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Thomas C Smyrk

Publications and source records attributed to Thomas C Smyrk.

At least 19 recordsLinked to original sources
PubMed2006

The epidemiology of microscopic colitis: a population based study in Olmsted County, Minnesota.

OBJECTIVE: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. DESIGN AND SETTING: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). MAIN OUTCOME MEASURES: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. RESULTS: We identified 130 incident cases for an overall rate of 8.6 cases per 100,000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100,000 early in the study to 19.6 per 100,000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100,000 for collagenous colitis and 5.5 per 100,000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100,000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). CONCLUSIONS: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.

Adult↗
PubMed2006

Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma.

Regulator of G-protein signaling-GAIP-interacting protein COOH terminus (GIPC) is involved in protein trafficking, endocytosis, and receptor clustering and is associated with insulin-like growth factor I receptor (IGF-IR), a receptor important for proliferation and anchorage-independent growth. Here, we described GIPC expression in different human pancreatic adenocarcinoma (PCA) cell lines and we examined the role of GIPC in the regulation of IGF-IR protein levels in PCA. Interestingly, inhibition of GIPC expression by RNA interference led to reduced IGF-IR protein levels and a subsequent decrease in proliferation of PCA cells. We also determined that the PDZ domain of GIPC is essential for the post-translational regulation and the binding of IGF-IR. The importance of GIPC in pancreatic cancer development and progression is supported by tissue microarray data of 300 pancreatic cancer specimens where GIPC is highly expressed in PCA. Taken together, our data suggest that GIPC is a central molecule for the stability of IGF-IR and could be a target for future therapy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Allergen-specific in vitro cytokine production in adult patients with eosinophilic esophagitis.

Although the pathogenesis of eosinophilic esophagitis (EE) likely involves hypersensitivity reactions against exogenous allergens, allergen-specific cellular immune responses have not been studied. We investigated allergen-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in adult patients with EE (n=15) and healthy controls (HC; n=9). PBMCs were incubated with nine common food and environmental allergens or a nonspecific mitogen, and the levels of interleukin (IL)-5, IL-10, IL-13, and interferon-gamma in the cell-free supernatants were determined. Spontaneous and mitogen-stimulated cytokine production did not differ between EE and HC. House dust mite, ragweed, Aspergillus, milk, and soy induced significantly higher IL-5 production in EE (P < 0.05). House dust mite also augmented IL-13 production in EE (P < 0.05). Furthermore, PBMCs from three EE patients without allergen-specific IgE vigorously produced IL-5 and IL-13 on allergen stimulation. Thus, immune responses in EE are characterized by enhanced production of Th2-like cytokines against both food and environmental allergens.

Adult↗
PubMed2006

IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis typically produces an enlarged pancreas with narrowing of the pancreatic duct, and can mimic carcinoma. Autoimmune pancreatitis usually responds to corticosteroid treatment, making it important to differentiate from pancreatic ductal adenocarcinoma. Affected patients often have an elevated serum IgG4. It has been proposed that increased numbers of IgG4-positive plasma cells in tissue might be a marker for the condition. We investigated the role of IgG4 staining in the diagnosis of autoimmune pancreatitis, first in resected pancreas specimens (29 autoimmune pancreatitis, nine chronic alcoholic pancreatitis and 25 pancreatic cancer), then in pancreatic needle biopsies. Immunohistochemical stains for IgG4 were scored as none, mild, moderate or marked, according to published criteria. Moderate to marked numbers of IgG4-positive plasma cells were seen in 21/29 autoimmune pancreatitis patients, and were distributed in and around ducts, in interlobular fibrous tissue and in peripancreatic fat. In contrast, eight of nine examples of chronic alcoholic pancreatitis and 22/25 ductal adenocarcinomas had scores of none or mild. When we subdivided autoimmune pancreatitis into the histologic subtypes lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-destructive pancreatitis, 16/17 lymphoplasmacytic sclerosing pancreatitis had moderate to marked staining, compared to five to 12 idiopathic duct-destructive pancreatitis. Needle biopsies from nine patients suspected of having autoimmune pancreatitis had increased numbers of IgG4 cells. We conclude that pancreatic tissue from patients with autoimmune pancreatitis often shows moderate or marked infiltration by IgG4-positive plasma cells (>10/HPF). This is particularly so in the subtype we have designated lymphoplasmacytic sclerosing pancreatitis. We rarely see IgG4 staining in patients with chronic alcoholic pancreatitis and pancreatic ductal adenocarcinoma. IgG4-positive plasma cells are a useful marker for the tissue diagnosis of autoimmune pancreatitis.

