With the precious new concentrate, however, our patient’s hemostasis during dental extractions was perfectly normal. Cutter could not produce much of this marvellous material because the yield of concentrated FVIII from plasma was low. Enter Dr. Judith Graham Pool. She had earned her Ph.D. in physiology from the University of Chicago in 1946 and had joined the faculty of Stanford Temozolomide chemical structure University in 1953, investigating coagulation with particular attention to FVIII. With Jean Robinson, she had developed the ‘two-stage’ assay for FVIII in 1959.

In the early 1960s she used that method to assay FVIII in plasma fractions prepared by Cutter’s Drs. Albert Pappenhagen and Edward Hershgold. Their starting material

was pooled plasma, frozen in large containers, which they thawed cautiously. They knew that the potency of FVIII in plasma dwindled at room temperature, so they were careful not to thaw the plasma completely. www.selleckchem.com/products/PD-0332991.html But Dr. Pool found very little FVIII in their thawed supernatant. She then tested the small amount of unthawed, fibrous-looking paste at the bottom of the containers, and, in 1964, found the FVIII [5]. The genius of Dr. Pool was her leap from that laboratory observation to the practical idea of using the last-to-thaw property of FVIII to separate ‘cryoprecipitate’ from whole plasma in an ordinary blood bank, re-freezing the small volume in its own sterile plastic bag and storing bags in a freezer so that eventually several could be given to a patient at one time [4]. Meanwhile, the thawed plasma could be used for extraction of other plasma proteins. The method was so simple, and

cost so little for the additional materials, that it was rapidly copied by blood banks around the world. Cryoprecipitate became widely available not only for patients with haemophilia A or von Willebrand disease but also for patients deficient in fibrinogen or factor XIII. It was a great, miraculous gift to the world. Many tens of thousands of patients have benefitted. Meanwhile, more highly concentrated commercial, lyophilized FVIII preparations were developed, using various technologies (often including selleck products cryoprecipitation). The first was licensed in the USA at the end of the 1960s and then cost ten cents (U.S.$0.10) per FVIII unit in Los Angeles. We quickly adopted its use and, by 1970, started to introduce our haemophilia patients to self-infusion at home. Our local blood bank had switched from the use of glass bottles for blood collection to plastic bags only in the late 1960s, delaying the development of cryoprecipitate. Furthermore, instead of charging only the incremental costs of the additional processing required to extract cryoprecipitate from plasma, they divided the total cost of blood processing among all components.

With the precious new concentrate, however, our patient’s hemostasis during dental extractions was perfectly normal. Cutter could not produce much of this marvellous material because the yield of concentrated FVIII from plasma was low. Enter Dr. Judith Graham Pool. She had earned her Ph.D. in physiology from the University of Chicago in 1946 and had joined the faculty of Stanford http://www.selleckchem.com/products/PLX-4032.html University in 1953, investigating coagulation with particular attention to FVIII. With Jean Robinson, she had developed the ‘two-stage’ assay for FVIII in 1959.

In the early 1960s she used that method to assay FVIII in plasma fractions prepared by Cutter’s Drs. Albert Pappenhagen and Edward Hershgold. Their starting material

was pooled plasma, frozen in large containers, which they thawed cautiously. They knew that the potency of FVIII in plasma dwindled at room temperature, so they were careful not to thaw the plasma completely. RXDX-106 But Dr. Pool found very little FVIII in their thawed supernatant. She then tested the small amount of unthawed, fibrous-looking paste at the bottom of the containers, and, in 1964, found the FVIII [5]. The genius of Dr. Pool was her leap from that laboratory observation to the practical idea of using the last-to-thaw property of FVIII to separate ‘cryoprecipitate’ from whole plasma in an ordinary blood bank, re-freezing the small volume in its own sterile plastic bag and storing bags in a freezer so that eventually several could be given to a patient at one time [4]. Meanwhile, the thawed plasma could be used for extraction of other plasma proteins. The method was so simple, and

