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Keywords = adjunct cancer therapy

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27 pages, 767 KB  
Review
Phytochemicals from Agro-Industrial By-Products for Breast Cancer Prevention and Therapy: Molecular Mechanisms and Circular Bioeconomy Perspective
by Angela Maffia, Federica Alessia Marra, Santo Battaglia, Carmelo Mallamaci, Mariateresa Russo and Adele Muscolo
Pharmaceuticals 2026, 19(6), 934; https://doi.org/10.3390/ph19060934 (registering DOI) - 13 Jun 2026
Viewed by 32
Abstract
Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their [...] Read more.
Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their pleiotropic biological activities and relatively low toxicity. In parallel, increasing attention has been directed toward agro-industrial by-products generated during food processing, which represent abundant and sustainable sources of valuable phytochemicals. This review provides a comprehensive overview of recent advances in the identification, extraction, and biological evaluation of phytochemicals derived from plants and agro-industrial residues, using pomegranate (Punica granatum) peels, onion (Allium cepa) skins, and citrus by-products as representative examples of phytochemical-rich agro-industrial residues. These by-products are rich in polyphenols, flavonoids, and other secondary metabolites—including punicalagins, ellagic acid, quercetin, hesperidin, and naringin—that have demonstrated significant antioxidant, anti-inflammatory, and anticancer properties. Recent in vitro and in vivo studies indicate that these compounds can modulate key molecular pathways involved in breast cancer initiation and progression, such as oxidative stress regulation, apoptosis induction, inhibition of cell proliferation, and suppression of signaling cascades including PI3K/Akt, NF-κB, and MAPK pathways. Furthermore, the valorization of agro-industrial waste offers a sustainable strategy to recover high-value bioactive compounds while reducing environmental impact. Overall, phytochemicals obtained from plant materials and food processing by-products represent promising functional agents for breast cancer prevention and therapy, although further studies are required to improve bioavailability, elucidate mechanisms of action, and validate their clinical potential. Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants—4th Edition)
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22 pages, 1510 KB  
Systematic Review
Osteopathic Manipulative Treatment as a Complementary and Integrative Approach for Cancer Supportive Care: A Systematic Review
by Stuti Patel, Christopher J. Thimons, Hannah Steele, Misha Mathur, David Boesler and Anupam Bishayee
Cancers 2026, 18(12), 1881; https://doi.org/10.3390/cancers18121881 - 9 Jun 2026
Viewed by 266
Abstract
Background: Cancer is one of the leading causes of disability in both the United States and worldwide. Its high global prevalence is accompanied not only by the burden of the disease itself but also by the adverse effects of treatment, which can [...] Read more.
Background: Cancer is one of the leading causes of disability in both the United States and worldwide. Its high global prevalence is accompanied not only by the burden of the disease itself but also by the adverse effects of treatment, which can significantly diminish patients’ quality of life (QoL). Osteopathic manipulative treatment (OMT), an emerging complementary therapy, seems to show promise in the improvement in quality of life (QoL) in these patients. The purpose of this systematic review is to evaluate the effectiveness of OMT as a complementary and integrative therapy for the relief of symptoms and improved functional capabilities in cancer patients. Methods: The literature search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using PubMed, Scopus, Science Direct and Web of Science databases. A risk of bias analysis was conducted by evaluating the included randomized controlled trials to assess domains, such as randomization, intended intervention, incomplete outcome data, outcome measurement, and selective reporting. Between the 20 randomized controlled trials and observational studies, information regarding OMT in the treatment of general cancers, oral, pediatric, head and neck, gynecological, breast, and gastric cancers was collected. Results: Our analysis displayed a patient-reported increase in QoL, especially through the reduction in pain and lymphedema, as well as an increase in overall functional capabilities. Conclusions: Overall, the findings underscore the potential role of OMT as an adjunctive therapy for patients with a wide range of cancers, contributing to symptomatic management and enhanced QoL. Full article
(This article belongs to the Special Issue Supportive Care in Cancer)
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14 pages, 1438 KB  
Article
Capsaicin as a Phytochemical Adjuvant Enhancing Cisplatin Efficacy in Nsclc: In Vitro and In Vivo Evidence
by Onur Onguncan, Nevruz Alis, Tulay Mutlu, Abdullah Yalcin, Oner Sonmez, Buse Birinci, Aybike Sarioglu-Bozkurt, Elif Bayram and Sabire Guler
Pharmaceuticals 2026, 19(6), 884; https://doi.org/10.3390/ph19060884 - 1 Jun 2026
Viewed by 209
Abstract
Background/Objectives: Non-small-cell lung carcinoma (NSCLC) accounts for approximately 85% of lung cancers and remains a leading cause of cancer-related mortality. Although cisplatin is a cornerstone chemotherapeutic agent, its clinical effectiveness is limited by drug resistance and systemic toxicity. Capsaicin (CAP), a bioactive [...] Read more.
