Quercetagetin inhibits macrophage-derived chemokine in HaCaT human keratinocytes via the regulation of signal transducer and activator of transcription 1, suppressor of cytokine signalling 1 and transforming growth factor-ß1.

BACKGROUND: Inflammatory chemokines, such as macrophage-derived chemokine (MDC/CCL22), are elevated in the serum and lesioned skin of patients with atopic dermatitis (AD), and are ligands for C-C chemokine receptor 4, which is predominantly expressed on T helper 2 lymphocytes, basophils and natural killer cells. We have previously reported that quercetagetin has an inhibitory activity on inflammatory chemokines, which is induced by interferon (IFN)-γ and tumour necrosis factor (TNF)-α, occurring via inhibition of the signal transducer and activator of transcription 1 (STAT1) signal. OBJECTIVES: To investigate the specific mechanisms of quercetagetin on the STAT1 signal. METHODS: We confirmed the inhibitory activity of quercetagetin on MDC and STAT1 in HaCaT keratinocytes. The interaction between STAT1 and IFN-γR1 was investigated using immunoprecipitation. The small interfering RNA approach was used to investigate the role of suppressor of cytokine signalling 1 (SOCS1) and transforming growth factor (TGF)-ß1 induced by quercetagetin. RESULTS: Quercetagetin inhibited the expression of MDC at both the protein and mRNA levels in IFN-γ- and TNF-α-stimulated HaCaT human keratinocytes. Moreover, quercetagetin inhibited the phosphorylation of STAT1 through upregulation of SOCS1. Increased expression of SOCS1 disrupted the binding of STAT1 to IFN-γR1. Furthermore, quercetagetin augmented the expression of TGF-ß1, which is known to modulate the immune response and inflammation. CONCLUSIONS: These results suggest that quercetagetin may be a potent inhibitor of the STAT1 signal, which could be a new molecular target for anti-inflammatory treatment, and may thus have therapeutic applications as an immune modulator in inflammatory diseases such as AD.

Cutaneous metastasis resembling acute dermatitis in patient with advanced gastric cancer.

The most common metastatic sites from gastric cancer are the liver, intra-abdominal lymph nodes, ovary and peritoneal cavity. Cutaneous metastasis of gastric cancer is rare, and most cutaneous metastases are typically solitary, nodular, have a firm consistency, and are red or hyperpigmented. Thus, cutaneous metastasis is easily distinguished from other skin disease. We report a case of a 60-year-old woman with cutaneous metastasis of gastric cancer, whose facial skin showed painless pruritic eczema, resembling acute dermatitis. She had earlier undergone a total gastrectomy for advanced gastric cancer in our hospital. After 14 months, she developed eczematous facial lesions; the presumptive diagnosis was acute dermatitis. However, skin biopsy unexpectedly revealed cutaneous metastasis of gastric cancer. After 6 months of systemic chemotherapy with capecitabine and cisplatin, the cutaneous metastasis was markedly improved and a clinically complete remission was accomplished.

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma.

AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.