CT showed focal thickening of the small-bowel wall. Double-contrast radiography of the small-bowel showed a stricture with proximal dilation in the ileum (Figure 1a). Anal double-balloon endoscopy (DBE) revealed a severe stricture with a circular ulcer in the ileum, together with coarse, granular mucosa in the distal side (Figure 1b–c). Partial resection of the ileum was

performed, because of the repeated symptoms. Histological examination of the resected specimen disclosed a diffuse infiltrate of small to medium-sized atypical lymphoid MI-503 nmr cells with lymphoepithelial lesions involving the whole thickness of the ileal wall and extending to the mesenteric adipose tissue (Figure 2a–b). The cells were immunohistochemically CD20+, BCL2+, CD3−, CD5−, CD10−, and cyclinD1−. t(11;18)/API2-MALT1 was detected by fluorescence in situ hybridization. Based on these findings, a diagnosis of MALT lymphoma was established. The stenotic area contained irregularly thickened muscularis mucosae and submucosal fibrosis with an eosinophilic infiltrate. Apoptotic bodies

were frequently observed in the cryptal epithelium in areas of both circular ulcer and MALT lymphoma (Figure 2c). selleck chemical These histological findings were compatible with NSAID-induced enteropathy. Since the patient had stage IIE disease, as determined by post-operative staging work-ups, he underwent 8 cycles of rituximab monotherapy. During the subsequent two-year period, no signs of recurrence have been found. To date, only a few cases of MALT lymphoma of the small-bowel showed annular stricture, as medchemexpress seen in our patient. Based on the characteristic macroscopic and histologic findings, the circular ulcer in our case was presumably induced by NSAID. This is the first report of a case of intestinal MALT lymphoma, accompanied by NSAID-induced enteropathy. Contributed by “
“We read with great interest the review by Fabbrini et al.,1 and we thought

it is a valuable contribution. We are willing to shift the attention to another area related to metabolic syndrome and obesity. Brown adipose tissue (BAT) is present in some animals permanently, particularly in rodents. In humans, BAT is found predominantly in newborns and young children and is thought to be a rudimentary tissue in adult humans. Although white adipose tissue (WAT) stores extra energy as triacylglycerol, BAT scatters energy as heat via uncoupling protein-1 (UCP1), a proton transporter which is available only in the inner mitochondrial membrane of brown adipocytes.2 In contrast to WAT, which has been intensely studied, the importance of BAT in humans was unknown and had been poorly studied until recently. With the understanding of BAT availability in humans,3-5 some metabolic consequences regarding metabolic syndrome and obesity have been extracted from related clinical studies. We could think of BAT as a heat producer and fat burner in the body that creates a negative energy balance.

CT showed focal thickening of the small-bowel wall. Double-contrast radiography of the small-bowel showed a stricture with proximal dilation in the ileum (Figure 1a). Anal double-balloon endoscopy (DBE) revealed a severe stricture with a circular ulcer in the ileum, together with coarse, granular mucosa in the distal side (Figure 1b–c). Partial resection of the ileum was

performed, because of the repeated symptoms. Histological examination of the resected specimen disclosed a diffuse infiltrate of small to medium-sized atypical lymphoid Selleckchem Proteasome inhibitor cells with lymphoepithelial lesions involving the whole thickness of the ileal wall and extending to the mesenteric adipose tissue (Figure 2a–b). The cells were immunohistochemically CD20+, BCL2+, CD3−, CD5−, CD10−, and cyclinD1−. t(11;18)/API2-MALT1 was detected by fluorescence in situ hybridization. Based on these findings, a diagnosis of MALT lymphoma was established. The stenotic area contained irregularly thickened muscularis mucosae and submucosal fibrosis with an eosinophilic infiltrate. Apoptotic bodies

were frequently observed in the cryptal epithelium in areas of both circular ulcer and MALT lymphoma (Figure 2c). Vadimezan clinical trial These histological findings were compatible with NSAID-induced enteropathy. Since the patient had stage IIE disease, as determined by post-operative staging work-ups, he underwent 8 cycles of rituximab monotherapy. During the subsequent two-year period, no signs of recurrence have been found. To date, only a few cases of MALT lymphoma of the small-bowel showed annular stricture, as MCE公司 seen in our patient. Based on the characteristic macroscopic and histologic findings, the circular ulcer in our case was presumably induced by NSAID. This is the first report of a case of intestinal MALT lymphoma, accompanied by NSAID-induced enteropathy. Contributed by “
“We read with great interest the review by Fabbrini et al.,1 and we thought

