Side Effects Of Anticancer Drugs Research Articles

Nutraceuticals Health Benefits in Cancer

Abstract: Cancer is one of the leading causes of death worldwide, with multiple pathological components. Genetic abnormalities, infection or inflammation, poor diet, radiation exposure, work stress, and/or ingestion of toxic substances have all been associated with cancer development and progression. Early detection and treatment of cancer have been shown to increase the chances of survival and recovery and reduce the side effects of anticancer drugs. Anticancer drugs continue to cause negative side effects that negate treatment benefits in terms of hospitalization and survival. Many naturally occurring bioactive compounds are shown to have anticancer properties. That is, they can eliminate altered and cancer cells without harming their healthy counterparts. In particular, the following activities have been reported to support nutrition during cancer treatment: cell growth inhibition, antioxidant activity, anti-inflammatory activity, and minimized negative effects due to natural antioxidants. Keeping the side effects minimum helps patients adhere to anticancer therapy. Among currently available anticancer agents, dietary supplementation can be considered in conjunction with current chemotherapy to improve response and compliance in cancer patients. However, it should be noted that before discussing data from studies on bioactive plant supplements, it is important to ensure that the tests were performed according to protocol.

Adverse Event Signal Detection Using Patients' Concerns in Pharmaceutical Care Records: Evaluation of Deep Learning Models.

Early detection of adverse events and their management are crucial to improving anticancer treatment outcomes, and listening to patients' subjective opinions (patients' voices) can make a major contribution to improving safety management. Recent progress in deep learning technologies has enabled various new approaches for the evaluation of safety-related events based on patient-generated text data, but few studies have focused on the improvement of real-time safety monitoring for individual patients. In addition, no study has yet been performed to validate deep learning models for screening patients' narratives for clinically important adverse event signals that require medical intervention. In our previous work, novel deep learning models have been developed to detect adverse event signals for hand-foot syndrome or adverse events limiting patients' daily lives from the authored narratives of patients with cancer, aiming ultimately to use them as safety monitoring support tools for individual patients. This study was designed to evaluate whether our deep learning models can screen clinically important adverse event signals that require intervention by health care professionals. The applicability of our deep learning models to data on patients' concerns at pharmacies was also assessed. Pharmaceutical care records at community pharmacies were used for the evaluation of our deep learning models. The records followed the SOAP format, consisting of subjective (S), objective (O), assessment (A), and plan (P) columns. Because of the unique combination of patients' concerns in the S column and the professional records of the pharmacists, this was considered a suitable data for the present purpose. Our deep learning models were applied to the S records of patients with cancer, and the extracted adverse event signals were assessed in relation to medical actions and prescribed drugs. From 30,784 S records of 2479 patients with at least 1 prescription of anticancer drugs, our deep learning models extracted true adverse event signals with more than 80% accuracy for both hand-foot syndrome (n=152, 91%) and adverse events limiting patients' daily lives (n=157, 80.1%). The deep learning models were also able to screen adverse event signals that require medical intervention by health care providers. The extracted adverse event signals could reflect the side effects of anticancer drugs used by the patients based on analysis of prescribed anticancer drugs. "Pain or numbness" (n=57, 36.3%), "fever" (n=46, 29.3%), and "nausea" (n=40, 25.5%) were common symptoms out of the true adverse event signals identified by the model for adverse events limiting patients' daily lives. Our deep learning models were able to screen clinically important adverse event signals that require intervention for symptoms. It was also confirmed that these deep learning models could be applied to patients' subjective information recorded in pharmaceutical care records accumulated during pharmacists' daily work.

Current Status and Issues of Collaboration Between Physicians and Pharmacists in Fertility Preservation.

