Synthesis and evaluation of (S)-5'-C-aminopropyl and (S)-5'-C-aminopropyl-2'-arabinofluoro modified DNA oligomers for novel RNase H-dependent antisense oligonucleotides.

We designed and synthesized two novel thymidine analogs: (S)-5'-C-aminopropyl-thymidine and (S)-5'-C-aminopropyl-2'-ß-fluoro-thymidine. Then, DNA oligomers containing these analogs were synthesized, and their functional properties were evaluated. Compared with the naturally occurring thymidine, it was revealed that (S)-5'-C-aminopropyl-2'-arabinofluoro-thymidine was sufficiently thermally stable, while (S)-5'-C-aminopropyl-thymidine featured thermal destabilization. The difference in thermal stability resulted from a moderate change in the secondary structure of the DNA/RNA duplexes and a molecular fluctuation in monomers derived from the (S)-5'-C-aminopropyl side chain, as well as from a variation in sugar puckering derived from the 2'-arabinofluoro modification. Meanwhile, the incorporation of these analogs significantly enhanced the nuclease resistance of the DNA oligomers. Moreover, the (S)-5'-C-aminopropyl-2'-arabinofluoro-modified DNA/RNA duplexes showed a superior ability to activate RNase H-mediated cleavage of the RNA strand compared to the (S)-5'-C-aminopropyl-modified DNA/RNA duplexes.

Primary invasive micropapillary carcinoma of the stomach.

Reported herein is the case of a 74-year-old man with an unusual gastric carcinoma that developed at the lesser curvature of the stomach. The tumor consisted of small clusters of carcinoma cells surrounded by clear spaces, with histopathology similar to invasive micropapillary carcinoma (IMPC) of the breast. The carcinoma cells, which had downregulation of E-cadherin expression, invaded the subserous tissue and metastasized to the perigastric lymph nodes. IMPC, an unusual subtype of invasive breast carcinoma, is known to have frequent lymph node metastases, resulting in a poor clinical outcome. Although IMPC has been reported in breast, urinary bladder, ureter, lung, salivary gland and colon, to the best of the authors' knowledge this is the first report of IMPC arising in the stomach. Presented here are the clinicopathological features of primary IMPC of the stomach.

Primary non-Hodgkin's lymphoma of the main hepatic duct junction.

A rare case of primary non-Hodgkin's lymphoma of the main hepatic duct junction is reported. A 71-year-old man was admitted for treatment of obstructive jaundice. Radiological examination revealed stenosis of the main hepatic duct junction. Biliary drainage was not necessary because total bilirubin decreased spontaneously. A left hepatic and caudate lobectomy, combined with resection of bile ducts and lymph node dissection, was performed with the preoperative diagnosis of cholangiocarcinoma of the main hepatic duct junction. Macroscopic examination of the resected specimen revealed tumorous growth in the main hepatic duct junction. Histological and immunochemistry findings disclosed a mucosa-associated lymphoid tissue (MALT) lymphoma. The patient received three courses of combination chemotherapy [cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)], and there was no evidence of recurrence 45 months after the surgery. Although primary non-Hodgkin's lymphoma of the main hepatic duct junction is extremely rare and difficult to diagnose preoperatively, aggressive surgery followed by chemotherapy, as here, is a possible curative option.

Adult cecoanal intussusception caused by cecum cancer: report of a case.

We report a case of cecoanal intussusception caused by cecum cancer in a 29-year-old woman. The patient presented to our hospital with a mass protruding from the anus. We manually pushed the mass back into the rectum and performed a gastrograffin enema, which showed a cup-shaped filling defect in the rectum. The defect was moved back to oral side with the pressure of the enema, revealing a tumor originating in the cecum. Colonoscopy showed a protrusion, 5 x 3 cm in size, in the cecum. Laparotomy confirmed that the tumor originated at the bottom of the appendix in the cecum. We performed partial resection of the cecum containing the tumor and appendix. The pathological finding was submucosal adenocarcinoma in adenoma. Cecoanal intussusception is extremely rare and, to our knowledge, this adult case represents the first report documented in the world scientific literature.

The relationship between bone metastasis from human breast cancer and integrin alpha(v)beta3 expression.

BACKGROUND: Osteoclast activation plays an essential role in the development of bone metastasis (BM). Integrin alpha(v)beta3 mediates the attachment of osteoclasts to bone matrix, and it is overexpressed in bone-residing breast cancer cells. We studied BM from breast cancer in relation to its Integrin alpha(v)beta3 expression. MATERIALS AND METHODS: Integrin alpha(v)beta3 expression in 4 human breast cancer cell lines (MDA-MB-231, MDA-MB-435, MKL-4 and T-47D) was determined by immunohistochemistry, flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Integrin alpha(v)beta3 was expressed in MDA-MB-231 and MDA-MB-435, but not in MKL-4 or T-47D, using both immunohistochemistry and flow cytometry. By RT-PCR, positive bands for both alpha(v) and beta3 subunits were identified in MDA-MB-231 and 435, while only the alpha(v) subunit mRNA was present in MKL-4 and T-47D. BM was common in vivo following inoculation with MDA-MB-231 or 435, but not with MKL-4. CONCLUSION: Integrin alpha(v)beta3 expression appears to play a key role in the development of BM from breast cancer.

Inhibition of bone metastasis from breast cancer with pamidronate resulting in reduction of urinary pyridinoline and deoxypyridinoline in a rat model.

BACKGROUND: Breast cancers frequently metastasize to bone, in a process in which osteoclasts play a major role. Bisphosphonate pamidronate, a specific inhibitor of osteoclasts, has been widely used in the treatment of bone metastasis (BM). In this study, using an animal model of BM, we examined the prophylactic and treatment effects of pamidronate against BM and clarified the relationships between BM, pamidronate and bone resorption markers such as urinary pyridinoline and deoxypyridinoline. METHODS: Bone metastases were established by inoculating c-SST-2 (spontaneously developed rat mammary adenocarcinoma) cells into the thoracic aorta of 27 rats, which were then divided into three groups of rats: the untreated control group, the pre-treatment group, consisting of rats treated with pamidronate (10 mg/kg) injected subcutaneously a day before tumor inoculation, and the post-treatment group, in which rats were injected with pamidronate a week after tumor inoculation. Three weeks after tumor inoculation, blood and urine samples were collected. The subjects were then sacrificed to harvest the thoracic and lumbar vertebrae for histological examination, consisting of staining with hematoxylin and eosin and tartrate resistant acid phosphatase (TRACP). RESULTS: The incidence of BM was 70.0%, 44.4% and 37.5% in the control, pre-treatment and post-treatment groups, respectively. Although there was no significant difference among the groups, the rate of BM in the treated groups was lower than that of the control group and no bone destruction was observed in treated rats. The TRACP-stained specimens revealed that there were numerous osteoclasts contributing to the control group tumor burden. The urinary levels of pyridinoline and deoxypyridinoline were reduced by pamidronate. CONCLUSION: Our results suggest that pamidronate prevents the development of BM and the destruction of bone associated with BM. Maintaining the values of Pyr and Dpyr at low levels with pamidronate might lead to inhibition of the incidence and development of BM.