Side Effects Of Chemotherapy Research Articles

Relationship between oral health literacy and oral health-related quality of life in patients with bladder cancer

IntroductionBladder cancer is one of the most important diseases that threatens oral and dental health due to its nature and side effects of chemotherapy. Therefore, the present study was conducted to investigate the relationship between oral health literacy and oral health-related quality of life in patients with bladder cancer.MethodsThis cross-sectional study was conducted on patients with bladder cancer in Ahvaz, 2023. Subjects were selected randomly from the patients those were registered in Cancer Registry Center in Ahvaz Jundishapur University of Medical sciences and invited to Golestan Hospital for data collection through clinical evaluation, the Oral Health Literacy Adult Questionnaire (OHL-AQ), and the Oral Health Impact Profile-14 (OHIP-14PER) questionnaire. The data were analyzed using Pearson correlation coefficient, independent t-test, and analysis of variance.ResultsThe number of participants was 194. The mean oral health literacy in patients with bladder cancer was 9.74 ± 2.39, indicating insufficient oral health literacy. A significant association was observed between OHL-AQ and DMFT index, but no significant association was found between OHIP-14PER and DMFT index. Furthermore, a significant correlation was found between OHL-AQ and OHIP-14PER (r = −0.68) in patients with bladder cancer.ConclusionBased on the findings of the present study, all dimensions of oral health literacy have correlation with the oral health-related quality of life in patients with bladder cancer. Therefore, adopting oral health behaviors and increasing oral health literacy can be the best way to improve the oral health-related quality of life to among patients with bladder cancer.

Taste alteration and its relationship with nutritional status among cancer patients receiving chemotherapy, cross-sectional study

The aim of this study is to determine the prevalence of taste alterations (TAs) during chemotherapy and their association with nutritional status and malnutrition. In addition to the associated factors with TA, including sociodemographic health-related factors and clinical status, and to investigate coping strategies to manage TA. A multicenter cross-sectional design study was conducted on 120 cancer patients aged at least 18 who had been undergoing at least one round of chemotherapy. TAs were evaluated using the chemotherapy-induced taste alteration scale (CiTAS), the malnutrition universal screening tool (MUST) was used for nutritional screening, the antineoplastic side effects scale (ASES) was used for subjective assessment of chemotherapy side effects, and the Charlson comorbidity index (CCI) was used for comorbidity assessment. SPSS21 software was used to analyze the data, and the independent T-test and one-way ANOVA test were used to determine the association between TAs and a variety of related variables. The prevalence of TAs was 98.3%. Among participants, 48.3% were at low risk of malnutrition, 20% at medium risk, and 31.7% at high risk. Malnutrition risk was associated with taste disorders (p<0.05). Patients’ age, gender, educational level, and physical status were associated with TAs (p<0.05). Type of cancer, chemotherapy regimen, and number of chemotherapy cycles were also associated with TAs (p<0.05). A variety of antineoplastic side effects were associated with TAs (p<0.05), including nausea, vomiting, dry mouth, sore mouth and throat, excessive thirst, swallowing difficulty, appetite changes, weight loss, dizziness, lack of energy, disturbed sleep, anxiety, and difficulty concentrating. TAs were associated with an increased number of comorbidities, and individuals with diabetes, pulmonary diseases, and hypertension were associated with TAs (P<0.05). Patients in this study rarely practice self-management strategies to cope with TAs. A high prevalence (98.3%) of TAs in cancer patients receiving chemotherapy was found, and it was linked to a variety of negative outcomes. Chemotherapy-induced TAs are an underestimated side effect that requires more attention from patients and health care providers.

Effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the Structure and Function of the Intestinal Flora in Rabbits Undergoing Hepatic Artery Infusion Chemotherapy.

Few studies have explored the biological mechanism by which probiotics alleviate adverse reactions to chemotherapy drugs after local hepatic chemotherapy perfusion by regulating the intestinal flora. This study investigates the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the intestinal microbial structure and intestinal barrier function, as well as the potential mechanism in rabbits after local hepatic chemotherapy infusion. Eighteen New Zealand White rabbits were randomly divided into a control group, a hepatic local chemotherapy perfusion group, and a hepatic local chemotherapy perfusion + Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets group to assess the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the adverse reactions. The administration of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets alleviated the intestinal flora disorder caused by local hepatic perfusion chemotherapy, promoted the growth of beneficial bacteria, and inhibited the growth of harmful bacteria. The Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets also reduced the levels of serum pro-inflammatory cytokines and liver injury factors induced by local hepatic perfusion chemotherapy. Our findings indicate that Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets can ameliorate the toxicity and side effects of chemotherapy by regulating intestinal flora, blocking pro-inflammatory cytokines, reducing liver injury factors, and repairing the intestinal barrier. Probiotics may be used as a potential alternative therapeutic strategy to prevent the adverse reactions caused by chemotherapy with local hepatic perfusion.