Purpose: This study addresses the critical issue of fertility preservation among young patients with cancer in Japan, recognizing the brief decision-making window and the need for comprehensive support. Pharmacists, well-versed in the side effects of anticancer drugs, can play a vital role in this support process. However, the extent of pharmacists' involvement in fertility preservation remains unclear. We aimed to investigate pharmacists' roles in addressing cancer treatment-induced fertility concerns and their collaboration with physicians, offering insights into enhancing pharmacist participation in fertility preservation. Methods: A survey conducted between April and July 2022 targeted doctors and pharmacists at cancer treatment hospitals, along with pharmacists affiliated with the Japanese Society of Pharmaceutical Health Care and Sciences. Results: Our findings indicated that although pharmacists had limited knowledge about gonadotoxicity and fertility, they expressed readiness to conduct research and provide information when consulted. Approximately 10%-20% of the pharmacists participated in explaining the primary disease at diagnosis. Pharmacists played a more prominent role after establishing chemotherapy regimens, with less involvement in its formulation. Notably, treatment decision case conferences emerged as crucial forums for gathering patient data, confirming treatment plans, and identifying those in need for fertility preservation information. Roughly half of the pharmacists attended these conferences, suggesting a need for increased participation. Conclusion: Enhancing physician-pharmacist collaboration could be pivotal for effective fertility preservation. This requires augmenting the knowledge and awareness of both professions and encouraging greater participation in case conferences to create a conducive environment for addressing this critical aspect of cancer care.

A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.

While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments havealso come to the fore. These side effects include cardiotoxicity, which can cause irreversible cardiac damages withlong-term morbidity and mortality. Despite the continuous in-depth research on anti-cancer drugs, an improvedknowledge of the underlying mechanisms of cardiotoxicity are necessary for early detection and management ofcardiac risk.Although most reviews focus on the cardiotoxic effect of a specific individual chemotherapeutic agent, the aim of our review is to provide comprehensive insight into various agents that induced cardiotoxicity and their underlying mechanisms. Characterization of these mechanisms are underpinned by research on animal models and clinical studies. In order to gain insight into these complex mechanisms, we emphasize the role of inflammatory processes and oxidative stress on chemotherapy-induced cardiac changes.A better understanding and identification of the interplay between chemotherapy and inflammatory/oxidativeprocesses hold some promise to prevent or at least mitigate cardiotoxicity-associated morbidity and mortalityamong cancer survivors.

A Nanoplatform Based on Pillar[5]arene Nanovalves for Combined Drug Delivery and Enhanced Antitumor Activity.

Modern nanodrug delivery technologies offer new approaches in the fight against cancer. However, due to the heterogeneity of tumors and side effects of anticancer drugs, monotherapies are less effective. Herein, we report a novel pH and light dual-responsive nanodrug delivery platform. The platform was formed by sulfonate-modified gold nanoparticles loaded with the anticancer drugs doxorubicin (DOX) and glucose oxidase (GOx) and then covered by water-soluble pillar[5]arene as a nanovalve. The nanovalve formed by the host-guest interaction between pillar[5]arene and the sulfonic acid group grafted onto the gold nanoparticle increased the drug loading capacity of the nanoplatform and enabled sustained release of the drug in a simulated weakly acidic tumor environment. The released GOx can consume intracellular glucose, namely, starvation therapy, while the generated hydrogen peroxide can further kill tumor cells, complementing DOX chemotherapy. Gold nanoparticles have good photothermal conversion ability and can enhance the drugs release rate under specific wavelengths of light irradiation. The results of in vitro and in vivo experiments showed that this novel nanodrug delivery platform has good biocompatibility and better therapeutic efficacy relative to monotherapy. This study successfully developed a combined chemo/starvation therapy strategy with good tumor suppression, providing a new approach for cancer treatment.

Research Progress of Polysaccharide-Gold Nanocomplexes in Drug Delivery.

Clinical drug administration aims to deliver drugs efficiently and safely to target tissues, organs, and cells, with the objective of enabling their therapeutic effects. Currently, the main approach to enhance a drug's effectiveness is ensuring its efficient delivery to the intended site. Due to the fact that there are still various drawbacks of traditional drug delivery methods, such as high toxicity and side effects, insufficient drug specificity, poor targeting, and poor pharmacokinetic performance, nanocarriers have emerged as a promising alternative. Nanocarriers possess significant advantages in drug delivery due to their size tunability and surface modifiability. Moreover, nano-drug delivery systems have demonstrated strong potential in terms of prolonging drug circulation time, improving bioavailability, increasing drug retention at the tumor site, decreasing drug resistance, as well as reducing the undesirable side effects of anticancer drugs. Numerous studies have focused on utilizing polysaccharides as nanodelivery carriers, developing delivery systems based on polysaccharides, or exploiting polysaccharides as tumor-targeting ligands to enhance the precision of nanoparticle delivery. These types of investigations have become commonplace in the academic literature. This review aims to elucidate the preparation methods and principles of polysaccharide gold nanocarriers. It also provides an overview of the factors that affect the loading of polysaccharide gold nanocarriers with different kinds of drugs. Additionally, it outlines the strategies employed by polysaccharide gold nanocarriers to improve the delivery efficiency of various drugs. The objective is to provide a reference for further development of research on polysaccharide gold nanodelivery systems.

