Levels In Cancer Patients Research Articles

Caspase-9 and p53 Protein Levels in Cancer Patients after Different Anesthesia Techniques

Caspase-9 and p53 Protein Levels in Cancer Patients after Different Anesthesia Techniques

Effect of Music on Anxiety and Fatigue in Cancer Patients Undergoing Chemotherapy: A Randomized Controlled Trial.

Anxiety and fatigue are symptoms typically experienced by cancer patients undergoing chemotherapy. In dealing with these symptoms, listening to music may help patients. The randomized controlled study was conducted between May 1, 2022 and November 10, 2022 with 60 patients treated in the outpatient chemotherapy unit. The data were gathered using a patient information form, Brief Fatigue Inventory, and the State Trait Anxiety Inventory. In addition to standard treatment and care, 30-minute music was played with a passive listening method in a total of three cycles of chemotherapy in the intervention group patients who completed the first cycle and visited for the second cycle of chemotherapy. According to the analysis of covariance (ANCOVA) findings, the group variable significantly affected the post-test state anxiety scores when an adjustment was made for pre-test state anxiety scores (F=240.398, P<0.001, η²=0.808). In addition, pre-test state anxiety scores affected post-test results (F=7.925, P=0.007, η²=0.122). According to the ANCOVA findings, the group variable significantly affected the post-test trait anxiety scores (F=235.243, P<0.001, η²=0.805). In addition, pre-test trait anxiety scores affected post-test results (F=34.977, P<0.001, η²=0.380). According to ANCOVA results, the group variable significantly affected post-test fatigue scores (F=79.201, P<0.001, η²=0.582). In addition, pre-test scores affected post-test scores (F=11.082, P=0.002, η²=0.163). We observed that music had positive effects on fatigue and anxiety levels in cancer patients undergoing chemotherapy. It may be recommended to include music intervention in nursing practices for cancer patients during chemotherapy. The study results demonstrated that music intervention can be used in nursing practices for cancer patients during chemotherapy. Its low-cost and non-invasive nature also provide ease of application. Therefore, we can recommend the application of music intervention in outpatient chemotherapy units.

Analysis of metalothionein in patients with malignant liver tumors.

Malignant liver tumors are highly aggressive with a poor prognosis. Metalothionein (MT) is a low-molecular intracellular protein, whose primary function is to regulate the homeostasis of heavy metals in many organisms. There are only few studies focusing on the molecular mechanisms of MT expression. Recent studies show its significant relations to carcinogenesis, spontaneous mutagenesis and efficiency of antitumor medicine. In previous studies, the increase of MT levels in cancer patients was proven. The aim of this work is to study MT as well as to increase the efficiency of malignant liver tumor diagnosis. In our pilot study (2022-2023) we observed a group of 15 patients with hepatocellular carcinoma (diagnosis C220) and a group of 15 patients with hepatoblastoma (diagnosis C222). The control group included 20 healthy probands. We developed our own modified method for the analysis. Blood serum samples of the probands were denaturated (99 ˚C, 20 min). MT was determined by an electrochemical method. Obtained data were stored and processed in the laboratory information system QINSLAB. In denaturated blood serum samples, we obtained voltametric curves of MT. We determined concentrations of MT by evaluating the area under the curve (AUC). To differentiate normal and abnormal concentrations of MT, blood samples of healthy probands were used (N = 20), with the average MT levels of 2.0 ± 1.3 µg/L and median 1.9 µg/L. In patients diagnosed with HCC, the average MT levels were 9.1 ± 6.5 µg/L and median 9.0 µg/L. The receiver operating characteristic (ROC) analysis showed AUC 0.864 (95% CI 0.736-0.992), sensitivity 0.74 and specificity 0.75. In patients diagnosed with hepatoblastoma, the average MT concentrations measured were 11.5 ± 7.5 µg/L and the median was 10.9 µg/L. The ROC analysis displayed AUC 0.868 (95% CI 0.751-0.993), sensitivity 0.84 and specificity 0.86. The correlation analysis showed correlation between MT and carcinoembryonic antigen (CEA) (r = 0.99), uric acid (r = -0.86) and potassium ions (r = -0.94). In this pilot study, we observed the association of MT levels in healthy probands and malignant liver tumor patients. Many previous studies show that MT concentrations are increasing as the illness progresses. We assume that this increase is connected to the high metabolic activity of cancer cells. This study will continue with collecting a larger number of samples.

A whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer.

Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. Here, we investigated the impact of a whole food, plant-based diet on lowering the serum levels of amino acids in patients with cancer. Patients with metastatic breast cancer (n=18) were enrolled in clinical trial NCT03045289 . An ad libitum whole food, plant-based diet was implemented for 8 weeks without calorie or portion restriction. We found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF-1 were reduced in participants. The diet contained lower levels of essential and non-essential amino acids. Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids). These findings provide a tractable approach to limiting amino acid levels in cancer patients. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities.

Comparison of essential amino acid levels in cancer patients: plant versus animal-derived oral nutritional supplements

Comparison of essential amino acid levels in cancer patients: plant versus animal-derived oral nutritional supplements

BAFF as a Potential Marker for Toxoplasma Gondii Seroprevalence Among Cancer Patients on Chemotherapy

Background: Toxoplasmosis is a global zoonotic disease, that is mainly asymptomatic in healthy persons, but critical and life-threatening in immunocompromised patients. The infection is caused by an opportunistic obligate intracellular parasite protozoon “Toxoplasma gondii” (T. gondii) that can cause fatal complications in immunosuppressed patients. Cancer patients are being immunocompromised from the cancer itself and on the other hand cancer therapy they receive may reactive a latent T. gondii infection that leaves them at high risk. The B-cell activating Factor (BAFF) is a cytokine that plays an essential role in the activation, maturation, and survival of B cells. It is vital for the appropriate functioning of the immune system. Monitoring BAFF levels in cancer patients undergoing chemotherapy could be important for preventing or controlling infections in these vulnerable patients. Objectives: This study aimed to detect seroprevalence of T. gondii in cancer patients receiving chemotherapy and assess the levels of BAFF in those patients. Materials and Methods: 150 serum samples were collected from oncology patients having different types of cancer and receiving chemotherapy, from different ages. And 30 samples from healthy people for control. In this cross-sectional study, samples were collected from the 1st of October 2023 to the 1st of March 2024, at Kirkuk Oncology and Hematology center. The method used was the Sandwich Enzyme-Linked Immunosorbent Assay (Sandwich-ELISA) technique. Results: the overall anti-T. gondii IgG and IgM seropositive samples were found to be 67 (37.2%) in the total study population and 67(44.7%) in cancer patients. BAFF levels were elevated in cancer patients infected with T. gondii compared with the cancer patients with no infection and the healthy control group. A significant difference was indicated with (p-value 0.0004). Conclusions: A high rate of T. gondii seroprevalence was revealed among oncology patients receiving chemotherapy with elevated levels of BAFF associated with T. gondii infection in those patients.

Hypothesis paper: GDF15 demonstrated promising potential in Cancer diagnosis and correlated with cardiac biomarkers

BackgroundCardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction).MethodsAnalysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG).ResultsGDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort.ConclusionGDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.

Relationship between the white blood cell count and some lipid profile parameters in cancer patients with myocardial infarction

