Cancer Therapy Research Articles

Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy.

In the field of precision and personalized medicine, the next generation sequencing method has begun to take an active place as genome-wide screening applications in the diagnosis and treatment of diseases. Studies based on the determination of the therapeutic efficacy of personalized drug use in cancer treatment in the size of the transcriptome and its extension, lncRNA, have been increasing rapidly in recent years. Targeting and/or regulating noncoding RNAs (ncRNAs) consisting of long noncoding RNAs (lncRNAs) are promising strategies for cancer treatment. Within the scope of rapidly increasing studies in recent years, it has been shown that many natural agents obtained from biological organisms can potentially alter the expression of many lncRNAs associated with oncogenic functions. Natural agents include effective small molecules that provide anti-cancer effects and have been used as chemotherapy drugs or in combination with standard anti-cancer drugs used in routine treatment. In this review, it was aimed to provide detailed information about the potential of natural agents to regulate and/or target non-coding RNAs and their mechanisms of action to provide an approach for cancer therapy. The discovery of novel anti-cancer targets and subsequent development of effective drugs or combination strategies that are still needed for most cancers will be promising for cancer treatment.

TRAIL as a Warrior in Nano-Sized Trojan Horse: Anticancer and Anti-Metastatic Effects of Nano-Formulations of TRAIL in Cell Culture and Animal Model Studies

Cancer is a therapeutically challenging and genomically complicated disease. Pioneering studies have uncovered multifaceted aspects of cancer, ranging from intra- and inter-tumor heterogeneity, drug resistance, and genetic/epigenetic mutations. Loss of apoptosis is another critical aspect that makes cancer cells resistant to death. A substantial fraction of mechanistic information gleaned from cutting-edge studies has enabled researchers to develop near-to-complete resolution of the apoptotic pathway. Within the exciting frontiers of apoptosis, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) has garnered phenomenal appreciation by interdisciplinary researchers principally because of its unique capability to target cancer cells. TRAIL-based monotherapies and combinatorial therapies have reached phase II and phase III clinical trials. Rapidly upgrading the list of clinical trials substantiates the clinically valuable role of TRAIL-based therapeutics in cancer therapy. However, there is a growing concern about the poor bioavailability and rapid clearance of TRAIL-based therapeutics. Excitingly, the charismatic field of nanotechnology offers solutions for different problems, and we have witnessed remarkable breakthroughs in the efficacy of TRAIL-based therapeutics using nanotechnological approaches. In this review, we have attempted to provide a summary about different nanotechnologically assisted delivery methods for TRAIL-based therapeutics in cell culture studies and animal model studies for the inhibition/prevention of cancer.

PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.

Cancer involves the uncontrolled, abnormal growth of cells and affects other tissues. Kinase has an impact on proliferating the cells and causing cancer. For the purpose of treating cancer, PIM kinase is a potential target. The pro-viral Integration site for moloney murine leukaemia virus (PIM) kinases is responsible for the tumorigenesis, by phosphorylating the proteins that control the cell cycle and cell proliferation. PIM-1, PIM-2, and PIM-3 are the three distinct isoforms of PIM kinases. The JAK/STAT pathway is essential for controlling how PIM genes are expressed. PIM kinase is also linked withPI3K/AKT/mTOR pathway in various types of cancers. The overexpression of PIM kinase will cause cancer. Currently, there are significant efforts being made in medication design and development to target its inhibition. A few small chemical inhibitors (E.g., SGI-1776, AZD1208, LGH447) that specifically target the PIM proteins' adenosine triphosphate (ATP)-binding domain have been identified. PIM kinase antagonists have a remarkable effect on different types of cancer. Despite conducting clinical trials on SGI-1776, the first PIM inhibitory agent, was prematurely withdrawn, making it unable to generate concept evidence. On the other hand, in recent years, it has aided in hastening the identification of multiple new PIM inhibitors. Cyanopyridines and Pyrazolo[1,5-a]pyrimidinecan act as potent PIM kinase inhibitors for cancer therapy. We explore the involvement of oncogenic transcription factor c-Mycandmi-RNA in relation to PIM kinase. In this article, we highlight the oncogenic effects, and structural insights into PIM kinase inhibitors for the treatment of cancer.