Synthesis, design, biological evaluation, and computational analysis of some novel uracil-azole derivatives as cytotoxic agents

The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil–azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure–activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil–azole hybrids can be considered as potential cytotoxic agents.

Atorvastatin protects against cyclophosphamide-induced thyroid injury in rats via modulation of JNK/ ERK/ p38 MAPK signaling pathway

BackgroundCancer chemotherapy is associated with various tissue toxicities that limit its use. Cyclophosphamide (CYC) is one of the most commonly used antineoplastic and immunosuppressive agent. Thyroid dysfunction is a critical side effect of anticancer drugs. Atorvastatin (ATV) is antihyperlipedemic drug with different tissue protective activities. The aim of this study was to determine the potential protective effect of ATV against CYC-induced thyroid injury in rats. MethodsATV was administered in the presence and absence of CYC. Thirty-two adult Wistar rats were randomly divided into four groups: control group, ATV group (20 mg/kg/day, p.o. for 14 day), CYC group (200 mg/kg, i.p. on day 9) and ATV/CYC group. Triiodothyronine (T3), thyroxine (T4), reduced glutathione (GSH), malondialdehyde (MDA), total nitrite/nitrate (NOx), p38 mitogen-activated protein kinase (P38MAPK), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) were measured. In addition, thyroid histopathology and caspase 3 immunohistochemistry were performed. ResultsCYC significantly increased thyroid MDA, NOx, P38MAPK, ERK and JNK with decrease in GSH, T3 and T4 levels. Histopathological features of thyroid lesions and increased caspase 3 immune expression were appeared. ATV significantly normalized distributed oxidative, inflammatory and apoptotic indicators, resulting in an improvement of histopathological features and reduction of caspase 3 immunoexpression. ConclusionThese findings suggest that ATV protects against CYC-induced thyroid injury by regulating the JNK/ERK/p38-MAPK signaling pathway.

The Effect of Beta-lactoglobulin Nanocapsules Containing Astaxanthin and 5-fluorouracil on the Antioxidant Enzymes Activity of Superoxide Dismutase, Catalase and Glutathione Peroxidase in HCT116 Colorectal Cancer Cell Line

Background: The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anticancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and antiapoptotic properties used to prevent and treat some cancers. Objectives: In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined. Methods: In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group in which HCT116 cells were not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT, and GPX was measured by a colorimetric method in HCT116 cells. Results: Different treatments reduced the cell viability and increased apoptotic cells in a timedependent manner, which was significant for beta-lactoglobulin nanocapsules treatment (P<0.05). It means receiving more 5-FU or ATX in the encapsulated form by HCT116 cells. The antioxidant enzyme activity of SOD, CAT, and GPX in HCT116 cells treated with beta-lactoglobulin nanocapsule treatment significantly increased compared to the control group (P<0.001). Moreover, the antioxidant activity of these enzymes in different treatments containing ATX (free or encapsulation) was significantly higher than in other treatments (P<0.05). The most increase in the activity of antioxidant enzymes is recorded in the treatment of nanocapsules containing ATX and 5-FU simultaneously. Conclusion: Increased activity of antioxidant enzymes in addition to the induction of apoptosis in colorectal cancer cells by various treatments of beta-lactoglobulin nanocapsules indicates more effective drug administration in encapsulated form as well as synergistic thera[peutic effects of ATX and 5-FU. Moreover, the main increase in antioxidant enzyme activity may be related to ATX.

