Wnt3a/GSK3ß/ß-catenin Signalling Modulates Doxorubicin-associated Memory Deficits in Breast Cancer.

BACKGROUND: Chemobrain is widespread in breast cancer patients receiving chemotherapy. However, the exact mechanism, especially the associated signalling pathway, is not currently clear. This study was to evaluate the behavioural changes in breast cancer mice after chemotherapy and to further explore the role of Wnt3a/glycogen synthase kinase (GSK3ß)/ß-catenin signalling in chemobrain. METHODS: MMTV-PyMT(+) breast cancer mice were injected intraperitoneally with doxorubicin (4 mg/kg) once a week for three weeks to establish a chemobrain model. The Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and memory ability. Electron microscopy was used to observe the structural changes in the hippocampal CA1 region. The brain tissue of breast cancer mice after chemotherapy was taken out for mRNA-seq detection. Then, the expression levels and phosphorylation of key proteins in the Wnt3a/GSK3 ß/ß-catenin signalling pathway were evaluated through Western blotting (WB) and immunofluorescence. RESULTS: Doxorubicin-induced spatial and short-term memory impairment was observed in breast cancer mice, and obvious neuronal damage could be seen in the hippocampal CA1 region. Immunofluorescence staining for GSK3ß was increased. Wnt signalling pathway is highly enriched from mRNA-seq analysis, with GSK3ß genes at important nodes. The relative protein levels of p-PI3K, p-AKT, p-GSK3 ß, Wnt3a and TCF-1 were decreased significantly, while the p-ß-catenin level was increased. After injection of the GSK3ß inhibitor sb216763 (1 ng/0.5 µl/side), hippocampal neuronal injury was alleviated to some extent, and the changes in the expression of proteins upstream and downstream of this signalling pathway were reversed. CONCLUSION: Wnt3a/GSK3 ß/ß-catenin signalling is likely involved in doxorubicin-induced memory impairment. This result provides basic evidence for the further study of chemobrain in breast cancer.

GSK3ß rs3107669 polymorphism implicates chemotherapy-associated retrospective memory deficits in breast cancer survivors.

Glycogen synthase kinase-3ß (GSK-3ß) plays an important role in the development of neurodegenerative diseases. However, the underlying effect of GSK-3ß polymorphism on chemobrain in cancer survivors is unclear. This study aimed to evaluate the correlation between GSK-3ß polymorphism and chemotherapy-associated retrospective memory deficits in breast cancer survivors. The difference in GSK-3ß gene expression between breast cancer patients and healthy controls was confirmed using bioinformatics technology. All participants (197 with breast cancer and 40 healthy controls) underwent prospective and retrospective memory tests, and five single-nucleotide polymorphism loci of GSK-3ß (rs3107669, rs1154597, rs334543, rs334558 and rs3755557) were genotyped from peripheral blood. Breast cancer survivors had memory impairment after chemotherapy (P<0.0001). The expression difference of the GSK-3ß gene was determined through bioinformation analysis, and a genotype frequency difference of GSK-3ß rs3107669 was found between the breast cancer and healthy control groups. GSK-3ß rs3107669 was a genetic risk in comparison to the healthy controls (OR=0.382; 95% CI=0.186-0.786; P=0.009). Breast cancer with the GSK-3ß rs3107669 (C/A+A/A) genotype was a protective factor for chemobrain (Beta=-0.306; 95% CI=-5.556~-2.145; P<0.0001) from multiple linear regression. The C/A+A/A genotype carrier performed better on the retrospective memory test than the C/C genotype (z=-4.302, P<0.0001). Breast cancer patients with chemotherapy who also carried the GSK-3ß rs3107669 (C/C) genotype more easily presented cognitive deficits. The GSK-3ß rs3107669 polymorphism was a feasible genetic risk factor for chemotherapy-associated retrospective memory impairments in breast cancer survivors.

Effects of the CALM intervention on resilience in Chinese patients with early breast cancer: a randomized trial.

