Adverse Effects Of Anticancer Therapy Research Articles

Impact of Physical Exercise on Melanoma Hallmarks: Current Status of Preclinical and Clinical Research.

In recent years, accumulating evidence from preclinical and clinical studies consistently indicated that physical activity/exercise plays a crucial role in reducing the incidence and recurrence of various malignancies, by exerting a beneficial modulation of cancer hallmarks. Moreover, physical activity is suggested to attenuate certain adverse effects of anticancer therapy, including the reduction of cardiovascular toxicity and symptoms related to depression and anxiety, among others, while preserving muscular strength. In the case of melanoma, the relationship with physical activity has been critically debated. Historically, several cohort studies and meta-analyses reported a positive association between physical activity/exercise and melanoma risk. This association was primarily attributed to outdoor activities that may expose the skin to UV radiation, a well-known risk factor for melanocyte transformation. However, more recent evidence does not support such association and recognizes physical activity/exercise role in both melanoma prevention and progression. Nevertheless, sun protection is recommended during outdoor training to minimize UV radiation exposure. This narrative review summarizes preclinical and clinical data about physical activity effects on melanoma hallmarks. Specifically, experimental evidence is reported concerning (i) invasion and metastasis, (ii) reprogramming of energy metabolism, (iii) angiogenesis, (iv) resistance to cell death, (v) evasion from immune destruction, and (vi) tumor-promoting inflammation.

Cardiovascular and oncological diseases — focus on modifiable risk factors and modern pathogenetic aspects

Currently, in modern medicine, there has been a sharp increase in interest in the combined pathology of cardiovascular diseases (CVD) with other nosologies, such as diabetes mellitus, chronic kidney disease, and oncopathology. Over the past decades, there have been large positive shifts in survival in this cohort of patients. An integral specialty of cardio-oncology is rapidly developing, which is aimed at improving the results of treatment of oncological patients. Due to increased life expectancy and improved long-term prognosis in cancer patients, in particular, the adverse effects of anticancer therapy have attracted great attention from researchers. The causal relationship between cancer and CVD can be partly explained by a common profile of modifiable and non-modifiable risk factors. There is also strong evidence that a systemic inflammatory response is a common pathophysiological determinant of cancer and CVD. General risk factors for development and progression, as well as pathogenetic mechanisms, contribute to high mortality rates. Increasing knowledge of pathophysiological mechanisms will help elucidate the general molecular aspects of carcinogenesis and cardiovascular disease. This review presents general modifiable risk factors and current pathogenetic aspects of cardiovascular and oncological diseases.

Cardio-Oncology Rehabilitation-Present and Future Perspectives.

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, one caused mainly due to anti-cancer drugs. Among the harmful mechanisms of these drugs are DNA damage, endothelial dysfunction, and oxidative stress. Cancer patients can suffer reduced cardiorespiratory fitness as a secondary effect of anti-cancer therapies, tumor burden, and deconditioning. In the general population, regular exercise can reduce the risk of cardiovascular morbidity, mortality, and cancer. Exercise-induced modifications of gene expression result in improvements of cardiovascular parameters and an increased general fitness, influencing telomere shortening, oxidative stress, vascular function, and DNA repair mechanisms. In cancer patients, exercise training is generally safe and well-tolerated; it is associated with a 10–15% improvement in cardiorespiratory fitness and can potentially counteract the adverse effects of anti-cancer therapy. It is well known that exercise programs can benefit patients with heart disease and cancer, but little research has been conducted with cardio-oncology patients. To date, there are a limited number of effective protective treatments for preventing or reversing cardiotoxicity caused by cancer therapy. Cardiac rehabilitation has the potential to mitigate cardiotoxicity based on the benefits already proven in populations suffering from either cancer or heart diseases. Additionally, the fact that cardiotoxic harm mechanisms coincide with similar mechanisms positively affected by cardiac rehabilitation makes cardiac rehabilitation an even more plausible option for cardio-oncology patients. Due to unstable functional capacity and fluctuating immunocompetence, these patients require specially tailored exercise programs designed collaboratively by cardiologists and oncologists. As the digital era is here, with the digital world and the medical world continuously intertwining, a remote, home-based cardio-oncology rehabilitation program may be a solution for this population.