Molecular screening reveals Variolin B as a multitargeted inhibitor of lung cancer: a molecular docking-based fingerprinting and molecular dynamics simulation study

Lung Cancer is the topmost death causing cancer and results from smoking, air pollution, cigar, exposure to asbestos or radon-like substances, and genetic factors. The cases of Lung Cancer in south Asian developing nations are being seen most due to heavy pollution and unbalanced lifestyle and putting a considerable burden on healthcare systems. The Food and Drug Administration of the USA has approved almost 100 drugs against SCLC and NSLC and a few drugs that are given to minimise the side effect of anticancer drugs. However, the drugs are shown to be resistant at significantly higher stages and non-affective on cancerous cells and have long-term side effects due to designing the drug by keeping one protein/gene target while designing or repurposing the drugs. In this study, we have taken five main lung cancer protein targets- Nerve growth factor protein (1SG1), Apoptosis inhibitor survivin (1XOX), Heat shock protein (3IUC), Protein tyrosine phosphate (3ZM3), Aldo-keto reductase (4XZL) and screened the complete prepared Drug Bank library of 155888 compounds and identified Variolin B (DB08694) as a multitargeted inhibitor against lung cancer using HTVS, SP and XP sampling algorithms followed by MM\\GBSA calculation to sort the best pose. Variolin B is a natural marine antitumor and antiviral compound, so we analysed the ADMET properties and interaction patterns and then simulated all five P-L complexes for 100 ns in water using the NPT ensemble to check its selves against lung cancer. The docking results, ADMET and fingerprints have shown a good performance, and RMSD and RMSF results were with least deviation and fluctuations (<2Å) and produced a huge contact with other residues making the complex stable. The complexes initially fluctuated and deviated due to changes in the solute medium and sudden heat and stabilise after a few ns. However, extensive experimental validation is required before human use. Communicated by Ramaswamy H. Sarma

Investigation of In-vitro Antiproliferative activity of Ampelocissus latifolia root extract on MCF-7 breast cancer cells Ampelocissus latifolia root extract against MCF-7 breast cancer cells.

Background: Breast cancer is one of the leading causes of cancer related death in women worldwide. Treatment of cancer has been plagued with toxic side effects of anticancer drugs. The need of the hour is the development of novel compounds with maximum cytotoxic effect on cancer cells with minimal toxicity to normal cells. The current direction of researchers worldwide is to identify anticancer compounds from natural sources. In India, traditional medicine has employed use of herbaceous climbers of grape family for treatment of ailments ranging from snakebites to diabetes. In the current study, an attempt has been made to explore the in vivo antiproliferative property of ethanolic extract of root of Ampelocissus latifolia against MCF-7 breast cancer cell line. Materials and Methods: The antiproliferative effect of Ethanolic extract of root of Ampelocissus latifolia (ERAL) was estimated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl--tetrazolium bromide (MTT) assay. The MCF -7 cell viability in various concentrations of ERAL including 7.8mcg/ml, 15.6mcg/ml, 31.2mcg/ml, 62.5mcg/ml, 125mcg/ml, 250mcg/ml, 500mcg/ml and 1000mcg/ml was tested. The IC50 value was calculated. All the experiments were done in triplicates. This was followed up with DNA fragmentation assay and fluorescent staining and microscopy. Results: The MCF -7 cell viability in various concentration of ERAL including 7.8mcg/ml, 15.6mcg/ml, 31.2mcg/ml ,62.5mcg/ml, 125mcg/ml, 250mcg/ml, 500mcg/ml and 1000mcg/ml was found to be 69.01%, 62.39%, 55.04%, 48.00%, 41.17%, 33.82%, 26.78% and 20.06% respectively .The IC50 concentration was found to be in the range of 62.5mcg/ml.The cell viability was found to be dose dependant.DNA fragmentation assay and DAPI and PI staining of cells treated with IC50 concentration of ERAL were indicative of significant cell death. Conclusion: The concentration dependent inhibition of MCF-7 cells supported by DNA fragmentation and fluorescent staining indicate that Ampelocissus latifolia can be a source of novel anticancer molecules.

