Abstract Biofield therapies (BTs) are gaining attention as potential complementary treatments for cancer. Some devices have been developed to mimic the energetic or electromagnetic fields emitted by BT practitioners. We previously reported that BT significantly inhibited growth and invasiveness of pancreatic cancer cells in vitro and in relevant animal models. To identify which steps of the metastatic cascade are affected by BT and to elucidate potential antimetastatic mechanisms in pancreatic ductal adenocarcinoma (PDAC), we conducted in vivo studies using metastatic mouse models. In a KPCY orthotopic model, BT treatment significantly reduced the percentage of visible liver nodules by 61.3% and 54.6% compared with the colony control (CC) and sham control (SC) groups, respectively (p < 0.05). Imaging of YFP+ cells in the liver tissues revealed a significant reduction in disseminated tumor cells in the BT group relative to CC and SC groups (p < 0.05). In a tail-vein injection model, lung tissues from BT treated mice exhibited a significant 59.6% reduction in YFP+ signal intensity compared with SC mice, supporting the conclusion that BT suppresses metastatic dissemination of PDAC cells. BT treated mice bearing PANC-1 orthotopic tumors had significantly lower levels of tumor cell-free DNA (11.5 ± 4.6 ng/μl) compared with sham control (24.7 ± 7.9 ng/μl; p < 0.01), suggesting that BT treatment impairs tumor cell intravasation. This is consistent with our previous findings that BT inhibits EMT in human PDAC PANC-1 cells. Additionally, BT induced anoikis in PANC-1 cells, indicating that BT may also reduce PDAC cell survival in circulation. To investigate whether BT affects metastatic colonization, both PANC-1 and KPCY cells were exposed to BT and subjected to adhesion assay using phalloidin staining and fibronectin quantification, as fibronectin is a key regulator of cell adhesion. PANC-1 cells exposed to BT for 15 mins showed an average of 14 ± 4 adhered cells per field, compared with 96 ± 35 in the SC group (p < 0.0001). Similarly, fibronectin-based cell adhesion measurements showed a 58.3% decrease in BT-treated PANC-1 cells relative to SC (p < 0.001). BT also significantly reduced F-actin intensity in PANC-1 cells (p < 0.01), with similar results observed in KPCY cells after 30 min of treatment. Epigenetic profiling further revealed that BT modulated the expression of genes involved in actin cytoskeleton regulation. Collectively, these results demonstrated that biofield therapy suppressed multiple metastatic steps including cell invasion/migration, intravasation, survival in circulation, and colonization ultimately contributing to its antimetastatic effects in PDAC models. These processes may be mediated in part through alterations in cytoskeleton organization, particularly actin dynamics. Citation Format: Peiying Yang, Sharmistha Chakraborty, Phuong Nguyen, Defeng Deng, Amanda Eckstrom, Andrew Cusimano, Daoyan Wei, Lorenzo Cohen. Biofield therapy inhibits pancreatic cancer invasion and metastasis by modulating multiple steps of metastatic cascade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2228.

ABSTRACT Background The high mortality of pancreatic ductal adenocarcinoma (PDAC) underscores the need for novel treatments. We investigated the potential role of human biofield therapy (BT) in modifying tumorigenic processes in murine and human PDAC cells through a series of in vitro and in vivo studies. Methods Cell viability and ultrastructure changes were examined by PrestoBlue assay and Transmission Electron Microscope, respectively. Cell voltage potentials were assessed using DiBAC4 staining. Both FOXM1 CRISPR KO and Tet‐on FOXM1 overexpressing PDAC cells were used for the mechanistic studies. Antitumor efficacy was tested in orthotopic models using human PANC‐1 and mouse KPCY cells. Results Multiple mouse and human PDAC cell lines exposed to BT (three different therapists using a standardized procedure) showed significantly reduced proliferation compared to sham control (SC) and incubator control (IC) cells across multiple studies. BT induced swollen mitochondria in PANC‐1 cells and increased G1 cell cycle arrest in PANC‐1, L3.7, and COLO357 cells. BT also downregulated key cell cycle regulators including FOXM1 in PANC‐1 and L3.7 cells (p < 0.05). BT led to a 36.7% reduction of cell voltage potential measured in PANC‐1 cells (p < 0.01), with similar effects in MiaPaCa‐2 and KPCY cells. Furthermore, BT reduced the invasiveness in PANC‐1, L3.7, and COLO357 cells, an effect influenced by FOXM1 gene expression. BT inhibited the primary tumor growth and liver metastasis of PANC‐1 and KPCY cells in orthotopic mouse models (p < 0.05). Conclusions These novel findings support the potential of BT to influence growth and metastasis of pancreatic cancer cells and warrant further investigation.

