Cancer Therapy Research Articles

The Alteration Level of VEGF of Colon Cancer Cell After Induction with Mandarin Orange (<i>Citrus Reticulata</i>) Peel Ethanol Extract

The natural ingredient-based therapy extracted from various plants is assumed more tolerable to cancer patients’ bodies than synthetic drugs. To tell successful novel cancer therapy, an indicator is needed to confirm the result. VEGF is a pro-angiogenic factor that leads the cancer cells’ invasion to another organ and is associated with high mortality in patients. Hence, the VEGF level is widely used as one of the successful cancer therapy indicators. Purposed of research elucidated the effect of Mandarin orange peel ethanol extract (EEKJM) to improve the reduction of VEGF levels in colon cancer in vitro. This study was an experimental posttest and control group design to analyze different level of VEGF on cancer cells at end of the study. Research began with the preparation of EEKJM followed by a cytotoxic extract test using the MTT assay method. Furthermore, the measurement of VEGF levels by the VEGF ELISA kit protocol. One Way ANOVA was performed to analyze data.Results showed the cytotoxic test of the EEKJM and doxorubicin against WiDr cells was 240 g/ml and 1.59 µg/ml. VEGF levels showed decreasing after being induced with EEKJM and doxorubicin with doses ½ IC50 and ¼ IC50. Conclusion: EEKJM was able to reduce VEGF levels and viability of WiDr colon cancer cells. The advantages are as much as initial evidence of the ability of the orange to treat cancer even though further animal studies or evidence of a pathway of decrease of the VEGF or other signals are required.

Side effects of Immune Checkpoint Inhibitors : Diagnostics and Management-an Update

Immune checkpoint inhibitors (ICI) represent a breakthrough in cancer therapy. They are effective in various tumor entities and can be used in more and more treatment settings. This leads to an increase in the number and complexity of cases with immune-related adverse events (irAE). The most common irAE are cutaneous, gastrointestinal and endocrine side effects, whereas less common irAE include pneumonitis, nephritis, myocarditis or neurological reactions. IrAE can usually be successfully treated, mainly with corticosteroids or other immunosuppressants, but they can also result in long-term sequelae or death. The optimal management of patients with steroid-refractory or steroid-dependent side effects still remains unclear. Broad awareness of these irAE across specialties is therefore of crucial importance to ensure early diagnosis and to improve irAE management.

Clinical efficacy and safety of immune checkpoint inhibitors plus anlotinib as secondline or subsequent therapy in extensive stage small cell lung cancer: a retrospective study.

Treatments are limited for extensive stage small cell lung cancer (ES-SCLC) patients in secondline or subsequent setting. This study aimed to explore the clinical efficacy and safety of immune checkpoint inhibitors (ICIs) plus anlotinib as secondline or subsequent therapy in ES-SCLC. We retrospectively analyzed 116 patients with ES-SCLC at Shandong Provincial Qianfoshan Hospital between January 2019 and March 2024. According to the different therapy regimes, they were divided into three groups, ICI plus anlotinib as secondline or subsequent therapy group (ICI + anlotinib group), single ICI as secondline or subsequent therapy group (single ICI therapy group), single chemotherapy as secondline therapy group (single chemotherapy group). Kaplan-Meier method was used to compare the progression-free survival (PFS) and the overall survival time (OS) among these three groups. Cox regression analysis was used to analyze different factors which correlated to PFS and OS. The adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Kaplan-Meier analysis showed that patients in ICI + anlotinib group had a longer PFS and OS compared to patients in single ICI therapy group (median PFS [mPFS]: 6.7months vs. 4.6months, P = 0.007; median OS [mOS]:12.4months vs. 8.4months, P = 0.041) and single chemotherapy group (mPFS: 6.7months vs. 3.0months, P < 0.001; mOS: 12.4months vs. 7.2months, P = 0.002). The Cox regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastasis, brain metastasis and treatment regimes were independent predictors that affecting the PFS and OS of all the enrolled patients. The common adverse events (AEs) were wleukopenia and fatigue. There was no significant statistical difference in other AEs among the three groups except for leukopenia. ICI + anlotinib as secondline or subsequent therapy has better efficacy than single ICI group and single chemotherapy group and with tolerable toxicities for patients with ES-SCLC.

