• Title/Summary/Keyword: renal cancer

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Mirogabalin: could it be the next generation gabapentin or pregabalin?

  • Kim, Jae-Yeon;Abdi, Salahadin;Huh, Billy;Kim, Kyung-Hoon
    • The Korean Journal of Pain
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    • v.34 no.1
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    • pp.4-18
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    • 2021
  • Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige®) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.

Expression of ERCC1, RRM1 and LRP in Non-small Cell Lung Cancers and their Influence on Chemotherapeutic Efficacy of Gemcitabine Concomitant with Nedaplatin

  • Qiu, Zhen-Qin;Zhao, Kun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7303-7307
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    • 2014
  • Objective: To explore the clinical efficacy of gemcitabine concomitant with nedaplatin and drug resistance in the treatment of non-small cell lung cancer (NSCLC) and associated molecular predicators. Materials and Methods: A total of 68 patients diagnosed with NSCLC by histology served as the study objects and were randomly divided into an observation group treated with gemcitabine concomitant with nedaplatin and a control group with cisplatin concomitant with gemcitabine, 34 cases for each group. Short-term and long-term efficacies, adverse responses as well as the expression of nucleotide excision repair cross complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and lung resistance-related protein (LRP) in NSCLC tissues in both groups were assessed. Results: The short-term objective response rate (ORR) and disease control rate (DCR) were 35.3% (12/34) and 76.5% (26/34) in the observation group and 38.2% (13/34) and 85.3% (29/34) in the control group, respectively, the differences not being statistically significant. The time to progression (TTP) in both groups were 1~12 months, while the median TTP was 135 d and 144 d, respectively. Though the survival was slightly higher in the control group, there were no significant differences in TTP and survival time. The rates of decreased hemoglobin, vomiting and nausea as well as renal toxicity were evidently lower in the observation group, while other adverse responses demonstrated no significant difference. The positive expression rates of ERCC1, RRM1 and LRP were 47.1% (16/34), 61.8% (21/34) and 64.7% (22/34) in the observation group, respectively. Compared with negative ERCC1 expression, ORR had decreasing trend and the overall survival time (OS) decreased significantly in patients with positive ERCC1 expression, which were markedly decreased by the positive expressions of RRM1 and LRP. Conclusions: Gemcitabine concomitant with nedaplatin has significant effects in the treatment of NSCLC, with an adverse response rate obviously lower than for cisplatin concomitant with gemcitabine, suggesting that wider use in the clinic is warranted. Additionally, the positive expressions of ERCC1, RRM1 and LRP may increase patient drug resistance, so they can be applied as the chemotherapeutic predicators to guide individualized therapy of NSCLC patients.

Hepatoprotective Activity of Salidroside Isolated from Acer Termentosum Max on D-galactosamine Induced Hepatotoxicity in Rats (산겨릅나무에서 분리한 salidroside의 간보호 효과)

  • Kim, Sung-Hoon;Park, Hee-Juhn;Choi, Jon-Won
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1525-1531
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    • 2008
  • Acer tegmentosum Max which is one of the specialized wildness medicinal herbs in gangwon province, has been widely used for hepatitis, liver cirrhosis, hepatic cancer, leukemia, diabetes mellitus, renal necrosis and edema, etc. In this study, the antioxidative and hepatoprotective effects of in vitro and in vivo were investigated in order to evaluate the possibility as hepatoprotective agents. Oral administration of methanol and butanol extact of Acer tegmentosum Max to d-galactosamine (D-GaIN) induced experimental liver injured rats was significantly reduced activities of marker enzymes(AST, ALT) and LDH activity in serum. Salidroside(Sal) isolated from the BuOH extract of Acer termentosum Max potenty showed the scavenzing effect on DPPH and inhibitory effect on lipid peroxidation. And significantly decrcease of MDA level in liver and activities of SOD GSH-Px and catalase were significantly improved by the treatment of Sal. Results of this study revealed that Sal could afford a significant protection in the alleviation of D-GaIN-induced hepatocellular injury.