An In-Vivo Study to Evaluate the Efficacy of Padmaka (Prunus Cerasoides) as a Vedanasthapak in Supti (Numbness) Caused by Neuropathy in Wistar Rats

This research article attempts to address the main symptom of chemotherapy-induced neuropathy, which is ‘numbness’. Neuropathic pain is a common side effect of anticancer drugs that significantly reduces a patient's quality of life. This work redefines the term "Vedanasthapan" by explaining the act of regaining sensation along with its analgesic properties. This study was carried out by using an animal model of rats prepared by using an anti-cancer agent cisplatin. Before inducing cisplatin, normal latency periods of all rats were noted by ‘Hot plate’ method. Cisplatin was given to the rats to induce numbness with the interval of a week for two weeks. Four groups of rats having six rats in each group were labelled as – ‘control group’ treated with daily diet only, ‘vehicle group’ treated with carboxymethyl cellulose, ‘positive control’ treated with pregabalin, and ‘test drug group’ treated with ‘Padmaka’. After the treatment period, all groups were tested on a hot plate to record the latency time of rats. All obtained data were processed by ANOVA test and Tukey-Kramer multiple comparison test. It showed that the means of all groups differed significantly from each other. The mean time of the positive control group was 9.06 seconds and that of the experimental drug group was 12.9 seconds, which is close to the mean time in the normal state (7.36 seconds). While the control group and the vehicle group were far apart. This means that the experimental drug Padmaka is also useful in reversing cisplatin-induced numbness. Further clinical studies are needed to fully understand its range of action.

Tubular scaffold made by gelatin/polylactic acid nanofibers for breast ductal carcinoma in situ tumor modeling

Ductal carcinoma in situ (DCIS), the outcome of abnormal cells inside a breast milk duct, has a twenty percent prevalence in females with breast cancer. Providing an appropriate DCIS model is critical to study the natural complexity of tumor tissues and cell-cell interactions and treating them. To this end, we designed and developed a biodegradable tubular 3D scaffold made of core-shell nanofibers obtained through emulsion electrospinning. The results showed that the nanofibers with 16.9 wt.% gelatin (as a core) and 83.1 wt.% polylactic acid (PLA; as a shell) unveiled a uniform porous structure with a nanofiber size of around 440 nm. The fabricated tubular 3D scaffold by these nanofibers had an outer and inner diameter of 900 and 416 μm, respectively, in the range of natural ductal carcinoma. Cellular studies showed that the MCF-7 breast cancer cells could well attach and spread out on the scaffold's inside and outside surface, confirming their potential applicability for DCIS modeling in drug screening, drug discovery, and drug efficacy before any pre-clinical studies. Furthermore, as an additional functionality, the scaffold's potency for a drug delivery platform was assessed by loading anticancer docetaxel (DTX) drug on the scaffold, followed by the investigation of in vitro drug release kinetic. The results unfolded a pH-dependency of the scaffold for DTX release. So, the drug release was intensified at pH 6.5 rather than pH 7.4, making it a suitable platform for intensive drug delivery to tumor tissues with acidic environment. In the following, the potential of the prepared tubular scaffold in local drug delivery was studied in vitro in a designed hollow agarose culture media. The released DTX from the DTX-loaded tubular scaffold eradicated MFC-7 cells intensively in comparison with the DTX-free tubular scaffold confirming its capability of local chemotherapy to avoid any side effects of anticancer drugs. In other words, this ability makes these scaffolds a promising candidate for transplanting at the surgery site to reduce the probability of tumor recurrence through localized chemotherapy.

A review on emerging role of multifunctional carbon nanotubes as an armament in cancer therapy, imaging and biosensing

The use of traditional chemotherapy to treat cancer is often limited by the toxic side effects of anti-cancer drugs on the body. Additionally, there are major challenges in the form of higher incidence of cell mutations, diverse tumour microenvironments, and unequal patient needs. Therefore, there is a need for the development and implementation of novel approaches to improve the safety and efficacy of chemotherapy. One promising approach is the use of theranostic multifunctional carbon nanotubes (mf-CNTs) as a carrier for potent therapeutics in the diagnosis and treatment of various types of cancers. The functionalization characteristics of carbon nanotubes provide a powerful platform for the fabrication of suitable materials, such as therapeutic agents, imaging agents, and specific ligands. The ability of mf-CNTs to deliver small molecules and macromolecules, enable real-time imaging of tumours and targeted drug delivery, has made them a highly sought-after carrier among other nanocarriers. The physicochemical and biopharmaceutical properties of mf-CNTs, such as their significant uptake by specific tumour cells, long time blood circulation, complete elimination through the body, and biocompatibility, indicate a promising approach for anticancer therapy with highly toxic and potent anticancer agents. Therefore, the therapeutic uses of multifunctional CNTs based nanoplatform have tremendous potential for the treatment of cancers in the future. These advancements in nanotechnology have the potential to revolutionize cancer treatment and provide patients with a more effective and safer approach to combating this devastating disease.

