European Journal of Cancer Care

Objective. Matrix metalloproteinase-2 (MMP2) overexpression has been considered as a hallmark of tumor aggressiveness. The significant roles of MMP2 in other human disorders, such as cardiovascular diseases and dental caries, have also been demonstrated. Herein, we used in silico approaches to evaluate the binding affinity of selected cinnamic acids to the MMP2 catalytic domain. The obtained findings were subsequently juxtaposed with those attributed to oleandrin, utilized as a reference pharmaceutical agent. Methods. This research employed the AutoDock software to assess the affinity of 19 herbal compounds derived from cinnamic acid to the catalytic cleft of MMP2. The ligands attaining the most negative scores, as determined by the Gibbs free binding energy assessments, were accorded the highest rankings. The interactions between the MMP2 and cinnamic acids ranked highest were elucidated using the Discovery Studio Visualizer tool. Molecular dynamics simulations were performed to investigate the structural stability of MMP2 backbone atoms when forming complexes with both the top-ranked inhibitor from this study and a standard drug. Results. Eight cinnamic acids were indicated with values less than −10 kcal/mol. Cynarin emerged as the most potent inhibitor of the enzyme, with the score and inhibition constant value of −15.19 kcal/mol and 7.29 pM, respectively. The MMP2 backbone atoms achieve stability around the 20 ns mark, displaying a root mean square deviation of approximately 3.2 Å when influenced by the top-ranked cinnamic acid, the standard drug, or in their free form. Conclusion. The inhibition of MMP2 by cinnamic acids, particularly cynarin, holds promise as a valuable therapeutic strategy for various human disorders, encompassing cancer, cardiovascular conditions, and dental caries.

Objective. Lung cancer (LC) patients suffer from multiple cooccurring symptoms. Interventions that have the potential to impact more than one symptom within a symptom cluster should be identified. The aim of this review was to examine nonpharmacological interventions that were effective in the management of one or more of the following symptoms in LC patients: dyspnea, fatigue, physical functioning (PF), and role functioning (RF). Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting this systematic review. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (using the PubMed interface), Embase (using the embase.com interface), and Web of Science were used as electronic databases. Randomized controlled studies were included if they assessed the effects of nonpharmacological interventions on dyspnea, fatigue, PF, and/or RF in patients with LC. Studies were evaluated with the Cochrane risk of bias tool, and relevant data were extracted and narratively summarized. Results and Conclusions. In total, 89 articles were included. Search results (until April 2023) show that most evidence was found for exercise interventions, followed by multicomponent, psychoeducational, diet, acupuncture, and other interventions. Studies that had an effect on multiple symptoms were observed to have the most frequent instances of positively affecting dyspnea, followed by PF, fatigue, and RF.

Women around the world are most frequently afflicted with breast cancer, and it is one of the most frequent causes of cancer death in females. Breast cancer is usually classified according to biomarker status, triple‐negative breast cancer (TNBC) represents a distinct subtype characterized by immunohistochemical findings that denote negativity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2) on cancer tissue. It is more common in younger women than in other subtypes. As an invasive breast cancer subtype with a unique drug-resistant phenotype and metastatic burden, it has limited treatment options, and patients have a poor prognosis with high rates of local, distant recurrence and mortality, and there is still a lack of standardized treatment protocols for TNBC. In this review, we delve into the current treatment strategies for TNBC and explore the potential for new approaches and targets in the future. This trial is registered with NCT03997123.