Adenocarcinoma↗
PubMed2006

Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: association with kinase activity and tumor dedifferentiation.

PURPOSE: We have shown recently that glycogen synthase kinase-3 (GSK-3) beta regulates nuclear factor-kappaB (NF-kappaB)-mediated pancreatic cancer cell survival and proliferation in vitro. Our objective was to determine the localization of GSK-3beta in pancreatic cancer cells and assess the antitumor effect of GSK-3 inhibition in vivo to improve our understanding of the mechanism by which GSK-3beta affects NF-kappaB activity in pancreatic cancer. EXPERIMENTAL DESIGN: Immunohistochemistry and cytosolic/nuclear fractionation were done to determine the localization of GSK-3beta in human pancreatic tumors. We studied the effect of GSK-3 inhibition on tumor growth, cancer cell proliferation, and survival in established CAPAN2 tumor xenografts using a tumor regrowth delay assay, Western blotting, bromodeoxyuridine incorporation, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. RESULTS: We found nuclear accumulation of GSK-3beta in pancreatic cancer cell lines and in 62 of 122 (51%) human pancreatic adenocarcinomas. GSK-3beta nuclear accumulation is significantly correlated with human pancreatic cancer dedifferentiation. We have found that active GSK-3beta can accumulate in the nucleus of pancreatic cancer cells and that inhibition of GSK-3 kinase activity represses its nuclear accumulation via proteasomal degradation within the nucleus. Lastly, we have found that inhibition of GSK-3 arrests pancreatic tumor growth in vivo and decreases NF-kappaB-mediated pancreatic cancer cell survival and proliferation in established tumor xenografts. CONCLUSIONS: Our results show the antitumor effect of GSK-3 inhibition in vivo, identify GSK-3beta nuclear accumulation as a hallmark of poorly differentiated pancreatic adenocarcinoma, and provide new insight into the mechanism by which GSK-3beta regulates NF-kappaB activity in pancreatic cancer.

Adenocarcinoma↗
PubMed2006

Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience.

BACKGROUND & AIMS: The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. METHODS: We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. RESULTS: Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with > or =1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. CONCLUSIONS: AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.

Adolescent↗
PubMed2006

Clinical, pathologic, and immunohistochemical characteristics of gastrointestinal stromal tumors of the colon and rectum: implications for surgical management and adjuvant therapies.

INTRODUCTION: This study was designed to review the clinical characteristics of surgically treated gastrointestinal stromal tumors of the colon and rectum, evaluate their immunohistochemical and pathologic features based on the current National Institutes of Health criteria, and correlate clinicopathologic findings with the subsequent clinical course. METHODS: Patient and disease characteristics at presentation, pathologic features, surgical management, and clinical outcomes of 18 patients with gastrointestinal stromal tumors (4 colon and 14 rectum) diagnosed and primarily treated at our institution between 1979 and 2004 were evaluated. RESULTS: Tumors were classified on basis of size and mitotic rate according to current National Institutes of Health recommendations: 67 percent (n = 12) were high-risk, 5 percent (n = 1) were intermediate-risk, 17 percent (n = 3) were low-risk, and 11 percent (n = 2) were very low-risk gastrointestinal stromal tumors. Fifteen of 18 tumors were KIT-positive. The three KIT-negative tumors were platelet-derived growth factor receptor alpha positive. All patients with colonic gastrointestinal stromal tumors (n = 4) underwent segmental resection, whereas patients with rectal gastrointestinal stromal tumors had local excision (n = 5) or radical resection (n = 9). Sixty-six percent (8/12) of patients with high-risk colorectal gastrointestinal stromal tumors developed metastases. None of the patients (n = 6) with intermediate-risk, low-risk, or very low-risk gastrointestinal stromal tumors died of their disease after a median follow-up of 65 (range, 15-266) months. CONCLUSIONS: The majority of gastrointestinal stromal tumors of the colon and rectum are high-risk. Patients with high-risk colorectal gastrointestinal stromal tumors have a significant likelihood of developing metastases that is associated with poor prognosis. These patients need to be closely followed for an extended period and should be considered for adjuvant therapy with tyrosine kinase inhibitors.

