In vivo versus in vitro individual radiosensitivity analysed in healthy donors and in prostate cancer patients with and without severe side effects after radiotherapy

2012 ◽  
Vol 88 (5) ◽  
pp. 405-413 ◽  
Author(s):  
Kinga Brzozowska ◽  
Michael Pinkawa ◽  
Michael J. Eble ◽  
Wolfgang-Ullrich Müller ◽  
Andrzej Wojcik ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Individual Radiosensitivity ◽  
Healthy Donors

scholarly journals Dual PI3 K/mTOR inhibition reduces prostate cancer bone engraftment altering tumor-induced bone remodeling

Tumor Biology ◽  
2018 ◽  
Vol 40 (4) ◽  
pp. 101042831877177 ◽  
Author(s):  
Andrea Mancini ◽  
Alessandro Colapietro ◽  
Simona Pompili ◽  
Andrea Del Fattore ◽  
Simona Delle Monache ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Therapeutic Potential ◽  
Disease Free Survival ◽  
Bone Lesions ◽  
Metastatic Progression ◽  
Mtor Inhibition ◽  
Osteoblast Activity

Morbidity in advanced prostate cancer patients is largely associated with bone metastatic events. The development of novel therapeutic strategies is imperative in order to effectively treat this incurable stage of the malignancy. In this context, Akt signaling pathway represents a promising therapeutic target able to counteract biochemical recurrence and metastatic progression in prostate cancer. We explored the therapeutic potential of a novel dual PI3 K/mTOR inhibitor, X480, to inhibit tumor growth and bone colonization using different in vivo prostate cancer models including the subcutaneous injection of aggressive and bone metastatic (PC3) and non-bone metastatic (22rv1) cell lines and preclinical models known to generate bone lesions. We observed that X480 both inhibited the primary growth of subcutaneous tumors generated by PC3 and 22rv1 cells and reduced bone spreading of PCb2, a high osteotropic PC3 cell derivative. In metastatic bone, X480 inhibited significantly the growth and osteolytic activity of PC3 cells as observed by intratibial injection model. X480 also increased the bone disease-free survival compared to untreated animals. In vitro experiments demonstrated that X480 was effective in counteracting osteoclastogenesis whereas it stimulated osteoblast activity. Our report provides novel information on the potential activity of PI3 K/Akt inhibitors on the formation and progression of prostate cancer bone metastases and supports a biological rationale for the use of these inhibitors in castrate-resistant prostate cancer patients at high risk of developing clinically evident bone lesions.

scholarly journals Blood platelets contain tumor-derived RNA biomarkers

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3680-3683 ◽  
Author(s):  
R. Jonas A. Nilsson ◽  
Leonora Balaj ◽  
Esther Hulleman ◽  
Sjoerd van Rijn ◽  
D. Michiel Pegtel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Personalized Medicine ◽  
Cancer Patients ◽  
Expression Profiling ◽  
Blood Platelets ◽  
Companion Diagnostics ◽  
Rna Biomarkers

Abstract Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.

scholarly journals Exploring the Value of BRD9 as a Biomarker, Therapeutic Target and Co-Target in Prostate Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1794
Author(s):  
Nafisa Barma ◽  
Timothy C. Stone ◽  
Lina Maria Carmona Echeverria ◽  
Susan Heavey
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Therapeutic Target ◽  
Advanced Prostate Cancer ◽  
Signalling Pathways ◽  
Gleason Grade ◽  
Clinical Biomarkers ◽  
Prostate Cancer Treatments

Background and aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA M.expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression, and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signalling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

scholarly journals The Natural Compound Myricetin Effectively Represses the Malignant Progression of Prostate Cancer by Inhibiting PIM1 and Disrupting the PIM1/CXCR4 Interaction

2018 ◽  
Vol 48 (3) ◽  
pp. 1230-1244 ◽  
Author(s):  
Chen Ye ◽  
Chao Zhang ◽  
Hai Huang ◽  
Bo Yang ◽  
Guangan Xiao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Integration Site ◽  
Leukemia Virus ◽  
In Vivo Studies ◽  
Prostate Cancer Cells ◽  
Clinicopathologic Characteristics

