We hypothesized that matrix metalloproteinase (MMP)-9 plays an important role in FLF progression, and investigated MMP-9 behaviors in a murine FLF model, especially at the coma stage. The murine FLF model with azoxymethane recapitulates FLF in humans. The detailed coma status was evaluated, on the assumption that LT is screening assay indicated at early, but not late, stage 3. To investigate whether MMP-9 deletion

or reduction has beneficial effects, an MMP-9 inhibitor (GM6001) and transfection of tissue inhibitor of metalloproteinases (TIMP)-1 cDNA were used. Mice were divided into five groups: control; FLF; FLF with GM6001 pretreatment; FLF with TIMP-1 plasmid transfection 24 h before disease onset; and FLF with TIMP-1 plasmid transfection 48 h before disease onset. Neurological findings, including survival, were followed. Samples were obtained at early and late stage 3. Biochemical examinations and histopathological assessments were performed. The expression and function of MMP-9 and TIMP-1 were evaluated by western blotting and zymography. A brain permeability study was also performed. MMP-9 was strongly increased in FLF. The MMP-9 inhibitions CX-4945 purchase worked well, and prolonged the survival, interval to stage 3 and duration of early stage 3. MMP-9 inhibition improved the liver and subsequent brain injuries at early stage 3,

with no remarkable 上海皓元医药股份有限公司 improvements at late stage 3. MMP-9 has therapeutic potential for FLF progression. “
“In Wilson’s disease, liver transplantation can constitute the only option for patients presenting with fulminant hepatic failure or decompensated liver

disease unresponsive to drug therapy. We report the case of a 29-year-old woman receiving a liver transplant for end-stage Wilson’s disease who developed neurological complications after transplantation. After an accurate evaluation of possible differential causes of neurological complications developing as the result of liver transplantation, moyamoya disease was diagnosed. Moyamoya disease is a rare cerebrovascular disease of unknown etiology. However, data exist supporting a possible role for some immunosuppressive regimens in determining the peculiar vascular alterations observed in moyamoya disease. To the best of our knowledge, the association with post-transplantation state for Wilson’s disease has not been previously described. “
“The liver comprises two stem/progenitor cell systems: fetal and adult liver stem/progenitor cells. Fetal hepatic progenitor cells, derived from foregut endoderm, differentiate into mature hepatocytes and cholangiocytes during liver development. Adult hepatic progenitor cells contribute to regeneration after severe and chronic liver injuries. However, the characteristics of these somatic hepatic stem/progenitor cells remain unknown.

6% of male population comparisons (Table 2). Whales of both sexes from South Africa in 1936 or 1983 were smaller than those from the Tay Estuary, Scotland, while those from the 1983 stranding were also smaller than both sexes from Japan or Chile, and Chilean whales

of both sexes were larger than those from Tasmania. No significant differences were found between whales of both sexes from the Tay Estuary, Japan, and Chile. In other examples, a significant difference in size between areas was confined to only one sex. Overall geographical patterns are difficult to establish, and perhaps should not be sought, given the sparse nature of the data and in most cases a lack of accompanying age information. Nevertheless, it appears that adult false killer whales from different areas (and even from the same area) can differ significantly see more SCH772984 in mean body size by as much as 0.5–0.6 m. Assuming variation in body size is genetically based and an evolved response, the observed differences in body size could be the result of any one, or a combination, of several selective forces to which the populations have been exposed in their respective environments. These include different ambient sea temperatures and differing food availabilities, especially seasonally and/or spatially—current data on the diet and feeding behavior of (particularly South African)

false killer whales are insufficient to determine whether there are differences with those from Japan. Further regional studies of growth, especially in tropical regions, are needed to clarify the issue. The growth curves constructed in this paper differed greatly from those previously published by Purves and Pilleri (1978) for a group of false killer whales stranded at Dornoch Firth, Scotland, which failed to reach an asymptote. Even though the body lengths of the oldest Scottish specimens were roughly comparable to those of the oldest Japanese specimens, their ages were much younger, 18–23 compared to 55–65 yr. The teeth from the Scottish animals medchemexpress were not decalcified or stained, and only dentine layers were counted using a low power lens and reflected light (Purves and Pilleri 1978). Thus it seems

likely that their ages were underestimated, particularly in older animals where age is more difficult to determine accurately from dentinal layers only. Consequently the differences between the growth curves of the Scottish sample and our samples from South Africa and Japan were methodological rather than real. A marked geographic difference between our samples was the lower incidence of pregnant animals and juveniles of presumed suckling age in the South African sample. While this could be attributed to a temporary loss of fertility in the population (or a biased representation of reproductive classes in the stranding), the significantly lower ovulation rate in the South African whales suggested that these alternative explanations are unlikely, and that the St.

