Integrative Cancer Therapies

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.

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).

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.

To evaluate the feasibility and the preliminary estimate of effect of a 12-week Guolin Qigong (GQ) intervention, a mind-body exercise, on the fatigue-sleep disturbance-depression symptoms among breast, lung and colon cancer survivors.

Forty-one breast, lung, and colon cancer survivors with moderate to severe fatigue as measured by the Brief Fatigue Index were randomised to a GQ intervention (n = 21) or a waitlist control (n = 20). Outcome measures were assessed at baseline, 6, 12 weeks (post-intervention), and 16 weeks (4 weeks post-intervention). The primary feasibility was assessed using recruitment, retention, class attendance, home practice, safety and quantum of missing data. Secondary outcomes of symptom differences across timepoints in fatigue, sleep, and depression were assessed using a Generalised Estimating Equations (GEE) model with a Gaussian family, independent link, exchangeable correlation structure, and robust variance estimation.

Forty-one cancer survivors were successfully recruited with a recruitment rate of 72%. Retention was 95% (GQ) and 80% (control) at Week-12 and Week-16. GQ intervention class attendance was 86% for the 12-weeks duration with home practice averaging 5 day/week and 394 minutes/week. Missing data were less than 10%. There were no intervention-related serious adverse events. From baseline to Week 12 or Week 16, the average decreases in fatigue, sleep quality, and depression were 0.66, 0.11, and 1.79 respectively, after adjusting for gender and cancer-type imbalances.

GQ was feasible and safe for cancer survivors with fatigue-sleep disturbance-depression symptoms, within the defined small sample size. A larger randomised trial is needed for statistical validation.

To investigate acupuncture-induced changes in targeted glutathione metabolites in breast cancer survivors with psychoneurological symptoms (PNS) and to examine associations between these metabolic changes and PNS improvements.

This exploratory phase II single-arm study (N = 42) evaluated a 10-session, 5-week acupuncture intervention for PNS management in breast cancer survivors. Targeted glutathione metabolites (ie, reduced glutathione (GSH), oxidized glutathione (GSSG), cysteine-glutathione disulfide (CySSG), GSH/GSSG ratio) and reactive oxygen species (ROS) were measured pre- and post-treatment. Paired t-test and Wilcoxon signed-rank tests assessed changes in these biomarkers. The PNS were assessed using Patient-Reported Outcomes Measurement Information System (PROMIS)-29.

ROS levels significantly increased post-treatment (2.34 ± 1.02-2.83 ± 1.23 μmol/L, P = .017), while GSSG levels significantly decreased (0.19 ± 0.23-0.12 ± 0.23 µmol/L, P < .001). GSH/GSSG ratio significantly increased (2.73 ± 1.21-5.38 ± 1.99, P < .001), indicating a shift toward reduced oxidative stress. GSH and CySSG levels showed non-significant increases after acupuncture (GSH: 0.38 ± 0.14-0.42 ± 0.16 µmol/L, P = .07; CySSG: 0.00503 ± 0.00082-0.00532 ± 0.00076 µmol/L, P = .06). No significant correlations were found between changes in GSH metabolites and PNS composite scores or individual symptom scores.

Acupuncture may modulate GSH metabolism, improve redox balance, and enhance antioxidant capacity in breast cancer survivors with PNS. However, these biochemical changes were not correlated with PNS improvement, suggesting that alternative pathways may mediate acupuncture’s therapeutic effects.

The study was registered in ClinicalTrials.gov (Identifier: NCT05417451).

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.

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.

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.

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

Lung cancer is the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 80% to 85% of cases. While surgery and chemotherapy are primary treatments, their side effects—such as nausea, vomiting, and immunosuppression—significantly impact quality of life (QoL). Acupuncture and moxibustion, commonly used in Traditional Asian Medicine (TAM), are proposed to alleviate these effects, though their efficacy in NSCLC remains uncertain. This systematic review and meta-analysis evaluated their impact on QoL, chemotherapy-induced nausea and vomiting (CINV), and immune function in NSCLC patients.

