Drugs For Cancer Therapy Research Articles

Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

AbstractHerein we report the synthesis of ten newly substituted 3‐phenyl‐5‐aryl‐3,5‐dihydro‐4H‐benzo[6,7]chromeno[2,3‐d]pyrimidin‐4,6,11‐triones (“benzochromenopyrimidines”) in a one‐step reaction, by reacting ethyl 2‐amino‐4‐aryl‐5,10‐dioxo‐5,10‐dihydro‐4H‐benzo[g]chromene‐3‐carboxylates with aniline, and triethyl orthoformate, under acidic catalyst and solvent‐free conditions. These benzochromenopyrimidines were submitted to biological evaluation for in vitro anti‐cancer activity, several derivatives showing higher activity than commonly used chemotherapeutic agents such as oxaliplatin, 5‐fluorouracil, and paclitaxel. In particular, the 5‐(2‐Methoxyphenyl)‐3‐phenyl‐3,5‐dihydro‐4H‐benzo[6,7]chromeno[2,3‐d]pyrimidine‐4,6,11‐trione was identified as the most potent inhibitor among all the new ligands, showing significant cytotoxic activity against all the cancer cell lines tested [human colon cancer cell lines, LoVo and HCT‐116; human lung cancer cells (A549 line)], as evidenced by the significant decrease in IC50 values, while maintaining low cytotoxicity against normal cells. These promising results suggest that this compound deserves further investigation as a potential hit compound for the development of a selective anticancer drug in cancer therapy.

Botanical Sources, Pharmacokinetics, and Therapeutic Efficacy of Palmatine and Its Derivatives in the Management of Cancer: A Comprehensive Mechanistic Analysis

Natural compounds and their derivatives have been identified as valuable sources of therapeutic ingredients for cancer treatment. The naturally occurring phytochemical palmatine (isoquinoline alkaloid) is extracted from plant parts (rhizomes, roots, stems, stem barks, and others) and has protective effects including antioxidant, anti‐inflammatory, and anticancer. This study aims to summarize the anticancer potential of palmatine and its derivatives in the treatment of numerous types of cancer with molecular mechanisms. We also include the pharmacokinetic features, botanical origin, and toxicological characteristics of palmatine and its derivatives. For this, data have been collected from plausible different electronic databases, including PubMed, Google Scholar, PubChem, Science Direct, Web of Science, Scopus, Springer Link, and Wiley Online. The findings demonstrate that palmatine and its derivatives have a protective anticancer effect against a variety of cancers, including breast, colorectal, gastric, ovarian, prostate, pancreatic, skin, hepatocellular cancer, and mammary gland tumors. They provoke their anticancer properties against various cancer cell lines via modifying molecular mechanisms like induction of oxidative stress, cytotoxicity, apoptosis, inhibition of cell invasion and migration, arresting the cell cycle at the S phase, antiproliferative, and antiangiogenic effects. It is suggested that palmatine and its derivatives may be a good option in the development of novel drugs for cancer therapy in the future.

Application of cisplatin and other platinum-containing drugs in cancer therapy: Comprehensive review

A well-known chemotherapy medication is a cisplatin, also referred to as cis-diamminedichloroplatinum or cisplatinum(II). Cancers such as bone metastases, lymphomas, germ cell tumors, and carcinomas can all be treated with it. Its mode has been takenpertaining to its capability to cross-link with purine biological branches, obstructing DNA repair processes, generating DNA damage, and, as a result, cancerous cells undergo apoptosis. Nevertheless, due to drug resistance and a number of unfavorable side effects, including severe kidney problems, allergic reactions, lowered immunity to infections, gastrointestinal problems and others, have also been used. For overcoming drug resistance and reducing adverse effects, cisplatin- based combination therapies with other pharmaceuticals have also garnered considerable investigation. This in-depth analysis looks at the isotopes of the properties cisplatin and associated platinum-based drugs, as well as how they can be is employed to treat a range of health maligancies. Particular focus is placed on its unfavorable side effects and molecular mechanisms of action. The current paper provides a pharmacological assessment of the drug, outlining its clinical applications, toxic effects, and mechanisms of resistance. The ability of cisplatin to form DNA adducts by crosslinking with urine bases on DNA has been connected to its mode of action. As a result, cancer cells experience apoptosis, which stops DNA damage from being repaired. The drug does, however, display certainly improved DNA damage repair, decreased drug accusation inside cells, and cisplatin deactivation in the cytosol are all signs of resistance. The drug also has some negative adverse consequences, including vomiting, kidney damage, cardiotoxicity, liver toxicity, and neurodegeneration.