Long-Term Effect of Anticancer Therapy on Dentition in Childhood Cancer Survivors: An Observational, Cross-Sectional Study.

To evaluate the presence of developmental dental anomalies, like microdontia, hypodontia, abnormally shaped teeth (AST), and developmental defects of enamel (DDE) in childhood cancer survivors and compare it with the healthy controls. This cross-sectional analytical study was conducted in 2 groups: childhood cancer survivors (CCS) group including children (> 12 y, m/f) who had undergone anticancer therapy (ACT) before 8 y of age and healthy control group (> 12 y, m/f) without any systemic disease. Pearson chi-square test was used to analyze the difference between the CCS group and the control group for microdontia, hypodontia, AST, DDE and for intragroup analysis in CCS group. Odds ratio was also calculated. A total of 120 and 121 children were included in CCS and control group, respectively. The prevalence of microdontia, hypodontia, abnormally shaped teeth, and DDE was 17.5% (21), 5% (6), 8.33% (10), and 37.5% (45), respectively in CCS group. It was 8.2% (10), 2.5% (3), 1.65% (2), and 22.3% (27), respectively in the control group. A statistically significant difference was seen in microdontia (p = 0.032), abnormally shaped teeth (p = 0.017) and DDE (p = 0.01). Higher prevalence was seen when ACT began at an early age. An association between developmental dental anomalies and anticancer therapy (ACT) exists with significantly higher difference in microdontia, abnormally shaped teeth and DDE among survivors of childhood cancer as compared to healthy population. These known adverse effects of ACT on developing teeth should be considered during treatment planning of the children having cancers.

The Enigmatic Emerging Role of the C-Maf Inducing Protein in Cancer.

The C-Maf-Inducing protein (CMIP) was first described as overexpressed in T cell subpopulations of idiopathic nephrotic syndrome (INS) patients. Later, it was found concomitantly upregulated in podocytes. CMIP expression has also been reported in several types of cancer, including blood malignancies and solid tumors, in many cases accompanied by nephrotic syndrome. In addition to these observations, the duality of CMIP overexpression in the kidney and INS lesions, has been extensively reported as one of the adverse effects of anticancer therapy based on anti-receptor tyrosine kinase drugs. As a consequence, a growing body of evidence points at CMIP as playing a role in cancer. This includes its reciprocal regulatory ties with NF-κB and WT1, and the more recent reports showing an involvement in regulatory circuits in cancer cells. The ensemble of the current information justifies to propose CMIP as an important piece of the puzzle of biological systems involved in cancer and other diseases and its potential as a target.

Rationale and proposal for cardio-oncology services in Italy.

In the last 20 years, a substantial improvement in the efficacy of cancer treatment has induced a progressive increase in cancer survival, with an obvious parallel increase in morbidity and mortality related to the adverse effects of anticancer therapy, in particular, cardiovascular complications. In relation to the peculiar aspects related to cardiac and vascular toxicity, clinical management of patients should be ideally reserved for experts in the field of this novel medical discipline, which has been defined as cardio-oncology. The rationale for this choice corresponds to the aim of identifying patients more prone to developing cardiovascular damage, prevent overt cardiotoxicity and conduct active surveillance of treated patients for early identification of cardiac and vascular involvement during short- and long-term follow-up. Due to the burden of treated cancer patients, the development of dedicated cardio-oncology services has become one of the main goals of contemporary medicine, needed to accomplish the peculiar mission of guiding the patients through the narrow path of cancer survival without the expense of cardiovascular damage. The main purpose of cardio-oncology services is to provide dedicated cardiologic care to cancer patients affected by concomitant (subclinical or overt) cardiovascular diseases, either preexisting the cancer onset or acquired during and after the time course of anticancer therapy. In this article, we describe a possible spoke-hub model of cardio-oncology services, which could be appropriately applied in Italy. Rationale, organization, definition of referral criteria, strategies, interventional programs, long-term surveillance and home assistance of this model are described and discussed.