Background/Objectives: Non-small-cell lung carcinoma (NSCLC) accounts for approximately 85% of lung cancers and remains a leading cause of cancer-related mortality. Although cisplatin is a cornerstone chemotherapeutic agent, its clinical effectiveness is limited by drug resistance and systemic toxicity. Capsaicin (CAP), a bioactive phytochemical derived from chili peppers, has demonstrated anticancer activity in several tumor types and has been investigated as a potential adjunct to conventional chemotherapy. Methods: An experimental study was conducted using A549 NSCLC cells and a xenograft mouse model. Cells were treated with CAP (50–300 µM), cisplatin (1 µg/mL), or their combination. Cell proliferation and apoptosis were evaluated using sulforhodamine B (SRB) assay, immunocytochemistry, and Western blot analysis. In vivo, tumor growth inhibition, histopathological alterations, and immunohistochemical expression of Ki-67 and cleaved caspase-3 were assessed. Results: Low CAP concentrations (50–100 µM) slightly increased proliferation, whereas concentrations ≥ 150 µM significantly reduced cell viability and induced apoptosis. Cisplatin monotherapy markedly suppressed proliferation and activated apoptosis. Bliss independence analysis demonstrated concentration-dependent synergy between CAP and cisplatin, with maximal synergy scores reaching 28.1 at 100 µM CAP. Combination treatment at CAP concentrations ≥ 150 µM produced the strongest antiproliferative effect in vitro and the highest tumor growth inhibition in vivo (88%). CAP did not further enhance cisplatin-induced apoptosis but significantly reinforced proliferation suppression with reduced Ki-67 expression. Conclusions: CAP exhibits biphasic dose-dependent effects in NSCLC and enhances cisplatin antitumor efficacy predominantly through proliferation suppression, supporting its further evaluation as an adjunctive phytochemical in cisplatin-based NSCLC therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
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25 pages, 560 KB  
Review
What Does Bacteria Have to Do with Cancer? The Influence of the Body’s Microbiota on Cancer in Cats and Dogs
by Patrycja Kasperska, Iga Horodyska, Julia Mateja, Aleksandra Sobierajewicz, Marta Miszczak, Karolina Bierowiec and Joanna Bubak
Int. J. Mol. Sci. 2026, 27(11), 5005; https://doi.org/10.3390/ijms27115005 - 1 Jun 2026
Viewed by 386
Abstract
The body’s microbiota plays a fundamental role in maintaining homeostasis and influences immune function, metabolism, and tissue integrity. A growing body of research suggests that fluctuations in the composition and abundance of individual microbiota populations may influence cancer development and the effectiveness of [...] Read more.
