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Membrane contact sites (MCS) are specialized regions where organelles are closely interconnected through membrane structures, facilitating the transfer and exchange of ions, lipids, and other molecules. This proximity enables a synergistic regulation of cellular homeostasis and functions. The formation and maintenance of these contact sites are governed by specific proteins that bring organelle membranes into close apposition, thereby enabling functional crosstalk between cellular compartments. In eukaryotic cells, lipids are primarily synthesized and metabolized within distinct organelles and must be transported through MCS to ensure proper cellular function. Consequently, MCS act as pivotal platforms for lipid synthesis and trafficking, particularly in cancer cells and immune cells within the tumor microenvironment, where dynamic alterations are critical for maintaining lipid homeostasis. This article provides a comprehensive analysis of how these cells exploit membrane contact sites to modulate lipid synthesis, metabolism, and transport, with a specific focus on how MCS-mediated lipid dynamics influence tumor progression. We also examine the differences in MCS and associated molecules across various cancer types, exploring novel therapeutic strategies targeting MCS-related lipid metabolism for the development of anticancer drugs, while also addressing the challenges involved. [ABSTRACT FROM AUTHOR]

Background/Objectives: This nationwide retrospective study evaluated the effects of anticancer therapy on osteoporosis in 126,132 Korean breast cancer survivors from 2002 to 2020. Methods: The Cox proportional hazards model assessed the effects of treatment on osteoporosis. To circumvent the guarantee-time bias for osteoporosis development, a landmark analysis was employed. A stabilized inverse probability of treatment weighting was performed to control any confounding bias. The propensity score was calculated using a multinomial logistic regression model with age, national health insurance, and the Charlson comorbidity index. Results: During a median follow-up of 4.22 years, 28,603 cases of osteoporosis were documented. Aromatase inhibitors (AIs) were associated with a higher risk of osteoporosis development in comparison to tamoxifen (TMX) or chemotherapy. Notably, AIs administered subsequent to a combination of chemotherapy and anti-HER2 therapy exhibited the highest risk of osteoporosis development. Subgroup analysis revealed that the mean interval from breast cancer diagnosis to osteoporosis development was 5.00 years for women diagnosed with cancer at age < 50 and 3.89 years for those diagnosed at age ≥ 60. TMX increased the risk of osteoporosis in women diagnosed with cancer at age < 50, whereas chemotherapy was not a significant risk factor for osteoporosis development in those diagnosed at age ≥ 60. The impact of anticancer therapy on osteoporosis development was more pronounced in women diagnosed with breast cancer at a younger age compared to those diagnosed at an older age. Conclusions: Effective prevention and active management strategies should be implemented to address bone loss in both younger and older breast cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Histone modifications are crucial epigenetic mechanisms for regulating gene expression. Histone acetyltransferases and deacetylases (HDACs) catalyze histone acetylation, a process that mediates transcription. Over recent decades, studies have demonstrated that targeting histone acetylation can be effective in cancer treatment, leading to the development and approval of several HDAC inhibitors. Areas covered: A comprehensive literature review was conducted using the PubMed database to identify studies evaluating the anticancer efficacy of approved and novel HDAC inhibitors. Expert opinion: Accumulating evidence highlights the promising benefits of combining HDAC inhibitors with other anticancer agents. Additionally, HDAC-targeting therapeutics could enhance the sensitivity of cancer cells to chemotherapeutics or targeted tyrosine kinase inhibitors, thereby improving overall treatment outcomes. Future clinical studies must focus on optimizing combination therapies to ensure efficacy while maintaining manageable safety profiles. [ABSTRACT FROM AUTHOR]

The tumor microenvironment is characterized by several hallmarks such as an acidic pH and high glucose levels in tumor tissues and increased expression of specific proteins and/or sugars on the surface of tumor cells. These unique hallmarks of tumors can be considered in the design of multifunctional drug delivery nanosystems to improve the efficiency of tumor therapy through targeted drug delivery and specific drug release in the tumor tissue. In this study, phenylboronic acid-modified pH- and glucose-responsive polymer micelles were designed for the targeted delivery of anticancer drugs. The polymeric micelles demonstrated prolonged and pH/glucose-triggered drug release and enhanced cellular internalization by B16F10 cells through a receptor-mediated endocytosis pathway. The polymeric micellar system could inhibit the proliferation of B16F10 cells with IC50 values lower than those of unmodified micelles. In addition, the polymeric micellar system could markedly suppress cell migration, colony formation, and invasion and promote the apoptosis of B16F10 cells, indicating good anticancer efficiency in vitro. Therefore, this polymeric nanocarrier provides a potential platform for targeted anticancer therapy. [ABSTRACT FROM AUTHOR]

