Treatment Outcomes In Cancer Patients Research Articles

Tumor Hypoxia and Radioresistance

Tumor hypoxia is a prevalent feature of solid tumors, significantly contributing to increased tumor aggressiveness, metastatic potential, and resistance to conventional therapies such as radiotherapy. This review explores the complex relationship between tumor hypoxia and radioresistance, highlighting the molecular mechanisms involved and potential therapeutic strategies to enhance radiotherapy efficacy in hypoxic tumors. Key mechanisms include the role of hypoxia-inducible factors (HIFs), particularly HIF-1α, which regulates numerous genes involved in tumor survival, proliferation, and resistance under hypoxic conditions. The review also discusses the oxygen enhancement ratio (OER) and its impact on radiotherapy outcomes, emphasizing how hypoxia leads to reduced radiosensitivity by limiting the formation of radiation-induced DNA damage. Despite the development of various strategies to counteract hypoxia-induced radioresistance, such as HIF inhibitors, hypoxia-targeted gene therapy, and hypoxia-activated prodrugs (HAPs), clinical results have been mixed, necessitating further research. Additionally, advances in imaging techniques for detecting tumor hypoxia are explored, which may allow for more personalized radiotherapy approaches, such as dose painting. The future of overcoming tumor hypoxia in radiotherapy lies in the integration of innovative therapeutic strategies, personalized medicine, and improved imaging technologies, offering hope for enhanced treatment outcomes in cancer patients.

Alcohol consumption in cancer patients receiving psycho-oncologic care analysis of socio-demographic, health-related and cancer-related factors.

The carcinogenic effects of alcoholic beverages and the negative impact of alcohol consumption on cancer progression and treatment outcomes are well established in oncology research. Many cancer patients experience significant psychological distress, often manifesting as elevated levels of depression and anxiety. In the general population, alcohol consumption is commonly used as a coping mechanism for such distress. For cancer patients facing substantial psychological challenges, psycho-oncology care is available to help manage their symptoms and the overall impact of their condition. However, there is limited understanding of the alcohol consumption patterns in this particularly vulnerable group of patients, as well as the disease-related factors that may influence their drinking behavior. This study aims to examine the prevalence of potentially risky alcohol consumption in cancer patients receiving psycho-oncology care and to identify sociodemographic, health-related, and psychosocial factors associated with alcohol consumption after cancer diagnosis. By understanding drinking patterns and the factors associated with them, we aim to promote healthier behaviors and enhance treatment outcomes for cancer patients receiving psycho-oncology care. A consecutive sample of 1.225 patients from the psycho-oncology outpatient clinic of the University Medical Center Hamburg Eppendorf (UKE) was analyzed with regard to their alcohol consumption behavior using the Alcohol Use Disorders Identification Test-Consumption Items (AUDIT-C). Self-report questionnaires were employed to assess sociodemographic, health-related, and cancer-specific information. For statistical analysis, multiple linear regression was utilized. In the sample of cancer patients receiving psycho-oncology support one in six of both female and male patients showed risky alcohol drinking behavior (e.g. AUDIT-C above three for women and four for men). In the analysis (R-Square: 0.056) male gender (regression coefficient B 0.686, 95% CI: 0.453-0.919) and patientsreporting a higher physical health-related quality of life (SF8-PCS) (B 0.021, 95% CI: 0.011-0.032) were associated with higher levels of alcohol consumption, whereas having children (B -0.481, 95%CI: -0.700- -0.262) was associated with lower alcohol consumption. With regard to cancer type, a single-factor analysis of variance with gender as the centered covariate showed that patients with gastrointestinal cancer had had lower average consumption levels compared to the groups of patients with breast cancer, melanoma, genitourinary cancer, and lymphoma. Also, patients with sarcoma had lower average consumption levels than patients with lymphoma. The results allow to identify patient characteristics and cancer types associated with higher or lower alcohol consumption levels and higher likelihood of risky consumption behavior in this sample of cancer patients receiving psycho-oncological support. Cancer patients are particularly susceptible to the hazardous effects of alcohol consumption. The results of this study help to identify cancer patients at risk of worsening prognosis due to alcohol consumption and to develop intervention programs to minimize alcohol consumption in this group.

