• Title/Summary/Keyword: Partial response

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A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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A Prospective Clinical Trial on the Mg Oxidized Clinical Implants (마그네슘 양극산화 임플란트의 성공률에 관한 전향적 임상연구)

  • Im, So-Min;Kim, Dae-Gon;Park, Chan-Jin;Cho, Lee-Ra;Um, Heung-Sik;Lee, Jae-Kwan
    • Journal of Dental Rehabilitation and Applied Science
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    • v.27 no.1
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    • pp.25-39
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    • 2011
  • In animal studies, Magnesium (Mg) - incorporated oxidized implants showed significant enhancement of the bone response. This prospective clinical trial was performed to investigate the success rate, implant stability and marginal bone loss of Mg oxidized clinical implant. The experimental protocol was approved by Institutional Review Board of the Gangneung-Wonju National University Dental Hospital. Fifty healthy patients had partial edentulism were included in this study. Mg oxidized clinical implants (Implant M, Shinhung, Korea) were installed and restored with conventional protocol. The patients were recalled at 1, 3, 6 months after functional loading. Implant stability quotient (ISQ) was measured and periapical radiographic images were obtained. Amount of marginal bone loss was calculated with calibrated images from periapical radiographs. Repeated measured analysis of variance and post hoc Tukey test were used to compare the mean ISQ and bone level. A total of 101 implants were analyzed. The mean ISQ values increased continuously with time lapse from 68.4 at fixture installation to 71.5 at 6 months after loading. Implant stability was correlated with gender, fixture diameter, bone quality and implant sites. The mean marginal bone loss during 6 months after loading was 0.26 mm. There was no failed implant and six-month success rate was 100%. Within the limitations of this study, the six-month success rate of Mg oxidized implant was satisfactory. The implant stability and marginal bone level were excellent. However, further longer clinical studies will be needed to confirm the success of Mg oxidized clinical implant.

DEU-7 Derived from Ulmus macrocarpa Improved Immune Functions in Cyclophosphamide-treated Mice (면역억제 마우스 모델에서 왕느릅나무 유래 DEU-7의 면역기능 증강)

  • Kang, Kyung-Hwa;Go, Ji Su;Lee, Inhwan;Lee, Sang Ho;Lee, Sung Do;Kim, Deok Won;Lee, Jong-Hwan;Hwang, HyeJin;Hyun, Sook Kyung;KIM, Byoung Woo;Kim, Chul Min;Chung, Kyung Tae
    • Journal of Life Science
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    • v.25 no.10
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    • pp.1156-1163
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    • 2015
  • The present study investigated the immunomodulatory properties of four different medicinal plants in a cyclophosphamide-treated Balb/c mouse model. One of the four plants, Ulmus macrocarpa, showed partial resistance against immune suppression induced by cyclophosphamide. The bark of U. macrocarpa, commonly known as the Chinese elm, has been used as a pharmaceutical material in Korean traditional medicine to treat bacterial inflammation and induce wound healing. In this study, water extract of U. macrocarpa, named DEU-7, was used for its immunomodulating functional activity. DEU-7 increased the weight of the spleen and the number of splenocytes but did not significantly affect the liver, kidney, and thymus in vivo. A splenocyte viability assay confirmed that DEU-7 influenced ex vivo splenocyte survival. DEU-7 also increased the levels of cytokines, such as IL-2 and IL-4, and immunoglobulins, such as IgM, IgG, and IgA. These results indicated that DEU-7 is involved in the activation of T and B lymphocytes. In addition, DEU-7 was able to maintain the production of cytokines, such as TNF-α, IL-12, and IFN-γ, in the condition of cyclophosphamide-induced immune suppression, suggesting that DEU-7 activated innate immune cells, even under immune suppression. We concluded that DEU-7 aids immunological homeostasis, thereby preventing immune suppression, and aids both innate and adaptive immune response by maintaining the levels of various cytokines and immunoglobulins. Consequently, it is worth investigating the potential of DEU-7 as a supplemental source for immune-enhancing agents.

