The Rationale for Repurposing Sildenafil for Lung Cancer Treatment

2018 ◽  
Vol 18 (3) ◽  
pp. 367-374 ◽  
Author(s):  
Theodore Keats ◽  
Rhonda J. Rosengren ◽  
John C. Ashton
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Investigation ◽  
Tumour Size ◽  
Chemotherapeutic Agents ◽  
Metabolic Effects ◽  
Clinical Effects ◽  
Lung Cancer Treatment

There is now a considerable body of evidence for sildenafil possessing anticancer properties. In this article, we argue the case for testing sildenafil as a lung cancer therapy chemoadjuvant. Currently, lung cancer is a disease with insufficient treatment options, with only 20% of patients responding to systemic chemotherapy, and even incremental potential improvements should be explored. We review the literature concerning the biochemical, physiological and metabolic effects on cancer cells by sildenafil alone, and when combined with chemotherapeutic agents. Most studies have shown that sildenafil is cytotoxic to cancer cells, both as a monotherapy and as a chemoadjuvant. Sildenafil enhances cancer cell apoptosis when used as a chemoadjuvant both in vitro and in vivo. In particular, in rodent experiments sildenafil has decreased tumour size compared to chemotherapy alone. Sildenafil has also been proven as an agent to decrease drug-efflux by cancer cells and increases blood perfusion to lung tissue, which can potentially increase the dosage of chemotherapeutic agents delivered to lung cancer cells compared to healthy tissue. In addition, the proven clinical effects of sildenafil on other lung diseases suggest that it could improve other patient outcomes, such as right ventricular function and quality of life. Sildenafil may also extend the half-life of docetaxel and some small molecule inhibitors used in lung cancer treatment by acting as an inhibitor of CYP3A4. We conclude that the evidence strongly warrants clinical investigation into the use of sildenafil as an agent for the treatment of lung-cancer.

scholarly journals The Synergistic Anticancer Effect of Dual Drug- (Cisplatin/Epigallocatechin Gallate) Loaded Gelatin Nanoparticles for Lung Cancer Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yin-Ju Chen ◽  
Zhi-Weng Wang ◽  
Tung-Ling Lu ◽  
Clinton B. Gomez ◽  
Hsu-Wei Fang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Inductively Coupled Plasma ◽  
Cisplatin Resistance ◽  
Epigallocatechin Gallate ◽  
Gelatin Nanoparticles ◽  
Lung Cancer Treatment ◽  
Dual Drug

Lung cancer has the highest mortality of any cancer worldwide, and cisplatin is a first-line chemotherapeutic agent for lung cancer treatment. Unfortunately, cisplatin resistance is a common cause of therapeutic failure. The ability to overcome chemoresistance is crucial to the effective treatment of lung cancer. Recently, epigallocatechin gallate (EGCG), a type of polyphenol extracted from tea, has been shown to suppress the rapid proliferation of cancer cells, including lung cancer. We tested whether nanoparticles (NPs) carrying a dual drug load, cisplatin and EGCG, could overcome chemoresistance to cisplatin, by working together to kill lung cancer cells. Self-assembling gelatin/EGCG nanoparticles (GE) were synthesized, and cisplatin was then incorporated, to construct a dual drug nanomedicine (EGCG/cisplatin-loaded gelatin nanoparticle, named as GE-Pt NP). The particle size and zeta potential were examined by dynamic light scattering (DLS). The morphological structure of GE-Pt NPs was observed by transmission electron microscopy (TEM). In vitro testing was performed using a human lung adenocarcinoma cell line (A549). A cytotoxicity examination was performed, using a WST-8 cell proliferation assay. Intracellular cisplatin content was quantified by inductively coupled plasma mass spectrometry (ICP-MS). In conclusion, we successfully prepared GE-Pt NPs, as spherical structures, approximately 75 nm in diameter, with a positive charge (+19.83±0.25 mV). The encapsulation rate of cisplatin in GE-Pt was about 63.7%, and the EGCG loading rate was around 89%. A relatively low concentration of GE-Pt NPs (EGCG 5 μg/mL : cisplatin 2 μg/mL) exhibited significant cytotoxicity, compared to cisplatin alone. The GE-Pt NPs are freely taken up by cells via endocytosis, raising the intracellular cisplatin concentration to a therapeutic level. We consider that combination therapy of cisplatin and EGCG in nanoparticles (GE-Pt NPs) may help overcome cisplatin resistance and could effectively be used in the treatment of lung cancer.