Orchestrated Copper-Loaded Nanoreactor for Simultaneous Induction of Cuproptosis and Immunotherapeutic Intervention in Colorectal Cancer

Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient intracellular Cu ions transported by existing Cu ionophores, which are small molecules with short blood half-lives, inevitably hamper the effectiveness of cuproptosis. Herein, the ESCu@HM nanoreactor, self-assembled from the integration of H-MnO2 nanoparticles with the Cu ionophore elesclomol (ES) and Cu, was fabricated to facilitate cuproptosis and further induce relevant immune responses. Specifically, the systemic circulation and tumoral accumulation of Cu, causing irreversible cuproptosis, work in conjunction with Mn2+, resulting in the repolarization of tumor-associated macrophages (TAMs) and amplification of the activation of the cGAS-STING pathway by damaged DNA fragments in the nucleus and mitochondria. This further stimulates antitumor immunity and ultimately reprograms the tumor microenvironment (TME) to inhibit tumor growth. Overall, ESCu@HM as a nanoreactor for cuproptosis and immunotherapy, not only improves the dual antitumor mechanism of ES and provides potential optimization for its clinical application, but also paves the way for innovative strategies for cuproptosis-mediated colorectal cancer (CRC) treatment.

Clinical evaluation of performance, stability, and longevity of an accelerator system designed for boron neutron capture therapy utilising a beryllium target.

Boron neutron capture therapy for recurrent head and neck cancer has been approved as an insurance covered treatment in Japan since June 2020. The Kansai BNCT Medical Center has installed the NeuCure® BNCT system developed by Sumitomo Heavy Industries. This system utilises a beryllium target with a 30 MeV proton beam to generate neutrons. To date, the center has treated over 300 patients and the system is also used for quality control and fundamental research experiments. Information on the stability and longevity of the system is important for facilities and hospitals considering installation of a BNCT system in the future, particularly after an exchange of a major component, such as the target. The beam output (neutron and gamma ray) was measured before and after the exchange of the target. The thermal neutron, fast neutron and gamma ray distribution inside a water phantom was evaluated and the results showed no significant change in the beam quality after the exchange of the target. Furthermore, no significant change in the neutron flux as a function of increasing number of accumulated protons on the target was observed up to a value of just under 400 mAh. The NeuCure® BNCT system has been shown to be highly stable and the frequency of target replacement was much less than lithium target-based accelerators.

Quality and mechanical efficiency of automated knowledge-based planning for volumetric-modulated arc therapy in head and neck cancer.

This study aimed to examine the effectiveness of the automated RapidPlanin assessing plan quality and to explore how beam complexity affects the mechanical performance of volumetric modulated arc therapy for head and neck cancers. The plans were first generated using automated RapidPlan with scripting application programming interface (API) and then further refined through manual optimization (RP+MP) to improve plan quality. The quality of 20 plans was assessed, taking into account dose statistics and clinical plan acceptability. The impact of beam complexity on mechanical performance was analyzed using parameters such as leaf speed (LS), leaf acceleration (LA), mean-field area (MFA), cross-axis score (CAS), closed leaf score (CLS), small aperture score (SAS), and monitor units per control point (MU/CP). Patient-specific quality assurance (PSQA) was conducted to determine differences between the RP+MP and original plans. No differences in the heterogeneity index and conformity number were observed between the RP+MP and original plans. The RP+MP plan was superior to the original plan for sparing the left cochlea, left and right internal auditory canals, chiasm, and left optic nerve. Significant differences (p<0.05) were identified in CAS, SAS1mm, SAS2mm, and SAS10mm. However, there was no significant difference in PSQAbetween the RP+MP and original plans. The RP+MP plan without any modifications was clinically acceptable in 45% of cases. The automated RP with scripting API followed by MP (RP+MP) yielded a high-quality plan in terms of dose statistics and clinical acceptability. The RP+MP plan yielded a higher CAS and SAS compared with the original plan. Nevertheless, there was no significant difference in PSQAbetween the RP+MP and original plans.

Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of less than 10% making it one of the most fatal cancers. A lack of early measures of prognosis, challenges in molecular targeted therapy, ineffective adjuvant chemotherapy, and strong resistance to chemotherapy cumulatively make pancreatic cancer challenging to manage. The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer. Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC. Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer. This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Discovery of novel CDK4/6 inhibitors from fungal secondary metabolites

The development of targeted therapies for breast cancer, particularly those focusing on cyclin-dependent kinases 4/6 (CDK4/6), has significantly improved patient outcomes. However, the currently approved CDK4/6 inhibitors are associated with various side effects, underscoring the need for novel compounds with enhanced efficacy and safety profiles. This study aimed to identify potential CDK4/6 inhibitors from MeFSAT, a database of fungal secondary metabolites using an in-silico screening approach. The virtual screening process incorporated drug-likeness filters, ADME and toxicity predictions, consensus molecular docking, and 200 ns molecular dynamics simulations. Out of 411 initial compounds, two molecules demonstrated favorable binding interactions and stability with the CDK4/6 protein complex. The MTT assay showed that MSID000025 had dose-dependent cytotoxicity against MCF7 breast cancer cells. This suggests that MSID000025 could be a good candidate CDK4/6 inhibitor for treating breast cancer. Our study highlights the potential of fungal secondary metabolites as a source of novel compounds for drug discovery. It provides a framework for identifying CDK4/6 inhibitors with improved therapeutic properties.

Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

Phase I trial and preclinical data of ACT using neoantigen-reactive TIL for patients with advanced epithelial and ICB-resistant solid cancers

Background and PurposeACT of ex vivo expanded TIL can mediate objective tumor regression in 28-49% of metastatic melanoma patients. However, the efficacy of TIL therapy in most epithelial cancers remains limited. We present the design of a phase I clinical study that aims to assess the safety and efficacy of NEXTGEN-TIL, a TIL product selected based on ex vivo neoantigen recognition, in patients with advanced epithelial tumors and ICB-resistant solid tumors. MethodsPreREP TIL cultures expanded in high dose IL-2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous TCL and/or neoantigens. 6 GMP validations of preREP TIL expansion were performed and TIL cultures from these 6 intermediate products were selected to perform the clinical scale GMP validation of the REP. ResultsTIL expanded in 82% of patient-derived tumor biopsies across different cancer types and these contained tumor- and neoantigen-reactive T cells. During GMP-validations, a variable number of TILs expanded, constituting the intermediate products (preREP). Three finished products (REP) were manufactured which reached cell doses ranging from 4.3e9 to 1.1e11 and met the established specifications. The NEXTGEN-TIL clinical trial entails a first expansion of TIL from tumor fragments in HD-IL-2 followed by TIL screening for neoantigen-recognition and REP of selected neoantigen-reactive TIL cultures. Treatment involves a classical non-myeloablative lymphodepleting chemotherapy followed by NEXTGEN-TIL product administration together with HD-IL-2. ConclusionsNEXTGEN-TIL consists of selected neoantigen-reactive TIL and aims to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TIL.

Molecular MR Imaging of T-Cell Immune Response to Cryoablation in Immunologically Hot vs. Cold Hepatocellular Carcinoma.