Poor prognosis among radiation associated bladder cancer is defined by clinicogenomic features.

Radiation therapy (RT) for prostate cancer has been associated with an increased risk for the development of bladder cancer. We aimed to integrate clinical and genomic data to better understand the development of RT-associated bladder cancer. A retrospective analysis was performed to identify control (CTRL; n= 41) and RT-associated (n=41) bladder cancer patients. RT and CTRL specific features were then identified through integration and analysis of the genomic sequencing data and clinical variables. RT-associated bladder tumors were significantly enriched for alterations in KDM6A and ATM, while CTRL tumors were enriched for CDKN2A mutation. Globally, there was an increased number of variants within RT tumors, albeit at a lower variant allele frequency. Mutational signature analysis revealed three predominate motif patterns, with similarity to SBS2/13 (APOBEC3A), SBS5 (ERCC2/Smoking) and SBS6/15 (MMR). Poor prognostic factors in the RT cohort include, a short tumor latency, smoking status, the presence of the smoking and XRT mutational signatures, and CDKN2A copy number loss. Based on the clinical and genomic findings, we suggest, at least two potential pathways leading to RT-associated bladder cancer; the first, occurs in the setting of field cancerization, related to smoking or pre-existing genetic alterations and leads to the development of more aggressive bladder tumors, and the second, in which RT initiates the oncogenic process in otherwise healthy urothelium, leading to a longer latency and less aggressive disease.

68Ga/177Lu-Labeled Bivalent Agents for Targeting Hypoxia and PSMA-Binding in Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is an excellent target for cancer detection and therapy. Hypoxia is prevalent in solid tumors, and various nitroimidazole (NI) radioligands can be trapped inside hypoxic cells for diagnosis and therapy. To enhance tumor uptake and retention, we designed bivalent agents (compounds 1-8) incorporating a hypoxia-sensitive NI-moiety and a PSMA-targeting group. Ligands 1-8 were successfully prepared and labeled with 68Ga or 177Lu. Among them, [68Ga]Ga-8 ([68Ga]Ga-AAZTA-NI-PSMA-093) demonstrated significantly higher cellular accumulation under hypoxic conditions than under normoxic conditions, suggesting hypoxia-selective trapping by the introduction of NI group. PET/CT imaging at 60 min postinjection of [68Ga]Ga-8 revealed high tumor uptake (SUVmax: 10.68%ID/mL) in the tumor-bearing mice model. SPECT/CT imaging of [177Lu]Lu-8 at 24 and 48 h postinjection demonstrated excellent accumulation and retention. Preliminary studies indicate that [68Ga]Ga/[177Lu]Lu-8 may be promising bivalent agents targeting hypoxia and PSMA binding for diagnosis and radiotherapy.

Enhancing Bioactivity of N,N,N-Chelating Rhodium(III) Complexes with Ionic Liquids: Toward Targeted Cancer Therapy.

This study investigates the potential of using ionic liquids as cosolvents to enhance the solubility and activity of poorly soluble rhodium(III) complexes, particularly those with diene, pyridine derivatives, and camphor-derived bis-pyrazolylpyridine ligands, in relation to 5'-GMP, CT-DNA, and HSA as well as their biological activity. Findings indicate that ionic liquids significantly increase the substitution activity of these complexes toward 5'-GMP while only marginally affecting DNA/HSA binding affinities with molecular docking, further confirming the experimental results. Lipophilicity assessments indicated good lipophilicity. Notably, cytotoxicity studies show that Rh2 is selectively effective against HeLa cancer cells, with IL1 and IL10 modulating the cytotoxic effects. Redox evaluations indicate that rhodium complexes induce oxidative stress in cancerous cells while maintaining redox balance in noncancerous cells. By elucidating the role of ionic liquids in modulating these effects, the study proposes a promising avenue for augmenting the efficacy and selectivity of cancer treatments, thus opening new horizons in cancer therapeutics.

