• Title/Summary/Keyword: Prognostic research

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Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

  • Awan, Tashfeen;Iqbal, Zafar;Aleem, Aamer;Sabir, Noreen;Absar, Muhammad;Rasool, Mahmood;Tahir, Ammara H.;Basit, Sulman;Khalid, Ahmad Mukhtar;Sabar, Muhammad Farooq;Asad, Sultan;Ali, Agha Shabbir;Mahmood, Amer;Akram, Muhammad;Saeed, Tariq;Saleem, Arsalan;Mohsin, Danish;Shah, Ijaz Hussain;Khalid, Muhammad;Asif, Muhammad;Haq, Riazul;Iqbal, Mudassar;Akhtar, Tanveer
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5469-5475
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    • 2012
  • Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

A Study on the Frequency of Occurrence of the Aortic Dissection using CT (CT 검사에서 대동맥박리(aortic dissection)의 발생빈도에 관한 고찰)

  • Dong, Kyung-Rae;Choi, Sung-Kwan;Jang, Young-Ill;Ro, Sang-Ho
    • Journal of radiological science and technology
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    • v.31 no.2
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    • pp.115-121
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    • 2008
  • Purpose: Aortic Dissection is very dangerous, prognostic disease, which the bloodstream flow out of the true lumen of the aorta by the bursting of aortic intima resulting in a rapid dissociation of inner and outer layer from the media. It is difficult to diagnose aortic dissection clinically by normal X-ray. This study was to investigate the occurrence frequency by age and number of patients who are identified to be aortic dissection by CT (Computed Tomography) scan. Materials and methods: We investigated the trend of yearly fluctuation, gender, age, and department of clinical research of the 112 patients who conducted CT scan in C- University Hospital for two years from January 2005 to December 2006. The MIP and SSD which reconstructed CT image and the VRT image were obtained for the accurate observation. The result was investigated by comparing normal X-ray and CT scan. Results and Conclusion: 1. The yearly check of 112 patients conducted CT scan showed 37 people (41.9%) in 2005, and it was increased to 65 (58.1%) in 2006 by 1.4 times. 2. The gender distribution of patients given a CT scan showed 45 males (40.1%), and female 67 (59.9 %). The aortic dissection patients were 9 (20%) out of 45 males, 21 (31.3%) out of 67 females and women were 1.6 times more than men. Women are also 1.5 times more than men in the number of examinee. 3. The age distribution of patient's who conducted CT scan revealed that there was no patient under 30 years old while 88.3% of all patients were through 41 to 80 years old. The higher the age was, the higher the occurrence of aortic dissection was. The difference in the occurrence frequency of age was statistically significant (p<0.01). 4. The departments that requested CT scan were the emergency department 46 (41.1%), circulatory internal medicine 37 (33.0%), chest surgery 13 (11.6%), and others 6 (14.3%). The combined ratio of emergency medicine and circulatory internal medicine was 74.1% of all. The results show that the aortic dissection is a very dangerous disease whose patients visit mainly via the emergency room. 5. The aortic dissection patients had normal X-ray readings in 22 (73.3%) out of 30, and only 8 (26.7 percent) are abnormal in the X-ray diagnosis. Therefore, the CT scan needs to be enforced in order to assess accurately the disease of aortic dissection.

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High-Resolution Numerical Simulations with WRF/Noah-MP in Cheongmicheon Farmland in Korea During the 2014 Special Observation Period (2014년 특별관측 기간 동안 청미천 농경지에서의 WRF/Noah-MP 고해상도 수치모의)

  • Song, Jiae;Lee, Seung-Jae;Kang, Minseok;Moon, Minkyu;Lee, Jung-Hoon;Kim, Joon
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.17 no.4
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    • pp.384-398
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    • 2015
  • In this paper, the high-resolution Weather Research and Forecasting/Noah-MultiParameterization (WRF/Noah-MP) modeling system is configured for the Cheongmicheon Farmland site in Korea (CFK), and its performance in land and atmospheric simulation is evaluated using the observed data at CFK during the 2014 special observation period (21 August-10 September). In order to explore the usefulness of turning on Noah-MP dynamic vegetation in midterm simulations of surface and atmospheric variables, two numerical experiments are conducted without dynamic vegetation and with dynamic vegetation (referred to as CTL and DVG experiments, respectively). The main results are as following. 1) CTL showed a tendency of overestimating daytime net shortwave radiation, thereby surface heat fluxes and Bowen ratio. The CTL experiment showed reasonable magnitudes and timing of air temperature at 2 m and 10 m; especially the small error in simulating minimum air temperature showed high potential for predicting frost and leaf wetness duration. The CTL experiment overestimated 10-m wind and precipitation, but the beginning and ending time of precipitation were well captured. 2) When the dynamic vegetation was turned on, the WRF/Noah-MP system showed more realistic values of leaf area index (LAI), net shortwave radiation, surface heat fluxes, Bowen ratio, air temperature, wind and precipitation. The DVG experiment, where LAI is a prognostic variable, produced larger LAI than CTL, and the larger LAI showed better agreement with the observed. The simulated Bowen ratio got closer to the observed ratio, indicating reasonable surface energy partition. The DVG experiment showed patterns similar to CTL, with differences for maximum air temperature. Both experiments showed faster rising of 10-m air temperature during the morning growth hours, presumably due to the rapid growth of daytime mixed layers in the Yonsei University (YSU) boundary layer scheme. The DVG experiment decreased errors in simulating 10-m wind and precipitation. 3) As horizontal resolution increases, the models did not show practical improvement in simulation performance for surface fluxes, air temperature, wind and precipitation, and required three-dimensional observation for more agricultural land spots as well as consistency in model topography and land cover data.

The Clinical and Histopathologic Features according to Loss of LKB1 Protein Expression on Primary Lung Cancer (원발성 폐암에서 LKB1 단백질 발현 소실에 따른 임상 양상 및 조직병리학적 특성)

  • Hwang, Ki Eun;Jo, Hyang-Jeong;Lee, Kang Kyoo;Sim, Hyeok;Song, Jung Sup;Shin, Jeong Hyun;Shin, Seong Nam;Park, Seong-Hoon;Hong, Kyeong-Man;Park, Jung-Hyun;Jeong, Jong-Hoon;Kim, Hui Jung;Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.5
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    • pp.362-368
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    • 2008
  • Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.

Expression of Matrix Metalloproteinases-9 and Stromelysin-3 in Peripheral Blood in Patients with Lung Cancer (폐암 환자의 말초혈액에서 Matrix metalloproteinase-9 및 Stromelysin-3의 발현)

  • Lim, Seong-Yang;Koh, Won-Jung;Kim, Cheal-Hong;Ahn, Young-Mee;Kwon, Young-Mee;Kang, Kyeong-Woo;Kim, Ho-Cheal;Suh, Gee-Young;Chung, Man-Pya;Lim, Si-Young;Kim, Ho-Joong;Kwon, O-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.2
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    • pp.107-116
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    • 2002
  • Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.