Chemical Anticancer Drugs Research Articles

Application of injectable hydrogels in cancer immunotherapy.

Immunotherapy is a revolutionary and promising approach to cancer treatment. However, traditional cancer immunotherapy often has the disadvantages of limited immune response rate, poor targeting, and low treatment index due to systemic administration. Hydrogels are drug carriers with many advantages. They can be loaded and transported with immunotherapeutic agents, chemical anticancer drugs, radiopharmaceuticals, photothermal agents, photosensitizers, and other therapeutic agents to achieve controlled release of drugs, extend the retention time of drugs, and thus successfully trigger anti-tumor effects and maintain long-term therapeutic effects after administration. This paper reviews recent advances in injectable hydrogel-based cancer immunotherapy, including immunotherapy alone, immunotherapy with combination chemotherapy, radiotherapy, phototherapy, and DNA hydrogel-based immunotherapy. Finally, we review the potential and limitations of injectable hydrogels in cancer immunotherapy.

Resveratrol as a Chemopreventive Agent in Lung Cancer Therapy

For decades, lung cancer has been the most widespread cancer in the world and the leading cause of cancer death. Lung malignancy is the superior cause of death in Indonesia, accompanying the second topmost number of new cases. The low survival rate of lung cancer patients reflects the therapy's low success rate due to side effects and cancer cells' resistance to chemotherapy and radiotherapy. Combination therapy, which includes the use of chemopreventive agents, can reduce the risk of side effects and resistance. Natural product-based chemopreventive agents used together with accompanying chemical anti-cancer drugs and/or actinotherapy can overcome cancer cell resistance, improve therapy effectiveness, and reduce side effects. Resveratrol is a compound belonging to the non-flavonoid polyphenolic group contained, particularly in vine fruits, berries, and some nuts. Resveratrol exhibits anti-cancer activity, according to considerable in vitro and in vivo studies, and hence has what it takes to be reasonably applied as a chemopreventive compound. The discovery of resveratrol's chemopreventive mechanism against lung cancer is expected to enable the development of a chemopreventive compound that can be used together with accompanying chemical anti-cancer drugs and/or actinotherapy.

Antioxidant and antineoplastic activities of leaves of Hibiscus sabdariffa Lina against Ehrlich ascites carcinoma cells in Swiss albino mice

Background: Since chemical anticancer drugs are found to have adverse effect on body, nowadays people are motivated towards natural agents to treat cancer. Fruits and vegetables are potential source of natural anticancer agents that protect our body against cancer by scavenging and neutralizing free radicals. Objective: The study was aimed to explore antioxidant and anticancer properties of methanolic extract of leaves of Hibiscus sabdariffa L. (MEHSL). Methods: In vitro assays were used to examine the different types of phytochemical content and antioxidant properties of MEHSL. In vitro and in vivo assays were performed to study the effects of MEHSL on Ehrlich ascites carcinoma (EAC) cells. Chemical constituents were also analyzed by GC–MS. Results: Total phenolic and flavonoid contents of MEHSL were found to be 26.23±0.30 and 131.13±1.40 mg/g of extract in terms of gallic acid and catechin equivalent, respectively. The MEHSL exhibited remarkable scavenging effect on DPPH, ABTS, nitric oxide scavenging activity and inhibition of lipid peroxidation with IC50 values 6.768, 11.54, 29.84 and 17.55, respectively, compared to the positive control, catechin. In vitro cytotoxic study shows that MEHSL reduced the viability of Ehrlich ascites carcinoma (EAC) cells in dose dependent manner. In in vivo, significant inhibition of EAC cells growth and proliferation, reduction of tumor weight and increased of survival time of EAC-bearing mice were noted following by intraperitoneal MEHSL treatment at the doses of 5 and 10 mg/ kg/day (p<0.05). Moreover, the MEHSL also altered the depleted hematological parameters like RBC, WBC, and percentage of hemoglobin (Hb %) of EAC bearing mice towards normal. Furthermore, administration of MEHSL induced apoptosis of EAC cells as observed in Hoechst-33342 stained cells under fluorescence microscope. Hexadecanoic acid, methyl ester (2.845%), hexadecanoic acid (9.858%), linolenic acid methyl ester (2.142%), 9,12- -octadecadien -1-Ol (2.063), alpha-glyceryl linolenate (6.138), arachidic acid (23.280%) and phthalic acid, 6-ethyloct-3-yl 2-ethylhexyl ester (74.926%) were identified as the major constituents of MEHSL by GC-MS analysis. Conclusion: Findings of the present study suggested that the leaves of H. sabdariffa can therefore be considered as a promising resource in cancer chemotherapy. Bangladesh Med Res Counc Bull 2021; 47(2): 156-164

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.

In vivo murine breast cancer targeting by magnetic iron nanoparticles involving L. GG cytoplasmic fraction.

