10%) with recurrent hemoptysis and five patients (25%) with lesions involving high recurrence-rate received the operation. Operations included nine cases (40%) of pneumonectomy, nine cases (45%) of lobectomy, and three cases of lobectomy with segmentectomy. The average follow-up period of patients stood at 23 months. Result: There was no post-operative death, and found were a total of eleven cases involving complications were found: three cases of long-term air leakage, three cases of bleeding requiring re-operation, two cases of empyemas due to broncho-pleural fistula, and one case of atelectasis, wound infection and chest wall fistula each. Eleven cases (85%) of negative conversion were completed immediately after the operation, and two cases failed negative conversion. Eleven months after the operation, the disease recurred in one case of negative conversion patients, and the patient was cured by completion pneumonectomy. Conclusion: If patients' lung function was sufficient and appropriate resection was possible, multi-drug resistance tuberculosis could achieve high-rate negative conversion and cure using combination of surgical and medical treatment, and also there were not many serious complications.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2575-2580
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• 2015

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.

• Proceedings of the Microbiological Society of Korea Conference
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• 2002.10a
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• pp.40-50
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• 2002

Fruit fly, Drosophila melanogaster has developed efficient immune mechanisms to prevent microbial infection, which are consisted of cellular and humoral responses. During the systemic or local infection, two distinct pathways (Toll and Imd) play major roles in antimicrobial peptide synthesis. The Toll pathway is required to defend Gram-positive bacterial and fungal infections, whereas the Imd pathway is important in Gram-negative bacterial infection. We have shown that the infection of the opportunistic Gram-negative bacterium, Pseudomonas aeruginosa strain PA14 (PA14) into fly dorsal thorax can kill the flies within 48 h ($100\%$ mortality) in our optimized infection condition, suggesting that the PA14 strain can cause disease progress in fly model system. We found that flies carrying a constitutively activated mutant form of the Toll receptor $(Tl^{10b})$ showed increased resistance to P. aeruginosa infection and that flies carrying mutations in the Toll signaling pathway as well as in the Imd signaling pathway was more susceptible to PA14 infection. All these results imply that the Toll pathway might be important in the resistance to this pathogenic Gram-negative bacterial infection.