Strategy For Cancer Therapy Research Articles

DNA nanotechnology-based strategies for gastric cancer diagnosis and therapy.

Gastric cancer (GC) is a formidable adversary in the field of oncology. The low early diagnosis rate of GC results in a low overall survival rate. Therefore, early accurate diagnosis and effective treatment are the key to reduce the mortality of GC. With the advent of nanotechnology, researchers continue to explore new possibilities for accurate diagnosis and effective treatment. One such breakthrough is the application of DNA nanotechnology. In this paper, the application of exciting DNA nanomaterials in the diagnosis and treatment of GC is discussed in depth. Firstly, the biomarkers related to GC and the diagnostic strategies related to DNA nanotechnology are summarized. Second, the latest research progress of DNA nanomaterials in the GC targeted therapy are summarized. Finally, the challenges and opportunities of DNA nanomaterials in the research and clinical application of GC are prospected.

Multi-drug sequential release systems: Construction and application for synergistic tumor treatment.

In tumor treatment, the sequence and timing of drug action have a large influence on therapeutic efficacy. Multi-drug sequential release systems (MDSRS) enable the sequential and/or on-demand release of multiple drugs following the single administration of a therapeutic agent. Several researchers have explored MDSRS, providing fresh strategies for synergistic cancer therapy. This review article first introduces the main characteristics of MDSRS. It then elaborates on the design principles of MDSRS. Subsequently, it summarizes the various structures of carriers used for constructing MDSRS, including core-shell structure, Layer-by-layer structure, Janus structure and hydrogel. Next, through specific examples, the article emphasizes the application of MDSRS in cancer treatment, focusing on their role in remodeling the tumor microenvironment (TME) and enhancing therapeutic effects through multiple mechanisms. Finally, the article discusses the current limitations and challenges of these systems and proposes potential future solutions. Overall, this review underscores the importance of the sequence and timing of drug therapy in cancer treatment, providing valuable theoretical and technical guidance for pharmaceutical research.

RES-CMCNPs Enhance Antioxidant, Proinflammatory, and Sensitivity of Tumor Solids to γ-irradiation in EAC-Bearing Mice.

Resveratrol (Res) is a bifunctional compound found in numerous plants, including grapes and mulberries. Nanotechnology has promising applications in medicine. The ability of various nanomaterials to serve as radiosensitizers against tumor cells were reported in several manuscripts. The present investigation aimed to assess the antitumor and radiosensitizing effects of Res-CMCNPs on EAC-bearing mice. Res-CMCNPs have been developed using the CMC emulsification cross-linking technique. Entrapment efficiency (%), particle size, Polydispersity index and ZETA potential, UV, FTIR spectra, and drug release were evaluated and described for RES-CMCNPs. The radiosensitizing properties of RES-CMCNPs were also evaluated in vitro and in vivo against EAC-carrying rodents. The LD50 of Res-CMCNPs was estimated and its 1/20 LD50 was prepared for treating EAC transplanted mice. The results revealed that the Res-CMCNPs exhibited a high entrapment efficiency (85.46%) and a size of approximately 184.60 ±17.36 nm with zeta potential value equals -51.866 mv. Also, the UV spectra of Res and Res-CMCNPs have strong absorption at 225 and 290 nm. The percentage of resveratrol release at pHs 5.8 and 7.4 was found to be 56.73% and 51.60%, respectively, after 24 h at 100 rpm. Also, the FTIR analysis confirmed the chemical stability of resveratrol in Res-CMCNPs cross-linking. The IC50 values of Res-CMCNPs against EAC cells viability were 32.99, 25.46, and 22.21 μg after 24-, 48- and 72 h incubation, respectively, whereas those of Res- CMCNPs in combination with γ-irradiation after 6-, 10 and 12-mins exposure were 24.07, 16.06 and 7.48 μg, respectively. Also, the LD50 of Res-CMCNPs was 2180 mg/kg.b.w. The treatment of EAC-bearing mice with Res-CMCNPs plus γ-irradiation improved plasma levels of NO, caspase-3, P53 and NF-kB levels as well as liver MDA, GSH, SOD, CAT, LT-B4, aromatase, Bax, Bcl2 and TGF-β levels and exhibited more significant anticancer activity than administration of Res- CMCNPs and/or exposure to γ-irradiation individually. On the other hand, administration of Res- CMCNPs in combination with γ-irradiation attenuated liver mRNAs (21, 29b, 181a, and 451) gene expression. Grafting resveratrol onto carboxymethyl chitosan appears to be a promising strategy for cancer therapy as a radiosensitizer, potentiating tumor cells' sensitivity to radiation by improving levels of proinflammatory features and antioxidant biomarkers.