Theranostic Nanoplatform Based on Polydopamine-Coated Magnetic Mesoporous Silicon for Precise Cancer Triplex Nanotherapy and Multimodal Imaging.

Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.

Simultaneous estimation of paclitaxel and bortezomib via LC-MS/MS: pharmaceutical and pharmacokinetic applications.

Aim & Objective: This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. Materials & Methods: The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Results: Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10mM ammonium acetate. The size of nanoformulation was 133.9±1.97nm, PDI 0.19±0.01 and zeta potential -19.20±1.36mV. Pharmacokinetics showed higher Cmax for PTX-BTZ-NE (313.75±10.71ng/ml PTX, 11.92±0.53ng/ml BTZ) versus free PTX-BTZ (104±13.06ng/ml PTX, 1.9±0.08ng/ml BTZ). Conclusion: Future findings will contribute to the treatment of breast cancer using PTX and BTZ.

Electron Nuclear Dynamics of H+ + C2H2 at ELab = 30, 200, and 450 eV.

We present a complete simplest-level electron nuclear dynamics (SLEND) investigation of H+ + C2H2 at collision energies ELab = 30, 200, and 450 eV. This reaction is relevant in astrophysics and provides a computationally feasible prototype for proton cancer therapy reactions. SLEND is a time-dependent, variational, direct, and nonadiabatic method that adopts a classical-mechanics description for the nuclei and a Thouless single-determinantal wave function for the electrons. We perform this study with our code PACE, which incorporates the One Electron Direct/Electron Repulsion Direct (OED/ERD) atomic integrals package developed by the Bartlett group. Current SLEND simulations with the 6-31G** basis set involves 2,646 trajectory calculations from 9 nonredundant, symmetry-inequivalent projectile-target orientations. For H+ + C2H2 at ELab = 30 eV, SLEND/6-31G** simulations predict one simple scattering process, and three reactive ones: C2H2 hydrogen substitution, C2H2 fragmentation into two CH moieties, and C2H2 fragmentation into CHC and H moieties, respectively. We reveal and analyze the mechanisms of these processes through computer animations; this valuable chemical information is inaccessible by experiments. The SLEND/6-31G** scattering angle functions exhibit primary and secondary rainbow scattering features that vary with the projectile-target orientations and collision energies. SLEND/6-31G** predicts 1-electron-transfer (1-ET) integral cross sections at ELab = 30, 200, and 450 eV in good agreement with their experimental counterparts. SLEND/6-31-G** predicts 1-ET differential cross sections (DCSs) at ELab = 30 eV that agree well with their experimental counterparts over all the measured scattering angles. In addition, SLEND/6-31G** predicts 0-ET DCSs at ELab = 30 eV that agree well with their experimental counterparts at low scattering angles, but less satisfactorily at higher ones. Remarkably, both the 0- and 1-ET DCSs from SLEND/6-31G** exhibit distinct primary rainbow scattering signatures in excellent agreement with their experimentally inferred counterparts. Furthermore, both SLEND/6-31G** and the experiment indicate that the primary rainbow scattering angles from the 0- and 1-ET DCSs are identical (an unusual fact in proton-molecule collisions). Through these rainbow scattering predictions, SLEND has also validated a procedure to extract primary rainbow angles from structureless DCSs. We analyze the obtained theoretical results in comparison with available experimental data and discuss forthcoming developments in the SLEND method.