Hokkaido University (Tsumita T, 2022) researchers found that endothelial cells accumulate low-density lipoproteins (LDL) in tumor blood vessels. At the same time, the endothelium carries out neutrophil chemotaxis, which perform an immunosuppressive function contributing to cancer progression.Aim. To search for the relationship between the white blood cell (WBC) count and some lipid profile parameters in cancer patients with myocardial infarction (MI).Material and methods. We examined 319 patients who were treated at Dzhanelidze Research Institute of Emergency Medicine in 2018-2023, which were divided into three groups: MI in combination with an active cancer — 132 patients (Group I), MI+cancer in history — 58 patients (Group II), MI without cancer — 129 patients (Group III). Following laboratory data used in routine practice were assessed: WBC count, relative neutrophil count, total cholesterol, low-density lipoproteins.Results. Cancer patients with MI are characterized by higher WBC and neutrophil count than in other samples However, the total cholesterol level was significantly lower in this sample, and the LDL level was not significantly different. Patients with MI and previous cancer occupied an intermediate position between groups I and III in terms of studied parameters.Conclusion. In general, data on the role of cholesterol levels in cancer patients are contradictory. In particular, some studies have shown that elevated cholesterol levels are a potential risk factor for cancer. In our study, as in a number of others, no significant associations were identified between elevated cholesterol levels and the presence of cancer. Our study is a step towards understanding the connection between the cholesterol concentration and the immune response in cancer patients with MI.

Exploring the effects of post operative hyperoxic intermittent stimuli on reticulocyte levels in cancer patients: a randomized controlled study

BackgroundAnemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries.MethodsThis is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression.ResultsThe final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values.ConclusionsThis study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings.Trial registrationThe study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

The utility of procalcitonin in febrile neutropenia.

12040 Background: The utility of procalcitonin (PCT) in febrile neutropenia (FN) in oncology patients on active therapy has not been well validated. FN constitutes a critical oncologic emergency, often characterized by subtle manifestations of infection, and timely diagnosis and treatment is vital. Although a potential harbinger of dangerous infection, FN can also occur without an identifiable infection, in which case hospitalization and antibiotics may be unnecessary. PCT, an amino acid, is elevated specifically during bacterial infections in the non-cancer population and correlates with infection severity. Clinicians employ PCT levels as a diagnostic adjunct, discerning bacterial from viral infections and analyzing PCT changes to guide treatment decisions. We examined oncology patients presenting with FN to correlate PCT levels and trends with confirmed infections. Methods: We identified patients with neutropenic fever, cancer, and a PCT result seen at our institution from 12/1/2017-12/1/2022. Patients were determined to have a confirmed infection if they had a positive bacterial blood culture. Demographics and clinical characteristics were compared between infection status and induction chemotherapy or transplant status using a Wilcoxon Rank Sum test for continuous variables and a Chi-Square or Fisher’s Exact test for categorical variables. Baseline (at time of initial FN) and highest PCT levels were compared by patient and disease characteristics and proven infection using Wilcoxon Rank Sum test. Logistic regression was used to determine the association of log-transformed PCT (baseline and highest) with proven infection (yes/no) while adjusting for covariates. All tests were two-tailed with p&lt; 0.05 considered statistically significant. Results: Of 365 patients, 61 (16.7%) had an identified infection. Median baseline and peak PCT of 1.26 and 1.51 ng/mL, respectively, were significantly greater for these patients as compared to those with negative cultures at 0.54 and 0.65 ng/mL, respectively (P= 0.01 and &lt;0.01). For every unit increase in the log transformed baseline PCT, the odds of having a proven infection increased by 23%. There were no significant differences in patient or clinical characteristics between those with and without infection. Of those admitted for induction chemotherapy and transplant who developed FN, PCT at time of initial fever was higher at 0.97 vs 0.56 ng/mL (p=0.02). Interestingly, median baseline and median peak PCT differed between gender with females 0.51 and males 0.72 ng/mL (p=0.02) at baseline, and 0.63 vs 0.83 ng/mL (p=0.04), respectively, at peak. Conclusions: PCT levels in cancer patients with FN are significantly associated with culture positive infection. This data can help guide treatment and de-escalation of antibiotics in cancer patients admitted with FN. Further evaluation should be taken to determine how to best use PCT to determine the need for admission and antibiotic prescription.

Development and Validation of a Simple and Reliable HPLC-UV Method for Determining Gemcitabine Levels: Application in Pharmacokinetic Analysis.

