Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body radiation, develop oral mucositis. To date, there is no FDA approved drug to treat oral mucositis in cancer patients. The key challenges for oral mucositis treatment are to repair and protect ulcerated oral mucosa without promoting cancer cell growth. Oral mucositis is the result of complex, multifaceted pathobiology, involving a series of signaling pathways and a chain of interactions between the epithelium and submucosa. Among those pathways and interactions, the activation of nuclear factor-kappa B (NF-κB) is critical to the inflammation process of oral mucositis. We recently found that activation of TGFβ (transforming growth factor β) signaling is associated with the development of oral mucositis. Smad7, the negative regulator of TGFβ signaling, inhibits both NF-κB and TGFβ activation and thus plays a pivotal role in the prevention and treatment of oral mucositis by attenuating growth inhibition, apoptosis, and inflammation while promoting epithelial migration. The major objective of this review is to evaluate the known functions of Smad7, with a particular focus on its molecular mechanisms and its function in blocking multiple pathological processes in oral mucositis.
Animals ; Humans ; Mouth Diseases ; metabolism ; pathology ; prevention & control ; Smad7 Protein ; metabolism ; Stomatitis ; metabolism ; pathology ; prevention & control

Antineoplastic Agents/adverse effects* ; Head and Neck Neoplasms ; Humans ; Radiotherapy/adverse effects* ; Stomatitis/prevention & control*

In recent years, more head and neck cancer patients have been treated with radiotherapy. Radiation-induced mucositis is a common and dose limiting toxicity of radiotherapy among patients with head and neck cancers. Patients undergoing radiation therapy for head and neck cancer are also at increased risk of developing oral candidiasis. A number of new agents applied locally or systemically to prevent or treat radiation-induced mucositis have been investigated, but there is no widely accepted prophylactic or effective treatment for mucositis. Topical Aloe vera is widely used for mild sunburn, frostbites, and scalding burns. Studies have reported the beneficial effects of Aloe gel for wound healing, mucous membrane protection, and treatment of oral ulcers, in addition to antiinflammatory, immunomudulation, antifungal, scavenging free radicals, increasing collagen formation and inhibiting collagenase. Herein the author postulates that oral Aloe vera mouthwash may not only prevent radiation-induced mucositis by its wound healing and antiinflammatory mechanism, but also may reduce oral candidiasis of patients undergoing head and neck radiotherapy due to its antifungal and immunomodulatory properties. Hence, Aloe vera mouthwash may provide an alternative agent for treating radiation-induced oral mucositis and candidiasis in patients with head and neck cancers.
Aloe ; chemistry ; Clinical Trials as Topic ; Head and Neck Neoplasms ; radiotherapy ; Humans ; Mouthwashes ; therapeutic use ; Radiation Injuries ; drug therapy ; etiology ; prevention & control ; Stomatitis ; drug therapy ; etiology ; prevention & control

Drugs, Chinese Herbal ; Humans ; Lichen Planus ; drug therapy ; Medicine, Chinese Traditional ; Mouth Diseases ; drug therapy ; prevention & control ; Mouth Neoplasms ; drug therapy ; Orthodontics ; Periodontal Diseases ; drug therapy ; Stomatitis, Aphthous ; drug therapy

OBJECTIVETo observe the clinical effect of Chinese medicine for nourishing yin and clearing heat therapy (CM therapy) in treating nasopharyngeal carcinoma (NPC) patients with yin deficiency-induced inner heat syndrome, and suffered from acute radiation oral mucositis.

METHODSSixty patients with NPC fitting to the inclusion criteria and undergoing initial dose radiotherapy were assigned to two groups. The 31 patients in the treatment group received CM therapy, and the 29 in the control group were treated with standard Western medical therapy. The condition of oral mucosa and epidermal growth factor (EGF) content in saliva of patients during the therapeutic period were observed, meanwhile the quality of life (QOL) of patients was estimated with the quality of life questionnaire-core 30 (QLQ-C30) issued by European Organization for Research and Treatment of Cancer (EORTC).