OBJECTIVE: Resilience is an important regulating factor for anxiety and depression in breast cancer. The Managing Cancer and Living Meaningfully (CALM) intervention has been confirmed to improve anxiety and depression in patients, but the role of resilience is still unclear. This study explores this issue. METHODS: In this study, a cohort of 124 patients diagnosed with breast cancer was recruited and randomly assigned to either the intervention group (IG) or the control group (CG). In addition, we enrolled a group of cancer-free women (regular control group) and assessed their resilience. All patients were evaluated using the Connor-Davidson Resilience Scale (CD-RISC), Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy (FACT-B) and Perceived Stress Scale (PSS) at different time points. The primary outcomes were resilience, quality of life, anxiety, depression, and perceived stress. A repeated measures ANOVA was used to compare the scores of the IG and CG groups. The relationship between resilience and quality of life was analyzed using Pearson's correlation test. The paired-sample t-test was used to compare the changes in each score at different time points. RESULTS: The intervention group showed significant differences in resilience, adamancy, optimism, tenacity, anxiety, depression, perceived stress and QOL scores before and after 6, 12, and 24 weeks (F = 17.411, F = 226.55, F = 29.096, F = 50.67, F = 82.662, F = 105.39, F = 62.66, F = 72.43, F = 34.561, respectively; P < 0.001). Compared to the control group, the intervention group demonstrated significant improvement in resilience and quality of life (t = -11.517, p < 0.001; t = - 4.929, p < 0.001), as well as a significant reduction in anxiety, depression, and perceived stress scores (t = 5.891, p < 0.001; t = 2.654, p < 0.001; t = 4.932, p < 0.001). In the intervention group, a significant positive correlation was observed between resilience in breast cancer survivors and quality of life (QOL) scores. (before CALM treatment: r = 0.3204, P = 0.0111; after 6 weeks: r = 0.3619, P = 0.0038; after 12 weeks: r = 0.3355, P = 0.0077; after 24 weeks: r = 0.2801, P = 0.0274). CONCLUSIONS: A positive impact of the CALM intervention can be seen in improved resilience and reduced anxiety and depression, supporting its use as an effective psychological management tool and intervention strategy in the early stages of long-term breast cancer recovery.

The role of the oxytocin system in the resilience of patients with breast cancer.

Breast cancer is a grave traumatic experience that can profoundly compromise patients' psychological resilience, impacting their overall quality of life. The oxytocin system represents one of the essential neurobiological bases of psychological resilience and plays a critical role in regulating resilience in response to social or traumatic events during adulthood. Oxytocin, through its direct interaction with peripheral or central oxytocin receptors, has been found to have a significant impact on regulating social behavior. However, the precise mechanism by which the activation of peripheral oxytocin receptors leads to improved social is still not completely comprehended and requires additional research. Its activation can modulate psychological resilience by influencing estrogen and its receptors, the hypothalamic-pituitary-adrenal axis, thyroid function, 5-hydroxytryptamine metabolism levels, and arginine pressure release in breast cancer patients. Various interventions, including psychotherapy and behavioral measures, have been employed to improve the psychological resilience of breast cancer patients. The potential effectiveness of such interventions may be underpinned by their ability to modulate oxytocin release levels. This review provides an overview of the oxytocin system and resilience in breast cancer patients and identifies possible future research directions and interventions.

Advances in the study of the molecular biological mechanisms of radiation-induced brain injury.

Radiation therapy is one of the most commonly used treatments for head and neck cancers, but it often leads to radiation-induced brain injury. Patients with radiation-induced brain injury have a poorer quality of life, and no effective treatments are available. The pathogenesis of this condition is unknown. This review summarizes the molecular biological mechanism of radiation-induced brain injury and provides research directions for future studies. The molecular mechanisms of radiation-induced brain injury are diverse and complex. Radiation-induced chronic neuroinflammation, destruction of the blood-brain barrier, oxidative stress, neuronal damage, and physiopathological responses caused by specific exosome secretion lead to radiation-induced brain injury.

Music therapy, quality of life and efficacy of immunotherapy for NSCLC.

