Adverse Effects Of Cancer Therapy Research Articles

Single versus intermittent cycle exposure effect of 6-mercaptopurine in juvenile Sprague-Dawley rat: a germ cell-specific mechanistic study.

Infertility is a frequent long-term adverse effect of cancer therapy for children. Compromised testicular functions in adolescence are frequent observations after chemotherapy and there are currently no well-established alternatives to avoid this damage. Antimetabolites such as 6-mercaptopurine (6-MP) are used to treat a variety of cancer; however, its treatment-associated adverse effects on the male reproductive functions are overlooked. Here, the molecular processes underlying 6-MP-induced male germ cell damage in juvenile Sprague-Dawley (SD) rats (3weeks) have been investigated. Rats were administered with low (5mg/kg), medium (10mg/kg), and high (20mg/kg) doses of 6-MP per orally either singly (1week × 1 cycle) or intermittently (1week treatment followed by 1week remission period × 3 cycles). The toxicity was evaluated in terms of genotoxicity and testes- and sperm-related cellular and molecular parameters. Single cycle of exposure either produced mild or no toxic manifestations at the end of the 6th week. Intermittent cycles of exposure, particularly at the 10 and 20mg/kg, decreased body and organ weights, increased micronucleated cells in the peripheral blood, induced oxidative/nitrosative stress, altered sperm chromatin quality, reduced serum testosterone and follicle stimulating hormone (FSH) levels, increased testicular structural aberrations, DNA damage, and apoptosis, and upregulated TNF-α expression and downregulated p-AMPK and β-catenin expressions. Conclusively, intermittent cycles of exposure at 10 and 20mg/kg doses to the juvenile rats significantly induced oxidative stress, genotoxicity, and cellular and molecular perturbations in the testes and sperm of adult rats.

MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis

ObjectivesMRI-derived extracellular volume (ECV) allows characterization of myocardial changes before the onset of overt pathology, which may be caused by cancer therapy cardiotoxicity. Our purpose was to review studies exploring the role of MRI-derived ECV as an early cardiotoxicity biomarker to guide timely intervention.Materials and methodsIn April 2022, we performed a systematic search on EMBASE and PubMed for articles on MRI-derived ECV as a biomarker of cancer therapy cardiotoxicity. Two blinded researchers screened the retrieved articles, including those reporting ECV values at least 3 months from cardiotoxic treatment. Data extraction was performed for each article, including clinical and technical data, and ECV values. Pooled ECV was calculated using the random effects model and compared among different treatment regimens and among those who did or did not experience overt cardiac dysfunction. Meta-regression analyses were conducted to appraise which clinical or technical variables yielded a significant impact on ECV.ResultsOverall, 19 studies were included. Study populations ranged from 9 to 236 patients, for a total of 1123 individuals, with an average age ranging from 12.5 to 74 years. Most studies included patients with breast or esophageal cancer, treated with anthracyclines and chest radiotherapy. Pooled ECV was 28.44% (95% confidence interval, CI, 26.85−30.03%) among subjects who had undergone cardiotoxic cancer therapy, versus 25.23% (95%CI 23.31−27.14%) among those who had not (p = .003).ConclusionA higher ECV in patients who underwent cardiotoxic treatment could imply subclinical changes in the myocardium, present even before overt cardiac pathology is detectable.Clinical relevance statementThe ability to detect subclinical changes in the myocardium displayed by ECV suggests its use as an early biomarker of cancer therapy–related cardiotoxicity.Key Points• Cardiotoxicity is a common adverse effect of cancer therapy; therefore, its prompt detection could improve patient outcomes.• Pooled MRI-derived myocardial extracellular volume was higher in patients who underwent cardiotoxic cancer therapy than in those who did not (28.44% versus 25.23%, p = .003).• MRI-derived myocardial extracellular volume represents a potential early biomarker of cancer therapy cardiotoxicity.