Regulatory function of endoplasmic reticulum stress in colorectal cancer: Mechanism, facts, and perspectives.

Colorectal cancer (CRC) is an exceedingly common and profoundly impactful malignancy of the digestive system, posing a grave threat to human health. Endoplasmic reticulum stress (ERS) is an intracellular biological reaction that mobilizes the unfolded protein response (UPR) to tackling dysregulation in protein homeostasis. This process subtly modulates the cell to either restore normal cellular function or steer it towards apoptosis. The high metabolic demands of CRC cells sculpt a rigorous tumor microenvironment (TME), compelling CRC cells to experience ERS. Adaptive responses induced by mild ERS furnish the necessary conditions for the survival of CRC cells, whereas the cell death mechanisms triggered by sustained ERS could be considered a prospective strategy for cancer therapy. Considering the complex regulation of ERS in cancer development, this article offers a comprehensive review of the molecular mechanisms through which ERS influences CRC fate. It provides crucial insights for exploring the role of ERS in the occurrence and progression of CRC, laying a new theoretical foundation for devising precise therapeutic strategies targeting ERS. Furthermore, by synthesizing extensive clinical and preclinical studies, we delve into therapeutic strategies targeting ERS, including the potential of targeting ERS in immunotherapy, the utilization of native compounds, advancements in proteasome inhibitors, and the potential synergies of these strategies with traditional chemotherapy agents and emerging therapeutic approaches.

Targeting intracellular cancer proteins with tumor-microenvironment-responsive bispecific nanobody-PROTACs for enhanced therapeutic efficacy.

Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity. In this study, we engineered BumPeD, a novel bispecific nanobody-targeted PROTACs-like platform, by fusing two nanobodies with a Furin protease cleavage site (RVRR) and a degron sequence (ALAPYIP or KIGLGRQKPPKATK), enabling the tumor microenvironment to direct the degradation of intracellular proteins. We utilized KN035 and Nb4A to target PD-L1(programmed death ligand 1) on the cell surface and intracellular Survivin, respectively. In vitro experiments showed that BumPeD triggers Survivin degradation via the ubiquitin-proteasome pathway, inducing tumor apoptosis and suppressing bladder tumor cell proliferation and migration. In vivo experiments further confirmed BumPeD's robust anti-tumor efficacy, underscoring its potential as a precise protein degradation strategy for cancer therapy. Our platform provides a systematic approach to developing effective and practical protein degraders, offering a targeted theoretical basis and experimental support for the development of novel degradative drugs, as well as new directions for cancer therapy.

Targeting p62 by sulforaphane promotes autolysosomal degradation of SLC7A11, inducing ferroptosis for osteosarcoma treatment.

Osteosarcoma (OS) is the most prevalent malignant bone tumor in children and adolescents worldwide. Identification of novel therapeutic targets and development of targeted drugs are one of the most feasible strategies for OS treatment. Ferroptosis, a recently discovered mode of programmed cell death, has been implicated as a potential strategy for cancer therapy. Sulforaphane (SFN), the main bioactive compound derived from cruciferous vegetables, has shown potential anti-cancer effects with negligible toxicity. However, the role of ferroptosis in the effect of SFN on OS remains unknown. In the present study, we found that SFN acted as a potent ferroptosis inducer in OS, which was demonstrated by various inhibitors of cell death. The SFN-induced ferroptotic cell death was characterized by elevated ROS levels, lipid peroxidation, and GSH depletion, which was dependent on decreased levels of SLC7A11. Mechanically, SFN directly targeted p62 protein and enhanced p62/SLC7A11 protein-protein interaction, thereby promoting the lysosomal degradation of SLC7A11 and triggering ferroptosis. Notably, both subcutaneous and intratibial OS models in nude mice confirmed the ferroptosis associated anti-cancer efficacy of SFN in vivo. Hence, our findings demonstrate that SFN exerts its anti-cancer effects through inducing SLC7A11-dependent ferroptosis in OS, providing compelling evidence for the application of SFN in OS treatment.

A tumor microenvironment-responsive multifunctional MoS2-Ru nanocatalyst with photothermally enhanced chemodynamic activity.