In this case study, a self-described biofield therapy (BT) therapist and a sham therapist participated in multiple (n = 24) treatment and control (non-treatment) sessions under double-blind conditions. During the treatment phases, BT and sham therapists attempted to influence mice with cancer and control mice, alternating BT with rest phases where no such efforts were made. Both the 64-channel EEG of the human participants and the simultaneous 3-channel EEG and 1-channel EMG of the mice were recorded. For human participants and for the analysis of human and mouse EEG comodulation, the EEG experimental setup was a 2 × 2 design, contrasting mouse type (cancer vs. control) against session type (BT vs. non-treatment; N = 8 in each of the four groups). For the mice EEG, the experimental setup was a 2x2x2 design, contrasting mouse type (cancer vs. control) against session type (treatment vs. non-treatment) and human participant (BT participant vs. sham participant). Although no changes in spectral power were detected in mice, a significant increase in theta band coherence indicates that this type of biofield therapy may influence large-scale neural coordination rather than localized activity. Concurrently, robust and reproducible alterations in the therapist's EEG across all frequency bands during treatment periods, irrespective of mouse condition, suggest a consistent physiological signature associated with the act of intentional BT. Treatment was associated with changes in EEG coherence and spectral correlation between human and mouse signals. In particular, we observed an interaction in which treatment differentially affected brain-to-brain coherence in cancer versus control mice. These findings describe condition-dependent alterations in coupled physiological measures and suggest a complex relationship between human and mouse neural activity during BT sessions, while remaining agnostic about the underlying mechanism. We also outline the study's limitations and potential for follow-up investigations, acknowledging that these exploratory physiological findings do not have any clinical implications and should not be interpreted as justification for cancer treatment or as a substitute for evidence-based medical care.

Importance: Lifestyle and supportive care interventions may improve treatment tolerance, long-term health behaviors, and survivorship outcomes among breast cancer patients receiving radiotherapy. Few randomized trials have integrated nutrition, exercise, stress management, and psychosocial counseling concurrently with radiotherapy and extended across survivorship. Objective: To evaluate the effects of a comprehensive lifestyle intervention (CompLife) initiated during radiotherapy and maintained for 12 months on body composition, fitness, quality of life, symptoms, and nutrition. Design, Setting, and Participants: Randomized clinical trial at a single cancer center. Eligible women were aged ≥18 years with stage II/III breast cancer scheduled for radiotherapy, BMI ≥ 24.5, and ≥2 lifestyle risk factors. Participants were randomized to CompLife or standard of care (SOC). Assessments occurred at baseline, end of radiotherapy, and 3, 6, and 12 months. The primary outcome of recurrence is ongoing; this report examines prespecified secondary outcomes. Interventions: CompLife included 6 weeks of in-person counseling integrating nutrition, physical activity, mindfulness, stress management, and psychosocial support; twice-weekly exercise, diet, and mind-body sessions during radiotherapy; and telehealth counseling for 12 months. SOC participants received standard educational materials. Main Outcomes and Measures: Secondary outcomes included visceral adipose tissue (VAT), weight, waist circumference, fitness (VO2 max, strength), SF-36 Physical and Mental Component Summary scores, MD Anderson Symptom Inventory scores, mindfulness (FFMQ), and dietary fiber intake. Results: Ninety-five women were randomized (CompLife, n = 50; SOC, n = 45). CompLife participants had lower VAT at 3 and 6 months (e.g., 3 months: 118 vs. 141 cm2; p = 0.044) and greater improvements in VO2 max at 3 (23.4 vs. 18.8 mL/kg/min; p = 0.025) and 6 months. SF-36 Physical scores improved to within population norms for CompLife at all follow-ups but remained below norms in SOC. CompLife participants reported fewer symptoms at 12 months (MDASI: 1.3 vs. 2.5; p = 0.014). Fiber intake was consistently higher in CompLife participants (20.5 g vs. 14.0 g; p < 0.001). The results should be interpreted with caution due to the large number of comparisons among the secondary outcomes. Conclusions and Relevance: A multidisciplinary lifestyle intervention delivered during radiotherapy and extended across survivorship produced clinically meaningful improvements in body composition, fitness, diet, and patient-reported outcomes. The findings suggest potential value in integrating structured lifestyle and psychosocial counseling into oncology care and warrant confirmation in larger multicenter trials with mature recurrence endpoints.