Disparities in cardio-oncology: Implication of angiogenesis, inflammation, and chemotherapy

Cancers and cardiovascular diseases are the top two causes of death in the United States. Over the past decades, novel therapies have slowed the cancer mortality rate, yet cardiac failures have risen due to the toxicity of cancer treatments. The mechanisms behind this relationship are poorly understood and it is crucial that we properly treat patients at risk of developing cardiac failure in response to cancer treatments. Currently, we rely on early-stage biomarkers of inflammation and angiogenesis to detect cardiotoxicity before it becomes irreversible. Identification of such biomarkers allows healthcare professionals to decrease the adverse effects of cancer therapies. Angiogenesis and inflammation have a systemic influence on the heart and vasculature following cancer therapy. In the field of cardio-oncology, there has been a recent emphasis on gender and racial disparities in cardiotoxicity and the impact of these disparities on disease outcomes, but there is a scarcity of data on how cardiotoxicity varies across diverse populations. Here, we will discuss how current markers of angiogenesis and inflammation induced by cancer therapy are related to disparities in cardiovascular health.

Mesoporous Silica Nanoparticles for pH-Responsive Delivery of Iridium Metallotherapeutics and Treatment of Glioblastoma Multiforme

Using nanoparticles for controlled drug delivery to cancer, in response to its weakly acidic environment, represents a promising approach toward increasing the effectiveness and reducing the adverse effects of cancer therapy. Hence, the aim of this study is to construct novel mesoporous silica nanoparticle (MSN)-based acidification-responsive drug delivery systems for targeted cancer therapy. Herein, the surface of MSN is covalently functionalized with Ir(III)-based complex through a pH-cleavable hydrazone-based linker and characterized by nitrogen sorption, SEM, FTIR, EDS, TGA, DSC, DLS, and zeta potential measurements. Enhanced release of Ir(III)-complexes is evidenced by UV/VIS spectroscopy at the weakly acidic environments (pH 5 and pH 6) in comparison to the release at physiological conditions. The in vitro toxicity of the prepared materials is tested on healthy MRC-5 cells while their potential for the efficient treatment of glioblastoma multiforme is demonstrated on the U251 cell line.

Development of a Treatment Pathway and Patient Education Tool for Chemotherapy Induced Peripheral Neuropathy

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of cancer therapy seen with platinum agents, taxanes, vinca alkaloids, and proteasome inhibitors that can have a profound and lasting impact on quality of life. Although recognized during treatment with dose reductions and pain management, there may be an opportunity for a more uniform approach to help reduce the severity and enhance recovery. Our interdisciplinary team developed a clinical pathway and educational tool for managing neuropathy in patients who received systemic antineoplastic therapy. The gynecologic oncology team developed the pathway that now will be used in the hematologic malignancy team, especially for our patients with lymphoid malignancies who also often experience CIPN. Methods: A multidisciplinary team of specialists, including physicians, advanced practice providers, nurses, and social workers from gynecologic oncology, medical oncology, physical medicine and rehabilitation (PM&R), and physical and occupational therapy (PT/OT), was convened. A literature review was performed to collate evidence-based practices for neuropathy management. The review informed the development of the clinical pathway and led to the creation of provider-facing and patient-facing materials. Dissemination and access to the pathway included uploading a schematic onto a shared health system clinical care platform (Dorsata). The tool provides clinical decision support to providers by standardizing the approach to triage, navigation, and multi-modality neuropathy treatment. The pathway structure is based on symptoms' severity and includes social needs. Implementation included clinical decision support built within the electronic medical records platform (EPIC) using smart phrases. These interventions facilitated PMR, PT/OT, Neurology & Palliative Care referrals. Simultaneously, patient-facing materials were also made accessible through EPIC. The content included the causes of neuropathy, interventions for management, and injury prevention. Armed with this knowledge, we aim to empower patients in understanding and taking control of their symptoms. Results: There have been 35 views since the pathway was published in April 2022. This pathway increased clinician recognition of neuropathy as a highly prevalent and burdensome side effect of antineoplastic therapy. The standardized pathway allowed the entire treatment team to facilitate care easily and without added time. Patients were highly interested in strategies to ameliorate neuropathy symptoms and learned that multi-modality treatment options are available. Feedback from the pilot process thus far has resulted in plans to: (1) utilize a nurse navigator and clinical nurses to assist in triaging patients through this clinical care pathway, (2) collect validated neuropathy assessments pre and post-multimodal intervention, (3) expand to all oncology services lines within the health system. Conclusion: We developed and piloted a clinical care pathway to manage neuropathy by leveraging expertise from a multidisciplinary team of oncology-centered providers. Preliminary results suggest it improved provider-based recognition, treatment for neuropathy, strong patient interest, and satisfaction for improved access to multi-modality neuropathy treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Preventive Effect of Probiotics on Oral Mucositis Induced by Cancer Treatment: A Systematic Review and Meta-Analysis.