Strength and Deformation Capacities of Short Concrete Columns with Circular Section Confined by GFRP (GFRP로 구속된 원형단면 콘크리트 단주의 강도 및 변형 능력)

  • Cho, Soon-Ho
    • Journal of the Korea Concrete Institute
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    • v.19 no.1
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    • pp.121-130
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    • 2007
  • To investigate the enhancement in strength and deformation capacities of concrete confined by FRP composites, tests under axial loads were carried out on three groups of thirty six short columns in circular section with diverse GFRP confining reinforcement. The major test variables considered include fiber content or orientation, wrap or tube type by varying the end loading condition, and continuous or discontinuous confinement depending on the presence of vortical spices between its two halves. The circumferential FRP strains at failure for different types of confinements were also investigated with emphasis. Various analytical models capable of predicting the ultimate strength and strain of the confined concrete were examined by comparing to observed results. Tests results showed that FRP wraps or tubes provide the substantial increase in strength and deformation, while partial wraps comprising the vertical discontinuities fail in an explosive manner with less increase in strength, particularly in deformation. A bilinear stress-strain response was observed throughout all tests with some variations of strain hardening. The failure hoop strains measured on the FRP surface were less than those obtained from the tensile coupons in all tests with a high degree of variation. In overall, existing predictive equations overestimated ultimate strengths and strains observed in present tests, with a much larger scatter related to the latter. For more accuracy, two simple design- oriented equations correlated with present tests are proposed. The strength equation was derived using the Mohr-Coulomb failure criterion, whereas the strain equation was based on entirely fitting of test data including the unconfined concrete strength as one of governing factors.

The Effect of Adjuvant Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma after Induction Chemotherapy (국소진행 두경부 상피세포암에서 선행유도약물요법 후 보조약물요법의 효과)

  • Kim Cheol-Woo;Roh Jae-Kyung;Ahn Joong-Bae;Park Joon-Oh;Chung So-Young;Lee Seok;Lee Hey-Ran;Lee Kyung-Hee;Chung Hyun-Cheol;Kim Joo-Hang;Kim Byung-Soo;Suh Chang-Ok;Kim Gwi-Eon
    • Korean Journal of Head & Neck Oncology
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    • v.10 no.1
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    • pp.13-24
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    • 1994
  • Despite optimal local therapy such as surgery and/or radiotherapy, the long term outcome is poor for patients with advanced squamous cell carcinomma of head and neck, due to frequent loco-regional recurrence and distant metastases. We studied to determine whether the combination chemotherapy, especially as an adjuvant chemotherapy, would improve the survival of these patients. Between January, 1986 and December, 1992, 57 patients with previously untreated, locally advanced squamous cell arcinoma of head and neck were assigned to receive 2-3 cycles of induction chemotherapy consisting of 5-fluorouracil(F) and cisplatin(P) every 3 weeks and standard local therapy such as surgery and/or radiotherapy followed by adjuvant chemotherapy with the same FP regimens. Of the 57 enroled patients, 45 patients were evaluable. The obtained results were as following: 1) Among 45 evaluable patients, 18 patients finished all treatment protocol including adjuvant chemotherapy and 27 patients had no adjuvant chemotherapy. The difference of age, sex, performance status, disease stage, and tumor differentiation was not significant statistically between adjuvant chemotherapy group and no-adjuvant chemotherapy group. 2) After induction chemotherapy, 7/45(15.4%), 30/45(67%) achieved complete remission and partial remission respectively with 82.4% overall response rates in entire patients. 3) The 4year progression free survival was 43.3% in adjuvant chemotherapy group and 24.1% in no-adjuvant chemotherapy group(p>0.05). The 4year overall survival was 56.9% and 25.5% respectively(p>0.05). There was no significant different in the patterns of local recurrence and distant metastasis between the two groups. 4) Adverse reactions from combination chemotherapy included nausea, vomiting, mucositis, diarrhea and hematologic bone marrow depression. These were mild and tolerated by patients, and these was no episode of any life threatening toxicities. In conclusion, adjuvant chemotherapy after induction chemotherapy and local therapy did not show statistically significant survival improvement, but there was trend of prolongation of survival when compared to no adjuvant chemotherapy. Thus, large scale phase III randomized controlled studies are strongly recommended.

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The Change of Squamous Cell Cancer Antigen (SCC Ag) Level as A Tumor Marker in Squamous Cell Lung Cancer (편평세포 폐암환자에서 Squamous Cell Cancer Antigen(SCC 항원)의 변화)