Magnetic Resonance-Guided Cancer Therapy Radiomics and Machine Learning Models for Response Prediction.

Magnetic resonance imaging (MRI) is known for its accurate soft tissue delineation of tumors and normal tissues. This development has significantly impacted the imaging and treatment of cancers. Radiomics is the process of extracting high-dimensional features from medical images. Several studies have shown that these extracted features may be used to build machine-learning models for the prediction of treatment outcomes of cancer patients. Various feature selection techniques and machine models interrogate the relevant radiomics features for predicting cancer treatment outcomes. This study aims to provide an overview of MRI radiomics features used in predicting clinical treatment outcomes with machine learning techniques. The review includes examples from different disease sites. It will also discuss the impact of magnetic field strength, sample size, and other characteristics on outcome prediction performance.

Foundations for a Personalized Psycho-Oncology: The State of the Art.

Personalized psycho-oncology represents a major challenge for the holistic care of cancer patients. It focuses on individualized psychotherapeutic and psychiatric interventions to address specific psychological needs. This narrative review summarizes the current literature on personalized psycho-oncology and highlights the prevalence and impact of psychiatric/psychological disorders in cancer patients. Personalized approaches, including tailored interventions and interdisciplinary collaboration, have been shown to be effective in improving mental health and overall quality of life. The integration of inflammatory biomarkers into treatment plans is a promising but challenging way to alleviate mental health problems. In addition, there is a need for specific diagnostic tools and treatment guidelines that take into account the specific psychological impact of different types of cancer. Future research should aim to refine these personalized strategies, improve diagnostic accuracy, and evaluate the cost-effectiveness of these interventions to improve both the psychological well-being and treatment outcomes of cancer patients.

Exploring the Potential Use of Natural Products Together with Alkalization in Cancer Therapy

Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with supplementation with natural products may confer benefits to cancer patients, by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A systematic review.

In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment. The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023. Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion. By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.

Precision Phenotypic Profiling and Capture of Circulating Tumor Cells via a Vertical Laminar Flow-Stacked Microfluidic Chip.

The heterogeneity of circulating tumor cells has a significant impact on the diagnosis, treatment, and monitoring of cancer. Research on the subtypes of circulating tumor cells can bring better treatment outcomes for cancer patients. Here, we proposed a microfluidic chip for the magnetic capture of subtypes of circulating tumor cells from the whole blood and phenotypic profiling by stacking laminar flow vertically. Circulating tumor cells were sorted and captured by the three-dimensional regulation of both magnetic fields in the vertical direction and flow fields in the lateral direction. Using EpCAM-magnetic beads, we achieved sorting and sectional capture of target cells in whole blood and analyzed the surface expression levels of the captured cells, confirming the functionality of the microfluidic chip in sorting and capturing subtypes of circulating tumor cells. This microfluidic chip can also aid in the subsequent subtype analysis of other rare cells.

Role of mitochondria in doxorubicin-mediated cardiotoxicity: From molecular mechanisms to therapeutic strategies.

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control, including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Abstract 2312: Integrating spatial multi-omics data with spatial quantitative pharmacology (spQSP) model to simulate human neoadjuvant immunotherapy clinical trial of hepatocellular carcinoma