Selective expansion of renal cancer stem cells using microfluidic single-cell culture arrays for anticancer drug testing.

The suboptimal prognosis associated with drug therapy for renal cancer can be attributed to the presence of stem-cell-like renal cancer cells. However, the limited number of these cells prevents conventional drug screening assays from effectively assessing the response of renal cancer stem cells to anti-cancer agents. To address this issue, the present study employed microfluidic single-cell culture arrays to expand renal cancer stem cells by exploiting the anti-apoptosis and self-renewal properties of tumor stem cells. A microfluidic chip with 18 000 hydrophilic microwells was designed and fabricated to establish the single-cell culture array. Over a 7 day culture, the large-scale single-cell culture yielded a limited quantity of single-cell-derived tumorspheres. The sphere formation rates for Caki-1, 786-O, and ACHN cells were determined to be 8.74 ± 0.53%, 12.02 ± 1.43%, and 4.98 ± 1.68%, respectively. The expanded cells exhibited stemness characteristics, as indicated by immunofluorescence, flow cytometry, serial passaging, and in vitro differentiation assays. Additionally, the comparative transcriptomic analysis showed significant differences in the gene expression patterns of the expanded cells compared to the differentiated renal cancer cells. The drug testing indicated that renal cancer stem cells exhibited reduced sensitivity towards the tyrosine kinase inhibitors sorafenib and sunitinib, compared to differentiated renal cancer cells. This reduced sensitivity can be attributed to the elevated expression levels of tyrosine kinase in renal cancer stem cells. This present study provides evidence that the utilization of microfluidic single-cell culture arrays for selective cell expansion can facilitate drug testing of renal cancer stem cells.

Nrf2 in human cancers: biological significance and therapeutic potential.

The nuclear factor-erythroid 2-related factor 2 (Nrf2) is able to control the redox balance in the cells responding to oxidative damage and other stress signals. The Nrf2 upregulation can elevate the levels of antioxidant enzymes to support against damage and death. In spite of protective function of Nrf2 in the physiological conditions, the stimulation of Nrf2 in the cancer has been in favour of tumorigenesis. Since the dysregulation of molecular pathways and mutations/deletions are common in tumors, Nrf2 can be a promising therapeutic target. The Nrf2 overexpression can prevent cell death in tumor and by increasing the survival rate of cancer cells, ensures the carcinogenesis. Moreover, the induction of Nrf2 can promote the invasion and metastasis of tumor cells. The Nrf2 upregulation stimulates EMT to increase cancer metastasis. Furthermore, regarding the protective function of Nrf2, its stimulation triggers chemoresistance. The natural products can regulate Nrf2 in the cancer therapy and reverse drug resistance. Moreover, nanostructures can specifically target Nrf2 signaling in cancer therapy. The current review discusses the potential function of Nrf2 in the proliferation, metastasis and drug resistance. Then, the capacity of natural products and nanostructures for suppressing Nrf2-mediated cancer progression is discussed.

Cytotoxic and Anti-Cervical Cancer Effects of the Camellia sinensis Byproducts from Various Kenyan Factories

Cervical cancer is a significant global health challenge and necessitates the search for innovative and patient-friendly therapies due to the limitations and challenges posed by conventional treatments. This study explored the largely overlooked potential of Camellia sinensis processing wastes as a natural source for developing effective and safe anticancer compounds. Tea waste samples from Kenyan processing facilities demonstrated concentration-dependent cytotoxic effects on normal epithelial cells (Vero), with the fluff sample from Chelal displaying superior efficacy. Median inhibitory concentration (IC50) values highlighted the potency of the samples, especially the fluff sample from Chelal (IC50: 483.99µg/ml). Selectivity indices revealed favorable safety profiles, indicating selective potential anticancer effects against cervical cancer cells. This study contributes substantively to understanding tea waste’s anticancer potential, providing valuable insights for drug development. The study offers a foundation for continued research into sustainable and impactful anticancer drug discovery, emphasizing specific results that pinpoint promising tea waste samples and their potential applications in cervical cancer therapy and anticancer drug development.

Towards voltammetric point of care detection of leucovorin.