it is a valuable contribution. We are willing to shift the attention to another area related to metabolic syndrome and obesity. Brown adipose tissue (BAT) is present in some animals permanently, particularly in rodents. In humans, BAT is found predominantly in newborns and young children and is thought to be a rudimentary tissue in adult humans. Although white adipose tissue (WAT) stores extra energy as triacylglycerol, BAT scatters energy as heat via uncoupling protein-1 (UCP1), a proton transporter which is available only in the inner mitochondrial membrane of brown adipocytes.2 In contrast to WAT, which has been intensely studied, the importance of BAT in humans was unknown and had been poorly studied until recently. With the understanding of BAT availability in humans,3-5 some metabolic consequences regarding metabolic syndrome and obesity have been extracted from related clinical studies. We could think of BAT as a heat producer and fat burner in the body that creates a negative energy balance.

Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application. “
“While hepatitis B virus (HBV) prevalence is known to vary greatly between countries,

systematically collected population-level prevalence data from some countries is limited. Antenatal HBV screening programs in countries with substantial migrant populations provide the opportunity to systematically examine HBV prevalence in order to inform local and regional HBV estimates. A comprehensive register of Australian mothers giving birth from January 2000 to December 2008 was linked to a register of HBV notifications. Age-standardized prevalence of chronic HBV were calculated overall and by the mother’s country of birth.

Multiple logistic regression was used to investigate other factors associated with HBV prevalence. Five hundred twenty-three thousand six hundred sixty-five women Z-VAD-FMK purchase were included and linked to 3861 HBV notifications. The age-standardized HBV prevalence was low (0.75%, 95% confidence interval 0.72–0.79). The highest HBV prevalence rates were observed in women born in Cambodia (8.60%), Taiwan (8.10%), Vietnam (7.49%), China (6.80%), Ulixertinib and Tonga (6.51%). Among Australia-born women, those who smoked during pregnancy, were from a more disadvantaged socioeconomic background, and lived in remote areas were more likely to have HBV. There was also a trend suggesting a decrease in the prevalence of HBV over time. Antenatal screening for HBV can provide systematic population estimates of HBV prevalence in migrants and also identify other high prevalence groups. Longer follow-up will be required to confirm the small decrease in HBV prevalence observed in this study. “
“Aim:  There is little information available on the efficacy of pegylated interferon (PEG IFN) therapy for children with chronic hepatitis C. The aim of this study was to evaluate the MCE公司 efficacy and tolerability of PEG IFN-α2a monotherapy for children infected by chronic hepatitis C virus (HCV). Methods:  From 2004–2006, we

conducted a prospective, open-label, multicenter study of 22 patients aged 4–18 years, including eight with genotype 1 and 14 with genotype 2. None had previously received IFN. The patients were treated with s.c. PEG IFN-α2a at a dose of 3 µg/kg once a week for 48 weeks. Rapid virological response (RVR) was defined as: undetectable serum HCV RNA at week 4; early viral response (EVR) as a 2 or more log reduction or undetectable serum HCV RNA at week 12; and sustained viral response (SVR) as undetectable serum HCV RNA at 24 weeks after the cessation of treatment. Results:  SVR was achieved in 10 (45%) of the 22 patients (three with genotype 1, seven with genotype 2). Retrospectively, the patients with SVR included five with RVR (one with genotype 1, four with genotype 2) and five with EVR (two with genotype 1, three with genotype 2).

Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application. “
“While hepatitis B virus (HBV) prevalence is known to vary greatly between countries,

systematically collected population-level prevalence data from some countries is limited. Antenatal HBV screening programs in countries with substantial migrant populations provide the opportunity to systematically examine HBV prevalence in order to inform local and regional HBV estimates. A comprehensive register of Australian mothers giving birth from January 2000 to December 2008 was linked to a register of HBV notifications. Age-standardized prevalence of chronic HBV were calculated overall and by the mother’s country of birth.

