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.

Analysis of Immune Resistance Mechanisms in TNBC: Dual Effects Inside and Outside the Tumor.

Triple-negative breast cancer (TNBC) is a unique subtype of breast cancer characterized by the lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC exhibits a high degree of aggressiveness, metastatic potential, and a poor prognosis. Despite the limited success of conventional treatments, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutics for TNBC. Therefore, understanding the mechanisms underlying innate and acquired resistance to ICIs in TNBC is essential. Numerous studies suggest that intrinsic and extrinsic factors significantly contribute to the development of ICI resistance in TNBC. Intrinsic resistance may result from alterations in tumor-intrinsic signaling pathways, such as dysregulation of interferon (IFN) signaling or other signaling pathways. In contrast, extratumoral mechanisms may develop due to alterations in the tumor microenvironment, changes in T cell-related factors or adaptations within the immune system itself. In this paper, we endeavor to elucidate the underlying mechanisms of immune resistance by systematically examining immune mechanisms, the present state of immunotherapy, and the processes of immune resistance. Nonetheless, enhancing our understanding of the mechanisms underlying intratumoral and extratumoral resistance to ICIs in TNBC is crucial for optimizing patient outcomes in this challenging disease. Persistent efforts to identify novel targets for combination therapies, biomarkers that can predict the response to immunotherapy, and resistance mechanisms will be instrumental in achieving this objective.

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.

Psychological distress as a risk factor for the efficacy of chemotherapy in advanced gastric cancer patients.

AIM: To assess the relationship between psychological distress and quality of life (QoL), cancer-related fatigue (CRF), and chemotherapy efficacy in advanced gastric cancer patients. METHODS: Advanced gastric cancer patients (39 with psychological distress and 35 without psychological distress) completed the Distress Thermometer (DT), QoL, and CRF test before receiving chemotherapy and assessed the efficacy after completing 2 courses of chemotherapy. RESULTS: Psychological distress was a significant factor in the efficacy of chemotherapy in advanced gastric cancer patients (χ2 = 6.324; p = 0.042). Compared to advanced gastric cancer patients with no psychological distress, advanced gastric cancer patients with psychological distress had a poorer QoL (50.41 ± 6.17 vs. 60.01 ± 7.94, t = - 5.882, p < 0.01) and more pronounced CRF (5.75 ± 1.16 vs. 3.22 ± 0.75, t = 11.231, p < 0.01) while receiving chemotherapy. FACT-G (p = 0.0035, r = - 0.4568), as well as PFS (p < 0.0001, r = 0.6599), correlated significantly with efficacy for patients in the psychological distress group. The FACT-G (p = 0.0134, r = - 0.4139) of patients in the no psychological distress group correlated significantly with efficacy. CONCLUSION: Psychological distress has a negative impact on QoL, CRF, and efficacy and may be a potential risk for the efficacy of palliative chemotherapy in advanced gastric cancer patients.

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.

A Predictive Model for the Early Death of Breast Cancer With Synchronous Liver Metastases: A Population-Based Study.

BACKGROUND: Breast cancer liver metastasis (BCLM) is a severe condition often resulting in early death. The identification of prognostic factors and the construction of accurate predictive models can guide clinical decision-making. METHODS: A large sample of data from the Surveillance, Epidemiology, and End Results (SEER) database was analyzed, including 3711 patients diagnosed with de novo BCLM between 2010 and 2015. Predictive models were developed using histograms, and stepwise regression addressed variable collinearity. Internal validation was performed, and results were compared to similar studies. RESULTS: In this study of 3711 BCLM patients, 2571 didn't have early death. Out of the 1164 who died early, 1086 had cancer-specific early death. Prognostic factors for early death, including age, race, tumor size, and lymph node involvement, were identified. A nomogram based on these factors was constructed, accurately predicting early all-cause and cancer-specific death. CONCLUSIONS: Valuable insights into the prognosis of BCLM patients were provided, and important prognostic factors for early death were identified. The developed nomogram can assist clinicians in identifying high-risk patients for early death and inform treatment decisions.

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.

Managing Cancer and Living Meaningfully (CALM) alleviates chemotherapy related cognitive impairment (CRCI) in breast cancer survivors: A pilot study based on resting-state fMRI.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) is a type of memory and cognitive impairment induced by chemotherapy and has become a growing clinical problem. Breast cancer survivors (BCs) refer to patients from the moment of breast cancer diagnosis to the end of their lives. Managing Cancer and Living Meaningfully (CALM) is a convenient and easy-to-apply psychological intervention that has been proven to improve quality of life and alleviate CRCI in BCs. However, the underlying neurobiological mechanisms remain unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) has become an effective method for understanding the neurobiological mechanisms of brain networks in CRCI. The fractional amplitude of low-frequency fluctuations (fALFF) and ALFF have often been used in analyzing the power and intensity of spontaneous regional resting state neural activity. METHODS: The recruited BCs were randomly divided into the CALM group and the care as usual (CAU) group. All BCs were evaluated by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) before and after CALM or CAU. The rs-fMRI imaging was acquired before and after CALM intervention in CALM group BCs. The BCs were defined as before CALM intervention (BCI) group and after CALM intervention (ACI) group. RESULTS: There were 32 BCs in CALM group and 35 BCs in CAU group completed the overall study. There were significant differences between the BCI group and the ACI group in the FACT-Cog-PCI scores. Compared with the BCI group, the ACI group showed lower fALFF signal in the left medial frontal gyrus and right sub-gyral and higher fALFF in the left occipital_sup and middle occipital gyrus. There was a significant positive correlation between hippocampal ALFF value and FACT-Cog-PCI scores. CONCLUSIONS: CALM intervention may have an effective function in alleviating CRCI of BCs. The altered local synchronization and regional brain activity may be correlated with the improved cognitive function of BCs who received the CALM intervention. The ALFF value of hippocampus seems to be an important factor in reflect cognitive function in BCs with CRCI and the neural network mechanism of CALM intervention deserves further exploration to promote its application.

