Granulocyte colony-stimulating factor (G-CSF) is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells (MDSCs) promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer (CAC) model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for colitis-associated cancer.
Animals ; Carcinogenesis ; Colitis ; complications ; Colorectal Neoplasms ; complications ; drug therapy ; immunology ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Granulocyte Colony-Stimulating Factor ; genetics ; metabolism ; Immunotherapy ; Mice ; Molecular Targeted Therapy ; Myeloid Cells ; immunology ; metabolism ; pathology

BACKGROUND/AIMS: Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. METHODS: This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. RESULTS: The mean duration of follow-up for the 72 patients was 43.16+/-19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. CONCLUSIONS: The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.
Antiviral Agents/*therapeutic use ; Case-Control Studies ; Cohort Studies ; Colectomy/utilization ; Colitis, Ulcerative/complications/*drug therapy ; *Cytomegalovirus ; Cytomegalovirus Infections/complications/*drug therapy ; Ganciclovir/*therapeutic use ; Humans ; Longitudinal Studies ; Remission Induction ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; *Virus Activation

Hemophagocytic syndrome (HPS) is an uncommon hematological disorder that manifests as fever, splenomegaly, and jaundice, with hemophagocytosis in the bone marrow and other tissues pathologically. Secondary HPS is associated with malignancy and infection, especially viral infection. The prevalence of cytomegalovirus (CMV) infection in ulcerative colitis (UC) patients is approximately 16%. Nevertheless, HPS in UC superinfected by CMV is very rare. A 52-year-old female visited the hospital complaining of abdominal pain and hematochezia for 6 days. She was diagnosed with UC 3 years earlier and had been treated with sulfasalazine, but had stopped her medication 4 months earlier. On admission, her spleen was enlarged. The peripheral blood count revealed pancytopenia and bone marrow aspiration smears showed hemophagocytosis. Viral studies revealed CMV infection. She was treated successfully with ganciclovir. We report this case with a review of the related literature.
Antiviral Agents/therapeutic use ; Colitis, Ulcerative/*complications/drug therapy ; Cytomegalovirus Infections/*complications/drug therapy ; Female ; Ganciclovir/therapeutic use ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Hemorrhage/etiology ; Humans ; Lymphohistiocytosis, Hemophagocytic/drug therapy/*virology ; Middle Aged ; Sulfasalazine/therapeutic use ; Superinfection/*complications

Takayasu arteritis (TA) is a chronic vasculitis that affects the aortic arch and its primary branches. Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Patients diagnosed with both TA and UC have rarely been reported. The pathogenesis of TA and UC is uncertain, but cell-mediated mechanisms play an important role in both diseases, and a genetic factor is thought to have an effect on the coincidence of these two diseases. We herein report a 38-year-old female with TA who had a history of UC with optic neuritis. We believe that this is the first case of the coexistence of TA and UC in Korea.
Adult ; Anti-Inflammatory Agents/therapeutic use ; Aortography/methods ; Colitis, Ulcerative/*complications/diagnosis/drug therapy ; Colonoscopy ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Optic Neuritis/*complications/diagnosis/drug therapy ; Positron-Emission Tomography ; Republic of Korea ; Steroids/therapeutic use ; Takayasu Arteritis/*complications/diagnosis/drug therapy ; Tomography, X-Ray Computed ; Treatment Outcome

Colitis, Ulcerative ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Psoriasis ; complications ; drug therapy ; Pyoderma Gangrenosum ; drug therapy ; etiology

Segmental colitis associated with diverticular disease (SCAD) is a colonic inflammatory disorder with localized non-granulomatous inflammation at sigmoid colon, and associated with colonic diverticulosis. SCAD is an apparently uncommon disorder in Western. We experienced a rare case of SCAD in a 46-year-old woman who visited the hospital due to abdominal discomfort. Colonoscopic examination showed multiple sigmoid diverticula in association with a segment length colitis. Colonoscopic biopsies of the sigmoid colon demonstrated cryptitis and crypt abscess along with chronic inflammatory cells infiltration. The biopsies of the rectum was histologically normal. The patient was given the diagnosis of SCAD and treated with oral mesalamine. This is the first case of SCAD reported in Korea.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Colitis/complications/*diagnosis/drug therapy ; Colon, Sigmoid/pathology ; Colonoscopy ; Diverticulitis, Colonic/complications/*diagnosis/drug therapy ; Female ; Humans ; Mesalamine/therapeutic use ; Middle Aged

A 21-year-old man admitted complaining of sudden severe epigastric pain for 1 day. He had been diagnosed as ulcerative colitis (UC) and taking mesalazine for two months. UC was in nearly complete remission at admission. He never drank an alcohol, and serum amylase was 377 IU/L. CT scan showed inferior vena cava (IVC) thrombosis in addition to mild acute pancreatitis. To evaluate the cause of acute pancreatitis and IVC thrombosis, magnetic resonance cholangiopancreatogram (MRCP), endoscopic ultrasonogram (EUS), lower extremity Doppler ultrasonogram (US) and blood test of hypercoagulability including factor V, cardiolipin Ab, protein C, protein S1, antithrombin III, and anti phospholipids antibody were performed. There was no abnormality except mild acute pancreatitis and IVC thrombosis in all the tests. He was recommended to stop taking mesalazine and start having anticoagulation therapy. After all symptoms disappeared and amylase returned normal, rechallenge test with mesalazine was done. Flare-up of abdominal pain occurred and the elevation of serum amylase was observed. Ulcerative colitis came to complete remission with short-term steroid monotherapy. Acute pancreatitis and IVC thrombosis were completely resolved after 3-month anticoagulation therapy with no more mesalazine. We postulated that IVC thrombosis occurred due to hypercoagulable status of UC and intra-abdominal inflammation caused by mesalazine-induced pancreatitis.
Acute Disease ; Amylases/blood ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects/therapeutic use ; Anticoagulants/therapeutic use ; Cholangiopancreatography, Magnetic Resonance ; Colitis, Ulcerative/complications/*diagnosis/drug therapy ; Endosonography ; Humans ; Male ; Mesalamine/*adverse effects/therapeutic use ; Pancreatitis/chemically induced/*diagnosis/ultrasonography ; Tomography, X-Ray Computed ; Ultrasonography, Doppler ; *Vena Cava, Inferior/ultrasonography ; Venous Thrombosis/complications/*diagnosis/drug therapy ; Young Adult