Current healthcare trends have seen an increased emphasis on the move towards personalised precision medicine to tailor treatments to the individual and their response to diseases and disease therapies. This highlighting a transition from traditional "one size fits all" to a more nuanced approach. Despite advancements in fundamental knowledge to facilitate personalised prevision approaches, lack of resources to implement such plans remains one of the largest hurdles to overcome. Monitoring of drug therapies is one key aspect that could aid in the evolution of precision medicine alongside the development of drugs and targeted treatment systems. This contribution illustrates the potential of square wave voltammetry (SWV) as a proof-of-concept for monitoring of circulating blood concentrations of treatment therapies within artificial urine, using leucovorin calcium (LV) as a model cancer therapy drug. A low cost, easy-to-use and portable sensor has been developed and successfully employed for the detection of LV over the linear range 0.5-30 μM which represents the therapeutically relevant concentrations for LV within artificial urine without any prior sample preparation required with a limit of detection of 2.63 μM and initial investigations into saliva and serum as biological matrices. The developed sensor describe herein exhibits a proof-of-concept for the engagement of such electrochemical sensors as point-of-care devices, where the sensors ease of use and removal of time-consuming and complex sample preparation methods will ultimately increase its usability by physicians, widening the avenues where electrochemical sensors could be employed.

Etlingera elatior Compounds as Anticancer Agents of Breast Cancer Through Inhibition of Progesterone Receptor: An In Silico Study

Breast cancer is the leading cause of cancer-related death in women globally. Progesterone receptor (PR) is known as the prime example of receptors amenable to targeted breast cancer drug therapy. Etlingera elatior is an herbal plant that has been renowned to have anticancer effect. This study aimed to identify the potential compounds derived from Etlingera elatior as anticancer agents of PR in breast cancer using molecular docking method. This study used fifteen compounds from Etlingera elatior along with lonaprisan as the comparative drug. The PR was downloaded from RCSB, whereas compounds and lonaprisan were from Pubchem. The drug-likeness test based on Lipinski’s rule of five was conducted using SwissADME. Toxicity analysis using admetSAR 2.0 was used to predict toxicological profile of the compounds. Compounds and lonaprisan were docked on PR using AutoDock tools 1.5.6 and AutoDock Vina 1.1.2. Molecular interactions were visualized by Discovery Studio v16. A total of nine compounds met the criteria as drugs based on drug-likeness and toxicity tests. All nine compounds except caffeic acid and vanillic acid had higher binding affinities on PR compared with lonaprisan. Ergosterol peroxide exhibited the highest binding affinity on PR with values of -9.8 kcal/mol. Moreover, ergosterol peroxide-PR interaction had thirteen hydrophobic bonds and a hydrogen bond with amino acid residues were found in the active site of PR. Most of the compounds found in Etlingera elatior have the potential to be anticancer agents of PR in breast cancer with ergosterol peroxide being the most potential compound. Further in vitro and in vivo research are needed.Keywords: breast cancer, ergosterol peroxide, Etlingera elatior, progesterone receptor, in silico.

Current stage of preclinical and clinical development of guggulsterone in cancers: Challenges and promises.

Throughout human history, the utilization of medicinal herbs has been recognized as a crucial defense against various ailments, including cancer. Natural products with potential anticancer properties, capable of inducing apoptosis in cancer cells, have garnered substantial attention. One such agent under investigation is guggulsterone (GS), a phytosterol derived from the gum resin of the Commiphora mukul tree. This review aims to provide a comprehensive summary of recent studies elucidating the anticancer molecular mechanisms and molecular targets of GS, guiding future research and potential applications as an adjuvant drug in cancer therapy. Recent in vivo and in vitro studies have explored the biological activities of the active ingredients in Commiphora mukul. Specifically, GS emerges as a potential cancer chemopreventive and therapeutic agent. The investigations delve into the impact of GS on constitutively activated survival pathways, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-kB), and PI3-kinase/AKT signaling pathways. These pathways regulate antiapoptotic and proinflammatory genes, exerting control over growth and inflammatory responses. The findings highlight the potential of GS in disrupting survival pathways crucial for cancer cell viability. The inhibition of JAK/STAT, NF-kB, and PI3-kinase/AKT signaling pathways positions GS as a promising candidate for cancer therapy. The review synthesizes evidence from diverse studies, underscoring the multifaceted biological activities of GS in cancer prevention and treatment. To advance our understanding, future clinical and translational studies are imperative to determine effective doses in humans. Additionally, there is a need for the development of new pharmaceutical forms of GS to optimize therapeutic effects. This comprehensive review provides a foundation for ongoing research, offering insights into the potential of GS as a valuable addition to the armamentarium against cancer.

