Sterically stabilized liposomes targeting P21 (RAC1) activated kinase-1 and secreted phospholipase A2 suppress prostate cancer growth and metastasis.

Sterically stabilized liposomes targeting P21 (RAC1) activated kinase-1 and secreted phospholipase A2 suppress prostate cancer growth and metastasis. Oncol Lett. 2020 Nov;20(5):179 Authors: Verma A, Najahi-Missaoui W, Cummings BS, Somanath PR Abstract Metastatic prostate cancer (PCa) has a very high mortality rate in men, in Western countries and lacks reliable treatment. The advanced-stage PCa cells overexpress P21 (RAC1) activated kinase-1 (PAK1) and secreted phospholipase A2 (sPLA2) suggesting the potential utility of pharmacologically targeting these molecules to treat metastatic PCa. The small molecule, inhibitor targeting PAK1 activation-3 (IPA3) is a highly specific allosteric inhibitor of PAK1; however, it is metabolically unstable once in the plasma thus, limiting its utility as a chemotherapeutic agent. In the present study, the efficacy and specificity of IPA3 were combined with the stability and the sPLA2-targeted delivery method of two sterically stabilized liposomes [sterically stabilized long-circulating liposomes (SSL)-IPA3 and sPLA2 responsive liposomes (SPRL)-IPA3, respectively] to inhibit PCa growth and metastasis. It was found that twice-a-week administration of either SSL-IPA3 or SPRL-IPA3 for 3 weeks effectively suppressed the growth of PC-3 cell tumor xenografts implanted in athymic nude mice. Both drug formulations also inhibited the metastasis of intravenously administered murine RM1 PCa cells to the lungs of C57BL/6 mice. Whereas...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

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AbstractLike other malignancies, prostate tumors are thought to contain cancer stem-like cells (CSCs) that are responsible for growth, metastasis, and therapy resistance. ΔNp63 (also called p40) is a regulator of normal prostate stem/progenitor cell activities and a marker of normal basal epithelial cells. The levels of ΔNp63 are reduced in prostate adenocarcinomas, although there is also evidence that ΔNp63 is involved in CSC regulation and drives metastasis to t he bone. We studied metastatic deposits of prostate cancers with isoform-specific ΔNp63 and TAp63 antibodies. We identified p63-positive ...
Source: Virchows Archiv - Category: Pathology Source Type: research
Conclusion: Our study demonstrated that lncRNA DSCAM-AS1 was transcriptionally activated by super-enhancers driven by FOXA1 and exhibited lineage-specific expression pattern. DSCAM-AS1 can promote cancer progression by interacting with YBX1 and regulating expression of FOXA1 and ERα.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
CONCLUSION: At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures. PMID: 33011207 [PubMed - as supplied by publisher]
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - Category: Radiology Authors: Tags: Radiother Oncol Source Type: research
Morphological and functional alterations of the prostate tissue during clinical progression in hormonally-naïve, hormonally-treated and castration-resistant patients with metastatic prostate cancer. Oncol Lett. 2020 Nov;20(5):201 Authors: KorĨek M, Sekerešová M, Makarevich AV, Gavurová H, Olexíková L, Pivko J, Barreto L Abstract Since commony used tools in oncological practice for the diagnosis of castration-resistent prostatic acinar adenocarcinoma are based on clinical criteria, such as castrate testosterone level, continuous rise in serum prostate-specific an...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Abstract F-box and WD repeat domain containing (FBXW) family of E3 ligases has 10 members that ubiquitinate substrate proteins for proteasome-mediated degradation. Publicly archived datasets from The Cancer Genome Atlas (TCGA), Prostate Cancer Transcriptome Atlas (PCTA), and cBioPortal were analyzed for mRNA expression and genetic alterations of 10 FBXW genes. We found that FBXW7 mRNA expression was significantly decreased in primary prostate cancers compared to normal prostate tissues, whereas mRNA expression of FBXW8-10 was significantly increased in primary prostate cancers compared to normal prostate tissues. ...
Source: Clinical Prostate Cancer - Category: Cancer & Oncology Authors: Tags: Am J Clin Exp Urol Source Type: research
CONCLUSION: This study demonstrates that NKX3.1 and HOXB13 are more sensitive markers than PSA for the detection of prostate carcinoma metastatic to the bone following the decalcification process. We recommend use of NKX3.1 and HOXB13, rather than PSA, in the diagnosis of bone metastases originating from prostate cancer. PMID: 32979741 [PubMed - as supplied by publisher]
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
In this study of Chinese men with biochemical recurrence, added value for the detection of lesions compatible with sites of PCa was found with68Ga-PSMA-11 PET/CT over conventional imaging. The observed patterns of disease spread may have implications for understanding the biology of early prostate cancer metastasis.
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
Condition:   Prostate Adenocarcinoma Intervention:   Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT) Sponsor:   Alpha Tau Medical LTD. Not yet recruiting
Source: - Category: Research Source Type: clinical trials
Galectin-3 (Gal-3) is an extracellular matrix glycan-binding protein with several immunosuppressive and pro-tumor functions. The role of Galectin-3 in cancer stem-like cells (CSCs) is poorly investigated. Here, we show that prostate CSCs also colonizing prostate-draining lymph nodes of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice overexpress Gal-3. Gal-3 contributes to prostate CSC-mediated immune suppression because either Gal-3 silencing in CSCs, or co-culture of CSCs and T cells in the presence of the Gal-3 inhibitor N-Acetyl-D-lactosamine rescued T cell proliferation. N-Acetyl-D-lactosamine also rescued...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
CONCLUSION: Systematic biopsies should still be considered in patients with PI-RADS 1/2 findings. Our findings also suggest a stronger benefit of the combined strategy of targeted and systematic biopsies than the findings of previous studies concerning the detection of CSPCa in biopsy-naïve patients. PMID: 32865086 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Urology - Category: Urology & Nephrology Tags: Scand J Urol Source Type: research
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