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.

Advances of neuroimaging in chemotherapy related cognitive impairment (CRCI) of patients with breast cancer.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) has seriously affected the quality of life (QOL) of patients with breast cancer (BCs), thus the neurobiological mechanism of CRCI attracted widespread attention. Previous studies have found that chemotherapy causes CRCI through affecting brain structure, function, metabolism, and blood perfusion. FINDINGS: A variety of neuroimaging techniques such as functional magnetic resonance imaging (fMRI), event-related potential (ERP), near-infrared spectroscopy (NIRS) have been widely applied to explore the neurobiological mechanism of CRCI. CONCLUSION: This review summarized the progress of neuroimaging research in BCs with CRCI, which provides a theoretical basis for further exploration of CRCI mechanism, disease diagnosis and symptom intervention in the future. Multiple neuroimaging techniques for CRCI research.

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 is involved in CRCI in breast cancer survivors via mediating cytokine levels.

BACKGROUND: Cancer-related cognitive impairment (CRCI) is a frequent consequence in breast cancer survivors after chemotherapy and lowers their quality of life (QOL). Psychological distress is frequently experienced by breast cancer survivors. There are currently few studies investigating the role of psychological distress in the genesis of CRCI. METHODS: In total, 122 breast cancer survivors after standard chemotherapy within a year were recruited and assessed using the Psychological Distress Thermometer (DT). Sixty breast cancer survivors had non-psychological distress (NPD group) and sixty-two breast cancer survivors with psychological distress (PD group). The scores of the Mini-Mental State Examination (MMSE), prospective and retrospective memory (PM and RM) Questionnaire (PRMQ), and Functional Assessment of Cancer Therapy-General (FACT-G) and the levels of cytokines including interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-4 (IL-4) were compared between the two groups. Using PROCESS, we investigated whether psychological distress predicted cognitive function based on MMSE through IL-1ß, TNF-α, and IL-4. RESULTS: The PD group had higher scores on RM, PM, and FACT-G and lower scores on MMSE than the NPD group (t = -11.357, t = -10.720, t = -15.419, t = 10.162, respectively; p < 0.05). Meanwhile, a higher level of IL-1ß, TNF-α, and IL-4 was observed in the PD group than in the NPD group (t = -3.961, t = -3.396, t = -3.269, respectively; p < 0.05). The link between psychological distress and cognitive function as measured by the MMSE was also mediated by IL-1ß, TNF-α, and IL-4 (effect size: 26%, 25%, and 24%). CONCLUSION: Breast cancer patients with psychological distress displayed poor cognitive function, poor memory, and inferior quality of life, which was accompanied by higher cytokine levels of IL-1ß, TNF-α, and IL-4. This study demonstrated IL-1ß, TNF-α, and IL-4 as potential pathways to CRCI in response to ongoing psychological distress, which provided evidence for the involvement of psychological distress in CRCI in breast cancer survivors.

A comprehensive computational analysis to explore the importance of SIGLECs in HCC biology.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive, malignant cancer with a complex pathogenesis. However, effective therapeutic targets and prognostic biomarkers are limited. Sorafenib provides delaying cancer progression and survival improvement in advanced HCC. But despite 10 years of research on the clinical application of sorafenib, predictive markers for its therapeutic effect are lacking. METHODS: The clinical significance and molecular functions of SIGLEC family members were assessed by a comprehensive bioinformatic analysis. The datasets included in this study (ICGC-LIRI-JP, GSE22058 and GSE14520) are mainly based on patients with HBV infections or HBV-related liver cirrhosis. The TCGA, GEO, and HCCDB databases were used to explore the expression of SIGLEC family genes in HCC. The Kaplan-Meier Plotter database was used to evaluate relationships between the expression levels of SIGLEC family genes and prognosis. Associations between differentially expressed genes in the SIGLEC family and tumour-associated immune cells were evaluated using TIMER. RESULTS: The mRNA levels of most SIGLEC family genes were significantly lower in HCC than in normal tissues. Low protein and mRNA expression levels of SIGLECs were strongly correlated with tumour grade and clinical cancer stage in patients with HCC. Tumour-related SIGLEC family genes were associated with tumour immune infiltrating cells. High SIGLEC expression was significantly related to a better prognosis in patients with advanced HCC treated with sorafenib. CONCLUSIONS: SIGLEC family genes have potential prognostic value in HCC and may contribute to the regulation of cancer progression and immune cell infiltration. More importantly, our results revealed that SIGLEC family gene expression may be used as a prognostic marker for HCC patients treated with sorafenib.