BACKGROUND & AIMS:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major omega-3 polyunsaturated fatty acids (ω-3 PUFAs), derived from fish oil are widely used as dietary supplements and are United States Food and Drug Administration (FDA)-approved for treating hypertriglyceridemia. However, studies evaluating their effects on colorectal tumorigenesis (CRT) have produced conflicting results, and the underlying reasons for this variability remain unclear. 15-Lipoxygenase-1 (ALOX15), a key enzyme involved in the generation of resolvins from EPA and DHA, is frequently lost in the human colon during CRT. We therefore investigated whether ALOX15 expression in the colon influences the effects of EPA and DHA on resolvin production and CRT. METHODS:The effects of intestinal transgenic ALOX15 expression on resolvin generation and colorectal tumor formation in response to various formulations of EPA and DHA dietary supplementations were evaluated using multiple mouse models that closely recapitulate human CRT. Transgenic human ALOX15 was expressed in colonic epithelial cells under the control of various promoters in the mice. EPA, DHA and their metabolite resolvin levels were assessed in colonic epithelial cells and sera by liquid chromatography and tandem mass spectrometry, whereas production of chemokines and cytokines (eg, C-C motif chemokine ligand 3-5 [CCL3-5], interleukin-1 beta [IL-1β], interleukin-6 [IL-6]) was measured. Abundance of tumor-associated macrophages and CD8+ T cells was evaluated by immunohistochemistry and immunofluorescence staining. RESULTS:Dietary EPA and DHA supplementation in control mice lacking transgenic human ALOX15 expression resulted in minimal changes in resolvin production and had variable effects on CRT. In contrast, EPA and DHA uniformly inhibited colorectal tumor formation in mice engineered to express human ALOX15 in their intestinal epithelial cells. These antitumorigenic effects were associated with increased resolvin production, reduced colonic expression of CCL2, IL-1β, and IL-6, decreased tumor-associated macrophages, and enhanced infiltration of CD8α+ T cells in the tumor microenvironment. In vitro, resolvin E (RvE)1 and resolvine D (RvD)5-the predominant resolvins generated by ALOX15-suppressed CCL2, IL-1β, and IL-6 production and promoted phagocytic activity in murine macrophages. CONCLUSIONS:Colonic ALOX15 expression is essential for enabling EPA and DHA to generate resolvins and consistently suppress CRT. The status of colonic ALOX15 expression should be taken into account when developing prevention strategies that utilize EPA and DHA to decrease the risk of colon cancer.

BackgroundThere is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.MethodsIn this double-blind, double dummy, randomized, 2 x 2 crossover trial, patients with >= 4 cancer-related pain were randomly assigned to receive either iv hydromorphone 1 mg administered over 2 minutes (fast iv push) or 15 minutes (slow iv piggyback) during the first treatment period. Participants crossed over to receive the alternate treatments during the second period after a 6-hour washout period.ResultsEighty-three eligible patients were allocated to slow-fast (42, 51%) or fast-slow (41, 49%). Both treatments produced low abuse potential scores with no difference between them (mean peak Drug Effect Questionnaire "drug liking" subscale of fast [24.00] vs. slow [24.34], p = .82). A total of 92% and 94% of slow and fast iv hydromorphone recipients, respectively, had similar improvements in pain scores over 120 minutes (odds ratio, 0.67; 95% confidence interval, 0.06-5.82, p = .65). Drowsiness was more frequent with the fast than the slow rate (50% vs. 29% at 15 minutes [p = .03] and 52% vs. 31% at 60 minutes [p = .03]).ConclusionsSlow iv hydromorphone infusion resulted in similar abuse liability potential and pain improvement but less sedation than fast injection. These findings, taken together, suggest that the slow infusion may be considered as a first-line modality for iv opioid administration in hospitalized patients requiring intermittent opioids for pain.

