Chemotherapy-induced Side Effects Research Articles

Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.

Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments. The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations. The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals. Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities. The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

Acupuncture in Oncology – Update 2024

Acupuncture, as a promising complementary therapy for cancer patients, offers personalized symptom management and improved quality of life alongside conventional treatments. With its proven efficacy in alleviating chemotherapy-induced side effects such as nausea, fatigue, and pain, acupuncture stands as a holistic approach to cancer care. Tailored to individual needs and boasting a favorable safety profile, acupuncture addresses both physical symptoms and psychological distress, promoting resilience and quality of life. By integrating specific acupuncture points into treatment protocols, practitioners can provide targeted relief and support for patients, fostering holistic healing and emotional well-being amidst the challenges of cancer treatment.

Abstract 4767: Changes in the NSE and S100B levels following treatment with peripheral neuropathy-inducing drugs

Abstract Neo-adjuvant chemotherapy is considered the standard of care for patients with multiple myeloma (MM). Peripheral neuropathy (PN) is one of the most common chemotherapy-induced side effects that impact 50% of all patients who receive chemotherapy and can lead to discontinuation of drug treatment. Treatment with Bortezomib (BTZ), Cisplatin (CIS), and Vincristine (VIN) has been established as the most common trigger of Chemotherapylnduced Peripheral Neuropathy (CIPN) among cancer patients. Since CIPN can lead to disabling long-term adverse effects, many cancer patients discontinue or limit their treatment regimen once they see signs or symptoms of CIPN. Therefore, it was hypothesized that developing diagnostic/prognostic biomarkers that can accurately predict the onset or progression of CIPN would help to determine the chemotherapy eligibility with the above-mentioned drugs and proactively prepare for protective care. Hence, our initial goal was to elucidate the molecular mechanisms underlying the onset and progression of CIPN that would allow for the identification of suitable biomarkers that can be used for monitoring before or during chemotherapy with BTZ, CIS, and VIN. Initially, we conducted in vitro studies to identify the underlying molecular mechanisms activating CIPN related pathways. We used neuronal Schwann cells (RT4), for testing the neurotoxic effects of BTZ, CIS, and VIN that might precede or coincide with the onset of CIPN in an in vivo condition. Interestingly, the BTZ treatment was able to significantly reduce the intracellular level of NSE and S100B in RT4 cells compared to the untreated controls, when they were measured using an immunofluorescence assay and Western blot. Furthermore, we conducted an in vivo study to determine the CIPN using rats. We used the sciatic nerve (SN) from drug-treated animals to check the S100B level using the ELISA method. Our preliminary results showed that levels of S100B in the SN of Rats were reduced following 8 weeks of treatment with the PN-inducing chemo drugs. We anticipate that this study will enrich our understanding of how chemotherapy medications induce PN in cancer patients and guide us to identify reliable biomarkers (This project was supported by the PFRDG grant of the Nova Southeastern University, Ft. Lauderdale Florida, and the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida). Citation Format: Priya R. Vontikommu, Shriya Selvakumar, Umamaheshwari Natarajan, Appu Rathinavelu. Changes in the NSE and S100B levels following treatment with peripheral neuropathy-inducing drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4767.

Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects.

Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy.

Ozone Therapy for Breast Cancer: An Integrative Literature Review.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

Irinotecan cause the side effects on development and adult physiology, and induces intestinal damage via innate immune response and oxidative damage in Drosophila

Chemotherapy leads to significant side effects in patients, especially in the gut, resulting in various clinical manifestations and enhanced economic pressure. Until now, many of the underlying mechanisms remain poorly understood. Here, we used Drosophila melanogaster (fruit fly) as in vivo model to delineate the side effects and underlying mechanisms of Irinotecan (CPT-11). The results showed that administration of CPT-11 delayed larval development, induced imbalance of male to female ratio in offspring, shortened lifespan, impaired locomotor ability, changed metabolic capacity, induced ovarian atrophy, and increased excretion. Further, CPT-11 supplementation dramatically caused intestinal damages, including decreased intestinal length, increased crop size, disrupted gastrointestinal acid-based homeostasis, induced epithelial cell death, and damaged the ultrastructure and mitochondria structure of epithelial cells. The cross-comparative analysis between transcriptome and bioinformation results showed that CPT-11 induced intestinal damage mainly via regulating the Toll-like receptor signaling, NF-kappa B signaling, MAPK signaling, FoxO signaling, and PI3K-AKT signaling pathways. In addition, CPT-11 led to the intestinal damage by increasing ROS accumulation. These observations raise the prospects of using Drosophila as a model for the rapid and systemic evaluation of chemotherapy-induced side effects and high-throughput screening of the protective drugs.