Selective Cytotoxicity of Novel Platinum(II) Coordination Complexes Containing DL-2-Hydroxy 3-Methylbutyric Acid (DL-2 하이드록시 3-메틸 부틸산물 배위자로 한 새로운 항암성 백금(II) 착체의 위암세포와 정상신장세포에 대한 선택적 세포독성)

  • 정지창;홍언표;최승기;장성구;육창수;노영수
    • Biomolecules & Therapeutics
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    • v.11 no.2
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    • pp.91-98
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    • 2003
  • A new series of highly water soluble platinum(II) complexes[Pt(II)(DL-2-hydroxy-3-methylbutyrate)(trans-l-1,2-dimninocyc1ohexane)] (PC-1) and [Pt(II)DL-2-hydroxy-3-methylbutyrate](cis-1,2-diaminocyclohexane)](PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared(IR), $^{13}C$-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II)complexes was tested against MKN-45, MKN/ADM and MKN/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 and PC-2 showed active against MKN-45/P, MKN/ADM and MKN/CDDP human gastric cancer cell lines, and the antitumor activity of these compounds were comparable or superior to that of cisplatin. The nephrotoxicities of PC-1 and PC-2 were found quite less then that of cisplatin using MTT and [$^3H$] thymidine uptake tests in rabbit proximal tubule cells, human kidney cortical cells human renal cortical tissues. Based on these results, these novel platinum(II) complex compounds(PC-1 & PC-2) represent a valuable lead in the development of the new anticancer chemotherapeutic agents capable of improving antitumor activity and low nephrotoxicity.

Arsenic Poisoning (비소 중독)

  • Kim Yang Ho;Lee Ji Ho;Sim Chang Sun;Jeong Kyoung Sook
    • Journal of The Korean Society of Clinical Toxicology
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    • v.2 no.2
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    • pp.67-71
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    • 2004
  • Arsenic poisoning has three types of poisoning. First, acute arsenic poisoning is usually caused by oral intake of large amount of arsenic compound with purpose of homicide or suicide. Second, chronic arsenic poisoning is caused by inhalation of arsenic in the occupational setting or by long-term oral intake of arsenic-contaminated well water. Third, arsine poisoning occurs acutely when impurities of arsenic in non-ferrous metal react with acid. Clinical manifestation of acute arsenic poisoning is mainly gastrointestinal symptoms and cardiovascular collapse. Those of chronic poisoning are skin disorder and cancer. Arsine poisoning shows massive intravascular hemolysis and hemoglobinuria with acute renal failure. Exposure evaluation is done by analysis of arsenic in urine, blood, hair and nail. Species analysis of arsenic is very important to evaluate inorganic arsenic acid and mono methyl arsenic acid (MMA) separated from dimethyl arsenic acid (DMA) and trimethyl arsenic acid (TMA) which originate from sea weed and sea food. Treatment with dimercaprol (BAL) is effective in acute arsenic poisoning only.

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Clinical Analysis of Ssophagovisceral Anastomosis (식도 장 문합수술의 임상적 고찰)

  • Baek, Hyo-Chae;Lee, Du-Yeon
    • Journal of Chest Surgery
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    • v.28 no.11
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    • pp.1025-1031
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    • 1995
  • Thirty patients who underwent esophageal resections due to esophageal carcinoma and benign strictures, and esophagovisceral anastomoses were performed by hand suture in 11 patients[Group I and by using the end to end anastomosis[EEA stapler in 19 patients[Group II . Anastomoses were performed in the thoracic cavity in 24 patients[Right 19, Left 5 and in the cervical area in 6 patients. There was one operative mortality[3.3% in a cancer patient who underwent Ivor-Lewis operation using EEA stapler. She expired on POD 38 days due to renal failure and sepsis. There were two anastomotic leakage in the sutured group and no anastomotic leakage in the stapled group. Late anastomotic strictures occurred in 10 patients[52.6% in the stapled group compared to 2 patients[18.1% in the sutured group. Most of the patients with late anastomotic strictures responded to one or two trials of TTS dilations. Using EEA stapler in performing esophagovisceral anastomosis is a safe method with acceptable range of complication rate, and total admission period after the operation for group I was 30.3 days compared to 25.4 days in group II although it had no clinical significance. The follow up was possible in 23 patients; 5 patients in group I died within mean 12.6 months and 9 patients in group II within mean 14.2 months.

