scholarly journals Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation

2017 ◽  
Vol 8 ◽  
pp. 1307-1317 ◽  
Author(s):  
Kati Erdmann ◽  
Jessica Ringel ◽  
Silke Hampel ◽  
Manfred P Wirth ◽  
Susanne Fuessel
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Mitomycin C ◽  
Death Rate ◽  
Carbon Nanomaterials ◽  
Cell Death Rate ◽  
Wide Range ◽  
The Impact

We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects.

scholarly journals Antioxidant supplementation decreases the cell death rate in the prostatic stromal tissue of long-term castrated rats

2012 ◽  
Vol 38 (3) ◽  
pp. 419-425 ◽  
Author(s):  
Guilherme Fartes ◽  
Fábio Lorenzetti ◽  
Larissa Beloti Salvador ◽  
Valdemar Ortiz ◽  
Miriam Dambros
Keyword(s):  
Cell Death ◽  
Death Rate ◽  
Antioxidant Supplementation ◽  
Cell Death Rate ◽  
Stromal Tissue

Clinical availability of chemotherapy response assay using adenosine triphosphate in breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10592-10592
Author(s):  
J. Jeong ◽  
S. Lee ◽  
S. Yoon ◽  
W. Jung ◽  
H. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Death Rate ◽  
Chemotherapeutic Agents ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Cell Death Rate ◽  
Her 2

10592 Background: The response to chemotherapeutic agents of breast cancer is heterogeneous from patient to patient. Several methods were developed to decide chemotherapeutic agents which were sensitive to individual patients but so far, there are no ways which is commonly used in the clinic to tailor the treatment. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. Methods: From March 2004 to February 2005, 65 breast cancer patients were enrolled in this study. After elimination of normal contaminated cells, cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer(doxorubicin, epirubicin, 5-FU, paclitaxel, docetaxel, vinorelbine, and gemcitabine). 7 Drug-treated cancer cells and untreated cancer cells were cultured for 48 hours and then ATP was measured. To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean death rate of doxorubicin, epirubicin and paclitaxel by HER-2 status. Results: The ATP-CRA was performed sucessfully in 62 patients. (95.4%) In all cases, we can get the results within 7 days. The range of cell death rate was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean cell death rate (35.7%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.58 and 0.2 between paclitaxel and epirubicin. In HER-2 positive group, mean cell death rate of epirubicin and paclitaxel was significantly higher than in HER-2 negative group (p = 0.017, p = 0.036) and same trend was seen in doxorubicin but not statistically significant (p = 0.060). Conclusions: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. With indirect comparison, it showed similar results with in vivo studies but for clinical use, the prospective randomized controlled trial should be preceded. No significant financial relationships to disclose.

507 CARBON NANOMATERIALS SENSITIZE PROSTATE CANCER CELLS TO MITOMYCIN C AND DOCETAXEL

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Jessica Ringel ◽  
Kati Erdmann ◽  
Kai Kraemer ◽  
Susanne Fuessel ◽  
Manfred P. Wirth
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Mitomycin C ◽  
Carbon Nanomaterials ◽  
Prostate Cancer Cells

Investigating the Impact of OGT Inhibition on Doxorubicin- and Docetaxel-Induced Cytotoxicity in PC-3 and WPMY-1 Cells

2020 ◽  
Vol 39 (6) ◽  
pp. 586-593 ◽  
Author(s):  
Vivek Makwana ◽  
A/Prof Shailendra-Anoopkumar Dukie ◽  
Santosh Rudrawar
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Enzyme Level ◽  
Treatment Strategies ◽  
Concomitant Treatment ◽  
Prostate Cancer Cells ◽  
Drug Induced ◽  
Combination Approach ◽  
The Impact