Relationships among marital status, oxytocin, and chemotherapy-induced behavioral side effects in female breast cancer patients

Relationships among marital status, oxytocin, and chemotherapy-induced behavioral side effects in female breast cancer patients

The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.

Oxidative stress is increasingly recognized as a central player in a range of gastrointestinal (GI) disorders, as well as complications stemming from therapeutic interventions. This article presents an overview of the mechanisms of oxidative stress in GI conditions and highlights a link between oxidative insult and disruption to the enteric nervous system (ENS), which controls GI functions. The dysfunction of the ENS is characteristic of a spectrum of disorders, including neurointestinal diseases and conditions such as inflammatory bowel disease (IBD), diabetic gastroparesis, and chemotherapy-induced GI side effects. Neurons in the ENS, while essential for normal gut function, appear particularly vulnerable to oxidative damage. Mechanistically, oxidative stress in enteric neurons can result from intrinsic nitrosative injury, mitochondrial dysfunction, or inflammation-related pathways. Although antioxidant-based therapies have shown limited efficacy, recognizing the multifaceted role of oxidative stress in GI diseases offers a promising avenue for future interventions. This comprehensive review summarizes the literature to date implicating oxidative stress as a critical player in the pathophysiology of GI disorders, with a focus on its role in ENS injury and dysfunction, and highlights opportunities for the development of targeted therapeutics for these diseases.

The effects of synbiotics supplementation on reducing chemotherapy-induced side effects in women with breast cancer: a randomized placebo-controlled double-blind clinical trial

BackgroundThe prevalence of breast cancer and its mortality rate are increasing rapidly among women worldwide. On other hand, the courses of chemotherapy as the main treatment for these patients are too much exhaustive and annoying. This study was designed to evaluate the use of synbiotics (probiotics + prebiotics) supplementation as a safe and inexpensive adjuvant treatment in reducing common chemotherapy side effects in women with breast cancer.MethodsThe current study was conducted on 67 women with definitive diagnosis of breast cancer who were hospitalized to receive one-day chemotherapy sessions, and met the inclusion criteria. The patients were randomly allocated to the intervention or control group to receive synbiotics or placebo, respectively. They received oral consumption of synbiotics supplements twice a day for 8 weeks. The primary outcome was the changes in severity or experience of chemotherapy complication, analyzed by intention to treat (ITT). The instruments included 7 validated questionnaires which were used to assess chemotherapy complications in the initiation, 4 weeks and 8 weeks after intervention. Dietary intake was measured by 24-h dietary recall at the beginning, week 4 and week 8. Data were analyzed by SPSS software version 24. P-value < 0.05 was considered as statistically significant.Results67 breast cancer patients participated in the study. 8 weeks after intervention and adjusting the confounders, the severity of chemotherapy complications including unnormal defecation (P = 0.005) and fatigue (P < 0/001) decreased significantly in the synbiotics group compared to the placebo group. Furthermore, nausea/vomiting (P = 0.015), and anorexia (P < 0.001) were decreased at the end of the study compared to the first visit, but it was not statistically significant compared to the placebo group.ConclusionsSynbiotics supplementation during chemotherapy can potentially reduce the severity of fatigue and abnormal defecation. It can help reduce anorexia and nausea/vomiting.Trial RegistrationThis study was registered in the Iranian Registry of Clinical Trials (IRCT) (registered code: IRCT20091114002709N56) (date of registration: 5/5/2021). Direct link to the trial page: https://www.irct.ir/trial/54559.

Chimeric Peptide Engineered Nanomedicine for Synergistic Suppression of Tumor Growth and Therapy-Induced Hyperlipidemia by mTOR and PCSK9 Inhibition.

Chemotherapy-induced side effects restrain anti-tumor efficiency, with hyperlipidemia being the most common accompanying disease to cause treatment failure. In this work, a chimeric peptide-engineered nanomedicine (designated as PRS) was fabricated for the synergistic suppression of tumor growth and therapy-induced hyperlipidemia. Within this nanomedicine, the tumor matrix-targeting peptide palmitic-K(palmitic)CREKA can self-assemble into a nano-micelle to encapsulate Rapamycin (mTOR inhibitor) and SBC-115076 (PCSK9 inhibitor). This PRS nanomedicine exhibits a uniform nano-distribution with good stability which enhances intracellular drug delivery and tumor-targeting delivery. Also, PRS was found to synergistically inhibit tumor cell proliferation by interrupting the mTOR pathway and reducing Rapamycin-induced hyperlipidemia by increasing the production of LDLR. In vitro and in vivo results demonstrate the superiority of PRS for systematic suppression of tumor growth and the reduction of hyperlipidemia without initiating any other toxic side effects. This work proposes a sophisticated strategy to inhibit tumor growth and also provides new insights for cooperative management of chemotherapy-induced side effects.