Targeted therapy has considerable promise for the effective eradication of cancer at the primary tumor site prior to subsequent metastasis. Using this therapeutic approach, gaining an understanding of mechanistic cancer models is essential for facilitating the inhibition or suppression of tumor growth. Among different oncogenes and proteins, the protein interacting with never-in-mitosis kinase-1 (Pin1) is particularly important. The interaction between Pin1 and phosphorylated threonine-proline motifs results in significant alterations in protein structure and function. In this review, we provide a comprehensive summary of the processes involving Pin1 and its mechanisms in the context of cancer therapy. Pin1 enhances signaling pathways in a number of different human cancers and plays a pivotal role in the suppressive mechanisms relevant to cancer treatment. It is essential for the regulation of proline-directed phosphorylation and for modulating tumor suppressors. Inhibitors of Pin1, particularly naturally occurring substances, have been found to inhibit the carcinogenic activity of Pin1, and consequently this protein could represent an excellent candidate for novel cancer treatment strategies, offering a valuable therapeutic target in carcinogenesis and treatment resistance. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) and cancer constitute two major public health burdens, and both are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. The potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anticancer therapies, i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anticancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia and other metabolic abnormalities because of a decreased glomerular filtration rate. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy are very limited and only single cases or small case series have been published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively. [ABSTRACT FROM AUTHOR]

Introduction: Paraneoplastic neurological syndrome (PNS) is associated with small‐cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real‐world data from patients with PNS complicated by SCLC. Methods: Patients diagnosed with Stage II–IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results: A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3–4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). Conclusions: A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS. [ABSTRACT FROM AUTHOR]

Yizhuo Xie,1 Ming Zhu,1 Han Bao,1 Kejia Chen,1 Shanshan Wang,1 Jingwen Dai,1 Hongzhu Chen,1 He Li,1 Qi Song,2 Xinlu Wang,2 Liangping Yu,2 Jin Pei1 1Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People’s Republic of China; 2Department of Clinical Pharmacy, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jin Pei, Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, No. 1163 Xinmin Street, Changchun, 130021, People’s Republic of China, Tel +86-431-85619725, Email peijin@jlu.edu.cn Liangping Yu, Department of Clinical Pharmacy, the First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130061, People’s Republic of China, Tel +86 431 81879802, Email liangpingyu@jlu.edu.cnPurpose: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Oxaliplatin (OXA) is currently the primary chemotherapeutic agent for CRC, but its efficacy is limited by the tumor microenvironment (TME). Here, we present a combined approach of chemotherapy and TME modulation for CRC treatment. A multifunctional nanosystem (Rg3-Lip-OXA/CaO2) was established using Ginsenoside Rg3 liposomes targeting glucose transporter 1 overexpressed on the surface of CRC cells to co-deliver OXA and calcium peroxide (CaO2).Methods: The CaO2 nanoparticles were synthesized via the CaCl2-H2O2 reaction under alkaline conditions and characterized using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Rg3-Lip-OXA/CaO2 was prepared through a thin-film hydration approach and characterized; additionally, its stability and release behavior were studied. The O2, H2O2, and Ca2+ generation ability of Rg3-Lip-OXA/CaO2 in solution and HCT116 cells were measured. The in vitro cellular uptake was observed via fluorescence microscope and flow cytometry. In vitro cytotoxicity was evaluated using the CCK-8 assay, flow cytometry, and live/dead cell staining. The in vivo targeting effect as well as antitumor efficacy were determined in HCT116 tumor-bearing mice. Finally, the acute toxicity of Rg3-Lip-OXA/CaO2 was investigated in ICR mice to explore its safety.Results: The XRD and XPS analyses confirmed the successful synthesis of CaO2 nanoparticles. The Rg3-Lip-OXA/CaO2 exhibited an average particle size of approximately 92.98 nm with good stability and sustained release behavior. In vitro and in vivo studies confirmed optimal targeting by Rg3-Lip and demonstrated that the nanosystem effectively produced O2, H2O2 and Ca2+, resulting in significant cytotoxicity. Additionally, in vivo studies revealed substantial tumor growth suppression and reduced tumor-associated fibroblasts (TAFs) and collagen. Acute toxicity studies indicated that Rg3-Lip-OXA/CaO2 markedly reduced the toxicity of chemotherapeutic drugs.Conclusion: This multifunctional nanosystem enhances chemotherapy efficacy and reduces toxicity, offering a promising approach for optimizing CRC treatment and potential clinical application. Keywords: tumor microenvironment, multifunctional nanosystem, oxaliplatin, calcium peroxide, targeted drug delivery, anticancer therapy

Currently, the literature has limited information on potential risks of pulmonary toxicity in patients receiving anticancer therapy. Nevertheless, this complication is not uncommon in some patients and can manifest in various patterns of changes in the lung parenchyma.

