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Mucoadhesive carriers for oral drug delivery. J Control Release 2022; 351:504-559. [PMID: 36116580 PMCID: PMC9960552 DOI: 10.1016/j.jconrel.2022.09.024] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 09/10/2022] [Accepted: 09/12/2022] [Indexed: 12/24/2022]
Abstract
Among the various dosage forms, oral medicine has extensive benefits including ease of administration and patients' compliance, over injectable, suppositories, ocular and nasal. Despite of extensive demand and emerging advantages, over 50% of therapeutic molecules are not available in oral form due to their physicochemical properties. More importantly, most of the biologics, proteins, peptide, and large molecular drugs are mostly available in injectable form. Conventional oral drug delivery system has limitation such as degradation and lack of stability within stomach due to presence of highly acidic gastric fluid, hinders their therapeutic efficacy and demand more frequent and higher dosing. Hence, formulation for controlled, sustained, and targeted drug delivery, need to be designed with feasibility to target the specific region of gastrointestinal (GI) tract such as stomach, small intestine, intestine lymphatic, and colon is challenging. Among various oral delivery approaches, mucoadhesive vehicles are promising and has potential for improving oral drug retention and controlled absorption to treat local diseases within the GI tract, as well systemic diseases. This review provides the overview about the challenges and opportunities to design mucoadhesive formulation for oral delivery of therapeutics in a way to target the specific region of the GI tract. Finally, we have concluded with future perspective and potential of mucoadhesive formulations for oral local and systemic delivery.
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Akkol EK, Karpuz B, Sobarzo-Sánchez E, Khan H. A phytopharmacological overview of medicinal plants used for prophylactic and treatment of colitis. Food Chem Toxicol 2020; 144:111628. [PMID: 32738379 DOI: 10.1016/j.fct.2020.111628] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/26/2020] [Accepted: 07/14/2020] [Indexed: 12/26/2022]
Abstract
Inflammatory bowel diseases are chronic diseases that develop on the genetic background. They are characterized by an idiopathic, chronic course and periods of activation and remission. However, genetic and environmental factors are thought to play a role in its pathogenesis. Significant improvements in treatment strategies have been witnessed. Depending on the severity of the disease, mesalamine, immunosuppressants, anti-TNF, anti-integrin, Janus kinase inhibitors, and thiopurines can be used for treatment. However, these treatments have side effects such as headache, dizziness, nausea, loss of appetite, hair loss, gas, vomiting, rash, fever, and decreased white blood cell count. The search for treatment that may be a safer alternative, immunomodulatory, and immunosuppressive therapy has gained importance nowadays. Herbal medicine is preferred to treat a wide range of acute and chronic gastrointestinal diseases, including ulcerative colitis. Preclinical and clinical studies show that plants are promising in terms of their use in treating pathological conditions. The effectiveness of plants in treating ulcerative colitis has been determined. However, more studies are needed to explore the long-term effects of these herbal medicines. The present review presents information on medicinal plants and phytochemicals reported for use or potential of application in ulcerative colitis, a type of inflammatory bowel diseases.
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Affiliation(s)
- Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey.
| | - Büşra Karpuz
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey
| | - Eduardo Sobarzo-Sánchez
- Instituto de Investigación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, 8330507, Santiago, Chile; Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan.
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Tripathi K, Feuerstein JD. New developments in ulcerative colitis: latest evidence on management, treatment, and maintenance. Drugs Context 2019; 8:212572. [PMID: 31065290 PMCID: PMC6490072 DOI: 10.7573/dic.212572] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 03/21/2019] [Accepted: 03/21/2019] [Indexed: 12/12/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder that involves any part of the colon starting in the rectum in a continuous fashion presenting typically with symptoms such as bloody diarrhea, abdominal pain, and rectal urgency. UC is diagnosed based on clinical presentation and endoscopic evidence of inflammation in the colon starting in the rectum and extending proximally in the colon. The clinical presentation of the disease usually dictates the choice of pharmacologic therapy, where the goal is to first induce remission and then maintain a corticosteroid-free remission. There are multiple classes of drugs that are available and are used based on the clinical severity of the disease. For mild-to-moderate disease, oral or rectal formulations of 5-aminosalicylic acid are used. In moderate-to-severe UC, corticosteroids are usually used in induction of remission with or without another class of medications such as thiopurines or biologics including anti-tumor necrosis factor, anti-integrins, or Janus kinase inhibitors for maintenance of remission. Up to 15% of the patients may require surgery as they fail to respond to medications and have risk of developing dysplasia secondary to longstanding colitis.
