[A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX Adjuvant Chemotherapy].

Lynch syndrome is an inherited syndrome with the development of the colorectal and various other cancers. Lynch syndrome is caused by mutations in the mismatch repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX compared with 5-FU in patients who have colorectal cancer with Lynch syndrome. Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for colorectal cancer in lynch syndrome patients.

[A Case of Consciousness Disturbance Caused by Hyperammonemia during a mFOLFOX6 Regimen for Metastatic Colon Cancer].

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU.

Effects of Hura crepitans and its active ingredient, daphne factor F3, on dihydrotestosterone-induced neurotrophin-4 activation and hair retardation.

Neurotrophin (NT)-4 is known to be an inducer of catagen in the hair cycle, but little is known of its role in the pathogenesis of androgenetic alopecia (AGA). We previously studied the gene expression of dermal papilla cells from AGA patients and controls and found that NT-4 was up-regulated in the AGA patients. In the present study, the etiological relationship between NT-4 and androgen, which is one of the causes of AGA, and the effect of an NT-4 inhibitor on hair growth were investigated. We established a NT-4 luciferase reporter assay system using a roughly 2-kb region upstream of the NT-4 transcriptional start site and investigated an accelerating effect of androgen on NT-4 transcription. We also screened for a NT-4 inhibitor by using the NT-4 reporter assay and evaluated the effects of NT-4 inhibitors on hair growth by using dihydrotestosterone (DHT)-implanted mice. The results show that transcriptional activity of NT-4 was accelerated by androgen, and extract of Hura crepitans L. inhibited the DHT-induced NT-4 transcriptional activation and ameliorated the retardation of hair regrowth by DHT-implanted mice. We also isolated the active ingredient in H. crepitans and found its structure to be that of 6,7-epoxy-5-hydroxyresiniferonol-14-(2,4-tetradecadienoate), i.e., daphne factor F3. These findings demonstrated that NT-4 activity accelerated by androgen might contribute to the pathogenesis of AGA and indicated that NT-4 inhibitors such as H. crepitans and daphne factor F3 might have a salutary effect on AGA.