Magnolin Inhibits Paclitaxel-Induced Cold Allodynia and ERK1/2 Activation in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anti-cancer drugs. The main symptoms often include sensory disturbances and neuropathic pain, and currently there is no effective treatment for this condition. This study aimed to investigate the suppressive effects of magnolin, an extracellular signal-regulated kinase (ERK) inhibitor substance derived from a 95% EtOH extract of the seeds of Magnolia denudata, on the symptoms of CIPN. A taxol-based anti-cancer drug paclitaxel (PTX) was repeatedly injected (2 mg/kg/day, total 8 mg/kg) into mice to induce CIPN. A neuropathic pain symptom was assessed using a cold allodynia test that scores behaviors of licking and shaking paw after plantar administration of acetone drop. Magnolin was administered intraperitoneally (0.1, 1, or 10 mg/kg) and behavioral changes to acetone drop were measured. The effect of magnolin administration on ERK expression in the dorsal root ganglion (DRG) was investigated using western blot analysis. The results showed that the repeated injections of PTX induced cold allodynia in mice. Magnolin administration exerted an analgesic effect on the PTX-induced cold allodynia and inhibited the ERK phosphorylation in the DRG. These results suggest that magnolin could be developed as an alternative treatment to suppress paclitaxel-induced neuropathic pain symptoms.

3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60–80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.

Effects of Antibacterial Agents on Cancerous Cell Proliferation.

Myelosuppression, a side effect of anticancer drugs, makes people more susceptible to infectious diseases by compromising the immune system. When a cancer patient develops a contagious disease, treatment with an anticancer drug is suspended or postponed to treat the infectious disease. If there was a drug that suppresses the growth of cancer cells among antibacterial agents, it would be possible to treat both infectious diseases and cancer. Therefore, this study investigated the effect of antibacterial agents on cancer cell development. Vancomycin (VAN) had little effect on cell proliferation against the breast cancer cell, MCF-7, prostate cancer cell, PC-3, and gallbladder cancer cell, NOZ C-1. Alternatively, Teicoplanin (TEIC) and Daptomycin (DAP) promoted the growth of some cancer cells. In contrast, Linezolid (LZD) suppressed the proliferation of MCF-7, PC-3, and NOZ C-1 cells. Therefore, we found a drug that affects the growth of cancer cells among antibacterial agents. Next, when we examined the effects of the combined use of existing anticancer and antibacterial agents, we found VAN did not affect the growth suppression by anticancer agents. However, TEIC and DAP attenuated the growth suppression of anticancer agents. In contrast, LZD additively enhanced the growth suppression by Docetaxel in PC-3 cells. Furthermore, we showed that LZD inhibits cancer cell growth by mechanisms that involve phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway suppression. Therefore, LZD might simultaneously treat cancer and infectious diseases.

Education Aimed at Patient Safety Management of Chemotherapy Conducted at University Education Sites

The School Education Law was revised in 2006, and the university pharmacy education system and the national pharmacist examination system were changed. In line with the advancement of medical technology and the division of labor, 16 years have passed since the length of undergraduate pharmacy education was extended from 4 to 6 years in order to foster highly qualified pharmacists. During this period, the curriculum for practical training has been revised, and lectures and exercises focused on clinical education have been incorporated to foster pharmacists who can be useful in the medical field. In the area of cancer drug therapy, the university provides students with opportunities to learn about the basic mechanisms of action and side effects of anticancer drugs, but there is little coverage of clinical guidelines and pharmacological management of the latest therapies, such as cancer immunotherapy. Prior to my arrival at Hoshi University, I was involved in clinical work and clinical research at an oncology hospital for 13 years. Since my arrival, I have been exploring the gap between oncology pharmacotherapy and pharmacy education, and have been working to fill it. We have incorporated new curricula, such as exercises in formulation suggestions, lectures to deepen understanding of guidelines and supportive care, and information on the latest cancer drug therapies, such as cancer immunotherapy. This paper outlines the pharmacy education required to produce pharmacists who can practice safe cancer drug therapy.