Introduction: In general, platelet counts fluctuate in cancer patients receiving anticancer therapy. It may include thrombocytopenia caused by bone marrow suppression due to cytotoxic anticancer agents and thrombocytosis due to rebound during recovery. This should not be the case in the case of administration of immune checkpoint inhibitors, given their mechanism of action. Case Presentation: However, we have experienced a case of thrombocytosis in a patient treated with an immune checkpoint inhibitor. We present a platelet count pattern in patient with bladder cancer underwent Gemcitabine and Cisplatin (GC) therapy and pembrolizumab monotherapy. Conclusion: This case underscores the need for a diverse perspective on platelet behavior in clinical settings.

Simple Summary: Green healthcare relates to using naturally derived sources as medicines to treat and personalize treatments for various diseases. Cancer is one primary global health concern due to its rapid evolution and high prevalence, especially lung cancer. Cinobufagin (CB), a bufadienolide derived primarily from the parotid glands of frogs, has shown promise in combating lung cancer. Our objective with this systematic review is to synthesize the current evidence on CB's effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. Our results indicated that CB reduces lung cancer tumor growth via increased apoptosis by reducing cancer cells' viability. In addition, CB also has impacted migration and invasion across multiple lung cancer cell lines and xenograft models. The molecular pathways involved Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. CB achieved these effects with minimal toxicity. Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB's effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB's ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer continues to be a leading cause of death globally. Advances in effective treatment have been hindered by difficulties in personalized therapy, especially among patients with comorbid conditions. The use of artificial intelligence (AI) in patient profiling presents a promising strategy for enhancing individualized cancer therapy. AI technologies, such as machine learning (ML), deep learning (DL), and natural language processing (NLP), have become crucial in identifying genetic and molecular biomarkers for cancer and migraine. These technologies facilitate predictive analytics to evaluate the impact of migraine on cancer treatment in patients with comorbidities, helping to forecast outcomes and supporting clinical decision-making through real-time treatment adjustments. AI has considerable potential to enhance the precision and efficacy of managing cancer patients with comorbid migraine. However, challenges related to data integration, clinical validation, and ethical considerations must be addressed. Background: Cancer remains a leading cause of death worldwide. Progress in its effective treatment has been hampered by challenges in personalized therapy, particularly in patients with comorbid conditions. The integration of artificial intelligence (AI) into patient profiling offers a promising approach to enhancing individualized anticancer therapy. Objective: This narrative review explores the role of AI in refining anticancer therapy through personalized profiling, with a specific focus on cancer patients with comorbid migraine. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar. Studies were selected based on their relevance to AI applications in oncology and migraine management, with a focus on personalized medicine and predictive modeling. Key themes were synthesized to provide an overview of recent developments, challenges, and emerging directions. Results: AI technologies, such as machine learning (ML), deep learning (DL), and natural language processing (NLP), have become instrumental in the discovery of genetic and molecular biomarkers of cancer and migraine. These technologies also enable predictive analytics for assessing the impact of migraine on cancer therapy in comorbid cases, predicting outcomes and provide clinical decision support systems (CDSS) for real-time treatment adjustments. Conclusions: AI holds significant potential to improve the precision and effectiveness of the management and therapy of cancer patients with comorbid migraine. Nevertheless, challenges remain over data integration, clinical validation, and ethical consideration, which must be addressed to appreciate the full potential for the approach outlined herein. [ABSTRACT FROM AUTHOR]

One of the primary challenges associated with current chemotherapy lies in its inherent toxicity to healthy cells, leading to severe side effects. Recognizing the need for a more targeted approach, we have focused on tumor-specific drug delivery. Cancer cells, being highly metabolic, exhibit a significant increase in glucose consumption approximately 200 times more than normal cells for their rapid growth. To address this, we have engineered GLcNAc-modified solid lipid nanoparticles (SLNPs) designed to be actively internalized by cancer cells, thereby facilitating precise drug delivery to tumors. The developed GLcNAc-TMX-SLNPs are characterized by a size range of 200 to 250 nm and a surface charge of -25 to -35 mV. Their structural properties were thoroughly examined using techniques such as DSC, FTIR, and TEM. In the evaluation of drug release within the tumor microenvironment pH, a biphasic release pattern was observed, with 73.54 ± 0.73% release of TMX within 48 h. Importantly, the hemolysis caused by these developed SLNPs was found to be less than 5%, indicating their suitability for intravenous administration. Cellular uptake studies conducted on MDA-MB-231 cells underscored the targeted characteristics of the developed formulations. With a stable lipid composition, these SLNPs present a promising and stable platform for anticancer treatment. By minimizing off-target effects and enhancing drug delivery precision, our approach holds potential to improve the therapeutic efficacy of chemotherapy while mitigating its impact on healthy cells. [ABSTRACT FROM AUTHOR]