cost so little for the additional materials, that it was rapidly copied by blood banks around the world. Cryoprecipitate became widely available not only for patients with haemophilia A or von Willebrand disease but also for patients deficient in fibrinogen or factor XIII. It was a great, miraculous gift to the world. Many tens of thousands of patients have benefitted. Meanwhile, more highly concentrated commercial, lyophilized FVIII preparations were developed, using various technologies (often including check details cryoprecipitation). The first was licensed in the USA at the end of the 1960s and then cost ten cents (U.S.$0.10) per FVIII unit in Los Angeles. We quickly adopted its use and, by 1970, started to introduce our haemophilia patients to self-infusion at home. Our local blood bank had switched from the use of glass bottles for blood collection to plastic bags only in the late 1960s, delaying the development of cryoprecipitate. Furthermore, instead of charging only the incremental costs of the additional processing required to extract cryoprecipitate from plasma, they divided the total cost of blood processing among all components.

“
“In this article, we hope to summarize current understanding of pediatric headache. We discuss epidemiology, genetics, classification, diagnosis, outpatient, emergency and inpatient treatment options, prevention strategies, and behavioral approaches. For each section, we end with a series of questions for future research and consideration. “
“Idiopathic intracranial hypertension (IIH) is most often diagnosed in young obese females of childbearing years. The diagnosis is made based on the buy AZD6244 modified Dandy criteria and the exclusion of alternate causes of raised intracranial

pressure. The focus of this review is to provide an overview of the diagnosis and treatment options for patients with IIH. There are long-term consequences for patients experiencing IIH, with visual loss being the most serious. We conclude that the diagnosis of IIH is not usually difficult. An ophthalmologic examination

is essential in patients with IIH to monitor learn more visual function. A neurologist or neurosurgeon may be needed at some point for medical and/or surgical intervention. “
“Nummular headache, considered a primary headache in the 3rd edition of the International Classification of Headache Disorders, has nonetheless been attributed in several occasions to underlying epicranial anomalies. Vascular imaging of the head in 2 patients with nummular headache revealed fusiform aneurysms of the scalp vessel in close relation to the painful area. One of the patients underwent surgical resection of the aneurysm with excellent response. A response to triptans was noted in both. In selected patients with nummular headache, vascular imaging of the scalp may reveal anomalies amenable to surgical treatment or triptan administration, sometimes resulting in disappearance of the pain. “
“(Headache 2010;50:1104-1114) Background.— Diet and lifestyle are seen as

factors which influence headache in adults. However, population-based studies on this issue in adolescents are rare. Objective.— selleck Aim of the present study was to investigate associations between diet and lifestyle factors and different types of headache, ie, migraine and tension-type headache (TTH) in adolescents. Methods.— A total of 1260 adolescents from the 10th and 11th grades of high schools filled in questionnaires on intake of meals, coffee, nonalcoholic and alcoholic drinks, smoking, and physical activity. Type of headache was classified according to the International Classification of Headache Disorders – 2nd edition. Multiple logistic regression models, adjusted for sex and grade, were calculated. Results.— High consumption of cocktails (odds ratio = 3.4; 95% confidence interval 1.9-6.0) and coffee (2.4; 1.3-4.7), smoking (2.7; 1.4-5.1), and lack of physical activity (2.2; 1.3-3.