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Affiliation(s)
| | - Joseph D Feuerstein
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Mueller R, Ziade F, Pittet V, Fournier N, Ezri J, Schoepfer A, Schibli S, Spalinger J, Braegger C, Nydegger A. Quality of Life in Swiss Paediatric Inflammatory Bowel Disease Patients: Do Patients and Their Parents Experience Disease in the Same Way? J Crohns Colitis 2016; 10:269-76. [PMID: 26519462 PMCID: PMC4957466 DOI: 10.1093/ecco-jcc/jjv199] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 10/21/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel diseases (IBDs) may impair quality of life (QoL) in paediatric patients. We aimed to evaluate in a nationwide cohort whether patients experience QoL in a different way when compared with their parents. METHODS Sociodemographic and psychosocial characteristics were prospectively acquired from paediatric patients and their parents included in the Swiss IBD Cohort Study. Disease activity was evaluated by the Paediatric Crohn's Disease Activity Index (PCDAI) and the Paediatric Ulcerative Colitis Activity Index (PUCAI). We assessed QoL using the KIDSCREEN questionnaire. The QoL domains were analysed and compared between children and parents according to type of disease, parents' age, origin, education and marital status. RESULTS We included 110 children and parents (59 Crohn's disease [CD], 45 ulcerative colitis [UC], 6 IBD unclassified [IBDU]). There was no significant difference in QoL between CD and UC/IBDU, whether the disease was active or in remission. Parents perceived overall QoL, as well as 'mood', 'family' and 'friends' domains, lower than the children themselves, independently of their place of birth and education. However, better concordance was found on 'school performance' and 'physical activity' domains. Marital status and age of parents significantly influenced the evaluation of QoL. Mothers and fathers being married or cohabiting perceived significantly lower mood, family and friends domains than their children, whereas mothers living alone had a lower perception of the friends domain; fathers living alone had a lower perception of family and mood subscores. CONCLUSION Parents of Swiss paediatric IBD patients significantly underestimate overall QoL and domains of QoL of their children independently of origin and education.
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Affiliation(s)
- Rebekka Mueller
- Division of Pediatric Gastroenterology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Farah Ziade
- Division of Pediatric Gastroenterology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Valérie Pittet
- Institute of Social and Preventive Medicine, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland
| | - Jessica Ezri
- Division of Pediatric Gastroenterology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Alain Schoepfer
- Division of Gastroenterology and Hepatology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Susanne Schibli
- Division of Gastroenterology, University Children’s Hospital of Bern, Bern, Switzerland
| | - Johannes Spalinger
- Division of Gastroenterology, University Children’s Hospital of Bern, Bern, Switzerland,Division of Gastroenterology, Children’s Hospital of Lucerne, Lucerne, Switzerland
| | - Christian Braegger
- Division of Gastroenterology and Nutrition, University Children’s Hospital of Zurich, Zurich, Switzerland
| | - Andreas Nydegger
- Division of Pediatric Gastroenterology, University Hospital of Lausanne, Lausanne, Switzerland
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Manolakis AC, Kapsoritakis AN, Kapsoritaki A, Tiaka EK, Oikonomou KA, Lotis V, Vamvakopoulou D, Davidi I, Vamvakopoulos N, Potamianos SP. Readressing the role of Toll-like receptor-4 alleles in inflammatory bowel disease: colitis, smoking, and seroreactivity. Dig Dis Sci 2013; 58:371-380. [PMID: 22918682 DOI: 10.1007/s10620-012-2348-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2012] [Accepted: 07/28/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. AIMS To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. METHODS TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. RESULTS UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). CONCLUSIONS The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.
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Affiliation(s)
- Anastassios C Manolakis
- Department of Gastroenterology, University Hospital of Larissa, University of Thessaly, School of Medicine, 41110, Larissa, Greece.
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Lian LH, Lau TP, Lee VL, Lee WS, Hilmi I, Goh KL, Chua KH. Lack of association between TYK2 and STAT3 genes and Crohn's disease in the Malaysian population. GENETICS AND MOLECULAR RESEARCH 2013; 12:167-74. [PMID: 23408403 DOI: 10.4238/2013.january.24.9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.
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Affiliation(s)
- L H Lian
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Tonelli F, Giudici F, Liscia G. Is lymphatic status related to regression of inflammation in Crohn's disease? World J Gastrointest Surg 2012; 4:228-33. [PMID: 23443404 PMCID: PMC3582160 DOI: 10.4240/wjgs.v4.i10.228] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2012] [Revised: 09/14/2012] [Accepted: 09/21/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the status of the lymphatic vessels in the small bowel affected by Crohn’s disease (CD) at the moment of surgery.
