Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.

Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP. Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP. Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468). Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.

Obesity and related metabolic disorders, including chronic inflammation and enhanced oxidative stress, are closely associated with the development and progression of colorectal cancer. Previous epidemiological studies have demonstrated that increased serum uric acid is associated with the risk for various types of cancer, including colon cancer. This study examined the effects of a xanthine oxidase inhibitor allopurinol, widely used as a uric acid lowering medicine, on colorectal tumorigenesis in obese mice. Male C57BL/KsJ-db/db mice were injected with azoxymethane (15 mg/kg body weight) and then received drinking water containing allopurinol (30 mg/kg body weight) for fourteen weeks. At the time of sacrifice, allopurinol treatment significantly inhibited the development of colonic premalignant lesions. In the allopurinol-treated group, cellular proliferation in colonic mucosa was significantly suppressed, which was evaluated by the expression of proliferating cell nuclear antigen. Allopurinol also inhibited macrophage infiltration in the adipose tissue and decreased the serum level of TNF-α. The values of oxidative stress markers were markedly decreased in the allopurinol-treated group compared to those in the control group. These findings suggest that allopurinol attenuated chronic inflammation and decreased oxidative stress, preventing the development of colonic pre-neoplastic lesions in obesity-associated colon tumorigenesis model.

The present study describes the case of a 56-year-old male who was admitted to hospital due to pancytopenia. He was diagnosed as having acquired severe aplastic anemia (SAA). Immunosuppressive therapy with cyclosporine was transiently effective; however, the pancytopenia recurred. Bone marrow aspiration did not reveal an increased number of blasts, although it revealed trilineage dysplasia. Chromosomal analysis of the bone marrow demonstrated der(1;7) with abnormalities on chromosome 1. A diagnosis of a transformation from SAA to myelodysplastic syndrome (MDS) was made. High-grade fever and lower abdominal pain developed at approximately the same time. The patient was diagnosed as having Crohn's disease (CD). Treatment consisting of mesalazine and adalimumab was commenced. After two courses of azacitidine treatment, allogeneic bone marrow transplantation was performed, preceded by a reduced-intensity conditioning regimen, including fludarabine, cytarabine and cyclophosphamide. Tacrolimus and short-term methotrexate were used as prophylaxis against graft-versus-host disease. Chromosomal analysis of the bone marrow revealed a 100% donor-derived abnormal karyotype. The patient has since then remained in complete remission of both MDS and CD. On the whole, the present study demonstrates that allogeneic hematopoietic stem cell transplantation may be a promising treatment strategy for patients with combined MDS and CD. However, its use should be carefully considered.

Tryptophan (TRP) metabolism via the indoleamine 2,3-dioxygenase (IDO) subset of the kynurenine (KYN) pathway is one of the most important mechanisms of immune escape in cancer. TRP is converted into several biologically active KYN metabolites. However, the role of KYN metabolic products and related enzymes has not been clarified in patients with hematological malignant tumors. Here, we examined the serum concentrations of TRP, KYN, and the KYN metabolites kynurenic acid, anthranilic acid, and 3-hydroxyanthranilic acid in 157 patients stratified into five different hematological malignant tumors. KYN was the most abundant product of the TRP metabolic pathway among all five diagnostic categories. Serum KYN was increased in myelodysplastic syndrome (MDS) patients. The KYN/TRP ratio was significantly higher in MDS patients than in acute myeloid leukemia patients. In conclusion, IDO activity is increased in MDS patients, and IDO inhibitors might represent a new therapeutic approach for MDS treatment.