Double primary adenocarcinomas of the jejunum and descending colon with lung metastases presenting rare immunohistochemical phenotypes: a case report.

We report a male patient with double advanced tumors in the jejunum and descending colon and multiple lung tumors. The intestinal cancers were surgically resected. Immunoprofiling of the specimens revealed a rare phenotype: the jejunal cancer was positive for cytokeratin (CK) 7, partially positive for CK20, and Cdx-2-negative, whereas the colon cancer was CK7(+), CK20(-), and Cdx-2(-). Biopsied lung tumor was diagnosed as tubular adenocarcinoma, and CK7(+)/CK20(+)/Cdx-2(-). Together with clinical information, we deduced that the jejunal adenocarcinoma had presumably metastasized to the lung. Moreover, postoperative oxaliplatin, including chemotherapy, significantly reduced the lung metastases, suggesting that this regimen is a promising treatment option for advanced small bowel adenocarcinoma.

[Clinical genetics for hereditary cancers: from the viewpoint of physicians working at a hospital specialized in cancer].

In our daily practice, we provide clinical genetic consultation for patients at risk for hereditary cancers. The clinical characteristics of hereditary cancer syndromes in adults differ from those of hereditary diseases in children, although both involve genetic disease. One major difference is the difficulty in diagnosing hereditary cancers. Genetic testing has enabled us to diagnose HNPCC and familial breast and ovarian cancers. Another difference is the possibility to improve the outcomes of hereditary cancer syndromes by medical intervention. Intentional surveillance thus plays a key role in the management of hereditary cancer syndromes. These features make genetic counseling essential for hereditary cancer syndromes, including genetic testing and lifelong disease management. Networking among genetic disease specialists is particularly necessary. Clinical geneticists should be responsible for not only genetic disease but also for genomic information about cancer, with the ultimate goal of providing "order-made" medical consultation and services. Another important goal is the establishment of systems for the comprehensive care of patients and for the career development of specialists to provide regional-based care for persons who have or are at risk for hereditary cancers, including future generations.

Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives.

Polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives on a poly-L-glutamine backbone are described. Aiming for a longer retention time of 4-guanidino-Neu5Ac2en (zanamivir) in bronchi and lungs, we focused on supermolecules bearing 4-guanidino-Neu5Ac2en derivatives bound at their C-7 position through noncleavable alkyl ether linkages. We first found that alkylation of the 7-hydroxyl group of sialic acid derivative 8 proceeded smoothly, and produced 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives 13, which exhibited equipotent inhibitory activity against not only influenza A virus sialidase but also influenza A virus in the cell culture. Next, we synthesized poly-L-glutamine bearing 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives linked by amide bonds, 26, which showed enhanced antiviral activity against influenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.

Synthesis and anti-influenza evaluation of orally active bicyclic ether derivatives related to zanamivir.

We synthesized bicyclic ether sialidase inhibitors such as tetrahydro-furan-2-yl, tetrahydro-pyran-2-yl, and oxepan-2-yl derivatives related to zanamivir. These compounds substituted by diol at the C-3' and C-4' positions resulted in the retention of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. Compound 11a in particular showed comparable efficacy in vivo relative to that of oseltamivir phosphate.