OBJECTIVE: Our study examines how non-small cell lung cancer (NSCLC) survivors undergoing immunotherapy can experience reduced anxiety and psychological distress, improved quality of life (QOL) and increased immunotherapy efficacy. METHODS: 133 men and 20 women with NSCLCs were enrolled. In a randomised controlled trial involving a care as usual group (CG) and a music therapy group (MTG), the researchers employed various tools such as the Self-Rating Anxiety Scale, Symptom Distress Thermometer, Functional Assessment of Cancer Therapy-General version 4 and Response Evaluation Criteria in Solid Tumours. These measures were used to evaluate anxiety, psychological distress, QOL and immunotherapy efficacy in patients undergoing immunotherapy before and after patients' completion. RESULTS: After the intervention, patients in the MTG demonstrated a noteworthy reduction in anxiety (t=6.272, p≤0.001) and distress (t=10.111, p≤0.001), as well as an increase in QOL (t=-7.649, p≤0.001). Moreover, compared with patients in the CG, those in the MTG demonstrated a remarkable drop in anxiety (t=-4.72, p≤0.001) and distress (t=-7.29, p≤0.001), a significant increase in QOL (t=5.363, p≤0.001) and a significant improvement in immunotherapy efficacy (z=-2.18, p≤0.05) after the intervention. CONCLUSIONS: The use of individual music therapy sessions appears to be effective in reducing anxiety and distress, while also increasing QOL and immunotherapy efficacy in patients with NSCLCs undergoing immunotherapy.

Positive influence of managing cancer and living meaningfully (CALM) on fear of cancer recurrence in breast cancer survivors.

To evaluate the effectiveness and feasibility of managing cancer and living meaningfully (CALM), an intervention used to reduce the fear of cancer recurrence (FCR) in breast cancer survivors and improve their quality of life (QoL). A total of 103 breast cancer survivors were enrolled. Participants were randomly assigned to the CALM group or the care as usual (CAU) group. The participants completed a survey at baseline (T0) and after two (T1), four (T2), and six (T3) intervention sessions. The patients were assessed using the Cancer Worry Scale (CWS), Psychological Distress Thermometer (DT), Functional Assessment of Cancer Therapy-Breast (FACT-B) and Hospital Anxiety and Depression Scale (HADS). After the intervention, the CALM group showed a significant decrease in levels of FCR, distress, anxiety, and depression (χ2=154.353, χ2=130.292, χ2=148.879, and χ2=78.681; P<0.001, 0.001, 0.001, and 0.001, respectively) and an increased QoL (χ2=122.822, P<0.001). Compared with the CAU group, the CALM group showed significant differences in FCR, distress, QoL, anxiety and depression (F=292.431, F=344.156, F=11.115, F=45.124, and F=16.155; P<0.001, P<0.001, P=0.01, P<0.001, and P<0.001, respectively). Negative correlations were found between CWS and FACT-B scores in the CALM group (T0: r=-0.6345, P<0.001; T1: r=-0.4127, P=0.0017; T2: r=-0.2919, P=0.0306; and T3: r=-0.3188, P=0.0177) and in the CAU group (T0: r=-0.7714, P<0.0001; T1: r=-0.6549, P<0.0001; T2: r=-0.5060, P=0.0002; and T3: r=-0.3151, P=0.0291). Thus, the CALM intervention reduced FCR, distress, anxiety and depression in breast cancer survivors and improved QoL.

Effects of CALM intervention on neutrophil-to-lymphocyte ratio (NLR), fear of cancer recurrence and quality of life in patients with lung cancer.