Cell death is a critical biological process necessary for development, tissue maintenance, and defense against diseases. To date, more than 20 forms of cell death have been identified, each defined by unique molecular pathways. Understanding these different forms of cell death is essential for investigating the pathogenesis of diseases such as cancer, neurodegenerative disorders, and autoimmune conditions and developing appropriate therapies. Paraptosis is a distinct form of regulated cell death characterized by cytoplasmic vacuolation and dilatation of cellular organelles like the mitochondria and endoplasmic reticulum (ER). It is regulated by several signaling pathways, for instance, those associated with ER stress, calcium overload, oxidative stress, and specific cascades such as insulin-like growth factor I receptor (IGF-IR) and its downstream signaling pathways comprising mitogen-activated protein kinases (MAPKs) and Jun N-terminal kinase (JNK). Paraptosis has been observed in diverse biological contexts, including development and cellular stress responses in neuronal, retinal, endothelial, and muscle cells. The induction of paraptosis is increasingly important in anticancer therapy, as it targets non-apoptotic stress responses in tumor cells, which can be utilized to induce cell death. This approach enhances treatment efficacy and addresses drug resistance, particularly in cases where cancer cells are resistant to apoptosis. Combining paraptosis-inducing agents with traditional therapies holds promise for enhancing treatment efficacy and overcoming drug resistance, suggesting a valuable strategy in anticancer therapy. [ABSTRACT FROM AUTHOR]

Aims: We aimed to describe treatment of lung cancer patients in Germany based on health claims data, focusing particularly on differences by age. Materials and methods: Using the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population) we identified lung cancer patients diagnosed in 2015–2018 based on a previously developed algorithm and followed them until death, end of continuous insurance or end of 2020. We described initial treatment patterns after diagnosis and survival, stratified among others by age. Results: We included 42,629 incident lung cancer patients (58% male). Surgery within three months after diagnosis was performed in 36%, 31%, 29% and 18% of patients aged < 50, 50–69, 70–79 and ≥ 80, respectively. Among patients without surgery, systemic therapy was administered in 77%, 72%, 54% and 25% of patients aged < 50, 50–69, 70–79 and ≥ 80, respectively. Monoclonal antibodies were administered in 15–30% of patients across age groups, and 4% to 15% received protein kinase inhibitors. Overall, 21% of patients remained untreated. In the age groups < 50, 50–69, 70–79 and ≥ 80, this proportions was 9%, 12%, 22% and 48%, respectively. Conclusion: In conclusion, our study provides a comprehensive overview of the therapy of lung cancer patients in Germany and quantitatively demonstrates the considerable differences between age groups. In terms of clinical cancer registration, the results are useful to estimate the completeness of data for the different types of treatment. [ABSTRACT FROM AUTHOR]

Cysteine cathepsins are a fascinating group of proteolytic enzymes that play diverse and crucial roles in numerous biological processes, both in health and disease. Understanding these proteases is essential for uncovering novel insights into the underlying mechanisms of a wide range of disorders, such as cancer. Cysteine cathepsins influence cancer biology by participating in processes such as extracellular matrix degradation, angiogenesis, immune evasion, and apoptosis. In this comprehensive review, we explore foundational research that illuminates the diverse and intricate roles of cysteine cathepsins as diagnostic markers and therapeutic targets for cancer. This review aims to provide valuable insights into the clinical relevance of cysteine cathepsins and explore their capacity to advance personalised and targeted medical interventions in oncology. • Cysteine cathepsins are pivotal in many cancer processes, making them desirable therapeutic targets. • Irregular cysteine cathepsin levels can serve as diagnostic and prognostic biomarkers in various cancers. • Development of molecular probes for cysteine cathepsins enhances diagnostic imaging and image-guided surgery. • Selective inhibitors and novel drug delivery systems targeting cysteine cathepsins hold promise for innovative cancer treatments. • Advances in antibody-drug conjugates utilizing cysteine cathepsins offer major potential in cancer treatment. [ABSTRACT FROM AUTHOR]