Background and aimsThe increasing enthusiasm for integrating locoregional therapy in primary liver cancer with systemic immunotherapy underscores the need for non-invasive imaging biomarkers. This study aims to establish advanced molecular magnetic resonance imaging (MRI) tools for monitoring T-cell responses to cryoablation in murine models, distinguishing between immunologically "hot" and "cold" hepatocellular carcinoma (HCC). Materials and methodsImmunocompetent 7-10-weeks-old C57BL/6J and BALB/cJ mice (n = 18 each) received carbon tetrachloride for 12 weeks to induce liver cirrhosis. Intrinsically immunogenic Hepa1-6 (“hot”) and non-immunogenic TiB75 (“cold”) cells were orthotopically implanted in C57BL/6 or BALB/c mice, respectively, to generate focal HCC lesions. After one week, animals were randomly assigned to (A) partial cryoablation (pCryo) (1.2 mm cryoprobe, -40°C) or (B) no treatment groups (n=8 per group and tumor type). Gadolinium 160 (160Gd)-labeled CD8+ antibody was administered intravenously either one week after tumor induction (control) or one-week post (pCryo) (treatment). T1-weighted MRI scans were performed using a 9.4 Tesla MRI scanner. Radiological-pathological correlation included imaging mass cytometry (IMC) and immunohistochemistry. ResultsPCryo-treated Hepa1-6 tumors displayed peritumoral ring enhancement on T1-weighted MRI with 160Gd-CD8, correlating with IMC signal patterns. Untreated Hepa1-6 tumors lacked such enhancement. Radiological-pathological correlation confirmed significantly increased tumor-infiltrating CD8+ T-lymphocytes in pCryo Hepa1-6 tumors compared with untreated tumors (p < 0.001), and a stronger local response compared with systemic lymph nodes (p=0.0415). Increased T-lymphocyte infiltration was not observed in TiB75 tumors, as indicated by MRI and histopathology. ConclusionPCryo induced increased T-cell infiltration in Hepa1-6 tumors compared to TiB75 tumors. T1-weighted MRI, following 160Gd-CD8 antibody administration, reproducibly detected the ablation-induced changes. These findings encourage further investigation of MR-based molecular imaging biomarkers to assess immune responses in local tumor therapies. Impact and implicationsThis study successfully established reliable MR-based molecular imaging tools to visualize CD8+ anti-tumor specific T-cell infiltration following partial cryoablation (pCryo) in murine tumor models. The study's significance lies in advancing our understanding of immune responses within induced cirrhosis and distinguishing between "hot" and "cold" tumor phenotypes. The findings not only build upon previous proof-of-principle data but also extend this technology to include different immune cell types in hepatocellular carcinoma (HCC). The study reveals that pCryo may exert specific effects on the tumor microenvironment, augmenting the anti-tumor immune response in immunogenic tumors while displaying a weaker local effect in non-immunogenic tumors.

Enhancing Estimation Accuracy of Prostate Cancer VMAT Planning: A Knowledge-based Approach Using Multiple Collimator Angles.

This study aimed to determine whether a knowledge-based planning model incorporating treatment plans with multiple collimator angles (Multi-coll. model) provides superior estimation accuracy and plan quality for a range of collimator angles compared with a typical institutional model (Inst. model). Five institutions using volumetric modulated arc therapy for prostate cancer participated in the study. The Inst. model comprised plans using a fixed collimator angle, whereas the Multi-coll. model registered plans using single arcs and collimator angles of 10°, 30°, 50°, and 70°. The coefficient of determination and mean squared error were calculated, and the estimation accuracy and dosimetric results for three validation cases at each institution were compared for each model. Dosimetric parameters included volumes receiving at least 20%, 50%, and 90% of the prescription dose (V20, V50, and V90, respectively) at each collimator angle. The Multi-coll. model yielded a higher coefficient of determination and lower mean squared error than the Inst. model, although overfitting of data was a concern at two institutions. The mean absolute errors between estimated and calculated values were (Inst. model vs. Multi-coll. model): 4.41% vs. 2.60% (V20), 4.03% vs. 2.27% (V50), and 2.07% vs. 1.09% (V90) for the rectum; 3.48% vs. 3.42% (V20), 2.24% vs. 3.65% (V50), and 1.11% vs. 0.73% (V90) for the bladder. The Multi-coll. model exhibited a lower rectal and vesical V20 than the Inst. The Multi-coll. model had a greater estimation accuracy and slightly higher plan quality than the Inst.

The Use of Lipid-based Nanocarriers to Improve Ovarian Cancer Treatment: An Overview of Recent Developments.