In this case study, a self-described biofield therapy (BT) practitioner (participant) took part in multiple (n = 60) treatment and control (non-treatment) sessions under double-blind conditions. During the treatment phases, the participant provided BT treatment at a distance of about 12 inches from the cells, alternating with rest phases where no such efforts were made. Human pancreatic cancer cell activity was assessed using three markers - cytoskeleton changes (tubulin and β-actin) and Ca2+ uptake. The study examined changes in the participant's physiological parameters including electroencephalogram (EEG) and heart rate measures during the treatment of: (1) live cells and (2) either dead cells or medium only with no cells (control group). Changes in cellular outcomes and if there was an association between the participant's physiological parameters and cellular outcomes were examined. The experimental setup was a 2 × 2 design, contrasting cell type (live vs. control) against session type (treatment vs. non-treatment). Parallel sham-treated control cells were examined for changes in the cell parameters over time while controlling for the presence of a person in front of the cells mimicking the distance and movements of the participant. The participant's physiological data, including 64-channel EEG and heart rate, were continuously monitored throughout these sessions. We observed significant (p < 0.01) spectral changes in the participant's EEG during BT treatment in all frequency bands of interest, as well as in heart rate variability (HRV) (RMSSD measure; p < 0.01). We also observed significant differences in beta and gamma EEG and HRV (pNN50 measure) when the participant treated live but not control cells (p = 0.02). However, no interaction between treatment and cell type (live vs. dead cells/medium-no cells) was observed. We observed Ca2+ uptake increased over time during both BT and sham treatment, but the increase was significantly less for the BT group relative to the sham-treatment controls (p = 0.03). When using Granger causality to assess causal directional associations between cell markers and participant's physiological parameters, EEG measurements showed significant bidirectional causal effects with cell metrics, especially β-actin and intracellular Ca2+ levels (p < 0.000001). These outcomes suggest a complex relationship between physiological responses and cellular effects during BT treatment sessions. Given the study's limitations, follow-up investigations are warranted.

Pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) remain the leading causes of cancer-related mortality, with poor outcomes. This study comprehensively evaluated the mechanisms of polymeric micelles co-encapsulating cyclopamine (CPA) and paclitaxel (PTX) (M-CPA/PTX, ONP-001) and the effectiveness against HCC and PDAC. The dual-drug delivery system targets embryonic signaling pathways, such as Hedgehog (Hh), which drives tumor progression and resistance. CPA and PTX were encapsulated in micelles (∼55 nm in size) to improve bioavailability and tumor concentrations. Preclinical experiments included in vitro assays for cytotoxicity, tumorsphere, and colony formation in both cancer cell lines. In vivo models included orthotopic Kras* cell implanted PDAC and spontaneous HCC in transgenic LAP-tTA/TRE-MYC mice. The antitumor efficacy was examined by intravenously injection of ONP-001 at 2.5, 5.0, and 7.5 mg/drug equivalent/kg thrice weekly for 4 weeks, as well as combination regimens with irreversible electroporation (IRE) and an immune checkpoint inhibitor. Survival, tumor burden, immune modulation, and cytokine profiles were analyzed using Kaplan-Meier survival curves, bioluminescence imaging, and multiplex cytokine assays. In the PDAC model, ONP-001 significantly extended median survival at 2.5 mg equivalent drug/kg (p<0.01), 5.0 mg/kg (p<0.0001), and 7.5 mg/kg (p<0.05) compared untreated control. ONP-001 administered at 7.5 mg/kg displayed shorter median survival than 5.0 mg/kg suggesting that the optimal regimen tested was 5 mg/kg. ONP-001 reprogrammed tumor stroma, and reduced cancer stem cell (CSC)-associated tumorsphere formation. Combination of ONP-001 with IRE and anti-PD-1 further enhanced survival and immune infiltration, overcoming PDAC’s immunosuppressive microenvironment. In HCC, ONP-001 significantly inhibited tumor growth and colony formation. Tumor cytokine profiling revealed significant reductions in markers associated with CSC maintenance (e.g., IL-15, IL-33) and tumor progression, highlighting an anti-inflammatory effect on the tumor microenvironment. Studies in the transgenic HCC model also confirmed significantly greater antitumor efficacy for ONP-001, with no observed hepatotoxicity, compared to sorafenib treatment. ONP-001 was an effective therapeutic strategy for PDAC and HCC, targeting CSCs, modulating the stroma, and enhancing immunotherapy, at 5.0 mg/kg, TIW, with enhanced benefits when in combination regimens. Ongoing studies will further characterize the pharmacokinetics, tumor uptake and biodistribution of both drugs. The data supports further development of ONP-001 for potential future clinical development. Qiu-Xu Teng, Guodong Zhang, Lu Dai, Defeng Deng, Ping Pan, Diana S-L Chow, Guorong Ma, Peiying Yang, Chun Li. Development and comprehensive preclinical evaluation of dual-drug polymeric micelles ONP-001 for PDAC and HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3141.