“
“In this article, we hope to summarize current understanding of pediatric headache. We discuss epidemiology, genetics, classification, diagnosis, outpatient, emergency and inpatient treatment options, prevention strategies, and behavioral approaches. For each section, we end with a series of questions for future research and consideration. “
“Idiopathic intracranial hypertension (IIH) is most often diagnosed in young obese females of childbearing years. The diagnosis is made based on the 26s Proteasome structure modified Dandy criteria and the exclusion of alternate causes of raised intracranial

pressure. The focus of this review is to provide an overview of the diagnosis and treatment options for patients with IIH. There are long-term consequences for patients experiencing IIH, with visual loss being the most serious. We conclude that the diagnosis of IIH is not usually difficult. An ophthalmologic examination

is essential in patients with IIH to monitor Carfilzomib visual function. A neurologist or neurosurgeon may be needed at some point for medical and/or surgical intervention. “
“Nummular headache, considered a primary headache in the 3rd edition of the International Classification of Headache Disorders, has nonetheless been attributed in several occasions to underlying epicranial anomalies. Vascular imaging of the head in 2 patients with nummular headache revealed fusiform aneurysms of the scalp vessel in close relation to the painful area. One of the patients underwent surgical resection of the aneurysm with excellent response. A response to triptans was noted in both. In selected patients with nummular headache, vascular imaging of the scalp may reveal anomalies amenable to surgical treatment or triptan administration, sometimes resulting in disappearance of the pain. “
“(Headache 2010;50:1104-1114) Background.— Diet and lifestyle are seen as

factors which influence headache in adults. However, population-based studies on this issue in adolescents are rare. Objective.— learn more Aim of the present study was to investigate associations between diet and lifestyle factors and different types of headache, ie, migraine and tension-type headache (TTH) in adolescents. Methods.— A total of 1260 adolescents from the 10th and 11th grades of high schools filled in questionnaires on intake of meals, coffee, nonalcoholic and alcoholic drinks, smoking, and physical activity. Type of headache was classified according to the International Classification of Headache Disorders – 2nd edition. Multiple logistic regression models, adjusted for sex and grade, were calculated. Results.— High consumption of cocktails (odds ratio = 3.4; 95% confidence interval 1.9-6.0) and coffee (2.4; 1.3-4.7), smoking (2.7; 1.4-5.1), and lack of physical activity (2.2; 1.3-3.

There was up-reg-ulation of transforming growth factor-β in biliary epithelial cells and blocking OPN, transforming R788 growth factor-β or both reduced collagen-I expression in hepatic stellate cells. Conclusion: OPN emerges as a key matricellular cytokine driving ductular reaction and

contributing to scarring and liver fibrosis via transforming growth factor-β. Disclosures: The following people have nothing to disclose: Xiaodong Wang, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Xiaodong Ge, Raquel Urtasun, Tung Ming Leung, M. Isabel Fiel, Natalia Nieto Congenital hepatic fibrosis (CHF), the most common extra-hepatic manifestation of autosomal recessive polycystic kidney disease (ARPKD), is associated with excessive extracellular matrix (ECM) deposition which encapsulates ductal plate cell-derived cysts. The precise mechanisms of hepatic cystogenesis and associated CHF are not known. Therapeutic options for ARPKD/CHF are extremely limited. Here, making use www.selleckchem.com/products/z-vad-fmk.html of the polycystic kidney (PCK) rat which harbors the same mutation found in ARPKD patients, we characterized the development of hepatic fibrosis from post natal day (PND) 0 to 3 months after birth.

Sprague-Dawley (SD) rats were used as controls. Liver to body weight ratios were greater in PCK rats compared to controls, consistent with the development and growth of intrahep-atic cysts. At three months, PCK rats had increased hepatic mRNA accumulation of αSMA (myofibroblast marker), type I collagen, elastin (portal fibroblast marker), desmin (hepatic stellate cell marker) and connective tissue growth factor (CTGF) compared to SD rats. Consistent with those findings, 3-month old PCK rats exhibited increased type 1 collagen, Sirius red staining and CTGF protein relative to SD rats. Time

