RE: Prostatakarzinom - 7

Hier geht es um den Kastrations- und auch sonst "austherapierten" Prostatakrebs. Androgene hemmen das Krebszellenwachstum! @Wolfgang aus Berlin und andere haben in diesem Faden schon mehrfach von diesem Paradigmenwechsel im Verständnis dieser Krebsart berichtet.



Testosterone metabolites inhibit proliferation of castration- and therapy-resistant prostate cancer.


Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosterone-metabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects. We used the prostate cancer cell lines LNCaP, PC-3, VCaP, and the non-neoplastic BPH-1. VCaP cells were treated with 1 nmol/L testosterone over 20 passages, yielding the cell line VCaPrev, sensitive to hormone therapies. In contrast, LNCaP cells were grown for more than 100 passages yielding a high passage therapy resistant cell line (hiPLNCaP). VCaP and hiPLNCaP cell lines were treated with 5 μmol/L AA for more than 20 passages, respectively, generating the AA-tolerant-subtypes VCaPAA and hiPLNCaPAA. Cell lines were treated with testosterone, dihydrotestosterone (DHT), R1881, and the androgen-metabolites 3β-androstanediol and 3α-androstanediol. 3β-androstanediol or 3α-androstanediol significantly reduced proliferation in all cell lines except the BPH-1 and androgen receptor-negative PC-3 and markedly downregulated AR and estrogen receptor alpha (ERα). Whereas ERβ expression was increased in all cell lines except BPH-1 or PC-3. In summary, 3β-adiol or 3α-adiol, as well as DHT and R1881, significantly reduced tumour cell growth in CRPC cells. Thus, these compounds represent novel potential therapeutic approaches to overcome drug-resistance in CRPC, especially with regard to AR-V7 function in therapy resistance. Furthermore, these data confirm the tumour suppressor properties of ERβ in CRPC.

neue Behandlung mit Radioaktivität:

https://www.focus.de/gesundheit/ratgeber...id_9591516.html

Die Androgen-Ablatio wird mit jeder neuen Veröffentlichung diskreditiert. Das ist tragisch, denn es gibt Ärzte und Forscher, die das seit Jahrzehnten gesagt haben.



Neue Veröffentlichung, Februar 2019, Uniklinik Montreal. Große Kohorte, Zeitraum 5 Jahre. Und auch hier deutet an die Dinge leider nur an statt Ross und Reiter zu benennen.


https://www.ncbi.nlm.nih.gov/pubmed/30733309

A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer.

Background: In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression.

Methods: The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models.Results: The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054).

Conclusions: In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease.Impact: The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.

https://www.oncogen.org/articles/the-sup...tate-cancer.pdf


Case Report aus 2019:

Androgen-independent advanced prostate cancer is a terminal malignancy that generally results in death within five years. Its cause has been unknown, and a treatment did not exist. Prevailing views have mistakenly implicated impaired androgen receptor activity in the development of androgen-independent malignancy; which has deterred the existence of an effective treatment. Instead, recent reports have provided evidence that prolactin promotes the development and progression of androgen-independent malignancy; which follows androgen ablation treatment for androgen-dependent prostate cancer. That relationship dictates that a treatment for advanced prostate cancer should suppress the concentration plasma prolactin. This has been achieved with cabergoline (dopamine agonist; Dostinex) treatment of a patient that resulted in 88% decreased plasma prolactin, and terminated the malignancy. That likely represents the first effective treatment for advanced prostate cancer. It remains to establish if this treatment will be successful for other patients with advanced prostate cancer

https://www.ncbi.nlm.nih.gov/pubmed/30928381
Activation of PSGR with β-ionone suppresses prostate cancer progression by blocking androgen receptor nuclear translocation.