scholarly journals Aerosolized Niosome Formulation Containing Gemcitabine and Cisplatin for Lung Cancer Treatment: Optimization, Characterization and In Vitro Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 59
Author(s):  
Norfatin Izzatie Mohamad Saimi ◽  
Norazlinaliza Salim ◽  
Noraini Ahmad ◽  
Emilia Abdulmalek ◽  
Mohd Basyaruddin Abdul Rahman
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Normal Lung ◽  
Alternative Formulation ◽  
Treatment Optimization ◽  
Lung Cancer Treatment ◽  
Diffusion Technique ◽  
Dialysis Bag ◽  
Cytotoxicity Effects

Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment, but they are highly toxic in high dosages. This research aimed to develop a niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulation for lung cancer treatment. NGC was prepared using a very simple heating method and was further optimized by D-optimal mixture design. The optimum NGC formulation with particle size, polydispersity index (PDI), and zeta potential of 166.45 nm, 0.16, and −15.28 mV, respectively, was obtained and remained stable at 27 °C with no phase separation for up to 90 days. The aerosol output was 96.22%, which indicates its suitability as aerosolized formulation. An in vitro drug release study using the dialysis bag diffusion technique showed controlled release for both drugs up to 24 h penetration. A cytotoxicity study against normal lung (MRC5) and lung cancer (A549) cell lines was investigated. The results showed that the optimized NGC had reduced cytotoxicity effects against both MRC5 and A549 when compared with the control (Gem + Cis alone) from very toxic (IC50 < 1.56 µg/mL) to weakly toxic (IC50 280.00 µg/mL) and moderately toxic (IC50 = 46.00 µg/mL), respectively, after 72 h of treatment. These findings revealed that the optimized NGC has excellent potential and is a promising prospect in aerosolized delivery systems to treat lung cancer that warrants further investigation.

scholarly journals 2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

Biosensors ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 40
Author(s):  
Mahek Sadiq ◽  
Lizhi Pang ◽  
Michael Johnson ◽  
Venkatachalem Sathish ◽  
Qifeng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Small Cell ◽  
Gas Chromatography Mass Spectrometry ◽  
High Signal ◽  
Research Attention ◽  
Lung Cancer Treatment ◽  
Anti Cancer ◽  
Cox 2

Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related deaths among both men and women around the world. A lot of research attention has been directed toward diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (cyclooxygenase-2) inhibitors. This is because COX-2 is commonly overexpressed in lung cancer and also the abundance of its enzymatic product prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we introduce a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6) fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX-2 expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di does not only limit the metabolic product, PGE2, but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. In this paper, we mainly report on a novel sensor, which is based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, or Ti3C2 MXene. The preliminary results have proven to sensitively, selectively, precisely, and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. The capability of the sensor to detect trace level 8-HOA in A549 has been verified in comparison with the traditional gas chromatography–mass spectrometry (GC–MS) method. The sensing principle could be due to the unique structure and material property of Ti3C2 MXene: a multilayered structure and extremely large surface area, metallic conductivity, and ease and versatility in surface modification. All these make the Ti3C2 MXene-based sensor selectively adsorb 8-HOA molecules through effective charge transfer and lead to a measurable change in the conductivity of the material with a high signal-to-noise ratio and excellent sensitivity.

scholarly journals Aptamers in Non-Small Cell Lung Cancer Treatment

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3138 ◽  
Author(s):  
Irena Wieleba ◽  
Kamila Wojas-Krawczyk ◽  
Paweł Krawczyk
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Production Costs ◽  
Small Cell Lung ◽  
Lung Cancer Treatment

Aptamers are short, single-stranded oligonucleotides which are capable of specifically binding to single molecules and cellular structures. Aptamers are also known as “chemical antibodies”. Compared to monoclonal antibodies, they are characterized by higher reaction specificity, lower molecular weight, lower production costs, and lower variability in the production stage. Aptamer research has been extended during the past twenty years, but only Macugen® has been accepted by the Food and Drug Administration (FDA) to date, and few aptamers have been examined in clinical trials. In vitro studies with aptamers have shown that they may take part in the regulation of cancer progression, angiogenesis, and metastasis processes. In this article, we focus on the potential use of aptamers in non-small cell lung cancer treatment.