Applications of Biodegradable Polymers in the Encapsulation of Anticancer Metal Complexes

AbstractMetal complexes have recently attracted a lot of attention, particularly as anticancer and antibacterial agents, owing to their versatile mechanisms and easily tunable characteristics. However, the application of such compounds in a medical context, especially in cancer treatment, has been hampered due to their limited solubility and stability in water and aqueous solutions, as well as a lack of selectivity. To address these limitations, several approaches have been developed to improve the targeted delivery of these compounds and their solubility. The first strategy involves the physical encapsulation of these metal complexes within carriers to facilitate controlled drug release. The second strategy involves covalently linking metal complexes to polymers, creating prodrugs that can be converted to active drugs at a more controllable rate. Despite the increasing variety of polymers available, the need to develop those able to be metabolized by the body, producing non‐toxic residues, remains crucial for effective treatment, particularly in the area of diseases such as cancer. In this perspective article, an overview of recent developments in the encapsulation of metal complexes using biodegradable polymers for cancer therapy is provided. It is specifically highlighting how the formed nanoparticles (NPs) enhance the selectivity and toxicity toward cancer cells compared to the parent metal complex, while simultaneously reducing the harmful side effects of traditional chemotherapies, opening the door for using them in combination therapies (PDT, PTT).

Impact of exercise on chemotherapy-induced peripheral neuropathy in survivors with post-treatment primary breast cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of neurotoxic chemotherapy. Exercise activates neuromuscular function and may improve CIPN. We examined the association between exercise and CIPN symptoms in breast cancer survivors. In a retrospective cross-sectional study, we included patients completing a survey assessing exercise exposure and neuropathy symptoms in a tertiary cancer center survivorship clinic. We evaluated exercise duration and intensity using a standardized questionnaire quantified in metabolic equivalent tasks (MET-h/wk). We defined exercisers as patients meeting the National Physical Activity Guidelines' criteria. We used multivariable logistic regressions to examine the relationship between exercise and CIPN and if this differed as a function of chemotherapy regimen adjusting for age, gender, and race. We identified 5444 breast cancer survivors post-chemotherapy (median age 62years (interquartile range [IQR]: 55, 71); median 4.7years post-chemotherapy (IQR: 3.3, 7.6)) from 2017 to 2022. CIPN overall prevalence was 34% (95% confidence interval [CI]: 33%, 36%), 33% for non-taxane, and 37% for taxane-based chemotherapy. CIPN prevalence was 28% (95% CI: 26%, 30%) among exercisers and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Compared to patients with low (<6 MET-h/wk) levels of exercise (42%), 11% fewer patients with moderate (6-20.24 MET-h/wk) to high (>20.25 MET-h/wk) levels of exercise reported CIPN. Exercise was associated with reduced prevalence of all CIPN symptoms regardless of chemotherapy type. CIPN may persist several years following chemotherapy among patients with breast cancer but is significantly reduced by exercise in a dose-dependent manner.

Chemical analysis and antibacterial activity of the Achillea millefolium extract

Achillea millefolium L., a traditional medicinal plant from the Asteraceae family, is known for its anti-inflammatory, anti-ulcer, and anti-cancer properties, attributed to its rich content of phytochemicals (such as flavonoids, alkaloids, ter¬penes, tannins, and phenolic acids). This study has focused on the chemical analysis of the oil extracted from the aerial parts of Achillea millefolium subsp. millefolium, cultivated and harvested in Kurdistan, Iraq. The oil was extracted by using a Clevenger apparatus for hydro-distillation and was analysed by using gas chromatography with a flame ionization detector and an HP-5 MS capillary column. The analysis revealed the presence of 1,8-cineole (eucalyptus oil), Artemisia ketone, camphor, linalyl acetate, and D-limonene, with Artemisia ketone having the highest concentra¬tion at 15.04% and D-limonene the lowest at 7.51%. The extract of Achillea millefolium has been shown to aid in the treatment of oral mucositis (a common side effect of anticancer chemotherapy), likely due to the flavonoids and tannins present in the plant.