Reduction in sensitivity in terms of cytotoxicity is responsible for therapy failure in patients undergoing chemotherapy with first-line anticancer drug molecules. A plethora of literature evidence points out that increased O-linked β- N-acetylglucosamine transferase (OGT) enzyme level/hyper- O-GlcNAcylation has direct implications in development of cancer and interferes with clinical outcomes of chemotherapy via interaction with oncogenic factors. The aim of this research was to evaluate the combination approach of anticancer drugs with an OGT inhibitor (OSMI-1) as an alternative way to resolve issues in the treatment of prostate cancer and assess the benefits offered by this approach. Effect of combination of doxorubicin and docetaxel with OSMI-1 on drug-induced cell death and synergism/antagonism was investigated using resazurin assay. Reduction in OGT enzyme level was evaluated using ELISA kit. Caspase-3/7 fluorescence assay was performed to detect apoptosis induction in PC-3 cells after treatment with the combinations of doxorubicin and OGT inhibitor to further understand the mechanism of cell death by concomitant treatment. Studies reveal that combination approach is indeed effective in terms of reducing the half-maximum growth inhibition value of doxorubicin when concomitantly treated with OSMI-1 and has synergistic effect in prostate cancer cells. PC-3 cells exhibited elevated levels of OGT enzyme in comparison to WPMY-1, and OSMI-1 has potential to inhibit OGT enzyme significantly. Data show that OSMI-1 alone and in combination with doxorubicin reduces OGT enzyme level significantly accompanied by increased apoptosis in prostate cancer cells. Combination of doxorubicin with OSMI-1 reduced the elevated OGT level which led to a drastic increase in sensitivity of PC-3 cells toward doxorubicin in comparison to doxorubicin alone. This finding provides important insight regarding alternative treatment strategies for effective management of cancer.

scholarly journals Calcitriol Reverses Induced Expression of Efflux Proteins and Potentiates Cytotoxic Activity of Gemcitabine in Capan-2 Pancreatic Cancer Cells

2017 ◽  
Vol 20 ◽  
pp. 295 ◽  
Author(s):  
Hamed Gilzad-Kohan ◽  
Shabnam Sani ◽  
Mehdi Boroujerdi
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Atpase Activity ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Death Rate ◽  
Cell Death Rate ◽  
Pancreatic Cancer Cells ◽  
Pre Treatment ◽  
Efflux Proteins

Purpose. Efflux and influx proteins play a major role in chemo-resistance by affecting the net cellular uptake of anti-cancer drugs. Hence, alteration of the efflux and influx protein expression may result in variations of chemotherapeutics uptake and consequently cell death rate. The present study investigated the effects of pre-treatment of capan-2 pancreatic cancer cells with calcitriol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) or silibinin on the induction of three major efflux proteins and the main gemcitabine influx protein. The influence of the pre-treatments on the net cellular uptake of gemcitabine, total ATPase activity, and cell death rate were also evaluated. Methods. Capan-2 pancreatic cancer cells were pre-treated for 24 h with calcitriol, BHT, BHA, or silibinin, followed by gemcitabine treatment. The concentration of gemcitabine was quantified using ultra-performance liquid chromatography (UPLC). Real-time polymerase chain reaction (RT-PCR) was utilized in order to investigate the expression of the mRNAs. The expression of the proteins was assessed using western blotting. Measurement of the ATPase activity was conducted utilizing a colorimetric method and viability of the cells was determined using a luminescent cell viability assay. Results. Protein expression studies showed that BHT, silibinin, and BHA increased expression of the efflux proteins and decreased the overall uptake of gemcitabine, whereas calcitriol significantly inhibited expression of the efflux proteins and increased gemcitabine uptake. Expression of specific mRNAs correlated reasonably well with the levels of corresponding proteins. Additionally, the expression of efflux proteins and ATPase activity were well correlated, signifying that the induced efflux proteins are functionally active. Moreover, pre-treatment with calcitriol resulted in a significant increase in cell death with gemcitabine treatment, whereas, BHA significantly reduced the cell death rate. On the other hand, pre-treatment with BHT and silibinin had no significant effect on the cell death rate. Conclusions. Pre-treatment of the pancreatic cancer cells with calcitriol significantly increased gemcitabine cellular uptake and consequently decreased cell viability after treatment with gemcitabine, whereas BHA significantly reduced gemcitabine uptake and decreased cell death rate, which were at least partially attributed to the alteration of expression of efflux and influx proteins. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

2013 ◽  
Vol 3 (3) ◽  
pp. 66 ◽  
Author(s):  
Vanessa Hörmann ◽  
Sivanesan Dhandayuthapani ◽  
James Kumi-Diaka ◽  
Appu Rathinavelu
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Treatment Options ◽  
Attractive Alternative ◽  
Intrinsic Apoptotic Pathway ◽  
Prostate Cancer Cells ◽  
Apoptotic Pathway ◽  
Combination Treatments

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

scholarly journals Impact of Diagnosed and Undiagnosed Respiratory Pseudomonas on VAP and VAE During Long-Term Acute Care

2020 ◽  
Vol 41 (S1) ◽  
pp. s258-s259
Author(s):  
James Harrigan ◽  
Ebbing Lautenbach ◽  
Emily Reesey ◽  
Magda Wernovsky ◽  
Pam Tolomeo ◽  
...  
Keyword(s):  
Bacterial Community ◽  
Acute Care ◽  
Statistical Significance ◽  
Rrna Gene ◽  
Care Hospital ◽  
16S Sequencing ◽  
Increased Risk ◽  
Wide Range ◽  
The Impact