Radiation‑induced lung injury (RILI) is a prevalent complication following thoracic radiation, and currently there is a lack of effective intervention options. The present study investigated the potential of Compound Kushen Injection (CKI), a botanical drug, to mitigate inflammatory responses in mice with RILI, along with its underlying mechanisms of action. C3H mice underwent total lung irradiation (TLI) and intraperitoneal injection of CKI (2, 4 or 8 ml/kg) once daily for 8 weeks. Pre‑radiation treatment with 4 or 8 ml/kg CKI starting 2 weeks before TLI or concurrent treatment of 8 ml/kg CKI with TLI led to a significantly longer overall survival compared with the TLI vehicle‑treated group. Micro‑computed tomography evaluations showed that concurrent treatment with 8 ml/kg CKI was associated with a significantly lower incidence of RILI. Histological evaluations revealed that concurrent CKI (4 and 8 ml/kg) treatment significantly reduced grades of lung inflammation. Following radiation at 72 h, TLI plus vehicle‑treated mice had significantly elevated serum IL6, IL17A, and transforming growth factor β (TGF‑β) levels compared with non‑irradiated normal mice. Conversely, mice that received TLI plus CKI displayed lower cytokine levels than those in the TLI plus vehicle‑treated mice. Immunohistochemistry staining showed a reduction of TGF‑β positive cells in the lung tissues of TLI mice after CKI treatment. The concurrent TLI CKI‑treated mice had a significantly reduced cyclooxygenase 2 (COX‑2) activity and COX‑2 metabolites compared with TLI vehicle‑treated mice. These data highlight that CKI substantially reduced radiation‑induced lung inflammation, mitigated RILI incidence, and prolonged overall survival.

Statistically significant violations of the Clauser–Horne–Shimony–Holt (CHSH) inequality are the “gold standard” test for quantum entanglement between spatially separated systems. Here, we report an experimental design that implements a CHSH test between bioelectric state variables for a human subject and bioelectric and/or biochemical state variables for cultured human cells in vitro. While we were unable to obtain evidence for entanglement with this design, observing only classical correlation, we report lessons learned and suggest possible avenues for future studies.

Background: The SPIRIT-TCM Extension 2018 was created to guide the design and reporting of Traditional Chinese Medicine (TCM) clinical trial protocols. This study aims to investigate the extent of concordance with this guideline in the relevant field of cancer care research. Methods: A scoping review of TCM cancer trial protocols published in English and Chinese since January 2019 was conducted. Five major academic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, and China National Knowledge Infrastructure) were searched. Concordance with the SPIRIT-TCM Extension 2018 was assessed by descriptive analysis. Results: Fifty-three TCM cancer care trial protocols were identified, comprising 23 acupuncture, 26 Chinese herbal medicine (CHM), and 4 Tai Chi/Qigong (TCQ) interventions. The majority of the checklist items had a low rate of concordance, especially in the reporting of quality control and safety, dosage, TCM diagnostic patterns, possible interactions between Western Medicine and TCM interventions, and TCM-related outcome assessments. Conclusions: Although the SPIRIT-TCM Extension 2018 guideline was established through extensive Delphi consultation, there are low rates of concordance between published TCM cancer care clinical trial protocols with the guideline. Further research is necessary to understand the low rate of concordance and how scientific rigors of reporting can be improved in TCM cancer care research.

ImportancePatients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia.ObjectiveTo compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia.Design, Setting, and ParticipantsA randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia.InterventionsParticipants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment.Main Outcomes and MeasuresPatient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy–General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat.ResultsA total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, −6.67; 95% CI, −11.08 to −2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, −4.41; 95% CI, −8.62 to −0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy–General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001).Conclusions and RelevanceThe findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH.Trial RegistrationClinicalTrials.gov Identifier: NCT02589938