Gastric Metastasis from Primary Lung Adenocarcinoma: A Case Report

&lt;p&gt;原發性肺癌是臨床上常見的癌症，目前研究對於肺癌的診斷、臨床及病理表現、治療等等日新月異。然而，原發性肺癌合併腸胃道轉移的個案則是相當罕見，因為其常以無症狀或非特異性症狀表現，在臨床上容易被忽略或誤診。原發性肺癌合併胃部轉移與原發性胃癌在組織學的表現十分相似，需要依靠免疫組織化學染色（包含腫瘤細胞角蛋白7 (CK7)、甲狀腺轉錄因子-1 (TTF-1)、腫瘤細胞角蛋白20 (CK20)）協助鑑別診斷。此篇病例報告呈現一位原發性肺癌合併胃部轉移的個案，臨床表現包含長久的消化不良以及體重減輕，在追蹤期間被診斷為化療造成的不適，最後經免疫組織化學染色確診為原發性肺癌合併胃部轉移。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Primary lung cancer is very common and fatal. However, cases of primary lung cancer with gastrointestinal metastases are relatively rare. We present a case of gastric metastasis from primary lung adenocarcinoma with clinical manifestations including dyspepsia and weight loss. The patient was initially thought to undergo chemotherapy-induced side effects but later diagnosed as gastric metastasis from primary lung cancer (GMLC) through special immunohistochemical staining of tissue for thyroid transcription factor-1 (TTF-1) and cytokeratin-7 (CK-7). Since the gastrointestinal (GI) tract remains a rare site of metastasis of primary lung cancer, GMLC is primarily described in case series. The incidence is considered underestimated, and the main reason is that it mostly presents with asymptomatic and nonspecific symptoms which sometimes may be regarded as the side effects of chemotherapy, hence misidentified as primary gastric cancer. Complications such as acute gastric bleeding and gastric perforation occur in patients with gastric metastasis and may result in death in severe cases. The presentation of gastric metastasis is difficult to differentiate from primary gastric cancer under endoscopy, leading to misdiagnosis and inadequate treatment. As the histological appearance of primary lung cancer with gastric metastasis is highly similar to that of primary gastric cancer, immunohistochemistry (IHC) staining is needed to assist in differential diagnosis.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Chemotherapy periodization to maximize resistance training adaptations in oncology.

Engaging in exercise programs during cancer treatment is challenging due to the several chemotherapy-induced side effects. Using a pre-clinical model that mimics chemotherapy treatment, we investigated if a periodized-within-chemotherapy training strategy can maximize resistance training (RT) adaptations such as increasing muscle mass and strength. Swiss mice were randomly allocated into one of the following five groups (n = 14): control (C), resistance training (RT), chemotherapy-treated non-exercised group (Ch), resistance training chemotherapy treated (RTCh), and resistance training periodized-within-chemotherapy (RTPCh). Doxorubicin (i.p.) was weekly injected for a total of 3 weeks (total dose of 12mg/kg). Resistance training consisted of ladder climbing with progressive intensity, three times a week for 3 weeks, during chemotherapy treatment. RTPCh prescriptions considered "bad day" adjustments while RTCh did not. "Bad day" adjustments considered the presence or absence of clinical signs (e.g., severe weight loss, diarrhea, mice refusing to train) to replace RT sessions. At the end of the third week, animals were euthanized. Weekly doxorubicin injection promoted progressive body weight loss, muscle atrophy, strength loss, local oxidative stress, and elevated inflammatory mediators, such as TNF-α and IL-6. Non-periodized-within-chemotherapy RT promoted mild protection against doxorubicin-induced skeletal muscle disturbances; moreover, when periodized-within-chemotherapy was applied, RT prevented elevated skeletal muscle inflammatory mediators and oxidative damage markers and promoted muscle mass and strength gains. Considering chemotherapy-induced side effects is a crucial aspect when prescribing resistance exercise during cancer, it will maximize the effectiveness of exercise in enhancing muscle mass and strength.