Background/Aims: Natural compounds are a promising resource for anti-tumor drugs. Myricetin, an abundant flavonoid found in the bark and leaves of bayberry, shows multiple promising anti-tumor functions in various cancers. Methods: The cytotoxic, pro-apoptotic, and anti-metastatic effects of myricetin on prostate cancer cells were investigated in both in vitro and in vivo studies. Short-hairpin RNA knockdown of the proviral integration site for Moloney murine leukemia virus-1 (PIM1), pull-down and co-immunoprecipitation assays, and an intracellular Ca2+ flux assay were used to investigate the potential underlying mechanism of myricetin. ONCOMINE database data mining and immunohistochemical analysis of prostate cancer tissues were used to evaluate the expression of PIM1 and CXCR4, as well as the correlation between PIM1 and CXCR4 expression and the clinicopathologic characteristics and prognoses of prostate cancer patients. Results: Myricetin exerted selective cytotoxic, pro-apoptotic, and anti-metastatic effects on prostate cancer cells by inhibiting PIM1 and disrupting the PIM1/CXCR4 interaction. Moreover, PIM1 and CXCR4 were coexpressed and associated with aggressive clinicopathologic traits and poor prognosis in prostate cancer patients. Conclusion: These results offer preclinical evidence for myricetin as a potential chemopreventive and therapeutic agent for precision medicine tailored to prostate cancer patients characterized by concomitant elevated expression of PIM1 and CXCR4.

scholarly journals The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2682 ◽  
Author(s):  
Miguel Muñoz ◽  
Rafael Coveñas
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Cancer Patients ◽  
Antitumor Agent ◽  
Antitumor Action ◽  
Tumor Mass ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Neurokinin-1 receptor (NK-1R) antagonists exert antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exert multiple actions against cancer: antiproliferative and anti-Warburg effects and apoptotic, anti-angiogenic and antimetastatic effects. These multiple effects have been shown for a broad spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as an antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed, as is the possible link, through the substance P (SP)/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant, and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

scholarly journals BRD9 Expression, Alteration, Survival And Pathway Analysis In 11 Independent Prostate Cancer Cohorts

2021 ◽  
Author(s):  
Nafisa Barma ◽  
Timothy C Stone ◽  
Lina Maria Carmona Echeverria ◽  
Susan Heavey
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Pathway Analysis ◽  
Therapeutic Target ◽  
Advanced Prostate Cancer ◽  
Gleason Grade ◽  
Targeted Inhibition ◽  
Prostate Cancer Treatments

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

EFFECT OF RADIOTHERAPY-INDUCED ALTERATION OF INDIVIDUAL RADIOSENSITIVITY ON DEVELOPMENT OF SIDE EFFECT IN CANCER PATIENTS

2021 ◽  
Vol 30 (7) ◽  
pp. 48-52
Author(s):  
Olga Sevriukova ◽  
Aista Plieskienė ◽  
Kamilė Guogytė ◽  
Rima Ladygienė ◽  
Julius Žiliukas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Reaction ◽  
Side Effects ◽  
Ionizing Radiation ◽  
Cancer Patients ◽  
G2 Checkpoint ◽  
Individual Radiosensitivity ◽  
Radiation Induced ◽  
Gi Toxicity ◽  
The Common

Ionizing radiation is commonly used for cancer treatment. Human response to the same dose of ionizing radiation can vary among individuals, therefore individual radiosensitivity (IRS) was proposed to be an important factor for development of radiotherapy (RT) related side effects. Ionizing radiation especially at low doses can modify organism sensitivity causing its sensitization or adaptation to further exposure, thus IRS of cancer patient can change during RT and so effect the development of normal tissue toxicity as well. Therefore, objective of our study was to determine the correlation between IRS of prostate cancer patients during RT and outcome of treatment adverse reactions. This pilot study included six prostate cancer patients without previous exposure to ionizing radiation treated with salvage RT. IRS was assessed using G2 chromosomal radiosensitivity assay with G2-checkpoint abrogation by caffeine three times for each patient: prior RT, after first fraction, and after completing treatment and acute genitourinary (GU) and gastrointestinal (GI) toxicity were reported. It was found that three of selected patients experienced grade 1-2 RT acute GU/GI toxicity. According to IRS tests, before RT two patients were classified as normal, two – as radiosensitive, and two – as highly radiosensitive. After the first fraction there were three individuals classified as nor-mal, one patient remained radiosensitive and two others felt to the highly radiosensitive group. After completion of treatment, the distribution of IRS in selected patients recovered to that observed before the treatment. Despite that pattern of IRS changes during RT varied in every patient, the common tendencies and their correlation with the development of toxicity was observed. It was found that, IRS of patient experienced adverse reaction riced during RT, meanwhile in patients without side effects it decreased. So, it could be concluded that difference in radiation-induced IRS alteration tendency could be reflected in pattern of adverse reaction development. This phenomenon could be associated with attribute of preexposure to initiate individually either an adaptive response increasing resistance to further irradiation or sensitization. Therefore, further investigations of more RT patients employing G2 assay are foreseen to reveal the possible correlation between IRS and adverse clinical outcome of RT.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

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