Abstract The NIH categorizes Biofield Therapy (BT) as therapeutic approaches within energy medicine that involve using the body's energy field (biofield) for therapeutic benefit. Although controversial, in some cases devices have been developed that mimic the electromagnetic fields (EMF) that are emitted from people when delivering BTs. We previously reported that BT significantly inhibited the growth of pancreatic cancer cells and liver metastasis in their relevant animal models mediated in part through modification of the cell cycle, reductions in cell voltage potentials, and down regulation of PI3K/Akt pathways. We expanded this research to examine the potential role of BT in anti-invasiveness in human pancreatic ductal adenocarcinoma (PDAC) cells and animal models. We found that PANC-1 cells treated with BT (15 min) displayed 55% less invading cells than that of untreated incubator control and sham control cells (P < 0.001). Similar results were observed in human PDAC L3.7 cells and mouse pancreatic cancer KPCY cells. These experiments were replicated 8 times for Panc-1 cells and 4 times for L3.7 cells. Additionally, migration capacity was tested using the transwell migration and scratch assays. Consistent with the result of cell invasion assays, BT treatment also led to significant reduction of migration of PANC-1 and L3.7 cells by 34% and 41%, respectively, compared to sham controls. Two additional therapists independently replicated the anti-invasiveness and anti-migratory effects of BT on these PDAC cells. This suggests the replicability of these findings across studies and therapists. In a repeated PANC-1 mouse orthotopic model, we found that only a third of BT treated mice had visible liver nodules whereas liver metastasis was observed in more than half of mice in the untreated colony control and sham control groups. Furthermore, BT treatment significantly reduced liver tumor burden by 73% compared to that of the sham control group (p < 0.05), which was similar to that observed in the previous study. Similar to the prior PANC-1 mouse model, in the current study BT treatment had only a moderate impact on the growth of primary pancreatic tumor. We assessed certain markers indicative of cell status as well as pathways associated with migration and invasion and these will be presented at the meeting. Our findings suggest that exposure to BT reduced cellular invasion and migration processes and profoundly reduced metastasis of pancreatic tumor in an animal model. This study is in part supported by Emerald Gate Charitable Trust. Citation Format: Peiying Yang, Sharmistha Chakraborty, Phuong Nguyen, Defeng Deng, Andrew Cusimano, Daoyan Wei, Lorenzo Cohen. Biofield therapy suppressed invasion and metastases of human pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4128.

Abstract Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are widely used dietary supplements and FDA-approved treatments. The reported impacts of fish oil, DHA, and EPA on colorectal carcinogenesis (CRC) have spurred debates, as certain studies suggest promotional effects while numerous others emphasize suppressive effects. Nevertheless, resolvins, oxidative metabolites of EPA and DHA, exhibit the ability to inhibit crucial pathways (such as TNF-α and IL-1β) that contribute to CRC. 15-lipoxygenase-1 (ALOX15) plays a crucial role in the oxidative metabolism of DHA and EPA, ultimately leading to the formation of resolvins. However, ALOX15 expression is commonly lost during human CRC. Whether loss of ALOX15 expression modulates the effects of DHA and EPA on CRC remains to be elucidated. We therefore conducted the experiments in preclinical CRC mouse models induced by Azoxymethane or Apc gene mutation to explore the hypothesis that ALOX15 expression in colonic epithelial cells regulates DHA and EPA metabolism to generate resolvins, subsequently influencing CRC outcomes. We found that 1) DHA and EPA exert differential effects on CRC, which can be further modified by factors such as their formulation (e.g., ethyl ester versus triglyceride); 2) targeted transgenic expression of ALOX15 in the intestines of mice (referred to as ALOX15-Gut mice) markedly augmented the production of resolvins and concurrently suppressed CRC; 3) the predominant products from the expressed ALOX15 enzymatic activity were identified as 17-HDHA and resolvin D5; and 4) the effects ALOX15 on increasing resolvin generation and suppressing CRC were consistent across various promoters used to drive ALOX15 transgenic expression in mice. These findings collectively underscore the profound importance of ALOX15 intestinal expression as a host-related factor in resolvin generation from EPA and DHA, which subsequently contributes to the suppression of CRC. Citation Format: Xiangsheng Zuo, Yoshiyuki Kiyasu, Yi Liu, Micheline Moussalli, Bo Wei, Peiying Yang, Imad Shureiqi. 15-lipoxygenase-1 modulation of colonic resolvin production to suppress colorectal carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2182.