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Kidneys with bad ends (신장 기능과 틸로미어)

  • Suh, Dong-Chul
    • Childhood Kidney Diseases
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    • v.12 no.1
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    • pp.11-22
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    • 2008
  • Telomeres consist of tandem guanine-thymine(G-T) repeats in most eukaryotic chromosomes. Human telomeres are predominantly linear, double stranded DNA as they ended in 30-200 nucleotides(bases,b) 3'-overhangs. In DNA replication, removal of the terminal RNA primer from the lagging strand results in a 3'-overhang of uncopied DNA. This is because of bidirectional DNA replication and specificity of unidirectional DNA polymerase. After the replication, parental and daughter DNA strands have unequal lengths due to a combination of the end-replication problem and end-processing events. The gradual chromosome shortening is observed in most somatic cells and eventually leads to cellular senescence. Telomere shortening could be a molecular clock that signals the replicative senescence. The shortening of telomeric ends of human chromosomes, leading to sudden growth arrest, triggers DNA instability as biological switches. In addition, telomere dysfunction may cause chronic allograft nephropathy or kidney cancers. The renal cell carcinoma(RCC) in women may be less aggressive and have less genomic instability than in man. Younger patients with telomere dysfunction are at a higher risk for RCC than older patients. Thus, telomeres maintain the integrity of the genome and are involved in cellular aging and cancer. By studying the telomeric DNA, we may characterize the genetic determinants in diseases and discover the tools in molecular medicine.

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T Lymphocyte Development and Activation in Humanized Mouse Model

  • Lee, Ji Yoon;Han, A-Reum;Lee, Dong Ryul
    • Development and Reproduction
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    • v.23 no.2
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    • pp.79-92
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    • 2019
  • Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.

A Literatural Study on Basements, Methods, Clinical Applications of Anal Therapy (肛腸治療의 原理, 常用方法 및 臨床應用에 對한 文獻的 考察)

  • Roh, Hun-Jung;Moon, goo
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.12 no.2
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    • pp.124-145
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    • 1999
  • Anal Therapy is taken valid compound of herb med and has many kinds of treatments. As one of the anal therapy, retention enema is most common and useful way. This study was performed in order to literatural basements of clinical treatments. we had cleared manifest about the origin and literatural basement of anal therapy, methods of management, classification of indication, clinical application and so forth. The results were summerised as follows. 1. It explained relationships between anus and Ojang-yukbu(五臟六腑), Sibie-geongmaek(十二經脈). But in fact the origin of anal therapy is Milgeon-dobub(蜜煎導法) and Jedamjib-dobub(猪膽汁導法) in Sanghan-jabbyungron(傷寒雜病論) of Han Dynasty. 2. The effect of anal therapy can be reached to the destination through theory of the organism which is called Jung-chei theory(整體論) and local medical action. We can find a little in Naegeong(內經), which is basement of Hang-jang therapy. 3. Anal Therapy have Kwanjaogbub(灌腸法), Guhangbub(灸肛法), Dohangbub(塗肛法), Hoonhangbub(熏肛法), Saekhangbub(塞肛法), Youkhangbub(浴肛法), Jwajeombub(坐점法) e.t.c. 4. Anal Therapy is available when person can't taken by mouth. Its benefits are fast effect and low side effect about liver because it is not taken trough liver mostly. 5. Anal Therapy has been used for the treatment of diseases such as stroke, high fever, pneumonia, ulcerative colitis, prostatitis, renal failure, pelvic inflammation. cancer and so on.

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Expression of the FHIT gene Located in Chromosome 3p14.2 in Human Lung Cancer Cell Lines (폐암 세포주에서 염색체 3p14.2에 위치한 FHIT 유전자의 발현 이상에 대한 연구)

  • Kim, Cheol-Hyeon;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.984-991
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    • 1998
  • Background: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. Methods: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed. first strand cDNAs were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. Results: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. Conclusion: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.

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