Oral mucositis is a common adverse effect of cancer therapy. Probiotics have been shown to exert anti-inflammatory and immunomodulatory effects. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate whether probiotics can prevent cancer therapy-induced oral mucositis. We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for trials related to probiotics and oral mucositis published before September 2022; no language restrictions were applied. The primary outcome was the incidence of oral mucositis and severe oral mucositis. Secondary outcomes were the requirement for enteral nutrition during treatment, body weight loss, and decreased quality of life. The study has been registered in PROSPERO (number: CRD 42022302339). Eight RCTs, including 708 patients, were reviewed; however, a meta-analysis of only seven trials could be performed. Three trials using Lactobacilli-based probiotics reported that the incidence of oral mucositis in the probiotic group was significantly low (risk ratio [RR] = 0.84, 95% confidence interval [CI] = 0.77-0.93, p = 0.0004). Seven trials reported a significantly low incidence of severe oral mucositis in the probiotic group (RR = 0.65, 95% CI = 0.53-0.81, p < 0.0001). The requirement of enteral nutrition was significantly low in the probiotic group (odds ratio = 0.34, 95% CI: 0.13-0.92, p < 0.05). This study demonstrated the effectiveness of probiotics in the prevention and mitigation of cancer therapy-induced oral mucositis. We recommend the use of probiotics to prevent and treat oral mucositis during cancer therapy.

Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms.

The incidence of cancer has been growing worldwide. Better survival rates following the administration of novel drugs and new combination therapies may concomitantly cause concern regarding the long-term adverse effects of cancer therapy, for example, second primary malignancies. Moreover, overcoming tumour resistance to anticancer agents has been long considered as a critical challenge in cancer research. Some low toxic adjuvants such as herb-derived molecules may be of interest for chemoprevention and overcoming the resistance of malignancies to cancer therapy. Apigenin is a plant-derived molecule with attractive properties for chemoprevention, for instance, promising anti-tumour effects, which may make it a desirable adjuvant to reduce genomic instability and the risks of second malignancies among normal tissues. Moreover, it may improve the efficiency of anticancer modalities. This paper aims to review various effects of apigenin in both normal tissues and malignancies. In addition, we explain how apigenin may have the ability to protect usual cells against the genotoxic repercussions following radiotherapy and chemotherapy. Furthermore, the inhibitory effects of apigenin on tumours will be discussed.

Cardio-Oncology: Mechanisms, Drug Combinations, and Reverse Cardio-Oncology.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy have brought hope to cancer patients. With the prolongation of survival of cancer patients and increased clinical experience, cancer-therapy-induced cardiovascular toxicity has attracted attention. The adverse effects of cancer therapy that can lead to life-threatening or induce long-term morbidity require rational approaches to prevention and treatment, which requires deeper understanding of the molecular biology underpinning the disease. In addition to the drugs used widely for cardio-protection, traditional Chinese medicine (TCM) formulations are also efficacious and can be expected to achieve “personalized treatment” from multiple perspectives. Moreover, the increased prevalence of cancer in patients with cardiovascular disease has spurred the development of “reverse cardio-oncology”, which underscores the urgency of collaboration between cardiologists and oncologists. This review summarizes the mechanisms by which cancer therapy induces cardiovascular toxicity, the combination of antineoplastic and cardioprotective drugs, and recent advances in reverse cardio-oncology.