METHODS: During the period January 2011-June 2011, 25 consecutive patients affected by CD were operated on in our Institution. During surgery, Patent Blue V was injected subserosally and the way it spread along the subserosa of the intestinal wall, through the mesenterial layers towards the main lymphatic collectors and eventually to the lymph nodes was observed and recorded. Since some patients had been undergone strictureplasty at previous surgery, we also examined the status of intestinal lymph vessels after previous strictureplasties. The same procedure was performed in a control group of 5 patients affected by colorectal cancer. Length of lesions, caliber, maximal thickness of the diseased intestinal wall, thickness of the wall at injection site and thickness of the mesentery were evaluated at surgery.
RESULTS: We observed three features after the injection of Patent Blue V in the intestinal loops: (1) Macroscopically healthy terminal ileum of patients with CD or colon cancer showed thin lymphatic vessels linearly directed toward the mesentery; (2) In mild lesions in which the intestinal wall did not reach 8 mm of thickness, we observed short, wide and tortuous lymphatic vessels directed longitudinally along the intestinal axis toward disease-free areas and then transversally toward the mesentery; and (3) Injection in the severely affected lesions, that had a thickness of the intestinal wall over 10 mm, did not show any feature of lymphatic vessels at least on the subserosal surface. There was a correlation between the thickness of the parietal wall and the severity of the lymphatic alterations. Normal lymphatic vessels were observed at previous strictureplasties in the presence of complete regression of the inflammation.
CONCLUSION: Injection of Patent Blue V in the intestinal wall could help distinguish healthy tracts of the small bowel from those macroscopically borderline.
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Affiliation(s)
- Francesco Tonelli
- Francesco Tonelli, Francesco Giudici, Gadiel Liscia, Department of Clinical Physiopathology, University of Florence, Surgical Unit, 50134 Florence, Italy
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Benharush D, Cohen MJ, Kasirer Y, Turner D. Short chain fatty acids (butyrate) for induction of remission in ulcerative colitis. Hippokratia 2010. [DOI: 10.1002/14651858.cd008730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- David Benharush
- The Hebrew University; Faculty of Medicine; Jerusalem Israel
| | - Matan J Cohen
- Hadassah Medical Center; Center for Clinical Quality & Safety; Ein Kessem Campus Box 53, POB12000 Jerusalem Israel 91120
| | - Yair Kasirer
- Shaare Zedek Medical Center; Pediatric Gastroenterology Unit; P.O.B 3235 Jerusalem 91031 Israel
| | - Dan Turner
- Shaare Zedek Medical Center; Pediatric Gastroenterology Unit; P.O.B 3235 Jerusalem 91031 Israel
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Pagán B, Isidro AA, Coppola D, Chen Z, Ren Y, Wu J, Appleyard CB. Effect of a neurokinin-1 receptor antagonist in a rat model of colitis-associated colon cancer. Anticancer Res 2010; 30:3345-3353. [PMID: 20944107 PMCID: PMC3733557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
AIM The role of substance P and the neurokinin-1 receptor (NK-1R) in the transition from inflammation to dysplasia in inflammatory bowel disease is not clear. MATERIALS AND METHODS Colitis-associated dysplasia was induced in Sprague-Dawley rats by intracolonic, then systemic, administration of trinitrobenzene sulfonic acid. One group of animals received the NK-1R antagonist SR140333; the rest received vehicle. Colons were removed and analyzed for damage and expression of NK-1R downstream components. RESULTS The NK-1R antagonist-treated animals had significantly reduced macroscopic and microscopic damage and decreased incidence of inflammatory bowel disease. Twice as many of these animals had a normal diagnosis in any region of the colon. A decrease in proliferation index, Cox-2 expression, and active Erk1/2 was found compared with the vehicle-treated group. In Caco-2 cells, Erk1/2 was activated by substance P and prostaglandin E2. CONCLUSION A selective NK-1R antagonist may delay the development of further colonic damage, offering a potential treatment for patients with long-standing colitis.
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Affiliation(s)
- Beatriz Pagán
- Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce PR, 00732, USA
| | - Angel A. Isidro
- Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce PR, 00732, USA
| | - Domenico Coppola
- Departments of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Zhengming Chen
- Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Yuan Ren
- Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Jie Wu
- Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Caroline B. Appleyard
- Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce PR, 00732, USA
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Abstract
The clinical course of heel pain can be frustrating to the clinician and the patient. Most heel pain responds to conservative care in a short period of time. However, other causes should be considered, especially if the heel pain is recalcitrant to treatment. A detailed history and physical examination, along with appropriate laboratory tests and radiological studies, can direct the physician toward the correct diagnosis. There are many systemic causes of heel pain, some common and others uncommon. Regardless of the incidence, a strong index of suspicion is raised whenever the heel pain fails to respond as routine plantar fasciitis should.