Nine databases (PubMed, Embase, Cochrane Library, CNKI, OASIS, ScienceON, KISS, KMBASE, and RISS) were searched for randomized controlled trials (RCTs) published until April 2025. RCTs comparing acupuncture or moxibustion with standard care in NSCLC patients were included. Primary outcomes were QoL (QLQ-C30, KPS); secondary outcomes included CINV and immune markers (CD3, CD4, CD8, CD4/CD8 ratio, TNF-α). Data were analyzed using Review Manager 5.4, and risk of bias was assessed using the Cochrane RoB tool.

Thirty-nine RCTs (N = 3610) were included. Acupuncture and moxibustion significantly improved QoL (QLQ-C30 MD = 12.39; KPS MD = 8.22; both P < .00001), reduced CINV incidence (RR = 0.32, P < .00001), and enhanced symptom relief (RR = 1.16, P < .00001). Immune function markers, including CD3 (MD = 7.20, P = .0002), CD4 (MD = 4.89, P = .0003), and the CD4/CD8 ratio (MD = 0.22, P < .00001), were significantly increased, while TNF-α levels decreased (MD = −11.05, P = .04).

Acupuncture and moxibustion improve QoL, reduce CINV, and modulate immune function in NSCLC, supporting their complementary role.

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.

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.

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.

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.

Hepatic metastases are a leading cause of mortality in gastrointestinal cancers, often exacerbated by the limited efficacy of conventional chemotherapeutics. Biobran/MGN-3, a rice bran-derived arabinoxylan, has shown promise in sensitizing cancer cells to paclitaxel.

This study evaluates the hepatoprotective potential of Biobran/MGN-3 in a murine model of Ehrlich ascites carcinoma (EAC).

Female Swiss mice inoculated with EAC were treated with paclitaxel (10 mg/kg) and Biobran (40 mg/kg) concomitantly for 30 days. Tumor volume along with liver function enzymes were quantified, and hepatic tissue was examined using Masson’s trichrome staining, histopathology, and transmission electron microscopy.

Biobran administration significantly reduced tumor volume and liver enzyme levels, indicating improved hepatic function. Collagen deposition around hepatic capillaries was markedly diminished. Histological analysis revealed restoration of normal lobular architecture, while ultrastructural examination showed enhanced nuclear integrity, bile duct morphology, and cytoplasmic organelle preservation. Notably, Biobran activated Kupffer cells to target neoplastic cells infiltrating hepatic parenchyma.

Biobran/MGN-3, in combination with paclitaxel, confers substantial hepatoprotective effects in EAC-bearing mice, supporting its potential as a nutraceutical adjunct in cancer therapy.

Chronic lymphedema is a common late effect after completion of head and neck cancer (HNC) treatment, contributing to substantial symptom burden and negatively impacting quality of life. No effective approaches are available to treat this progressive condition. This study aimed to evaluate the preliminary efficacy of photobiomodulation (PBM) therapy for chronic lymphedema in HNC survivors.

This was a pilot, randomized, wait-list controlled trial. Eligible HNC survivors included those with chronic lymphedema after completion of complete decongestive therapy. Participants were randomized (1:1) to 1 of 2 arms: intervention group (active) or wait-list control group (control). The active group received 12 PBM therapy sessions (twice a week for 6 weeks). The control group completed the study assessments and was then offered the same dose of PBM therapy as the active group. Lymphedema and fibrosis (LEF), symptom burden, jaw range of motion, and neck range of motion were measured at baseline, end-of-intervention, 4-week, and 8-week post-intervention.

Twenty five HNC survivors were randomized to the active group (n = 12) and the control group (n = 13). About 91.7% planned PBM treatment sessions were completed. No adverse events were reported. Compared to the control group, the active group demonstrated improvements at 8-week post-intervention in the severity of external LEF (P < .001), symptom burden (eg, Soft Tissue and Neurologic Toxicity subscale, Cohen’s d = − 0.47), and neck range of motion (eg, extension, Cohen’s d = 0.65).

PBM therapy may improve chronic lymphedema-associated outcomes. Future large randomized controlled trials are warranted to examine the efficacy of PBM therapy for HNC-related chronic lymphedema.

Colorectal cancer is one of the most common and fatal cancers worldwide. Despite therapeutic advancements, patients with stage II and III colon cancer often experience recurrences and metastases, particularly to the liver, leading to suboptimal disease-free survival (DFS) rates and decreased long-term survival. Qu-Shi-Jie-Du decoction (QSJDD), a traditional Chinese herbal formula, may prevent cancer recurrence and spread by boosting immunity, reducing inflammation, and inhibiting tumour growth. Preliminary studies have demonstrated that QSJDD reduces liver metastasis in patients with colon cancer. However, robust clinical evidence is required to confirm its efficacy and safety.