Influence of TLR4 signaling on Cannabidiol’s antitumor effectiveness in lung adenocarcinoma cells

Abstract Objectives Lung cancer remains a predominant cancer type with high incidence and low survival rates. Key challenges in its treatment include impaired cellular mechanisms, notably resistance to apoptosis and altered immune responses. A critical aspect in this context is the heightened TLR4-mediated signaling, known to promote cell survival, metastasis, and resistance to cell death, particularly impacting immune microenvironment regulation. This study focuses on evaluating the impact of TLR4 signaling activation on potential therapeutic strategies. Methods Our research utilizes Cannabidiol (CBD), a compound already employed in mitigating chemotherapy side effects in lung adenocarcinoma, recognized for its antitumor properties including antiproliferative, antimetastatic, and apoptosis-inducing effects. However, the effectiveness of CBD in lung cancer cells with elevated TLR4 signaling remains uncertain. Results Our findings reveal that the combination of CBD and TLR4 agonist affects cell viability, proliferation, cell cycle progression, apoptosis, and gene expression related to immune response and extracellular matrix regulation. In lung adenocarcinoma cells with activated TLR4, CBD shows an increased IC50 value, reflecting reduced antiproliferative capacity. Furthermore, its efficacy in arresting the cell cycle and inducing apoptosis is also compromised. The influence on immune response and extracellular matrix regulation is also altered in TLR4-activated cells. Conclusions These results indicate that TLR4 activation significantly diminishes the antitumor efficacy of CBD. This highlights the importance of considering TLR4 signaling activation in future research on therapeutic agents like CBD for cancer treatment.

Abstract PO1-11-12: Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy

Abstract Background Cancer patients often consider CINV as one of the most disturbing side effects of cytotoxic chemotherapy. Adriamycin and cyclophosphamide (AC), considered by many to be part of the standard adjuvant regimen for breast cancer patients, is highly emetogenic. Despite adopting optimal antiemetic prophylaxis, the control of CINV remains modest for some patients. Among Chinese breast cancer patients receiving adjuvant AC chemotherapy, the present analysis aims to determine the association of the number of risk factors for CINV with (i) likelihood of antiemetic treatment failure; (ii) time to first vomiting in 1st AC cycle. Methods: We retrieved data from three previously reported prospective antiemetic studies on patients who received AC, in whom different antiemetic regimens were administered. Treatment failure was defined as (i) not achieving CR (CR= no vomiting and no use of rescue medication over 120 hours after start of AC), or (ii) experiencing nausea (nausea VAS &amp;gt;/= 5mm during the 120 hours). Multivariate logistic regression models were applied to identify potential factors associated with the development of CINV. The Cochran–Armitage trend test was utilized to assess possible trends in the relationship between treatment failure and number of identified risk factors. The time-to-treatment failure curves, as classified by the number of identified factors in each subgroup, were evaluated using the Kaplan–Meier method. Results: Based on multivariate analysis of 303 breast cancer patients, not achieving CR was more likely among non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, history of motion sickness and history of vomiting in pregnancy. Experience of nausea was more likely in non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, and history of motion sickness. Treatment failure in terms of ‘no CR’ was associated with increased number of risk factors that an individual patient displayed; the figures increased from 18.8% for those with 0 risk factor to 94.1% for those with 4 risk factors (p &amp;lt; 0.0001). Treatment failure in terms of nausea was associated also with increased number of risk factors; the figures increased from 25.9% for those with 0 risk factor to 83.3% for patients with 3 risk factors (p &amp;lt; 0.0001). Time to first vomiting was significantly related to number of identified factors (p &amp;lt; 0.0001). Among patients who had 0, 1, 2 and 3 risk factors, the 24-hour rate of ‘no vomiting’ were 81.3%, 80.3%, 66.7%, 53.7% and 17.7%, respectively; similar trends were observed for analyses on 48-hour and 72-hour rates. Conclusions: The present study confirmed that reported risk factors for CINV in the literature were important in Chinese breast cancer patients receiving AC chemotherapy. Furthermore, patients who had more risk factors had increased likelihood of treatment failure and shorter time to first vomiting. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research Citation Format: Winnie Yeo, Nicole Ngai, Horatio Yeo, Dong Lai, Elizabeth Pang, Carol Kwok, Thomas Lau, Frankie Mo. Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-12.

