Cytotoxic constituents ofPilea mongolica

Bioassay-guided fractionation of the aerial parts ofPilea mongolica (Urticaceae) afforded two cytotoxic triterpenoids, epi-oleanolic acid (I) and oxo-oleanolic acid (II). The structures of the compounds were confirmed by spectral and synthetic evidences. CompoundI and compoundII exhibited cytotoxicity against cultured human tumor cell lines, A549 (non small cell lung adenocarcinoma), SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), XF498 (CNS) and HCT15 (colon) with ED(50) values of 3.2 approximately 8.1 mug/ml and 0.7 approximately 6.8 mug/ml, respectively.     

Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.     

(-)-Epiafzelechin: cyclooxygenase-1 inhibitor and anti-inflammatory agent from aerial parts of Celastrus orbiculatus.

An inhibitor of cyclooxygenase (COX)-1 activity of prostaglandin H2 synthase was isolated from aerial parts of Celastrus orbiculatus Thunb. (Celastraceae), an oriental folk medicine for rheumatoid arthritis by activity-guided column chromatographic methods. The COX inhibitor was identified as (-)-epiafzelechin, a member of flavan-3-ols by the structural analysis with HR-EI-mass, 1H-NMR and 13C-NMR spectral data. The compound exhibited a dose-dependent inhibition on the COX activity with an IC50 value of 15 microM. (-)-Epiafzelechin exhibited about 3-fold weaker inhibitory potency on the enzyme activity than indomethacin as a positive control. (-)-Epiafzelechin exhibited significant anti-inflammatory activity on carrageenin-induced mouse paw edema when the compound (100 mg/kg) was orally administrated at 1 h before carrageenin treatment.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Two new lignans fromLindera obtusiloba blume

Two new furanolignans (3, 5), together with three known lignans (1, 2, 4), were isolated from the stem of Lindera obtusiloba (Lauraceae). The structures of the compounds were determined as actifolin (1), pluviatilol (2), 5,6-dihydroxymatairesinol (3), (+)-syringaresinol (4), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (5) on the basis of physicochemical and spectroscopic evidences. Compounds 1, 2, 3, and 5 showed cytotoxicity against a small panel of human tumor cell lines with ED50 values of 3.40 to approximately 19.27 microg/ml.     

Smooth muscle distribution in the extrahepatic bile duct: histologic and immunohistochemical studies of 122 cases

The distribution of smooth muscle fibers in the extrahepatic bile duct (EBD) wall is not well characterized. We analyzed 101 consecutive Whipple's operation specimens and 21 autopsy specimens for the pattern of smooth muscle distribution in EBD using the Masson-trichrome stain and the desmin immunohistochemical stain. The patterns were categorized as continuous, interrupted, scattered, and no muscle layer. EBDs were divided into lower, middle, and upper portions, and the distribution pattern of smooth muscle fibers was analyzed separately in each portion. Because most surgically resected specimens contained the middle and lower EBDs with only a portion of the upper EBD, only the length of the middle and lower EBDs (common bile duct, CBD) was measured. The mean length of CBD in surgically resected specimens was 6.4 +/- 1.4 cm (men, 6.6 +/- 1.3 cm; women, 6.1 +/- 1.5 cm). The mean length of CBD in autopsy specimens was 6.8 +/- 1.0 cm. The predominant patterns of the lower third of the EBD were interrupted (49%) and continuous (43%). The predominant patterns of the middle third of the EBD were scattered (63%) and interrupted (23%). Those of the upper third of the EBD were no muscle fiber (58%) and scattered (39%). In conclusion, different patterns of smooth muscle distribution were observed in different portions of the EBD. Because scattered muscle fibers or no muscle fibers were the main features of the upper third of the EBD, understanding of this pattern may be helpful for assessment of the depth of invasion or staging of carcinoma of the upper third of the EBD.     

Intravesical adipose tissue: a quantitative study of its presence and location with implications for therapy and prognosis

Accurate pathologic staging of carcinomas of the urinary bladder involves assessment of invasion by the tumor into the bladder wall and beyond into perivesical soft tissue. The presence of tumor within perivesical soft tissue implies pathologic stage pT3 (AJCC/UICC system, 1997). In traditional textbooks of histology, anatomy, pathology, and in the literature, other than a single case report and a brief reference in another paper, there is no information on the presence of adipose tissue in the lamina propria or muscularis propria of the urinary bladder. Nine hundred forty-three sections from 139 cystectomy specimens were evaluated for the presence, location, and quantity of adipose tissue within the lamina propria and muscularis propria. The histology of the perivesical soft tissues and the nature of its delineation from muscularis propria were also analyzed. Adipose tissue was seen within the lamina propria in 53% (74 of 139) of cystectomies and in 17.6% (166 of 943) of the examined sections. It was located predominantly in the deep lamina propria (at or below the muscularis mucosae) in 81.1% (60 of 74) of the cystectomies and in 91% (151 of 166) of the sections. Within the lamina propria it was predominantly seen as small localized aggregates in 92% (153 of 166) of sections. All cases showed adipose tissue within the muscularis propria. Adipose tissue was identified within the superficial (inner) muscularis propria in 54% (512 of 943) of sections and was predominantly in small aggregates in 80.5% (412 of 512) of sections. It was in moderate to abundant quantities within the deep (outer) muscularis propria in 60.7% (572 of 943) of sections. The perivesical soft tissue was almost exclusively composed of adipose tissue with variable vascularity. Delineation of the perivesical adipose tissue from the deep (outer) muscularis propria was typically indistinct because muscle bundles of the latter haphazardly merged with the perivesical adipose tissue. Based on these findings, we conclude that adipose tissue is frequently present in the lamina propria and muscularis propria of the urinary bladder wall, and is usually scant in the former location and frequently abundant in the latter. Awareness of the high frequency of adipose tissue within the urinary bladder wall has prognostic and therapeutic implications. In transurethral resection of bladder tumor (TURBT) specimens, misinterpretation of tumor infiltrating adipose tissue within lamina propria (pT1) as perivesical soft tissue involvement (pT3) may potentially result in unwarranted aggressive management. Substaging of muscle invasive tumors should be performed in cystectomy specimens only, because the junction of muscularis propria and the perivesical adipose tissue is typically ill-defined. Muscularis propria adipose tissue in TURBT specimens may be erroneously assumed to be perivesical adipose tissue, potentially leading to overstaging of the primary tumor.