Targeted biocompatible Zn-metal–organic framework nanocomposites for intelligent chemotherapy of breast cancer cells

Finding a novel drug delivery system (DDS) represents one of the most challenging endeavors in cancer therapy. Hence, in this study, we developed a new biocompatible and biodegradable zinc-based nanoscale metal–organic framework (Zn-NMOF) coated with folic acid (FA) functionalized chitosan (CS) to facilitate targeted delivery of doxorubicin (D), a standard chemotherapeutic agent, into breast cancer cells. The synthesis of the NMOF-CS-FA-D nanocomposite preceded its comprehensive characterization via FT-IR, DLS, XRD, SEM, and TEM analyses. Subsequent in vitro studies were conducted on MCF-7 breast cancer cells and HFF-1 normal cells, encompassing assessments of cell viability, expression levels of apoptotic and autophagy genes, cell cycle arrest, and apoptotic analyses. The size of the NMOF-CS-FA-D particles was determined to be less than 80 nm, with a drug loading efficiency of 72 ± 5%. The release kinetics of DOX from the nanocomposite were investigated, revealing controlled release behavior at pH 7.4 and accelerated release at pH 5.0, which is conducive to drug delivery into cancer cells. In vitro results indicated a 17.39% ± 6.34 cell viability after 24 h of treatment with a 40 nM concentration of the NMOF-CS-FA-D nanocomposite. Furthermore, the expression levels of Caspase-9 and BAX, key apoptotic genes, along with BECLIN1, an autophagy gene, were found to increase by two-fold, four-fold, and two-fold, respectively, following 5 h of treatment with the nanocomposite. Additionally, analysis of cell cycle distribution revealed 15.4 ± 2% of cells in the sub-G1 phase, indicative of apoptotic cells, and 31.9% of cells undergoing early and late apoptosis in MCF-7 cells. Collectively, these findings underscore the potential of the NMOF-CS-FA-D nanocomposite in inhibiting cancer cell proliferation with low side effects.

Spiky tubular nanoparticles with low protein corona can realize efficient and non-destructive penetration through endothelial barrier

Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy, and pursue high drug-load NPs with surface designs. Compared to solid and mesoporous NPs, we found the spiky tubular NPs reserved the NPs' antifouling properties (or shedding of “protein corona”), promoted better endothelial penetration and less destruction in vitro and in vivo. Such effects could be attributed to their spiky surface structures, which can limit the NP-protein interaction area and promote the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy and lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of vascular endothelia. As a result, the spiky tubular NPs demonstrated its advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Exploiting such spiky tubular surface modification, we can improve the NP delivery efficiency and prohibit the leakiness of vascular endothelia, helping address challenges faced by tumor migration in nanomedicine applications for cancer therapy.

The Emerging Role of Herbal Medicines in Cancer by Interfering with Posttranslational Modifications.

Significance: Herbal medicines have a long history of comprehensive cancer treatment through various posttranslational modifications (PTMs). Recently, emerging evidence revealed that dysregulation of reactive oxygen species (ROS) and ROS-regulated signaling pathways influence cancer initiation, growth, and progression in a paradoxical role with either low levels or increasing levels of basal ROS. However, ROS-triggered modifications of target proteins in the face of ROS-mediated signal transduction are not fully understood in the anticancer therapies of herbal medicines. In this review, we briefly introduce the PTM-dependent regulations of herbal medicines, and then focus on the current ideals that targeting ROS-dependent PTMs via antioxidant and redox signaling pathways can provide a promising strategy in herbal-based anticancer effects. Recent Advances: Advanced development in highly sensitive mass spectrometry-based techniques has helped utilize ROS-triggered protein modifications in numerous cancers. Accumulating evidence has been achieved in laboratory to extensively ascertain the biological mechanism of herbal medicines targeting ROS in cancer therapy. Two general mechanisms underlining ROS-induced cell signaling include redox state and oxidative modification of target protein, indicating a new perspective to comprehend the intricate dialogues between herbal medicines and cancer cellular contexts. Critical Issues: Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that ROS-dependent PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating ROS-triggered PTMs implicated in cell signaling, apoptosis, and transcriptional regulation function, and the possible cellular signaling, has provided important information about the contribution of many ROS targeting herbal therapies in anticancer effects. Continued optimization of proteomic strategies for PTM analysis in herbal medicines is also briefly discussed. Future Directions: Rigorous evaluations of herbal medicines and proteomic strategies are necessary to explore the aberrant regulation of ROS-triggered antioxidant and redox signaling contributing to the novel protein targets and herbal-associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents.

