Antiangiogenic and antimetastatic properties of Neovastat (Æ-941), an orally active extract derived from cartilage tissue

A novel naturally occurring antiangiogenic agent isolated from cartilage, referred to as Neovastat (AE-941), was examined for its efficacy against tumor neovascularization and progression. Exposure to Neovastat results in ex ovo antiangiogenic properties in the chorioallantoid membrane of chicken embryo (71% decrease in the angiogenic index as compared to the basic fibroblast growth factor (bFGF) treated control embryos, P < 0.0001). Oral administration of Neovastat inhibits bFGF-induced angiogenesis in the Matrigel mouse model (87.5% decrease in hemoglobin as compared to the bFGF-treated control implants, P < 0.0001). Neovastat also induces a dose response decrease of lung metastases in the Lewis lung carcinoma model (oral administration; 69.1% of inhibition obtained at the maximal dose of 0.5 ml/day, P < 0.0001). Combined with a sub-optimal dose of cisplatinum (2 mg/kg, i.p.), Neovastat (0.5 ml/day) improved the therapeutic index by increasing the antimetastatic efficacy and by exerting a protective activity against cisplatinum-induced body weight loss and myelosuppression. In summary, our experimental data provide evidence of antiangiogenic and antimetastatic properties of Neovastat, following oral administration.     

Organization of receptive fields of tonic and phasic neurons of the pulvinar in the cat

The receptive fields (RF) of 163 neurons of the pulvinar were investigated by the method of point testing the RF surface with a stationary, flashing light spot. The RFs of 26% of the neurons were characterized by a phasic pattern of response in all regions studied, while the RFs of 15% of the neurons consisted of only tonic elements. A complex RF organization, consisting of tonic and phasic subfields, was characteristic of 59% of the neurons. On the basis of this fact the postulate is advanced concerning the convergence of two types of afferents on a single pulvinar neuron. The cell population receiving inputs from purely tonic or purely phasic afferents comprises 41% of all cells investigated. The measurement of the latent periods of neuron responses to a stationary, flashing light spot showed that neurons with a phasic type of response are distinguished by a shorter latent period compared to neurons with tonic and mixed types of responses.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 69, No. 1, pp. 19–25, January, 1983.     

Identification of a latent state arising in the hippocampus following the cessation of long-term potentiation

The possibility of the restoration of long-term potentiation in the CA1 region and the dentate gyrus of the hippocampus during stimulation respectively of the dorsal raphé nuclei and locus coeruleus, with stimulus parameters inducing behavioral reactions, was investigated in freely-behaving rats. It was demonstrated that stimulation of the locus coeruleus, which was ineffective prior to the tetanization of the perforant path, led to the restoration of extinguished long-term posttetanic potentiation in the dentate gyrus of the hippocampus induced by tetanization of the perforant path. Stimulation of the dorsal raphé nucleus, which was ineffective prior to the tetanization of the Schaffer collaterals, led to the restoration of long-term posttetanic potentiation in the CA1 region of the hippocampus induced by tetanization of the Schaffer collaterals. A mathematical model is proposed which has made it possible to describe the restoration of long-term posttetanic potentiation on the basis of the notion of the existence of several states of calcium/calmodulin-dependant protein kinase. The restoration of long-term potentiation during stimulation of emotiogenic zones was examined as a model of the phenomenon of emotional reminding. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I.P. Pavlova, Vol. 43, No. 4, pp. 770–777, July–August, 1993.     

Syndemic Health Disparities and Sexually Transmitted Infection Burden Among Black Men Who Have Sex with Men Engaged in Sex Work in the U.S.

Archives of Sexual Behavior - Black men who have sex with men (MSM) engaged in sex work (BMSM-SW) experience elevated HIV and sexually transmitted infection (STI) prevalence. Further, BMSM-SW have...     

P53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas

The p53 gene located at chromosome 17pl3 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twentyone patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-respon-ders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.     

A trace element preparation increases antitumor activity in mice

A trace element preparation (Béres Drops Plus, BDP) produced immunomodulatory effects in previous in vitro and in vivo experiments. Here, C57B1/6 inbred mice were transplanted with either Lewis lung tumor or with B16 melanoma. BDP was given intraperitoneally a. before transplantation; b. after transplantation or c. after the removal of the primary tumor. As a result, BDP pretreatment could slow down the tumor progression by decreasing the number and the volume of metastases as well as the proportion of mice with metastases without influencing the growth of the primary tumors. Furthermore, BDP treatment improved the immunological activity of the tumor-bearing host, too. These preliminary data suggest that the parenteral administration of the practically non-toxic BDP could help to control tumor progression in experimental models.     

Blood filtration through polymer gauze filters

Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 10, pp. 68–71, September–October, 1991.     

Expression of invasion markers CD44v6/v3, NM23 and MMP2 in laryngeal and hypopharyngeal carcinoma

Twelve laryngeal squamous cell carcinoma cases (7 laryngeal and 5 hypopharyngeal cancer; 15 samples) were analysed by immunohistochemistry for the expression of invasion markers CD44v6/v3, NM23 and matrix metalloproteinase, MMP2. The laryngeal epithelium showed CD44v6⁺v3⁺NM23^- /MMP2^- phenotype. When tumors were grouped into TNM categories the phenotype of the T2 and T3 tumors was similar, characterised by decreased CD44v3⁺ and lack of MMP2 expressions. Meanwhile the NM23 expression was more frequent in T3 tumors. In T4 stage the frequency of NM23 and MMP2 positive cases increased (5/6 and 4/6, respectively) but there was no correlation with the appearence of lymph node metastasis. Comparison of the phenotype of laryngeal and hypopharyngeal tumors, irrespective of the TNM stages, revealed characteristic differences: T2 stage laryngeal tumors showed decreased CD44v3 and occasional NM23 and MMP2 positivity, while in T3 stage these tumors were characterised by increased frequency of NM23 positivity. The phenotype of the hypopharyngeal tumors was significantly different with a high frequency of MMP2 positive cases (5/6) and NM23⁺1ow CD44v3⁺ phenotype. The sharp differences in the phenotypes of laryngeal and hypopharyngeal carcinomas were connected to the differences in their invasive capacity unlike to the size of the tumors, since the T4 stage hypopharyngeal tumors had a significantly smaller size than laryngeal ones, even at lower stages. This work was supported by the Hungarian Ministry of Welfare: ETT No: T-11-100/93