Abstract PO2-20-06: Using the Australian Cardio-Oncology Registry to study long-term cancer therapy related cardiac dysfunction in adult oncology patients – The Chris O’Brien Lifehouse experience

Abstract Background Cancer therapy related cardiac dysfunction (CTRCD) is a significant side effect of several chemotherapies, targeted agents, and immunotherapies integral to treatment. Anthracyclines are an example of a commonly used chemotherapy drug class that can cause irreversible early and late onset heart failure. CTRCD often leads to dose reductions and treatment delays or cessation, limiting treatment success and contributing to increased mortality and life-long morbidity in oncology survivors. In Australia, there are currently no multi-centre, longitudinal studies examining CTRCD in adult oncology patients. Trial design The Australian Cardiology-Oncology Registry (ACOR) is a prospective observational non-interventional study involving 14 sites across Australia. Patient information is obtained from hospital medical records and de-identified upon entry into the registry. Patient demographics, medical history, cancer diagnosis, treatment, cardiac evaluations, and the management of demonstrated CTRCD are recorded. Data is collected at baseline (prior to treatment), and then at six-monthly intervals thereafter. Additionally, patients who develop anthracycline-induced cardiotoxicity (ACT) will be asked to participate in the biobanking study, which will involve a one-off 12mL peripheral blood draw that will be processed at an external site for whole genome exome sequencing and the development of pluripotent derived stem cell cardiomyocytes. Eligibility criteria Inclusion Criteria • Adult oncology patients (&amp;gt;18+ years of age) treated with cardiotoxic therapies within the last 5-years Exclusion Criteria • Diagnosis of Trisomy 21 • Patients being treated with palliative intent Specific aims Chris O’Brien Lifehouse aims to use the ACOR to explore the epidemiology, clinical presentation, and management of CTRCD amongst adult oncology patients receiving cardiotoxic therapies. In addition, a biobanking sub-study will attempt to identify gene polymorphisms predisposing individuals to developing ACT. It is hoped that such longitudinal data collection can lead to the introduction of an ACT susceptibility genetic screening test allowing for the inclusion of patient risk stratification prior to anthracycline exposure in routine cancer treatment. Statistical methods Descriptive statistics will be used for variables for quantitative analysis. Kaplan Meier analyses will be used for survival curves, freedom from cardiac failure since enrolment and freedom from arrhythmia since enrolment. An annual report will be produced. Present accrual and target accrual At the time of submission, 224 adult oncology patients have been recruited to the ACOR via Chris O’Brien Lifehouse with the opening of the biobanking sub-study currently in progress. The ACOR anticipates with full registered site capacity to capture 600 patients annually. Citation Format: Jocelyn Finney, Ben Felmingham, Sanjeev Kumar, Alina Mahmood, Lisa Horvath, David Celermajer, Rachel Conyers. Using the Australian Cardio-Oncology Registry to study long-term cancer therapy related cardiac dysfunction in adult oncology patients – The Chris O’Brien Lifehouse experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-06.

Translation of paclitaxel-induced peripheral neurotoxicity from mice to patients: the importance of model selection.

Paclitaxel-induced peripheral neurotoxicity (PIPN) is a potentially dose-limiting side effect in anticancer chemotherapy. Several animal models of PIPN exist, but their results are sometimes difficult to be translated into the clinical setting. We compared 2 widely used PIPN models characterized by marked differences in their methodologies. Female C57BL/6JOlaHsd mice were used, and they received only paclitaxel vehicle (n = 38) or paclitaxel via intravenous injection (n = 19, 70 mg/kg) once a week for 4 weeks (Study 1) or intraperitoneally (n = 19, 10 mg/kg) every 2 days for 7 times (Study 2). At the end of treatment and in the follow-up, mice underwent behavioral and neurophysiological assessments of PIPN. At the same time points, some mice were killed and dorsal root ganglia, skin, and sciatic and caudal nerve samples underwent pathological examination. Serum neurofilament light levels were also measured. The differences in the neurotoxicity parameters were analyzed using a nonparametric Mann-Whitney test, with significance level set at P < 0.05. Study 1 showed significant and consistent behavioral, neurophysiological, pathological, and serological changes induced by paclitaxel administration at the end of treatment, and most of these changes were still evident in the follow-up period. By contrast, study 2 evidenced only a transient small fiber neuropathy, associated with neuropathic pain. Our comparative study clearly distinguished a PIPN model recapitulating all the clinical features of the human condition and a model showing only small fiber neuropathy with neuropathic pain induced by paclitaxel.