Multiple logistic regression was used to investigate other factors associated with HBV prevalence. Five hundred twenty-three thousand six hundred sixty-five women Saracatinib clinical trial were included and linked to 3861 HBV notifications. The age-standardized HBV prevalence was low (0.75%, 95% confidence interval 0.72–0.79). The highest HBV prevalence rates were observed in women born in Cambodia (8.60%), Taiwan (8.10%), Vietnam (7.49%), China (6.80%), CP-690550 chemical structure and Tonga (6.51%). Among Australia-born women, those who smoked during pregnancy, were from a more disadvantaged socioeconomic background, and lived in remote areas were more likely to have HBV. There was also a trend suggesting a decrease in the prevalence of HBV over time. Antenatal screening for HBV can provide systematic population estimates of HBV prevalence in migrants and also identify other high prevalence groups. Longer follow-up will be required to confirm the small decrease in HBV prevalence observed in this study. “
“Aim:  There is little information available on the efficacy of pegylated interferon (PEG IFN) therapy for children with chronic hepatitis C. The aim of this study was to evaluate the 上海皓元医药股份有限公司 efficacy and tolerability of PEG IFN-α2a monotherapy for children infected by chronic hepatitis C virus (HCV). Methods:  From 2004–2006, we

conducted a prospective, open-label, multicenter study of 22 patients aged 4–18 years, including eight with genotype 1 and 14 with genotype 2. None had previously received IFN. The patients were treated with s.c. PEG IFN-α2a at a dose of 3 µg/kg once a week for 48 weeks. Rapid virological response (RVR) was defined as: undetectable serum HCV RNA at week 4; early viral response (EVR) as a 2 or more log reduction or undetectable serum HCV RNA at week 12; and sustained viral response (SVR) as undetectable serum HCV RNA at 24 weeks after the cessation of treatment. Results:  SVR was achieved in 10 (45%) of the 22 patients (three with genotype 1, seven with genotype 2). Retrospectively, the patients with SVR included five with RVR (one with genotype 1, four with genotype 2) and five with EVR (two with genotype 1, three with genotype 2).

Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application. “
“While hepatitis B virus (HBV) prevalence is known to vary greatly between countries,

systematically collected population-level prevalence data from some countries is limited. Antenatal HBV screening programs in countries with substantial migrant populations provide the opportunity to systematically examine HBV prevalence in order to inform local and regional HBV estimates. A comprehensive register of Australian mothers giving birth from January 2000 to December 2008 was linked to a register of HBV notifications. Age-standardized prevalence of chronic HBV were calculated overall and by the mother’s country of birth.

Multiple logistic regression was used to investigate other factors associated with HBV prevalence. Five hundred twenty-three thousand six hundred sixty-five women RO4929097 research buy were included and linked to 3861 HBV notifications. The age-standardized HBV prevalence was low (0.75%, 95% confidence interval 0.72–0.79). The highest HBV prevalence rates were observed in women born in Cambodia (8.60%), Taiwan (8.10%), Vietnam (7.49%), China (6.80%), Silmitasertib and Tonga (6.51%). Among Australia-born women, those who smoked during pregnancy, were from a more disadvantaged socioeconomic background, and lived in remote areas were more likely to have HBV. There was also a trend suggesting a decrease in the prevalence of HBV over time. Antenatal screening for HBV can provide systematic population estimates of HBV prevalence in migrants and also identify other high prevalence groups. Longer follow-up will be required to confirm the small decrease in HBV prevalence observed in this study. “
“Aim:  There is little information available on the efficacy of pegylated interferon (PEG IFN) therapy for children with chronic hepatitis C. The aim of this study was to evaluate the 上海皓元医药股份有限公司 efficacy and tolerability of PEG IFN-α2a monotherapy for children infected by chronic hepatitis C virus (HCV). Methods:  From 2004–2006, we

conducted a prospective, open-label, multicenter study of 22 patients aged 4–18 years, including eight with genotype 1 and 14 with genotype 2. None had previously received IFN. The patients were treated with s.c. PEG IFN-α2a at a dose of 3 µg/kg once a week for 48 weeks. Rapid virological response (RVR) was defined as: undetectable serum HCV RNA at week 4; early viral response (EVR) as a 2 or more log reduction or undetectable serum HCV RNA at week 12; and sustained viral response (SVR) as undetectable serum HCV RNA at 24 weeks after the cessation of treatment. Results:  SVR was achieved in 10 (45%) of the 22 patients (three with genotype 1, seven with genotype 2). Retrospectively, the patients with SVR included five with RVR (one with genotype 1, four with genotype 2) and five with EVR (two with genotype 1, three with genotype 2).