Targeting the unique characteristics of the tumor microenvironment (TME) has emerged as a highly promising strategy for cancer therapy. Chemodynamic therapy (CDT), which leverages the TME's intrinsic properties to convert H2O2 into cytotoxic hydroxyl radicals (˙OH), has attracted significant attention. However, the effectiveness of CDT is often limited by the catalytic efficiency of the materials used. Although Molybdenum disulfide (MoS2) exhibits remarkable chemodynamic and photothermal properties, its limited efficiency in catalyzing the conversion of endogenous H2O2 into ˙OH radicals remains a significant challenge. To overcome this, we developed a nanocomposite of MoS2 and ruthenium (MoS2-Ru), by incorporating Ru into MoS2 nanosheets. The MoS2-Ru nanocomposite demonstrated significantly enhanced catalytic activity at a low concentration (500 ng mL-1), whereas the same effect was achieved only with 20 μg mL-1 of MoS2. The low Michaelis-Menten constant (Km) of 4.69 mM further confirmed the superior catalytic activity of the nanocomposite, indicative of the enhanced enzyme-like activity. Additionally, the integration of Ru in MoS2 reduced the bandgap to 1.18 eV, facilitating near-infrared (NIR) absorption with a high conversion efficiency of 41%. Electron paramagnetic resonance (EPR) analysis confirmed robust ˙OH radical generation driven by the combined chemodynamic and photothermal effects. In vitro studies using triple-negative breast cancer (TNBC) cells validated the synergistic activity of CDT and PTT, demonstrating significant ˙OH radical production under TME conditions, leading to effective cancer cell death. This study underscores the potential of MoS2-Ru nanocomposites as a versatile and powerful platform for multimodal cancer therapy, seamlessly integrating CDT and PTT to achieve synergistic, precise, and highly effective treatment outcomes.

Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth

IntroductionVitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity.MethodsLiposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed.ResultsVD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile.DiscussionLiposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration.

Abstract IA10: Immune side effects in ferroptosis-targeted therapy

Abstract Ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising strategy in cancer therapy, complementing established modalities such as chemotherapy, immunotherapy, and radiotherapy. While the mechanisms of ferroptosis are highly context-dependent, the classical approach to inducing ferroptosis involves targeting the GPX4 (glutathione peroxidase 4) pathway. GPX4 is a critical enzyme that detoxifies lipid hydroperoxides (L-OOH) by reducing them to non-toxic lipid alcohols (L-OH) using glutathione (GSH) as a cofactor, thereby preventing lipid peroxidation and ferroptotic cell death. Although targeting GPX4 effectively induces ferroptosis in cancer cells, its widespread expression in both tumor and normal cells presents challenges. Direct inhibition of GPX4 can lead to unintended immune cell death, potentially impairing antitumor immunity by reducing the activity of cytotoxic T cells and other immune effectors essential for robust immune responses. This immunosuppressive effect could undermine the therapeutic benefits of ferroptosis-targeted therapies. To overcome this limitation, alternative strategies have been explored. For instance, non-direct targeting of GPX4, such as inducing TRIM25-mediated degradation of GPX4, has shown promise in selectively killing cancer cells while sparing normal tissues and preserving immune function. This approach minimizes toxicity and maintains the activity of key immune cells, including cytotoxic T cells, enhancing the overall efficacy of ferroptosis-based treatments. Understanding the potential risks and immune-related side effects of ferroptosis-targeted therapies is critical for their successful clinical translation. Citation Format: Daolin Tang. Immune side effects in ferroptosis-targeted therapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA10

Natural Compounds and Histone Deacetylase Inhibitors: A Combined Approach Against mCRPC Cells