Complete radiological response when using pembrolizumab in the mono mode in the 2nd-line drug therapy of MSI-h / dMMR-positive advanced endometrial cancer. A clinical case

Until recently, the prognosis of patients with advanced endometrial cancer remained disappointing despite the standard treatment methods. None of the drugs in the arsenal of oncologists-chemotherapists provided long-term disease control and long-term survival of patients who received standard platinum-containing first-line chemotherapy. It is obvious that the poor results of treatment in patients with advanced endometrial cancer required a change in treatment approaches and indicated the need to develop more effective treatment regimens. A deeper understanding of the mechanisms of carcinogenesis, the emergence of new molecular classification of endometrial cancer and division of treatment approaches depending on the tumor biological potential has led to significant breakthrough in the treatment of advanced endometrial cancer. One of the most significant achievements is discovery of the function of microsatellite instability (MSI) and disorders in the repair system of unpaired bases of deoxyribonucleic acid (MMR) as a predictor of high efficient immunotherapy – a new direction of systemic drug therapy for the advanced endometrial cancer. The paper presents a clinical case of successful treatment of MSI-h / dMMR-positive advanced endometrial cancer using pembrolizumab as a second-line therapy (in the presence of refractoriness to standard platinum-based chemotherapy of the 1st line) in a mono mode with a complete radiological response of the tumor to treatment.

Discovery of 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea as a promising anticancer drug via synthesis, characterization, biological screening, and computational studies

Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC50 = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored − 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and − 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.

Calcium Influx Pathways in Breast Cancer: Opportunities for Pharmacological Intervention

Numerous cellular processes, including the release of neurotransmitters and the contraction of muscles, are largely triggered and regulated by Ca2+ inflow via Ca2+ permeable ion channels. In addition, Ca2+ influx regulates cellular migration and proliferation, two mechanisms linked to cancer. This study focuses on calcium influx in breast cancer cells and discusses how future drugs for breast cancer therapy may be pharmacological modulators of particular Ca2+ influx channels. Certain breast tumors have altered expression of particular calcium permeable ion channels. Such alterations may occasionally be connected to the prognosis and subtype of breast cancer. These days, models both in vivo and in vitro have assisted in identifying particular Ca2+ channels that are crucial for the growth and invasiveness of of cancerous breast cells. Nonetheless, additional research is still needed to fully understand several features of Ca2+ influx in breast cancer. These include figuring out the processes behind the changed expression and the best treatment plan to target breast cancer cells via particular Ca2+ channels. In the upcoming ten years, research should concentrate on the function of Ca2+ influx in mechanisms other than the migration and proliferation of breast cancer cells.

MgO-ZnO nanoparticle as an efficient photocatalyst in the synthesis of substituted chromeno[4, 3-b]chromenes as effective drugs in gastrointestinal cancer therapy

Chromeno[4,3-b]chromenes are biologically active compounds that have many applications in medicine, especially, in gastrointestinal field because of their anti-inflammatory and antioxidant properties. In this study, an efficient and environmental benign photocatalyst MgO-ZnO is proposed for the synthesis of a range of substituted chromenes under irradiation of a common green laser. To characterize MgO-ZnO techniques such as FT-IR, DRS, XRD, and FE-SEM are employed to ascertain the structure and physicochemical properties of the nanomaterial. Furthermore, an in-vitro cellular toxicity test was achieved on HCT-116 human gastrointestinal cancer cell line by MTT assay.

Pharmacological Therapeutic Potential in Breast Cancer through Calcium Influx Pathways

Numerous cellular processes, including the release of neurotransmitters and the contraction of muscles, are largely triggered and regulated by Ca2+ inflow via Ca2+ permeable ion channels. In addition, Ca2+ influx regulates cellular migration and proliferation, two mechanisms linked to cancer. This study focuses on calcium influx in breast cancer cells and discusses how future drugs for breast cancer therapy may be pharmacological modulators of particular Ca2+ influx channels. Certain breast tumors have altered expression of particular calcium permeable ion channels. Such alterations may occasionally be connected to the prognosis and subtype of breast cancer. These days, models both in vivo and in vitro have assisted in identifying particular Ca2+ channels that are crucial for the growth and invasiveness of cancerous breast cells. Nonetheless, additional research is still needed to fully understand several features of Ca2+ influx in breast cancer. These include figuring out the processes behind the changed expression and the best treatment plan to target breast cancer cells via particular Ca2+ channels. In the upcoming ten years, research should concentrate on the function of Ca2+ influx in mechanisms other than the migration and proliferation of breast cancer cells