Background and Objectives: Gemcitabine has been used to treat various solid cancers, including, since 1997, metastatic pancreatic cancer. Here, we developed an HPLC-UV method to determine serum gemcitabine levels and use it in pharmacokinetic studies. Materials and Methods: The analysis was performed after a single protein precipitation step on a reversed-phase column, isocratically eluted with sodium phosphate buffer and methanol. For the pharmacokinetic study, NOD/SCID mice received a single dose of gemcitabine at 100 mg/kg by either subcutaneous (SC) or intraperitoneal (IP) administration. Blood samples were collected at 5, 15, and 30 min and 1, 2, 4, and 6 h after the administration of gemcitabine for further analysis. Results: The duration of the analysis was ~12.5 min. The calibration curve was linear (r2 = 0.999) over the range of 1-400 μM. The mean recovery of GEM was 96.53% and the limit of detection was 0.166 μΜ. T1/2, Tmax, Cmax, AUC0-t, and clearance were 64.49 min, 5.00 min, 264.88 μmol/L, 9351.95 μmol/L*min, and 0.0103(mg)/(μmol/L)/min, respectively, for the SC administration. The corresponding values for the IP administration were 59.34 min, 5.00 min, 300.73 μmol/L, 8981.35 μmol/L*min and 0.0108(mg)/(μmol/L)/min (not statistically different from the SC administration). Conclusions: A simple, valid, sensitive, and inexpensive method for the measurement of gemcitabine in serum has been developed. This method may be useful for monitoring gemcitabine levels in cancer patients as part of therapeutic drug monitoring.

Use of a wearable device to compare subjective and objective fatigue in lung cancer patients and cancer-free controls

PurposeThe study evaluates the use of heart rate variability (HRV), a measure of autonomic nervous system (ANS) modulation via wearable smart bands, to objectively assess cancer-related fatigue (CRF) levels. It aims to enhance understanding of fatigue by distinguishing between LF/HF ratios and LF/HF disorder ratios through HRV and photoplethysmography (PPG), identifying them as potential biomarkers. MethodsSeventy-one lung cancer patients and 75 non-cancer controls wore smart bands for one week. Fatigue was assessed using Brief Fatigue Inventory, alongside sleep quality and daily interference. HRV parameters were analyzed to compare groups. ResultsCancer patients showed higher fatigue and interference levels than controls (64.8% vs. 54.7%). Those with mild fatigue had elevated LF/HF disorder ratios during sleep (40% vs. 20%, P = 0.01), similar to those with moderate to severe fatigue (50% vs. 20%, P = 0.01), indicating more significant autonomic dysregulation. Notably, mild fatigue patients had higher mean LF/HF ratios than controls (1.9 ± 1.34 vs. 1.2 ± 0.6, P = 0.01), underscoring the potential of disorder ratios in signaling fatigue severity. ConclusionsUtilizing wearable smart bands for HRV-based analysis is feasible for objectively assess CRF levels in cancer patients, especially during sleep. By distinguishing between LF/HF ratios and LF/HF disorder ratios, our findings suggest that wearable technology and detailed HRV analysis offer promising avenues for real-time fatigue monitoring. This approach has the potential to significantly improve cancer care by providing new methods for managing and intervening in CRF, particularly with a focus on autonomic dysregulation as a crucial factor.

A cross-cultural analysis of the relationship between the level of depression and attitudes toward death in cancer patients