Abstract Human clinical trials provided tremendous insights to advance novel systemic therapies and to improve treatment outcomes for cancer patients. The few durable treatment options have led to a critical need to advance new therapeutics in hepatocellular carcinoma (HCC). Recent human clinical trials have demonstrated that new combination of immunotherapeutic regimens provide augmented clinical response in a subset of patients. Computational methods that can simulate tumors from mathematical equations describing cellular and molecular interactions are emerging as promising tools to simulate the impact of therapies entirely in silico. To facilitate designing dosing regimens and selecting potential predictive biomarkers, we developed a new computational model to track tumor progression at organ scale while reflecting the spatial heterogeneity in the tumor at cellular and molecular scale in HCC. This computational model is called a spatial quantitative systems pharmacology (spQSP) platform and it is also designed to simulate the effects of combination immunotherapy. The model is first calibrated using clinical outcomes and measured immune cell densities based on recent neoadjuvant HCC clinical trial combining anti-PD-1 immunotherapy and a multitargeted tyrosine kinase inhibitor (TKI) cabozantinib (NCT03299946). Then, we validate the results from the spQSP model by leveraging real-world spatial multi-omics data from the same clinical trial. The model output is compared with spatial data from Imaging Mass Cytometry (IMC). Both IMC data and simulation results suggest closer proximity between CD8 T cell and Arginase 1 (Arg1) positive macrophages among non-responders while the reverse trend was observed for responders. We also compared the model output with Visium spatial transcriptomics analyses of samples from post-treatment tumor resections in the original clinical trial. Both spatial transcriptomic data and simulation results identify the role of spatial patterns of tumor vasculature and TGFβ in tumor and immune cell interactions. To our knowledge, this is the first spatial tumor model for virtual clinical trials at a molecular and cellular scale that is grounded in high-throughput spatial multi-omics data from a human clinical trial. Citation Format: Shuming Zhang, Atul Deshpande, Babita K. Verma, Hanwen Wang, Haoyang Mi, Long Yuan, Won Jin Ho, Elizabeth M. Jaffee, Qingfeng Zhu, Robert A. Anders, Mark Yarchoan, Luciane T. Kagohara, Elana J. Fertig, Aleksander S. Popel. Integrating spatial multi-omics data with spatial quantitative pharmacology (spQSP) model to simulate human neoadjuvant immunotherapy clinical trial of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2312.

Effects of Curcumin on Treatment Outcome in Patients with Cancer Diagnosis

Introduction: Treatment options for palliative care in patients with cancer aim to improve quality of life, and, in this context, alternative, complementary treatments are under study to reduce treatment side effects and increase traditional treatment efficacy. Curcumin is a food supplement derived from the plant Curcuma longa, which has recently received increasing attention because of its antioxidant and anti-inflammatory effects. Previous clinical trials, with different results, investigated Curcumin’s efficacy in cancer treatment. We aimed to explore the effect of Curcumin on treatment outcomes in patients with cancer diagnosis. Methods: In this systematic mini-review, conducted to answer the research question "What is the effect of curcumin on treatment outcome of cancer patients?" we searched four portals/databases (Pubmed/Medline, BVS/Lilacs, Scielo, and Cochrane). The PICOT strategy adopted was: P - patients with cancer; I - Curcumin; C- not applicable; O - treatment outcome; T- RCT and cohort studies. Independent reviewers checked for eligibility and study quality. Results: We included six studies regarding prostate cancer, head and neck tumors, colorectal cancer, breast cancer, and bladder cancer. Studies showed good tolerability for Curcumin with mild adverse effects. However, it showed no significant difference in survival or tumor progression. On the contrary, researchers observed exciting findings concerning preventing and relieving chemotherapy-related adverse effects. Discussion: Curcumin appears to be an intriguing potential adjuvant therapy in patients with cancer. Further studies on the topic are needed to investigate its possible concrete applications and to address the known problem of its poor bioavailability.

Preparation and in vitro evaluation of BBG-250 loaded liposomal formulation for anticancer potential