Advances in the roles of glycyrrhizic acid in cancer therapy.

Since the first 70years of reporting cancer chemotherapy, malignant tumors have been the second most common cause of death in children and adults. Currently, the commonly used anti-cancer methods include surgery, chemotherapy, radiotherapy, and immunotherapy. Although these treatment methods could alleviate cancer, they lead to different forms of side effects and have no particularly significant effect on prolonging the patients' life span. Glycyrrhizic acid (GL), a native Chinese herbal extract, has a wide range of pharmacological effects, such as anti-cancer, anti-inflammatory, antioxidant, and immune regulation. In this review, the anti-cancer effects and mechanisms of GL are summarized in various cancers. The inhibition of GL on chemotherapy-induced side effects, including hepatotoxicity, nephrotoxicity, genotoxicity, neurotoxicity and pulmonary toxicity, is highlighted. Therefore, GL may be a promising and ideal drug for cancer therapy.

The effect of cognitive behavioral therapy on chemotherapy-induced side effects and immune function in colorectal cancer patients undergoing chemotherapy: study protocol for a randomized controlled trial.

Colorectal cancer (CRC) was one of the most widely diagnosed cancers in the United States in 2021. CRC patients may experience significant psychological stress and are susceptible to depression and anxiety. Previous studies have shown that cognitive behavioral therapy (CBT) can reduce fatigue and improve quality of life among breast cancer patients. However, as a non-pharmaceutical treatment, it remains unclear whether CBT improves chemotherapy-induced side effects and immune function in CRC patients. In this study, we will conduct a randomized controlled trial (RCT) among CRC patients undergoing chemotherapy to determine whether CBT can reduce the side effects of chemotherapy and improve the immune function of CRC patients. The study will be a single-center RCT. CRC patients undergoing chemotherapy will receive either eight sessions of group-based CBT (every 2-3 weeks) or usual care (usual oncology care). Each participant will undergo assessments at baseline (T0), immediately post-intervention (T1), 3 months post-intervention (T2), and 6 months post-intervention (T3). The primary outcome will include chemotherapy-induced side effects in CRC patients. The secondary outcome will be immune function (measured by levels of inflammatory cytokines). Other outcomes will include the levels of tumor markers, assessments of psychological status (perception of stress, depression and anxiety, self-efficacy, sleep quality, quality of life, social support condition, and cognitive function), and necessary laboratory examinations (biochemical index and blood cell counts) among CRC patients undergoing chemotherapy. Our study will provide clinical evidence regarding whether CBT should be generalized in clinical treatment and the extent to which CBT reduces chemotherapy-induced side effects for CRC patients. ClinicalTrials.gov registration number NCT04741308.

Mannose antagonizes GSDME-mediated pyroptosis through AMPK activated by metabolite GlcNAc-6P

Pyroptosis is a type of regulated cell death executed by gasdermin family members. However, how gasdermin-mediated pyroptosis is negatively regulated remains unclear. Here, we demonstrate that mannose, a hexose, inhibits GSDME-mediated pyroptosis by activating AMP-activated protein kinase (AMPK). Mechanistically, mannose metabolism in the hexosamine biosynthetic pathway increases levels of the metabolite N-acetylglucosamine-6-phosphate (GlcNAc-6P), which binds AMPK to facilitate AMPK phosphorylation by LKB1. Activated AMPK then phosphorylates GSDME at Thr6, which leads to blockade of caspase-3-induced GSDME cleavage, thereby repressing pyroptosis. The regulatory role of AMPK-mediated GSDME phosphorylation was further confirmed in AMPK knockout and GSDMET6E or GSDMET6A knock-in mice. In mouse primary cancer models, mannose administration suppressed pyroptosis in small intestine and kidney to alleviate cisplatin- or oxaliplatin-induced tissue toxicity without impairing antitumor effects. The protective effect of mannose was also verified in a small group of patients with gastrointestinal cancer who received normal chemotherapy. Our study reveals a novel mechanism whereby mannose antagonizes GSDME-mediated pyroptosis through GlcNAc-6P-mediated activation of AMPK, and suggests the utility of mannose supplementation in alleviating chemotherapy-induced side effects in clinic applications.

Patient Perspectives and Side-Effects Experience on Chemotherapy of Non-Small Cell Lung Cancer: A Qualitative Study.

