Correlation Between PSMA and VEGF Expression as Markers for LNCaP Tumor Angiogenesis

Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF), prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), androgen receptor (AR), and epidermal growth factor receptor (EGFR). The effect of paclitaxel treatment on AR expression was the most significant (P = .005). Of particular interest was identifying a significant correlation (P < .000801) between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases

A Heretic from a Good Family? A New Look at Why Levi b. Abraham b. Ḥayim Was Hounded

Levi b. Abraham b. Ḥayim, a popularizer of rationalist philosophy active around 1300 in Occitania, was identified as a transgressor by proponents of a ban on the study of philosophy. The nature of Levi's transgressive activities and the reasons why he was targeted have remained elusive, though a consensus view suggests that his socioeconomic standing and genuinely radical ideas contributed to his being singled out. In fact, a careful reassessment of the extant sources demonstrates that Levi, as an established member of the elite class, was an inadvertent target, identified in the course of a misunderstanding between Solomon Ibn Adret and his confidant in Perpignan, Crescas Vidal. No more radical than others and one of many popularizers of rationalism, Levi became a convenient exemplar and test case for ban proponents. They struggled to define the nature of Levi's potentially dangerous effects on his students, however, and Levi remained an equivocal figure even to his detractors. Though vilified and forced out of the home of his patron, Levi was accorded basic respect and often defended; he was never subject to excommunication, censure, or any type of halakhic prosecution

THE EFFECT OF SALICYLATE ON MACROMOLECULAR SYNTHESIS IN MAMMALIAN AND BACTERIAL CELLS.

THE EFFECT OF SALICYLATE ON MACROMOLECULAR SYNTHESIS IN MAMMALIAN AND BACTERIAL CELLS

In LNCaP cells enhanced expression of the androgen receptor compensates for Bcl-2 suppression by antisense oligonucleotides

Background and methods: Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth stimulatory gene products. While most oligos have targeted growth factors or their receptors, others have been directed against inhibitors of apoptosis. In LNCaP cells we evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein Bcl-2. LNCaP cells adapted to this restoration of apoptosis with a compensatory suppression of caspase-3 expression, a nontargeted promoter of this process. In a continuation of this study we now evaluate the expression of the androgen receptor (AR) following oligo mediated regulation of apoptosis with suppression of Bcl-2

Southville Revisted

Southville Revisited is a quantitative-descriptive study which examined (1) the extent to which Jews in Memphis identify with traditional Jewish values; (2) the effectiveness of current goals and objectives of the Memphis Jewish communal agencies in satisfying the needs of the community; (3) the comparison of the 1979 sample of the population with the respondents in the Southville Survey of 1959; and (4) new directions in planning and in expanding Jewish communal services to meet changing needs evidenced in the current study. In order to accomplish these goals, the researchers utilized approximately 75 percent of the questions derived from the 1959 Southville Survey of Jewish Attitudes. In addition, the researchers added seventeen questions pertaining to the Jewish educational level of the respondents, their views on Israel, and programming for the elderly and Russian immigrants. Sixty-four questions, covering 10 pages, were asked of the respondents in a self-administered questionnaire. Selection of the 1979 sample was based on a systematic random selection of Jewish heads of households. A master list of current heads of households was obtained from the Memphis Jewish Federation from which every thirtieth name was selected. The target population was to represent 3 percent of the Jewish heads of households in Memphis, approximately one hundred persons. The researchers were able to obtain seventy-five completed questionnaires. The process of dissemination and completion of the questionnaires by the sample selected began in the month of October 1978 and was completed in January of 1979. Major findings of the Southville Revisited study included the following: (1) the present sample appears to be an older and more financially and occupationally secure population than the 1959 respondents; (2) the age, income, education, and length of residence of the respondents appears to have a significant influence on the Jewish identity of those questioned; and (3) the importance of Jewish communal agencies (e.g., Jewish Community Center, Jewish Service Agency) indicated by the respondents seems to be offset by the lack of Jewish identification seen in their programming. A lack of Jewish educational background among the 1979 sample was also noticed. Many of the findings of the 1979 sample were seen to be similar to those in the 1959 study in areas such as commitment to Israel. With the knowledge gained from the 1979 sample, a number of program implications became evident. These recommendations included, among others, that communal agencies design programs that appeal to an educated population. These programs should incorporate identifiable Jewish values and customs. Programs related to single parents, separated, divorced, or widowed, should be initiated into the local Jewish community. Programs as well as direct services by the Jewish communal agencies must therefore be positively identified with Jewish values and practices in order to have impact upon the Jewish population in Memphis

Increased expression of the androgen receptor with p300 and interleukin-6 coactivators compensate for oligonucleotide suppression of bcl-2: no increased CREB binding protein or interleukin-4 expression

Background: Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth regulatory proteins. While most oligos have targeted growth factors or their receptors, others have been directed against inhibitors of apoptosis and mediators of androgen action. We previously evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein bcl-2. LNCaP cells adapted to this restoration of apoptosis with suppression of caspase 3 (an apoptosis promoter) and an enhanced expression of the androgen receptor (AR), suggesting an increased sensitivity to androgens. Methods and results: In a continuation of this study, we evaluated the expression of AR coactivators p300, its homolog CREB binding protein (CREBBP) and cytokines interleukin (IL)-4 and IL-6, finding p300 and IL-6 similarly enhanced. Conclusions: LNCaP cells are hormone sensitive and untreated cells express minimal p300 activity. Therefore, the enhanced expression which followed oligo treatment makes its induction more impressive and implies a pattern of gene expression more associated with later stage (androgen insensitive) disease. This suggests that oligo treatment directed against bcl-2 can be evaded through compensatory changes in AR expression and some coactivators, promoting tumor growth, and may promote transformation of the tumor to a more aggressive phenotype

In LNCaP cells enhanced expression of both androgen receptor and costimulatory protein p300 compensate for antisense oligonucleotide suppression of bcl-2

Background: Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth stimulatory gene products. While most oligos have targeted growth factors or their receptors, others have been directed against inhibitors of apoptosis and mediators of androgen action. In LNCaP cells we evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein bcl-2. LNCaP cells adapted to this restoration of apoptosis with an enhanced expression of the androgen receptor (AR) suggesting an increased sensitivity to androgens. In a continuation of this study, we now evaluate the expression of p300, an AR coactivating protein expressed in the later stages of prostate cancer