Objective(s):Use of chemical anti-cancer drugs frequently creates serious side effects. However, probiotics are natural and treat different kinds of cancer without undesired effects.Materials and Methods:In this study, a nano delivery system was planned to transport the Lactobacillus rhamnosus GG (L. GG) cytoplasmic fraction (Cf) to cancerous tissue in a mouse model. Magnetic iron nanoparticles (MINPs) were synthesized and loaded with L. GG-Cf(0, 0.312, 0.625, 1.25, and 2.5 mg/ml) and were administrated for three weeks to treat experimentally induced murine breast cancer in a constant magnetic field. At the end of the trial, the treating efficacy of this complex molecule was evaluated via western blotting, immunohistochemistry, and qPCR.Results:Results showed that MINPS can deliver and accumulate L. GG-Cf in cancer tissue, and reduce the size and volume of the tumors. Additionally, in cancer tissues of treated mice with 2.5 mg/ml of Cf-MINPs, significantly induced apoptosis was seen compared with untreated mice (control), and our data proved that this induction may be due to the caspase-3 pathway.Conclusion:L. GG-Cf could treat murine breast cancer, and MINPs are a suitable candidate for drug delivery because of their safety, uniformity, and magnetic properties.

In use stability of chemical anticancer drugs and biologics

Background. For hospital pharmacists and nurses it is critical to have real data about the stability of injectable drugs in practical situations: opened drug formulation, after the reconstitution of lyophilized production or after the dilution in various vehicles. Unfortunately, these data are seldom available. The manufacturer’s stability data are usually quoted as “stable for 24 hours at 4 °C” not for the true reasons, but considering the possible bacterial contamination or due to the fact that stability tests were only conducted during a very short period. This problem is of paramount importance for therapeutic proteins, mainly monoclonal antibodies, because the latter are very expensive.
 Objective. To define the in use stability of anticancer drugs.
 Materials and methods. Analysis of literature data on this topic; own study on diluted rituximab stability.
 Results and discussion. Biologic drugs have revolutionized the treatment and prevention of many debilitating and life-threatening diseases. Biologics are much bigger and have a much more complicated structure than classical drugs. Principal causes of biologics’ instability include temperature changes, dilution, absorption, oxidation, shaking and shearing etc. Protein instability can be divided into physical and chemical instability. The former includes aggregation, denaturation and absorption on surfaces, and the latter – desamidation, disulfide bonds breakage and formation, oxidation, hydrolysis, isomerization, non-disulfide cross-linking, and deglycosylation. Instability of anticancer drugs and biologicals can lead to their toxicity, immunogenicity and efficacy loss. Instability can be overcome by the centralization of pharmacy handling, but firstly it needs to be thoroughly studied with the help of modern methods. The own study has revealed that the diluted rituximab is stable up to 6 months in polyolefin bags stored at 4 or 22 °C. The preparations can be realized without any problems. There also no fear of instability in case of thermal excursions. Such findings if introduced in practice can save about 150,000 euros a year.
 Conclusions. 1. In-use analysis of proteins requires several methods. 2. Instabilities are divided into physical and chemical. 3. Aggregation is an initial response to any stress and must be completely eliminated.

Finding and isolation of novel peptides with anti-proliferation ability of hepatocellular carcinoma cells from mung bean protein hydrolysates

Abstract Mung bean protein hydrolysate has shown some biological properties. Isolated mung bean proteins were hydrolyzed by papain and tested for antiproliferative effects on cancer cells. It was confirmed that the mung bean peptides could inhibit the proliferation of tumor cells in mice, without the side effects of chemical anticancer drugs, and that the mung bean peptides promoted apoptosis of HepG2 cells and arrested the cell cycle in the S phase at a low dose and the G0/G1 phase at a high dose. Subsequently, the hydrolysates were purified through ultrafiltration and Sephadex G-15 gel chromatography. Fraction A, obtained following size-fractionation (

Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system

Targeting delivery of anticancer agents is a promising field in anticancer therapy. Inherent tumor-tropic and migratory properties of mesenchymal stem cells (MSCs) make them potential vehicles for targeting drug delivery systems for tumors. Although, MSCs have been successfully studied and discussed as a vehicle for cancer gene therapy, they have not yet been studied adequately as a potential vehicle for traditional chemical anticancer drugs. In this study, we have engineered MSCs as a potential targeting delivery vehicle for paclitaxel (TAX)-loaded nanoparticles (NPs). The size, surface charge, starving time of MSCs, incubating time and concentration of NPs could influence the efficiency of NPs uptake. In vitro release of TAX from CTS (chitosan)-TAX-NP-MSCs and the expression of P-glycoprotein demonstrated that release of TAX from MSCs might involve both passive diffusion and active transport. In vitro migration assays indicated that MSCs at passage number 3 have the highest migrating ability. Although, the migration ability of CTS-TAX-NP-MSCs could be inhibited by uptake of CTS-TAX-NPs, this ability could recover 6 days after the internalization.