This study aimed to explore patients' experiences of palliative chemotherapy for non-small cell lung cancer (NSCLC), how patients adapt to their new and challenging life after chemotherapy, their beliefs, and their quality of life. The study used an exploratory descriptive qualitative approach that was designed to explore the experiences and side effects of NSCLC patients on chemotherapy in Pakistan. The study was designed to obtain a deeper understanding of 22 NSCLC patients' experiences, using a face-to-face approach and interviews were conducted. Patients who have completed chemotherapy agreed to participate in semi-structured interviews. The data were arranged into five themes: hospital facilities and environment, patient's beliefs in alternative treatments, presenting a positive/negative face, life is for living, and health insurance coverage. The major complaints related to bad experiences of chemotherapy-induced side effects, but these patients still managed to complete the full course of their respective chemotherapy. Additionally, the current study revealed the real experience of patients with NSCLC which had been less studied. The patient's experience was summarized into four themes and several subthemes. This study aid healthcare providers when deciding on treatment options that will improve shared decision-making between clinicians and treatment outcomes.

Therapeutic Effects of Medicinal Mushrooms on Gastric, Breast, and Colorectal Cancer: A Scoping Review.

Cancer is the leading cause of mortality globally. With anticancer medications causing severe adverse effects, understanding the role of alternative and efficacious anticancer treatments with minimal or no side effects can be beneficial. Edible mushrooms have been associated with certain health benefits and exhibit a broad range of pharmacological activities, including anti-inflammatory and immunomodulating activities. The anticancer potential of different mushrooms is now being tested. The goal of this scoping review was to discuss the most recent and available evidence on the therapeutic uses of medicinal mushrooms in cancer treatment, specifically those cancers with some of the highest mortality rates (i.e., gastric, breast, and colorectal cancer).Randomly controlled trials, clinical trials, and retrospective cohort studies (with placebo group) with human subjects published between 2012-2023 were searched using the databases Embase, Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL), and Alt HealthWatch. The initial search yielded 2,202 articles. After removing 853 duplicate citations, 1,349 articles remained and were screened for study eligibility and accessibility, leaving 26 articles. The inclusion and exclusion criteria were then used to assess the remaining 26 full-text articles and nine articles were selected for the final review. The characteristics of the nine studies reported the efficacy of medicinal mushrooms Lentinus edodes (Shiitake), Coriolus versicolor (Turkey Tail), and Agaricus Sylvaticus (Scaly Wood), in treating symptoms, medication side effects, anti-tumor effects, and survival outcomes in gastric, breast, and colorectal cancers. Findings from this review suggest that medicinal mushrooms have the potential to prevent lymph node metastasis, prolong overall survival, decrease chemotherapy-induced side effects (e.g., diarrhea, vomiting), affect the immune system, and help maintain immune function and quality of life in patients with certain cancers. More research is needed with human subjects using RCTs with larger samples to ensure accurate outcomes and ascertain the most efficacious dosages.

Abstract 4935: Cannabidiol and cannabis extract protect cells against platinum-based chemotherapy via cellular uptake

Abstract Cannabinoids including cannabidiol belong between constituents of cannabis sp. (marijuana plant). Purified or as a part of cannabis products, the compounds are frequently used by cancer patients to attenuate chemotherapy-induced side effects such as pain, nausea, and vomiting. The presence of cannabis products on the public market expands each year while the illegality status weakens in an increasing number of countries. U.S. Food and Drug Administration has approved several cannabis-based drugs for seizures induced by Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex, also for the lost appetite of AIDS patients, and chemotherapy-induced nausea and vomiting. Oncological patients are further and strongly motivated to take the drugs in combination with chemotherapy by numerous reports demonstrating the anticancer effects of cannabinoids. Nevertheless, here we present unsettling data that cannabis extract together with CBD negatively interferes with worldwide approved platinum-based drugs cisplatin, carboplatin, and oxaliplatin. The phenomenon is proven across three cellular models including primary cells. Even low concentrations of cannabidiol or cannabis extract reduced the toxicity of platinum-based drugs using long-term colony forming assay and/or short-term crystal violet assay. Increased resistance of cells was also accompanied by decreased cellular stress as evaluated by quantitative immunofluorescence microscopy and immunoblotting. Most importantly, concomitant cannabidiol and cisplatin exposure results in the decreased presence of cisplatin-modified DNA. Following the information, we determined platinum content in cells by ICP-MS. The experiment uncovered significantly decreased intracellular platinum content indicating an effect on cellular transport. Furthermore, the mechanism is translational independent as shown by the experiment with cycloheximide. This study offers crucial information that patients and physicians should take into account regarding possible interactions between platinum-based drugs and cannabis-based products. Furthermore, the study on the contradictory effects of cannabis products in cancer treatment may be motivated by this project. Citation Format: Tereza Buchtová, Lucie Beresova, Katarina Chroma, Martin Mistrik. Cannabidiol and cannabis extract protect cells against platinum-based chemotherapy via cellular uptake. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4935.