Adult↗
PubMed2006

Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota.

BACKGROUND & AIMS: The risk for colorectal cancer in Crohn's disease and ulcerative colitis patients from the United States currently is unknown. We estimated the risk for small-bowel and colorectal cancer in a population-based cohort of 692 inflammatory bowel disease patients from Olmsted County, Minnesota, from 1940 to 2001. METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal and small-bowel cancer. The cumulative probability of cancer and standardized incidence ratios (SIR) were estimated using expected rates from Surveillance, Epidemiology, and End Results, white patients from Iowa, from 1973 to 2000, and Olmsted County, from 1980 to 1999. RESULTS: Colorectal cancer was observed in 6 ulcerative colitis patients vs 5.38 expected (SIR, 1.1; 95% confidence interval [CI], 0.4-2.4), but 4 of these occurred among those with extensive colitis or pancolitis (SIR, 2.4; 95% CI, 0.6-6.0). Six Crohn's disease patients (vs 3.2 expected) developed colorectal cancer (SIR, 1.9; 95% CI, 0.7-4.1). Three Crohn's disease patients developed small-bowel cancer vs 0.07 expected (SIR, 40.6; 95% CI, 8.4-118). CONCLUSIONS: The risk for colorectal cancer was not increased among ulcerative colitis patients overall, but appeared to be increased among those with extensive colitis. The colorectal cancer risk was increased slightly among Crohn's disease patients, who also had a 40-fold excess risk for small-bowel cancer.

Adolescent↗
PubMed2006

Incidence and prognosis of colorectal dysplasia in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota.

BACKGROUND AND AIMS: The risk, fate, and ideal management of colorectal dysplasia in inflammatory bowel disease (IBD) remain debated. We estimated the incidence, long-term outcome, and risk factors for progression of colorectal dysplasia (adenomas [adenoma-associated lesions or masses (ALMs)], flat dysplasia, and dysplasia-associated lesions or masses [DALMs]) in a population-based IBD cohort from Olmsted County, Minnesota. MATERIALS AND METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal dysplasia. Medical records were reviewed for demographic and clinical characteristics. Histology slides were reviewed by a pathologist blinded to previous pathology reports. The cumulative incidence of dysplasia was estimated, and the association between patient characteristics and recurrence/progression of dysplasia was assessed using proportional hazards regression. RESULTS: Twenty-nine (4%) IBD patients developed flat dysplasia (n = 8), DALMs (n = 1), ALMs in areas of IBD (n = 18), or ALMs outside areas of IBD (n = 2). Among 6 patients with flat low-grade dysplasia (fLGD) who did not undergo colectomy, none progressed during a median of 17.8 (range 6-21) years of observation with a median of 3 (range 0-12) surveillance colonoscopies. Four (22%) patients with ALMs in areas of IBD who did not undergo surgery developed LGD or DALMs. Primary sclerosing cholangitis and dysplasia located proximal to the splenic flexure were significantly associated with risk for recurrence/progression of dysplasia. CONCLUSIONS: This population-based cohort study from Olmsted County, Minnesota did not confirm an increased risk of cancer related to fLGD, whereas 22% of patients with ALMs in areas of IBD developed fLGD or DALMs.

Adenoma↗
PubMed2006

Microscopic colitis is not associated with cholecystectomy or appendectomy.

BACKGROUND: Microscopic colitis is a common cause of chronic watery diarrhea of unknown origin. Some patients develop diarrhea after cholecystectomy, and some patients with microscopic colitis have evidence of bile acid malabsorption. However, the association between cholecystectomy and microscopic colitis has not been studied. A protective effect of appendectomy on the development of ulcerative colitis also has been reported, but its relationship with microscopic colitis has not been studied. The aim of this study was to assess cholecystectomy and appendectomy as potential risk factors for the development of microscopic colitis in a nested case-control study. MATERIALS AND METHODS: Using the Rochester Epidemiology Project, we identified all Olmsted County (Minnesota) residents with an initial diagnosis of microscopic colitis between January 1, 1985, and December 31, 2001. Rates of antecedent cholecystectomy or appendectomy in patients with microscopic colitis were compared with age-, gender-, and calendar year-matched community controls through conditional logistic regression. RESULTS: Microscopic colitis was identified in 130 cases. Cholecystectomy preceded the diagnosis of microscopic colitis in 12 cases (9%) compared with 17 (13%) in the control group (odds ratio [OR] 0.7; 95% CI 0.3-1.5). Appendectomy preceded the diagnosis of microscopic colitis in 39 subjects (30%) compared with 28 (22%) in the control group (OR 1.6; 95% CI 0.9-2.7). Similar results were obtained when the analysis was restricted to microscopic colitis subtype (lymphocytic colitis or collagenous colitis). CONCLUSIONS: In this population-based nested case-control study, no significant association was seen between cholecystectomy or appendectomy and the development of microscopic colitis or its subtypes.