6% of male population comparisons (Table 2). Whales of both sexes from South Africa in 1936 or 1983 were smaller than those from the Tay Estuary, Scotland, while those from the 1983 stranding were also smaller than both sexes from Japan or Chile, and Chilean whales

of both sexes were larger than those from Tasmania. No significant differences were found between whales of both sexes from the Tay Estuary, Japan, and Chile. In other examples, a significant difference in size between areas was confined to only one sex. Overall geographical patterns are difficult to establish, and perhaps should not be sought, given the sparse nature of the data and in most cases a lack of accompanying age information. Nevertheless, it appears that adult false killer whales from different areas (and even from the same area) can differ significantly click here selleck products in mean body size by as much as 0.5–0.6 m. Assuming variation in body size is genetically based and an evolved response, the observed differences in body size could be the result of any one, or a combination, of several selective forces to which the populations have been exposed in their respective environments. These include different ambient sea temperatures and differing food availabilities, especially seasonally and/or spatially—current data on the diet and feeding behavior of (particularly South African)

false killer whales are insufficient to determine whether there are differences with those from Japan. Further regional studies of growth, especially in tropical regions, are needed to clarify the issue. The growth curves constructed in this paper differed greatly from those previously published by Purves and Pilleri (1978) for a group of false killer whales stranded at Dornoch Firth, Scotland, which failed to reach an asymptote. Even though the body lengths of the oldest Scottish specimens were roughly comparable to those of the oldest Japanese specimens, their ages were much younger, 18–23 compared to 55–65 yr. The teeth from the Scottish animals 上海皓元医药股份有限公司 were not decalcified or stained, and only dentine layers were counted using a low power lens and reflected light (Purves and Pilleri 1978). Thus it seems

likely that their ages were underestimated, particularly in older animals where age is more difficult to determine accurately from dentinal layers only. Consequently the differences between the growth curves of the Scottish sample and our samples from South Africa and Japan were methodological rather than real. A marked geographic difference between our samples was the lower incidence of pregnant animals and juveniles of presumed suckling age in the South African sample. While this could be attributed to a temporary loss of fertility in the population (or a biased representation of reproductive classes in the stranding), the significantly lower ovulation rate in the South African whales suggested that these alternative explanations are unlikely, and that the St.

6% of male population comparisons (Table 2). Whales of both sexes from South Africa in 1936 or 1983 were smaller than those from the Tay Estuary, Scotland, while those from the 1983 stranding were also smaller than both sexes from Japan or Chile, and Chilean whales

of both sexes were larger than those from Tasmania. No significant differences were found between whales of both sexes from the Tay Estuary, Japan, and Chile. In other examples, a significant difference in size between areas was confined to only one sex. Overall geographical patterns are difficult to establish, and perhaps should not be sought, given the sparse nature of the data and in most cases a lack of accompanying age information. Nevertheless, it appears that adult false killer whales from different areas (and even from the same area) can differ significantly HKI-272 manufacturer AZD6244 cost in mean body size by as much as 0.5–0.6 m. Assuming variation in body size is genetically based and an evolved response, the observed differences in body size could be the result of any one, or a combination, of several selective forces to which the populations have been exposed in their respective environments. These include different ambient sea temperatures and differing food availabilities, especially seasonally and/or spatially—current data on the diet and feeding behavior of (particularly South African)

false killer whales are insufficient to determine whether there are differences with those from Japan. Further regional studies of growth, especially in tropical regions, are needed to clarify the issue. The growth curves constructed in this paper differed greatly from those previously published by Purves and Pilleri (1978) for a group of false killer whales stranded at Dornoch Firth, Scotland, which failed to reach an asymptote. Even though the body lengths of the oldest Scottish specimens were roughly comparable to those of the oldest Japanese specimens, their ages were much younger, 18–23 compared to 55–65 yr. The teeth from the Scottish animals MCE were not decalcified or stained, and only dentine layers were counted using a low power lens and reflected light (Purves and Pilleri 1978). Thus it seems

likely that their ages were underestimated, particularly in older animals where age is more difficult to determine accurately from dentinal layers only. Consequently the differences between the growth curves of the Scottish sample and our samples from South Africa and Japan were methodological rather than real. A marked geographic difference between our samples was the lower incidence of pregnant animals and juveniles of presumed suckling age in the South African sample. While this could be attributed to a temporary loss of fertility in the population (or a biased representation of reproductive classes in the stranding), the significantly lower ovulation rate in the South African whales suggested that these alternative explanations are unlikely, and that the St.