The body’s microbiota plays a fundamental role in maintaining homeostasis and influences immune function, metabolism, and tissue integrity. A growing body of research suggests that fluctuations in the composition and abundance of individual microbiota populations may influence cancer development and the effectiveness of therapy. The condition of microbiota dysbiosis has been demonstrated to induce chronic inflammation, immune system dysregulation, and, most significantly, modulation of molecular pathways that promote tumorigenesis. The efficacy and toxicity of cancer treatment can be influenced by the composition of the microbiota. Bacteria can modify the effectiveness and toxicity of chemotherapy and immunotherapy by affecting drug metabolism and the body’s immune response. In contrast, the development of anticancer therapies that utilize bacteria is gaining increasing interest. This alternative to conventional treatment utilizes the natural ability of certain bacterial species to selectively colonize hypoxic and necrotic environments. The exploration of natural and genetically modified bacteria as vectors for the delivery of cytotoxins, immunomodulators, or therapeutic genes in the combat of cancer is a current area of research. In addition, their capacity to stimulate an antitumor immune response is also exploited. Preclinical investigations in animals have demonstrated the efficacy of this therapeutic approach, underscoring the promise of bacterial therapies as either an adjunct to conventional treatment or as a standalone strategy for combating cancer. This article synthesizes the current knowledge regarding the role of microbiota in carcinogenesis in animals and discusses recent developments in the field of bacterial therapies. The text also addresses the challenges, safety considerations, and future perspectives associated with translating microbiota-targeted and bacterial therapies into veterinary and comparative oncology. Full article
(This article belongs to the Section Molecular Oncology)
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26 pages, 13892 KB  
Review
Xenobiotic Sulforaphane in Head and Neck Cancer: Beyond the Nrf2 Pathway
by Alessandro Polizzi, Rossella Rotondo, Sabrina Donati Zeppa, Monia Cecati, Magdalena Smolik, Valentina Schiavoni, Angelo Montana, Valentina Pozzi, Davide Sartini, Roberto Campagna and Gaetano Isola
J. Xenobiot. 2026, 16(3), 99; https://doi.org/10.3390/jox16030099 - 1 Jun 2026
Viewed by 353
Abstract
Head and neck cancers (HNCs) represent a major global health burden and remain associated with substantial morbidity and limited therapeutic options, particularly in advanced or recurrent disease. Increasing interest has focused on naturally derived bioactive compounds with potential chemopreventive and therapeutic properties. Sulforaphane, [...] Read more.
Head and neck cancers (HNCs) represent a major global health burden and remain associated with substantial morbidity and limited therapeutic options, particularly in advanced or recurrent disease. Increasing interest has focused on naturally derived bioactive compounds with potential chemopreventive and therapeutic properties. Sulforaphane, a dietary xenobiotic isothiocyanate derived from glucoraphanin in cruciferous vegetables, has attracted attention due to its ability to modulate redox balance, epigenetic regulation, and multiple oncogenic signaling pathways. This manuscript reviews current evidence regarding the biological effects of sulforaphane in HNCs. Particular attention is given to the molecular mechanisms underlying its modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a key regulator of cellular antioxidant and detoxification responses that can be activated by sulforaphane. Several studies indicate that sulforaphane can inhibit tumor growth through several mechanisms beyond Nrf2 activation, including induction of apoptosis, cell cycle arrest, epigenetic modulation, and suppression of oncogenic signaling pathways. In addition, sulforaphane has been shown to enhance the efficacy of conventional treatments, including chemotherapy, radiotherapy, and photodynamic therapy. Overall, the literature suggests that sulforaphane may represent a promising chemopreventive or therapeutic adjunct in HNC, although further clinical investigation is required to clarify its translational potential. Full article
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21 pages, 2468 KB  
Article
Peripheral CD8+ T Cell Dynamics and Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Following Bronchoscopic Cryotherapy and Pembrolizumab-Based Therapy
by Gediminas Vasiliauskas, Evelina Žemaitė, Erika Skrodenienė, Lina Poškienė, Skaidrius Miliauskas and Marius Žemaitis
Cancers 2026, 18(11), 1793; https://doi.org/10.3390/cancers18111793 - 31 May 2026
Viewed by 193
Abstract
Background: Bronchoscopic cryotherapy may enhance anti-tumor immunity and improve the effect of immune checkpoint blockade, but CD8+ T cell dynamics after cryotherapy combined with pembrolizumab-based therapy in metastatic non-small cell lung cancer (NSCLC) remain insufficiently characterized. Methods: In this prospective, exploratory, [...] Read more.