In this work, we conceived and developed antibody-drug conjugates (ADCs) that could efficiently release the drug after enzymatic cleavage of the linker moiety by tumoral proteases. The antibody-drug linkers we used are the result of a rational optimization of a previously reported PEGylated linker, PUREBRIGHT® MA-P12-PS, which showed excellent drug loading capacities but lacked an inbuilt drug discharge mechanism, thus limiting the potency of the resulting ADCs. To address this limitation, we chose to incorporate a protease-sensitive trigger into the linker to favor the release of a "PEGless" drug inside the tumor cells and, therefore, obtain potent ADCs. Currently, most marketed ADCs are based on the Val-Cit dipeptide followed by a self-immolative spacer for releasing the drug in its unmodified form. Here, we selected two untraditional peptide sequences, a Phe-Gly dipeptide and a Val-Ala-Gly tripeptide and placed one or the other in between the drug on one side (N-terminus) and the rest of the linker, including the PEG moiety, on the other side (C-terminus), without a self-immolative group. We found that both linkers responded to cathepsin B, a reference lysosomal enzyme, and liberated a PEG-free drug catabolite, as desired. We then used the two linkers to generate ADCs based on trastuzumab (a HER2-targeting antibody) and DM1 (a microtubule-targeted cytotoxic agent) with an average drug-to-antibody ratio (DAR) of 4 or 8. The ADCs showed restored cytotoxicity in vitro , which was proportional to the DM1 loading and generally higher for the ADCs bearing Val-Ala-Gly in their structure. In an ovarian cancer mouse model, the DAR 8 ADC based on Val-Ala-Gly behaved better than Kadcyla® (an approved ADC of DAR 3.5 used as control throughout this study), leading to a higher tumor volume reduction and more prolonged median survival. Taken together, our results depict a successful linker optimization process and encourage the application of the Val-Ala-Gly tripeptide as an alternative to other existing protease-sensitive triggers for ADCs. [Display omitted] • Hydrophilic linkers are necessary to accommodate high drug loadings on antibodies. • The proposed linker features two pendant PEG arms to create a hydrated shell around the drug. • The proposed linker uses a protease-sensitive trigger for controlled "PEGless" drug release. • The linker optimization process led to a DAR 8 ADC active in a xenograft tumor model. [ABSTRACT FROM AUTHOR]

Mitoxantrone (MTX) is a therapeutic agent used in the treatment of solid tumors and multiple sclerosis, recognized for its cardiotoxicity, with underlying molecular mechanisms not fully disclosed. The cardiotoxicity is influenced by risk factors, including age. Our study intended to assess the molecular effect of MTX on the cardiac muscle of old male CD-1 mice. Mice aged 19 months received a total cumulative dose of 4.5 mg/kg of MTX (MTX group) or saline solution (CTRL group). Two months post treatment, blood was collected, animals sacrificed, and the heart removed. MTX caused structural cardiac changes, which were accompanied by extracellular matrix remodeling, as indicated by the increased ratio between matrix metallopeptidase 2 and metalloproteinase inhibitor 2. At the metabolic level, decreased glycerol levels were found, together with a trend towards increased content of the electron transfer flavoprotein dehydrogenase. In contrast, lower glycolysis, given by the decreased content of glucose transporter GLUT4 and phosphofructokinase, seemed to occur. The findings suggest higher reliance on fatty acids oxidation, despite no major remodeling occurring at the mitochondrial level. Furthermore, the levels of glutamine and other amino acids (although to a lesser extent) were decreased, which aligns with decreased content of the E3 ubiquitin-protein ligase Atrogin-1, suggesting a decrease in proteolysis. As far as we know, this was the first study made in old mice with a clinically relevant dose of MTX, evaluating its long-term cardiac effects. Even two months after MTX exposure, changes in metabolic fingerprint occurred, highlighting enduring cardiac effects that may require clinical vigilance. [Display omitted] • First study regarding late-onset chronic cardiotoxicity in aged MTX-treated mice. • Cardiac metabolic remodeling remained in aged heart two months post-MTX treatment. • Molecular outcomes include increased FAO and oxidation of amino acids after MTX. • Decreased glycolysis and UPP-mediated proteolysis were also seen in these aged mice. [ABSTRACT FROM AUTHOR]

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most common tumors worldwide, and new approaches and antitumor drugs for therapy are being investigated. Among the promising biomolecules of natural origin for antitumor research are gastropodan hemocyanins—highly immunogenic multimeric glycoproteins used as antitumor agents and components of therapeutic vaccines in human and mouse cancer models. A murine melanoma model established in C57BL/6 mice of the B16F10 cell line was used to study anticancer modified oxidized hemocyanins (Ox-Hcs) that were administered to experimental animals (100 μg/mouse) under different regimens: mild, intensive, and with sensitization. The solid tumor growth, antitumor response, cell infiltration in tumors, and survival were assessed using flow cytometry, ELISA, and cytotoxicity assays. Therapy with Ox-RtH or Ox-HaH resulted in the generation of enhanced specific immune response (increased levels of tumor-infiltrated mature NK cells (CD27+CD11b+) in sensitized groups and of macrophages in the intensively immunized animals) and tumor suppression. Beneficial effects such as delayed tumor incidence and growth as well as prolonged survival of tumor-bearing animals have been observed. High levels of melanoma-specific CTLs that mediate cytotoxic effects on tumor cells; tumor-infiltrating IgM antibodies expected to enhance antibody-dependent cellular cytotoxicity; type M1 macrophages, which stimulate the Th1 response and cytotoxic cells; and proinflammatory cytokines, were also observed after Ox-Hcs administration. The modified Hcs showed strong antitumor properties in different administration regimens in a murine model of melanoma with potential for future application in humans. [ABSTRACT FROM AUTHOR]