Adult↗
PubMed2006

Airway manifestations of pediatric eosinophilic esophagitis: a clinical and histopathologic report of an emerging association.

OBJECTIVES: Pediatric eosinophilic esophagitis (EE) typically presents with dysphagia, vomiting, dyspepsia, or food impaction. The purpose of this study was to highlight the emerging association of pediatric EE and airway disease. An additional goal of this study was to describe the unique histopathologic findings found in EE and specifically explore the potential role of the cytotoxic protein called eosinophil major basic protein (MBP) in the pathophysiology of the disease. METHODS: A retrospective review of 3 children with EE and airway symptoms included symptom presentation, aerodigestive tract endoscopic findings, ambulatory 24-hour dual pH-metry, allergy tests, treatment modalities, and treatment response. Esophageal tissue obtained from biopsies of each patient was evaluated by hematoxylin and eosin to determine the number of eosinophils per high-power field, by immunofluorescent anti-MBP staining to determine the presence of MBP, and by standard light and transmission electron microscopy to evaluate eosinophil migration patterns. RESULTS: All patients had airway inflammation that included nonspecific laryngeal edema and grade I or II subglottic stenosis. Allergy testing was positive in the 2 patients who were tested. All patients had symptoms refractory to standard reflux therapy. Ambulatory pH-metry findings were normal in 2 patients and abnormal in 1 patient despite maximum treatment. Two patients had visual abnormalities seen during esophageal examination. The number of eosinophils ranged from 20 to 45 per high-power field. Intracellular and extracellular MBP deposition was found in all esophageal biopsy specimens. All patients were treated with swallowed fluticasone, and 2 had symptom relapses that required repeat treatment. CONCLUSIONS: The spectrum of pediatric EE can include upper airway disease. Intracellular and extracellular MBP deposition is present in EE, which potentially releases cytotoxic mediators that explain the esophageal and airway clinical symptoms seen in those with the disease. Eosinophilic esophagitis should be considered in patients with a history of atopic diseases and unexplained upper airway findings refractory to reflux treatment. Treatment with swallowed fluticasone is successful; however, relapses are common and require repeat treatment and close follow-up.

Adolescent↗
PubMed2005

Outcome of untreated grade II rejection on solitary pancreas allograft biopsy specimens.

BACKGROUND: The most widely used grading scheme for acute pancreas allograft rejection grades biopsy specimens from 0 (normal) to V (severe rejection). Although the more advanced grades correlate strongly with immunologic graft loss, it is unclear how lesser grades impact graft outcome. The authors therefore report the outcomes of untreated grade II (minimal) rejection of solitary pancreas biopsy specimens. METHODS: The authors retrospectively analyzed all solitary pancreas transplants performed at the Mayo Clinic between January 2001 and November 2002. The authors selected all patients who were found with grade II findings on biopsy. Whether patients underwent follow-up biopsies, what the results were, and graft survival at the end of the study period were then determined. RESULTS: A total of 88 pancreas transplants were performed; 20 pancreas transplant recipients (23%) developed grade II (minimal) rejection and were followed for a mean of 22.8+/-8.7 months. Eighteen patients underwent biopsy for protocol purposes and two patients underwent clinically indicated biopsies. Of the patients who underwent biopsy as per protocol, 15 of the patients had a total of 25 follow-up biopsies: 10 were grade 0; 3 were grade I; and 10 were unchanged (grade II). Rejection in one patient progressed to grade III and in another patient to grade IV. The three patients who did not undergo repeat biopsy had a functioning allograft pancreas at the end of the study period. Of the two patients with grade II biopsy specimens obtained for clinical reasons, one had resolution of all inflammation noted on three follow-up biopsies, and the other patient did not undergo follow-up biopsy and died with a functioning graft. CONCLUSIONS: Grade II (minimal) rejection of solitary pancreas allograft rarely progresses to more severe degrees of inflammation. Morphologic findings in this category may not have unfavorable prognoses over a period of 2 years when untreated.