Background: Bronchoscopic cryotherapy may enhance anti-tumor immunity and improve the effect of immune checkpoint blockade, but CD8+ T cell dynamics after cryotherapy combined with pembrolizumab-based therapy in metastatic non-small cell lung cancer (NSCLC) remain insufficiently characterized. Methods: In this prospective, exploratory, randomized, controlled, single-center study, metastatic NSCLC patients were assigned to bronchoscopic cryotherapy performed 7 ± 1 days before first-line pembrolizumab-based therapy or to standard treatment alone. Peripheral blood mononuclear cells were analyzed by flow cytometry at baseline, week 3, and week 6. CD8+ T cell subsets defined by CD45RO, CD28, granzyme B (GzB), IFNγ, Ki-67, and PD-1 were evaluated in relation to treatment group, radiologic response, progression-free survival (PFS), and overall survival (OS). Results: Flow cytometry was performed in 76 patients, including 34 in the cryotherapy group and 42 in the control group. Cryotherapy was associated with a treatment-specific increase in circulating GzB+ CD8+ T cells by week 6. In contrast, Ki-67+ CD8+ and GzB+Ki-67+ cells increased in both treatment groups, suggesting that early peripheral CD8+ proliferation was largely shared across pembrolizumab-based therapy. Radiologic responders demonstrated more sustained proliferative CD8+ dynamics, most consistently reflected by increased CD28+ Ki-67+ cells. In exploratory landmark survival analyses, a higher week-3-to-baseline GzB+ Ki-67+ CD8+ ratio showed a hypothesis-generating association with longer PFS and OS. Conclusions: In metastatic NSCLC patients receiving first-line pembrolizumab-based therapy, the addition of bronchoscopic cryotherapy was associated with peripheral CD8+ T cell remodeling toward enhanced cytotoxic activity. Proliferative CD8+ T cell changes were associated with radiologic response and better survival. These findings support bronchoscopic cryotherapy as a potential immune-modulating adjunct and warrant validation in larger studies. Full article
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15 pages, 3315 KB  
Article
Oxidative Stress-Related DNA Damage in Patients with Idiopathic Granulomatous Mastitis: A Prospective Case–Control Study
by Ceren Gonultas, Adem Akcakaya, Abdurrahim Kocyigit, Gulnihal Sisman, Berrin Papila, Mehmet Velidedeoglu and Hasan Dagmura
J. Clin. Med. 2026, 15(11), 4228; https://doi.org/10.3390/jcm15114228 - 30 May 2026
Viewed by 232
Abstract
Background/Objectives: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory disease of the breast that may present with recurrent and treatment-resistant courses and can clinically and radiologically mimic breast cancer. Despite its benign nature, IGM may significantly impair quality of life, [...] Read more.
Background/Objectives: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory disease of the breast that may present with recurrent and treatment-resistant courses and can clinically and radiologically mimic breast cancer. Despite its benign nature, IGM may significantly impair quality of life, and its underlying pathophysiology remains unclear. This study aimed to evaluate oxidative stress and DNA damage in patients with IGM. Methods: In this prospective case–control study, 28 patients with clinically and histopathologically confirmed idiopathic granulomatous mastitis who had not received corticosteroid or immunosuppressive therapy within the previous six months were enrolled. An age-matched control group of 27 healthy women was included. Venous blood and urine samples were collected for the assessment of total oxidant status (TOS), total antioxidant status (TAS), and calculation of the oxidative stress index (OSI). Mononuclear leukocyte DNA damage was evaluated using the alkaline Comet assay, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured by ELISA. Sociodemographic data, laboratory and imaging results of the patients were also evaluated. Results: The mean ages of the patient and control groups were 37.3 ± 5.3 and 35.4 ± 8.6 years, respectively, with no significant difference (p = 0.081). Patients exhibited significantly higher inflammatory markers and oxidative stress parameters, including TOS, OSI, and urinary 8-OHdG (p < 0.05), whereas TAS did not differ between groups (p = 0.534). Comet assay analysis demonstrated significantly increased tail intensity (%) and tail moment in the patient group (p = 0.029 and p = 0.016). Conclusions: IGM is associated with increased oxidative stress and mononuclear leukocyte DNA damage. These findings suggest that oxidative stress-induced DNA damage may play a role in the pathophysiology of IGM and highlight the potential value of antioxidant-based therapeutic strategies as adjunctive treatment options. Full article
(This article belongs to the Section General Surgery)
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17 pages, 10110 KB  
Article
Integrated Epithelial Models Reveal Anti-Inflammatory and Barrier Modulatory Properties of Ozoile in Inflammatory Bowel Disease
by Daniele Bravoco, Giuseppina di Paola, Valeria Lucci, Carlo Calabrese, Serena Vella, Domenico Montesano, Rosarita Tatè, Rebecca Leandri, Gionata De Vico, Salvatore Valiante, Teresa Barra, Geppino Falco, Giuliana Napolitano and Pellegrino Mazzone
Antioxidants 2026, 15(6), 664; https://doi.org/10.3390/antiox15060664 - 25 May 2026
Viewed by 262
Abstract
Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition, with therapy-resistant patients undergoing surgery and a high risk of developing colorectal cancer. Novel therapeutic approaches have shown limited efficacy in IBD treatment, highlighting the need for safer and more personalized strategies. [...] Read more.
Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition, with therapy-resistant patients undergoing surgery and a high risk of developing colorectal cancer. Novel therapeutic approaches have shown limited efficacy in IBD treatment, highlighting the need for safer and more personalized strategies. The potential of natural compounds to modulate inflammation suggests their use as a potential adjunct therapy for IBD patients. Methods: Intestinal epithelial cells organoids (IECOs) were derived from IBD and non-IBD tissues from IBD patients, and levels of inflammation markers and epithelial barrier permeability were assayed using qRT-PCR, WB, IF and leaking assays in the presence of Ozoile, an extra virgin olive oil enriched in ozonides. The Luciferase-based IBD-like organoid platform was generated for preliminary screening of anti-inflammatory drugs. Results: In this study, we showed that IBD-ECOs recapitulate tissue architecture and pathological state. We showed that Ozoile has anti-inflammatory and epithelial barrier modulatory effects and that the Luciferase IBD-like organoid model is sensitive to anti-inflammatory compounds. Conclusions: Using IECOs, the specific anti-inflammatory and regenerative properties of Ozoile were assessed. Notably, our study highlights the potential of an IBD-like organoid platform to use in high-throughput screenings for rapid selection of anti-inflammatory drugs. Full article
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18 pages, 563 KB  
Review
The Role of Laser Modalities in Melanoma Management: Critical Analysis of Local Control and Palliative Applications
by Francesco Russano, Luigi Dall’Olmo, Francesco Callegarin, Davide Brugnolo, Paolo Del Fiore, Giuseppe Sciacca, Rocco Caminiti, Marco Rastrelli and Simone Mocellin
Cancers 2026, 18(10), 1672; https://doi.org/10.3390/cancers18101672 - 21 May 2026
Viewed by 426
Abstract
Cutaneous melanoma is an aggressive skin cancer. While laser therapy is established for non-melanoma skin cancers, its role in melanoma remains controversial and largely unsupported by robust clinical evidence. The gold standard for melanoma management remains surgical excision, as it allows for definitive [...] Read more.
Cutaneous melanoma is an aggressive skin cancer. While laser therapy is established for non-melanoma skin cancers, its role in melanoma remains controversial and largely unsupported by robust clinical evidence. The gold standard for melanoma management remains surgical excision, as it allows for definitive histopathological diagnosis, Breslow thickness measurement, and surgical margin assessment, which are essential for accurate staging. This narrative review analyzed preclinical and clinical studies evaluating various laser modalities, including Nd:YAG, CO2, pulsed dye, photodynamic therapy (PDT) and photothermal therapy (PTT), for efficacy, recurrence rates, and limitations in cutaneous melanoma management. Nd:YAG laser (1064 nm) showed potential for local control in thin stage I melanomas, reporting a low local recurrence rate of 0–0.7% and favorable 5-year survival in small, non-randomized cohorts. CO2 laser (10,600 nm) provides effective palliation and local control for in-transit or unresectable metastases, but local recurrence is highly variable, reaching up to 46.7%. Photodynamic therapy showed variable efficacy, although Chlorin e6 achieved complete local regression in a small series of metastases. A critical limitation of laser therapy is the irreversible destruction of tissue, which precludes these vital assessments. Therefore, laser treatment should be cautiously reserved for cases where standard surgery is not feasible, acknowledging that it may interfere with the evaluation of curative outcomes and accurate staging. Laser therapy is a valuable minimally invasive adjunct for local control in selected patients who are poor surgical candidates or require palliative care. Routine use is restricted by the lack of randomized controlled trials. Future studies should prioritize combination strategies with systemic or immunotherapeutic approaches to enhance overall outcomes. Full article
(This article belongs to the Section Methods and Technologies Development)
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11 pages, 362 KB  
Article
Neutrophil–Lymphocyte–Platelet Ratio for Predicting Bacteremia in Immunosuppressed Cancer Patients: A Retrospective Diagnostic Accuracy Study
by José Manuel Martinez, Ana Espírito Santo, Pedro Leite, Ana Pinho, Ana Rita Carneiro, Ana Maria Oliveira, Diana Ramada and Rui Medeiros
Biomedicines 2026, 14(5), 1170; https://doi.org/10.3390/biomedicines14051170 - 21 May 2026
Viewed by 343
Abstract
Background: Early identification of bacteremia in immunosuppressed cancer patients remains difficult, especially in neutropenia. This study evaluated the diagnostic accuracy of NLR, PLR, and NLPR for identifying bacteremia and sepsis in patients undergoing blood culture episode. Methods: We conducted a retrospective diagnostic accuracy [...] Read more.