PEGylated reduced graphene oxide as nanoplatform for targeted gene and drug delivery

Combination therapies involving anticancer drugs and gene therapy agents have become a potential treatment for different cancer types reducing the side effects of anticancer drugs while enhancing their effectiveness. Here, we improved our previously published strategy that uses multiple pyrene groups of poly(ethylene glycol) (PEG) brushed graft copolymer to enhance the biological use of reduced graphene oxide (rGO) and introduced an azide containing monomer in the copolymer for further modifications to carry hydrophobic drugs like doxorubicin (Dox) along with oligonucleotides such as small interfering RNAs (siRNA). Azide functionality on the side chain of coated copolymer enables not only the conjugation of alkyne end group functional cationic copolymer but also allows the addition of targeting moieties like EPPT1 peptide that selectively binds MUC1, an early hallmark of tumorigenesis. To achieve the outlined carrier, first, a well-defined PEG, pyrene, azide, and methyl methacrylate containing poly[(poly(ethylene glycol) methyl ether methacrylate)-co-(3-azidopropyl methacrylate)-co-(methyl methacrylate)-co-(1-pyrenemethyl methacrylate)] (P(PEGMA-co-AzPMA-co-MMA-co-PMA), PAMP) copolymer was synthesized via ATRP and through its azide group another well-defined, cationic copolymer composed of hexyl methacrylate, 2-dimethyl amino ethyl methacrylate, and N,N,N-trimethylaminoethyl methacrylate iodide (P(HMA-co-DMAEMA-co-TMAEMA) was coupled via copper-catalyzed azide-alkyne cycloaddition (CuAAC). This cationic copolymer was synthesized using a unique ATRP initiator to allow click reaction as described as well as pH-dependent degradation through its hydrazone linkage. The obtained graft copolymer (PAMP-CP) was then coated on a graphene oxide (GO) surface and GO was in situ reduced to rGO (PAMP-CP-rGO) to have an rGO-based PEGylated nanoplatform that can be highly loaded with doxorubicin and successfully condensed with anti-GAPDH siRNA. Consequently, this dual drug delivery nanoplatform showed a controlled drug release that switches between release kinetics by the change of pH and high transfection efficiency regarding targeted GAPDH protein levels. Moreover, in vitro cytotoxicity tests showed that EPPT1-targeted Dox-loaded PAMP-CP-rGO shows concentration-dependent and selective cellular toxicity against cancer cells compared to its non-targeted versions. These results demonstrated the potential of a highly adaptable, multifunctional nanoplatform for safely and selectively transporting different cargoes to the tumor site.

Drawbacks in the efficient monitoring of gold nanoparticle-based cisplatin delivery systems formation by HPLC-ICP-MS.

Since chemotherapy suffers many limitations related to side effects of anticancer drugs (e.g. cisplatin - CDDP), nanoparticles are probed as carriers in targeted drug delivery. Gold nanoparticles (AuNPs) are broadly investigated due to their biocompatibility, nontoxicity, and tunable surface. Despite many AuNPs-cisplatin systems (AuNP-CS) reports found in the literature, only a few include studies of their synthesis and formation efficiency using analytical tools providing simultaneously qualitative and quantitative analytical information. Therefore, this research continues our previous study of AuNP-CS formation investigated by capillary electrophoresis with inductively coupled plasma mass spectrometry (ICP-MS). Namely, it presents the analogical approach but employs the coupling of another separation technique: isocratic reversed-phase high-performance liquid chromatography. The study concerns the difficulties of analytical method optimization path and contains a discussion of the observed problematic issues related to the analysis and preparation of AuNP-CS. Moreover, the presented work confronts the performance and applicability of both tools for the scrutiny of AuNP-CS, especially considering the comparison of their resolution power.