RESULTSAcute radiation oral mucositis occurred in all patients, but the severity in the treatment group was milder than that in the control group (P < 0.01). Salivary EGF content decreased along with the increasing radiation dosage, it decreased significantly when 40 Gy radiated and down to the minimum when 70 Gy radiated, but the decrement in the treatment group was less than that in the control group (P < 0.01). Comparison of QOL by QLQ-C30 scale showed that after radiotherapy the global health status in the treatment group was superior to the control group (P < 0.01).

CONCLUSIONChinese medicine for nourishing yin and clearing heat therapy could actually postpone the occurrence of acute radiation oral mucositis, lessen the adverse reaction of radiotherapy and improve patient's QOL, show a favorable effect in prevention and treatment, and has definite application value for clinical spreading.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Phytotherapy ; Quality of Life ; Radiotherapy ; adverse effects ; Stomatitis ; drug therapy ; etiology ; prevention & control ; Yin Deficiency ; drug therapy ; Young Adult

Mucositis is the one of the most common complications during chemotherapy or radiotherapy. Once developed, mucositis influences the treatment outcome by severe pain, malnutrition, risk of infection, and prolonged hospitalization. Mucositis is usually developed in oral cavity and gastrointestinal tract. It is developed by the complex pathway, which is composed of initiation by reactive oxygen species, upregulation of various cytokine (e.g. TNF-alpha, IL-1beta, IL-6), and amplification of tissue injury, ulceration, and healing. Risk factors of mucositis include specific kinds of chemotherapy drug, hematopoietic stem cell transplantation, the site and dose of radiation, concurrent chemoradiation, malnutrition, salivary grand dysfunction, and poor oral hygiene. Routine oral care is very important for the prevention and treatment of oral mucositis and its administration should be included in patient education. Local anesthetics and systemic opioid can be used for severe pain of oral mucositis. Cryotherapy and low-level laser treatment is also useful for prevention of oral mucositis. Diarrhea, which is the most common symptom of gastrointestinal mucositis, can be controlled by loperamide or octreotide. More effective agents or procedures are needed for the prevention and treatment of chemotherapy related oral and gastrointestinal mucositis. The prevention is the most important approach in mucositis care and therefore multidisciplinary team approach including oncologists, dentists, nurses, and nutritionists is essential.
Anesthetics, Local ; Cryotherapy ; Dentists ; Diarrhea ; Gastrointestinal Tract ; Hematopoietic Stem Cell Transplantation ; Hospitalization ; Humans ; Loperamide ; Malnutrition ; Mouth ; Mucositis ; Octreotide ; Oral Hygiene ; Patient Education as Topic ; Primary Prevention ; Reactive Oxygen Species ; Risk Factors ; Stomatitis ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; Ulcer ; Up-Regulation

OBJECTIVETo study the effect of Qingre Liyan Decoction (QRLYD) in the prevention and treatment of acute radiative oral mucositis (AROM), and to explore the mechanism of QRLYD by detecting epidermal growth factor (EGF) and T lymphocytes (CD3, CD4, and CD8).

METHODSSixty patients conforming with the standard were randomly assigned to two groups, 30 patients in each group. Patients in the trial group were treated with QRLYD, and those in the control group were treated with Dobell's solution, both groups receiving conventional radiation treatment. The treatment course for both groups was 6 weeks on average. Blood routine test, CD3, CD4, and CD8 in the peripheral blood and EGF in the saliva were detected one day before and on the 14th and 28th day of radio-therapy.

RESULTSPatients in the trial group were in good condition with normal spirits and intake of food and drinks. The incidence of AROM is lower and the effect in preventing AROM is higher in the trial group than those in the control group (P<0.05). The EGF in saliva, and CD4 and CD8 in the blood of patients in the trial group were higher than those in the control group (P<0.05).

CONCLUSIONQRLYD can cure and prevent AROM. The mechanism may be related with its effects in enhancing body immunity and promoting salivary EGF.