For general dentists who were owners of a practice, the average net income in 2010 was $198,490, and the average net income among all specialists in private practice was $304,270. The mean net earnings data (Table 5) for prosthodontists, owner prosthodontists, and solo prosthodontists in 2010 are all greater than the estimates for all general dentists and owner general dentists but less than the average of $313,620 estimated for all specialists in the ADA briefing. Similar to other industries and Staurosporine clinical trial professions, average net earnings are used as one indicator of the economic health of the participants

in the industry. When examining the net earnings results based on the survey responses, however, the reliability of those estimates should also be examined. Since we did not ask every prosthodontist in private practice in the United States, there is a question about how

well the estimates from the sample reflect the average income of all prosthodontists. The reliability of the mean net income estimates calculated from the survey results is influenced by the size of the respondent sample and click here the size of the standard deviation of net income (i.e., the amount of variation in income reported by the prosthodontists). The larger the sample size and the smaller the amount of variation in the reported income, the greater the reliability of the estimates from the survey data. The calculation of a 95% confidence interval is one method

used to examine the reliability of the mean net earnings estimates. The confidence interval is computed as the mean net income “plus and minus” a factor that reflects the size of the standard deviation of net earnings and the size of the respondent sample.[12] The 95% confidence interval was calculated for the mean net earnings estimates in Table 5 and/or the difference in mean net earnings for 2010 and 2007. Results are shown in Table 7. The narrower the 95% confidence intervals, the greater the reliability that the calculated mean net income from the respondent sample is MCE a reliable estimate of the mean net income for all prosthodontists in private practice. The ratio of the confidence interval to the mean net income is a measure of the relative size of the confidence interval. This measure ranges from 21% to 23% in 2007, and from 29% to 33% in 2010. The “difference” in mean net earnings between 2007 and 2010 is also shown in Table 7. The results from calculating a 95% confidence interval for the “difference” indicate that: (1) the difference in mean net income per prosthodontist is statistically significant at the 10% level; (2) the difference in mean net income per owner is not statistically significant at a level of at least 10%; and (3) the difference in mean net income per solo prosthodontist is statistically significant at the 5% level.

However the result could be normal in the presence of symptoms. Methods: We reviewed the records of conventional esophageal manometries made at Gastroenterology Unit in Hospital Universitario Kinase Inhibitor Library San Ignacio (HUSI), between July 2008 and October 2011, selecting those patientes whose indication was dysphagia, and review the results of those analysis. Results: We found in our records a total of 2275 manometries made between 2008 to 2011, 581 of them (26%) whose indication was dysphagia. A total of 386 (66.4%) were female and we clasified the findings according to age, with age between 21–40 years old 66 (11.3%),

41–60 years 198 (34%) and 61–80 years 102 (17.5%). On the other hand 195 (33.5%) men with an age range of 21–40 years 50 (8.6%), 41–60 years 71 (12.2%), 61–80 years 50 (8.6%). The most common conditions encountered are in order: Normal 205 (35.3%), ineffective peristalsis 126 (21.7%), Achalasia 101 (17.4%), hypotonic lower esophageal sphincter 98 (16.9%), aperistalsis 23 (4%), and diffuse esophageal spasm 18 (3.1%). Conclusion: From the analyzed results we found that most of manometries

Protein Tyrosine Kinase inhibitor were normal. The most affected patients was in the fourth decade of life, identifying in this group esophageal motor disorders. The most common findings were ineffective peristalsis, Achalasia, hypotonic lower esophageal sphincter, with other pathologies in lesser percentage aperistalsis and diffuse esophageal spasm. We concluded that the percentage of patients with positive findings is not negligible, and the most common findings are related to gastroesophageal reflux disease, but primary disorders as achalasia should be always in mind.