Adult↗
PubMed2005

Defective DNA mismatch repair in long-term (> or =3 years) survivors with pancreatic cancer.

BACKGROUND/AIMS: Defective DNA mismatch repair (MMR) in pancreatic cancer, reported in up to 13% of sporadic pancreatic cancers, may predict a good prognosis. To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived > or =3 years after surgery. METHODS: We performed immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35 tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10 microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was defined as absence of protein expression on IHC and/or MSI in > or =30% of markers studied. RESULTS: On IHC, 3/35 (8.6%) tumors had defective DNA MMR. All 3 had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also had MSI; the third could not be tested. Definitely 2, and probably all 3 patients had hereditary nonpolyposis colon cancer as determined by clinical and genetic profiles. CONCLUSION: Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2005

The nonsteroidal anti-inflammatory drug, nabumetone, differentially inhibits beta-catenin signaling in the MIN mouse and azoxymethane-treated rat models of colon carcinogenesis.

The mechanisms through which beta-catenin signaling is inhibited during colorectal cancer chemoprevention by nonsteroidal anti-inflammatory agents is incompletely understood. We report that nabumetone decreased uninvolved intestinal mucosal beta-catenin levels in the MIN mouse with a concomitant increase in glycogen synthase kinase (GSK)-3beta levels, an enzyme that targets beta-catenin for destruction. However, in the azoxymethane-treated rat, where beta-catenin is frequently rendered GSK-3beta-insensitive, nabumetone failed to alter beta-catenin levels but did decrease beta-catenin nuclear localization and transcriptional activity as gauged by cyclin D1. In conclusion, we demonstrate that the differential mechanisms for beta-catenin suppression may be determined, at least partly, by GSK-3beta.

Animals↗
PubMed2005

The transcriptional repressor SNAIL is overexpressed in human colon cancer.

Overexpression of the transcriptional repressor, SNAIL, has been implicated in the pathogenesis of a number of malignancies; however, there are no previous reports on the role of SNAIL in colorectal cancers (CRCs). We, therefore, evaluated human CRC specimens for the presence of the SNAIL protein. Immunohistochemical studies were performed using samples obtained from archived CRC paraffin blocks and a tissue array. Tissue sections were probed with a polyclonal antibody to human SNAIL and scored by a gastrointestinal pathologist. SNAIL was not detectable in uninvolved mucosa, but immunoreactivity was evident in 78% of tumors. SNAIL protein expression did not correlate with subsite location or gender, however, SNAIL-positive tumors had an older mean age (58.9 +/- 12.7 versus 49.8 +/- 127; P = 0.028). Furthermore, there was a trend that CRCs with metastatic ability more frequently overexpressed SNAIL (100 versus 65%; P = 0.11). In conclusion, we demonstrate, for the first time, that SNAIL is upregulated in human colon cancer, which potentially may have significance in control of metastasis and possibly serve as a target for chemopreventive agents.

Aging↗
PubMed2005

Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis.

Herein, we show that the hematopoietic-specific GEF VAV1 is ectopically expressed in primary pancreatic adenocarcinomas due to demethylation of the gene promoter. Interestingly, VAV1-positive tumors had a worse survival rate compared to VAV1-negative tumors. Surprisingly, even in the presence of oncogenic KRAS, VAV1 RNAi abrogates neoplastic cellular proliferation in vitro and in vivo, thus identifying Vav1 as a growth-stimulatory protein in this disease. Vav1 acts synergistically with the EGF receptor to stimulate pancreatic tumor cell proliferation. Mechanistically, the effects of Vav1 require its GEF activity and the activation of Rac1, PAK1, and NF-kappaB and involve cyclin D1 upregulation. Thus, the discovery of prooncogenic pathways regulated by Vav1 makes it an attractive target for therapeutic intervention.

Adenocarcinoma↗