Acute Disease ; Adult ; Carcinoma ; radiotherapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Epidermal Growth Factor ; blood ; Female ; Head and Neck Neoplasms ; radiotherapy ; Humans ; Incidence ; Leukocyte Count ; Male ; Middle Aged ; Phytotherapy ; adverse effects ; Platelet Count ; Radiation Injuries ; drug therapy ; prevention & control ; Stomatitis ; drug therapy ; epidemiology ; etiology ; prevention & control ; T-Lymphocyte Subsets ; drug effects ; Treatment Outcome

The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P=0.002), duration of mucositis (P=0.003) and the average grade of mucositis (P=0.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.
Adolescent ; Allografts ; transplantation ; Anti-Inflammatory Agents ; therapeutic use ; Case-Control Studies ; Child ; Cohort Studies ; Cyclophosphamide ; therapeutic use ; Female ; Fibroblast Growth Factor 7 ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Myeloablative Agonists ; therapeutic use ; Parenteral Nutrition ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Radiotherapy Dosage ; Stomatitis ; classification ; drug therapy ; prevention & control ; Time Factors ; Transplantation Conditioning ; methods ; Treatment Outcome ; Whole-Body Irradiation

PURPOSE: This study was done to examine the incidence of oral mucositis in hematopoietic stem cell transplantation patients and to identify factors influencing oral mucositis and patient outcomes according to severity. METHODS: In this retrospective study, data were collected from electronic medical records of 222 patients who had received hematopoietic stem cell transplantation. Oral mucositis was evaluated using WHO's assessment scale. Data were analyzed using Chi-square test, Fisher exact test, Spearman's correlation, Ordinal logistic regression, ANOVA and Kruskal-Wallis test. RESULTS: A total of 69.8% of the patients evaluated developed oral mucositis (grade II and over). As a results of ordinal regression, factors influencing oral mucositis severity were found to be diagnosis, type of transplantation, oxygen inhalation and the number of antiemetics administration before transplantation. The severity of oral mucositis was found to increase the days of hospitalization, days of TPN administration, days of using antibiotics and the number and dosage of analgesics. CONCLUSION: The results would help predict severity of oral mucositis in hematopoietic stem cell transplantation patients and suggest that provision of appropriate nursing assessment and oral care would improve patient outcomes.
Adolescent ; Adult ; Analgesics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Body Mass Index ; Female ; *Hematopoietic Stem Cell Transplantation ; Hospitalization ; Humans ; Incidence ; Length of Stay ; Leukemia/therapy ; Logistic Models ; Male ; Middle Aged ; Oxygen Inhalation Therapy ; Parenteral Nutrition, Total ; Radiation Dosage ; Retrospective Studies ; Severity of Illness Index ; Stomatitis/*epidemiology/pathology/prevention & control ; Young Adult

OBJECTIVE: To explore the effect of quadruple fluid aerosol inhalation on oral mucositis induced by radiotherapy in nasopharyngeal carcinoma (NPC) and its mechanism. METHODS: One hundred and twenty NPC patients were divided into a treatment group (n=60) and a control group (n=60). Radiation therapy was administered conventionally over 7 weeks with 2.0 Gy daily fractions for 5 days each week at the 70 Gy. Patients in the control group accepted oral care conventionally, and patients in the treatment group used quadruple fluids aerosol inhalation before the radiotherapy. The saliva volume was measured by a nurse twice a week and the concentration of epidemal growth factor (EGF) was examined by ELISA. RESULTS: The number of patients with mucositis in the treatment group was significantly fewer than that in the control group when the total doses were up to 30 Gy and 60 Gy (P<0.05). The concentration of EGF in the control group significantly decreased when total doses were up to 30 Gy and 60 Gy (P<0.01). The concentration of EGF in the treatment group was not significantly different compared with pre-radiotherapy when the total doses were up to 30 Gy, but when total doses were up to 60 Gy, the concentration of EGF in the treatment group obviously decreased compared with that of pre-radiotherapy. CONCLUSION The quadruple fluid aerosol inhalation is effective to reduce oral mucositis resulted from radiotherapy in NPC patients, which is related to the delay of the EGF decrease in the saliva.
Administration, Inhalation ; Adult ; Aerosols ; administration & dosage ; Aged ; Drug Combinations ; Enzyme-Linked Immunosorbent Assay ; Epidermal Growth Factor ; metabolism ; Female ; Gentamicins ; administration & dosage ; Humans ; Male ; Menthol ; administration & dosage ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Procaine ; administration & dosage ; Radiotherapy ; adverse effects ; methods ; Saliva ; drug effects ; metabolism ; radiation effects ; Stomatitis ; etiology ; metabolism ; prevention & control ; Treatment Outcome ; Vitamin B 12 ; administration & dosage ; Vitamins ; administration & dosage