Background: Sodium butyrate (NaBu), a short-chain fatty acid, modulates global gene expression through histone deacetylase (HDAC) inhibition, suppressing proliferation and inducing apoptosis in various cancers. Rutin (RUT), a polyphenolic flavonoid found in many plants, exhibits notable anticancer properties. Combining chemotherapeutic agents with natural polyphenols represents a promising strategy for cancer therapy. This study aims to evaluate, for the first time, the potential effects of NaBu and RUT combination therapy on metastatic castration-resistant prostate cancer (mCRPC) cells. Methods: PC-3 cells were treated with varying concentrations of NaBu, RUT, and their combinations. Cell viability was assessed using the WST-1 assay. Based on combination index values, selected treatments were further analyzed for apoptosis (Annexin V assay), intracellular reactive oxygen species (ROS) production, mRNA expression levels, and changes in cell and nuclear morphology. Results: The combined treatment of NaBu and RUT significantly reduced cell viability compared to individual treatments. Enhanced apoptotic induction and elevated ROS levels were observed in combination-treated cells, alongside notable changes in cellular and nuclear morphology and mRNA expression levels. Conclusions: NaBu and RUT combination therapy exhibits a synergistic anticancer effect in mCRPC cells by inhibiting cell viability, inducing apoptosis, and increasing ROS production. These findings suggest a promising therapeutic approach that warrants further investigation to elucidate the underlying molecular mechanisms and assess its potential in preclinical and clinical settings.

Study of Histotripsy With Subsequent Heating on In Vitro VX2 Cancer Cells.

Focused ultrasound has emerged as a precise and minimally invasive modality for effective cancer treatment. In this study, we propose a novel method that integrates the mechanical effects of focused ultrasound, known as histotripsy, with heating to enhance both the immediate and sustained cytotoxic effects on cancer cells. Our investigation focused on VX2 cancer cells in suspension, examining five experimental groups: blank control, negative control, heating alone, histotripsy alone, and histotripsy with subsequent heating. B-mode ultrasound imaging was utilized to visualize cavitation bubble cloud formation and its motion during histotripsy. The suspension was contained in individually sealed compartments obtained from bubble wrap (referred to as bubble wrap compartments) embedded within the agarose phantom. Residual living cells were examined immediately after treatment and cultured for 96 hours to analyze the growth patterns. Additionally, CFDA SE staining was employed to assess cell proliferation. Furthermore, both intracellular and extracellular heat shock protein 70 (HSP70) levels were measured to investigate the potential initiation of an immune response. The combination of histotripsy and subsequent heating significantly reduced the normalized concentration of living cells immediately after treatment. It also decreased the proliferation rate of residual cells compared with the other experimental groups. Histotripsy with subsequent heating also increased the generation and release of HSP70, which might potentially enhance an innate anti-tumor immune response in vivo. Histotripsy and subsequent heating improved the immediate lethal impact on VX2 cancer cells and curtailed the proliferation of residual cancer cells in suspension. This study presents a promising strategy for cancer therapy in the future.

Niosomal Encapsulation of Anti-Cancer Peptides: A Revolutionary Strategy in Cancer Therapy.

Cancer treatment has evolved significantly over the years, incorporating a range of modalities including surgery, radiation, chemotherapy, and immunotherapy. However, challenges such as drug resistance, systemic toxicity, and poor targeting necessitate innovative approaches. Peptides have gained attention in cancer therapy due to their specificity, potency, and ability to modulate various biological pathways. Peptide-based drugs can act as hormones, enzyme inhibitors, or targeting ligands, contributing to their versatile role in cancer treatment. However, peptides face several challenges, including instability, rapid degradation, and poor bioavailability. One promising strategy is the use of niosomal delivery systems for peptidebased therapies. Niosomes, which resemble liposomes in structure, are vesicles based on nonionic surfactants. They are composed of a bilayer created through the self-assembly of non-ionic surfactants in water, enabling them to encapsulate hydrophilic, lipophilic, and amphiphilic drugs. Their unique properties, such as biocompatibility, biodegradability, and ability to encapsulate diverse therapeutic agents, make them suitable for drug delivery applications. This review aims to explore how the niosomal preparation of peptides can revolutionize oncology drugs by overcoming critical challenges like drug resistance, systemic toxicity, poor targeting, instability, rapid degradation, and low bioavailability. This review aims to explore how niosomes can specifically address key limitations in cancer therapy, including targeting, bioavailability, and stability of peptide-based drugs. By consolidating recent advancements, the review sheds light on how niosomal encapsulation can overcome barriers in cancer treatment and improve therapeutic outcomes for patients.