Evaluation of risk factors for chemotherapy-induced nausea and vomiting in cisplatin and gemcitabine treatment for biliary tract cancer: acid suppressants do not prevent nausea.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most serious adverse effects of cancer therapy. Cancer patients frequently use acid suppressants (AS) for palliation of gastrointestinal symptoms associated with malignancy and/or anticancer therapy. AS are suggested as an additional option for CINV management in several antiemetic guidelines, although their efficacy remains unknown. The aim of this study was to determine whether AS administration affects CINV incidence in cisplatin and gemcitabine treatment for biliary tract cancer. The primary endpoint was to evaluate whether AS administration was associated with the incidence of all-grade nausea in the first administration by logistic analysis. The secondary endpoints were to assess factors associated with anorexia. Prophylactic antiemetics were based on current guidelines. Nausea occurred in 34.2% of patients (grade 1, 31.7%; grade 2, 2.5%). Patients exhibiting vomiting and anorexia represented 4.2% and 39.1%, respectively, without grade 3/4 symptoms. Multivariate analysis suggested that the independent risk factors for nausea as female sex, and no- or less-alcohol drinking habit and regular narcotics administration were associated with anorexia. In contrast, AS administration was not associated with nausea and anorexia incidence (odds ratio, 95% confidence interval: 1.43, 0.64-3.23; P =0.38 for nausea, 1.62, 0.71-3.68; P =0.25 for anorexia). In conclusion, we found that AS administration is not associated with CINV incidence, and female sex is a risk factor for nausea, and non-alcohol drinking habits and regular narcotic use are factors associated with anorexia in cisplatin and gemcitabine treatment for biliary tract cancer. We should correctly administer AS depending on the patient's situation. Successful CINV management needs effective monitoring and administration of prophylactic antiemetics and counter-measure medicines for patients at risk.

Anti-inflammatory mouthwashes for the prevention of oral mucositis in cancer therapy: an integrative review and meta-analysis

Mucositis is severely painful and often reported as one of the most distressing adverse effects of cancer therapy; it is a significant threat to quality of life as well as life itself. Anti-inflammatory agents may modulate physiologic mechanisms that perpetuate mucositis and be useful in prevention efforts. Because systemic anti-inflammatory agents are not appropriate for many patients, locally acting agents (mouthwashes) may be more feasible for use. This review and meta-analysis evaluates the role that anti-inflammatory mouthwashes have in preventing or reducing oral mucositis associated with chemotherapy and radiation therapy. A systematic literature review was conducted to identify studies evaluating the efficacy of anti-inflammatory mouthwashes to prevent therapy-associated mucositis. Meta-analysis was conducted to determine efficacy in preventing any mucositis and dose-limiting mucositis. Eight peer-reviewed publications were identified; corticosteroid and nonsteroidal anti-inflammatory mouthwashes are effective in reducing overall incidence of mucositis and are associated with lower severity of mucositis. Meta-analysis reveals significant reduction in symptomatic mucositis incidence (OR 6.00, 95% CI 4.39-8.20, p < 0.0001) and reduction of dose-limiting mucositis (OR 2.12, 95% CI 1.07-4.28, p = 0.032). Mouthwashes containing anti-inflammatory agents are a potential effective means to prevent or reduce mucositis associated with cancer therapy. There are limited adverse effects from these agents, and adherence is high, indicating safety and feasibility of use. Anti-inflammatory mouthwashes should be considered for supportive care in persons at risk for mucositis and must be further evaluated to investigate efficacy across multiple chemotherapy agents, adverse effects, and impacts on symptoms, pain, and quality of life.

Sexual Dysfunction: Common Side Effect.