Importance Patients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia. Objective To compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia. Design, Setting, and Participants A randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia. Interventions Participants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment. Main Outcomes and Measures Patient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat. Results A total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, -6.67; 95% CI, -11.08 to -2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, -4.41; 95% CI, -8.62 to -0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy-General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001). Conclusions and Relevance The findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH. Trial RegistrationClinicalTrials.gov Identifier: NCT02589938

BackgroundPaclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors.Patients and methodsPatients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1.ResultsOur study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response.ConclusionsThe combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 polyunsaturated fatty acids (ω-3 PUFAs) derived from fish oil, are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. However, studies investigating the effects of EPA and DHA on colorectal carcinogenesis (CRC) have yielded conflicting results. The factors that determine these discrepant results remain unknown. Resolvins, oxidative metabolites of EPA and DHA, inhibit key pro-tumorigenic cytokine and chemokine signaling of colorectal cancer (e.g., IL-6, IL-1β, and CCL2). 15-lipoxygenase-1 (ALOX15), a critical enzyme for resolvin generation is commonly lost during human CRC. Whether ALOX15 expression, as a host factor, modulates the effects of EPA and DHA on CRC remains unknown. Therefore, we evaluated the effects of ALOX15 transgenic expression in colonic epithelial cells on resolvin generation by EPA and DHA and CRC in mouse models representative of human CRC. Our results revealed that 1) EPA and DHA effects on CRC were diverse, ranging from suppressive to promotive, and these effects were occasionally altered by the formulations of EPA and DHA (free fatty acid, ethyl ester, triglyceride); 2) EPA and DHA uniformly suppressed CRC in the presence of intestinal ALOX15 transgenic expression, which induced the production of resolvins, decreased colonic CCL3-5 and CXCL-5 expression and tumor associated macrophages while increasing CD8 T cell abundance in tumor microenvironment; and 3) RvD5, the predominant resolvin produced by ALOX15, inhibited macrophage generation of pro-tumorigenic cytokines. These findings demonstrate the significance of intestinal ALOX15 expression as a host factor in determining the effects of EPA and DHA on CRC. Significance:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. Studies of EPA and DHA effects on colorectal carcinogenesis (CRC) have revealed inconsistencies; factors determining the direction of their impact on CRC have remained unidentified. Our data show that EPA and DHA effects on CRC were divergent and occasionally influenced by their formulations. More importantly, intestinal 15-lipoxgenase-1 (ALOX15) expression modulated EPA and DHA effects on CRC, leading to their consistent suppression of CRC. ALOX15 promoted EPA and DHA oxidative metabolism to generate resolvins, which inhibited key pro-tumorigenic inflammatory cytokines and chemokines, including IL-6. IL-1β, and CCL2. ALOX15 is therefore an important host factor in determining EPA and DHA effects on CRC.

A. Three key criteria to define aberrant crypt include: (1) the area occupied by the crypt and its pericryptal zone is greater than the surrounding normal crypts; (2) irregular shape of the luminal opening; and (3) the epithelial lining is thicker and darker than that of the surrounding crypt. B. Images of ACF with various aberrant crypts/focus (40x magnification).

Abstract The poor prognosis and limited therapeutic options for human hepatocellular carcinoma (HCC), the most common form of liver cancer, highlight the urgent need to identify novel therapeutic modalities. Here, we describe the antitumor activity and underlying molecular mechanisms of a novel Na+/K+-ATPase inhibitor RX108 in human HCC cells and its xenograft model. RX108 dose-dependently inhibited HCC cell proliferation in vitro and tumor growth in a xenograft mouse model, and that the inhibition was associated with induction of apoptosis. Mechanistically, RX108 significantly downregulated alanine serine cysteine transporter 2 (ASCT2) protein expression and reduced glutamine and glutamate concentration in HCC cells and tumors. In addition, RX108 exposure led to a significant decrease in cell energy metabolism in Huh7 and Hep3B cells, including decreased levels of glutathione, NADH, NADPH, and mitochondrial respiration oxygen consumption rate. Furthermore, HCC cells exhibited evidence of glutamine addiction; the antiproliferative effect of RX108 was dependent on glutamine transport. Clinically, elevated ASCT2 mRNA expression in HCCs was associated with unfavorable survival. Taken together, these findings reveal a novel approach to target glutamine metabolism through inhibiting Na+/K+-ATPase and provide a rationale for using RX108 to treat HCC in patients whose tumors express ASCT2 at high levels. RX108 is currently under clinical development.