EGFR-targeting RNase A-cetuximab antibody-drug conjugate induces ROS-mediated apoptosis to overcome drug resistance in KRAS mutant cancer cells

Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR. In KRAS mutant SW-480 cells, RN-PEG-Cet significantly reduced cell viability at lower doses, with an IC50 of 11.7 µg/mL at 72 h. Compared to free Cet, RN-PEG-Cet demonstrated a ~ 2-fold increase in apoptosis and a ~ 3.5-fold increase in ROS production. The conjugate also disrupted the Nrf2/Keap1 pathway, with a significant upregulation of Keap1 (FC = 3.7, p ≤ 0.01) and downregulation of Nrf2 (FC = 3.3, p < 0.01), highlighting its role in impairing antioxidant defenses and promoting ROS-mediated cytotoxicity. These findings emphasize the potential of RN-PEG-Cet as a novel therapeutic approach for KRAS mutant CRC, offering superior apoptosis induction and targeted cytotoxicity compared to conventional therapies. This ADC could represent a new strategy for improving CRC treatment outcomes by effectively overcoming resistance mechanisms.

Marine-Derived Compound Targeting mTOR and FGFR-2: A Promising Strategy for Breast, Lung, and Colorectal Cancer Therapy.

The marine habitat is a plentiful source of diverse, active compounds that are extensively utilised for their medicinal properties. Pharmaceutical trends have currently changed towards utilising a diverse range of goods derived from the marine environment. This study aimed to examine the inhibitory effects of bioactive chemicals derived from marine algae and bacteria. The identification of these compounds was carried out through the process of Gas Chromatography-Mass Spectrometry (GC-MS) profiling. Subsequently, these compounds were subjected to docking simulations against a specific set of target proteins that are known to be frequently overexpressed in three distinct types of cancer. From the docking results, the ligand 1,4:3,6:5,7-Tribenzal-beta-mannoheptitol was found to be effective against the proteins mTOR (PDB ID: 4JSV) and FGFR2 (PDB ID:6V6Q). The findings of this study highlight the significant benefits offered by the tool under investigation, which effectively enhances the efficiency of the docking procedures. These compounds hold significant potential for further development and exploration in the field of cancer therapeutics.

Targeting KAT6A/B as a New Therapeutic Strategy for Cancer Therapy.

The lysine acetyltransferase 6A (KAT6A, MOZ, MYST3) is a member of the MYST family of protein acetyltransferases, which are essential for different biological processes such as craniofacial, embryonic, stem cell development, and hematopoiesis. KAT6A is an oncogene in human acute myeloid leukemia (AML), and KAT6A overexpression in AML is associated with metastases and poor prognoses. Furthermore, KAT6A mutations play an important role in cancer formation and progression and result in therapeutic resistance in both hematopoietic malignancies and solid tumors. In this review, we discuss the structural and biological functions of KAT6A and summarize the influence of KAT6A in the development of various tumors. In addition, the recent KAT6A/B inhibitors, their anticancer activities, challenges, and perspective of developing KAT6A/B inhibitors as anticancer drug candidates were introduced.

PdRu bimetallic nanoalloys with improved photothermal effect for amplified ROS-mediated tumor therapy.

An emerging strategy in cancer therapy involves inducing reactive oxygen species (ROS), specifically within tumors using nanozymes. However, existing nanozymes suffer from limitations such as low reactivity, poor biocompatibility, and limited targeting capabilities, hindering their therapeutic efficacy. In response, the PdRu@PEI bimetallic nanoalloys were constructed with well-catalytic activities and effective separation of charges, which can catalyze hydrogen peroxide (H2O2) to toxic hydroxyl radical (·OH) under near-infrared laser stimulation. Through facilitating electron transfer and enhancing active sites, the enhanced peroxidase-like (POD-like) enzymatic activity and glutathione (GSH) depletion abilities of nanozymes are boosted through a simple co-reduction process, leading to promising anti-tumor activity. The electron transfer between Pd and Ru of PdRu@PEI nanoalloys contributes to POD-like activity. Then, by oxidizing endogenous overexpressed GSH, enzymatic cycling prevents GSH from consuming ROS. Furthermore, the surface plasmon resonance effect of near-infrared laser on bimetallic nanoalloys ensures its photothermal performance and its local heating, further promoting POD-like activity. The integrated multi-modal therapeutic approach of PdRu@PEI has demonstrated significant anti-cancer effects in vivo studies. The nanozymes exhibit high catalytic efficiency and excellent biocompatibility, offering valuable insights for the development of nano-catalysts/enzymes for biomedical applications.

Integrative Machine Learning of Glioma and Coronary Artery Disease Reveals Key Tumour Immunological Links.

