Advanced Prostate Cancer
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Pulse Testosterone Supplementation

New Italian study below.

Does not involve Sam Denmeade & his BAT protocol, but the idea is similar - rapid T cycling.

"The rapid cycling from hypogonadal to physiological or supra-physiological T intraprostatic concentrations results in cytostatic and senescence effects in preclinical models of androgen-sensitive Pca. Our preclinical evidence provides relevant new insights in the biology of Pca response to pulsed T supplementation."

-Patrick

ncbi.nlm.nih.gov/pubmed/293...

Oncotarget. 2017 Nov 30;8(69):113792-113806. doi: 10.18632/oncotarget.22776. eCollection 2017 Dec 26.

Episode-like pulse testosterone supplementation induces tumor senescence and growth arrest down-modulating androgen receptor through modulation of p-ERK1/2, pARser81 and CDK1 signaling: biological implications for men treated with testosterone replacement therapy.

Gravina GL1, Marampon F1, Sanità P1, Festuccia C2, Forcella C1, Scarsella L2, Jitariuc A2, Vetuschi A2, Sferra R2, Colapietro A2, Carosa E1, Dolci S3, Lenzi A4, Jannini EA5.

Author information

1

Department of Biotechnological and Applied Clinical Sciences, Laboratory of Prostate Onco-pathology and Experimental Endocrinology, University of L'Aquila, 67100 L'Aquila, Italy.

2

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

3

Department of Biomedicine and Prevention, Section of Anatomy, Tor Vergata University of Rome, 00133 Rome, Italy.

4

Department of Experimental Medicine, Chair of Endocrinology, Sapienza University of Rome, 00161 Rome, Italy.

5

Department of Systems Medicine, Chair of Endocrinology and Medical Sexology (ENDOSEX), Tor Vergata University of Rome, 00133 Rome, Italy.

Abstract

Despite the growing body of knowledge showing that testosterone (T) may not significantly affect tumor progression in hypogonadal patients treated for prostate cancer (Pca), the use of this hormone in this population still remains controversial. The effects of continuous or pulsed T stimulation were tested in vitro and in vivo on androgen-sensitive Pca cell lines in order to assess the differential biological properties of these two treatment modalities. Pulsed T treatment resulted in a greater inhibition than continuous T supplementation of tumor growth in vitro and in vivo. The effects of pulsed T treatment on tumor growth inhibition, G0/G1 cell cycle arrest, and tumor senescence was more pronounced than those obtained upon continuous T treatments. Mechanistic studies revealed that G0/G1 arrest and tumor senescence upon pulsed T treatment were associated with a marked decrease in cyclin D1, c-Myc and SKp2, CDK4 and p-Rb levels and upregulation of p27 and p-ERK1/2. Pulsed, but not continuous, T supplementation decreased the expression levels of AR, p-ARser81 and CDK1 in both cellular models. The in vitro results were confirmed in an in vivo xenografts, providing evidence of a greater inhibitory activity of pulsed supraphysiological T supplementation than continuous treatment, both in terms of tumor volume and decreased AR, p-ARser81, PSA and CDK1 staining. The rapid cycling from hypogonadal to physiological or supra-physiological T intraprostatic concentrations results in cytostatic and senescence effects in preclinical models of androgen-sensitive Pca. Our preclinical evidence provides relevant new insights in the biology of Pca response to pulsed T supplementation.

KEYWORDS:

androgens; hypogonadism; prostate cancer; pulse treatment; testosterone

PMID: 29371946 PMCID: PMC5768363 DOI: 10.18632/oncotarget.22776

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Patrick, are you aware of the new Denmeade Trial called BATMAN---this would be, if I read it right, for metastatic Pca that has not gone Castrate Resistant. But I believe you have to be showing a PSA. They are now getting down to our leg of the Journey with High T.

Nalakrats

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Nala,

There was a Phase II paper in 2016, but nothing since.

BATMAN: Bipolar Androgen Therapy for Men With Androgen Ablation Naïve Prostate Cancer:

ncbi.nlm.nih.gov/pubmed/?te...

-Patrick

1 like
Reply

Nala,

Denmeade is big on acronyms. Here is a good one (due to complete in Dec):

TRANSFORMER:

Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance

-Patrick

4 likes
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My Geneticist---told me nearly 2 years ago that high T would remodulate both Zytiga and Xtandi--and had the ability to turn off the AR-V7 activity, which is the key to Remodulation, of the phase 2 Hormone Drugs.

Dr. D at Hopkins is testing something, some us like you and I already know.

Nalakrats

1 like
Reply

Am aware---thanks.

Nalakrats

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I wonder why pharma doesn't attach radioactive particles ( or chemo) to testosterone and inject testosterone it into patients instead of depriving patients of testosterone with ADT.

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