Mathematical Modeling of Tumor Immune Interactions: The Role of Anti-FGFR and Anti-PD-1 in the Combination Therapy.

Bladder cancer poses a significant global health burden with high incidence and recurrence rates. This study addresses the therapeutic challenges in advanced bladder cancer, focusing on the competitive mechanisms of ligand or drug binding to receptors. We developed a refined mathematical model that integrates the dynamics of tumor cells and immune responses, particularly targeting fibroblast growth factor receptor 3 (FGFR3) and immune checkpoint inhibitors (ICIs). This study contributes to understanding combination therapies by elucidating the competitive binding dynamics and quantifying the synergistic effects. The findings highlight the importance of personalized immunotherapeutic strategies, considering factors such as drug dosage, dosing schedules, and patient-specific parameters. Our model further reveals that ligand-independent activated-state receptors are the most essential drivers of tumor proliferation. Moreover, we found that PD-L1 expression rate was more important than PD-1 in driving the dynamic evolution of tumor and immune cells. The proposed mathematical model provides a comprehensive framework for unraveling the complexities of combination therapies in advanced bladder cancer. As research progresses, this multidisciplinary approach contributes valuable insights toward optimizing therapeutic strategies and advancing cancer treatment paradigms.

Gold(III)-Induced Amide Bond Cleavage In Vivo: A Dual Release Strategy via π-Acid Mediated Allyl Substitution.

Selective cleavage of amide bonds holds prominent significance by facilitating precise manipulation of biomolecules, with implications spanning from basic research to therapeutic interventions. However, achieving selective cleavage of amide bonds via mild synthetic chemistry routes poses a critical challenge. Here, we report a novel amide bond-cleavage reaction triggered by Na[AuCl4] in mild aqueous conditions, where a crucial cyclization step leads to the formation of a 5-membered ring intermediate that rapidly hydrolyses to release the free amine in high yields. Notably, the reaction exhibits remarkable site-specificity to cleave peptide bonds at the C-terminus of allyl-glycine. The strategic introduction of a leaving group at the allyl position facilitated a dual-release approach through π-acid catalyzed substitution. This reaction was employed for the targeted release of the cytotoxic drug monomethyl auristatin E in combination with an antibody-drug conjugate in cancer cells. Finally, Au-mediated prodrug activation was shown in a colorectal zebrafish xenograft model, leading to a significant increase in apoptosis and tumor shrinkage. Our findings reveal a novel metal-based cleavable reaction expanding the utility of Au complexes beyond catalysis to encompass bond-cleavage reactions for cancer therapy.

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Given that the original tumor microenvironment of oral cancer cannot be reproduced, predicting the therapeutic effects of irradiation using monolayer cultures and animal models of ectopic tumors is challenging. Unique properties of carbon-ion irradiation (CIR) characterized by the Bragg peak exert therapeutic effects on tumors and prevent adverse events in surrounding normal tissues. However, the underlying mechanism remains unclear. The biological effects of CIR were evaluated on three-dimensional (3D) in vitro models of normal oral mucosa (NOMM) and oral cancer (OCM3 and OCM4) consisting of HSC-3 and HSC-4 cells. A single 10- or 20-Gy dose of CIR was delivered to NOMM, OCM3, and OCM4 models. Histopathological and histomorphometric analyses and labeling indices for Ki-67, γH2AX, and TUNEL were examined after CIR. The concentrations of high mobility group box 1 (HMGB1) were measured. NOMM exhibited epithelial thinning after CIR, which could be caused by the decreased presence of Ki-67-labeled basal cells. The relative proportion of the thickness of cancer cells to the underlying stroma in cancer models decreased after CIR. This finding appeared to be supported by changes in the three labeling indices, indicating CIR-induced cancer cell death, mostly via apoptosis. Furthermore, the three indices and the HMGB1 release levels significantly differed among the OCM4 that received different doses and with different incubation times after CIR while those of the OCM3 models did not, suggesting more radiosensitivity in the OCM4. The three 3D in vitro models can be a feasible and novel tool to elucidate radiation biology.