A case of hemophagocytic syndrome associated with ulcerative colitis is very rare. A 32-year-old man visited the hospital complaining of fever and severe abdominal pain for 7 days. He was diagnosed to have ulcerative colitis 2 years ago and had been treated with sulfasalazine. Three months ago, he had abdominal pain, weight loss, and hematochezia, so prednisolone and mercaptopurine were added to the treatment. On admission, the physical examination showed splenomegaly. Peripheral blood counts revealed pancytopenia, and bone marrow aspirate smears showed many histiocytes with active hemophagocytosis. There was no evidence of viral and bacterial infections and other neoplasms, which were commonly associated with hemophagocytic syndrome. He was successfully treated with high dose steroid. We report this case along with a review of the related literatures.
6-Mercaptopurine/therapeutic use ; Adult ; Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Bone Marrow Cells/pathology ; Colitis, Ulcerative/complications/*diagnosis/drug therapy ; Colonoscopy ; Dexamethasone/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Lymphohistiocytosis, Hemophagocytic/complications/*diagnosis/drug therapy ; Male ; Prednisolone/therapeutic use ; Sulfasalazine/therapeutic use ; Syndrome ; Tomography, X-Ray Computed

Triptolide, a diterpenoid triepoxide from the traditional Chinese medicinal herb Tripterygium wilfordii Hook. f., is a potential treatment for autoimmune diseases as well a possible anti-tumor agent. It inhibits proliferation of coloretal cancer cells in vitro and in vivo. In this study, its ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK1, IL6R and phosphorylated STAT3 were all reduced by triptolide treatment. Triptolide prohibited Rac1 activity and blocked cyclin D1 and CDK4 expression, leading to G1 arrest. Triptolide interrupted the IL6R-JAK/STAT pathway that is crucial for cell proliferation, survival, and inflammation. This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development.
Animals ; Cell Transformation, Neoplastic/*drug effects ; Colitis/complications ; Colonic Neoplasms/chemically induced/*drug therapy/metabolism/pathology ; Dextran Sulfate/toxicity ; Dimethylhydrazines/toxicity ; Diterpenes/*administration & dosage ; Epoxy Compounds/administration & dosage ; Humans ; Interleukin-6/biosynthesis ; Janus Kinases/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Mice, Nude ; Neoplasm Transplantation ; Phenanthrenes/*administration & dosage ; STAT3 Transcription Factor/metabolism ; Signal Transduction/*drug effects ; Tumor Burden/drug effects ; rac1 GTP-Binding Protein/*biosynthesis

BACKGROUND/AIMS: The prevalence of Helicobacter pylori (H. pylori) infection has been reported to be lower in individuals with inflammatory bowel disease (IBD) in some Western countries. We investigated H. pylori infection in Korean patients with IBD and any possible associations of H. pylori infection with drug therapy for IBD and the phenotype of Crohn's disease (CD). METHODS: We studied 316 unselected patients with IBD, including 169 ulcerative colitis (UC) patients and 147 with CD, and the control group consisted of 316 age- and gender-matched healthy people who received a comprehensive medical examination for a regular checkup purpose. Infection rates of H. pylori as detected by the urea breath test were compared between the IBD patients and the controls. RESULTS: A statistically significant difference in H. pylori infection rate was noticed between the IBD patients (25.3%) and the controls (52.5%; p<0.001), and between UC (32.0%) and CD patients (17.7%; p=0.04). Among the IBD patients, the age group of <60 and individuals with a history of taking metronidazole (13.0%; p=0.038) or ciprofloxacin (6.7%; p=0.001) were found to have a meaningfully lower infection rate, but those who did not take antibiotics still showed H. pylori infection rate significantly lower than the controls (CD 22.0% vs. UC 33.8% vs. Control 52.5%, p<0.001). With an exception of age, phenotypic characteristics showed no significant relations with H. pylori infection rate in CD patients. CONCLUSIONS: Korean patients with IBD, particularly CD, were found to have a significantly lower H. pylori infection rate than the controls. This association was more evident in those <60 years old, which suggested that H. pylori infection might be deemed to lower possible risks of IBD in younger adults.
Adolescent ; Adult ; Age Factors ; Aged ; Colitis, Ulcerative/complications/diagnosis/drug therapy ; Crohn Disease/complications/diagnosis/drug therapy ; Female ; Helicobacter Infections/complications/diagnosis/*epidemiology ; *Helicobacter pylori ; Humans ; Inflammatory Bowel Diseases/*complications/diagnosis/drug therapy ; Korea ; Male ; Middle Aged ; Phenotype ; Prevalence