Ovarian cancer poses a formidable health challenge for women globally, necessitating innovative therapeutic approaches. This review provides a succinct summary of the current research status on lipid-based nanocarriers in the context of ovarian cancer treatment. Lipid-based nanocarriers, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), offer a promising solution for delivering anticancer drugs with enhanced therapeutic effectiveness and reduced adverse effects. Their versatility in transporting both hydrophobic and hydrophilic medications makes them well-suited for a diverse range of anticancer drugs. Active targeting techniques like ligand-conjugation and surface modifications have been used to reduce off-target effects and achieve tumour-specific medication delivery. The study explores formulation techniques and adjustments meant to enhance drug stability and encapsulation in these nanocarriers. Encouraging results from clinical trials and preclinical investigations underscore the promise of lipid-based nanocarriers in ovarian cancer treatment, providing optimism for improved patient outcomes. Notwithstanding these advancements, challenges related to clearance, long-term stability, and scalable manufacturing persist. Successfully translating lipidbased nanocarriers into clinical practice requires addressing these hurdles. To sum up, lipidbased nanocarriers are a viable strategy to improve the effectiveness of therapy for ovarian cancer. With their more focused medication administration and lower systemic toxicity, they may completely change the way ovarian cancer is treated and increase patient survival rates. Lipidbased nanocarriers need to be further researched and developed to become a therapeutically viable treatment for ovarian cancer.

Addition of Bevacizumab to Chemotherapy and Its Impact on Clinical Efficacy in Cervical Cancer: A Systematic Review and Meta-Analysis

Background and Objectives: Cervical cancer is the third leading cause of cancer-related mortality in females. One of the most successful therapeutic modalities to date is suppressing vascular endothelial growth factor (VEGF)-mediated angiogenesis. Bevacizumab is a monoclonal antibody that targets VEGF-A. The outcomes for cervical cancer patients treated with bevacizumab in combination with platinum-based chemotherapy have been explored in several studies. This study aimed to assess the impact of bevacizumab on progression-free survival (PFS) and overall survival (OS) in patients with metastatic cervical cancer. Materials and Methods: This systematic review was registered in PROSPERO (CRD42023456755). Following PRISMA guidelines, a comprehensive literature search on PubMed and Google Scholar identified 28 studies meeting the inclusion criteria. The outcomes of interest were PFS and OS. The statistical analysis computed hazard ratios (HRs) with 95% confidence intervals (CIs). The study also included a subgroup analysis by cervical cancer stage. Results: The pooled analysis revealed that bevacizumab-based therapy significantly improved both PFS with HR 0.77 (95% CI: 0.58–0.96; p &lt; 0.01; I2 = 58%) and OS with HR 0.63 (95% CI: 0.45–0.89; p &lt; 0.01; I2 = 41%) in cervical cancer patients. Subgroup analysis by stage of cervical cancer demonstrated better efficacy of bevacizumab in metastatic stage IVB cervical cancer patients indicated by HR for PFS (0.69, 95% CI: 0.54–0.79; p &lt; 0.01) and HR for OS (0.57, 95% CI: 0.46–0.73; p &lt; 0.01). Conclusions: Bevacizumab exhibits a significant increase in PFS and OS, underscoring the efficacy of anti-angiogenesis therapy in cervical cancer, particularly in stage IVB metastatic cervical cancer patients.

Exploring the Role of Unconventional Post-Translational Modifications in Cancer Diagnostics and Therapy.

