Integrative Cancer Therapies最新文献

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem with no widely applicable solutions. Modified Wen Luo Tong (mWLT) was designed specifically for paclitaxel-related CIPN, yet its efficacy and mechanisms remain unclear. This study aimed to investigate its therapeutic effects and potential mechanisms via network pharmacology and animal experimental validation.

Methods: Paclitaxel-induced CIPN rat models were treated with mWLT pediluvium. The effect of mWLT was estimated by behavior test. The components and targets of 5 herbs in mWLT were screened from TCMSP and TCMIP databases. CIPN-related targets were retrieved from Genecards and DisGeNET. Networks of gene ontology and pathway associations related to intersection targets were constructed and visualized. A pharmacological network encompassing the intersecting genes and active components was mapped out. A protein-protein interaction network was established for these intersecting targets and visualized using Cytoscape software. Finally, the findings derived from network pharmacology were validated through a series of in vivo experiments, including ELISA, Western Blot, immunohistochemistry and RT-qPCR. Molecular docking was used to predict binding sites between small molecules of mWLT and CX3CR1.

Results: mWLT ameliorates mechanical withdrawal threshold of CIPN model rats. Three hundred and three targets of mWLT against CIPN were identified through intersection analysis, and 8 hub targets such as IL6, TNF and STAT3 were pinpointed. Enrichment analysis of intersection targets highlighted cellular response to cytokine stimulus, JAK-STAT3 pathway and NF-κB pathway. Thus, we speculated that mWLT may exert its effects by acting on IL6 and TNF, subsequently regulating IL6-JAK-STAT3 and TNFα-NF-κB signaling pathway, ultimately mitigating CIPN. Experimental validation demonstrated that mWLT significantly decreased the levels of IL-6, IL-1β and TNF-α in both spinal cord and plasma. Additionally, mWLT downregulated the phosphorylation of JAK, STAT3 and NF-κB in spinal cord. Further analyses using Immunohistochemistry, Western Blot and ELISA confirmed that mWLT reduced the protein expression of CX3CL1. RT-qPCR results revealed downregulation of Cx3cl1 and Cx3cr1 mRNA level in spinal cord and dorsal root ganglia. Molecular docking predicts 4 potential of compounds derived from mWLT to treat CIPN targeting CX3CR1.

Conclusion: mWLT exerts therapeutic effects in the treatment of CIPN by inhibiting CX3CL1/CX3CR1 axis and modulating JAK-STAT3 and NF-κB pathway.

Despite advances in HER2-targeted therapies and CSC-directed agents, resistance remains a major barrier in breast cancer. Synthesize evidence for exercise as a precision strategy to disrupt HER2/CD44-driven resistance circuits. Preclinical and clinical data demonstrate that physical activity: (1) downregulates HER2/PI3K signaling via myokine-mediated pathways (IL-6/SPARC), (2) reduces CD44 through NK-dependent immune surveillance, and (3) synergizes with biologics to overcome cardiotoxicity and chemoresistance. Molecular subtype-specific exercise prescriptions are defined. Exercise reprograms the tumor-immune microenvironment to target therapy-resistant pathways, establishing a paradigm for exercise as adjuvant precision medicine.

Background: The NALLC trial (NCT01441752) demonstrated that postoperative adjuvant chemotherapy combined with traditional Chinese medicine (TCM) improved the quality of life (QoL) and survival in resected stage Ib-IIIa non-small-cell lung cancer (NSCLC) patients. This report updates disease-free survival (DFS) and other key outcomes.

Methods: Between December 2012 and August 2015, 334 patients were randomized to receive either adjuvant chemotherapy plus traditional Chinese herbal granules (n = 167) or adjuvant chemotherapy plus placebo (n = 167) across 7 centers. Patients continued herbal granules or placebo daily until chemotherapy completion. DFS updates data was conducted in the intention-to-treat (ITT) population.

Results: The median follow-up was 116.87 months. Median DFS was 71.83 months for the TCM group versus 43.60 months for the control (HR: .86; 95% CI: .64-1.15; P = .31). Two-year and 5-year DFS rates were 73.60% and 50.16% for TCM, compared to 67.45% and 44.08% for the control (P = .23). Median overall survival (mOS) was not reached in either group, with 75% OS at 63.40 months for TCM and 53.67 months for the control. Five-year OS rates were 76.15% for TCM and 69.81% for the control (P = .23). Subgroup analysis showed stage Ib patients benefited from TCM in both DFS (HR: .51; P = .02) and OS (HR: .34; P = .01).

Conclusions: Adjuvant chemotherapy combined with TCM showed a potential trend toward improved DFS in early-stage NSCLC patients.

Trial registration: This trial was registered with Clinical.

Trials: gov (Number: NCT01441752, July 14, 2011).

Cancer pain is a complex issue of significant importance in daily clinical practice, requiring a multidimensional approach. Approximately 90% of cancer pain cases can be effectively managed through the appropriate and often combined use of pharmacological and non-pharmacological treatments. In addition to the analgesic drugs outlined in the WHO analgesic ladder, the concurrent use of adjuvant drugs may be considered, which are sometimes essential for effective cancer pain management. These treatments can be adjusted based on the presence of inflammatory processes and oxidative stress.

Methodology: This is an observational, descriptive, retrospective, real-world data study conducted in daily practice at the Country Medical Center in Bogotá, Colombia. It involved patients with any type of cancer diagnosis who were receiving chemotherapy, radiotherapy, oncological surgery, and/or hormonal therapy. From 2018 to 2023, protocols for intravenous high dose of sodium ascorbate were applied, resulting in a sample of 92 patients.

Results: The administration of sodium ascorbate at dose of 100 to 300 and 300 to 600 mg/kg/day showed statistically significant improvements in quality of life (P = .000). However, only the 300 to 600 mg/kg/day dose demonstrated a statistically significant reduction in pain (P = .0061).

Conclusions: It is possible that by controlling or reducing inflammation, pain sensation can be decreased, therefore high dose of an antioxidant such as sodium ascorbate may be an alternative to improve oxidative stress and inflammation as an adjuvant to analgesic prescription according to pain management guidelines for cancer patients.

Cancer survivors experience a range of side effects during and after treatment. There is a need for a rigorous synthesis of the most recent and best available evidence on the role of nutritional supplements for supportive care in cancer, to inform shared decision-making. We searched 5 databases for umbrella reviews, meta-analyses and systematic reviews on nutritional supplements for supportive cancer care, excluding studies on pain, anxiety and depression, which are covered in recent guidelines. We found 52 reviews that reported on 250 RCTs on 18 supplements for 16 indications. Almost all reviews were of low/critically low quality (assessed using A MeaSurement Tool to Assess systematic Reviews version 2). There was moderate-certainty evidence for benefit from the following supplements: amino acids and oral proteolytic enzymes for severity of radiation-induced dermatitis, N-acetyl cysteine for prevention of chemotherapy-induced peripheral neuropathy (CIPN) in individuals with gastrointestinal cancers. There was low to very low certainty evidence that glutamine, zinc, probiotics and melatonin may be effective for oral mucositis; Vitamin E, omega-3 fatty acids, glutamine and other amino acids may be effective for preventing CIPN. Serious adverse events were reported for high-dose Vitamin A, and dose-related adverse events were reported with zinc and Vitamin E. However, the majority of nutritional supplements were associated with only minor adverse events. Due to the low to very low certainty of the majority of evidence, firm clinical recommendations cannot be made. Further research to conclusively evaluate benefit and harm, including potential impact on efficacy of standard treatments, should be conducted.