No abstract

A total of 191 gastric adenomas in 178 patients was studied macroscopically by endoscopy and histopathologically by endoscopic biopsy. Among the lesions, 85 in 74 patients were followed‐up for six months to 12 years. Gastric adenomas were found to be more frequent in the aged, with a rate of 0.1% in the third decade but 3.7% in the ninth decade, on gastroscopic examination. Gastric cancers coexistent with the gastric adenomas were seen in 14 cases (8%), and were more frequent in male than in female patients (sex ratio, 12:2). Only eight of the 85 lesions (9%) revealed macroscopic changes. Four of these showed a reduction in size, while the other four lesions showed enlargement. In 21 of the 85 lesions (25%), histologic changes were observed. Four (5%) changed from moderate dysplasia (Group III) to nondysplastic or intestinal metaplasia (Group I), eight lesions (9%) revealed histologic changes (Group III to IV, or vice versa) without malignant transformation, and nine lesions (11%) showed malignant changes. Neither submucosal invasion nor lymph node metastasis was found. These lesions consisted of carcinoma in situ with small foci in the lesions exhibiting moderate dysplasia, and a gradual transition from severe dysplasia to cancer was seen in resected lesions obtained by endoscopic polypectomy or surgical resection. In addition, a gradual increase in dysplasia of tissue from moderate to severe was revealed by repeated gastroscopic biopsy. These findings suggest that the gastric adenomas underwent malignant changes with gradual transformation from moderate through severe dysplasia.

Since the initial discovery of leukemia stem cells nearly a decade ago, a great deal of cancer research has focused on the identification of cancer stem cells (CSCs) in many types of solid tumors, including breast cancer. Through analysis of cell surface markers and xenotransplant models, a subpopulation of putative human breast cancer stem cells (BCSCs) that is CD24-negative/CD44-positive (CD24(-)/CD44+) and bears high aldehyde dehydrogenase 1 activity has been isolated in clinical samples of breast cancer tissues. Human BCSCs are considered to be derived from basal cells that reside in the basal membranes of alveolar units in human adult mammary glands. Furthermore, BCSCs have been shown to express higher levels of oxidative stress-responsive genes, which could confer part of their ability to resist anti-cancer therapy, than non-CSCs. The emerging picture of the biological properties of BCSCs would contribute for devising innovative therapies for breast cancer, targeting the intrinsic and extrinsic factors that maintain the BCSCs.

It is now well accepted that G protein-coupled receptors (GPCRs) can be directly associated, as either homo- or hetero-oligomers, to alter their functions. G protein-coupled purinergic receptors, classified as adenosine receptors, and P2Y receptors (ATP receptors) are also found to oligomerize each other to alter their pharmacology. Specifically, adenosine receptor of A1 subtype (A1R) is able to form a heteromeric complex with P2Y receptor of P2Y1 type (P2Y1R) either in heterologously transfected cells or in rat brain tissues, as demonstrated by coimmunoprecipitation or bioluminescence resonance energy transfer methods in addition to double immunocytochemistry. It is shown that the heteromerization between A1R and P2Y1R generates an adenosine receptor with P2Y-like agonistic pharmacology, i.e., a potent P2Y1R agonist, adenosine 5'-O-(2-thiodiphosphate), binds the A1R binding pocket of the A1R/P2Y1R complex and inhibits adenylyl cyclase activity via Gi/o protein. This hetero-oligomerization between adenosine receptor and P2Y receptor might be one of the mechanisms for the adenine nucleotide-mediated inhibition of neurotransmitter release. The oligomerization of purinergic receptors is thus considered as an important regulation system in the central nervous system.

ABSTRACT. The direct homo-and heteromeric association between G-protein-coupled receptors (GPCRs), adenosine A2A receptor (A2AR) and dopamine D2 receptor (D2R), occurs although little is known about the selectivity of their formation (A2AR/A2AR vs. A2AR/D2R). In order to stimulate the heteromerization of A2AR and D2R, we have designed a single-polypeptide-chain heterodimeric A2AR/D2R complex by fusing the C-terminus of the A2AR via transmembrane (TM) of a type II TM protein with the N-terminus of D2R in tandem. This was successfully expressed on the cell surface as a full-length protein with specific binding to the respective ligands and functional coupling to G-proteins comparable to wild-type receptors, suggesting the possible creation of physiologically relevant heteromeric A2AR/D2R. This expression system would be useful to exclusively clarify the properties of heteromeric GPCRs irrespective of homomeric receptors.