THE EFFECT OF INTRA-INFUSION EXERCISE ON CHEMOTHERAPY SIDE EFFECTS; AN INTERIM ANALYSIS

INTRODUCTION Chemotherapy treatment results in side effects that impact quality of life and physical activity behaviours. Aerobic exercise in parallel with chemotherapy reduces side effects particularly fatigue and improves quality of life. Our recent clinical pilot work has shown that an acute bout of aerobic exercise increases blood flow to tumours. Therefore, if exercise is performed during chemotherapy (intra-infusion exercise), the result may be increased drug delivery and treatment efficacy. Intra-infusion exercise also provides a supervised opportunity to overcome patient-reported barriers to exercise during a period where a patient would be otherwise sedentary. AIM: The aim of this ongoing randomised controlled trial is to determine the effects of aerobic intra-infusion exercise on chemotherapy side effects and physical activity behaviours. METHODS Adults under 75 years receiving chemotherapy with stage I-III breast, colorectal or ovarian cancer, and ECOG 0-2 were eligible. Four chemotherapy sessions were included, cycle 1 (C1) a baseline and cycles 2-4 (C2-4) included exercise intervention or usual care. The exercise task was 20-minutes of moderate intensity cycling (40-50% heart rate reserve) during infusion. All participants received exercise education. A 7-day symptom diary (including Brief Fatigue Inventory (BFI) and Edmonton Symptom Assessment System (ESAS)) was completed following C1-C4 and an activity monitor worn. RESULTS Nineteen participants have completed the trial (79% female), with no adverse events reported in either group. Physical symptoms increased across cycles in both groups (p=0.003). 1-week mean ESAS physical symptoms total in the exercise group (C1 16±9.8, C4 23±13.7) and control group (C1 18±7.1, C4 23±12.7) were similar. No significant effects were seen for fatigue or step count. CONCLUSION Intra-infusion exercise is safe and does not increase side effects in patients receiving chemotherapy. Expected increases in physical symptoms were observed without difference between usual care and exercise. Further analysis with ongoing recruitment will continue to examine any differences between groups.

COMPARING THE EFFECTS OF AROMATASE INHIBITORS AND SELECTIVE OESTROGEN RECEPTOR MODULATORS ON BODY COMPOSITION, EXERCISE TOLERANCE AND MARKERS OF CARDIOVASCULAR RISK IN FEMALES WITH BREAST CANCER

INTRODUCTION Adjuvant endocrine therapy (AET) blocks the action of estrogens and is commonly prescribed in hormone receptor-positive breast cancer. Given the putative cardioprotective role of estrogens in females, AET may exacerbate the negative metabolic side-effects of anthracycline chemotherapy. This study examined the early effects of combined anthracycline chemotherapy and AET on body composition, exercise tolerance and markers of cardiovascular risk in a cohort of females with breast cancer. METHODS This was a secondary analysis of the BReast cancer EXercise InTervention (BREXIT) Trial. Females with breast cancer (n=105, aged 51 ± 8 years, BMI 27.4 ± 5.1, mean ± SD) scheduled for anthracycline chemotherapy participated in this study. Aerobic exercise capacity, body composition, physical function, and blood pressure were measured before anthracycline treatment and after 4- and 12-months follow-up. Linear mixed models assessed whether aromatase inhibitors (AI) or selective estrogen receptor modulators (SERMS) affected exercise tolerance, body composition and markers of cardiovascular risk compared to non-endocrine breast cancer treatments. RESULTS Twelve months of anthracycline treatment combined with AI or SERMs decreased total body lean mass by 1.4 kg (2%; interaction p=0.01) and 1kg (1%; interaction p=0.16) respectively, when compared to non-endocrine therapies. There were trends for AET to decrease total fat (-1.5%, interaction p=0.05) and android fat (-2.3%, interaction p=0.07) mass compared to non-endocrine therapy after 12 months. AIs significantly increased both systolic (5.8mmHg, interaction p=0.05) and diastolic (4.0mmHg, interaction p=0.05) blood pressure after 12 months of treatment compared to SERMs or non-endocrine therapies. There was no effect of either AET or SERMS on VO2peak, leg press or seated row 1RM, 30 second sit to stand or handgrip strength. DISCUSSION AND CONCLUSION Short-term treatment with adjuvant endocrine therapies may accelerate muscle loss and increase blood pressure compared to non-endocrine therapies. However, these changes were not associated with worsening of physical function.