Recently, ribavirin has demonstrated effectiveness in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. Enhancing ribavirin's bioavailability can be achieved by utilizing intranasal stimuli-responsive systems that create a gel on the nasal mucosa. The research examined thermosensitive, pH-sensitive, and ion-selective polymers in various combinations and concentrations, chosen in line with the current Quality by Design (QbD) approach in pharmaceutical development. Following a thorough assessment of key parameters, the optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was formulated and subjected to in vivo testing. Through experiments on male rats, the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) was elucidated, showcasing drug accumulation in the olfactory bulbs and brain. [ABSTRACT FROM AUTHOR]

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. Methods: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (−0.05%/s or −0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. Results: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. Conclusions: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system. [ABSTRACT FROM AUTHOR]

Apitoxin therapy (BVT—bee venom therapy) is an emerging complementary treatment utilizing bee venom for various medical conditions. This review explores the potential and therapeutic mechanisms of bee venom, focusing on its chemical composition and the methods for its extraction and purification to enhance safety while maintaining bioactivity. Bee venom contains amphipathic peptides such as melittin and apamin, enzymes like phospholipase A2, and bioamines including histamine and catecholamines, contributing to its pleiotropic effects. The therapeutic applications of bee venom span anti-inflammatory, analgesic, antimicrobial, antiviral, neuroprotective, anti-arthritic, and anti-cancer activities. Clinical and laboratory studies have demonstrated its efficacy in treating chronic and autoimmune diseases, pain management, and improving quality of life. The immunogenic properties of bee venom necessitate ongoing research to mitigate allergic reactions, ensuring its safe and effective use in medical practice. This review summarizes the current state of research on bee venom therapy, highlighting its potential benefits and future research directions. [ABSTRACT FROM AUTHOR]

Cancer nanomedicines, characterized by submicrometer-sized formulations, aim to optimize the biodistribution of anticancer drugs by minimizing off-target effects, reducing toxicity, enhancing target site accumulation, and improving overall efficacy. Numerous nanomedicines have been developed to improve the effectiveness and safety of traditional anticancer treatments. These include formulations with carbon nanotubes, nanodiamonds, enzyme-responsive nanoparticles for controlled drug release, dendrimers as nanoparticle drug carriers, quantum dot nanocarrier systems for precise drug delivery, solid lipid nanoparticles, and polymeric nanoparticles designed for targeted drug delivery. Additionally, nanotechnology has been explored in cancer treatment through gene therapy. Despite these advances, the complex nature of carrier materials and functional integration presents challenges in preparing these candidates for clinical translation. Nanotechnology, with its unique features at the nanoscale, offers novel possibilities for developing cancer therapies while increasing efficacy and safety. Although only a few nanotherapeutics have obtained clinical approval, exciting uses for nanotechnology are on the horizon. Nanoparticles possess unique transport, biological, optical, magnetic, electrical, and thermal capabilities due to their small size within the light wavelength spectrum. This results in high surface area-to-volume ratios, allowing for the incorporation of various supporting components in addition to active medicinal substances. These properties aid in solubilization, degradation protection, delayed release, immune response evasion, tissue penetration, imaging, targeted distribution, and triggered activation. In summary, the future of nanomedicine holds promise for introducing innovative platforms in cancer treatment. The research presented underscores the potential for nanoparticles to revolutionize anticancer therapies, enhancing the overall therapeutic approach. [ABSTRACT FROM AUTHOR]

This review examines nanomedicine's dynamic landscape, emphasizing vanadium oxide nanoparticles (V2O5 NPs) and their pivotal role in antimicrobial and anticancer therapies. It elucidates V2O5 NPs' mechanisms, revealing their disruption of redox homeostasis, mitochondrial function, and potent anti-angiogenic effects. Highlighting significant findings, the research emphasizes V2O5 NPs' robust anticancer efficacy through apoptosis and ferroptosis induction in tumor cells. V2O5 NPs demonstrate versatile antioxidant properties and compelling anti-colorectal cancer effects. The nuanced interplay between V2O5 NP size and cytotoxicity underscores the importance of tailoring nanoparticle characteristics for enhanced therapeutic effectiveness. Despite promising results, translating V2O5 NPs to clinical practice faces challenges like safety concerns, optimizing therapeutic efficacy, and regulatory complexities. Collaborative efforts among the scientific community, industry partners, and regulatory bodies are crucial for advancing V2O5 NPs in antimicrobial and anticancer therapies. Collective commitment is vital for unlocking V2O5 NPs' full potential and revolutionizing medical applications. This collaborative endeavour promises innovative and effective therapeutic interventions, reshaping nanomedicine's landscape. [ABSTRACT FROM AUTHOR]