This confirms the epidemiological evidence that variant CJD is caused by BSE infection, and as such represents the only example of a human prion disease acquired from another species (Table 1). The most likely source of human exposure to BSE is the consumption

of contaminated meat products [13]. In keeping with an oral route of infection, both PrPSc and infectivity are detectable within lymphoid tissues, including the spleen, tonsil, lymph nodes, thymus and gut associated lymphoid tissue in variant CJD [9]; levels of infectivity in lymphoid tissues buy Autophagy Compound Library are approximately 2–3 logs lower than in brain tissue [14]. Abnormal PrP has been detected by immunohistochemistry in gut-associated lymphoid tissue within the appendix in two patients who had undergone appendicectomy up to 2 years before the onset of variant CJD [15]. These findings have lead to the suggestion that lymphocytes may carry infectivity in blood during the incubation period of variant CJD [16]. This suggestion has been reinforced by the detection of infectivity ROCK inhibitor in the blood of sheep experimentally infected with BSE before the animals develop clinical signs and symptoms [17]. By February 2010,

172 cases of variant CJD have been confirmed in the UK, with 47 additional cases in 10 other countries (Table 3). The incidence of variant CJD has declined in the UK since 1999–2000; however, the number of asymptomatic infections in the UK remains uncertain; the results of earlier studies to detect abnormal PrP in tonsil and appendix tissues suggests MCE a prevalence of around 1 per 10 000 of the UK population [15,18,19]. This figure is higher than the current numbers of variant CJD cases in the UK would suggest, indicating that some variant CJD cases may have a prolonged asymptomatic carrier state, which perhaps does not result in clinical disease in all cases. Prion infectivity

in blood has been demonstrated in rodent models during the incubation period and after the clinical onset of disease [20,21]; the levels of infectivity in whole blood as measured by bioassay are around 10 ID mL−1. Most infectivity was found to be associated with white blood cells, but infectivity was also present in plasma and red blood cells [20]. Experimental BSE and scrapie infection in sheep has also demonstrated infectivity in blood during the incubation period and after the clinical onset of disease. Transmission rates of at least 40% were reported following blood transfusion, with most transmissions occurring from blood samples taken during the second half of the incubation period; transmission of scrapie was also reported with a relatively small volume of a buffy coat preparation [17]. The Transfusion Medicine Epidemiology Review was established in the UK to investigate the possibility of transmission of variant CJD by blood transfusion [22].

The frequency of R61S fs*10 in this limited series of HCC and CGC was 17% and 13%, respectively, whereas C88A fs*16 was only found in HCC (17%). Previously described inactivating SNPs, whose minor allele frequency

has been calculated in larger populations (Table 1), appeared with different frequency in HCC and CGC (Table 2). When all OCT1 variants were considered together, the result was that at least one inactivating SNP was present in 48% HCC and 40% CGC. Sorafenib is a very active antitumor drug in most cancer cell lines, which include those derived from CGC and HCC.[7, 8] Unfortunately, the efficacy of this drug in clinical oncology is very different. Indeed, regimens that have incorporated this drug are far from optimal because a marked refractoriness to sorafenib is an initial characteristic of liver tumors.[9] PF-02341066 order Moreover, cancer Alectinib manufacturer cells often activate MOCs during treatment.[27] Regarding the refractoriness to sorafenib, the identified MOCs[28] include: (1) up-regulation of ABC proteins, such as MDR1 and ABCG2, which reduce intracellular drug content (MOC-1b); (2) enhanced drug inactivation