  • Kim, Young-Jun;Park, In-Won;Choi, Byung-Whui;Hue, Sung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.5
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    • pp.400-406
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    • 1992
  • Background: It has been known that see antigen was used in diagnosis of uterine cervical cancer and also known to be higher in squamous cell lung cancer. There has been no report about see antigen in squamous cell lung cancer in Korea. This study was designed to evaluate the usefulness of see antigen as a diagnostic tool and index for follow up after treatment. Method: The serum level of see antigen was measured in 12 cases with squamous cell lung carcinoma, 9 patients with other types of lung cancer, 7 patients with benign lung disease and 7 normal subjects by radioimmunoassay with Abott see Riabeap radioimmunoassay kit. We also measured see antigen after treatment in 6 patients who had received chemotherapy or sugery. Result: 1) The level of see antigen ($mean{\pm}1$ SD) was $2.27{\pm}1.53$, $0.67{\pm}0.38$, $0.62{\pm}0.53$, $0.53{\pm}0.36\;ng/ml$ respectively. 2) The see antigen activity in squamous cell lung carcinoma according to stage were as gollows. I; $2.07{\pm}1.56$, $III_a$; $5.04{\pm}0.53$ $III_b$; $1.94{\pm}0.7$ IV; $1.07{\pm}0.64$ (ng/ml). 3) In squamous cell lung cancer, 5 of 12 (42%) cases was shown more than 2.0 ng/ml see antigen. (sensitivity; 42%), but there was no case in any other type of lung cancer, benign lung disease, and in control groups (specificity; 100%). 4) The serum sec antigen level after treatment was significantly decreased in patients with partial or complete remission (p<0.01). Conclusion; It was suggested that see antigen might be used as a useful tumor marker for the response of treatment and assessment of prognosis in squamous cell lung cancer, but further study should be performed for the clinical use of see antigen.

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A STUDY ON THE DISTRIBUTION OF CALCITONIN GENE-RELATED PEPTIDE CONTAINING NERVE FIBERS IN RAT PULP FOLLOWING DENTINAL INJURY (상아질 손상 후 흰쥐 대구치 치수의 calcitonin gene-related peptide(CGRP) 함유 신경섬유 분포에 관한 연구)

  • Moon, Joo-Hoon;Park, Sang-Jin;Min, Byung-Soon;Choi, Ho-Young;Cho, Gi-Woon
    • Restorative Dentistry and Endodontics
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    • v.24 no.1
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    • pp.100-115
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    • 1999
  • The purpose of this study was to investigate the distribution of calcitonin gene-related peptide containing nerve fibers in rat pulp after dentinl injury by means of immunohistochemistry and confocal laser scanning microscope. The Spague-Dawley rats weighing about 250-300gm were used. The animals were devided into normal control and experimental groups. Experimental animals were sacrified 1, 2, 4, 7, 10, 21days after dentinal injury (dentin cutting, and then acid etching with 35% phosphoric acid) on the maxillary molar teeth. The maxillary teeth and alveolar bone were removed and immersed in the 4% paraformaldehyde in 0.1M phosphate buffer (pH 7.4), then were decalcified with 15% formic acid for 10 days. Serial frozen $50{\mu}m$ thick sections were cut on a cryostat. The rabbit CGRP antibody was used as a primary antibody with a dilution of 1:2000 in 0.01M PB. The sections were incubated for 48 hours at $4^{\circ}C$, and placed into biotinylated antirabbit Ig G as a secondary anti body with dilution of 1:200 in 0.01M PB and incubated in ABC(avidin-biotin complex). The peroxidase reaction was visualized by incubating the sections in 0.05% 3,3 diaminobenzidine tetrahydrochloride containing 0.02% $H_2O_2$. For the confocal laser scanning microscopic examination, Primary antibody reaction was same as immunoperoxidase stainning, but fluorescein isothiocyanate(FITC)-conjugate antirabbit IgG as a secondary antibody was used. The confocal laser scanning microscope was used for the examination. A series of images of optical sections was collected with a 20x objective at $3{\mu}m$ intervals throughout the depth of specimen. FITC fluerescence was registrated through a 488nm and 568nm excitation filter, and images were saved on optical disk. The stereoscopic images and three dimentionnal images were reconstructed by computer software, and then were analyzed. The results were as follows : 1. In normal control group, CGRP containing nerve fibers were coursed through the root with very little branching, and then formed a dense network of terminals in coronal pulp. 2. A slight increase in CGRP containing nerve fibers at 1 and 2day postinjury was noted subjacent to the injury site. In the 4day group, there were an extensive increase in the number of reactive fibers, followed by a partial return toward normal levels at 7~10 day postinjury, and return by 21days. 3. The sprouting of the CGRP containing nerve fibers was evident within 2day after dentinal injury, and by 4days there was a maximal increased, but was decreased at 7days and returned to normal 10~21 day postinjury. 4. In confocal laser scanning microscopic exammination, the distinct distribution pattern and sprouting reaction of CGRP containing nerve fibers were observed in stereoscopic images and three dimentional images. These results suggest that CGRP containing nerve fiber can be important role in the response to dental injury and pain regulation.