It is critical to appreciate the role of the tumour-associated microenvironment (TME) in developing strategies for the effective therapy of cancer, as it is an important factor that determines the evolution and treatment response of tumours. This work combines machine learning and single-cell RNA sequencing (scRNA-seq) to explore the glioma tumour microenvironment's TME. With the help of genome-wide association studies (GWAS) and Mendelian randomization (MR), we found genetic variants associated with TME elements that affect cancer and cardiovascular disease outcomes. Using machine learning techniques high dimensional data was analysed to obtain new molecular sub-types and biomarkers that are important for prognosis and treatment response. F3 was identified as a top regulator and revealed potential angiogenic and immunogenic characteristics within the TME that could be harnessed in immunotherapy. These results demonstrate the potential of machine-learning approaches in identifying and dissecting TME heterogeneity and informing treatment in precision oncology. This work proposes improving the immunotherapeutic response through targeted modulation of relevant cellular and molecular interactions.

Schiff bases of cellulose: Synthesis, characterization, and anticancer potency against hepatocellular carcinoma.

The development of innovative anticancer agents with minimal side effects is crucial. Polymeric Schiff bases have unique features that make them a promising option for therapeutic uses. They are well known for their biological properties, especially anticancer activity. Therefore, the current report describes the synthesis of Schiff bases derived from microcrystalline cellulose. Cellulose Schiff bases were synthesized through three steps. First, cellulose was periodate oxidized to produce dialdehyde cellulose (DAC). Afterwards, DAC was grafted with hyper-branched polyethylenimine (hPEI) to obtain aminated cellulose. Schiff bases were obtained by reacting hPEI-cellulose with various aldehydes. The final products were characterized by spectroscopic and thermal methods. The cellulose Schiff bases were evaluated for their anticancer activities, and it was observed that they were able to inhibit the growth of different types of cells. Importantly, one of the cellulose derivatives (SB4), which contains trimethoxy benzaldehyde moieties, was capable of inducing cell cycle arrest and apoptosis in hepatocellular carcinoma cells (Hep G2). Interestingly, SB4 could act as a pro-oxidant by inducing reactive oxygen species and oxidative stress with notable decline in the antioxidant system within Hep G2 cells. The results displayed that cellulose-based Schiff bases may offer a new strategy for liver cancer therapy.

Adipokines in Breast Cancer: Decoding Genetic and Proteomic Mechanisms Underlying Migration, Invasion, and Proliferation.

Adipokines, bioactive peptides secreted by adipose tissue, appear to contribute to breast cancer development and progression. While numerous studies suggest their role in promoting tumor growth, the exact mechanisms of their involvement are not yet completely understood. In this project, varying concentrations of recombinant human adipokines (Leptin, Lipocalin-2, PAI-1, and Resistin) were used to study their effects on four selected breast cancer cell lines (EVSA-T, MCF-7, MDA-MB-231, and SK-Br-3). Over a five-day proliferation phase, linear growth was assessed by calculating doubling times and malignancy-associated changes in gene and protein expression were identified using quantitative TaqMan real-time PCR and multiplex protein analysis. Migration and invasion behaviors were quantified using specialized Boyden chamber assays. We found significant, adipokine-mediated genetic and proteomic alterations, with PCR showing an up to 6-fold increase of numerous malignancy-associated genes after adipokine-supplementation. Adipokines further altered protein secretion, such as raising the concentrations of different tumor-associated proteins up to 13-fold. Effects on proliferation varied, however, with most approaches showing significant enhancement in growth kinetics. A concentration-dependent increase in migration and invasion was generally observed, with no significant reductions in any approaches. We could show a robust promoting effect of several adipokines on different breast cancer cells in vitro. Understanding the interaction between adipose tissue and breast cancer cells opens potential avenues for innovative breast cancer prevention and therapy strategies. Our findings indicate that antibodies against specific adipokines could become a beneficial component of clinical breast cancer treatment in the future.

An update on regulation and function of G protein-coupled receptors in cancer: A promising strategy for cancer therapy.

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in signal transduction and cellular communication. GPCR proteins are involved in a wide range of physiological processes, including cell growth, migration, and survival. Dysregulation of GPCR protein expression has been implicated in the pathogenesis of various diseases, including cancer, and GPCR proteins have been shown to modulate these processes in various types of cancer, highlighting their importance as potential therapeutic targets. In this review, we summarize the expression regulation of GPCRs in cancer cells, update the various ways by which the abnormal expression of GPCR protein affects the behavior of tumor cells, and discuss the current research directions and potentially facing problems of strategies on GPCR-targeting therapy.