Unconventional Post-Translational Modifications (PTMs) have gained increasing attention as crucial players in cancer development and progression. Understanding the role of unconventional PTMs in cancer has the potential to revolutionize cancer diagnosis, prognosis, and therapeutic interventions. These modifications, which include O-GlcNAcylation, glutathionylation, crotonylation, including hundreds of others, have been implicated in the dysregulation of critical cellular processes and signaling pathways in cancer cells. This review paper aims to provide a comprehensive analysis of unconventional PTMs in cancer as diagnostic markers and therapeutic targets. The paper includes reviewing the current knowledge on the functional significance of various conventional and unconventional PTMs in cancer biology. Furthermore, the paper highlights the advancements in analytical techniques, such as biochemical analyses, mass spectrometry and bioinformatic tools etc., that have enabled the detection and characterization of unconventional PTMs in cancer. These techniques have contributed to the identification of specific PTMs associated with cancer subtypes. The potential use of Unconventional PTMs as biomarkers will further help in better diagnosis and aid in discovering potent therapeutics. The knowledge about the role of Unconventional PTMs in a vast and rapidly expanding field will help in detection and targeted therapy of cancer.

Using New Technologies to Analyze Gut Microbiota and Predict Cancer Risk

The gut microbiota significantly impacts human health, influencing metabolism, immunological responses, and disease prevention. Dysbiosis, or microbial imbalance, is linked to various diseases, including cancer. It is crucial to preserve a healthy microbiome since pathogenic bacteria, such as Escherichia coli and Fusobacterium nucleatum, can cause inflammation and cancer. These pathways can lead to the formation of tumors. Recent advancements in high-throughput sequencing, metagenomics, and machine learning have revolutionized our understanding of the role of gut microbiota in cancer risk prediction. Early detection is made easier by machine learning algorithms that improve the categorization of cancer kinds based on microbiological data. Additionally, the investigation of the microbiome has been transformed by next-generation sequencing (NGS), which has made it possible to fully profile both cultivable and non-cultivable bacteria and to understand their roles in connection with cancer. Among the uses of NGS are the detection of microbial fingerprints connected to treatment results and the investigation of metabolic pathways implicated in the development of cancer. The combination of NGS with machine learning opens up new possibilities for creating customized medicine by enabling the development of diagnostic tools and treatments that are specific to each patient’s microbiome profile, even in the face of obstacles like data complexity. Multi-omics studies reveal microbial interactions, biomarkers for cancer detection, and gut microbiota’s impact on cancer progression, underscoring the need for further research on microbiome-based cancer prevention and therapy.

Ultrasonic chemical synthesis of zinc-manganese ferrites with improved magnetic properties

Zinc-Manganese spinel ferrites (Zn1-xMnxFe2O4) are nowadays very attractive magnetic materials for cancer diagnostic and therapy. With the help of intense ultrasonic waves, sonochemical synthesis method was used to prepare stoichiometric and chemically homogenous nanoparticles by varying the manganese content. The crystal structure along with the size and shape of the as-prepared nanoparticles were described using XRD, TEM and FT-IR techniques, while cations distribution was carefully investigated using XPS and Mössbauer spectroscopic techniques and supported with density functional theory calculations. The crystal structure study revealed the presence of a pure single cubic spinel phase, where the unit-cell and the size were observed to decrease as the manganese incorporation was increased with clear indication of cationic redistribution and degree of inversion variations. Due to the very small variation of the total energy between different configurations, the probability of formation of a mixed phase was found to be very high in such a way that the more mixed was the phase, the more stable it was. A relevant fact was the noticed quasi-systematic ionic exchange made possible by the very short reaction times and high energy offered by the ultrasonic waves. For manganese concentrations up to 60%, the systematic ionic process started by incorporating manganese ions into octahedral sites and pushing iron ions to migrate and replace those of zinc in tetrahedral sites. Such an ionic movement was of central importance for the improvement of the magnetic properties due to the establishment of super-exchange interactions. Such an ionic engineering should definitely open the way to promising applications in biomedical imaging.

