Exposure to 1-bromopropane causes ovarian dysfunction in rats.

Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.     

An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker.

We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor effects of E7820 in mice and discuss the feasibility of using platelet integrin alpha2 expression on platelets as a biological marker of the efficacy of E7820. Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820.     

A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients.

PURPOSE: The aim of this study was to examine the effect of a specific cyclooxygenase-2 inhibitor, rofecoxib, on rectal polyps in familial adenomatous polyposis patients. EXPERIMENTAL DESIGN: This was a randomized, double-blind, placebo-controlled study of the efficacy and safety of rofecoxib in the rectum. Initially, 21 patients were assigned randomly in a 1:1 ratio to receive either 25 mg rofecoxib once a day or a placebo p.o. for 9 months. Patients underwent endoscopy at the beginning of the study and then every 3 months thereafter. We reviewed the videotapes to measure the number and size of polyps in the same area throughout the study period in each individual patient. RESULTS: The polyp number, measured as the percentage of change from the baseline values, was significantly decreased in the rofecoxib group at 3, 6, and 9 months. At 9 months, the polyp number in the rofecoxib group decreased by 6.8% from the baseline values, whereas that in the placebo group increased by 3.1%. The 9.9% difference between the rofecoxib and placebo groups was statistically significant (P = 0.004). At 9 months, the rofecoxib group showed a significant reduction from the baseline in polyp size as compared with the placebo group (-16.2% versus 1.5%; P < 0.001). There was no statistically significant increase in the incidence of any adverse events in treatment with rofecoxib compared with placebo (P = 0.922). CONCLUSIONS: In this study, once-daily treatment with 25 mg rofecoxib, a cyclooxygenase 2-specific inhibitor, significantly decreased the number and size of rectal polyps in familial adenomatous polyposis patients.     

The change in tenascin expression in mouse uterus during early pregnancy

Purpose: Our aim was to examine the changes in spatiotemporal tenascin (TN) expression in mouse uterus during early pregnancy, when the uterine tissue undergoes a tremendous restructuring. Methods: Using immunohistochemistry and in situ hybridization, the changes in distribution of TN protein in mouse uterine tissues in pregnancy Day 0 through Day 5 were analyzed. Results: Immunoreactive TN and TN mRNA were expressed in the basement membrane of the epithelium as well as in the smooth muscle layer, and their distribution shifted from the subbasement region on Day 0–3 to the smooth muscle layer on Days 4 and 5. Conclusions: These results indicate that TN expression in the uterus during early pregnancy is spatiotemporally different and may be regulated by a different mechanism.     

Clinical significance of interstitial collagen deposition at the invading edge in oral cancer: Immunohistochemistry for type I collagen

Background Changes in interstitial collagen in human oral cancer have not yet been fully studied. We examined the relationship between the degree of interstitial collagen deposition at the invading edge of the tumor, and the clinical and pathologic findings in oral squamous cell carcinoma. We also investigated the therapeutic implication of the changes in distribution patterns of collagen deposition by comparing biopsy specimens and surgical specimens. Methods Immunohistochemical staining was performed by the streptavidin-biotin method using antibody against human type I collagen for visualizing interstitial collagen in 50 biopsy and 45 surgical specimens. Results Carcinomas with scanty interstitial collagen in biopsy specimens tended to have highly malignant characteristics. Large carcinomas with scanty deposition both in biopsy and surgical specimens were likely to have positive resection margins in spite of radical surgery. Conclusion Immunostaining patterns for type I collagen of oral squamous cell carcinomas can provide information of importance in determining safe resection margins.     

Yolk sac tumor with a unique uniform hepatoid pattern histology

Abstract Background: Yolk sac tumors (YST) exhibit several different histological subtypes and the mechanisms of cellular differentiation and prognosis of each subtype remain unknown.
Results: We report two infants with sacrococcygeal YST; one represented a typical histological subtype and the other showed a hepatoid subtype with uniform histology. The isoform of alpha-fetoprotein (AFP) in the patient with the hepatoid pattern was examined by lectin-affinity Immunoelectrophoresis and represented as a YST. but not hepatocellular, subtype. The patient with typical YST responded well to VAB-6 combination chemotherapy. However, this regimen was only partially effective to the patient with the pure hepatoid histological subtype, and an etoposide with ifosfamide and cisplatin (VIP) regimen as a salvage chemotherapy combined with complete tumor resection was useful to achieve complete remission (CR). Both of the patients have been in CR for more than four years.