Key Word(s): 1. DYSPHAGIA; 2. ESOPHAGEAL MANOMETRY; 3. MOTOR DISORDERS; Presenting Author: CHRISTOPHER KHOR Additional Authors: CHUNG KING CHIA, LEE GUAN LIM, FENG ZHU, KHEK YU HO, CHOON JIN OOI, KWONG MING FOCK, JIMMY SO, WEE CHIAN LIM, KHOON LIN LING, TIING LEONG ANG, ANDREW WONG, ANDREA 上海皓元 RAJNAKOVA, MING TEH, SUPRIYA SRIVASTAVA, KHAY GUAN YEOH Corresponding Author: CHRISTOPHER KHOR Affiliations: Singapore General Hospital; Tan Tock Seng Hospital; National University Hospital; National University of Singapore; Gleneagles Hospital; Changi General Hospital; Mount Elizabeth Medical Centre; National University of Signapore Objective: Gastric cancer is a curable disease if detected early. Endoscopy surveillance is the only way to detect gastric cancer in the early stages. More targeted screening and surveillance is required in countries with intermediate incidence rate of gastric cancer. The Gastric Cancer Epidemiology and Molecular Genetics Program (GCEP), initialized in 2004, is a prospective multicentre study with the ultimate goal of developing an optimal approach and cost-effective algorithm for targeted screening for gastric cancer in the Singapore Chinese population.

Quantitative PCR reactions were carried out using SYBR green PCR master mix (Applied Biosystems, Foster City, CA) in an ABI Prism 7900HT Sequence Detection System. Values were quantified using the comparative CT method, and samples were normalized to 18S ribosomal RNA. Liver tissue was homogenized with choline/acetylcholine assay buffer (Abcam, Cambridge, UK) and the homogenate centrifuged at 18,000g for 20 minutes. The supernatant Gefitinib order was subjected to determination of choline levels with the Choline/Acetylcholine Assay kit (Abcam). Protein was measured with the Micro BCA Protein Assay kit (Thermo Fisher

Scientific, Waltham, MA). Choline levels were normalized to total protein. Quantification of serum lysophosphatidylcholine was performed according to a reported method.21 Serum sphingomyelin levels were www.selleckchem.com/products/NVP-AUY922.html estimated with the Sphingomyelin Assay Kit (Cayman, Ann Arbor, MI). Hepatic N-stearoyl-D-erythro-sphingosine (C18-ceramide) and N-palmitoyl-D-erythro-sphingosine (C16-ceramide) levels were determined as described below. Liver tissue (20 mg) was homogenized with 600 μL of methanol:CHCl3 (2:1) solution including N-palmitoyl (D31)-D-erythro-sphingosine (Avanti Polar Lipids, Alabaster, AL) as internal standard, and sonicated. To the homogenate was added 400 μL of CHCl3, followed by vortexing for 2 minutes, addition of 400 μL 0.1M HCl, and vortexing for 2

minutes. The homogenate was centrifuged for 10 minutes and 200 μL of the organic phase was transferred to a new glass tube and dried with air. The pellet was suspended with a 79% methanol/20% water/1% formic acid solution and sonicated. Liquid chromatography/mass spectrometry (LC-MS) for ceramide detection was performed based on a reported method.22 Briefly, the sonicated samples were separated on a Phenomenex 2.1 × 100 mm Luna 3μ C18 column (Torrance, CA) using the following gradient: (A:B) 80:20

for 1 minute to 100% B at 5 minutes, held for 15 minutes, then equilibration at 80:20 for 1.5 minutes. The mobile phase consisted of (A) methanol-water-formic acid (74:25:1) MCE and (B) methanol-formic acid (99:1). Both A and B were also buffered with 5 mM ammonium formate. The LC-MS system consisted of a PE series 200 LC pump and auto-injector (Perkin Elmer, Waltham, MA) coupled to an API2000 mass spectrometer (Applied Biosystems) operated in positive electrospray ionization mode. Multiple reaction monitoring was performed: 538.5264.3 for C16-ceramide, 566.5264.3 for C18-ceramide, and 569.7264.2 for the internal standard. C16- and C18-ceramides were determined with the authentic chemicals (Avanti Polar Lipids) and the quantification was performed with standard curve. Primary hepatocytes were prepared based on a reported method.23 Cells were exposed to TGF-β for 6 hours, collected, and lysed for RNA analysis. Statistical analysis was performed using Prism v. 5.0c (GraphPad Software, San Diego, CA). A P-value less than 0.05 was considered significant.

In terms of etiology, 21 patients (27.3%) took NSAIDs or antiplatelet agents.

