A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells

BACKGROUND & AIMS: Constitutive expression of cyclooxygenase 2 (COX-2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. METHODS: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. RESULTS: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC-58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. CONCLUSIONS: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis. (Gastroenterology 1997 Dec;113(6):1883-91)     

Juvenile amyopathic dermatomyositis

We report a 15-year-old girl with a 10-year-old history of typical skin features of dermatomyositis (DM) without evidence of muscle involvement. Amyopathic dermatomyositis(ADM) is defined by the presence of biopsy confirmed classic cutaneous findings of dermatomyositis in the absence of any clinical or laboratory signs of muscle disease for at least 2 years after onset of skin pathology. To exclude muscle involvement muscle enzymes should be normal; moreover additional use of magnetic resonance imaging and muscle ultrasound is currently being proposed. It is as yet undetermined. whether early aggressive immunosuppressive treatment of ADM might prevent the development of myositis at a later date or influence the course of the skin disease. In a paediatric patient with ADM we advocate a more expectant attitude with careful and regular monitoring for possible development of muscle disease.     

Interstitial hyperthermia in combination with brachytherapy

Flexible coaxial cables were modified to serve as microwave antennas operating at a frequency of 915 MHz. These antennas were inserted into nylon afterloading tubes that had been implanted in tumors using conventional interstitial implantation techniques for iridium-192 seed brachytherapy. The tumor volume was heated to 42-45 degrees C within 15 minutes and heating was continued for a total of 1 hour per treatment. Immediately following a conventional brachytherapy dose and removal of the iridium seeds the tumors were heated again in a second treatment. This interstitial technique for delivering local hyperthermia should be compatible with most brachytherapy methods. The technique has proved so far to be practical and without complications. Temperature distributions obtained in tissue phantoms and a patient are described.     

Diet and other risk factors for cancer of the pancreas

The findings of a case - control study of cancer of the pancreas, which was conducted in the Baltimore metropolitan area, are reported. Two hundred one patients with pancreatic cancer were matched on age (+/- 5 years), race, and sex to hospital and non-hospital controls, the latter selected by random-digit-dialing (RDD). All subjects were interviewed regarding diet, beverage consumption, occupational and environmental exposures, and medical and surgical history. Significantly decreased risks were associated with consumption of raw fruits and vegetables and diet soda, and significantly increased risks were associated with consumption of white bread when cases were compared with hospital and RDD controls. A significantly reduced risk was associated with consumption of wine when cases were compared to RDD controls. Risk ratios for consumption of coffee were not significantly different from one, although there appeared to be a dose - response relationship in women. A moderate but statistically nonsignificant increase in relative odds was found for cigarette smoking, and cessation of smoking was associated with a marked reduction in risk. No significant associations were found with particular occupational exposures. Tonsillectomy was associated with a significantly reduced risk, a finding that has been observed for other cancers as well. The current evidence indicates that pancreatic cancer is likely to result from a complex interaction of factors and suggests that the study of its etiology requires a multidisciplinary approach involving both laboratory and epidemiologic components.     

The Effect of Hemorrhage on Plasma Iron Turnover

The plasma iron turnover rate in rats following a single hemorrhage reachesa maximum in about 48 hours and returns to normal between the seventh andtenth day. There is considerable variation in individual rats in both the maximum rate attained and the time required for recovery. No significant difference in response was observed due to the severity of hemorrhage uponremoval of 2.7 to 18 per cent of total red cells.

Submitted on June 20, 1960 Accepted on November 20, 1960     

Improved surface coil imaging in MR: decoupling of the excitation and receiver coils

We obtained magnetic resonance images with good sensitivity and radio frequency (RF) uniformity using separate transmitter and receiver coils. The excitation, namely, the rotation of the magnetization vector into a plane perpendicular to the magnetic field, was done by applying a homogeneous RF magnetic field produced by a large saddle-shaped coil. Surface coils were used for detection only. Because two coils that operated on the same resonance frequency were used, a coupling problem developed. This problem, which involved inhomogeneity of the RF magnetic field caused by the large current induced in the surface coil during excitation, could only be solved by minimizing the mutual inductance or maximizing the impedance of the surface coil resonance circuit during excitation. We were able to solve this problem using an electronic detuning method.     

Occasional essay: Jewish perspective on prenatal diagnosis and selective abortion of affected fetuses,including some comparisons with prevailing catholic beliefs

Prenatal diagnosis and selective abortion of affected fetuses are controversial subjects for many individuals. Much of the controversy centers around religious beliefs. In this paper we present prevailing Jewish and Catholic beliefs concerning these two subjects. We hope to resolve some of the controversy and emphasize the fact that physicians counsel and patients often make decisions based on their religious persuasion.