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Affiliation(s)
- Eric Lui
- Connecticut Surgical Group, 85 Seymour Street #409, Hartford, CT 06106, USA.
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Deng L, Zhou JF, Sellers RS, Li JF, Nguyen AV, Wang Y, Orlofsky A, Liu Q, Hume DA, Pollard JW, Augenlicht L, Lin EY. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis. THE AMERICAN JOURNAL OF PATHOLOGY 2010. [PMID: 20042677 DOI: 10.2353/ajpath.2010.090622.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Inflammatory bowel disease (IBD) is a high-risk condition for human colorectal cancer. However, our mechanistic understanding of the link between inflammation and tumorigenesis in the colon is limited. Here we established a novel mouse model of colitis-associated cancer by genetically inactivating signal transducer and activator of transcription 3 (Stat3) in macrophages, with partial deletion in other myeloid and lymphoid cells. Inflammation developed in the colon of mutant mice spontaneously, and tumor lesions, including invasive carcinoma, arose in the inflamed region of the intestine with a frequency similar to that observed in human IBD patients. The development of both inflammation and tumors in the mutant mice required the presence of microflora. Indeed, inflammation was associated with disruption of colonic homeostasis, fulminant epithelial/tumor cell proliferation, and activation of the mammalian target of rapamycin (mTOR)-Stat3 pathway in epithelial and tumor cells. The activation of this pathway was essential for both the excess proliferation of epithelial/tumor cells and the disruption of colonic homeostasis in the mutant mice. Notably, a similar abnormal up-regulation of mTOR-Stat3 signaling was consistently observed in the colonic epithelial cells of human IBD patients with active disease. These studies demonstrate a novel mouse model of IBD-colorectal cancer progression in which disrupted immune regulation, mTOR-Stat3 signaling, and epithelial hyperproliferation are integrated and simultaneously linked to the development of malignancy.
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Affiliation(s)
- Lin Deng
- Department of Medicine, Oncology Division, Albert Einstein Cancer Center, Bronx, NY 10467, USA
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Deng L, Zhou JF, Sellers RS, Li JF, Nguyen AV, Wang Y, Orlofsky A, Liu Q, Hume DA, Pollard JW, Augenlicht L, Lin EY. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis. THE AMERICAN JOURNAL OF PATHOLOGY 2009; 176:952-67. [PMID: 20042677 DOI: 10.2353/ajpath.2010.090622] [Citation(s) in RCA: 175] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Inflammatory bowel disease (IBD) is a high-risk condition for human colorectal cancer. However, our mechanistic understanding of the link between inflammation and tumorigenesis in the colon is limited. Here we established a novel mouse model of colitis-associated cancer by genetically inactivating signal transducer and activator of transcription 3 (Stat3) in macrophages, with partial deletion in other myeloid and lymphoid cells. Inflammation developed in the colon of mutant mice spontaneously, and tumor lesions, including invasive carcinoma, arose in the inflamed region of the intestine with a frequency similar to that observed in human IBD patients. The development of both inflammation and tumors in the mutant mice required the presence of microflora. Indeed, inflammation was associated with disruption of colonic homeostasis, fulminant epithelial/tumor cell proliferation, and activation of the mammalian target of rapamycin (mTOR)-Stat3 pathway in epithelial and tumor cells. The activation of this pathway was essential for both the excess proliferation of epithelial/tumor cells and the disruption of colonic homeostasis in the mutant mice. Notably, a similar abnormal up-regulation of mTOR-Stat3 signaling was consistently observed in the colonic epithelial cells of human IBD patients with active disease. These studies demonstrate a novel mouse model of IBD-colorectal cancer progression in which disrupted immune regulation, mTOR-Stat3 signaling, and epithelial hyperproliferation are integrated and simultaneously linked to the development of malignancy.