BackgroundLiposome-mediated drug delivery systems have emerged as a promising avenue for enhancing cancer treatment strategies. This study aims to develop and assess liposomal carriers loaded with Brilliant Blue G-250 (BBG-250), a potent P2X7 receptor antagonist that shows potential as an anti-tumor agent. Specifically, two types of liposomal formulations were designed: conventional liposomes composed of hydrogenated soya phosphatidylcholine (HSPC) and cholesterol, and pH-sensitive liposomes consisting of dioleoylphosphatidylethanolamine (DOPE), distearoylphosphatidylethanolamine-methoxy polyethylene glycol (DSPE-mPEG), dipalmitoylphosphatidylcholine (DPPC), and cholesterol. The investigation focuses on understanding the morphological characteristics, size, stability, drug incorporation efficiency, drug release profiles, blood compatibility, and cytotoxicity of these liposomal formulations.ResultsAdvanced photon correlation spectroscopy using the Nano Plus-3 instrument was employed to evaluate the liposomes. The optimized conventional liposomes (HSPC-cholesterol ratio 7:3) exhibited a size of 125 ± 0.3 nm with a polydispersity index (PDI) of 0.21, indicating uniformity. The pH-sensitive liposomes (DOPE:DPPC:DSPE-PEG2000: Cholesterol 4:3:3:0.3) demonstrated a size of 118 ± 1.2 nm with a PDI of 0.230. Zeta potential measurements confirmed the stability of both formulations under physiological conditions, with values of − 16.93 mV for conventional liposomes and − 25.21 mV for pH-sensitive liposomes. Higher drug-to-lipid ratios were found to enhance drug incorporation efficiency. pH-sensitive liposomes exhibited superior drug release characteristics, with 95% release over 24 h, compared to conventional liposomes, which released 70% of the drug. Blood compatibility assessments revealed the safety of both formulations for intravenous administration. Cytotoxicity studies conducted on A549 cell lines demonstrated the cytocompatibility of both liposomal types across a range of concentrations, with IC50 values surpassing those of the reference drug, docetaxel.ConclusionsThis study underscores the potential of liposomal carriers as effective vehicles for delivering BBG-250, highlighting their stability, biocompatibility, and controlled drug release properties. Despite being slightly less potent than the reference drug, docetaxel, these liposomal formulations hold promise for advancing anticancer strategies. The findings contribute to the evolving landscape of innovative cancer therapy drug delivery systems, offering a novel approach to improving treatment outcomes for cancer patients. The successful development and evaluation of these liposomal carriers pave the way for further investigations and potential clinical applications in the field of cancer therapeutics.

Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics.

Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.

Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.

Recombinant cytokine products have emerged as a promising avenue in cancer therapy due to their capacity to modulate and enhance the immune response against tumors. However, their clinical application is significantly hindered by systemic toxicities already at low doses, thus preventing escalation to therapeutically active regimens. One promising approach to overcoming these limitations is using antibody-cytokine fusion proteins (also called immunocytokines). These biopharmaceuticals leverage the targeting specificity of antibodies to deliver cytokines directly to the tumor microenvironment, thereby reducing systemic exposure and enhancing the therapeutic index. This review comprehensively examines the development and potential of antibody-cytokine fusion proteins in cancer therapy. It explores the molecular characteristics that influence the performance of these fusion proteins, and it highlights key findings from preclinical and clinical studies, illustrating the potential of immunocytokines to improve treatment outcomes in cancer patients. Recent advancements in the field, such as novel engineering strategies and combination strategies to enhance the efficacy and safety of immunocytokines, are also discussed. These innovations offer new opportunities to optimize this class of biotherapeutics, making them a more viable and effective option for cancer treatment. As the field continues to evolve, understanding the critical factors that influence the performance of immunocytokines will be essential for successfully translating these therapies into clinical practice.

Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Cannabinoids and the endocannabinoid system in immunotherapy: helpful or harmful?

Numerous studies in various cancer models have demonstrated that ingredients of cannabis can influence tumor growth through the endocannabinoid system (ECS), a network of molecules (mediators, receptors, transporters, enzymes) that maintains homeostasis and protection in many tissues. The main constituents of the ECS are the classical cannabinoid (CB) receptors, such as CB1 and CB2, their endogenous ligands (endocannabinoids), and the endocannabinoids’ synthesizing and degrading enzymes. The role of the ECS in cancer is still unclear and its effects often depend on the tumor entity and the expression levels of CB receptors. Many studies have highlighted the tumor cell-killing potential of CB1 agonists. However, cannabis is also known as an immunosuppressant and some data suggest that the use of cannabis during immunotherapy worsens treatment outcomes in cancer patients. CB receptors are widely present in immune cells, and together with monoacylglycerol lipase, the 2-arachidonoylglycerol degrading enzyme, they could be critically involved in the regulation of the immune cell profile of the tumor microenvironment (TME), and hence in tumor progression. So far, data on the impact of the ECS in the immune-TME are still vague. In this review, we discuss the current understanding of the ECS on immunoregulation during tumor growth, and how it might affect the outcome of cancer immunotherapy.

