• Title, Summary, Keyword: renal carcinoma

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Development and Validation of the Determination of Sorafenib in Human Plasma using Tandem Mass Spectrometry Coupled with Liquid Chromatography (고속액체크로마토그래피 텐덤질량분석기법을 이용한 사람 혈장 내 소라페닙 농도분석법의 개발 및 검정)

  • Park, Daejin;Lee, Sunggon;Kim, Woomi
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1456-1462
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    • 2012
  • Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.

Direct Intratumoral Injection of Ethanol in the Patients with Obstruction of Major Bronchus (주기관지 폐색환자에서 종양내 ETHANOL 주입치료 효과)

  • Lee, Bong-Chun;Yum, Ho-Kee;Choi, Soo-Jeon;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.5
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    • pp.495-500
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    • 1993
  • Background: For the relief of the occlusion of major bronchi, laser therapy, radiation therapy or combined therapy is generally used. But the effect of radiation therapy is very slow and not consistent and laser therapy requires expensive equipments and technical expertise with occasional serious side effects. Direct ethanol injection has been widely used for the control of bleeding in gastrointestinal lesion, esophageal varices or renal cell carcinoma with good results. So we tried direct injection of ethanol into the tumor to relieve the obstruction of major bronchus in 11 patients. Method: All procedures were done under the fiberoptic bronchoscopy with continuous oxygen supplement and aliquoted 0.5-1.0 ml of absolute ethanol directly into the tumor through the endobronchial aspiration needle. The tumor was endoscopically removed with a biopsy forceps immediately after ethanol injection. The whole procedure was repeated 3-4 days interval until the lumen opens. Usually after 2-3 trials of ethanol injection, the lumen opened up. Results: The immediate effect of ethanol injection was whitening of the mucosa and prompt cessation of bleeding. The late effect was necrosis of the tumor. The final results of this procedure were improvement of symptoms and reexpnasion of the lung in all patients. $FEV_{1.0}$ and FVC were improved and $PaO_2$ was increased from $68.1{\pm}9.2$ mmHg to $83.9{\pm}8.1$ mmHg, $SaO_2$: from $94{\pm}8.5%$ to $96.6{\pm}1.1%$, and $AaDO_2$ was reduced from $26.5{\pm}8.5$ mmHg to $10.9{\pm}9.1$ mmHg. Conclusion: Direct ethanol injection into the tumor tissue is a rapid, cheap and relatively safe method of relieving the complete occlusion of major bronchus.

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The Changes of Serum Angiotensin Converting Enzyme Activity in Lung Cancer Patients (폐암 환자의 혈청 Angiotensin Converting Enzyme 활성도의 변화)

  • Jeong, Ki-Ho;Choi, Hyung-Seok;Yoo, Chul-Gyu;Lee, Kye-Young;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.4
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    • pp.310-317
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    • 1992
  • Background: Angiotensin converting enzyme is a glycoprotein peptidyldipeptide hydrolase which cleaves the c-terminal dipeptides of several oligopeptides. It is a menbrane-bound protein mainly synthesized by the endothelial cells. Since the lung has the largest capillary bed of any organ in the body, it is here that ACE acts on circulating substrates like angiotensin I and bradykinin. It is well known that ACE correlates with disease activity in sarcoidosis and also there are reports that changes in serum ACE activity are found in many acute and chronic lung diseases. So we planned this study to see if serum ACE activity can act as a prognostic factor in lung cancer. Methods: Forty-one newly diagnosed lung cancer patients were included in the study group. There were 19 patients with squamous cell lung cancer, 13 with adenocarcinoma, and 9 with small cell carcinoma. Patients were excluded from the study if they had high blood pressure, heart disease, liver disease, renal disease, or other lung disease. Serum ACE activity was analyzed according to cell type, staging, mode of treatment, and clinical response to treatment. Results: 1) There was no difference in serum ACE activity between lung cancer patients and the control group. Also no difference in serum ACE activity was found according to cancer cell type or staging. 2) In patients who underwent curative resection of lung cancer, serum ACE activity was decreased significantly after the operation. 3) In patients who were diagnosed as non-small cell lung cancer and were treated with 4 cycles of anti-cancer chemotherapy without clinical improvement, changes in serum ACE activity were not seen after the treatment. 4) In patients diagnosed as small cell lung cancer treated with 4 cycles of anti-cancer chemotherapy with clinical improvement, changes in serum ACE activity were also not observed. Conclusion: Serum ACE activity was decreased after lung resection but had no relation to cell type, staging, or clinical response to treatment in lung cancer patients. Therefore, serum ACE activity is not suitable in predicting clinical outcome of lung cancer patients.