Introduction♦Over the last 10 years, the number of cancer patients in the world has increased by almost 23%, and the number of cancer deaths has also increased by about 10%. Malignant neoplasms still remain as one of the main causes of mortality in the population. Patients with oncopathology are characterized by a high level of depression which leads to inadequate attitudes towards the disease and its treatment, and this may further act as a risk factor for disease susceptibility and aggravate its course (Schulz-Kindermann, 2021). It is relevant to search for variables that act as a personal resource in coping with cancer. It is hypothesized that one such personal resource is the specificity of attitudes towards death.ObjectivesTo conduct a comparative analysis of the relationship between the level of depression and the peculiarities of the attitude to death in cancer patients in Russia and Germany.Methods▪Beck Depression Inventory to determine the level of depression severity.▪Death Attitude Profile-Revised to determine the type of attitude to death.For statistical processing of data, the SPSS 23.0 statistical package was used with a preliminary check for normality of distribution using the Kolmogorov-Smirnov statistical criterion.SELECTIONThe sample consisted of a total number of 50 cancer patients with 25 each undergoing treatment in Russia (Moscow) and in Germany (Munich). The study was based on the sample obtained from the P. A. Herzen Moscow Research Oncological Institute and the Helios Munich-West Clinic. Overall, the sample was relatively gender-balanced.ResultsThe following results were obtained from the study: 1.The mean value of depression level in cancer patients is higher in Russia than in Germany.2.The level of depression in cancer patients in both the countries is correlated with:▪marital status (p=0.36)▪stage of disease (p=0.001)▪type of treatment (p=0.001)▪belief in God (p=0.024)▪adherence to a particular religious denomination (p=0.008)3.The level of depression was correlated with a certain type of attitude towards death: a higher level of depression was associated with scores on the “fear of death” scale (p=0.000), and a lower level (or lack of ) with the “neutral acceptance of death” scale (p=0.000)4.The fear of death is seen to be most common in the sample of patients from Russia, while the neutral acceptance of death is more prevalent in the sample from Germany.ConclusionsThe results suggest that a positive attitude to death (neutral as one of these types) is correlated, along with other factors, with lower levels of depression, which may be a personal resource in coping with the disease.This allows us to make the assumption that when providing psychological support to cancer patients, it is necessary to pay attention not only to the attitude to life and illness, but also to the attitude to death.Disclosure of InterestNone Declared

Abstract 1026: Post-surgery sequelae unrelated to disease progression and chemotherapy revealed in follow-up of stage III colon cancer patients

Abstract A gap currently exists in our understanding of causes of elevated total circulating DNA (cirDNA) levels in cancer patients following tumor resection, and the influence of anesthesia or surgery on cirDNA release. Indeed, the post-surgery dynamics of cirDNA have been largely overlooked to date, despite their importance in determining the optimal timing for assessment of minimal residual disease (MRD). Since cirDNA levels were recently found to be associated with neutrophil extracellular traps (NETs) formation in various cancers, we investigated NETs and cirDNA post-surgery.We conducted two clinical studies to explore the dynamics of cirDNA quantity and of neutrophil extracellular traps (NETs) markers: (1) a peri-surgery study over a duration of up to 72 hours, which involved stage I-III colon (n=10), prostate (n=10), and breast (n=9) cancer patients; and (2) a post-surgery study that extended up to two years post-surgery, and which involved 74 stage III colon cancer patients. We assessed plasma levels of cirDNA using qPCR, and assessed two protein markers of NETs using ELISA, in both cancer patients and control group of healthy individuals (HI) (N=114). This second study is the first prospective, multicenter, blinded study of the dynamics of the total cirDNA post-surgery, for a period of up to two years.We observed that (i), NETs formation contributes to post-surgery conditions; (ii), peri- and post-surgery cirDNA levels were highly associated with NETs formation in colon cancer; (iii), each tumor type showed a specific pattern of the peri-surgery dynamics of cirDNA and NETs markers; peri-operative levels of these markers are significantly lower in breast cancer patients as compared to prostate and colorectal cancer patients; (iv), a significant proportion of patients showed pre- (58.1%) and post-surgery (80.4%) median marker values higher than in HI, even after 2 years following tumor resection, (v) these markers were either equal to or greater (23.2%) than their pre-surgery counterparts; and (vi), elevated values of these markers did not derive from chemotherapy toxicity.We provide evidence that, for cancer patients in the post-surgery period, cirDNA originates mainly from NETs. This finding calls into question the current method of assessing MRD according to the fraction of mutant cirDNA, given that the level of NETs formation appears to be patient dependant. The peri-surgery dynamics of NETs formation and cirDNA release vary according to the surgical procedure and cancer type. In a significant part of patients with colon cancer, NETs continue to persist for more than a year after surgery, irrespective of disease progression or chemotherapy use. Nevertheless, cirDNA and NETs marker levels vary in cases with post-surgery inflammatory/thrombotic adverse events. Our work highlights the existence of long-lasting “sequelae” effects of cancer, previously unreported. Citation Format: Andrei Kudriavtsev, Alexia Mirandola, Catalina I. Cofre Muñoz, Raquel Comas Navarro, Marco Macagno, Brice Pastor, Ekaterina Pisareva, Mireia Sanchis Marin, Javier Gonzalo Ruiz, Anna Sapino, Alice Bartolini, Massimo Di Maio, Cynthia Sanchez, Yann Gricourt, Xavier Capdevila, Gerald Lossaint, Evelyne Crapez, Marc Ychou, Ramon Salazar Soler, Elisabetta Fenocchio, Paula X. Fernandez Calotti, Philippe Cuvillon, Thibault Mazard, Cristina Santos Vivas, Elez M. Elez, Federica Di Nicolantonio, Alain R. Thierry. Post-surgery sequelae unrelated to disease progression and chemotherapy revealed in follow-up of stage III colon cancer patients [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 1026.