Exploring the Potential of Acupressure in Managing Chemotherapy Side Effects: A Case Study on Breast Cancer Patients in Bengkulu, Indonesia

Breast cancer is the most common cancer among women, with significant global mortality rates. The World Health Organization (WHO, 2012) reported that in 2011, over 508,000 women worldwide died from this disease, which accounts for the highest percentage of new cases at 43.3% and a mortality rate of 12.9%. Existing therapies, including surgery, radiotherapy, and chemotherapy, often accompany side effects such as pain, weakness, hair loss, and menstrual disorders. Acupressure, as a form of non-pharmacological therapy, has the potential to mitigate these side effects through the application on meridian points LI4, SP6, and LR3, selected for their relevance to the energy flow affecting pain and the reproductive system. This study investigates the impact of acupressure on points LI4, SP6, and LR3 concerning pain and menstrual disorders in patients with carcinoma mammae undergoing chemotherapy in Bengkulu City. Utilizing a quasi-experimental design and a two-group pretest-posttest with control approach, this study involved 30 participants divided into two groups: 15 in the control group and 15 in the intervention group, selected through purposive sampling. The findings indicated no significant differences in the reduction of pain and menstrual disorders between the groups, with a p-value showing no statistical significance. This suggests that acupressure might be more effective if applied continuously in the early stages of chemotherapy. These findings invite further research to explore the therapeutic potential of acupressure in managing breast cancer, particularly for mitigating chemotherapy side effects.

Proteomics Approach to Identify Anthracycline-induced Cardiotoxicity Mechanisms in Human Cardiac Fibroblasts

Doxorubicin-induced cardiotoxicity (DIC) is a major life-threatening side-effect of chemotherapy in cancer patients. DIC leading to heart failure is caused by numerous mechanisms, including impaired mitochondrial function, disruption of calcium homeostasis, and altered gene and protein response that triggers cell death and, eventually, fibrosis. We performed a preliminary investigation of the effect of doxorubicin (DOX) on the cardiac fibroblast proteome using mass-spectrometry. Quantitative analysis showed significantly altered expression of 186 proteins. Nine out of forty-two Dox-upregulated proteins and seventeen out of twenty-four Dox-downregulated proteins showed a reciprocal trend in expression upon inhibiting a structural scaffold protein involved in cardiac calcium channel regulation. Overall, our data suggests the involvement of pathways in regulating mitochondrial energy metabolism, matrix remodeling, cell cycle/arrest, and cell survival via Rho/Rac nuclear exchanger proteins. DIC is multifactorial, and based on our pilot data, modulation of calcium channel regulators may be a promising strategy to mitigate the progression of DIC to heart failure. Research support received from the American Heart Association, NIH and the University of Arkansas for Medical Sciences. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 μM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 μM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 μM), necroptosis inhibitor necrostatin-1 (10 μM), or pan-caspase inhibitor Z-VAD-FMK (10 μM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect ofbaicalein on CRC cells isassociated with ferroptosis induction. We revealed that baicalein (7.5-30 μM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. This is a prospective, single-institution pilot study evaluating children and AYAs aged≥2 years to≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.

Legal Protection for Tumor Surgeons on the Side Effects in Breast Cancer Chemotherapy Services

Legal protection for tumor surgeons in facing chemotherapy side effects in breast cancer patients is essential in contemporary medical practice. This study employed a narrative method and legal approach to explore the legal protection available to tumor surgeons in addressing risks and side effects during chemotherapy services. The narrative method was used to explore the role of the law in protecting tumor surgeons and providing a clear framework for addressing side effects in chemotherapy services. Literature analysis regarding medical practice standards, professional responsibilities, and relevant legal cases were used to formulate a comprehensive perspective of this legal protection. The research highlights the need for meticulous documentation of procedures, risks, and patient consent before undergoing chemotherapy. Additionally, legal protection also depends on adherence to applicable medical practice standards and effective communication between tumor surgeons and patients. In conclusion, the understanding of tumor surgeons is needed for the legal implications of their medical practices, including in the context of chemotherapy services. Thus, the use of narrative methods in this study provides valuable insights for tumor surgeons to protect themselves and provide safe and quality services to breast cancer patients.