For sexual dysfunction, standards of care are based on emerging evidence-based practice.&nbsp;Sexuality is an integral part of quality of life that can be radically altered by the adverse effects of cancer therapies. Following treatment, sexual dysfunction can arise from physical and psychological changes in body image and self-concept, altered sense of attractiveness, physical discomfort, and emotional distress, diminishing overall quality of life. Therefore, identification and management of sexual dysfunction are vital components of survivorship care.

Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer: Clinical Consensus.

With an estimated 3.8 million breast cancer survivors in the United States, obstetrician-gynecologists often are on the front lines of addressing survivorship issues, including the hypoestrogenic-related adverse effects of cancer therapies or early menopause in survivors (1). Although systemic and vaginal estrogen are used widely for symptomatic relief of genitourinary syndrome of menopause in the general population, among individuals with a history of hormone-sensitive cancer, there is uncertainty about the safety of hormone-based therapy, leading many individuals with bothersome symptoms to remain untreated, with potential negative consequences on quality of life (2). An effective management strategy requires familiarity with a range of both hormonal and nonhormonal treatment options, knowledge about the pharmaceutical mechanisms of action, and the ability to tailor treatment based on individual risk factors. This clinical consensus document was developed using an a priori protocol in conjunction with two authors specializing in urogynecology and gynecologic oncology. This document has been updated to review the safety and efficacy of newer hormonal treatment options as well as nonhormonal modalities.

Gut microbiota and its influence on ovarian cancer carcinogenesis, anticancer therapy and surgical treatment: A literature review.

Ovarian cancer (OC) is the most lethal gynecological malignancy and very little is known about the underlying tumorigenesis mechanisms. For other tumors, like colorectal cancer, a relationship between several opportunistic pathogens and cancer development and progression has been proven. Recent researches also underline a possible correlation between gut microbiota dysbiosis and cancer treatment efficacy and adverse effects. Several studies have also demonstrated a link between abdominal surgery and gut microbiota modifications. In this paper, we aim to review the available evidences of this issue in OC to understand if there is a relationship between gut microbiota modifications and efficacy and adverse effects of cancer therapies, either surgical and medical treatments. Well-designed clinical studies, with a robust translational component, are required to better understand the modulation of gut microbiota during OC treatment. The microbiota/microbiome composition analysis, in the near future, could represent a novel instrument to personalize anticancer therapies.

Abstract 13272: Modeling Cardiotoxicity Utilizing Human Pluripotent Stem Cell-Derived Cardiomyocytes: Towards Protective Therapy for the Heart

Introduction: Cardiotoxicity is one of the main adverse effects of cancer therapy and has been extensively assessed in animal models which are not predictive for drug-induced cardiotoxicity in humans. Human pluripotent stem cell (hPSC)-derived cardiomyocytes provide a reliable source of human cardiomyocytes and have already proven valuable for cardiotoxicity studies. We present here a versatile screening platform, utilizing hPSC-cardiomyocytes, for assessing different aspects of cardiotoxicity. Methods and Results: A well-known group of anticancer drugs that cause therapy induced cardiotoxicity are anthracyclines. To validate their toxicity on human cells we compared the uptake of Doxorubicin (DOXO) and two of its analogues Amrubicin (AMR) and Aclarubicin (ACLA) into cardiomyocytes and fast dividing hPSCs. We utilized high throughput time-lapse imaging of cardiomyocytes differentiated from an NKX2.5 eGFP -α-actinin mRuby2 hPSC reporter for assessment of viability and sarcomeric disarray by creating binary masks of the fluorescent area. After 5 days less than 25% of sarcomeres were still present and about 20% of cardiomyocytes survived treatment with 1 μM DOXO or ACLA. Moreover, we evaluated the cardiotoxic effect on a functional level by evaluating calcium transients and identified faster rates after DOXO or ACLA treatment. In addition to analysis in 2D monolayers, we also established a more advanced platform for creating 3D engineered heart tissues, more closely resembling the human heart, which allowed us to measure the effect of a cumulative drug dose on cardiac contraction. We quantified contractile force and kinetics every 12 h for 3 days and observed total loss of contraction 60 h after treatment with 5 or 10 μM DOXO, 75% reduction with 5 μM ACLA and no loss of contraction with 5 μM AMR.To study different damage mechanisms, we investigated apoptotic marker Annexin V, DNA damage marker pH2AX, calcium accumulation and expression of cardiac genes. Conclusion: These assays enabled us to study the cardiotoxic effect of DOXO and two analogues on hPSC-derived cardiomyocytes. Most importantly, treatment with AMR had no effect on cardiac function. Ultimately our platform for assessing cardiotoxicity will lead to a better and safer treatment of patients.