This study aims to evaluate the safety and efficacy of QSJDD in preventing colon cancer recurrence and liver metastasis, thereby offering a potential adjunctive therapy to improve patient outcomes.

This multicentre, double-blind, randomised, placebo-controlled trial involves 336 high-risk stage II or III colon cancer patients from 10 Chinese hospitals. Post-surgery and chemotherapy, 168 patients will receive either QSJDD compound granules or a placebo for 6 months, with a 3-year follow-up and evaluations every 6 months. The primary endpoint is to measure the 3-year DFS rate, while secondary endpoints include 1- and 2-year DFS rates, overall survival, and changes in the Traditional Chinese Medicine Dampness Syndrome Scale. Safety and adverse events will be tracked, and blood and gut microbiomes will be analysed to assess QSJDD’s impact on delaying colon cancer metastasis.

This trial will determine the efficacy and safety of QSJDD and provide evidence regarding its role in the adjuvant treatment of colon cancer.

To determine the safety of semi-permanent needles alone or combined with filiform needles in patients treated within a pediatric oncology unit during antineoplastic therapy.

A retrospective review of electronic medical records at the Pediatric Cancer Center Barcelona of Hospital Sant Joan de Déu, Spain. Data were collected from September 1, 2019, to September 30, 2021, including all oncology patients treated with semi-permanent needles at the integrative pediatric oncology unit. The primary outcome was the safety of acupuncture in pediatric cancer patients, specifically assessing infection and bleeding risks, considering sequential levels of neutropenia and thrombocytopenia.

A total of 196 patients (59.2% boys, 40.8% girls) underwent acupuncture. The median age at first treatment was 11.82 years (range: 0.2-34.0 years). The median number of treatments per patient was 4 (range: 1-44), totaling 1107 acupuncture sessions. Of these, 370 (33.4%) were performed in patients with neutropenia and 305 (27.6%) in patients with thrombocytopenia. A total of 9360 semi-permanent needles and 5125 filiform needles were used. No cases of sepsis, local infections, or skin irritation were reported within 72 hours post-removal. One self-limited adverse event—a superficial ear hematoma in a patient with grade 4 thrombocytopenia—was observed, which resolved spontaneously without complications.

Semi-permanent needle therapy, alone or combined with filiform needles, is a safe acupuncture modality when used within pediatric oncology settings, including care contexts that encompass a small number of adolescents and young adults. This study supports the feasibility of incorporating semi-permanent needles into integrative oncology protocols within pediatric oncology practice.

ClinicalTrials.gov (NCT05585463).

First-generation EGFR-TKIs in NSCLC frequently lose efficacy as a result of the secondary EGFR-T790M mutation and a “persistent-STAT3” prosurvival pathway that sustains STAT3–survivin signaling in the face of EGFR inhibition. Preclinical evidence demonstrates that phytochemicals in the JI017 herbal formulation (2:1:1, Angelica gigas: processed Aconitum carmichaeli: Zingiber officinale) can reinstate erlotinib sensitivity in T790M-positive NSCLC, and relevant molecular mechanisms have been examined.

Anti-proliferative activities were evaluated in A549 (EGFR-WT), HCC827 (EGFR Δ19), and H1975 (EGFR L858R/T790M) cells utilizing MTT assays, colony formation, and Annexin V/7-AAD flow cytometry. Mechanistic analyses included immunoblotting for p-EGFR (Tyr1068/1173), p-JAK2, p-STAT3 (Tyr705), PARP, Bcl-2, survivin, and AXL, complemented by RT-qPCR for BIRC5 and AXL transcripts. Drug interaction effects were determined using the Chou–Talalay combination index (CompuSyn). Anti-tumor efficacy was assessed in H1975 xenografts treated for 14 days with vehicle, JI017, erlotinib, or combination therapy; tumors underwent H&E staining and IHC for p-STAT3, survivin, and Ki-67.

