Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages.

Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

[A successful resected case of far-advanced cancer at the esophagogastric junction by chemoradiotherapy with docetaxel, nedaplatin and 5-fluorouracil].

The patient, a 73-year-old male, was admitted to our hospital because of dysphagia. A far-advanced cancer was diagnosed at the esophagogastric junction by upper gastrointestinal endoscopic examination. Pathological biopsy examinations revealed poorly-differentiated adenocarcinoma. Computed tomography (CT) of the chest and abdomen showed invasion to the diaphragm. Clinical Stage was IV in an unresectable far-advanced tumor. He received radiation therapy (40 Gy/total, 2 Gy/day×20 times) in combination with chemotherapy using docetaxel (40 mg/m², day 1), nedaplatin (10mg/body, days 1-5) and 5-fluorouracil (500 mg/body, days 1-5). After this combination chemoradiation therapy (CRT), macroscopic examinations showed significant reductions in the size of tumor, leading a partial response according to the RECIST guidelines. He underwent total gastrectomy, partial resection of the lower esophagus via left thoracotomy, and Roux-en Y reconstruction with jejunostomy. Pathological examination of the resected specimens revealed Stage IV (T3N2P1CY0). The postoperative course was uneventful. He was treated on an outpatient basis without adjuvant therapy, and died 6 months after the operation by liver, spleen and lymph node metastases.

[A case of ascending colon cancer with local recurrence responding completely to alternating modified-FOLFOX6 and FOLFIRI regimens(modified-FIREFOX regimen)].

A 58-year-old woman underwent right hemicolectomy with lymph node dissection(D2)for advanced ascending colon cancer which pathological examinations revealed to be moderately-differentiated adenocarcinoma. CEA and CA19-9 levels increased 6 months after the operation. She started adjuvant chemotherapy with oral administration of UFT-E(400 mg/day), but CEA and CA19-9 levels continued to elevate. However, a recurrent tumor was not detected by computed tomography(CT)and endoscopic examinations. A local recurrence in the right lateral abdominal wall was confirmed by PET-CT examination. We then conducted modified-FOLFOX6/FOLFIRI alternating regimen(modified- FIREFOX regimen). After this therapy, repeated PET-CT showed that the abnormal FDG-uptake concentration had disappeared, leading to a complete response(CR). The adverse event was grade 3 in leucopenia and grade 2 in gastrointestinal toxicity. She had maintained CR for the 12 months since undergoing chemotherapy. CEA and CA19-9 levels reduced to the normal range. We report this case with some review of the literature.