course analysis revealed that the peak hepatic mRNA accumulation of αSMA, Col 1a 1, CTGF and elastin was at PND 10-20. Hepatic αSMA protein also peaked at PND selleck kinase inhibitor 10. Hepatic CTGF mRNA and protein was induced in PCK rats at PND5, peaked at PND10 and remained increased throughout the time course. While cysts were observable PND 0, diffuse ECM deposition around hepatic cysts revealed by Sirius red staining began PND 5 in PCK rats; diffuse Sirius red staining increased until PND 20. In PND 30 and 3-month old PCK rats, Sirius red staining became intense and compressed around proliferating cysts. The increased hepatic fibrosis observed in PCK rat livers was corroborated by observations made in human PKD liver samples. Collectively, these data suggest that initiation of fibrogenesis in PCK rats occurs during early postnatal period and involves both portal fibroblast- and hepatic stellate cell-derived myofibroblasts. Furthermore, these data suggest that CTGF may be a driving force behind CHF in the PKC rat and reveal CTGF as a potential therapeutic target. These studies were supported by grants to U.A. and D.P.W. (P50 DK057301-11) and M.T.P (P20 GM103549 and R00 AA017918).

There was up-reg-ulation of transforming growth factor-β in biliary epithelial cells and blocking OPN, transforming learn more growth factor-β or both reduced collagen-I expression in hepatic stellate cells. Conclusion: OPN emerges as a key matricellular cytokine driving ductular reaction and

contributing to scarring and liver fibrosis via transforming growth factor-β. Disclosures: The following people have nothing to disclose: Xiaodong Wang, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Xiaodong Ge, Raquel Urtasun, Tung Ming Leung, M. Isabel Fiel, Natalia Nieto Congenital hepatic fibrosis (CHF), the most common extra-hepatic manifestation of autosomal recessive polycystic kidney disease (ARPKD), is associated with excessive extracellular matrix (ECM) deposition which encapsulates ductal plate cell-derived cysts. The precise mechanisms of hepatic cystogenesis and associated CHF are not known. Therapeutic options for ARPKD/CHF are extremely limited. Here, making use Y27632 of the polycystic kidney (PCK) rat which harbors the same mutation found in ARPKD patients, we characterized the development of hepatic fibrosis from post natal day (PND) 0 to 3 months after birth.

Sprague-Dawley (SD) rats were used as controls. Liver to body weight ratios were greater in PCK rats compared to controls, consistent with the development and growth of intrahep-atic cysts. At three months, PCK rats had increased hepatic mRNA accumulation of αSMA (myofibroblast marker), type I collagen, elastin (portal fibroblast marker), desmin (hepatic stellate cell marker) and connective tissue growth factor (CTGF) compared to SD rats. Consistent with those findings, 3-month old PCK rats exhibited increased type 1 collagen, Sirius red staining and CTGF protein relative to SD rats. Time

course analysis revealed that the peak hepatic mRNA accumulation of αSMA, Col 1a 1, CTGF and elastin was at PND 10-20. Hepatic αSMA protein also peaked at PND selleck chemicals 10. Hepatic CTGF mRNA and protein was induced in PCK rats at PND5, peaked at PND10 and remained increased throughout the time course. While cysts were observable PND 0, diffuse ECM deposition around hepatic cysts revealed by Sirius red staining began PND 5 in PCK rats; diffuse Sirius red staining increased until PND 20. In PND 30 and 3-month old PCK rats, Sirius red staining became intense and compressed around proliferating cysts. The increased hepatic fibrosis observed in PCK rat livers was corroborated by observations made in human PKD liver samples. Collectively, these data suggest that initiation of fibrogenesis in PCK rats occurs during early postnatal period and involves both portal fibroblast- and hepatic stellate cell-derived myofibroblasts. Furthermore, these data suggest that CTGF may be a driving force behind CHF in the PKC rat and reveal CTGF as a potential therapeutic target. These studies were supported by grants to U.A. and D.P.W. (P50 DK057301-11) and M.T.P (P20 GM103549 and R00 AA017918).