The prostate-specific G protein-coupled receptor (PSGR) is a class A G protein-coupled receptor (GPCR) that is specifically expressed in prostate epithelial cells, and its expression has been linked to prostate cancer (PCa) progression. Here, we show that activation of PSGR with its ligand β-ionone, an end-ring analog of β-carotenoid, can suppress PCa cell growth both in vitro and in vivo model. Dissection of the mechanism underlying this relationship reveals that activation of PSGR by β-ionone suppresses AR nuclear translocation via phosphorylation of AR at residue Ser650 by p38 and JNK, which leads to the suppression of AR transactivation, further suppressing PCa cell growth. Overall, we link a cancer cell-specific GPCR with the nuclear AR and show that targeting PSGR can provide us a new target to combat PCa better.


Kann jemand evtl. kurz erläutern, was sich da abspielt? PSGR bindet ß-Ionon, dadurch phoshoryliert der AR "anders als vorher". Und dann? Das verhindert die nuclear translocation. Also vom Zellkern wo hin? In die Zellemembran? Und as verhindert wiederrum die "transactivation" - durch welche Stoffe/Mechanismen würde das sonst erfolgen? Androgene nehme ich an - aber "translokiert" fördert das das Krebswachstum?

Testosteronmangel im Alter soll ein Prostatakarzinom fördern. Auch möglicherweise das Schlafapnoe-Syndrom (fragmentierter Schlaf) durch nächtlichen Sauerstoffmangel.

https://www.ncbi.nlm.nih.gov/pubmed/24448240

http://translate.google.com/translate?hl...2F74%2F5%2F1329

https://www.sciencedirect.com/science/ar...8246?via%3Dihub

INTERMITTENT DHT ADMINISTRATION ENHANCES EFFECT OF DOCETAXEL IN A XENOGRAFT MODEL BY MODULATION OF ERβ, AR AND NEK2

"...Introduction & Objectives: Estrogen signalling in advanced prostate cancer is still unclear. Estradiol (E2) and metabolites of DHT can selectively activate ERb, an estrogen receptor which proposed functions also include antiproliferative action. The aim of this xenograft model was to elucidate the function of ERb in a chemotherapy regimen with docetaxel and Estradiol E2 (high and low dose - on/off schedule) and DHT and its effects on tumor growth, expression of steroid receptors and a mitotic kinase, Nek2."

"...Material & Methods: Tumors were induced in 6 weeks old NMRI nude mice by injection of LnCaP cells (2x10^6 million cells) in both flans of the animals. Mice bearing tumors of > 200mm^3 were castrated, randomized in 5 groups and treatment with Docetaxel i.p. (40 mg/kg), Docetaxel and Estradiol in on-off schedule (High-dose: 1mg/kg or low-dose: 0.1mg/kg s.c., one week on, one week off) or Docetaxel and DHT (1mg/kg - on schedule weekly) started when tumors were considered as androgen independent. Mice were sacrificed when they were compromised by excessive tumor load. Yumors were harvested and immunohistochemical staining for ERb, AR, PSA, Ki-67 and Nek2 performed."

"...Results: Tumor growth was 2 fold increased in the high-dose E2 and low-dose E2 treated group compared to the control group. Interestingly, combination therapy of DHT and docetaxel caused a signficant reduction of tumor volume (30%-50%) and tumors <250mm^3 disappeared. Tumor size in docetaxel treated mice could only be stabilized over 2 cycles. Immunohistochemical staining showed a correlation of ERb expression, expression of Nek2 and AR in high-dose E2 treated mice and DHT treated mice."

"...Conclusions: Combination of docetaxel and intermittent DHT application reduced tumor volume significantly in this animal model. DHT might promote chemosensitivity to docetaxel by complex modulation of ERb, AR and mitotic kinases like Nek2."