Bilobalide has shown strong anti-inflammatory activity. Colorectal cancer (CRC) is closely associated with inflammation. However, no studies have reported on the use of bilobalide for treating CRC. This study aims to evaluate the effect of bilobalide on CRC prevention. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence showed that bilobalide significantly inhibits the M2 polarization of macrophages dependent on phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4). Analysis of signaling pathways showed that the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) was regulated. In particular, human CRC organoids were established. Western blotting, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and analysis of cell viability and morphology further supported the hypothesis that the anti-CRC effects of bilobalide could be explained by its ability to suppress M2 macrophage polarization and promote M1 transformation. C57BL/6 mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) were divided into three groups, i.e., control, AOM/DSS, low (2.5 mg/kg), and high (5 mg/kg). High-dose bilobalide markedly inhibited the progression of CRC, as evidenced by the increased body weight, decrease in disease activity index (DAI) death rate, and alleviation of colon length reduction and tumorigenesis. According to the in vivo results, reduced levels of inflammatory cytokines in the serum included tumor necrosis factor (TNF-α), IL-6, IL-1β, and IL-10. Bilobalide reduced oxidative stress indices, lipid peroxide (LPO), and malondialdehyde (MDA) and increased reduced glutathione (GSH). In addition, the expression of proliferating cell nuclear antigen (PCNA), Ki67, cellular Myc (c-Myc), and CD206 was downregulated in the drug-treated groups, as confirmed by the immunohistochemical staining. Collectively, these results indicated that bilobalide administration improve experimental CRC by inhibiting M2 macrophage polarization and oxidative stress. Thus, bilobalide may prevent CRC and serve as a potential therapeutic target for CRC.

Background. Circadian rhythm disruption involves tumorigenesis and tumor progression. However, the influences of circadian rhythm on the tumor microenvironment (TME) and the prognosis of hepatocellular carcinoma (HCC) are unknown. Methods. Bulk RNA-seq and single-cell RNA-seq from TCGA, ICGC, and GEO were used to comprehensively identify prognostic circadian control cells and circadian rhythm associated genes (CRRGs) using R and Python packages. Besides, the circadian rhythm-related prognostic signature was identified and validated. The biological function, immune infiltration, and therapeutic response associated with circadian rhythm-related (CR) risk were detected. Results. A total of 252 differentially expressed CRRGs in HCC were identified, and HCC with a high CR score revealed poor survival. We annotated 11 major cell types in TME; immune cells (B cells, myeloid, CD4+ cells, CD8+ cells, NK cells, Tregs) with high CR score, and hepatocyte, bio-potent cells, fibroblasts, and endothelial cells with low CR score were identified. Moreover, five CRRGs (RPL29, PFKFB3, RPS7, SLC6A6, and RPLP2) were selected and validated as the prognostic signature in HCC. The risk score was calculated based on the prognostic signature, and patients then were divided into high-risk and low-risk groups according to the median value of the risk score. High risk is linked to several metabolism-related pathways and canonical cancer-related pathways and is negatively associated with immunotherapeutic responses and positively associated with some chemotherapeutic drugs. Conclusion. Our finding provides the novel circadian rhythm-related prognostic signature and represents a novel viable “time-dependent” therapeutic option for HCC treatment.

Background. To investigate the effectiveness of prehabilitation in improving physical and nutritional status in patients undergoing gastric cancer resection. Methods. A total of 136 locally advanced gastric cancer patients who planned to undergo neoadjuvant chemotherapy (NAC) plus transabdominal radical surgery were involved. All participants were divided into the prehabilitation group and the control group using the odd-even method, with 68 cases in each group. Intervention consisted of preoperative exercise and nutrition optimization. Participants were adults awaiting elective gastric resection for cancer. The primary outcomes were changes in functional ability and nutritional status, as measured by relative changes in 6 minute walking distance (6MWD) and scores on the albumin and prealbumin. Preoperative (end of the prehabilitation period) and postoperative (from 4 to 6 weeks after surgery) data were compared between the two groups. Results. All 136 patients were randomized in this study. Compared with the control group, the prehabilitation group exhibited improved functional capacity both before surgery (6MWD change) and after surgery. Furthermore, it demonstrated significantly higher levels of albumin and prealbumin before and after surgery than the control group. Conclusion. Prehabilitation in gastric cancer patients can improve preoperative functional capacity and nutritional status. Maintaining a patient’s physical function and nutritional status may have a significant impact on the continuity of cancer care.