by uridine glucuronosyl transferase 1A (MOC-2); (3) the appearance of genetic variants in the intracellular targets of sorafenib (MOC-3); and (4) since sorafenib uptake is an essential requirement to be effective against tumor cells, changes in the expression/activity of the transporters involved in sorafenib uptake can also lead to drug resistance (MOC-1a). In this regard, OCT1 has been reported to be involved in sorafenib uptake by hepatocytes.[29] This and other carrier systems may account for sorafenib uptake by tumor cells. Thus, the present study indicates that sorafenib has a strong effect even on cell lines with very poor expression of OCT1. In agreement with previous studies,[3] we observed here a marked reduction in OCT1 expression in both HCC and CGC. In the case of HCC, this event may be at least partially due to an enhanced methylation and reduced activity of the SLC22A1 promoter.[30] OCT1 down-regulation has already been associated 上海皓元 with chemoresistance

in certain types of cancer, for instance, to cisplatin.[31] Moreover, OCT1 expression levels have been suggested to be a useful biomarker to predict the success of imatinib-based therapy for chronic myeloid leukemia.[32] The present study suggests that reduced OCT1-mediated sorafenib uptake may be involved in a poorer response to this drug. The functional consequences of some OCT1 SNPs found in HCC and CGC have already been studied. M408V and L160F variants, with relative high frequency in HCC and CGC, have been reported to maintain transport ability.[11] Although a trend to lower OCT1 expression has been reported in the livers from patients harboring the M408V variant, its impact on the clinical efficiency of metformin is minor.[11] Patients with chronic myeloid leukemia harboring the wildtype genotype GG of the c.

The frequency of R61S fs*10 in this limited series of HCC and CGC was 17% and 13%, respectively, whereas C88A fs*16 was only found in HCC (17%). Previously described inactivating SNPs, whose minor allele frequency

has been calculated in larger populations (Table 1), appeared with different frequency in HCC and CGC (Table 2). When all OCT1 variants were considered together, the result was that at least one inactivating SNP was present in 48% HCC and 40% CGC. Sorafenib is a very active antitumor drug in most cancer cell lines, which include those derived from CGC and HCC.[7, 8] Unfortunately, the efficacy of this drug in clinical oncology is very different. Indeed, regimens that have incorporated this drug are far from optimal because a marked refractoriness to sorafenib is an initial characteristic of liver tumors.[9] Romidepsin Moreover, cancer Cabozantinib datasheet cells often activate MOCs during treatment.[27] Regarding the refractoriness to sorafenib, the identified MOCs[28] include: (1) up-regulation of ABC proteins, such as MDR1 and ABCG2, which reduce intracellular drug content (MOC-1b); (2) enhanced drug inactivation

by uridine glucuronosyl transferase 1A (MOC-2); (3) the appearance of genetic variants in the intracellular targets of sorafenib (MOC-3); and (4) since sorafenib uptake is an essential requirement to be effective against tumor cells, changes in the expression/activity of the transporters involved in sorafenib uptake can also lead to drug resistance (MOC-1a). In this regard, OCT1 has been reported to be involved in sorafenib uptake by hepatocytes.[29] This and other carrier systems may account for sorafenib uptake by tumor cells. Thus, the present study indicates that sorafenib has a strong effect even on cell lines with very poor expression of OCT1. In agreement with previous studies,[3] we observed here a marked reduction in OCT1 expression in both HCC and CGC. In the case of HCC, this event may be at least partially due to an enhanced methylation and reduced activity of the SLC22A1 promoter.[30] OCT1 down-regulation has already been associated 上海皓元 with chemoresistance

in certain types of cancer, for instance, to cisplatin.[31] Moreover, OCT1 expression levels have been suggested to be a useful biomarker to predict the success of imatinib-based therapy for chronic myeloid leukemia.[32] The present study suggests that reduced OCT1-mediated sorafenib uptake may be involved in a poorer response to this drug. The functional consequences of some OCT1 SNPs found in HCC and CGC have already been studied. M408V and L160F variants, with relative high frequency in HCC and CGC, have been reported to maintain transport ability.[11] Although a trend to lower OCT1 expression has been reported in the livers from patients harboring the M408V variant, its impact on the clinical efficiency of metformin is minor.[11] Patients with chronic myeloid leukemia harboring the wildtype genotype GG of the c.