H. pylori infection was detected in 13 patients (16.9%). 45 patients (58.4%) had an idiopathic etiology. Ulcers were predominantly located at duodenal bulb (59.7%) or D1/D2 junction (28.6%), with either Forrest class Ib (33.8%) or IIa (42.9%) morphology. Although all patients were treated endoscopically, 9 patients required salvage therapy; angio-embolisation (6) or surgery (3). Surveillance was performed at a mean duration of 54.6 days (range 28–125). At surveillance, 68 (88.3%) had complete healing of duodenal ulcers. Diabetes mellitus (DM) was associated with persistence of ulcer at surveillance [Odds Ratio (OR) 5.6, 95% CI 1.2–24.6; p = 0.02]. DM patients had a mean HbA1C of 7.2%. When compared with Chinese race, Malay race had higher risk of persistent ulcer [OR 9.9, 95% CI 1.9–52.3; p = 0.007]. PF-01367338 mw Following multivariate logistic regression, Malay race was the only statistically significant predictor of persistent ulcer [OR 6.9,

95%CI 1.2–39.5; Selleck GDC 0068 p = 0.03]. Post-surveillance, 9 patients with persistent ulcer were given a longer course of PPI therapy (5) or changed to a more potent PPI (4). Conclusion: Following therapy, bleeding duodenal ulcers may have delayed healing, especially in the Malay patient with DM. Further larger prospective studies may establish the role of surveillance endoscopy in this group of patients. Key Word(s): 1. duodenal ulcer; 2. bleeding ulcer; 3. therapeutic endoscopy; 4. surveillance MCE Presenting Author: HYEWON LEE Additional Authors: EUN JUNG JEON, WOO CHUL CHUNG, CHANG NYOL PAIK, KANG MOON LEE Corresponding Author: HYEWON LEE Affiliations: St. Paul’s Hospital, St. Vincent’s Hospital, St. Vincent’s Hospital, St. Vincent’s Hospital Objective: To evaluate the clinical outcomes and severity of peptic ulcer bleeding (PUB) according

to the etiology – Helicobacter pylori (H. pylori) and drug (aspirin and nonsteroidal anti-inflammatory drug). Methods: A consecutive series of patients who had PUB and admitted to the hospital between 2006 and 2012 were retrospectively analyzed. A total of 232 patients were enrolled in this study, and we compared the clinical characteristics and outcomes according to the different etiologies (H. pylori, drug, H. pylori with drug and idiopathic). We also evaluated the severity using Blatchford score and Rockall score between four groups. Results: When H. pylori associated PUB compared with drug induced PUB, it was male dominant. In drug induced PUB, the longer duration of admission and larger ulcer were observed. Also, Blatchford score and Rockall score were the higher than H. pylori associated PUB. When idiopathic PUB compared with H. pylori associated PUB, the larger ulcer and more frequent rate of re-bleeding were observed. When idiopathic PUB compared with drug induced PUB, it was distinct of male predominance. Re-admission rate and re-bleeding rate after initial hemostasis were higher in idiopathic PUB.

In terms of etiology, 21 patients (27.3%) took NSAIDs or antiplatelet agents.

H. pylori infection was detected in 13 patients (16.9%). 45 patients (58.4%) had an idiopathic etiology. Ulcers were predominantly located at duodenal bulb (59.7%) or D1/D2 junction (28.6%), with either Forrest class Ib (33.8%) or IIa (42.9%) morphology. Although all patients were treated endoscopically, 9 patients required salvage therapy; angio-embolisation (6) or surgery (3). Surveillance was performed at a mean duration of 54.6 days (range 28–125). At surveillance, 68 (88.3%) had complete healing of duodenal ulcers. Diabetes mellitus (DM) was associated with persistence of ulcer at surveillance [Odds Ratio (OR) 5.6, 95% CI 1.2–24.6; p = 0.02]. DM patients had a mean HbA1C of 7.2%. When compared with Chinese race, Malay race had higher risk of persistent ulcer [OR 9.9, 95% CI 1.9–52.3; p = 0.007]. FDA approved Drug Library screening Following multivariate logistic regression, Malay race was the only statistically significant predictor of persistent ulcer [OR 6.9,