PURPOSE: To evaluate the feasibility and practicability of Managing Cancer and Living Meaningfully (CALM) as a psychological intervention to reduce neutrophil to lymphocyte ratio (NLR), fear of cancer recurrence, general distress, and improve quality of life in lung cancer survivors. METHODS: Eighty lung cancer patients with FCRI severity subscale (≥13 points) were recruited and randomly assigned to CALM or usual care (UC). NLR was recorded before and after treatment. The Fear of Cancer Recurrence Inventory (FCRI), Quality of Life Questionnaire Core 30 (QLQ-C30) and Depression-Anxiety-Stress Scale (DASS-21) were used to evaluate patients at baseline (T0), immediately after treatment (T1), and at 2 (T2) and 4 (T3) months. RESULTS: Compared with UC, NLR was significantly different before and after CALM intervention (z=-5.498; P=0.000). There were significant differences in the scores of QLQ, FCR and general distress before and after the T1, T2 and T3 interventions (F=220.30, F=315.20, F=290.10, respectively; P<0.001). NLR was negatively correlated with QOL both before (r=-0.763; P<0.0001) and after the intervention (r=-0.810, P<0.0001). FCR and general distress were negatively correlated with QOL in CALM (T0: r=-0.726, r=-0.776, respectively; P<0.0001; T1: r=-0.664, r=-0.647, respectively; P<0.0001; T2: r=-0.678, r=-0.695, respectively; P<0.0001; T3: r=-0.511, P = 0.0008; r=-0.650, P<0.0001). CONCLUSION: CALM intervention can effectively reduce the NLR, alleviate the recurrence fear and general distress and improve the quality of life in patients. This study suggests that CALM may be an effective psychological intervention for reducing symptoms associated with lung cancer survivors.

A cuproptosis-related lncRNA signature for predicting prognosis and immunotherapy response of lung adenocarcinoma.

BACKGROUND: Copper-induced cell death (cuproptosis) is a new regulatory cell death mechanism. Long noncoding RNAs (lncRNAs) are related to tumor immunity and metastasis. However, the correlation of cuproptosis-related lncRNAs with the immunotherapy response and prognosis of lung adenocarcinoma (LUAD) patients is not clear. METHODS: We obtained the clinical characteristics and transcriptome data from TCGA-LUAD dataset (containing 539 LUAD and 59 paracancerous tissues). By utilizing LASSO-penalized Cox regression analysis, we identified a prognostic signature composed of cuproptosis-related lncRNAs. This signature was then utilized to segregate patients into two different risk categories based on their respective risk scores. The identification of differentially expressed genes (DEGs) between high- and low-risk groups was carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We evaluated the immunotherapy response by analyzing tumor mutational burden (TMB), immunocyte infiltration and Tumor Immune Dysfunction and Exclusion (TIDE) web application. The "pRRophetic" R package was utilized to conduct further screening of potential therapeutic drugs for their sensitivity. RESULTS: We ultimately identified a prognostic risk signature that includes six cuproptosis-related lncRNAs (AP003778.1, AC011611.2, CRNDE, AL162632.3, LY86-AS1, and AC090948.1). Compared with clinical characteristics, the signature was significantly correlated with prognosis following the control of confounding variables (HR = 2.287, 95% CI = 1.648-3.174, p ˂ 0.001), and correctly predicted 1-, 2-, and 3-year overall survival (OS) rates (AUC value = 0.725, 0.715, and 0.662, respectively) in LUAD patients. In terms of prognosis, patients categorized as low risk exhibited more positive results in comparison to those in the high-risk group. The enrichment analysis showed that the two groups had different immune signaling pathways. Immunotherapy may offer a more appropriate treatment option for high-risk patients due to their higher TMB and lower TIDE scores. The higher risk score may demonstrate increased sensitivity to bexarotene, cisplatin, epothilone B, and vinorelbine. CONCLUSIONS: Based on cuproptosis-related lncRNAs, we constructed and validated a novel risk signature that may be used to predict immunotherapy efficacy and prognosis in LUAD patients.

The effects of Managing Cancer and Living Meaningfully (CALM) on psychological distress in esophageal cancer patients.

Aim: To evaluate the effectiveness of Managing Cancer and Living Meaningfully (CALM) in esophageal cancer with psychological distress during treatment. Materials & methods: The study assigned eligible patients to either a CALM group or a usual care group. Psychological distress, anxiety, depression and quality of life scores were assessed for both groups at baseline, during the intervention period and at the end of the intervention. Results: Patients showed a significant reduction in psychological distress, anxiety and depression and demonstrated improved quality of life after the CALM intervention, and the positive effect remained after 1 month of follow-up. Conclusion: This study suggests that CALM may be an effective approach for targeting psychological distress in patients with esophageal cancer.

Effects of fear of cancer recurrence on subjective physical and mental health in breast cancer patients: The intermediary role of heart rate variability.

