Integrative Cancer Therapies最新文献

Colon cancer is one of the most prevalent cancers worldwide and the second leading cause of cancer-related deaths. The goal of the present study was to investigate the role of Prodigiosin (PG) in promoting programed cell death in irradiated Caco-2 colon cancer cells. We examined the extent to which PG disrupts the BCL-2/caspase-3 and PPAR-γ signaling pathways and affects apoptosis in these cancer cells. The inflammatory markers COX2, PGE2, NO, TNFα, and the inflammosome NLRP-3, MAPK in addition to prooxidant/antioxidant balance is also under investigation. Caco-2 cells were irradiated with gamma rays (6 Gy) either with or without PG and the results revealed that, PG established IC50 equivalent to 357.27 μgl/ml in Caco-2 cells. The flowcytometric analysis (Annexin V), BCL-2 and caspase-3 showed that PG induces apoptosis for Caco-2 cells. Furthermore, the PG + gamma irradiated (R) group of Caco-2 cells showed significant down regulation in proliferation and inflammatory cascade induction followed by changes in redox tone (expressed by increase in SOD and GSH activities and decrease in MDA concentration), resulted in reduction of tumor growth. It could be concluded that PG has an anti-proliferative action on Caco-2 cells because of its capability to enhance apoptosis in addition to its capability to enhance response of Caco-2 cells to gamma radiation. Based on our findings in the present study we were able to demonstrate that the oxidative status as well as inflammatory responses are grave for determining the longevity, life span and reactivity of Caco-2 colon cancer cells upon exposure to PG unaccompanied or accompanied by gamma radiation. Prodigiosin might represent a valuable key in contesting development of drug resistance of cancer cells and it could raise the radio-sensitivity of cells when PG delivered in combination with radiation exposures.

Purpose: Hepatocellular carcinoma (HCC) poses a significant global health burden with limited therapeutic options. Traditional Chinese medicine (TCM), particularly Yangyin Fuzheng Jiedu Prescription (YFJP), has shown promise in improving patient outcomes, but its mechanisms are poorly understood. This study aimed to elucidate the key components and mechanisms of YFJP in treating HCC using an integrative approach combining network pharmacology, molecular docking, and experimental validation.

Patients and methods: We analyzed data from 1021 HCC patients (481 treated with YFJP and 540 with Western medicine alone) using propensity score matching to minimize bias. Network pharmacology identified key components and targets of YFJP, with a focus on Jiedu Prescription (JDP). Molecular docking and dynamics simulations validated the binding affinity between core components and targets. GO and KEGG analyses elucidated biological functions and pathways. In vivo experiments using a tumor-bearing mouse model further validated the mechanisms.

Results: YFJP significantly improved overall survival (P < .0001) and increased CD4⁺T and CD8⁺T cell counts (P < .05) in HCC patients compared to the control group. Network pharmacology analysis identified JDP as the core component of YFJP, with quercetin, luteolin, and apigenin as the key active compounds. GO and KEGG pathway analyses revealed that JDP modulates HCC through the regulation of cell death, immune response, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that JDP increases the proportion of CD8⁺T cells in the tumor microenvironment and inhibits apoptosis by downregulating the IL-6/STAT3 pathway. Molecular docking and dynamics simulations further confirmed the strong binding affinity of JDP's key compounds to STAT3, supporting their role in modulating this pathway.

Conclusion: YFJP, particularly its core component JDP, enhances anti-tumor immunity and improves survival in HCC patients by modulating the IL-6/STAT3 pathway. These findings highlight YFJP as a promising adjuvant therapy for HCC, offering a multi-target approach to enhance anti-tumor immunity.

Purpose: Preoperative chemotherapy in borderline resectable pancreatic cancer (BRPC) reduces tumor size to enable surgery but may cause physical function decline. This study aimed to examine changes in physical function before and after preoperative chemotherapy in patients with BRPC, and explored factors associated with the change.

Methods: This retrospective study included 17 patients with BRPC who underwent preoperative chemotherapy and surgery between January 2020 and December 2021. Physical function was assessed using grip strength and the 6-minute walking test (6MWT). Patients were divided into 2 groups based on changes in physical function: (1) those with maintained physical function and (2) those with reduced physical function. Physical function, treatment duration, and the number of chemotherapy sessions were compared between the groups.

Results: Grip strength (24.7 ± 6.8 vs 25.1 ± 6.8 kg, P = .462) and 6MWT (451.8 ± 95.7 vs 470.0 ± 82.5 m, P = .119) showed no significant decline after chemotherapy. On subgroup analysis, the reduced physical function group (6 patients) had significantly more chemotherapy sessions than the maintained group (5.0 ± 2.0 vs 2.0 ± 0.6, P = .042), suggesting that prolonged chemotherapy regimens may increase physical function decline risk due to cumulative toxicity.

Conclusion: These findings underscore the need for individualized treatment planning, balancing tumor reduction benefits with physical decline risk, especially in frail patients.