Can we improve therapeutic compliance in cancer patients? Report of a cross-sectional case series study in Morocco.

Therapeutic compliance (TC) refers to the patient's compliance with the prescriptions and recommendations of a doctor. Patients with cancer often exhibit unsatisfactory TC. The objective of our study was to assess TC levels in cancer patients and identify predictors of poor compliance. The authors conducted a cross-sectional study in March 2023 at the oncology centre, where the vast majority of medical activity is performed in the day hospital. TC was measured using a questionnaire or survey. Various parameters were analyzed to identify predictive factors of poor therapeutic compliance. The authors' study included 175 cancer patients with a mean age of 55 years. The study revealed that 85% exhibited good compliance (GC) as indicated by the CI [8.500 ± 0.075], signifying patients who consistently adhered to their medication schedule. Conversely, 15% demonstrated poor compliance (PC), as indicated by the confidence interval [0.825 ± 0.750]. Compliance status was assessed by considering patients who adhered to the prescribed medication timing as good compliance (GC) and those who did not adhere as poor compliance (PC). The analysis of our study results indicated that poor therapeutic compliance was associated with low socio-economic and educational levels. Therefore, it is important to utilize all available resources to improve therapeutic compliance. The majority of factors contributing to poor compliance can be mitigated through effective coordination between the patient and their support network.

The occurrence of immune-related adverse events is an independent risk factor both for serum HBsAg increase and HBV reactivation in HBsAg-positive cancer patients receiving PD-1 inhibitor combinational therapy.

Previous studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy. To explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr. A retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr. With the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr. PD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy.

Targeted Sequencing of Human Satellite 2 Repeat Sequences in Plasma cfDNA Reveals Potential Breast Cancer Biomarkers.

Liquid biopsies are revolutionizing the detection and management of malignant diseases. While repetitive DNA sequences, such as LINE-1 and ALU are established in cell-free DNA (cfDNA) research, their clinical applications remain limited. In this study, we explore human satellite 2 (HSATII), a prevalent repeat DNA sequence in plasma that exhibits increased levels in cancer patients, thereby positioning it as a potential pan-cancer biomarker. We employed targeted sequencing and copy number variation (CNV) analysis using two primer pairs to assess the differential abundance of HSATII sequences in the plasma of breast cancer patients compared to healthy individuals. PCR amplicons of HSATII from 10 patients and 10 control subjects were sequenced, generating 151 bp paired-end reads. By constructing a pooled reference dataset, HSATII copy ratios were estimated in the patients. Our analysis revealed several significant CNVs in HSATII, with certain sequences displaying notable gains and losses across all breast cancer patients, suggesting their potential as biomarkers. However, we observed pronounced fragmentation of cfDNA in cancer, leading to the loss of longer PCR amplicons (>180 bp). While not all observed losses can be attributed to fragmentation artifacts, this phenomenon does introduce complexity in interpreting CNV data. Notably, this research marks the first instance of targeted HSATII sequencing in a liquid biopsy context. Our findings lay the groundwork for developing sequencing-based assays to detect differentially represented HSATII sequences, potentially advancing the field of minimally-invasive cancer screening.