BACKGROUND: Fear of cancer recurrence (FCR) and psychological distress are common psychological problems in breast cancer (BC) patients and ultimately affecting their health-related quality of life (HRQoL). Heart rate variability (HRV) can reflect the activity of the parasympathetic nervous system. However, the pathways through which HRV influences between FCR and HRQoL are unclear. This study preliminarily explored the intermediary role of HRV in FCR and HRQoL in BC patients. METHODS: A total of 101 BC patients participated in this study. HRV parameters were measured by a 5-min dynamic electrocardiogram. FCR, psychological distress and HRQoL were evaluated by the Fear of disease progression simplified scale (FOP-Q-SF), Distress thermometer and SF-36 concise health survey. The intermediary effect model was established to test the intermediary effect of high frequency-HRV (HF-HRV) on FCR and HRQoL. RESULTS: FCR and psychological distress were negatively correlated with HRV in the time domain, negatively correlated with HF-HRV in the frequency domain, and positively correlated with low frequency/high frequency (LF/HF). HF-HRV had a partial mediating effect on the FCR and physical health and mental health, with effects of 30.23% and 9.53%, respectively. CONCLUSION: FCR and psychological distress are correlated with HRV parameters in the time domain and the frequency domain, and we preliminarily believe that parasympathetic nerves play an important intermediary role between FCR and subjective physical and mental health. This may provide intervention information for improving the HRQoL of BC patients.

Effects of Managing Cancer and Living Meaningfully on Cancer-Related Fatigue and Cytokine Levels in Gastrointestinal Cancer Patients.

OBJECTIVE: To evaluate the effects of managing cancer and living meaningfully (CALM), a psychological intervention with semi-structured interviews, on cancer-related fatigue (CRF), quality of life (QOL), and sleep quality in patients with gastrointestinal (GI) cancer, which may be accompanied by changes in cytokine levels. METHODS: A total of 152 GI cancer patients with CRF were enrolled in the study during treatment. Patients were randomly assigned to CALM or usual care (UC) groups. Patients in the CALM group received 12 weeks of CALM plus usual care, and patients in the UC group received usual care plus usual health education. All study participants were evaluated at baseline and at 12 weeks using the Revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30, and the Pittsburgh Sleep Quality Index scale, while cytokine levels were measured. RESULTS: At 12 weeks, the differences in total CRF, QOL, sleep quality, IL-6, IL-4, and TNF-α levels were statistically significant not only in the CALM group compared to patients in the UC group (t = -7.902, t = 2.163, t = -2.187, t = 3.313, t = -4.120, t = -3.853, respectively; P < .05), but also in the CALM group compared to baseline (t = 11.331, t = -5.492, t = 5.450, t = -2.418, t = 2.186, t = 2.699, respectively; P < .05). Additionally, the total CRF at 12 weeks was correlated with IL-4, IL-6, and TNF-α levels (r = -.30, r = .31, r = .32, respectively; P < .001). CONCLUSIONS: CALM alleviated CRF and improved QOL and sleep quality in patients with GI cancer, and these improvements were accompanied by changes in IL-4, IL-6, and TNF-α levels.

Psychological distress as risk factor for the efficacy of whole-brain radiotherapy in brain metastasis patients.

Aim: To evaluate the relationship between psychological distress and the efficacy of whole-brain radiotherapy (WBRT) in advanced brain metastasis patients. Methods: Brain metastasis patients (40 with psychological distress and 47 without psychological distress) completed distress thermometer tests before WBRT, and progression-free survival (PFS) was acquired during the follow-up period. Results: Psychological distress was a risk factor for poorer PFS in patients treated with WBRT (p < 0.01). The PFS of survivors who underwent WBRT was superior for those without psychological distress (hazard ratio: 0.295; 95% CI: 0.173-0.500; p < 0.01). Conclusion: The survival of brain metastasis patients receiving WBRT was influenced by psychological distress, which negatively affected the treatment outcome and is likely to be a potential risk indicator in advanced cancer patients receiving WBRT.