What is less clear, however, is how we as zoologists – and how the Journal of Zoology itself – can better anticipate and meet the needs of policy-makers and conservation practitioners. In this editorial, I will focus

on this question from the perspective of marine mammal research, but the central issues are relevant to both the current state of play in zoological research and the broader application of our knowledge to the conservation of species in increasingly human-dominated environments. Ken Norris, one of the pioneers of marine mammal science, once wrote that marine mammalogists were tasked with compiling ‘little truths on which future understandings … may be anchored’ (Pryor & Norris, 1991). This modest set of expectations reflects the fact that marine mammals are difficult to study because of their lifestyle; our studies http://www.selleckchem.com/products/MK-2206.html are often based on infrequent glimpses of animals at the surface. In 1970, Ehrenfeld

outlined traits that make species inherently vulnerable to extinction, inter alia large body size, long gestation period, small litter size or lengthy maternal care, formation of large breeding aggregations, high commercial value for body parts and (or) an unregulated hunt, highly restricted distribution or distribution in international High Content Screening waters and trans-boundary migration. This description, in whole or in part, describes most endangered marine mammal populations. Marine mammals are particularly interesting study species for zoologists

because they reach anatomical and physiological extremes, some species and populations are in dire straits, the status of many others is poorly known and our ability to conserve all of them depends on receiving the best possible advice from the zoologists who know their study animals the best. Zoologists play a vital role in efforts to understand 上海皓元医药股份有限公司 how anthropogenic activities affect wildlife, populations and ecosystems. Interpreting what is normal or abnormal cannot be done without knowing the timing of major life-history events, energy requirements, movement or migration patterns and behaviour. In setting conservation priorities, we need to know what it is about the biology of individual species that makes some of them more vulnerable to extinction than others, and how this knowledge can and should inform recovery plans. For example, marine mammals have evolved exquisite systems for underwater hearing. As our oceans become increasingly noisy places, it is crucial to understand how these top predators will respond. Even modest disturbances in the acoustic environment can disrupt whales’ foraging activities.

In these patients, palliative treatment is possible, employing systemic therapy. Genetic profiling has suggested that HCC progression is attributed buy Neratinib to a number of altered signaling pathways as well as epigenetic mechanisms. Thus, as in other tumor entities,

targeted agents are investigated as novel therapeutic options. Along this line, angiogenesis inhibition is a prime therapeutic target in solid tumors, especially in highly vascularized HCC. Since the successful completion of the SHARP study in 2007,2 the antiproliferative and angiostatic multi–tyrosin kinase inhibitor (TKI), sorafenib, has been approved as the first systemic agent for treatment of patients with unresectable or metastatic HCC and preserved liver function. Sorafenib primarily inhibits BRAF/vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor tyrosin kinases mediating

cell proliferation and angiogenesis; it also blocks many additional kinases, given its lack of selectivity.3 The mechanism underlying the antitumor effect of sorafenib is complex, and even RAF-independent signaling has recently been described as a significant pathway of sorafenib-induced cell death.4 At present, sorafenib represents the only drug with statistically significant, but clinically modest, benefit in terms of improvement in overall survival (OS), time to Selleck Atezolizumab progression (TTP), and disease control rate. Efficacy of sorafenib in HCC was demonstrated in two

large randomized, controlled trials (RCT): SHARP and the Asia-Pacific study,2, 5 sorafenib significantly reduces the risk of death and prolongs median OS by approximately 3 months. Survival benefit is based on an extended TTP. Sorafenib does not induce tumor-size reduction, and radiologic response has to be confirmed by a decrease in viable tumor mass. Therefore, to identify novel drugs with activity in HCC in future and medchemexpress ongoing trials, modified Response Evaluation Criteria In Solid Tumors criteria have been proposed.6 FGF3/4, fibroblast growth factors 3 and 4; FGFR, FGF receptor; HCC, hepatocellular carcinoma; OS, overall survival; RCT, randomized, controlled trial; TKI, multi–tyrosin kinase inhibitor; TTP, time to progression; VEGFR, vascular endothelial growth factor receptor. Sorafenib is associated with relevant toxicities, especially in patients with compromised liver function (stage Child-Pugh B). Patients with cirrhosis suffer from fatigue, and in such patients, sorafenib may cause a rapid deterioration in quality of life. Therefore, predictive (bio)markers to guide therapy with sorafenib are urgently needed. Many clinical parameters and serum markers as well as genomic signatures have been suggested; for example, development of hypertension and diarrhea, known side effects of sorafenib, under therapy seem to be associated with a favorable outcome.