Using a dedicated gene microarray, we identified 69 deregulated genes, including 10 metallopeptidases, 3 TIMPs, and 9 members of the

serine protease inhibitor family, related to protease activities in fibrosis tissues, compared to a pool of 10 histologically healthy liver samples (Supporting Table 1). This approach, which yields a listing of candidate genes, was complemented by the integration of both DNA microarray data and array-independent literature mining. Forty-two genes were clustered after prefiltering for genes connected with at least two members of the input set, according to PubMed abstracts (Fig. 1; see Supporting Information for details). The network graph of gene connections showed two major nodes, MMP2 and ADAMTS1. MMP2 is a well-known MMP secreted by activated HSCs and associated with the fibrosis process,17 and we recently demonstrated its involvement ABT-737 ic50 selleck screening library in CX3CL1 processing during chronic liver injury.8 In contrast, ADAMTS1 expression in the liver has been poorly documented and its role in fibrogenesis has never been investigated. To explore the possible role(s) of ADAMTS1,

we analyzed its expression in an independent set of 22 samples. Patients were 20 men and 2 women with a median age of 60.9 + 9.6 years; 3 were positive for HCV and 6 for hepatitis B virus (HBV). Steady-state ADAMTS1 mRNA levels in fibrotic tissues and control livers were measured by real-time PCR. ADAMTS1 mRNA levels were significantly increased in fibrotic liver samples, compared with healthy livers, and were correlated with grade of fibrosis: ADAMTS1 mRNA levels were significantly induced in cirrhotic (F4) livers, compared with F1-F3 livers (Fig. 2A). Moreover, up-regulation of ADAMTS1 was correlated with the known induction learn more of MMP2 expression in chronic liver disease. To identify the cellular source of ADAMTS1 in the liver, we analyzed its expression in isolated hepatic cells. ADAMTS1 was highly expressed in activated HSCs, compared to hepatocytes and enriched Kuppfer cell

fractions (Fig. 2B). We further investigated ADAMTS1 expression during HSC activation, which reflects the transition from a quiescent to a myofibroblastic-like phenotype, a change that can be mimicked by culturing freshly isolated HSCs in uncoated tissue-culture plastic plates. qPCR analyses were performed on total RNA extracts from 1- to 11-day-old cultures and after 1-6 cell passages. The quiescent and activated status of HSCs was confirmed by analysis of the expression of specific markers, including peroxisome proliferator-activated receptors (PPAR), alpha-smooth muscle actin (α-SMA), and type I collagen (COL1A2) (Supporting Fig. 1). In agreement with previous reports,18-21 the three PPAR isoforms were expressed in isolated HSCs over the first 4 days, with a maximum increase of PPARβ at day 4.

9% response rate). Twenty-eight thousand two hundred sixty-one (17.4%) reported “severe headache” in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders-2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime

for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, PCI-32765 in vivo headache-related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using

preventive pharmacologic treatment for headache. In this large, US population this website sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to

additional headache types and related factors. With few exceptions, it is well established that the majority of primary headache disorders have a higher prevalence in females than males. A review of global population estimates of primary headache subtypes of 107 studies from 6 continents reported prevalence of 42% for tension-type headache, 11% for migraine, and 3% chronic daily headache (3%).[1] Although the report found differences in the medchemexpress prevalence of headache across continents, all three of these headache types were more prevalent among females compared to males on every continent. Female to male sex prevalence ratios (PRs) are most dramatic in migraine and chronic daily headache but also exist in tension-type headache. In fact, the only primary headache types that have not demonstrated a female preponderance are the trigeminal autonomic cephalalgias. The majority of these headache types are more common in men, especially cluster headache, which has female to male sex prevalence estimates ranging from 1 : 3.5 to 1 : 7.