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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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Noncardiac Applications of Cardiopulmonary Bypass (비심장질환에서의 심폐바이패스 적용)

  • Kim, Won-Gon;Oh, Sam-Sae;Kim, Ki-Bong;Ahn, Hyuk;Kim, Chong-Whan
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.31 no.9
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    • pp.877-883
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    • 1998
  • Background: Cardiopulmonary bypass(CPB), a standard adjunct for open heart surgery, can also play an important role in treating patients with noncardiac diseases. Material and Method: We report a collective analysis of noncardiac applications of cardiopulmonary bypass experienced at Seoul National University Hospital from 1969 to 1996. Out of a total of 20 patients, 8 were treated for membranous obstruction of inferior vena cava(MOVC), 5 for malignant melanoma, 3 for pulmonary embolism, 1 for double lung transplantation, 1 for intracranial giant aneurysm(GA), 1 for renal cell carcinoma(RC), and 1 for liposarcoma. CPB was used to induce profound hypothermia with circulatory arrest in 6 patients(MOVC 4, GA 1, RC 1). Result: CPB time was 113 mins on average for MOVC, 161 mins for GA, and 156 mins for RC, while the lowest rectal temperature was 26$^{\circ}C$ on average in MOVC, and 19$^{\circ}C$ in GA and RC. Postoperative recovery was good in all MOVC patients. The patient with GA, who underwent reoperation for the removal of hematoma, died 14 days postoperatively. The patient with RC recovered from the operation in a good condition but died from metastatic spread 6 months later. CPB was instituted for pulmonary embolectomy in 3 patients, in whom postoperative courses were uneventful, except in 1 patient who showed transient neurologic symptoms. CPB was used in a patient with double-lung transplantation for hemodynamic and ventilatory support. The patient was weaned successfully from CPB but died from low output and septicemia 19 days postoperatively. CPB without circulatory arrest was used to treat in 4 patients with MOVC. These patients showed good postoperative courses. CPB was used to administer high concentrations of chemotherapeutic agents to the extremities in 6 patients(malignant melanoma 5, recurrent liposarcoma 1). CPB time was 153 mins on average. No complications such as edema and neurologic disability were found. Conclusion: Although CPB has a limited indication in noncardiac diseases, if properly applied, it can be a very useful adjunct in a variety of surgical cases.

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Tumor Prosthetic Replacement for the Metastatic Bone Tumors Involving the Proximal Femur (대퇴골 근위부 전이성 종양 환자의 종양 대치물 삽입술)

  • Sung, Ki-Sun;Chang, Moon-Jong
    • The Journal of the Korean bone and joint tumor society
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    • v.13 no.1
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    • pp.48-54
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    • 2007
  • Purpose: To evaluate clinical results of the tumor prosthetic replacement for pathologic fracture of the proximal femur with extensive bony destruction due to metastatic bone tumors. Materials and Methods: From 2005 October to 2006 October, resection of proximal femur and tumor prosthesis replacement was performed for metastatic bone tumors extensively involving trochanteric area in 6 patients. The mean age of overall patients was 61(range, 48~77). Mean clinical follow up was 10.5 months (range, 6~16). Primary tumor consisted with multiple myeloma in 2 patients, lung cancer in 1, breast cancer in 1, transitional cell carcinoma of the renal pelvis in 1, unknown origin in 1 patient. $MUTARS^{(R)}$ proximal femur (Implantcast, Munster, Germany) were used in all cases. The functional evaluation in the lower extremities was performed with Musculoskeletal Tumor Society 1993 scores. The degree of pain relief after surgical treatment was assessed with Visual Analogue Scale (VAS). Results: At the final follow up, all of the patients survived. The mean lower extremities functional score of Musculoskeletal Tumor Society 1993 was 17.8(59.3%)(range, 12~25). VAS was improved to 2.5 from 8.5 after the surgical treatment. Ambulation was encouraged as soon as possible and mean duration after surgery for ambulation was 7.3(range, 3~16) days. Post-operatively, there was no surgical infection, periprosthetic fracture or loosening. Dislocation occurred in one out of six cases. Conclusion: Resection of proximal femur and tumor prosthesis replacement for metastatic bone tumors around proximal femur extensively involving trochanteric area seems to be safe procedure in view of post-operative complication, and effective for functional restoration as well as pain relief. Thus, it is accordant to the treatment principle of the metastatic bone tumors.

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Small Animal PET Imaging with [$^{124}I$]FIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model (간암 동물 모델에서 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabinofuranosyl-5-[$^{124}I$iodo-uracil ($[^{124}I]FIAU$) 소동물 PET 영상 연구)

  • Chae, Min-Jeong;Lee, Tae-Sup;Kim, June-Youp;Woo, Gwang-Sun;Jumg, Wee-Sup;Chun, Kwon-Soo;Kim, Jae-Hong;Lee, Ji-Sup;Ryu, Jin-Sook;Cheon, Gi-Jeong;Choi, Chang-Woon;Lim, Sang-Moo
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.3
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    • pp.235-245
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    • 2008
  • Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.