Induction of aryl hydrocarbon hydroxylase in rat lung by marijuana smoke.

Rats were exposed to the smoke produced by burning four cigarettes of marijuana or of marijuana placebo material. Six hours later, maximally stimulated aryl hydrocarbon hydroxylase (AHH) activity was observed in the lung. Marijuana placebo material also induced pulmonary AHH activity. Actinomycin D (1 mg/kg) and cycloheximide (2 mg/kg), given ip 1 hr before exposure to marijuana smoke, partially blocked AHH induction. If rats were exposed repeatedly to marijuana smoke, they showed higher activities of pulmonary AHH within 6 hr of the last exposure than did animals exposed for the first time. Inhalation of marijuana smoke increased the number and size of debris-filled vacuoles in alveolar macrophages and in the ciliated cells of the bronchiolar epithelium. Smoke condensate from the marijuana material used in these studies contained 0.45 ng/mg of benzo(a)pyrene.     

Monosodium glutamate: Acute and chronic effects on rhythmic growth hormone and prolactin secretion, and somatostatin in the undisturbed male rat

The present investigation was designed to determine the chronic effects of neonatal monosodium glutamate (MSG) administration (4 g/kg s.c.) and the acute effects of MSG (1 g/kg i.p.) on episodic growth hormone (GH) and prolactin (PRL) secretion and brain somatostatin (SRIF) in unanesthetized, chronically cannulated male rats.Adult rats showed the typical physical characteristics that result from neonatal MSG administration. Analysis of episodic GH secretion showed a significant reduction in: (1) the amplitude of GH secretory peaks; and (2) the mean 5.5-h plasma level of GH. Bursts of plasma PRL were inhibited by MSG, but the mean 5.5-h plasma levels were not affected. SRIF concentrations in the medial basal hypothalamus were reduced by 60% after neonatal MSG. Acute administration of MSG to adult rats caused an immediate, long-lasting suppression of rhythmic GH secretion and a rapid, transient release of PRL.These results suggest: (1) neonatally administered MSG causes a marked disturbance in episodic GH and PRL secretion in adult rats; (2) MSG induces a decrease in hypothalamic SRIF and possibly GH-releasing factor; and (3) the acute effects of MSG on GH and PRL may be due to the inhibition and/or excitation of a complex neuronal network involving monoaminergic and peptidergic systems.     

The role of chromosome 15 in murine leukemogenesis. I. Contrasting behavior of the tumor vs. normal parent-derived chromosomes no. 15 in somatic hybrids of varying tumorigenicity

G-banding analysis was carried out on a series of hybrids derived from the fusion of a chromosome 15-trisomic murine T-cell leukemia of AKR origin and normal diploid fibroblasts or lymphocytes of the CBT6T6 strain. Due to the 14; 15 translocation involved in the generation of the T6 marker, the chromosomes No. 15 and 14 derived from the normal and the tumor parent can be distinguished cytogenetically. Highly tumorigenic, in vitro maintained hybrids, and high-tumorigenic segregants of originally low-tumorigenic in vitro hybrids, selected by in vivo passage, showed a similar cytogenetic pattern. It was characterized by the amplification of the tumor-derived chromosomes No. 15 from the expected 3 to 5.5 ± 0.2 copies and a concomitant decrease of the normal derived T(14;15)6 from 2 copies to 0.9 ± 0.2. All other autosomes except No. 14 showed only minor random variations, around the expected number of 4 copies. The tumor-derived chromosome 14 was amplified from the expected 2 to 3 copies. The lowtumorigenic hybrids showed the opposite pattern with a decrease in the number of the tumor-derived 15 chromosome from 3 to 2.6 ± 0.1 and the maintenance of the two normal parent derived T(14;15)6 chromosomes. These findings suggest the existence of a qualitative difference between the 15 chromosomes derived from the tumor vs. the normal parent, due to mutation or proviral DNA insertion in the tumor-derived homologue. Amplification of the changed locus and a decrease in the dosage of its normal counterpart appear to favor tumorigenicity.     