RUNX1 knockdown induced apoptosis and impaired EMT in high-grade serous ovarian cancer cells

Ovarian cancer is the leading cause of death from gynecologic illnesses worldwide. High-grade serous ovarian cancer (HGSOC) is a gynecological tumor that accounts for roughly 70% of ovarian cancer deaths in women. Runt-related transcription factor 1(RUNX1) proteins were identified with overexpression in the HGSOC. However, the roles of RUNX1 in the development of HGSOC are poorly understood. In this study, combined with whole-transcriptome analysis and multiple research methods, RUNX1 was identified as vital in developing HGSOC. RUNX1 knockdown inhibits the physiological function of ovarian cancer cells and regulates apoptosis through the FOXO1-Bcl2 axis. Down-regulated RUNX1 impairs EMT function through the EGFR-AKT-STAT3 axis signaling. In addition, RUNX1 knockdown can significantly increase the sensitivity to clinical drug therapy for ovarian cancer. It is strongly suggested that RUNX1 work as a potential diagnostic and therapeutic target for HGSOC patients with better prognoses and treatment options. It is possible to generate novel potential targeted therapy strategies and translational applications for serous ovarian carcinoma patients with better clinical outcomes.

A novel L-shaped ortho-quinone analog as PLK1 inhibitor blocks prostate cancer cells in G2 phase

Prostate cancer is the most common malignant tumor among men worldwide. Currently, the main treatments are radical prostatectomy, radiotherapy, chemotherapy, and endocrine therapy. However, most of them are poorly effective and induce side effects. Polo-like kinase 1 (PLK1) regulates cell cycle and mitosis. Its inhibitor BI2536 promotes the therapeutic effect of nilotinib in chronic myeloid leukemia, enhances the sensitivity of neural tube cell tumors to radiation therapy and PLK1 silencing enhances the sensitivity of squamous cell carcinoma to cisplatin. Therefore, the aim of this study was to evaluate the effect of the PLK1 inhibitor L-shaped ortho-quinone analog TE6 on prostate cancer. In vitro on prostate cancer cells showed that TE6 inhibited PLK1 protein expression and consequently cell proliferation by blocking the cell cycle at G2 phase. In vivo on a subcutaneous tumor model in nude mice confirmed that TE6 effectively inhibited tumor growth in nude mice, inhibited PLK1 expression and regulated the expression of cell cycle proteins such as p21, p53, CDK1, Cdc25C, and cyclinB1. Thus, PLK1 was identified as the target protein of TE6, these results reveal the critical role of PLK1 in the growth and survival of prostate cancer and point out the ability of TE6 on targeting PLK1, being a potential drug for prostate cancer therapy.

Design of Bioengineered Peptides/Proteases as Anti-cancer Reagents with Integrated Omics and Machine Learning Approaches.

Cancer is a heterogeneous disorder of uncontrolled growth of cells, which has proven to be a major burden worldwide. Many treatment options are available for cancer therapy, yet side effects and drug resistance remain major hurdles. Therefore, it is necessary to develop novel drugs for cancer therapy. Anti-cancer peptides (ACPs) are attractive candidates with remarkable potency, low toxicity, and high specificity advantages. However, traditional experimental identification of ACPs is time-consuming and expensive. Integrated omics combined with machine learning (ML) is considered a new powerful and cost-effective strategy to discover ACPs from natural products. In this chapter, we describe in detail experimental procedures for collecting both transcriptomic and proteomic data from venoms, followed by descriptive approaches to ML prediction.

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells.

Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer-DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.

Nephrotoxicity of combination drug therapy in metastatic renal cancer

The review covers reduced kidney function in the context of renal cell carcinoma. According to international studies, some patients already have chronic kidney disease at time of disease onset. Surgical treatment leads to a decrease in the total number of functioning nephrons. Drug therapy causes several adverse events including nephrotoxicity. The review discusses the problem of using combination regimens in patients with solitary kidney.