Background: Early identification of bacteremia in immunosuppressed cancer patients remains difficult, especially in neutropenia. This study evaluated the diagnostic accuracy of NLR, PLR, and NLPR for identifying bacteremia and sepsis in patients undergoing blood culture episode. Methods: We conducted a retrospective diagnostic accuracy study at a tertiary oncology center between January 2023 and December 2024. All bacteremia identified were included as cases. Culture-negative episodes were subsequently sampled as controls using a frequency-matching strategy. Hematological parameters were obtained within ±24 h of first blood culture episode. Diagnostic performance was assessed using ROC curve analysis and multivariable logistic regression. Results: Of 369 screened episodes, 337 from 323 unique patients were included after excluding 31 records. NLPR showed the highest accuracy for bacteremia (AUC 0.730; 95% CI 0.671–0.788). The optimal cut-off was 0.038 (sensitivity 69.2%, specificity 72.3%) and remained consistent after excluding episodes with antibiotic therapy (AUC 0.768), corticosteroids (AUC 0.708), or growth factor use (AUC 0.718). In severe neutropenia, NLPR showed the highest accuracy (AUC 0.887; 95% CI 0.797–0.978). In multivariable analysis (n = 304), NLPR remained independently associated with bacteremia (p < 0.001), with good model discrimination (AUC 0.815; 95% CI 0.763–0.866). Diagnostic performance for sepsis was lower and not statistically significant. Conclusions: These findings suggest that NLPR may represent a simple, inexpensive, widely accessible adjunctive biomarker to support early bacteremia risk stratification in immunosuppressed cancer patients, particularly in patients with severe neutropenia. Although its overall discrimination was comparable to isolated lymphocyte count, NLPR may provide clinically relevant contextual information by integrating multiple dimensions of immune dysregulation. Further prospective multicenter validation is warranted. Full article
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18 pages, 624 KB  
Review
Ketogenic and Low-Carbohydrate Diets in Prostate Cancer: Metabolic Rationale, Preclinical Evidence, and Preliminary Clinical Data
by Silvia Manfrini, Andrea Malgeri, Carmine Mone, Ludovica Di Francesco, Giulia Pecora, Rossella Mazzilli, Giuseppe Defeudis, Manon Yeganeh Khazrai and Antongiulio Faggiano
J. Clin. Med. 2026, 15(10), 3946; https://doi.org/10.3390/jcm15103946 - 20 May 2026
Viewed by 561
Abstract
Background: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Growing evidence indicates that metabolic syndrome components, including obesity, insulin resistance, and hyperglycemia, contribute to PCa development, and progression to more aggressive form. [...] Read more.