JI017 inhibited proliferation in all NSCLC cell lines tested, showing greatest effectiveness in H1975, where it triggered PARP cleavage and suppression of Bcl-2 and survivin expression. In H1975, co-treatment with JI017 and erlotinib led to synergistic growth inhibition, eradicated colony growth, and significantly elevated apoptotic cell populations compared to single treatments. While erlotinib alone reduced p-EGFR and p-JAK2, it left p-STAT3 largely unaltered, reflecting persistent-STAT3 activity. The combination regimen abrogated p-STAT3, further lowered p-EGFR and p-JAK2 levels, diminished BIRC5 mRNA, and decreased both AXL protein and transcript levels. In vivo, the drug combination achieved sustained tumor stasis relative to controls or monotherapy; combination group tumors displayed widespread necrosis and substantial decreases in p-STAT3, survivin, and Ki-67.

These data support the suppression of STAT3–survivin as the primary mechanism by which JI017 sensitizes EGFR-T790M models to erlotinib. The consistent down-regulation of AXL indicates the inhibition of an AXL-mediated bypass that may maintain STAT3 signaling during EGFR blockade, although causality has yet to be confirmed. The marked in-vivo tumor inhibition without observable toxicity underscores the translational promise as a low-toxicity therapeutic adjunct.

JI017 restores erlotinib sensitivity in EGFR-T790M NSCLC by inhibiting STAT3–survivin signaling and possibly reducing AXL-mediated resistance, resulting in durable antitumor effects both in vitro and in vivo. Additional preclinical studies and early-phase clinical assessment of JI017 in combination with erlotinib are justified.

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.

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.

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.

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

Cancer patients increasingly use YouTube for nutritional guidance, yet information quality varies substantially. Existing text-based assessment tools fail to capture audiovisual content characteristics. This study aimed to (1) develop a video-specific assessment tool, (2) evaluate German-language YouTube videos on cancer nutrition, and (3) identify quality indicators for laypersons.

A 20-criteria assessment tool integrating established instruments and video-specific elements was developed. The first 30 YouTube videos on cancer nutrition were systematically evaluated. Spearman correlation and Kruskal-Wallis tests identified associations between video characteristics and quality scores. Interrater reliability was assessed.

Intraclass correlation coefficient indicated good to very good interrater reliability (95% CI: 0.87-0.96). Overall video quality was poor (mean: 38.6/60, SD: 5.3). Videos from hospitals (P = .002) and healthcare organizations (P = .006) scored significantly higher than those from independent persons. Videos with clearly formulated goals (r_s = 0.71, P < .001) and cited references (r_s = 0.43, P = .019) demonstrated stronger evidence-based content. High-quality videos more frequently addressed missing evidence (r_s = 0.51, P = .004). Quality scores inversely correlated with likes (r_s = −0.55, P = .002) and views (r_s = −0.46, P = .01).

YouTube videos on cancer nutrition exhibit substantial quality deficits, even from institutional providers. The validated assessment tool identifies observable quality indicators including clear objectives, scientific citations, transparent discussion of evidence gaps, and institutional authorship. However, no single feature reliably predicts quality. Strengthening digital health literacy and improving evidence-based content production and visibility remain essential priorities.

Lung cancer represents a frequently seen respiratory system malignancy. Sini Decoction combined with cyclophosphamide is demonstrated to remarkably extend survival and improve quality of life of these patients; however, the associated anti-tumor mechanisms are largely unexplored.

The present work focused on investigating the inhibition of tumor cells by Sini Decoction plus cyclophosphamide within the orthotopic lung cancer model and exploring the mechanisms in terms of exosome-based tumor hypoxic microenvironment modulation.

A549-luc2-tdT-2 cells were implanted in left lung of nude mice for establishing the orthotopic lung cancer xenograft model. After 5 days, bioluminescence imaging was conducted for model validation. Mice were later randomized as 4 groups: model, Sini Decoction, cyclophosphamide, as well as Sini Decoction plus cyclophosphamide. Bioluminescence imaging was conducted to assess anti-tumor effects. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring liver and kidney function indicators (ALT, AST, Cr) in serum. Additionally, RT-qPCR and immunohistochemistry were carried out for detecting hypoxia-related factor levels (HIF-1α, VEGF, PDGF-β) within lung tissue. Additionally, characterizations of the separated exosomes were completed with transmission electron microscopy, BCA protein assay, nanoparticle tracking analysis, and Western blotting. Exosomal miR-20a-5p was chosen based on TargetScan database for analysis, while RT-qPCR was completed for validation.

Sini Decoction plus cyclophosphamide dramatically suppressed tumor growth within the orthotopic lung cancer model while ameliorating hepatorenal toxicities, as evidenced by serum liver and kidney function indicators and bioluminescence imaging. Meanwhile, immunohistochemistry showed that the combination therapy markedly downregulated HIF-1α expression in lung tissue and suppressed the expression of its downstream target genes VEGF and PDGF-β, which was also confirmed by RT-qPCR. Additionally, bioinformatic analysis suggested that tumor-derived exosomal miR-20a-5p could target HIF-1α. Isolation and RT-qPCR analysis of lung tissue-derived exosomes demonstrated that the combination therapy significantly downregulated the expression of exosomal miR-20a-5p.

This study indicates that the combination of Sini Decoction and cyclophosphamide can effectively inhibit lung cancer growth and alleviate hepatorenal toxicity. The mechanism may be associated with the amelioration of the tumor hypoxic microenvironment, inhibition of the HIF-1α-mediated tumor hypoxia signaling pathway, and regulation of exosomal miR-20a-5p expression.

Lung metastasis is the primary cause of mortality in aggressive breast cancers, particularly triple-negative breast cancer (TNBC), underscoring the urgent need for effective antimetastatic strategies.

This study aimed to evaluate the efficacy, safety, and molecular mechanisms of Scutellaria barbata water extract (SBW) against breast cancer lung metastasis, with a focus on ferroptosis induction and epithelial-mesenchymal transition (EMT) inhibition.

In vitro and in vivo experiments to evaluate the antitumor and antimetastatic activities of SBW. Proteomic and metabolomic analyses were performed to identify key pathways and bioactive components. Ferroptosis markers and EMT-related proteins were measured by biochemical assays and Western blotting. Arachidonic acid (AA) was validated using in vitro and in vivo functional experiments.

SBW dose-dependently reduced breast cancer cell viability, migration, and invasion in vitro. In vivo, SBW suppressed tumor growth and lung metastasis in 4T1 tumor-bearing mice without systemic toxicity. Proteomic analysis revealed that SBW induced ferroptosis, characterized by increased Fe²⁺, ROS, LPO levels, and upregulation of HO-1/NCOA4, concomitant with downregulation of GPX4. SBW also inhibited EMT by reducing Twist and N-cadherin expression without affecting E-cadherin. Metabolomic profiling identified AA as a critical bioactive component. Functional validation confirmed that AA induced ferroptosis in vitro and inhibited tumor growth/metastasis in vivo.

SBW exerts potent antimetastatic effects through dual mechanisms: induction of ferroptosis via GPX4 inhibition and suppression of EMT via Twist/N-cadherin downregulation. Arachidonic acid plays a central role in mediating ferroptosis.

Radiation-induced quantitative deficiency of T helper 1 (Th1) cells accelerates lung tumor development. Here, we evaluated IL-7R–STAT5 signaling in Th1 recovery after irradiation and examined how catalpol contributes to Th1 reconstitution by targeting this signaling axis in mice.

The recovery characteristics of irradiated Th1 cells, compared with other IFN-γ-producing (IFN-γ⁺) cells, were analyzed in local radiotherapy (LRT) mice challenged with lung melanoma and single low-dose total body irradiation (SLTBI) mice without tumor. IL-7R–STAT5 signaling of Th1 from LRT mice, treated with or without catalpol, was evaluated using flow cytometry and RT-qPCR. The role of IL-7–IL-7R–STAT5 signaling in irradiated Th1 cells was further confirmed in irradiated EL4 cells following administration of IL-7 or catalpol.

Th1 subsets showed delayed recovery in both LRT and SLTBI mice compared with other IFN-γ⁺ cells, and irradiated Th1 cells exhibited decreased activation of IL-7R–STAT5 signaling. Quantitative reduction of Th1 cells increased lung metastasis of B16 melanoma in irradiated mice. Irradiated EL4 cells also displayed decreased IL-7R–STAT5 signaling and reduced IFN-γ production in vitro. Treatment with catalpol could restore IL-7R–STAT5 signaling and promote Th1 recovery following irradiation both in vivo and in vitro. Catalpol-mediated restoration of IL-7R–STAT5 signaling in Th1 provided superior protection against B16 melanoma metastasis to the lung.

IL-7R–STAT5 signaling is required for Th1 recovery after irradiation. Catalpol effectively promotes Th1 cell reconstitution and decreases B16 melanoma metastasis to the lung by enhancing IL-7R–STAT5 signaling. These findings provide new strategies for improving radiotherapy and immunotherapy outcomes in cancer.

Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) or aromatase inhibitor-induced arthralgia (AIA), common side effects of long-term adjuvant endocrine therapy for breast cancer patients, can significantly affect quality of life. Preliminary clinical evidence suggests that fasting may alleviate these symptoms, as demonstrated in conditions such as rheumatoid arthritis and fibromyalgia. This study aims to evaluate the feasibility and acceptability of prolonged therapeutic fasting program, including structured behavioral and educational support, in patients with AIMSS/AIA and explore the applicability of validated measurement tools for assessing symptom burden in preparation for a confirmatory bicentric trial.

This is a bicentric, single-arm, prospective pilot study. We will enroll 54 participants undergoing endocrine therapy with aromatase inhibitors who suffer from AIMSS/AIA. All participants will receive a 7-day online- prolonged therapeutic fasting intervention (max. 350 kcal/day), consisting of vegetable juices and broths under medical supervision. The primary outcome is the feasibility of prolonged therapeutic fasting during aromatase inhibitor therapy assessed through participant adherence to the fasting protocol and completion rate. As a secondary endpoint, we will assess the feasibility of using validated measurement instruments to collect data on symptoms, quality of life, mindfulness, stress, and sleep quality in preparation for a confirmatory trial. The following well established tools will be used: Numeric Rating Scale (NRS), Visual Analog Scale (VAS), Brief Pain Inventory (BPI), Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire–Disability Index (HAQ-DI), WHO-5 Well-Being Index (WHO-5), Mindful Attention Awareness Scale (MAAS), Brief Fatigue Inventory (BFI) and Pittsburgh Sleep Quality Index (PSQI). Specifically, we aim to explore their applicability by evaluating completion rates, participant acceptability, and data completeness within this patient population. Exploratory parameters, including changes in dietary habits, anthropometric data, and cancer-related fatigue will be tracked to contextualize the feasibility findings and inform outcome selection for a future confirmatory trial. An accompanying N-of-1 trial using a mobile application (StudyU) and qualitative interviews will give more insight into individual and subjective changes.

If the intervention proves feasible and well accepted, these findings will support the development of a confirmatory trial designed to investigate the potential clinical benefits and underlying mechanisms of fasting in AIMSS/AIA. Long-term studies incorporating biomarkers and microbiota analysis could further explore the mechanisms underlying symptom improvement and guide personalized treatment strategies.

Trial registration: ClinicalTrials.gov.

NCT06172088. Registered 14 December 2023.

URL: https://clinicaltrials.gov/study/NCT06172088.

There is a lack of large-scale evidence regarding the prognostic impact of Chinese herbal medicine (CHM) on patients with lung cancer. This paper aimed to conduct a nationwide population-based study to investigate the role of CHM for patients with lung cancer with standard treatment.

Patients diagnosed with lung cancer and treated with standard therapy between 2013 and 2015 were retrospectively identified from National Health Insurance Research Database and Taiwan Cancer Registry. Patients were classified into a CHM group and a non-CHM group based on prior medical records. Kaplan-Meier analysis was performed to estimate overall survival (OS) between each group.

A total of 7351 matched patients were included in the outcome analysis and comparison, with 3677 patients in the CHM cohort and 3674 patients in the non-CHM cohort. The mean age of our patients was 60.68 ± 11.26 years, and 56% of our patients were female. Our results demonstrates that patients who received CHM had significantly longer OS compared to those who did not receive CHM (HR: 0.59, 95% CI: 0.556-0.625, P < .0001). In subgroup analysis, survival differences were not significant for stage I-II disease, whereas OS was significantly better in the CHM group among patients with stage III-IV disease. Multivariable analysis showed CHM usage was found to significantly influence OS. The most commonly used single CHM was Hedyotis diffusa Willd and compound CHM was San-Zhong-Kui-Jian-Tang.

Our nationwide population-based study suggested that CHM in conjugation with standard treatment was associated with improved survival in patients with advanced lung cancer. Integrating cancer treatment with CHM could be adopted in the treatment of lung cancer to improve prognosis.

This study delves into the therapeutic effects of combining GEM and Angelica polysaccharide (APS) on triple-negative breast cancer.

In vitro, proliferation, apoptosis of 4T-1 cells and MDSC were detected by flow cytometry. Migration of 4T-1 cell was detected by scratch healing experiment after treatment by GEM (0, 2.5, 5 μM), APS (160,320 mg/ml), or GEM + APS (2.5 μM + 160 mg/ml, 5 μM + 320 mg/ml). In vivo, 4T-1 cells were injected into the mammary fat pad under the mammary gland of BALB/c mice to establish an orthotopic breast cancer tumor model. They were randomly divided into control group (0.9% normal saline + ultrapure water), GEM group (0.9% normal saline preparation, 100 mg/kg, intraperitoneal injection twice a week), APS group (ultrapure water preparation, 200 mg/kg, intraperitoneal injection once a day), GEM + APS group (GEM 100 mg/kg, intraperitoneal injection twice a week and APS 200 mg/kg, intraperitoneal injection once a day) for 3 weeks. The proportion of immune cells in the spleen and tumor microenvironment were detected by flow cytometry, immunofluorescence and Mindray hematology analyzer. The tumor volume and weight, spleen index were recorded.

The in vitro experimental results revealed that GEM effectively inhibited the proliferation and migration of 4T-1 cells and induced apoptosis in both 4T-1 cells and MDSCs. In contrast, APS had no impact on 4T-1 cells or MDSCs. The in vivo experimental findings indicated that compared with the single-drug treatment groups, the combination treatment of GEM + APS more effectively regulated the proportion of peripheral and local anti-tumor MDSCs and T cells, and more significantly curbed the progression of breast cancer in mice.

APS can exert a synergistic effect through immune regulation to enhance the therapeutic efficacy of GEM on triple-negative breast cancer. It aims to offer novel insights for the clinical application of combining GEM with immunotherapy for patients with triple negative breast cancer.

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.

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.

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.

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.

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

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.

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.

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).

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

This trial was registered with Clinical.Trials.gov (Number: NCT01441752, July 14, 2011).

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related mortality worldwide. Exploring novel preventive and therapeutic strategies is thus imperative. This study evaluated the therapeutic and protective effects of boswellic acid (BA), both alone and in combination with low-dose gamma radiation, against diethylnitrosamine (DEN)-induced HCC in male albino rats.

A total of 90 rats were randomly assigned to 5 groups: Control, DEN, DEN + BA, DEN + Radiation, and DEN + Radiation + BA. Liver carcinogenesis was induced with DEN (20 mg/kg, administered orally for 6 weeks). BA (250 mg/kg) was administered orally for 8 weeks following cancer induction. Radiation (0.5 Gy, twice over 2 weeks) was applied to relevant groups after tumor induction. The study assessed serum biochemical markers, including colorimetric detection of liver enzymes (ALT and AST), oxidative stress markers (malondialdehyde, SOD activity), ELISA detection inflammatory cytokines Nuclear factor kappa-light-chain-enhancer of activated B cells, Tumor necrosis factor alpha (NF-κB and TNF-α), and the expression level of proliferation marker Janus kinase, Signal transducer and activator of transcription 3, Mitogen-activated protein kinase (JAK, STAT-3, and MAPK), via qRT-PCR, angiogenesis Vascular Endothelial Growth Factor, transforming growth factor beta (VEGFA, TGF-β), levels of apoptotic marker (Caspase-3, and Granzyme B) and Bax (Bcl-2-associated X protein), Bcl-2 (B-cell lymphoma 2) by ELISA. Histopathological examination was performed to evaluate tissue alterations.

Results demonstrated that BA, especially when combined with radiation, improved hepatic histopathology, reduced liver injury, suppressed oxidative stress and inflammation (NF-κB and TNF-α), and promoted apoptosis evidenced by increased Bax, caspase-3, granzyme B levels associated with significant decrease in Bcl-2 level. The combined treatment also inhibited tumor proliferation and angiogenesis by downregulating the expression levels of (JAK/STAT3, MAPK), VEGF-A, and TGF-β concentrations. These findings suggest that BA, synergistically with low-dose gamma radiation, offers a promising strategy for HCC therapy, supporting its potential as an adjuvant in HCC management.