Distress thermometer tests were carried out 1 week before whole-brain radiotherapy to assess psychological distress in 87 brain metastasis patients. The results demonstrated that the progression-free survival of brain metastasis patients with psychological distress was obviously inferior to that of patients without psychological distress. The negative effects of psychological distress could be recognized in advanced patients with brain metastases after whole-brain radiotherapy. Psychological distress is likely to be a potential risk indicator for radiotherapy in brain metastasis patients.

Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy-related cognitive impairment in patients with breast cancer who receive chemotherapy.

BACKGROUND: Chemotherapy-related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI. METHODS: This study enrolled one hundred and twenty-four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single-nucleotide polymorphisms (SNP) to explore these. The mini-mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT). RESULTS: We found that patients with ALDH2 gene genotypes of rs671_GG, rs886205_GG, rs4648328_CC, and rs4767944_TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671_GG of DST (z = 2.769, p = 0.006), VFT (t = 4.624, P<0.001); rs886205_GG of DST (z = 3.663, P<0.001); rs4648328_CC of DST (z = 2.850, p = 0.004), VFT (t = 3.477, p = 0.001); and rs4767944_TT of DST (z = 2.967, p = 0.003), VFT (t = 2.776, p = 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy (p < 0.05). The difference in ALDH2 rs671 was most obvious. CONCLUSION: Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single-nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians.

Safety and Efficacy of Treatment with/without Ramucirumab in Advanced or Metastatic Cancer: A Meta-Analysis of 11 Global, Double-Blind, Phase 3 Randomized Controlled Trials.

Ramucirumab, as a vascular endothelial growth factor receptor-2 inhibitor, was first approved in 2014 for treated advanced or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. This study deeply analyzed the efficacy and safety of advanced or metastatic cancer treated with ramucirumab, which included 11 global, double-blind, phase 3 randomized controlled trials with a total of 7410 patients. Subgroup analysis based on different cancer types showed that standard regimens plus ramucirumab significantly increased progression-free survival and overall survival compared with placebo groups in patients with advanced non-small-cell lung cancer (NSCLC), hepatocellular carcinoma, gastric cancer, or GEJ adenocarcinoma. Although a higher proportion of patients achieved overall response and disease control than those treated with placebo, the overall response was not statistically significant between the two groups in advanced NSCLC. Grade 3 or worse treatment-emergent adverse events (TEAEs) that occurred in at least 5% of patients were neutropenia (30.5% in the ramucirumab group vs. 23.5% in the placebo group), leucopenia (14.8% vs. 9.2%), weight decreased (14.2% vs. 8.0%), myalgia (11.7% vs. 7.7%), fatigue (10.9% vs. 7.7%), hypertension (9.2% vs. 2.3%), and anaemia (6.2% vs. 7.7%). In the TEAEs of special interest, the ramucirumab group had a significantly higher incidence of bleeding (mainly grade 1-2 epistaxis and gastrointestinal bleeding), hypertension, proteinuria, liver injury/failure (grade 1-2), venous thromboembolism (grade 1-2), and gastrointestinal perforation (grade ≧3) than the control group.

The Managing Cancer and Living Meaningfully (CALM) Intervention Alleviates Chemotherapy-Related Cognitive Impairment in Patients with Breast Cancer by Modulating Pan-Immune-Inflammation Values.

BACKGROUND: The number of patients with breast cancer is increasing worldwide, resulting in a growing number of patients with chemotherapy-related cognitive impairment (CRCI), which seriously affects their quality of life. CRCI is associated with inflammatory factors and systemic inflammatory markers such as pan-immune-inflammation value (PIV) and monocyte-to-lymphocyte ratio (MLR), which can reflect the level of inflammation in the body. While the Managing Cancer and Living Meaningfully (CALM) intervention has been demonstrated to alleviate CRCI in patients with breast cancer, the specific mechanism remains unclear. OBJECTIVE: This study evaluated the impact of the CALM intervention on systemic inflammation. METHODS: Ninety patients with breast cancer with CRCI were enrolled and randomized into care as usual (CAU) and CALM intervention groups. All patients were assessed using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Mini-Mental State Exam (MMSE), and Functional Assessment of Cancer Therapy-Breast (FACT-B) before and after the CAU/CALM intervention. The blood levels of inflammatory markers were also analyzed before and after the intervention. RESULTS: Compared to the CAU group, the CALM group showed significantly improved cognitive function and significantly decreased PIV (P < .05). PIV was significantly negatively correlated with FACT-Cog (P < .05). The levels of other inflammatory markers, including MLR, neutrophil-to-lymphocyte ratio (NLR), granulocyte-to-lymphocyte ratio (GLR), and systemic immune-inflammation index (SII), were also reduced in the CALM group. CONCLUSION: PIV is an important marker of inflammation. The CALM intervention may improve the cognitive function of patients by regulating the systemic inflammation marker PIV through the neuroimmune axis.