Elemental Profiling of different Cancer Patients by ICP-MS from River Indus Region Sindh, Pakistan

Background: The relationship between exposure to heavy metals and the development of cancer has been a subject of extensive research. Trace elements, both essential and non-essential, play significant roles in various biological processes, with imbalances potentially contributing to carcinogenesis. This study aims to investigate serum concentrations of selected metals in cancer patients and compare these levels with those of a healthy control group, highlighting the potential link between metal exposure and cancer risk. Objective: To quantify and compare the serum concentrations of sodium (Na), calcium (Ca), iron (Fe), cadmium (Cd), and arsenic (As) in cancer patients and a control group, thereby assessing the potential association between elevated levels of specific metals and cancer incidence. Methods: This cross-sectional study analyzed blood samples from cancer patients (n=30) and a matched control group (n=30) from the Jamshoro and Hyderabad areas. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was utilized to measure serum concentrations of Na, Ca, Fe, Cd, and As. Participants' demographic data, including age, gender, place of residence, degree of education, cancer type, and water sources, were collected through questionnaires. Statistical analyses were conducted to compare metal concentrations between groups, with P-values &lt;0.05 considered significant. Results: The average ages of cancer patients and controls were 55.3 ± 15.7 and 52.13 ± 23.7 years, respectively. Significantly higher serum Na levels were observed in cancer patients compared to controls (P &gt; 0.05), with an average concentration exceeding 32.04 µg/L. Cd levels were also higher in the cancer group (0.0046 ppm) compared to controls (0.0000 ppm), contrary to expectations. Conversely, no significant difference was found in As levels between groups. Serum Fe concentrations were substantially higher in cancer patients (P &gt; 0.4949), with Ca levels in cancer patients also elevated (3.302 ppm). Conclusion: The study found significant discrepancies in serum metal concentrations between cancer patients and healthy controls, suggesting an association between elevated levels of certain metals and increased cancer risk. These findings emphasize the need for further investigation into the role of metal exposure in carcinogenesis and the potential for incorporating metal concentration assessments into cancer risk evaluation protocols.

Serum Trace Element Levels in Cancer Patients Undergoing Chemotherapy: a Before-After Analysis.

Trace elements (TEs) play a crucial role in metabolism through their biochemical and catalytic effects, and alterations in their levels have been observed in various malignancies. Given that chemotherapy is a common treatment for cancer, it is important to understand how it may affect the levels of TEs in the body. By investigating changes in TEs levels before and after chemotherapy, this study aims to provide insights into the potential impact of chemotherapy on TEs levels in cancer patients. In the present study, analyses were performed on the serum level of some elements including Zn, Cu, Cd, and Se in 69 patients with leukemia, lymphoma, prostate and breast cancers before and after three courses of chemotherapy. The serum TEs were measured by atomic absorption spectroscopy. The serum Zn levels in patients with leukemia, lymphoma, and breast cancer significantly decreased after chemotherapy (P < 0.05). Significant reductions were also observed in the post-chemotherapy serum level of Cd in patients with prostate (P = 0.020) and breast cancer (P = 0.013). Moreover, the Se serum level significantly decreased after chemotherapy compared to before it in the breast cancer patients (P < 0.001). In contrast, the serum level of Cu was higher before than after chemotherapyin all the patients, but no significant difference was found (P > 0.05). The results show that chemotherapy can alter the level of TEs. The assessment of TEs in cancer patients may provide information about the side effects of chemotherapy as well as the use of appropriate strategies to better manage the clinical conditions of patients.