Evaluation of the Efficacy and Safety of the Herbal Formula PM014 in a Cisplatin- and Paclitaxel-Treated Tumor-Bearing Mouse Model.

PM014 (HL301) is a standardized herbal mixture derived from a traditional Korean medicine, Chung-Sang-Bo-Ha-Tang. Previously, we reported that PM014 treatment significantly suppressed pulmonary fibrosis, one of the frequent adverse effects of anticancer therapy in lung cancer. Before the clinical application of PM014 in anticancer therapy, the safety and efficacy of PM014 in combination with conventional anticancer drugs should be addressed to determine whether PM014 can be used in lung cancer. Lewis lung cancer–bearing mice were injected with 10 mg/kg of cisplatin or paclitaxel on day 5. Starting on day 7, the mice were administered 200 mg/kg PM014 every 2 days. On day 15, all mice were assessed by biochemical and histological analyses. PM014 did not block the antitumor activity of cisplatin and paclitaxel. Coadministration of PM014 and antitumor agents did not elevate the aspartate transaminase/alanine transaminase ratio or the blood urea nitrogen/creatinine ratio. Histopathological analysis also showed that PM014 did not induce hepatic or renal injury. Moreover, PM014 had no apparent inhibitory effects on drug metabolizing enzymes, indicating that PM014 did not alter the pharmacokinetics of chemotherapeutic drugs. Overall, these data show the safety and compatibility of combination therapy of PM014 and chemotherapies for the treatment of lung cancer.

Effects of Chemotherapy and Radiotherapy on Spermatogenesis: The Role of Testicular Immunology.

Substantial improvements in cancer treatment have resulted in longer survival and increased quality of life in cancer survivors with minimized long-term toxicity. However, infertility and gonadal dysfunction continue to be recognized as adverse effects of anticancer therapy. In particular, alkylating agents and irradiation induce testicular damage that results in prolonged azoospermia. Although damage to and recovery of spermatogenesis after cancer treatment have been extensively studied, there is little information regarding the role of differences in testicular immunology in cancer treatment-induced male infertility. In this review, we briefly summarize available rodent and human data on immunological differences in chemotherapy or radiotherapy.

Mucocutaneous Adverse Reactions of Cancer Chemotherapy and Chemoradiation.

Background:With the introduction of newer anti-cancer agents, the adverse effects have become more rampant which call for concern in the treatment of patients with cancer. Hence, the assessment and management of dermatological adverse effects of anti-cancer therapy have become a significant part of the care of patients with cancer and require proper and close collaboration between the dermatologists and the oncologists.Aims:To assess the frequency and pattern of mucocutaneous adverse reactions to cancer chemotherapy and chemoradiation and grade them according to their severity and to identify hematological and biochemical changes related to cancer chemotherapy-induced mucocutaneous adverse reactions.Materials and Methods:This was a descriptive study done among 226 patients in an Indian tertiary care hospital, who presented with mucocutaneous adverse reactions to either chemotherapy alone or combination of chemotherapy and radiation to dermatology, medical oncology and radiotherapy outpatient departments. Detailed history and examination were undertaken. Visual analog score (VAS) was employed to quantify pain and pruritus. Correlation of various biochemical and hematological parameters with chemotherapy-induced adverse reactions was attempted and grading of adverse reactions was done based on the severity scale of Common Terminology Criteria for Adverse Events (CTCAE).Results:The common cutaneous adverse reactions observed in our study were nail changes (194 patients; 85.84%), followed by skin changes (191; 84.51%), hair changes (159, 70.35%), mucosal changes (34, 15.04%), and other miscellaneous manifestations. Grade 1 manifestations comprised of 49.91% of total manifestations followed by Grade 2 (45.45%) and Grade 3 (5.64%). In addition to bleomycin, other chemotherapeutic agents also had been shown to produce flagellate dermatitis in our study.Conclusion:Nail changes, skin changes, hair changes and mucosal changes occurred frequently as a significant side effect of chemotherapy, which a physician should be aware of, while selecting a chemotherapeutic drug.

