Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis

Logan, Richard M.; Gibson, Rachel J.; Bowen, Joanne M.; Stringer, Andrea M.; Sonis, Stephen T.; Keefe, Dorothy

doi:10.1007/s00280-007-0570-0

Cited by 171 publications

(183 citation statements)

References 31 publications

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“…Another study 29 implicated the role of NF-κβ, proinflammatory cytokines, COX and MMPs in the pathogenesis of mucositis as these factors were being expressed at elevated levels in both serum and tissue following radiotherapy and/or chemotherapy 29 . Our findings have also been supported by studies done on an animal model by Logan et al that reported the changes in the expression of NF-κβ, TNF, IL-1β and IL-6 in the mucosa and serum following chemotherapy orated a statistically increased oral mucosal stain 17,30 . Another study done by Logan et al, on a human biopsy demonstrated the increased level of NF-κβ and COX-2 in patients with chemotherapy as well as radiotherapy 17 .…”

Section: Discussionsupporting

confidence: 79%

Profiling of pro-inflammatory cytokines in radiation induced oral mucositis (riom) among indian patients

et al. 2017

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Radiation-induced oral mucositis (RIOM) is aimed at evaluating the expression of NF-κβ, IL-1α, IL-6, IL-8 and TNF-α in patients with RIOM so as to validate their role in the pathobiology of the disease. Blood samples were collected and serum of 45 patients isolated with clinical signs and symptoms of mucositis and 10 healthy controls were also included in the study. The expression level of NF-κβ, IL-1α, IL-6, IL-8, TNF-α was investigated using ELISA. Mann Whitney U test was applied to find the significance of the expression of these markers in RIOM patients as compared to normal healthy controls and significant expression (P< 0.05) for NF-κβ, IL-6, TNF-α and non-significant expression (P > 0.05) IL-1α and IL-8 was found. No significant change in the expression level of the cytokines was observed for patients undergoing chemotherapy and radiation therapy as well as those receiving only the radiation therapy as a part of their treatment. We have also found less expression in grade 1 of mucositis as compared to grade 4. Pro-inflammatory cytokines indeed play a vital role in the pathogenesis as well as progression of RIOM.

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Section: Discussionsupporting

confidence: 79%

Profiling of pro-inflammatory cytokines in radiation induced oral mucositis (riom) among indian patients

et al. 2017

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“…6) Data from both animal and human studies support this hypothesis. [7][8][9] Furthermore, these same phases can lead to damage of the gastrointestinal tract, including cell death, which leads to villous atrophy and crypt ablation in the small intestine. This can affect the activity of hydolases, enzymes which participate in the metabolism of carbohydrates and are present at the border brush of enterocytes.…”

mentioning

confidence: 99%

In a Methotrexate-Induced Model of Intestinal Mucositis, Olmesartan Reduced Inflammation and Induced Enteropathy Characterized by Severe Diarrhea, Weight Loss, and Reduced Sucrose Activity

Araújo

Borba²,

Souza³

et al. 2015

Biological & Pharmaceutical Bulletin

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The aim of this study was to evaluate the effect of olmesartan (OLME), an angiotensin II receptor antagonist, on an intestinal mucositis model. Briefly, daily intraperitoneal (i.p.) injections of methotrexate (MTX) 7 mg/kg were administered to rats on 3 consecutive days. A subset of these rats was also pretreated with oral administration of OLME (0.5, 1.0, or 5.0 mg/kg) or vehicle as a control 30 min prior to MTX injection. Body weight, feces scoring, and death were recorded daily. On day 4, the rats were killed, and intestinal tissues were assayed for levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, myeloperoxidase and sucrose activity, and histopathological findings. A significant reduction in body weight was observed in the MTX 1.0 mg/kg OLME group (p<0.01). The feces scores for the MTX 0.5 mg/kg OLME and MTX 5.0 mg/ kg OLME groups were also significantly higher (p<0.001). Sucrose activity was reduced in all groups treated with OLME (p<0.05). Treatment with MTX OLM at all doses resulted in reduced inflammatory infiltration, ulcerations, vasodilation, and hemorrhagic areas ( p<0.05), as well as reduced concentrations of myeloperoxidase (p<0.001). The IL-1β and TNF-α levels were decreased in the MTX OLME 5.0 mg/kg (p<0.01 and p<0.05, respectively) compared with the MTX-alone group. Overall, antiinflammatory activity was observed in rats with MTX-induced intestinal mucositis that were administered OLME. However, further studies are needed to elucidate the adverse effects of OLME. Key words intestinal mucositis model; olmesartan; inflammationIt has been reported that 40% of cancer patients develop intestinal mucositis during a standard cancer chemotherapy regimen, while almost 100% of patients who receive high dose treatments are affected.1) Mucositis represents a dose-limiting toxicity of therapy and it currently affects approximately 500000 patients annually worldwide.2) The entire alimentary tract (mouth to anus) is affected, which leads to clinical symptoms that derive from ulcerations, and these include abdominal pain, nausea, vomiting, bloating, diarrhea, constipation, and subsequent weight loss.3) Furthermore, these complications can lead to longer hospitalisations and increasing health care costs. 4)Methotrexate (MTX) is a structural analogue of folic acid and is widely used in the treatment of leukaemia and other malignancies. Tissues with high rates of proliferation are affected by MTX, and these can include both tumor and normal tissues. When MTX affects gut tissues, gastrointestinal mucositis develops. Correspondingly, approximately 60% of cancer patients that receive a chemotherapy treatment that includes MTX experience diarrhoea. 5)The currently accepted hypothesis for the development of alimentary mucositis (AM) suggests there are five intertwined phases: (1) initiation, (2) up-regulation and generation of messenger signals, (3) signal amplification, (4) ulceration, and (5) healing.6) Data from both animal and human studies support this hypothesis.7-9) Furthermore, these same phases...

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“…At the same time, reactive oxygen species (ROS) are formed, starting downstream biological events. Nuclear factor kappa B (NFκB), cyclooxygenase-2 (COX-2) as well as pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumour-necrosis factor (TNF) have been suggested to play a key role in the development of GIM (17)(18)(19)(20). These overlapping steps are thought to be largely driven by the activation of NFκB, subsequently promoting key pro-inflammatory cytokines.…”

Section: Pathobiology Of Gimmentioning

confidence: 99%

A review of complementary therapies for chemotherapy induced gastrointestinal mucositis

Kuchay

2016

DD&T

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Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis

Cited by 171 publications

References 31 publications

Profiling of pro-inflammatory cytokines in radiation induced oral mucositis (riom) among indian patients

Profiling of pro-inflammatory cytokines in radiation induced oral mucositis (riom) among indian patients

In a Methotrexate-Induced Model of Intestinal Mucositis, Olmesartan Reduced Inflammation and Induced Enteropathy Characterized by Severe Diarrhea, Weight Loss, and Reduced Sucrose Activity

A review of complementary therapies for chemotherapy induced gastrointestinal mucositis

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