Construction of cuproptosis-related lncRNAs/mRNAs model and prognostic prediction of hepatocellular carcinoma.

Cuproptosis is a recently reported novel form of cell death, which is involved in the regulation of tumor progression. However, the specific role of cuproprosis in hepatocellular carcinoma (HCC) development remains unclear. In this study, we comprehensively analyzed the effect of cuproprosis-related lncRNAs/mRNAs on the prognosis of HCC patients based on the RNA-Seq transcriptome data and clinical data. We identified 6 cuproprosis-related signatures by Cox and Lasso regression analysis, including 3 mRNAs (FBXO30, RNF2, MPDZ) and 3 lncRNAs (PICSAR, LINC00426, AL590705.3). In addition, we constructed a prognostic prediction model for HCC. Risk analysis, RT-qPCR, and Kaplan-Meier analysis showed that the expression of FBXO30, RNF2, AL590705.3 and PICSAR was elevated in HCC, while the expression of MPDZ and LINC00426 was suppressed which was associated with better overall survival. Furthermore, immune response analysis suggested that HCC with high-risk score might respond favorably to immunotherapy. Moreover, the potential drugs that HCC might be sensitive to were screened by drug sensitivity profiling analysis. Taken together, our findings provided important information for the prediction of the prognosis of HCC patients and the development of personalized targeted therapy.

The alterations in event-related potential responses to pain empathy in breast cancer survivors treated with chemotherapy.

Background: Previous findings indicated that breast cancer patients often have dysfunction in empathy and other cognitive functions during or after chemotherapy. However, the manifestations and possible neuro-electrophysiological mechanisms of pain empathy impairment in breast cancer patients after chemotherapy were still unknown. Objective: The current study aimed to investigate the potential correlations between pain empathy impairment and event-related potentials (ERP) in breast cancer patients undergoing chemotherapy. Methods: Twenty-two breast cancer patients were evaluated on a neuropsychological test and pain empathy paradigm before and after chemotherapy, containing the Chinese version of the Interpersonal Reactivity Index (IRI-C), while recording ERP data. Results: The empathic concern scores were lower and personal distress scores were higher on IRI-C task compared with those before chemotherapy (t = 3.039, p < 0.01; t = -2.324, p < 0.05, respectively). Meanwhile, the accuracy rates were lower than those before chemotherapy for both pain and laterality tasks on the pain empathy paradigm (F = 5.099, P = 0.035). However, the response time was no significant differences before and after chemotherapy (F = 0.543, P = 0.469). Further, the amplitude of the N1 component was significantly increased (F = 38.091, P < 0.001), and the amplitude of the P2 component was significantly decreased (F = 15.046, P = 0.001) in the subsequent ERP study. A linear mixed effect model was used to analyze the correlation, the average amplitude of N1 and P2 were positively correlated with the accuracy rates in laterality tasks (r = 1.765, r = 1.125, respectively, P < 0.05). Conclusion: The results indicated that pain empathy impairment was performed in chemotherapeutic breast cancer patients, which was possibly correlated to the changes of N1 and P2 components in ERP. These findings provide neuro-electrophysiological information about chemo-brain in breast cancer patients.

Identification of hub genes related to CD4+ memory T cell infiltration with gene co-expression network predicts prognosis and immunotherapy effect in colon adenocarcinoma.