Targeting fibroblast activation protein with chimeric antigen receptor macrophages

Under the rapid advancement of chimeric antigen receptor T cell (CAR-T) technology, CAR-macrophages (CAR-Ms) are also being developed currently in the pre-clinical stage and have been shown to inhibit tumor growth in several mouse tumor models. Fibroblast activation protein (FAP) is a type II transmembrane serine protease, which is expressed in stromal fibroblasts of over 90 % of common human epithelial cancers and is upregulated in fibrotic diseases of the liver, lung and colon, etc. In this study, we firstly constructed FAP-CAR macrophages to target FAP+ cells through in vitro phagocytosis assays. In subsequent in vivo assays, we discovered that FAP-CAR-ΔZETA bone marrow-derived macrophages (BMDMs) rather than FAP-CAR BMDMs, exhibited a pronounced anti-tumor effect in mouse subcutaneous MC38 colon cancer model. In addition, FAP-CAR and FAP-CAR-ΔZETA BMDMs therapy could effectively improve CCl4-induced liver fibrosis in mice. Collectively CAR-Ms targeting FAP demonstrated great therapeutic potential in cancer and liver fibrosis therapy.

Measuring financial distress in German cancer patients: development and validation of the Financial Distress of Cancer Assessment Tool (FIAT)

Cancer diagnosis and therapy can lead to significant financial distress for those affected, even in universal health care systems. We present the development and validation of a patient-reported outcome measure for financial distress in German cancer patients. Validation of the newly developed instrument followed a two-step approach, including two quantitative paper-pencil surveys (N1= 111, N2= 267) with patients of all types of cancer and treatment status at two German university hospitals. Factorial validity, reliability, construct, and criterion validity were assessed using exploratory and confirmatory factor analysis, correlative and linear regression analysis. The Financial Distress of Cancer Assessment Tool (FIAT) comprises 19 items across three domains of subjective financial distress: (i) financial worries; (ii) dissatisfaction across various life domains, and (iii) challenging experiences with authorities and benefit providers (e.g. employment agency, health insurance). Confirmatory factor analysis confirmed the instrument's factorial structure. Composite reliability (Raykov's rho) ranges from 0.88 to 0.96, and retest reliability ranges from 0.64 to 0.75. Correlational analyses showed significant associations between FIAT scores and related constructs [e.g. correlations with the EORTC-QLQ-C30 financial distress subscale (Q28) ranging from 0.47 to 0.60], supporting its construct validity. Additionally, higher FIAT scores were significantly associated with lower health-related quality of life measured by Q29 and Q30 of the EORTC-QLQ-C30, with correlations ranging from-0.21 to-0.28. They were also positively correlated with depression (PHQ-4), with correlations ranging from 0.33 to 0.45, and anxiety (PHQ-4) with correlations ranging from 0.25 to 0.36, confirming its criterion validity. The newly developed patient-reported outcome measure is the first reported measurement tool to assess financial distress in German cancer patients. The instrument can be used for research purposes and to enable the provision of coordinated support services.

Insights into the anticancer effects of galangal and galangin: A comprehensive review

BackgroundsCancer continues to be the leading cause of death worldwide, significantly impacting both health and the economy. Natural products have emerged as promising sources for the development of new anticancer drugs, with galangal and their active ingredient, galangin, garnering substantial interest. PurposeThis study summarizes recent findings on the anticancer properties of galangal and galangin, highlighting their potential to target various cancer types. MethodsWe systematically searched the literature across PubMed, Web of Science, and Google Scholar, using keywords such as “Alpinia officinarum,” “Alpinia galanga”, “galangal,” and “galangin.” This thorough approach allowed us to gather and compile a comprehensive collection of existing research on the topic. ResultsThis article provided a thorough analysis of the distribution of galangal, the methods used to extract the active compounds of galangal, and the anticancer properties of both galangin and galangal. It is important to note that galangal and galangin primarily function by regulating the signaling pathways of PI3K/Akt, MAPK, AMPK, p53, NF-κB, and Ras/RAF/MEK/ERK, which in turn triggers apoptosis, autophagy, and ROS while preventing the migration and invasion of cancer cells. We also discussed their toxicity, bioavailability, and clinical uses. ConclusionIn conclusion, galangal extract and galangin have a lot of promise for treating cancer. It is anticipated that this review will further advance the use of galangal extract and galangin as potential cancer treatment medications. Moreover, the discovery and development of drugs based on galangal has enormous potential for the therapy of cancer.