Senescent cells in cancer therapy: why and how to remove them.

Cellular senescence is a stress response that imposes a growth arrest on cancer and nonmalignant cells during cancer therapy. By secreting a plethora of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP), therapy-induced senescent cells can promote tumorigenesis. Moreover, the SASP from senescent cells is also able to drive therapy resistance and mediate many adverse effects of cancer therapy. Because senescent cell production often occurs during cancer therapy, it is important to carefully consider these potential detrimental effects. Senotherapy, which refers to selective removal of senescent cells, has been proposed as a promising adjuvant approach to eliminate the adverse effects of senescent cells. Thus, in this review we summarize in detail the mechanisms by which senescent cells contribute to tumorigenesis and therapeutic resistance. Also, we thoroughly discuss the potential strategies regarding how to effectively circumvent the undesirable effects of therapy-induced senescent cells.

Right ventricle strain changes in patients with breast cancer during anthracycline therapy

Abstract Background Cardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for the early subclinical detection of cardiotoxic effect. We aimed to evaluate Right ventricle (RV) two-dimensional speckle tracking echocardiography (2D-STE) changes during ANT therapy and to assess the correlation between RV 2D-STE and the routine echocardiographic RV parameters. Methods Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline RV 2D-STE (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). RV 2D-STE was evaluated using the apical 4 chamber (4C) RV-focused view, assessing both the combined RV free wall and inter-ventricular septum (RV GLS) and solely the RV free wall strain (RV FWLS). Significant reduction in both RV GLS and RV FWLS was determined by either a relative reduction of &amp;gt;10% or an absolute value of &amp;gt;−25% for RV GLS and &amp;gt;−29% for RV FWLS. Results From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 238.5±9.4 mg/m2. RV FWLS showed significant correlation to Tricuspid annular plane systolic excursion. At T3, significant reduction in both RV GLS and RV FWLS was observed among 77% and 62% of the patients with a mean RV GLS and RV FWLS reduction from −26.8 (±4.7) % to −21.5 (±4.4) % and −28.9 (±5.1) % to −25.6 (±5.9) % (p&amp;lt;0.001, p=0.002), respectively. Left ventricle (LV) ejection fraction and LV GLS were within the normal range. Conclusions RV GLS and RV FWLS reduction are frequent and occur early in the course of ANT therapy, preceding LV dysfunction, which may imply for the role of RV 2D-STE in the detection of early cardiotoxicity. Funding Acknowledgement Type of funding sources: None.

Left Atrial Strain changes in patients with breast cancer during anthracycline therapy

BackgroundCardiotoxicity has become a significant adverse effect of cancer therapy, with Anthracyclines (ANT) in particular. There is a crucial need for new imaging techniques for the early subclinical detection of cardiotoxic effect. We aimed to evaluate left atrial strain (LAS) changes during ANT therapy and to assess the correlation between LAS and the routine echocardiographic diastolic parameters. Methods and resultsData were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). All female patients with breast cancer, planned for ANT therapy were included. All patients underwent serial echocardiography exams including baseline LAS (before chemotherapy, T1) and shortly after the completion of ANT therapy (T3). LAS was assessed in 3 phases: Reservoir (LASr), Conduit (LASc) and Pump (LASp). Significant reduction in LASr was determined by either a relative reduction of >10% or an absolute value of <35%. From September 2016 to June 2019, 40 patients were evaluated with a mean Doxorubicin (type of ANT) dose of 237±13.24mg/m2. At T3, significant reduction in LASr was observed among 50% of the patients with a mean LASr reduction from 40.15 ± 6.83% to 36.04 ± 7.73% (p < 0.001). LASc showed significant reduction as well (p < 0.004) as opposed to LASp (p=0.076). Both LASr and LASc showed significant correlation to the routine diastolic parameters. ConclusionsLASr and LASc reduction are frequent and occur early in the course of ANT therapy, showing significant correlation to the routine echocardiographic diastolic parameters, which may imply a role in the detection of early cardiotoxicity.