The outcome of treatment by tumorectory and radiotherapy of patients with operable breast cancer

We performed a retrospective study on 314 patients treated for a localized breast cancer by tumorectomy and radiotherapy to determine the overall survival, incidence of loco-regional failure and outcome of salvage surgery. All patients were followed for at least three years. Two hundred and fourteen patients had tumors ≤ 3 cm and 74 had tumors ≤ 6 cm. The three and five years absolute survival, free of disease (NED), is 88% ($\text{276}\text{314}$) and 84% ($\text{190}\text{225}$). The incidence of loco-regional failures was not dependent on tumor size and did not exceed 10% for the entire group. Recurrences were common (35%) in young patients (≤ 30). No patient older than 50 had recurrences. Eighty-one percent of failures appeared within three years. Salvage surgery was performed on 78% ($\text{14}\text{18}$) of patients with recurrences; 57% ($\text{8}\text{14}$) were free of disease (NED). Local failure in this group was not necessarily associated with disseminated cancer. Tumorectomy followed by radiotherapy is an acceptable alternative to mastectomy, particularly since salvage surgery can usually be successfully performed for recurrences.     

Pulmonary artery compression by haemorrhage from the aorta simulating pulmonary embolism

Franklin, D. H., and Jacques, J. (1974).Thorax, 29, 142-144. Pulmonary artery compression by haemorrhage from the aorta simulating pulmonary embolism. A case is presented in which pulmonary embolism was simulated by compression of the pulmonary artery by haematoma during an episode of acute bacterial endocarditis occurring 18 months after aortic valve replacement.     

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

The purpose of this study was to use the microarray technology to define expression profiles characteristic of thyroid autonomous adenomas and relate these findings to physiological mechanisms. Experiments were performed on a series of separated adenomas and their normal counterparts on Micromax cDNA microarrays covering 2400 genes (analysis I), and on a pool of adenomatous tissues and their corresponding normal counterparts using microarrays of 18,000 spots (analysis II). Results for genes present on the two arrays corroborated and several gene regulations previously determined by Northern blotting or microarrays in similar lesions were confirmed. Five overexpressed and 24 underexpressed genes were also confirmed by real-time RT-PCR in some of the samples used for microarray analysis, and in additional tumor specimens. Our results show: (1) a change in the cell populations of the tumor, with a marked decrease in lymphocytes and blood cells and an increase in endothelial cells. The latter increase would correspond to the establishment of a close relation between thyrocytes and endothelial cells and is related to increased N-cadherin expression. It explains the increased blood flow in the tumor; (2) a homogeneity of tumor samples correlating with their common physiopathological mechanism: the constitutive activation of the thyrotropin (TSH)/cAMP cascade; (3) a low proportion of regulated genes consistent with the concept of a minimal deviation tumor; (4) a higher expression of genes coding for specific functional proteins, consistent with the functional hyperactivity of the tumors; (5) an increase of phosphodiesterase gene expression which explains the relatively low cyclic AMP levels measured in these tumors; (6) an overexpression of antiapoptotic genes and underexpression of proapoptotic genes compatible with their low apoptosis rate; (7) an overexpression of N-cadherin and downregulation of caveolins, which casts doubt about the use of these expressions as markers for malignancy.     

CYP17 and breast cancer: no overall effect, but what about interactions?

Three large studies published in recent issues of Breast Cancer Research reported no overall evidence of an association between the CYP17 5'-untranslated region MspA1 polymorphism and breast cancer. The present commentary briefly highlights a few important observations and discusses some additional approaches to further assessment of associations between CYP17 common variants and breast cancer risk. In particular, the evolution of evidence on breast cancer and the CYP17 MspA1 variant suggests that determination of possible interactions between gene variants postulated to influence risk and nongenetic risk factors would be more efficiently accomplished by pooled analyses, ideally involving all studies of breast cancer, than by attempting to synthesize published information. Furthermore, such analyses would also be relevant to investigation of potential gene–gene interactions between CYP17 and other common variants in genes encoding enzymes that are involved in the synthesis and inactivation of sex steroid hormones, preferably using optimal sets of single nucleotide polymorphisms.     

Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling

While significant progress has been made in understanding the induction of tumor vasculature by secreted angiogenic factors, little is known regarding contact-dependent signals that promote tumor angiogenesis. Here, we report that the Notch ligand Jagged1 induced by growth factors via mitogen-activating protein kinase (MAPK) in head and neck squamous cell carcinoma (HNSCC) cells triggered Notch activation in neighboring endothelial cells (ECs) and promoted capillary-like sprout formation. Jagged1-expressing HNSCC cells significantly enhanced neovascularization and tumor growth in vivo. Moreover, the level of Jagged1 was significantly correlated with tumor blood vessel content and associated with HNSCC development. Our results elucidate a novel mechanism by which the direct interplay between tumor cells and ECs promotes angiogenesis through MAPK and Notch signaling pathways.