Background: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Growing evidence indicates that metabolic syndrome components, including obesity, insulin resistance, and hyperglycemia, contribute to PCa development, and progression to more aggressive form. At the same time, standard treatments such as androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) significantly improve oncologic outcomes but are associated with adverse metabolic effects, including increased fat mass, insulin resistance, and sarcopenia, potentially worsening patients’ overall metabolic profile and quality of life. Tumor progression in PCa is strongly driven by androgen receptor (AR) signaling, which is closely linked to cellular metabolic reprogramming, highlighting metabolism as a potential therapeutic target. Aim: The aim of this study was to evaluate and synthesize current evidence on the role of the ketogenic diet (KD) in PCa, with particular emphasis on its interaction with hormonal therapies, underlying metabolic and endocrine mechanisms, and its potential application as an adjunctive strategy in integrated oncologic care. Results: The KD, characterized by high fat and very low carbohydrate intake, induces a metabolic state of ketosis that reduces circulating glucose, insulin, and insulin-like growth factor 1 (IGF-1), potentially counteracting metabolic alterations associated with PCa and its treatments. Preclinical studies consistently demonstrate that carbohydrate restriction and KD can slow tumor growth, modulate key oncogenic pathways such as PI3K/AKT/mTOR, reduce systemic insulin signaling, and enhance survival in prostate cancer models. Additionally, emerging evidence suggests possible synergistic effects when KD is combined with standard therapies, including ADT and immunotherapy. Clinical data, although limited, indicate that low-carbohydrate dietary interventions may improve metabolic parameters and could delay biochemical progression, as suggested by increased prostate-specific antigen (PSA) doubling time. However, results across studies remain heterogeneous, and robust evidence on long-term oncologic outcomes is lacking. Conclusions: Overall, the KD represents a promising but still experimental strategy in PCa management, requiring careful nutritional supervision to avoid adverse effects such as unintended weight loss or sarcopenia. Further well-designed randomized clinical trials are needed to clarify its safety, efficacy, and role in routine clinical practice. Full article
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18 pages, 798 KB  
Article
Integrated Chinese and Western Medicine for Breast Cancer Patients with Depression—Association with Survival and Healthcare Utilization: A Nationwide Retrospective Cohort Study in Taiwan
by Chingying Liang, Yen-Chun Huang, Jiun-Liang Chen, Chi Wen Chen and Mingchih Chen
Healthcare 2026, 14(10), 1406; https://doi.org/10.3390/healthcare14101406 - 20 May 2026
Viewed by 342
Abstract
Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief [...] Read more.
Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article
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15 pages, 684 KB  
Case Report
Kinesio Taping as an Adjunctive Nursing Intervention for Lower Extremity Edema in ICU Patients: A Case Series
by Yeshua Aguilar-Salgado, Antonio Hernández-Bastida, María de la Paz Lara-Martínez, Blanca Estela García-Pérez, Lorena García-Morales and Alejandra Valdivia-Flores
Reports 2026, 9(2), 158; https://doi.org/10.3390/reports9020158 - 19 May 2026
Viewed by 273
Abstract
Background and Clinical Significance: Kinesio tape (KT) has gained popularity as an adjunctive approach for treating edema during the rehabilitation phase, following traumatic events, as well as for managing edema in breast cancer patients. Its goal is to reduce swelling and improve [...] Read more.
Background and Clinical Significance: Kinesio tape (KT) has gained popularity as an adjunctive approach for treating edema during the rehabilitation phase, following traumatic events, as well as for managing edema in breast cancer patients. Its goal is to reduce swelling and improve mobility in the affected extremity; however, its use in critically ill patients remains limited. To our knowledge, this is the first report of its application in this population. Case presentation: This case series involved three patients in the Intensive Care Unit (ICU) who presented with lower extremity edema. One patient developed a cerebrovascular event secondary to moderate traumatic brain injury and two patients experienced sepsis. KT was applied, and extremity circumference, Godet sign, and Stemmer sign were assessed. The bandage was reapplied every 24 h over a 5-day period, with daily evaluations performed by the same nursing staff to ensure measurement consistency. All three patients exhibited a reduction in extremity circumference, along with improvement or resolution of the Godet and Stemmer signs. No adverse effects associated with KT were observed. Conclusions: Our results suggest that KT may be a beneficial adjunctive therapy for edema reduction in ICU patients. Larger-scale studies are needed to confirm its clinical value. Full article
(This article belongs to the Section Critical Care/Emergency Medicine/Pulmonary)
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26 pages, 21655 KB  
Article