95%CI 1.2–39.5; mTOR inhibitor p = 0.03]. Post-surveillance, 9 patients with persistent ulcer were given a longer course of PPI therapy (5) or changed to a more potent PPI (4). Conclusion: Following therapy, bleeding duodenal ulcers may have delayed healing, especially in the Malay patient with DM. Further larger prospective studies may establish the role of surveillance endoscopy in this group of patients. Key Word(s): 1. duodenal ulcer; 2. bleeding ulcer; 3. therapeutic endoscopy; 4. surveillance 上海皓元 Presenting Author: HYEWON LEE Additional Authors: EUN JUNG JEON, WOO CHUL CHUNG, CHANG NYOL PAIK, KANG MOON LEE Corresponding Author: HYEWON LEE Affiliations: St. Paul’s Hospital, St. Vincent’s Hospital, St. Vincent’s Hospital, St. Vincent’s Hospital Objective: To evaluate the clinical outcomes and severity of peptic ulcer bleeding (PUB) according

to the etiology – Helicobacter pylori (H. pylori) and drug (aspirin and nonsteroidal anti-inflammatory drug). Methods: A consecutive series of patients who had PUB and admitted to the hospital between 2006 and 2012 were retrospectively analyzed. A total of 232 patients were enrolled in this study, and we compared the clinical characteristics and outcomes according to the different etiologies (H. pylori, drug, H. pylori with drug and idiopathic). We also evaluated the severity using Blatchford score and Rockall score between four groups. Results: When H. pylori associated PUB compared with drug induced PUB, it was male dominant. In drug induced PUB, the longer duration of admission and larger ulcer were observed. Also, Blatchford score and Rockall score were the higher than H. pylori associated PUB. When idiopathic PUB compared with H. pylori associated PUB, the larger ulcer and more frequent rate of re-bleeding were observed. When idiopathic PUB compared with drug induced PUB, it was distinct of male predominance. Re-admission rate and re-bleeding rate after initial hemostasis were higher in idiopathic PUB.

13 Furthermore, TGF-β derived from HSCs acted on tumor cells and governed tumorigenesis in a paracrine fashion, leading to tumor-progressive and autocrine TGF-β signaling in tumor cells.18 Recently, stromal cell-derived factor 1 (SDF-1) was found to be released by find more activated HSCs within the liver metastases, and CXCR4 (chemokine [C-X-C motif] receptor 4), the ligand of SDF-1, was found to be expressed in colorectal cancer cells.22In

vitro, this SDF-1/CXCR4 paracrine signaling promoted tumor cell invasion and protected tumor cells from apoptosis.22 In unpublished data, we have also demonstrated that myofibroblast-derived PDGF-BB is a potent survival factor for cholangiocarcinoma cells. Taken together, these data support the concept that activated PS-341 cost HSCs promote tumor cell growth by supplying them with growth factors and cytokines. A high degree of ECM remodeling favors tumor invasion and progression in the liver.23 Both MMP and TIMP2 play a key role in degrading basement membranes, thereby allowing cancer cells to cross tissue boundaries and develop into metastases. By performing

in situ hybridization and zymography, Musso et al. found that both MMP2 and TIMP2 messenger RNA were expressed in activated HSCs at the invasive front of liver metastases, and a higher level of MMP2 messenger RNA and enzymatic activity was detected in liver metastases than in nontumoral liver samples.24, 25 In addition, activated MCE HSCs at the invasive front of human liver metastases were found to express a secreted form of ADAM9 (a disintegrin and metallopeptidase 9).16 This molecule was shown to be able to cleave laminin and bind to tumor cells, thus promoting invasion of tumor cells.16 These data indicate that HSCs may facilitate tumor invasion by producing proteolytic enzymes involved in the degradation of ECM. Activated HSCs are a major cell type for ECM production during the pathogenesis of liver fibrosis,4, 5 and this process may

also contribute to the prometastatic growth effects of HSCs. In the liver tumor microenvironment, TGF-β1 released by tumor cells induces HSCs to produce increased amounts of ECM constituents such as fibronectin and collagen I. These ECM components constitute a microenvironment in which tumor cells adhere and grow. In addition to providing a physical support to tumor cells, these ECM components also regulate the adhesion, migration, and survival of tumor cells by binding to and activating integrins on the surface of tumor cells.26, 27 For example, ECM-mediated activation of phosphoinositide 3-kinase and its downstream targets in tumor cells protects tumor cells from genotoxin-induced cell cycle arrest and subsequent apoptosis, contributing to tumor chemoresistance.28 In addition, the poorly vascularized architecture associated with desmoplasia contributes to tumor chemoresistance by imposing a barrier to drug delivery.