SNORD88B-mediated WRN nucleolar trafficking drives self-renewal in liver cancer initiating cells and hepatocarcinogenesis

Whether small nucleolar RNAs (snoRNAs) are involved in the regulation of liver cancer stem cells (CSCs) self-renewal and serve as therapeutic targets remains largely unclear. Here we show that a functional snoRNA (SNORD88B) is robustly expressed in Hepatocellular carcinoma (HCC) tumors and liver CSCs. SNORD88B deficiency abolishes the self-renewal of liver CSCs and hepatocarcinogenesis. Mechanistically, SNORD88B anchors WRN in the nucleolus, promoting XRCC5 interacts with STK4 promoter to suppress its transcription, leading to inactivation of Hippo signaling. Moreover, low expression of STK4 and high expression of XRCC5 are positively correlated with HCC poor prognosis. Additionally, snord88b knockout suppresses mouse liver tumorigenesis. Notably, co-administration of SNORD88B antisense oligonucleotides (ASOs) with MST1 agonist adapalene (ADA) exert synergistic antitumor effects and increase overall murine survival. Our findings delineate that SNORD88B drives self-renewal of liver CSCs and accelerates HCC tumorigenesis via non-canonical mechanism, providing potential targets for liver cancer therapy by eliminating liver CSCs.

Translational history and hope of immunotherapy of canine tumors.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, makes them ideal subjects for studying cancer therapies. Tumors like osteosarcoma (cOSA), hemangiosarcoma (cHSA), soft-tissue sarcoma (cSTS), and non-Hodgkin lymphoma (cnHL) occur with greater frequency than their counterpart disease in humans. Canine brain tumors allow study of therapy strategies with imaging, surgery, and radiotherapy equipment in veterinary patients with near-human geometry. Non-specific immunostimulants, autologous and allogeneic vaccines, immune checkpoint inhibitors, and cellular therapies used treating canine cancers have been tested in veterinary clinical trials. These treatments have not only improved outcomes for dogs but have also provided valuable insights for human cancer treatment. Advancements in radiation technology and the development of tools to characterize canine immune responses have further facilitated the ability to translate veterinary clinical trial results to human applications. Advancements in immunotherapy of canine tumors have directly supported translation to human clinical trials leading to approved therapies for cancer patients around the world. The study of immunotherapy in dogs has been and will continue to be a promising avenue for advancing human cancer treatment.

MXene-Polydopamine-antiCEACAM1 Antibody Complex as a Strategy for Targeted Ablation of Melanoma.

Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.

Temporal Optimization in the Synthesis of Multifunctional Nano Agents for Enhanced MRI Contrast, Hyperthermia Therapy, and ROS Generation.

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments. The objective of this investigation is to scrutinize the relationship between the reaction duration and the characteristics of carbon-doped silica core-shell iron oxide nanoparticles (CSIONPs). Specifically, we focus on CSIONP-12, CSIONP-24, and CSIONP-36, synthesized by using varying reaction periods. Through a comprehensive analysis, we primarily evaluate the impact of these formulations on T1 and T2 magnetic resonance imaging (MRI), aiming to elucidate their mechanisms and therapeutic potential in promoting hyperthermia and ROS-mediated cancer therapy. CSIONP-24 emerges as a compelling candidate due to its dual influence on magnetic hyperthermia and ROS generation, suggesting its promise in enhancing cancer treatment outcomes. Furthermore, the findings underscore the exceptional T1-T2 MRI capabilities of this technology, underscoring its versatility and efficacy in the nuanced realm of cancer theranostic.

Prognostic genome and transcriptome signatures in colorectal cancers.

Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFβ pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy.