Integrative Cancer Therapies最新文献

With increasing survival rates for breast cancer (BC)-91% at 5 years and 80% at 15 years post-diagnosis-there is growing recognition of the importance of addressing long-term patient well-being. Beyond standard medical treatments, factors such as diet, psychological health, and quality of life significantly impact BC outcomes. Integrative oncology, which combines conventional oncology therapies with evidence-based complementary approaches (including nutrition, mind-body practices, and lifestyle modifications), has emerged as a patient-centered model aimed at improving symptom management, treatment adherence, and overall quality of life. This work describes the introduction of integrative oncology practices through the "AMICO" clinic, located within the Breast Surgery Unit at IRCCS-CROB in Rionero in Vulture, Southern Italy. As the first initiative of its kind in a public hospital in Italy, the clinic aims to provide a patient-centered approach for BC patients undergoing chemotherapy, radiation therapy, and/or breast surgery, with the mission to alleviate common side effects and improve their quality of life. During its first year of activity, the clinic has conducted joint consultations with nutritionists, organized mind-body laboratories (including Qigong sessions) and collected real-time clinical data These activities provide a foundation for the development of robust clinical databases and support a structured approach to patient-centered integrative care. By combining conventional oncology with evidence-based complementary therapies, the AMICO Clinic provides an example of a structured approach to personalization of cancer care. Ongoing and future research will further clarify the clinical value and potential benefits of integrative oncology in enhancing patient well-being.

Background: Emerging evidence suggests that the ketogenic diet (KD) may support cancer treatment by improving metabolic parameters and reducing treatment-related side effects. This review aimed to synthesize evidence from systematic reviews and meta-analyses on the effects of ketogenic diets in cancer, focusing on metabolic outcomes, body composition, quality of life, and tumor progression. Treatment-related complications were considered as exploratory outcomes.

Methods: A comprehensive review of meta-analyses were conducted following PRISMA guidelines. Databases including PubMed, Scopus, and Web of Science were searched for systematic reviews and meta-analyses exploring the effects of KD on cancer and treatment side effects. After screening 615 articles, 24 eligible reviews were examined to explore the effects of ketogenic diets on metabolism, quality of life, body composition, and cancer progression.

Results: KD improved metabolic markers such as glucose and triglycerides, and showed benefits in body composition and quality of life. Evidence on treatment-related complications, including radiotherapy side effects, was limited and heterogeneous.

Conclusions: KD shows promise as a safe and effective adjunctive therapy in cancer management. More evidence is needed to draw firm conclusions.

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.

This study compared Intraneural Facilitation (INF^®) therapy and standard physical therapy (PT) in preventing chemotherapy-induced peripheral neuropathy (CIPN) in women with newly diagnosed breast and gynecologic cancer. Thirty-eight women undergoing platinum and/or taxane-based chemotherapy, without prior peripheral neuropathy, were randomized into INF^® therapy (n = 20) and PT (n = 18). Treatments lasted 45 minutes, twice weekly, for 6 weeks. Neuropathy severity was evaluated using the Pain Quality Assessment Scale. Assessments were at baseline, 3 weeks, 6 weeks, and 3 months post-intervention. Acceptability, burden, and satisfaction were evaluated after 6 weeks. Among 38 patients, 12 (32%) experienced CIPN, with mean pain scores remaining mild (≤3) and no pharmacotherapy required until week 6. No adverse events were reported from the interventions. The INF^® therapy arm showed significant changes in numbness (F = 6.030, P = .001, partial η² = 0.262) after week 6, while the PT arm showed significant changes in numbness (Z = -2.39, P = .017), tingling (Z = -2.84, P = .004), cramping (Z = -2.120, P = .034), surface pain (Z = -2.75, P = .006), and deep pain (Z = -1.99, P = .046) between weeks 3 and 6. Nearly 80% of patients completed chemotherapy cycles with an average relative dose intensity of 90.4% (INF^® therapy: 87.73% vs PT: 73.44%). Ninety-four percent of patients were satisfied with their care, accepted the treatments, and perceived them as a low burden. The results demonstrated that INF^® therapy and PT are feasible options for CIPN, improving treatment adherence, outcomes, and quality of life for women with newly diagnosed breast and gynecological cancers.Trial Registration - The study was pre-registered on ClinicalTrials.gov (NCT03272919). August 8, 2017.

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).

Background: Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

Methods: A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety and tolerability. An exploratory aim was assessment of RH324's anti-neoplastic effects as measured by changes in tumor metabolism using [¹⁸F]-labeled 2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans performed before and after completing a 28-day RH324 monotherapy regimen. A total of 9 patients were enrolled, 5 of which completed the trial, including imaging, and were evaluable.

Results: All study safety and tolerability primary endpoints were met. Analysis revealed notable response rates across different SUV parameters (SUV_max, SUV_mean, and SUV_peak) and there were no new metastatic lesions identified, further supporting RH324's anti-neoplastic effects.

Conclusion: RH324 was safe and well tolerated as a monotherapy in advanced NSCLC. FDG-PET/CT provided a novel methodology as a short-term metabolic endpoint with an in vivo biomarker assessment of potential clinical efficacy using a metabolic surrogate of disease activity. This approach offered deeper insights into tumor metabolism and heterogeneity, underscoring the potential of RH324's anti-neoplastic effects in treating refractory NSCLC.

Clinical trial registration: ClinicalTrials.gov, Identifier: NCT05580172, Registered on October 17, 2022.

Prangos ferulacea is a widely recognized and valuable medicinal herb known for its diverse biological characteristics. Our study was conducted to evaluate the anticancer and immunomodulatory effects of P. ferulacea. Ethyl acetate, methanol, and aqueous extracts were prepared from P. ferulacea, and the MTT assay was used to measure antiproliferation activity against 5 cancer cell lines (MDA-MB231, T47-D, HeLa, EMT6/P, and Vero). The 3 extracts underwent a qualitative LC/MS spectrometry analysis to determine each extract's composition. The MTT test was used to measure the proliferation of lymphocytes. Extracts were evaluated for their effects on macrophages phagocytic activity and pinocytosis function using the nitro blue tetrazolium assay and the neutral red method, respectively. The impact of ethyl acetate and methanol was assessed in mice inoculated with EMT6/P using the in vivo model, and the tumor size was measured. Results showed that ethyl acetate and methanol extracts had the highest activity against T47-D with IC₅₀ values of 0.019 mg/ml. The ethyl acetate extract exhibited moderate effectiveness against the following cell lines: MDA-MB-231 and EMT6/P with IC₅₀ values of 0.104 and 0.255 mg/ml, respectively. Meanwhile, methanol extract showed activity against MDA-MB231 and EMT6/P cell lines and had IC₅₀ values of 0.214 and 0.31 mg/ml, respectively. Regarding immunomodulatory assays, the methanol extract, followed by the ethyl acetate extract, significantly increases lymphocyte proliferation and macrophage phagocytosis activity. Aqueous extracts increase the activity of pinocytosis. Both ethyl acetate and methanol extracts reduced tumor size by 61.46% and 34.47%, respectively. They also decreased the average weight of the tumor cells in the in vivo model. The results of P. ferulacea have valuable activity against cancer cells and stimulate the immune system. However, further molecular investigations are required to understand the mechanism of action of P. ferulacea activity.

Implementing cancer rehabilitation in primary care that addresses the physical, psychological, social, and existential consequences of cancer is considered important.

Aim: To describe primary care practitioners' self-reported preconditions-including facilitators and barriers-related to cancer rehabilitation and physical activity, as well as their interest in responding to questions about cancer rehabilitation.

Methods: This convergent mixed-methods study collected self-reported quantitative questionnaire data using 0 to 10 scales (10 = maximum) from 229 primary care practitioners (104 rehabilitation practitioners and 125 healthcare center practitioners), and written qualitative data from a sub-sample of 120.

Results: Among rehabilitation practitioners, 20% provided some form of cancer rehabilitation and 70% prescribed physical activity to consulting cancer survivors. Corresponding figures for healthcare center practitioners were 10% and 15%, respectively. Both rehabilitation and healthcare center practitioners reported a median score of 0 (no knowledge) regarding physical activity advice for cancer survivors, and 95% of participants had not read cancer rehabilitation guidelines. Rehabilitation practitioners gave median ratings of 8 and 9 for the importance of providing cancer rehabilitation and physical activity advice, respectively, compared with 6 and 7 among healthcare center practitioners. Median ratings among rehabilitation practitioners were 3 for workplace preparedness and 3 for sufficient time for cancer rehabilitation, compared with 2 and 0 (no time at all) among healthcare center practitioners. Facilitators of the implementation were that providing cancer rehabilitation was considered important, and that practitioners were experienced in rehabilitation and physical activity counseling in non-cancer populations. To have committed and motivated co-workers facilitated a positive work culture for cancer rehabilitation. Primary barriers were the limited knowledge and skills and perceived unsatisfactory organizational preconditions, shaping an uncertainty on if primary care has any responsibility for cancer rehabilitation. Of the 168 rehabilitation practitioners invited, 104 (62%) were interested in answering questions regarding cancer rehabilitation. Among the 1055 invited healthcare center practitioners, 125 (12%) were interested.

Conclusions: Given the limited preconditions for cancer rehabilitation and physical activity implementation, the described barriers and facilitators, and the varying interest among practitioners, educational interventions and support strategies tailored to both individuals and organizations appear necessary.