9% response rate). Twenty-eight thousand two hundred sixty-one (17.4%) reported “severe headache” in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders-2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime

for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, http://www.selleckchem.com/products/MK-2206.html headache-related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using

preventive pharmacologic treatment for headache. In this large, US population ALK inhibitor sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to

additional headache types and related factors. With few exceptions, it is well established that the majority of primary headache disorders have a higher prevalence in females than males. A review of global population estimates of primary headache subtypes of 107 studies from 6 continents reported prevalence of 42% for tension-type headache, 11% for migraine, and 3% chronic daily headache (3%).[1] Although the report found differences in the 上海皓元 prevalence of headache across continents, all three of these headache types were more prevalent among females compared to males on every continent. Female to male sex prevalence ratios (PRs) are most dramatic in migraine and chronic daily headache but also exist in tension-type headache. In fact, the only primary headache types that have not demonstrated a female preponderance are the trigeminal autonomic cephalalgias. The majority of these headache types are more common in men, especially cluster headache, which has female to male sex prevalence estimates ranging from 1 : 3.5 to 1 : 7.

This study indicates that the intrahepatic immune responses involved in the clearance of HCV are different between animals in which the immune system has been primed by vaccination and rechallenged animals where the immune system has been primed by natural infection with HCV. Low density arrays may be a useful method to select immune response markers to predict the outcome of HCV infection or the success of a vaccine. Disclosures: Esther Chang – Consulting: SynerGene Therapeutics, Inc. Kathleen F. Pirollo – Grant/Research Support: SynerGene Therapeutics, Inc Stephen Feinstone – Independent Contractor: Dynavax The following people have nothing to disclose: Hongying Duan, Iryna Zubkova, Youkyung Choi, Frances

Wells, Kris Krawczynski, Robert Lanford, Marian E. Major [Background] It has been reported that MDSC and Tregs were major suppressors of the immune response FK228 in vitro against Hepatocel-lular carcinoma (HCC). Sorafenib, an oral multi-kinase inhibitor, has been approved for the treatment of HCC. Sorafenib could inhibit the MAPK and VEGF signaling. VEGF signaling might affect MDSC development as well as angio-genesis. [Aim] The aim of this study is to analyze whether sorafenib could suppress MDSC and Tregs development in HCC patients ex vivo and in vitro. [Methods] ex vivo analysis: Thirty-five HCC patients who received http://www.selleckchem.com/products/DAPT-GSI-IX.html sorafenib were enrolled in this study. Sorafenib exhibits inter-individual

pharmacokinetic variability based MCE on the activity of CYP3A4. Therefore, we quantitated the sorafenib and sorafenib N-oxide in serum by an optimized HPLC-UV led method. The linear range of detection was 0.03–30 μg/ml. Peripheral blood mononuclear cells (PBMCs) were used for the analysis of MDSCs, Tregs and Th1. PBMCs were stained with CD3, CD4, CD25, CD127, CCR5, CXCR3, CD11 b, CD14, CD16, CD33, PD-L1, and HLA-DR antibody and analyzed by FACS canto-II. IL10 or IFN-γ secreting cells were analyzed by cytokine secreting assay. The mRNA expression of PBMCs was analyzed by deep sequence analysis (Transcriptome analysis) and realtime-PCR analysis (GM-CSF, IFN-γ,IL10,

TGF-β1, arginase 1, iNOS, PD-L1). in vitro analysis: Isolated PBMCs were used to analyze the induction of MDSC and Tregs by the soluble factor induced from various hepatoma cell lines (Hep3B, Li3, PLC etc.) in a 0.4μm pore tran-swell system. NOG mice were used for the transplantation of HCC with MDSC. [Results] ex-vivo: The frequency of MDSC in HCC patients was significantly higher than those in healthy subjects. The frequencies of PD-L1 high MDSCs and Tregs were significantly decreased after 8 weeks sorafenib treatment (p<0.01). On the other hand, the frequency of Th1 cells and the ability of IFN-γ secretion in T cells were significantly increased after 8 weeks sorafenib treatment (p<0.01). The expression of GM-CSF mRNA was significantly decreased after 8 weeks sorafenib treatment (p<0.05).