Background: CD4+ memory T cells (CD4+ MTCs), as an important part of the microenvironment affecting tumorigenesis and progression, have rarely been systematically analyzed. Our purpose was to comprehensively analyze the effect of CD4+ MTC infiltration on the prognosis of colon adenocarcinoma (COAD). Methods: Based on RNA-Seq data, weighted gene co-expression network analysis (WGCNA) was used to screen the CD4+ MTC infiltration genes most associated with colon cancer and then identify hub genes and construct a prognostic model using the least absolute shrinkage and selection operator algorithm (LASSO). Finally, survival analysis, immune efficacy analysis, and drug sensitivity analysis were performed to evaluate the role of the prognostic model in COAD. Results: We identified 929 differentially expressed genes (DEGs) associated with CD4+ MTCs and constructed a prognosis model based on five hub genes (F2RL2, TGFB2, DTNA, S1PR5, and MPP2) to predict overall survival (OS) in COAD. Kaplan-Meier analysis showed poor prognosis in the high-risk group, and the analysis of the hub gene showed that overexpression of TGFB2, DTNA, S1PR5, or MPP2 was associated with poor prognosis. Clinical prediction nomograms combining CD4+ MTC-related DEGs and clinical features were constructed to accurately predict OS and had high clinical application value. Immune efficacy and drug sensitivity analysis provide new insights for individualized treatment. Conclusion: We constructed a prognostic risk model to predict OS in COAD and analyzed the effects of risk score on immunotherapy efficacy or drug sensitivity. These studies have important clinical significance for individualized targeted therapy and prognosis.

The correlation between neutrophil-to-lymphocyte ratio, carcinoembryonic antigen, and carbohydrate antigen 153 levels with chemotherapy-related cognitive impairment in early-stage breast cancer patients.

Background: The changes in inflammation and tumor biomarkers are associated with the anti-tumor immunological processes. Early detection and intervention are of great significance to the clinical management of cancer-related diseases. Peripheral blood biomarkers [e.g., neutrophil-to-lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), and carbohydrate antigen 153 (CA153)] are obtained in real-timely, conveniently, and less invasively, and proved to availably predicted the disease states and prognosis of various cancers, including breast cancer (BC). Inflammation and poor disease management promote cognitive impairment. Chemotherapy-related cognitive impairment (CRCI) hazard long-term survival and quality of life (QOL) of BC patients, but its correlation with NLR, CEA, and CA153 is not clear. Purpose: This study aimed to investigate changes in NLR, CEA, and CA153 levels before and after chemotherapy and their correlation with CRCI in patients with early-stage BC. Materials and methods: The 187 patients with BC who were measured for NLR, CEA, and CA153 values within the first 24 hours of admission, were assigned into two groups: the before/after chemotherapy group (BCG/ACG). The ACG was assigned into two subgroups based on the cognitive assessment results: the cognitive normal/impaired group (CNG/CIG). Patients' self-perceived cognitive impairments were evaluated using a mini-mental state examination (MMSE), prospective and retrospective memory (PM and RM) questionnaire (PRMQ), and functional assessment of cancer therapy-cognitive function version 3 (FACT-Cog, version 3, including CogPCI, CogOth, CogPCA, and CogQOL). Their QOL was also evaluated. Results: The NLR and CA153 levels were elevated after chemotherapy (BCG vs ACG: Z = -1.996 and -1.615, P = 0.046 and 0.106, respectively), and significantly elevated in patients with CRCI (BCG vs CIG: Z = -2.444 and -2.293, P = 0.015 and 0.022; respectively). However, there was not reach significant difference in CEA levels between the four groups. In addition, there was a weak to moderate correlation between peripheral blood biomarkers (NLR, CEA, and CA153) levels and CRCI (r = -0.404, -0.205, -0.322; respectively; P < 0.001). Cognitive impairment scores (MMSE, PM, RM, and FACT-Cog) had a strong correlation with QOL in patients with early-stage BC (r = -0.786, 0.851, 0.849, and 0.938; respectively; P < 0.001). Conclusion: NLR and CA153 m be valuable diagnostic adjuncts of CRCI, and CRCI has a strong correlation with QOL in patients with early-stage BC.