Background: Clinically diagnosed ventilator-associated pneumonia (VAP) is common in the long-term acute-care hospital (LTACH) setting and may contribute to adverse ventilator-associated events (VAEs). Pseudomonas aeruginosa is a common causative organism of VAP. We evaluated the impact of respiratory P. aeruginosa colonization and bacterial community dominance, both diagnosed and undiagnosed, on subsequent P. aeruginosa VAP and VAE events during long-term acute care. Methods: We enrolled 83 patients on LTACH admission for ventilator weaning, performed longitudinal sampling of endotracheal aspirates followed by 16S rRNA gene sequencing (Illumina HiSeq), and bacterial community profiling (QIIME2). Statistical analysis was performed with R and Stan; mixed-effects models were fit to relate the abundance of respiratory Psa on admission to clinically diagnosed VAP and VAE events. Results: Of the 83 patients included, 12 were diagnosed with P. aeruginosa pneumonia during the 14 days prior to LTACH admission (known P. aeruginosa), and 22 additional patients received anti–P. aeruginosa antibiotics within 48 hours of admission (suspected P. aeruginosa); 49 patients had no known or suspected P. aeruginosa (unknown P. aeruginosa). Among the known P. aeruginosa group, all 12 patients had P. aeruginosa detectable by 16S sequencing, with elevated admission P. aeruginosa proportional abundance (median, 0.97; IQR, 0.33–1). Among the suspected P. aeruginosa group, all 22 patients had P. aeruginosa detectable by 16S sequencing, with a wide range of admission P. aeruginosa proportional abundance (median, 0.0088; IQR, 0.00012–0.31). Of the 49 patients in the unknown group, 47 also had detectable respiratory Psa, and many had high P. aeruginosa proportional abundance at admission (median, 0.014; IQR, 0.00025–0.52). Incident P. aeruginosa VAP was observed within 30 days in 4 of the known P. aeruginosa patients (33.3%), 5 of the suspected P. aeruginosa patients (22.7%), and 8 of the unknown P. aeruginosa patients (16.3%). VAE was observed within 30 days in 1 of the known P. aeruginosa patients (8.3%), 2 of the suspected P. aeruginosa patients (9.1%), and 1 of the unknown P. aeruginosa patients (2%). Admission P. aeruginosa abundance was positively associated with VAP and VAE risk in all groups, but the association only achieved statistical significance in the unknown group (type S error <0.002 for 30-day VAP and <0.011 for 30-day VAE). Conclusions: We identified a high prevalence of unrecognized respiratory P. aeruginosa colonization among patients admitted to LTACH for weaning from mechanical ventilation. The admission P. aeruginosa proportional abundance was strongly associated with increased risk of incident P. aeruginosa VAP among these patients.Funding: NoneDisclosures: None

scholarly journals Modeling Building Stock Development

2021 ◽  
Vol 13 (2) ◽  
pp. 723
Author(s):  
Antti Kurvinen ◽  
Arto Saari ◽  
Juhani Heljo ◽  
Eero Nippala
Keyword(s):  
Model Development ◽  
Housing Demand ◽  
Quality Data ◽  
Building Stock ◽  
Test Arena ◽  
Climate Targets ◽  
Wide Range ◽  
Key Variables ◽  
The Impact

It is widely agreed that dynamics of building stocks are relatively poorly known even if it is recognized to be an important research topic. Better understanding of building stock dynamics and future development is crucial, e.g., for sustainable management of the built environment as various analyses require long-term projections of building stock development. Recognizing the uncertainty in relation to long-term modeling, we propose a transparent calculation-based QuantiSTOCK model for modeling building stock development. Our approach not only provides a tangible tool for understanding development when selected assumptions are valid but also, most importantly, allows for studying the sensitivity of results to alternative developments of the key variables. Therefore, this relatively simple modeling approach provides fruitful grounds for understanding the impact of different key variables, which is needed to facilitate meaningful debate on different housing, land use, and environment-related policies. The QuantiSTOCK model may be extended in numerous ways and lays the groundwork for modeling the future developments of building stocks. The presented model may be used in a wide range of analyses ranging from assessing housing demand at the regional level to providing input for defining sustainable pathways towards climate targets. Due to the availability of high-quality data, the Finnish building stock provided a great test arena for the model development.

Sign in / Sign up

Export Citation Format

Share Document