Abstract Biomolecules with metals can form supramolecular nanomaterials through coordination assembly, opening new avenues for cancer theranostics and bringing unique insights into personalized nanomedicine. These biomaterials have been considered versatile and innovative nanoagents due to their structure‒function control, biological nature, and simple preparation methods. This review article summarized the recent developments in multicomponent nanomaterials formed from metal coordination interactions with amino acids, peptides, and proteins, together with anticancer drugs, for cancer theranostics. We discussed the role of functional groups anchored in building blocks for coordination interactions, and subsequently, the types of interactions were examined from a structure‒function perspective. Amino acids with different metals and anticancer drugs forming supramolecular nanomaterials and their anticancer mechanisms were highlighted. Peptides with different metals and anticancer drugs, proteins with metals and anticancer drugs used for material formations, and anticancer activity have been discussed. Ultimately, the conclusion and future outlook for multicomponent supramolecular nanomaterials offer fundamental insights into fabrication design and precision medicine.

Abstract Non-muscle myosin heavy chain IIA (MYH9), a member of the non-muscle myosin II (NM II) family, is widely expressed in cells. The interaction of MYH9 with actin in the cytoplasm can hydrolyze ATP, completing the conversion of chemical energy to mechanical motion. MYH9 participates in various cellular processes, such as cell adhesion, migration, movement, and even signal transduction. Mutations in MYH9 are often associated with autosomal dominant platelet disorders and kidney diseases. Over the past decade, tumor-related research has gradually revealed a close relationship between MYH9 and the occurrence and development of tumors. This article provides a review of the research progress on the role of MYH9 in cancer regulation. We also discussed the anti-cancer effects of MYH9 under special circumstances, as well as its regulation of T cell function. In addition, given the importance of MYH9 as a key hub in oncogenic signal transduction, we summarize the current therapeutic strategies targeting MYH9 as well as the ongoing challenges.

Background: Cancer patients are prone to developing acute kidney disease (AKD), yet this phenomenon remains understudied compared to acute kidney injury (AKI). AKD, which often develops insidiously, can cause treatment interruptions, extended hospital stays, and increased mortality. Summary: This perspective article explores the intricate relationship between AKD and cancer, focusing on prevalence, risk factors, implications for anticancer therapy, and long-term outcomes, including chronic kidney disease progression. Key Messages: To emphasize the importance of early detection and intervention, this work advocates for increased research and awareness among clinicians to improve patient outcomes and manage healthcare burdens associated with AKD in cancer patients.

Glioblastoma multiforme (GBM) is one of the most aggressive primary tumors of the central nervous system. It is associated with a very poor prognosis, with up to half of patients failing to survive the first year after diagnosis. It develops from glial tissue and belongs to the adult-type diffuse glioma group according to the WHO classification of 2021. Therapy for patients with GBM is currently based on surgical resection, radiation therapy, and chemotherapy, but despite many efforts, there has been minimal progress in tumor management. The most important chemotherapeutic agent in the treatment of this tumor is temozolomide (TMZ), a dacarbazine derivative that presents alkylating activity. It is usually administered to patients concurrently with radiation therapy after surgical resection of the tumor, which is defined as the Stupp protocol. Temozolomide demonstrates relatively good efficacy in therapy, but it could also present with several side effects. The resistance of GBM to the drug is currently the subject of work by specialists in the field of oncology, and its use in various regimens and patient groups may bring therapeutic benefits in the future. The aim of this review paper is to summarize the relevance of TMZ in the treatment of GBM based on recent reports.