Homeopathy and Complementary Integrative Medicine, Dietary and Lifestyle Advices to Reduce Adverse-Effects of Anti-Cancer Therapy: A Cohort Study with Breast Cancer Patients

Background. To face adverse-effects of anti-cancer treatment, the Homeopathic Clinic of Lucca, in collaboration with the Oncology Department, has set up an Integrative Oncology Outpatient Unit in the Public Hospital Campo di Marte, Aim. To present the results of complementary medicine (CM) treatment targeted towards reducing the adverse effects of anti-cancer therapy and cancer symptoms and improving the quality of life of breast cancer patients. Methods. This is a retrospective observational study conducted on 204 breast cancer patients (all females except 1 male) were consecutively visited from September 2013 to December 2017, mean age 54.8 (35-88) years. Almost all patients were referred by their medical oncologists. The intensity of symptoms was evaluated according to a grading system from G0 (absence of symptoms) to G1 (slight), G2 (moderate), and G3 (strong), as evaluated by the patient in conjunction with the doctor during the course of the visits. The severity of radiodermatitis was evaluated with the Radiation Therapy Oncology Group (RTOG) scale. Homeopathy was the main prescribed therapy, either exclusive (47.5%) or integrated with other complementary medicines (41.7%), mainly botanicals and acupuncture. The Banerji protocol was applied in 3.4% of patients. Results. The most frequently treated symptoms were the adverse-effects of anti-cancer therapies (84.3%): endocrine therapy (36.3%), chemotherapy (33.3%), radiotherapy (9.8%) and surgery (4.9%). The symptoms caused by cancer disease were 25.5%, and comorbidity 21.6%. Comparison of the clinical conditions before and after treatment allowed to observe a significant amelioration of the following symptoms: hot flashes (p < 0.01); nausea (p < 0.01); fatigue (p < 0.01); anxiety (p < 0.05); depression (p < 0.01); insomnia (p < 0.01); mucositis (p < 0.01); joint pain (p < 0.01) . Conclusions. A clinic of integrative oncology is an opportunity to reduce adverse-effects of anti-cancer therapy and to ameliorate cancer patients’ quality of life.

Complementary and Integrative Medicine to Reduce Adverse Effects of Anticancer Therapy.

To address the side effects of anticancer treatments, the Clinic for Complementary Medicine and Diet in Oncology was opened, in collaboration with the oncology department, at the Hospital of Lucca (Italy) in 2013. To present the results of complementary medicine treatment targeted toward reducing the adverse effects of anticancer therapy and cancer symptoms, and improving patient quality of life. Dietary advice was aimed at the reduction of foods that promote inflammation in favor of those with antioxidant and anti-inflammatory properties. This is a retrospective observational study on 357 patients consecutively visited from September 2013 to December 2017. The intensity of symptoms was evaluated according to a grading system from G0 (absent) to G1 (slight), G2 (moderate), and G3 (strong). The severity of radiodermatitis was evaluated with the Radiation Therapy Oncology Group (RTOG) scale. Almost all the patients (91.6%) were receiving or had just finished some form of conventional anticancer therapy. The main types of cancer were breast (57.1%), colon (7.3%), lung (5.0%), ovary (3.9%), stomach (2.5%), prostate (2.2%), and uterus (2.5%). Comparison of clinical conditions before and after treatment showed a significant amelioration of nausea, insomnia, depression, anxiety, fatigue, mucositis, hot flashes, joint pain, dysgeusia, neuropathy, and all symptoms. Moreover, in a subgroup of 17 patients in radiotherapy undergoing integrative treatment, the level of toxicities and the severity of radiodermatitis were much lower than in the 13 patients without integrative treatment. Twenty-one cancer patients (6.2%) either refused (18) or discontinued (3) conventional anticancer treatment against the recommendation of their oncologist; after the integrative oncology (IO) visit, 7 (41.2%) out of 17 patients with follow-up decided to accept standard oncologic treatments. An IO clinic may contribute to reducing the adverse effects of anticancer therapy and improving the quality of life of cancer patients.

Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study

BackgroundInterstitial lung diseases induced by anticancer agents (ILD-AA) are rare adverse effects of anticancer therapy. However, prognostic biomarkers for ILD-AA have not been identified in patients with advanced lung cancer. Our aim was to analyze the association between serum biomarkers sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), and clinical characteristics in patients diagnosed with ILD-AA.MethodsBetween April 2011 and March 2016, 1224 advanced lung cancer patients received cytotoxic agents and epidermal growth factor receptor tyrosine kinase inhibitors at Juntendo University Hospital and Juntendo University Urayasu Hospital. Of these patients, those diagnosed with ILD-AA were enrolled in this case control study. ΔKL-6 and ΔSP-D were defined as the difference between the levels at the onset of ILD-AA and their respective levels prior to development of ILD-AA. We evaluated KL-6 and SP-D at the onset of ILD-AA, ΔKL-6 and ΔSP-D, the risk factors for death related to ILD-AA, the chest high resolution computed tomography (HRCT) findings, and survival time in patients diagnosed with ILD-AA.ResultsThirty-six patients diagnosed with ILD-AA were enrolled in this study. Among them, 14 patients died of ILD-AA. ΔSP-D in the patients who died was significantly higher than that in the patients who survived. However, ΔKL-6 did not differ significantly between the two groups. Moreover, ΔSP-D in patients who exhibited diffuse alveolar damage was significantly higher than that in the other patterns on HRCT. Receiver operating characteristic curve analysis was used to set the optimal cut off value for ΔSP-D at 398 ng/mL. Survival time for patients with high ΔSP-D (≥ 398 ng/mL) was significantly shorter than that for patients with low ΔSP-D. Multivariate analysis revealed that ΔSP-D was a significant prognostic factor of ILD-AA.ConclusionsThis is the first research to evaluate high ΔSP-D (≥ 398 ng/mL) in patients with ILD-AA and to determine the risk factors for ILD-AA in advanced lung cancer patients. ΔSP-D might be a serum prognostic biomarker of ILD-AA. Clinicians should evaluate serum SP-D during chemotherapy and should carefully monitor the clinical course in patients with high ΔSP-D.

Effect of cytochrome c modification with co‐polymer on its apoptotic activity for cancer treatment (LB248)

Treating cancer, while avoiding devastating side effects, has been a challenge throughout the years. Active targeted delivery has been extensively studied to overcome the inherent adverse effects of anticancer therapy. The apoptotic protein cytochrome c (cyt c) is highly effective at causing cancer cells cytotoxicity but as most proteins, its delivery is challenging. In this project, we synthesized a co‐polymer of hyaluronic acid (HA) and folic acid (FA) followed by cyt c binding. Both compounds of the co‐polymer were selected due to their receptors overexpression on cancer cells surface allowing endocytosis of the cyt c system. We used TNBSA assay to determine the amount of modified lysines in cyt c when reacted to HA‐FA: 2.1 ± 0.4. The residual activity of the protein was measured before and after its incorporation in HA‐FA using a caspase cascade assay which showed caspase activation by cyt c‐HA‐FA: 105 ± 1 % while HA‐FA did not activate caspase: 1.6 ± 0.8 %. CD spectroscopy showed minor changes in heme group and tertiary structure of cyt c following modification. HeLa cells were incubated with cyt c‐HA‐FA (0.1 mg/ml) to measure cell viability with MTS assay. Cell viability was measured after 2 and 6 hours of incubation: 108 ± 14 % and 83 ± 8 %, respectively. According to these results we successfully synthesized a promising drug delivery system for anticancer applications.Grant Funding Source: Supported by NIH Research Initiative for Scientific Enhancement (RISE) Program with grant number: 2R25GM061151‐12.