Microbiome and cancer: from mechanistic implications in disease progression and treatment to development of novel antitumoral strategies.

Cancer is a very aggressive disease and one of mankind's most important health problems, causing numerous deaths each year. Its etiology is complex, including genetic, gender-related, infectious diseases, dysbiosis, immunological imbalances, lifestyle, including dietary factors, pollution etc. Cancer patients also become immunosuppressed, frequently as side effects of chemotherapy and radiotherapy, and prone to infections, which further promote the proliferation of tumor cells. In recent decades, the role and importance of the microbiota in cancer has become a hot spot in human biology research, bringing together oncology and human microbiology. In addition to their roles in the etiology of different cancers, microorganisms interact with tumor cells and may be involved in modulating their response to treatment and in the toxicity of anti-tumor therapies. In this review, we present an update on the roles of microbiota in cancer with a focus on interference with anticancer treatments and anticancer potential.

Effect of N-acetylcysteine on hair follicle changes in mouse model of cyclophosphamide-induced alopecia: histological and biochemical study

Chemotherapy-induced alopecia (CIA) represents one of the most severe side effects of chemotherapy, which forces some patients to reject cancer treatment. The exact pathophysiological mechanisms of CIA are not clearly understood, which makes it difficult to discover efficient preventive or therapeutic procedures for this adverse effect. N-acetylcysteine (NAC) has a strong antioxidant activity as it stimulates glutathione synthesis and acts as an oxygen radical scavenger. The current study tried to investigate the efficacy of NAC in preserving biochemical parameters and hair follicle structure against cyclophosphamide (CYP) administration. In total, 40 adult female C57BL/6 mice were induced to enter anagen by depilation (day 0) and divided into four groups: group I (control), group II (CYP) received a single dose of CYP [150 mg/kg body weight (B.W.)/intraperitoneal injection (IP)] at day 9, group III (CYP & NAC) received a single dose of CYP at day 9 as well as NAC (500 mg/kg B.W./day/IP) from day 6–16, and group IV (NAC) received NAC from day 6–16. CYP administration in group II induced an increase in malondialdehyde (MDA), decrease in superoxide dismutase (SOD), histological hair follicle dystrophy, disruption of follicular melanogenesis, overexpression of p53, and loss of ki67 immunoreactivity. NAC coadministration in group III reversed CYP-induced alterations in the biochemical parameters and preserved hair follicle structure, typical follicular melanin distribution as well as normal pattern of p53 and ki67 expression. These findings indicated that NAC could be used as an efficient and safe therapeutic option for hair loss induced by chemotherapy.

Evaluation of chemotherapy-induced nausea and vomiting in pediatric patients with high-grade glioma treated with lomustine—a case series

PurposeAlthough lomustine has been used as a chemotherapeutic agent for decades, no recommendation on appropriate chemotherapy-induced nausea and vomiting (CINV) prophylaxis is available. As CINV is considered one of the most bothersome side effects of chemotherapy, adequate prophylaxis is of relevance to improve quality of life during cancer treatment. The aim of this retrospective case series was to report the incidence and severity of CINV in pediatric patients with high-grade glioma treated with lomustine and to formulate recommendations for appropriate CINV prophylaxis.MethodsPediatric patients treated with lomustine for high-grade glioma according to the ACNS 0423 protocol were identified retrospectively. Two researchers independently reviewed and classified complaints of CINV and administered CINV prophylaxis. Treatment details, tumor localization, and response to therapy were systematically extracted from the patients’ files.ResultsSeventeen children aged 8–18 years received a median of four cycles of lomustine. CINV complaints and administered prophylaxis were evaluable in all patients. Moderate or severe CINV was observed in 13/17 (76%) patients. Administered prophylactic CINV regimens varied from no prophylaxis to triple-agent combinations.ConclusionIn this case series, we identified lomustine as a highly emetogenic chemotherapeutic agent. According to the current guidelines, CINV prophylaxis with a 5-HT3 receptor antagonist in combination with dexamethasone and (fos)aprepitant is recommended.