Wilms' Tumor 1 Functions As a Tumor Suppressor to Suppress FLT3-STAT Signaling and Epigenetic Remodeling in Acute Myeloid Leukemia (CALGB 8461, 9665 and 20202; Alliance)

The Wilms' Tumor 1 ( WT1) gene is a transcription factor that is recurrently mutated or commonly overexpressed in several cancer types. In acute myeloid leukemia (AML), frequent overexpression of WT1 and poor patient outcomes associated with WT1 mutations highlight its importance in the disease; however, there are no tailored treatments for these patients. Furthermore, WT1's fundamental role as either an oncogene or tumor-suppressor remains unresolved. Here we examine the roles of both wild-type and mutant WT1 in AML through epigenetic and mechanistic studies. Using our findings we propose a personalized treatment strategy. WT1 mutations are enriched in the NPM1 mut subset of AML; thus we first focused our study on a cohort of 581 patients with de novo AML and NPM1 mutations enrolled on Alliance for Clinical Trials in Oncology studies. Transcriptomic analyses revealed that WT1 mut patientsphenocopied a distinct, aberrant gene expression signature associated with FLT3 internal tandem duplications (ITD), a mutation known to activate STAT signaling and associated with poor outcome in AML. We observed that WT1 expression levels were remarkably elevated in FLT3-ITD patients and were driven by STAT5A binding to the WT1 promoter. STAT5A binding and subsequent WT1 upregulation were blocked by small molecule FLT3 inhibitors. These findings linking FLT3 activity with WT1 expression raise two possibilities: either WT1 is an oncogene cooperating with the FLT3-STAT pathway, or WT1 naturally functions to suppress FLT3 signaling in a negative feedback loop subverted by WT1 mutations. As WT1 interacts with TET2 to facilitate epigenetic remodeling and DNA binding, we performed genome-wide DNA methylation analysis on WT1 mut AML patients and observed selective hypermethylation of WT1 binding motifs consistent with loss of function. We confirmed that WT1 mutations in AML commonly cause truncation of the C-terminal DNA binding domain in our patient cohort. Using co-immunoprecipitation, ChIP-sequencing and luciferase reporter assays, we found that mutant WT1 functions as a dominant-negative, inhibiting WT1 derived from the wild-type allele. Investigation of WT1 target genes by intersecting transcriptomic and DNA methylation profiles identified hypermethylation and downregulation of miR-193a, leading to a significant downregulation of miR-193a-3p in WT1 mut AML patients. Overexpression of wild-type, but not mutated, WT1 rescued miR-193a expression in AML cell lines. Enforced expression of miR-193a significantly delayed AML onset in vivo. In addition, overexpression of miR-193a in multiple human AML cell lines and primary patient samples impaired AML cell growth and colony-forming capacity while promoting monocytic differentiation, underscoring its role as potent tumor suppressor. Therapeutic modulation of miRNA levels in cancer patients has been limited by inefficient delivery and tissue enrichment. To overcome this, we tested a novel lipid-nanoparticle (LNP) formulation of miR-193a-3p (INT-1B3), currently being investigated in a phase I clinical trial (NCT04675996). Biweekly i.v. treatments of INT-1B3 in the immunocompetent Hoxa9/Meis1 (H9M)-transduced model system prevented AML formation, highlighting the potent anti-leukemic activity of this miRNA based therapeutic. Overexpression of miR-193a-loaded LNPs downregulated FLT3 expression and suppressed STAT signaling in primary AML samples. Finally, treatment of primary AML cells with FLT3 inhibitors revealed enhanced sensitivity of WT1 mut cells in the absence of FLT3-ITD, highlighting the role of wild-type FLT3 in WT1 mut cells. In summary, we uncovered a critical negative-feedback loop maintained by WT1 to suppress FLT3 activity. Loss-of-function WT1 mutations subvert the tumor suppressor function of WT1 via failure to maintain miR-193a expression, leading to increased FLT3 expression and STAT5 signaling, subsequently impairing differentiation, increasing proliferation and disease aggressiveness in AML (Figure 1). Our findings advocate for use of FLT3 inhibition and miR-193a supplementation for treatment of WT1 mut patients, a subgroup with poor outcomes and no targeted treatment options.