Impact of Antioxidant on Altered Quantity of Testicular Leydig Cell During Anti Cancerous Therapy an Experimental Study

Statement of Problem: Patients undergoing chemotherapy has been struggling long with side effects on tissues which were not targeted for therapy. Chemotherapeutic agents Doxorubicin (DOX) used in this study induced testicular damage, had been a major concern of oncologists for decades. Studies so far has more focus on the adverse impact of drug on germ cells and very few observed its effect on Leydig cell secreting testosterone. To date few studies are available that have used antioxidant therapy like vitamin C to assuage the oxidative damage induced by DOX on supporting cell like Leydig. Objectives: To demonstrate the altered numbers of Leydig cells produced by DOX in testes of mice and designed to study the changes in quantity of Leydig cells in DOX affected interstitial cells with co-administration of antioxidant ascorbic acid. Research Design: An experimental study to determine the effect of dox on testicular leydig cells and to assess the ameliorating effects of vitamin c on it. Duration of Study: This study was conducted from June 2022 to February 2023 Place of Study: Research was conducted at Dow university of health sciences (DUHS) Karachi at institute of basic medical sciences with collaboration of its animal house and Dow Diagnostic Research and Reference Lab DUHS. Sampling technique: The samples were chosen randomly. In this experiment drugs used include doxorubicin hydrochloride, vitamin c and normal saline on 6th, 8th and 10th day of the study. Methodology: Male mice of five weeks old were segregated into 3 groups. Group- A mice were treated with normal saline, DOX alone was given to group- B animals and DOX + Vitamin C to group- C. At the end of experimental study, testes of sacrificed animals were preserved in Bouin’s fluid and later processing, staining etc. were performed. Results and Statistical Analysis: By using SPSSS version 16, statistical analysis was done, using ANOVA test to evaluate the significance of parameter among different groups studied. Widening of interstitium with significant Leydig hyperplasia (P &lt; 0.00) as compared to controls were seen in group B However co-administration of Vitamin C with DOX significantly decrease was observed in comparison to Group A. Practical Implications: The practical implications of this study for the community are that cancer patients undergoing chemotherapy can potentially benefit from co-administration of vitamin C to reduce the adverse effects on testicular tissue, which may help preserve fertility and hormone production. Improving the quality of life for cancer patients by providing an accessible and potentially effective way to manage chemotherapy-induced side effects. Conclusion: This study suggested that the antioxidant Vitamin C has a role in ameliorating the effects produced by DOX on testis by showing change in altered quantity of leydig cell. Keywords: Doxorubicin, Vitamin C, Mice, Antioxidant, Leydig cells

Barriers and Facilitators to Adherence to a Mediterranean Diet Intervention during Chemotherapy Treatment: A Qualitative Analysis

Patients undergoing chemotherapy are at risk for malnutrition and a high symptom burden, and nutritional interventions can address clinical and supportive care outcomes. Herein, we identified barriers and facilitators to adhering to a Mediterranean Diet (MedDiet) intervention during chemotherapy. Patients with cancer (any type) who were undergoing chemotherapy were enrolled into a clinical trial testing the effects of an 8-week MedDiet intervention on cancer-related fatigue. Participants were randomized 2:1, MedDiet:control. The intervention entailed food provision, education, a cookbook, a session with a nutritionist, and weekly check-ins. Post-intervention, all participants completed semi-structured exit interviews. The interviews were transcribed and open coding was conducted to describe the facilitators and barriers to MedDiet adherence. Participants (n = 29, n = 21 in the intervention group) were 51.0 ± 15.1 years old and 93.1% had breast cancer. Educational materials and convenient food delivery were the highest reported facilitators. Many patients offered that changing their diet gave a sense of control and empowerment. Barriers to adherence were that the frozen food was unappetizing, participants’ (or their spouse/children’s) food preferences did not align with the MedDiet, and chemotherapy-induced side effects that prevented food consumption (eg, mouth sores, lack of appetite). This project helps understand the patient experience within nutritional interventions to optimize dietary programs during chemotherapy treatment.