Luteolin verhindert Prostatakrebs-Wachstum, kann kombiniert werden mit Enzalutamid:

https://www.lifeextension.com/whatshot/2...ticles#luteolin

Zitat von wmuees im Beitrag #159

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Luteolin verhindert Prostatakrebs-Wachstum, kann kombiniert werden mit Enzalutamid:

https://www.lifeextension.com/whatshot/2...ticles#luteolin

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Wird Prostatakrebs von Viren ausgelöst?
Forscher finden Zusammenhang zwischen HPV-Infektion und Prostatakrebs
Infektion als Ursache? Die häufigste Krebserkrankung bei Männern könnte einen viralen Auslöser haben, wie eine Metastudie enthüllt. Demnach wird Prostatakrebs offenbar durch eine Infektion mit dem Humanen Papillomavirus (HPV) verursacht oder zumindest begünstigt. Indizien dafür ist die Präsenz des Virus in auffällig vielen Prostatatumoren. Eine HPV-Impfung sei daher auch für Jungen sinnvoll und wichtig, betonen die Forscher.
https://www.scinexx.de/news/medizin/wird...ren-ausgeloest/


Humane Papillomaviren könnten Prostatakrebs auslösen
Eine neue Metaanalyse erhärtet den Verdacht: Eine Infektion mit humanen Papillomaviren kann wahrscheinlich Prostatakrebs verursachen.
https://www.spektrum.de/news/humane-papi...sloesen/1751428

Sehr interessant! Ist denn eine HPV-Infektion nicht heilbar?

@Wolfgang aus Berlin hat ja als Betroffener in diesem Topic sehr viel Wertvolles Wissen beigesteuert.
Sein letzter Beitrag hier im Forum ist aus dem August 2018. Da ich hoffe, dass ihm nichts Übles zugestoßen ist, habe ich mich mal in den Weiten des NEtzes auf die Suche gemacht und konnte im Internet ein Lebenszeichen vom 22.09.2019 ausfindig machen....

Wie es ihm geht weiß ich nicht, hoffe für ihn aber das Beste.

Seine veröffentlichten Daten und Intervetionsbeschreibungen jedenfalls dürften hier auch von Interesse sein:
https://myprostate.eu/?req=user&id=102&page=report

LG
Bul

Zitat von bul im Beitrag #165

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@Wolfgang aus Berlin hat ja als Betroffener in diesem Topic sehr viel Wertvolles Wissen beigesteuert.
Sein letzter Beitrag hier im Forum ist aus dem August 2018. Da ich hoffe, dass ihm nichts Übles zugestoßen ist, habe ich mich mal in den Weiten des NEtzes auf die Suche gemacht und konnte im Internet ein Lebenszeichen vom 22.09.2019 ausfindig machen....

Wie es ihm geht weiß ich nicht, hoffe für ihn aber das Beste.

Seine veröffentlichten Daten und Intervetionsbeschreibungen jedenfalls dürften hier auch von Interesse sein:
https://myprostate.eu/?req=user&id=102&page=report

LG
Bul

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Zitat von Tizian im Beitrag #166

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Leidenszeit

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Zitat von jayjay im Beitrag #167

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Zitat von Tizian im Beitrag #166

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Leidenszeit

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Ich hoffe es war Lebenszeit.

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Leider hinter der Bezahlschranke, aber vielleicht möchte der eine oder andere mal dahinterschaun.

„Wirksam, verträglich, sicher“ - Endoradiotherapie als neue Methode gegen Prostatakrebs

https://www.welt.de/gesundheit/plus23346...-bekaempft.html

Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells
https://www.mdpi.com/2076-3921/10/10/1591/htm

Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism
https://pubmed.ncbi.nlm.nih.gov/35142655/

Prostatakrebs: Ursache der Metastasierung entdeckt

Schade, daß @Wolfgang aus Berlin nichts mehr zu diesem Thema und vor allem auch wie es ihm geht schreibt. Seine Posts waren ja schon allein aus Eigenkenntnis immer höchst interessant und kompetent. Wollen wir also hoffen, daß er wohlauf ist und den Krebs besiegen konnte.