The Role of Speckle Strain Echocardiography in the Diagnosis of Early Subclinical Cardiac Injury in Cancer Patients-Is There More Than Just Left Ventricle Global Longitudinal Strain?

With the improvement in survival rate, cardiotoxicity has emerged as a significant adverse effect of cancer therapy. Early diagnosis of subclinical cardiac injury may allow the initiation of cardioprotective therapy and preventing the interruption of optimal cancer therapy and the development of irreversible cardiac dysfunction. In this article, we review the role of two-dimensional speckle tracking echocardiography (2D-STE), beyond the common left ventricle global longitudinal strain in the diagnosis of early subclinical cardiac injury in patients treated with cancer therapies.

Self-efficacy in symptom management for adolescents and young adults with cancer: a systematic review.

Adolescents and young adults (AYAs) have more frequent and intense adverse effects from cancer therapy than other age groups. Self-efficacy, the ability for persons to maintain health-related behavior change, may assist with symptom management but the role it plays in AYAs with cancer has not been thoroughly investigated. This review explores the role that self-efficacy has in symptom management for AYAs with cancer and provides guidance for clinicians to utilize self-efficacy as a means to reduce side effects of therapy. A systematic review of peer-reviewed literature was conducted to identify works discussing self-efficacy and symptom management for AYAs with cancer. Five databases were searched with key terms and articles that discussed relationships between self-efficacy and cancer therapy symptoms were retained for analysis. Twelve manuscripts representing 1180 individuals age 12 to 43years were identified. Self-efficacy was found to be related to (1) health management behaviors, (2) psychosocial health, (3) sexual and reproductive health, and (4) physical symptoms. Self-efficacy had direct correlations with physical activity, nutritional intake, symptom regulation, mental health, sexual health, and fertility preservation. The included studies did not find significant relationships with medication adherence or pain management. Self-efficacy is an attribute that impacts behavior change, health maintenance, and overall wellness and can be changed over time and through interventions to improve symptoms of cancer therapy. Self-efficacy should be evaluated as a construct in relevant studies aimed at improving side effects of cancer therapy to better understand outcomes from interventions. Symptoms, toxicities, and adverse effects of cancer therapy may be improved by increasing self-efficacy of patients.

RETRACTED ARTICLE: Inhibition of EZH2 enhances the therapeutic effect of 5-FU via PUMA upregulation in colorectal cancer

Although the survival rate of patients with cancer have increased due to the use of current chemotherapeutic agents, adverse effects of cancer therapy remain a concern. The reversal of drug resistance, reduction in harmful side effects and accelerated increase in efficiency have often been addressed in the development of combination therapeutics. Tazemetostat (EPZ-6438), a histone methyltransferase EZH2 selective inhibitor, was approved by the FDA for the treatment of advanced epithelioid sarcoma. However, the effect of tazemetostat on colorectal cancer (CRC) and 5-FU sensitivity remains unclear. In this study, the enhancement of tazemetostat on 5-FU sensitivity was examined in CRC cells. Our findings demonstrated that tazemetostat combined with 5-FU exhibits synergistic antitumor function in vitro and in vivo in CRC cells. In addition, tazemetostat promotes PUMA induction through the ROS/ER stress/CHOP axis. PUMA depletion attenuates the antitumor effect of the combination therapy. Therefore, tazemetostat may be a novel treatment to improve the sensitivity of tumors to 5-FU in CRC therapy. In conclusion, the combination of 5-FU and tazemetostat shows high therapeutic possibility with reduced unfavorable effects.