Tumor necrosis factor (TNF) is a monocyte-derived protein cytotoxic or cytostatic for some tumor cell lines. Here we show that highly purified E. coli-derived recombinant human TNF stimulated the growth of human FS-4 diploid fibroblasts. Stimulation of cell growth was demonstrable at a TNF concentration of 10 pg/ml (3 X 10(-13) M). Maximal stimulation was attained at TNF concentrations of 10 ng/ml (3 X 10(-10) M) or higher. Growth-stimulatory activity of TNF was inhibited by an mAb neutralizing the cytotoxic activity of TNF. Growth stimulation was not inhibited by another mAb specific for TNF, lacking neutralizing activity for the cytotoxic activity of TNF. Growth stimulation by TNF was more marked and more sustained in the presence of greater than or equal to 10% FCS than in medium with less than or equal to 5% FCS. Addition of TNF to confluent FS-4 cultures also produced a marked stimulation of cell growth in the presence of fresh FCS, while a much less marked stimulation was seen in the absence of FCS. Stimulation of confluent cultures by TNF in serum-free medium was enhanced by insulin, suggesting that insulin or insulin-like growth factor(s) in the serum can act synergistically with TNF in producing growth stimulation. While the growth-stimulatory effects of TNF and insulin were synergistic, the actions of TNF and epidermal growth factor (EGF) were less than additive, suggesting that TNF and EGF may activate identical or similar pathways. We conclude that stimulation of cell growth is probably a physiological function of TNF, and that the cytotoxic and cytostatic actions of TNF may be the result of an anomalous growth signal transduction in neoplastic cells lacking the constraints of normal growth control mechanisms.

No abstract

In an earlier paper, we reported our scoring system for the diagnosis of adenomyosis by gray scale transvaginal sonography. In this study we evaluated 44 benign uterine masses (adenomyosis and myomas) and seven uterine malignancies. We used transvaginal color and pulsed Doppler imaging to determine whether this technique is useful to differentiate adenomyosis from uterine malignancies. The peak systolic velocity and the resistive index of I n an earlier paper, we reported our scoring system for the diagnosis of adenomyosis by gray scale transvaginal sonography. This method had a sensitivity of 87%, a specificity of 96%, and an accuracy of 91 %. 1 However, uterine malignancies occasionally are diagnosed as adenomyosis by this method. intratumoral vessels were studied. The differences in these parameters for adenomyosis and uterine malignancies were statistically significant. Our results suggest that this technique is useful to differentiate adenomyosis from uterine malignancies. KEY WORDS: Adenomyosis; Uterus, malignancies; Resistive index; Transvaginal sonography; Color Doppler sonography.Therefore, the objective of this study was to differentiate adenomyosis from uterine malignancies using pulsed and color Doppler imaging. As the previous study supports the view that neovascularization in malignant lesions consists of multiple abnormal feeding arteries,2 in this study we examined the resistive index and the peak systolic velocity of intratumoral vessels in 51 cases of adenomyosis, myomas, and uterine malignancies to assess the possibility of improving our scoring system for the diagnosis of adenomyosis by this method. PATIENTS AND METHODSFifty-one patients who were scheduled for hysterectomy were examined. Their pathologic condition included 44 benign uterine masses (22 adenomyosis and 22 myomas) and seven uterine malignancies (three uterine endometrial cancers, one uterine cervical cancer, and three sarcomas). Ages ranged from 37 to 69 years old. All patients were without major medical conditions and examinations were done in the

A favorable prognosis of endometrioid carcinomas with co-existing estrogen related factors (adenomyosis and endometrial hyperplasia) was suggested.

No abstract