Rehabilitation Exercises Supported by Monitor-Augmented Reality for Patients with High-Grade Glioma Undergoing Radiotherapy: Results of a Randomized Clinical Trial.

Exercise has been shown to improve quality of life (QoL) and even treatment outcomes in cancer patients. However, the evidence to support the benefits of exercise in patients with high-grade glioma (HGG) is limited. Therefore, we performed a randomized clinical trial (RCT) to examine the effect of augmented-reality-based rehabilitation exercises on physical and functional fitness, cognitive function, fatigue, mood, QoL, selected blood parameters, brain derived neurotrophic factor (BDNF), and S100 protein in patients with HGG. Adult patients with HGG scheduled to undergo radiotherapy after tumor resection were randomized to participate in an exercise program (experimental group, n = 25) or to receive usual care (controls, n = 22). Physical and mental fitness was measured at baseline, after the completion of radiotherapy, and at 3 months. The following tests were administered: Handgrip Strength Test; 6-Minute Walk Test; Time Up and Go test; Functional Independent Measure scale; Addenbrooke's Cognitive Examination III (ACE III); Hospital Anxiety and Depression Scale; Functional Cancer Therapy Assessment-Brain; and Functional Assessment of Chronic Illness Therapy-Fatigue. We also measured blood parameters, BDNF, and S100 protein levels. No significant changes were observed in the exercise group. However, the controls experienced a significant decrease in HGS and in the ACE III attention domain. No significant changes were observed in QoL, fatigue, BDNF, or S100 levels in either group. Augmented-reality-based exercise during radiation therapy may prevent loss of muscle strength and attention in patients with HGG.

Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity.

Cancer cell heterogeneity is a key contributor to therapeutic failure and post-treatment recurrence. Targeting cell subpopulations responsible for chemoresistance and recurrence seems to be an attractive approach to improve treatment outcome in cancer patients. However, this remains challenging due to the complexity and incomplete characterization of tumor cell subpopulations. The heterogeneity of cells exhibiting stemness-related features, such as self-renewal and chemoresistance, fuels this complexity. Notch signaling is a known regulator of cancer stem cell (CSC) features in colorectal cancer (CRC), though the effects of its heterogenous signaling on CRC cell stemness are only just emerging. In this review, we discuss how Notch ligand-receptor specificity contributes to regulating stemness, self-renewal, chemoresistance and cancer stem cells heterogeneity in CRC.

Cancer phototherapy with nano-bacteria biohybrids.

The utilization of light for therapeutic interventions, also known as phototherapy, has been extensively employed in the treatment of a wide range of illnesses, including cancer. Despite the benefits of its non-invasive nature, phototherapy still faces challenges pertaining to the delivery of phototherapeutic agents, phototoxicity, and light delivery. The incorporation of nanomaterials and bacteria in phototherapy has emerged as a promising approach that leverages the unique properties of each component. The resulting nano-bacteria biohybrids exhibit enhanced therapeutic efficacy when compared to either component individually. In this review, we summarize and discuss the various strategies for assembling nano-bacteria biohybrids and their applications in phototherapy. We provide a comprehensive overview of the properties and functionalities of nanomaterials and cells in the biohybrids. Notably, we highlight the roles of bacteria beyond their function as drug vehicles, particularly their capacity to produce bioactive molecules. Despite being in its early stage, the integration of photoelectric nanomaterials and genetically engineered bacteria holds promise as an effective biosystem for antitumor phototherapy. The utilization of nano-bacteria biohybrids in phototherapy is a promising avenue for future investigation, with the potential to enhance treatment outcomes for cancer patients.