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Influence of Sociocultural Services on Brand Image and Loyalty of Cafe (카페의 브랜드 이미지와 충성도에 대한 사회문화성서비스 영향)

  • Kim, Yeon Jong;Seol, Byung Moon;Mun, Hee Jung
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.12 no.5
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    • pp.163-175
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    • 2017
  • The purpose of this study is to find out how to improve the brand image and loyalty of cafe by recognizing that social culture of middle school cafe, which is an important service quality in cafe establishment, emerges as a main characteristic of new coffee business. First, reliability, confidentness, professionalism, accessibility, and socio - culturality of the service quality of coffee specialty shops improve brand image. Confidence and professionalism play an important role in enhancing brand loyalty, and brand image has a significant effect on brand loyalty. Respectively, Among the service quality, social culture has a strong influence on brand image but it is not a direct influence on brand loyalty. Second, in the relationship between brand loyalty of coffee service quality, brand image shows full mediation effect on reliability, partial mediation effect on confidence, professionalism, accessibility, socialcultural property, and mediation effect on response and empathy. Third, as a result of analyzing the moderating effects of coffee shop types on the relationship between service quality and brand image of coffee specialty shops, reliability, confidentiality, and accessibility are positive factors in the nationwide franchise. On the other hand, in the private $caf{\acute{e}}$, professionalism and socio-culturality are the main factors for improving the brand image. In the case of the local franchise, similar to the franchise in the country, the improvement of service quality for responsiveness and professionalism is a positive factor Respectively. As a result, nationwide franchise $caf{\acute{e}}s$ have priority in enhancing brand image and brand loyalty through accessibility and assurance of service quality. On the other hand, in case of local franchise $caf{\acute{e}}$, it can be seen that the service quality is enhanced and the brand image and brand loyalty can be further improved through service professionalism and accessibility. On the other hand, regional cafes are more important than national franchises or local franchise cafes, and a strategy to enhance customer loyalty is needed through service strategies emphasizing socio - cultural aspects.

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Mechanism of Inhibitory Effect of Imipramine on Isolated Rat Detrusor Muscle in Relation to Calcium Modulation (흰쥐 적출 방광 배뇨근의 수축성에 대한 Imipramine의 작용과 Calcium동원 기전과의 관계)

  • Lee, Jong-Bum;Yoo, Kae-Joon;Ha, Jeoung-Hee;Kwon, Oh-Cheol;Lee, Kwang-Youn;Kim, Won-Joon
    • The Korean Journal of Pharmacology
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    • v.28 no.1
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    • pp.81-89
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    • 1992
  • Enuresis is a common voiding disorder among children. There are several therapeutic regimens for the disorder available today; behavioral therapies, psychotherapy, bladder training, sleep interruption, hypnosis and drug therapy. Recently, the efficacy of drug therapy has been acknowledged, particularly of antidepressants. Among the tricyclic antidepressants, imipramine is most frequently employed for the treatment of enuresis. Present study was undertaken to investigate the mechanism of imipramine on the contractility of urinary bladder in relation to the calcium modulation using isolated strips of rat detrusor urinae. 1. The electric fileld stimulation-induced contraction was abolished by imipramine, but partially inhibited by atropine. 2. Imipramine reduced the basal tone and diminished the phasic activity of detrusor muscle concentration-dependently, which was similar to that of diltiazem, a calcium channel blocker. 3. Imipramine suppressed the maximal responses and shifted the concentration-response curves of bethanechol and ATP to right. 4. Imipramine inhibited the calcium-induced recovery of tension in calcium-free physiologic salt solution (PSS) with a mode of action similar to that of diltizaem. 5. A23187, a calcium ionophore recovered the basal tone which had been reduced by imipramine in normal PSS. 6. In calcium-free PSS, A23187 could recover the abolished basal tone with the pretreatment of imipramine, but it exerted a partial recovery with the pretreatment of TMB-8, an inhibitor of intracellular calcium release. Based on these results, it is suggested that the inhibitory action of imipramine on the detrusor muscle exerted in part by blockade of the muscarinic and purinergic receptors, and interference with the influx of extracellular calcium, but not with the release of intracellular stored calcium, is involved in its mechanism of action.

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Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

  • Berk, Veli;Kaplan, Mehmet Ali;Tonyali, Onder;Buyukberber, Suleyman;Balakan, Ozan;Ozkan, Metin;Demirci, Umut;Ozturk, Turkan;Bilici, Ahmet;Tastekin, Didem;Ozdemir, Nuriye;Unal, Olcun Umit;Oflazoglu, Utku;Turkmen, Esma;Erdogan, Bulent;Uyeturk, Ummugul;Oksuzoglu, Berna;Cinkir, Havva Yesil;Yasar, Nurgul;Gumus, Mahmut
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7367-7369
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    • 2013
  • Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.