Non-muscle myosin heavy chain IIA (MYH9), a member of the non-muscle myosin II (NM II) family, is widely expressed in cells. The interaction of MYH9 with actin in the cytoplasm can hydrolyze ATP, completing the conversion of chemical energy to mechanical motion. MYH9 participates in various cellular processes, such as cell adhesion, migration, movement, and even signal transduction. Mutations in MYH9 are often associated with autosomal dominant platelet disorders and kidney diseases. Over the past decade, tumor-related research has gradually revealed a close relationship between MYH9 and the occurrence and development of tumors. This article provides a review of the research progress on the role of MYH9 in cancer regulation. We also discussed the anti-cancer effects of MYH9 under special circumstances, as well as its regulation of T cell function. In addition, given the importance of MYH9 as a key hub in oncogenic signal transduction, we summarize the current therapeutic strategies targeting MYH9 as well as the ongoing challenges. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on the genetic characteristics of the tumors to detail their prognosis and tailor therapy. In the case of EC, genetic mutations have been shown to underlie their formation. It is very important to know the mechanisms of EC formation related to mutations induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed of nucleotide transcripts with very low protein-coding capacity, are proving to be important. Their expression patterns in many malignancies can inhibit tumor formation and progression. They also regulate protein coding at the epigenetic, transcriptional, and posttranscriptional levels. MicroRNAs (miRNAs), several varieties of which are associated with normal endometrium as well as its tumor, also play a particularly important role in gene expression. MiRNAs and long noncoding RNAs (lncRNAs) affect many pathways in EC tissues and play important roles in cancer development, invasion, and metastasis, as well as resistance to anticancer drugs through mechanisms such as suppression of apoptosis and progression of cancer stem cells. It is also worth noting that miRNAs are highly precise, sensitive, and robust, making them potential markers for diagnosing gynecologic cancers and their progression. Unfortunately, as the incidence of EC increases, treatment becomes challenging and is limited to invasive tools. The prospect of using microRNAs as potential candidates for diagnostic and therapeutic use in EC seems promising. Exosomes are extracellular vesicles that are released from many types of cells, including cancer cells. They contain proteins, DNA, and various types of RNA, such as miRNAs. The noncoding RNA components of exosomes vary widely, depending on the physiology of the tumor tissue and the cells from which they originate. Exosomes contain both DNA and RNA and have communication functions between cells. Exosomal miRNAs mediate communication between EC cells, tumor-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and play a key role in tumor cell proliferation and tumor microenvironment formation. Oncogenes carried by tumor exosomes induce malignant transformation of target cells. During the synthesis of exosomes, various factors, such as genetic and proteomic data are upregulated. Thus, they are considered an interesting therapeutic target for the diagnosis and prognosis of endometrial cancer by analyzing biomarkers contained in exosomes. Expression of miRNAs, particularly miR-15a-5p, was elevated in exosomes derived from the plasma of EC patients. This may suggest the important utility of this biomarker in the diagnosis of EC. In recent years, researchers have become interested in the topic of prognostic markers for EC, as there are still too few identified markers to support the limited treatment of endometrial cancer. Further research into the effects of ncRNAs and exosomes on EC may allow for cancer treatment breakthroughs. [ABSTRACT FROM AUTHOR]

Cancer is a complex disease that affects millions of people and remains a major public health problem worldwide. Conventional cancer treatments, including surgery, chemotherapy, immunotherapy, and radiotherapy, have limited achievements and multiple drawbacks, among which are healthy tissue damage and multidrug-resistant phenotype onset. Increasing evidence shows that many plants' natural products, as well as their bioactive compounds, have promising anticancer activity and exhibit minimal toxicity compared to conventional anticancer drugs. However, their widespread use in cancer therapy is severely restricted by limitations in terms of their water solubility, absorption, lack of stability, bioavailability, and selective targeting. The use of nanoformulations for plants' natural product transportation and delivery could be helpful in overcoming these limitations, thus enhancing their therapeutic efficacy and providing the basis for improved anticancer treatment strategies. The present review is aimed at providing an update on some phytocompounds (curcumin, resveratrol, quercetin, and cannabinoids, among others) and their main nanoformulations showing antitumor activities, both in vitro and in vivo, against such different human cancer types as breast and colorectal cancer, lymphomas, malignant melanoma, glioblastoma multiforme, and osteosarcoma. The intracellular pathways underlying phytocompound anticancer activity and the main advantages of nanoformulation employment are also examined. Finally, this review critically analyzes the research gaps and limitations causing the limited success of phytocompounds' and nanoformulations' clinical translation. [ABSTRACT FROM AUTHOR]

Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, antiproliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment. [ABSTRACT FROM AUTHOR]

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets. [ABSTRACT FROM AUTHOR]

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Glioblastoma multiforme (GBM) is one of the most aggressive primary tumors of the central nervous system. It is associated with a very poor prognosis, with up to half of patients failing to survive the first year after diagnosis. It develops from glial tissue and belongs to the adult-type diffuse glioma group according to the WHO classification of 2021. Therapy for patients with GBM is currently based on surgical resection, radiation therapy, and chemotherapy, but despite many efforts, there has been minimal progress in tumor management. The most important chemotherapeutic agent in the treatment of this tumor is temozolomide (TMZ), a dacarbazine derivative that presents alkylating activity. It is usually administered to patients concurrently with radiation therapy after surgical resection of the tumor, which is defined as the Stupp protocol. Temozolomide demonstrates relatively good efficacy in therapy, but it could also present with several side effects. The resistance of GBM to the drug is currently the subject of work by specialists in the field of oncology, and its use in various regimens and patient groups may bring therapeutic benefits in the future. The aim of this review paper is to summarize the relevance of TMZ in the treatment of GBM based on recent reports. [ABSTRACT FROM AUTHOR]