Pan-cancer analysis identifies the correlations of Thymosin Beta 10 with predicting prognosis and immunotherapy response.

The biological function and prognosis roles of thymosin β(TMSB) 10 are still unclear in pan-cancer. We retrieved The Cancer Genome Atlas and Genotype-tissue expression datasets to obtain the difference of TMSB10 expression between pan-cancer and normal tissues, and analyzed the biological function and prognosis role of TMSB10 in pan-cancer by using cBioPortal Webtool. The expression of TMSB10 in tumor tissues was significantly higher than normal tissues, and showed the potential ability to predict the prognosis of patients in Pan-cancer. It was found that TMSB10 was significantly correlated with tumor microenvironment, immune cell infiltration and immune regulatory factor expression. TMSB10 is involved in the regulation of cellular signal transduction pathways in a variety of tumors, thereby mediating the occurrence of tumor cell invasion and metastasis. Finally, TMSB10 can not only effectively predict the anti-PD-L1 treatment response of cancer patients, but also be used as an important indicator to evaluate the sensitivity of chemotherapy. In vitro, low expression of TMSB10 inhibited clonogenic formation ability, invasion, and migration in glioma cells. Furthermore, TMSB10 may involve glioma immune regulation progression by promoting PD-L1 expression levels via activating STAT3 signaling pathway. Our results show that TMSB10 is abnormally expressed in tumor tissues, which may be related to the infiltration of immune cells in the tumor microenvironment. Clinically, TMSB10 is not only an effective prognostic factor for predicting the clinical treatment outcome of cancer patients, but also a promising biomarker for predicting the effect of tumor immune checkpoint inhibitors (ICIs) and chemotherapy in some cancers.

Abstract 1747: Targeting metabolic and epigenetic programs to re-sensitize glioblastoma to chemotherapy

Abstract Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase 2A (MAT2A) and adenosylhomocysteinase (AHCY). Cell growth and survival were assessed by measuring protein expression of proliferation, oxidative stress and cell cycle arrest markers. EPIC array analysis and targeted bisulfite sequencing were conducted to identify changes in genome-wide and specific CpG island methylation. The Seahorse XF Analyzer measured mitochondrial respiratory capacity and oxidative metabolism. Induced pluripotent stem cell organoids were co-cultured with PDX tumor cells to determine if treatments mitigate tumor cell invasiveness. Compared to parental cells (PC), MAT2A gene expression was increased by 1.7-fold in acquired resistant and de novo resistant GBM cells (RC) [(transcript per million): PC, 7386 ± 412; RC, 12941 ± 1023; n=2; p=2.10e-8].Compared to TMZ-sensitive cells (TS), TMZ-resistant cells (TR) demonstrated a 56% increase in baseline oxygen consumption rate [(pmol/min): TS, 179 ± 6.7; TR, 279 ± 13; n=18; p=.0012] and 64% increase in maximal respiratory capacity [(pmol/min): TS, 403 ± 29; TR, 659 ± 35; n=6; p<.0001]. Both primary and recurrent GBM cells were subject to select MAT2A and AHCY inhibitor compounds and EC50s were determined. Recurrent cells demonstrated a vulnerability to TMZ-generated cell death both by genetically knocking down and pharmacologically inhibiting MAT2A and AHCY. MAT2A and AHCY contribute to TMZ resistance and recurrence by dysregulating methylation programs and upregulating antioxidant programs, respectively. These findings provide a foundation for developing novel combinatory therapeutic strategies and inform clinical studies intended to augment the practically negligible rate of remission for GBM and improve treatment outcomes for cancer patients. Citation Format: Emma Rowland, Jordan Walter, Anna Jermakowicz, Robert Suter, Rebecca Riggins, Nagi Ayad. Targeting metabolic and epigenetic programs to re-sensitize glioblastoma to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1747.