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Affiliation(s)
- Lin Deng
- Department of Medicine, Oncology Division, Albert Einstein Cancer Center, Bronx, NY 10467, USA
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Knight C, Murray KF. Hepatobiliary associations with inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2009; 3:681-91. [PMID: 19929587 DOI: 10.1586/egh.09.53] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatobiliary disease is not uncommon in patients with inflammatory bowel disease (IBD). The most common autoimmune hepatic associations are primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). The immunosuppressant medications used in the treatment of IBD also have potential hepatotoxicity. PSC is most commonly associated with IBD, specifically ulcerative colitis. AIH, a more classic autoimmune disease diagnosed commonly in isolation of other conditions in the same individual, is less commonly associated with IBD. Additionally, a subgroup of patients have features of both PSC and AIH, termed overlap syndrome, that is also sometimes seen in IBD patients. This review will discuss the most common liver disease associations seen in patients with IBD: PSC, AIH and overlap syndrome. Additionally, the most common drug-related hepatotoxicities encountered when treating IBD will be reviewed.
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Affiliation(s)
- Crystal Knight
- Seattle Children's and University of Washington School of Medicine, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, 4800 Sand Point Way, NE, PO Box 5371/W-7830, Seattle, WA 98105, USA.
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14
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Viola F, Civitelli F, Di Nardo G, Barbato MB, Borrelli O, Oliva S, Conte F, Cucchiara S. Efficacy of adalimumab in moderate-to-severe pediatric Crohn's disease. Am J Gastroenterol 2009; 104:2566-71. [PMID: 19550415 DOI: 10.1038/ajg.2009.372] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The use of tumor necrosis factor-alpha (TNF-alpha) antagonists has changed the therapeutic strategy for Crohn's disease (CD). Adalimumab (ADA), a fully human anti-TNF-alpha monoclonal antibody, is an effective therapy for patients with CD, both naive patients and those intolerant or refractory to Infliximab (IFX), a chimeric anti-TNF-alpha agent. However, the use of ADA is rarely reported in pediatric CD. We performed an open prospective evaluation of short- and long-term efficacy and safety of ADA in children with moderate-to-severe CD. METHODS A total of 23 pediatric CD patients (9 naive and 14 intolerant or unresponsive to IFX) received ADA subcutaneously as a loading schedule at weeks 0 and 2, and at every other week (eow) during a 48-week maintenance phase. Loading and maintenance doses were 160/80 and 80 mg eow in 13 cases, 120/80 and 80 mg eow in 2, and 80/40 and 40 mg eow in 8 cases. The primary efficacy outcomes were clinical remission and response at different scheduled visits along the maintenance phase. At baseline, 13 patients also received immunomodulators (IMs). RESULTS At weeks 2, 4, 12, 24, and 48, remission rates were 36.3, 60.8, 30.5, 50, and 65.2%, respectively, whereas response rates were 87, 88, 70, 86, and 91%, respectively. Four patients at week 24 and 2 at week 48 received IMs; the mean daily corticosteroid dose, disease activity index, C-reactive protein level, and erythrocyte sedimentation rate decreased significantly throughout the trial. No serious adverse events were recorded. CONCLUSIONS ADA can be an effective and safe biological agent for inducing and maintaining remission in children with moderate-to-severe CD, even in those with previous IFX therapy.
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Affiliation(s)
- Franca Viola
- Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, University Hospital Umberto I, Sapienza University of Rome, Rome 324-00161, Italy
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15
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Abstract
The considerable interindividual differences in efficacy and side effects of commonly used medications in Crohn’s disease are partly owing to genetic polymorphisms. Many genetic variants have been studied in genes possibly involved in the metabolism or mechanism of action of therapeutic agents such as glucocorticosteroids, azathioprine/6-mercaptopurine, methotrexate, calcineurin inhibitors or anti-TNF agents. However, the only test translated into clinical practice is thiopurine S-methyltransferase (TPMT) genotyping for hematological toxicity of thiopurine treatment. To date, there are no other meaningful applications for pharmacogenomics in clinical practice of Crohn’s disease. In the future, designed therapeutic trials should possibly permit the development of predictive models including genotypic markers, such as that proposed for the clinical outcome after infliximab therapy, which includes an apoptotic pharmacogenetic index. The recent identification of new susceptibility genes provides additional candidate markers that have possible effects on the outcomes of therapies, and prioritizes new therapeutic targets, such as the IL-23 pathway. Futher innovative approaches might be relevant for the pharmacogenetic investigation of gene variants implied in innate immune pattern recognition and autophagy.
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Affiliation(s)
- Helga-Paula Török
- University of Munich, Department of Internal Medicine II, Campus Großhadern, Marchioninistr. 15, D-81377 Munich, Germany
| | - Burkhard Göke
- University of Munich, Department of Internal Medicine II, Campus Großhadern, Marchioninistr. 15, D-81377 Munich, Germany
| | - Astrid Konrad
- University of Munich, Department of Internal Medicine II, Campus Großhadern, Marchioninistr. 15, D-81377 Munich, Germany
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