Aerosol-Derived Graphene Oxide Nanofilm Suppresses Adhesion-Dependent Survival and Migration in Pancreatic Ductal Adenocarcinoma Cells
by Aleksandra Ciechońska, Mateusz Wierzbicki, Barbara Nasiłowska, Barbara Wójcik, Wojciech Skrzeczanowski, Katarzyna Ziółkowska and Marta Kutwin
Int. J. Mol. Sci. 2026, 27(10), 4341; https://doi.org/10.3390/ijms27104341 - 13 May 2026
Viewed by 387
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive malignancy, characterized by rapid progression, early metastasis, and resistance to conventional therapies. Increasing evidence indicates that the behavior of residual tumor cells is strongly influenced by physicochemical properties of their microenvironment. Surface engineering strategies using [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive malignancy, characterized by rapid progression, early metastasis, and resistance to conventional therapies. Increasing evidence indicates that the behavior of residual tumor cells is strongly influenced by physicochemical properties of their microenvironment. Surface engineering strategies using nanostructured materials may therefore represent a complementary approach to modulating cancer cell activity. In this study, we investigated whether a graphene oxide (GO) aerosol nanofilm modifies the biological behavior of PDAC cells in vitro. The GO aerosol (4.5 g/L) was characterized using STEM, DLS, zeta potential measurements, LIBS, EDX, and FTIR spectroscopy. Ultrastructural analysis revealed thin, wrinkled GO sheets forming partially overlapping lamellar structures, while physicochemical characterization confirmed a highly oxidized stable nanomaterial. Human PDAC cell lines (BxPC-3 and AsPC-1) were cultured on GO-modified substrates to assess morphology (SEM), metabolic activity (XTT assay), migratory capacity (wound healing assay over 72 h), and expression of genes related to proliferation and epithelial–mesenchymal transition (EMT) by RT-qPCR. GO nanofilm significantly reduced cell viability and inhibited migration in both cell lines. SEM analysis demonstrated shortened cytoplasmic projections and altered membrane integrity. Gene expression profiling revealed cell line-dependent transcriptional responses, including modulation of components of the PI3K/AKT/mTOR pathway and EMT-associated markers. Collectively, our findings demonstrate that GO aerosol nanofilm alters PDAC cell morphology, viability, and migratory behavior in vitro. Surface-mediated modulation of tumor cell activity may represent a promising adjunct strategy for limiting residual cancer cell survival and metastatic potential. Full article
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Article
Identification of Changes in the Transcriptome Profile of Human Hepatoma HepG2 Cells Exposed to Combined Sorafenib and Cannabis Treatment
by Krittakarn Udomkritayachai, Theeraphat Thiamsuk, Takdanai Jarujamrat, Panaphas Kudikhong, Sira Raksakhom, Phitsamai Suphattana, Natthanan Khankham, Palapoom Thanawong and Supakit Khacha-ananda
Int. J. Mol. Sci. 2026, 27(10), 4342; https://doi.org/10.3390/ijms27104342 - 13 May 2026
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Abstract
Cannabis-derived compounds are increasingly used as adjuncts in cancer therapy due to their reported antiproliferative and pro-apoptotic effects. However, potential drug–herb interactions with standard anticancer agents—namely sorafenib—remain unclear. This study investigated the interaction between cannabis and sorafenib, together with transcriptomic alterations in human [...] Read more.
Cannabis-derived compounds are increasingly used as adjuncts in cancer therapy due to their reported antiproliferative and pro-apoptotic effects. However, potential drug–herb interactions with standard anticancer agents—namely sorafenib—remain unclear. This study investigated the interaction between cannabis and sorafenib, together with transcriptomic alterations in human hepatoma HepG2 cells. Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the Combenefit program. RNA sequencing was performed to characterize gene expression changes across treatment groups. Combination analysis demonstrated concentration-dependent synergistic effects at intermediate doses. Transcriptomic profiling revealed that the combination treatment induced a broader and more distinct set of differentially expressed genes compared with single treatments. Integrated enrichment analyses showed consistent activation of stress- and inflammation-related pathways, including tumor necrosis factor-α via nuclear factor-kappaB (TNF/NF-κB), mitogen-activated protein kinase (MAPK), janus kinase/signal transducers and activators of transcription (JAK–STAT), oxidative stress, and p53-mediated apoptosis, alongside suppression of metabolic and proliferative processes. While several pathways were shared across treatments, the combination group exhibited a more coordinated transcriptional response, including enrichment of integrated stress response, cytokine signaling, endoplasmic reticulum stress, and epigenetic regulation. These findings were supported by increased reactive oxygen species production and apoptosis, particularly in the combination group. Overall, cannabis may potentiate sorafenib activity through enhanced cellular stress and anti-proliferative signaling. Full article
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