scholarly journals In Vitro and in Vivo Antitumor Evaluation of Berbamine for Lung Cancer Treatment

2014 ◽  
Vol 15 (4) ◽  
pp. 1767-1769 ◽  
Author(s):  
Zhi-Bo Hou ◽  
Kai-Jin Lu ◽  
Xiao-Li Wu ◽  
Cong Chen ◽  
Xin-En Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Lung Cancer Treatment ◽  
Antitumor Evaluation

scholarly journals Novel Frog Skin-Derived Peptide Dermaseptin-PP for Lung Cancer Treatment: In vitro/vivo Evaluation and Anti-tumor Mechanisms Study

2020 ◽  
Vol 8 ◽  
Author(s):  
Ziyi Dong ◽  
Haiyan Hu ◽  
Xianglong Yu ◽  
Li Tan ◽  
Chengbang Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Frog Skin ◽  
Lung Cancer Treatment

scholarly journals 2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 29
Author(s):  
Mahek Sadiq ◽  
Lizhi Pang ◽  
Michael Johnson ◽  
Venkatachalem Sathish ◽  
Danling Wang
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Physical Adsorption ◽  
Small Cell ◽  
High Signal ◽  
Research Attention ◽  
Lung Cancer Treatment ◽  
Anti Cancer ◽  
Cox 2

Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related death among both men and women around the world. A lot of research attention has been attracted to diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (Cyclooxygenase-2) inhibitors. This is because COX-2 is commonly over expressed in lung cancer and also the abundance of its enzymatic product Prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we report a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6)fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di will not only limit the metabolic product, PGE2 but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. A novel sensor based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, Ti3C2 MXene, has proved to sensitively, selectively, precisely and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. Due to the multilayered structure and extremely large surface area, metallic conductivity and easy and versatile in surface modification, Ti3C2 MXene-based sensor will be able to selectively adsorb different molecules through physical adsorption or electrostatic attraction, and lead to a measurable change in the conductivity of the material with high signal-to-noise ratio and excellent sensitivity.

Evaluation of chemotherapy-related peripheral neuropathy in lung cancer treatment

2020 ◽  
pp. 030089162097586
Author(s):  
Gulay Dasdemir Ilkhan ◽  
Hakan Celikhisar
Keyword(s):  
Lung Cancer ◽  
Peripheral Neuropathy ◽  
Cancer Treatment ◽  
Clinical Symptoms ◽  
Chemotherapeutic Agents ◽  
Motor Symptoms ◽  
Peripheral Neuropathies ◽  
Lung Cancer Treatment ◽  
Group I ◽  
Group Ii

Objective: Chemotherapy-related peripheral neuropathies are observed frequently in lung cancer treatment in clinical practice. The present study aimed to evaluate the electrophysiologic findings and clinical symptoms in patients treated for lung cancer with different chemotherapy regimens who had the findings of peripheral neuropathy. Methods: Patients who had electromyography (EMG) examinations with the prediagnosis of peripheral neuropathy at two different centers between January 2011 and December 2019 were included. The demographic data, neurologic examination findings, symptoms, EMG findings, and chemotherapeutic agents used in the treatment were evaluated retrospectively. Results: A total of 742 patients were included in the study, with 630 (84.90%) male and 112 (15.10%) female patients. Of the patients included in the study, 406 (54.71%) had positive sensorial symptoms, 494 (66.57%) had negative sensorial symptoms, 162 (21.83%) had motor symptoms, and 254 (34.23%) had pain symptoms. The patients were classified into two groups on the basis of the presence of polyneuropathy detected via EMG as group I (n = 500, 67.38%) including the patients with polyneuropathy and group II (n = 242, 32.61%) including the patients without polyneuropathy. Negative sensorial symptoms and motor symptoms in group I along with dysesthesia and paresthesia symptoms in group II were observed at ratios that were higher at a statistically significant level ( p = 0.001, p = 0.001, p = 0.001, p = 0.001). Conclusion: Sensorial symptoms are observed most frequently in chemotherapy-related peripheral neuropathies in lung cancer treatment and motor symptoms may also increase according to the chemotherapy regimen.

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