Background-Posttransplant chronic allograft deterioration associated with development of transplant arteriosclerosis (TA) remains an unresolved problem. Recent studies suggest that the smooth muscle cells (SMCs) constituting the neointima are derived from recipient hematopoietic stem cells (HSCs). However, the underlying mechanisms of the process are not yet fully elucidated. Methods and Results-We examined the genes expressed in allografts at different stages of TA development using a mice aortic transplantation model. Genes were analyzed by a differential mRNA display technique. We show that stromal cell-derived factor-1␣ (SDF-1␣) is a critical molecular target for the treatment of TA. During the course of TA, intragraft SDF-1␣ expression was upregulated with time, and the circulating HSCs expressing its counterreceptor CXCR4 increased in the recipients receiving allografts. CXCR4-positive HSCs, derived from transplant recipients, migrated into allografts via microvessels in the adventitia and then toward the luminal side. The HSCs differentiated into SMC-like cells, contributing to the in situ formation of the neointima. In support of a functional role for these molecules, in vivo neutralization of SDF-1␣ inhibited HSC mobilization and significantly attenuated neointimal formation. Conclusions-Interaction between SDF-1␣ and CXCR4 plays a key role in TA development. Blockade of SDF-1␣ may become a new therapeutic modality for TA.

These results suggest signaling through CD154 in addition to blocking of CD154-CD40 interaction is important for the immunomodulatory effects of soluble CD40Ig. Taken together, our results provide new insight into the mechanism of immunomodulation by soluble CD40 constructs.

BackgroundThe incidence of axillary lymph node metastasis (ALNM) of colon cancer is very low, and there have been only a few reports of solitary ALNM. Neither the mechanism involved in solitary colon cancer ALNM nor the proper treatment has been elucidated. We encountered a case of solitary left ALNM after curative resection of carcinoma at the colostomy site.Case presentationA 53-year-old man underwent a Hartmann’s operation for Hirschsprung disease during his adolescence. He complained of a mass of the descending colon and was diagnosed with colon cancer at the colostomy site with pagetoid spread to the adjacent skin. The cancer at the stoma site was resected, and a transverse colostomy was performed. Nine years later, his carbohydrate antigen (CA) 19-9 level was high during a health screening. On physical examination, adenopathy was palpated in the left axilla. Computed tomography (CT) demonstrated a lymph node in the left axillary fossa that was 33 mm in diameter, and 18F-fluorodeoxyglucose positron emission tomography/CT showed high uptake in the lesion. We performed a curative resection of the left axillary lymph node. The lesion was pathologically diagnosed as left ALNM originating from the adenocarcinoma at the colostomy site. After lymph node resection, his serum CA19-9 level decreased compared to that observed at baseline. He has been receiving adjuvant chemotherapy (capecitabine plus oxaliplatin) without recurrence for 5 months after lymph node resection.ConclusionsThe present case report shows that carcinoma at the colostomy site with pagetoid spread can metastasize to the axillary lymph nodes through superficial abdominal lymphatic pathways, and surgical resection followed by adjuvant chemotherapy may be a potent strategy to treat solitary colon cancer ALNM.

F i g . 1 C o l o n o s c o p y r e v e a l e d a t y p e -2 t u mo r s u r r o u n d i n g t h e s i g mo i d c o l o n ; t h e a n a l e d g e o f t h e t u mo r wa s l o c a t e d 3 0 c m f r o m t h e a n a l v e r g e .

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