This study aimed to evaluate the long-term effects of a remotely supervised HIIT program implemented during six months NACT on quality of life (QoL) and physical health outcomes in women with breast cancer, assessed 18-24 months post-intervention. The HIIT intervention study was two arm randomized control trial implementing remotely supervised 4x4 min training at an intensity of 85-95% of peak heart rate for 6 months during NACT. Physical health was assessed by treadmill VO_2peak, 6MWT and sit-to-stand test, and QoL by the EORTC QoL30. Participants were 24 BC survivors who agreed to participate in follow-up 18-24 months after the intervention (HIIT= 13, CG = 11). Results: At follow-up, the HIIT group demonstrated significant difference in change of VO_2peak (p = .046, ES = .169) and time to exhaustion (p = .024, ES= .211). Both groups presented significantly higher 6MWT and sit to stand test results at follow-up compared to pre-NACT (p < .05), while the magnitude of change was not significant. HIIT group results demonstrated moderate associations between 6MWT and Physical Functioning (r = -.674, p = .012) and Emotional Functioning (- .567, p = .043). A remotely supervised 6-months HIIT during NACT showed positive effects on submaximal cardiorespiratory fitness, absolute VO_2peak and muscle strength at 18-24 months follow-up. Moderate negative association between 6MWT and perceived physical and emotional functioning highlighted the complex relationship between physiological outcomes and self-reported QoL. The HIIT can be recommended during NACT to maintain prolonged effects on physical health of BC survivors.

Aim: To determine effects of Coenzyme Q10 (CoQ10) supplementation in breast cancer patients receiving doxorubicin treatment.

Methods: Phase I randomized, placebo-controlled, cross-over, dose-finding study among women with stage I-III breast cancer receiving 4 cycles of doxorubicin plus cyclophosphamide. The study was designed to test effects on doxorubicin pharmacokinetic parameters when administering up to the maximum tolerated dose of CoQ10 of 1200 mg/day. Eligible patients were randomized to Arm A (CoQ10 after Cycle 3, followed by placebo after Cycle 4) or Arm B (placebo after Cycle 3, followed by CoQ10 after Cycle 4). CoQ10 concentrations and total antioxidant capacity (TAC) were measured before and after chemotherapy cycles. Non-compartmental pharmacokinetic parameters of doxorubicin and its active metabolites were measured with and without CoQ10. Paired t-tests assessed intra-patient differences in pharmacokinetic parameters, serum CoQ10 concentrations, TAC, and adverse events.

Results: Six patients received 300 mg/day of CoQ10 (Arm A [n = 3], Arm B [n = 3]). One patient received 600 mg/day of CoQ10 but was discontinued due to non-adherence. Serum CoQ10 concentrations were increased in patients receiving 300 mg/day (mean ± SD change: CoQ10, 1.6 ± 0.9 µg/mL; placebo, -0.01 ± 0.3 µg/mL; P = .01). There were no clinically significant pharmacokinetic interactions between 300 mg/day CoQ10 and doxorubicin and no differences in TAC or adverse events during treatment and nontreatment periods. The trial was closed early due to slow accrual.

Conclusion: 300 mg/day of CoQ10 with doxorubicin did not change doxorubicin pharmacokinetics and was not associated with treatment-related adverse events. Future studies should evaluate the long-term effects of CoQ10 at 300 mg/day and safety studies should examine higher doses.

Trial registration: ClinicalTrials.gov: NCT00976131.

Background: Lung cancer is the most diagnosed cancer worldwide and is associated with various unmet supportive care needs. To address these needs, a 6-week virtual program called Inspire Now was developed, integrating yoga, education, and group support. The primary objective of this mixed-methods observational study was to evaluate the program's impact on quality of life (QOL). Secondary objectives included changes in participant-identified concerns, participants' qualitative experiences, and acceptability of virtual delivery.

Methods: Eligible participants included people with primary lung cancer enrolled in the program. Questionnaires were administered at baseline and program completion. QOL and patient-identified concerns were evaluated by within-person changes in Functional Assessment of Cancer Therapy - Lung (FACT-L) and Measure Yourself Concerns and Wellbeing (MYCaW). Qualitative experiences and feasibility of virtual delivery were obtained by MYCaW and an internally developed questionnaire. FACT-L and MYCaW were analyzed using paired t-tests, and qualitative data was evaluated by an inductive thematic analysis.

Results: Forty-five participants were enrolled and 31 were eligible for analysis. Most were female (87%), had stage IV disease (68%), and were on active treatment (74%). Significant improvements were observed in FACT-General and Lung scores (mean changes: +6.1, 95% CI 2.2- 10.0, P = .003; +5.9, 95% CI 1.1-10.7, P = .02, respectively). MYCaW concerns and overall wellbeing were significantly improved. Participants viewed the virtual format favorably. Emotional support and connection were the most valued aspects of the program.

Conclusions: A 6-week virtual program of yoga, education, and group support improved QOL, patient-specific concerns, and wellbeing for those with lung cancer.