Search Results (8,778)

Interferons (IFNs) are well-known immunostimulants involved in both innate and adaptive immune responses. These multifunctional proteins mediate an early antiviral response and have pronounced immunomodulatory and antiproliferative properties. Due to their potency, IFNs have been used not only in the treatment of viral infections but also various other diseases. However, the use of IFNs in antitumor therapy has been limited by the frequent severe side effects, which reduced their appeal for the treatment of cancer. In this review, we focused on current data on recombinant IFNs used for anticancer therapy, as well as the development of promising IFN-based gene therapy approaches, with a focus on their safety and therapeutic efficacy. We also highlighted various types of IFNs and their application niches in the treatment of not only cancers in combination therapy but also of certain rare diseases. Taken together, this review improves our understanding of the existing IFN applications in cancer therapy, the disadvantages of using IFNs, and possible approaches for their improvement. Full article

Background: Cancer remains a major global health challenge, with current therapies often limited by high toxicity and poor selectivity. Lipopeptides, due to their amphiphilic architecture and synthetic accessibility, have emerged as promising anticancer agents. In this study, the in vitro cytotoxic potential and structure–activity relationships (SARs) of a library of 60 synthetic linear lipopeptides (LLPs), including lipopeptide–peptoid chimeras generated via the Ugi four-component reaction, were evaluated against four cancer cell lines (B16F10, HeLa, HT-29, and PC3). Methods: Cytotoxicity was assessed using MTT and crystal violet (CV) assays, and the natural cyclic lipopeptide surfactin was included as a reference. SAR analysis explored the effects of C-terminal functional groups, lipophilic tail length, peptide core size, and side chain modifications. Mechanistic studies involved cell cycle analysis, apoptosis markers (Annexin V/PI staining, caspase-3 activation), and oxidative stress assessment (ROS/RNS and NO production). Results: Several synthetic LLPs showed potent and selective anticancer activity, with IC₅₀ values approximately 3–15 times lower than that of surfactin and with minimal toxicity toward non-cancerous NIH3T3 fibroblasts. Key structural determinants for activity included the presence of a C-terminal ester group, a lipophilic tail of 14–19 carbon atoms, and a tetrapeptide core. LLPs containing phenyl or azide side chains further enhanced cytotoxicity in a cell line-dependent manner. Mechanistic investigations confirmed that active LLPs induce caspase-dependent apoptosis, cell cycle arrest, and oxidative stress. These findings highlight that the synthetic LLPs demonstrate high in vitro anticancer efficacy with favorable selectivity. Conclusions: Synthetic LLPs exhibit potent and selective anticancer activity in vitro. SAR insights and mechanistic findings support their development as next-generation lipopeptide-based therapeutics. Full article

Background: Dihydromyricetin (DHM), a natural dihydroflavonol, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, its potential mechanism of action in the individualized therapy of hepatocellular carcinoma (HCC) remains unclear. Methods: Potential therapeutic targets of DHM were identified using the Swiss Target Prediction database. The overlap between these targets and differentially expressed genes in HCC was analyzed to determine therapeutic targets. A prognostic model was constructed based on these genes, and patients were stratified into high- and low-risk groups. The associations between risk scores, clinical pathological characteristics, and overall survival were analyzed using Cox regression and Kaplan–Meier survival curves. The relationships between risk score and immune cell infiltration, immunosuppressive factors, and anticancer drug susceptibility were evaluated. Results: A three-gene prognostic model was established, comprising DTYMK, MAPT, and UCK2, designated as DHM-target genes (DHMGs). Patients in the high-risk group had significantly shorter overall survival than those in the low-risk group (p < 0.001; HR [95% CI] = 4.953 [2.544, 9.645]). Higher risk scores were correlated with more advanced tumor stages and grades. Comprehensive analysis of the tumor immune microenvironment revealed that high-risk patients exhibited significantly elevated TIDE scores, increased Treg cell infiltration, and markedly reduced stromal scores. Conclusions: This study developed a prognostic model based on the potential target genes of DHM in HCC. This model effectively stratifies HCC patients, identifying a high-risk subgroup characterized by an immunosuppressive microenvironment. These findings provide a theoretical foundation for exploring DHM as a promising natural adjuvant for cancer immunotherapy. Full article

Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. This complex disease arises from tissues such as the ovarian surface epithelium, fallopian tube epithelium, endometrium, or ectopic Müllerian components and is characterized by diverse histological and molecular traits. Standard treatments like surgery, chemotherapy, and radiation have limited effectiveness and high toxicity. Targeted therapies, including poly (ADP-ribose) polymerase PARP inhibitors, anti-angiogenics, and immune checkpoint inhibitors (ICIs), face obstacles such as adaptive resistance and microenvironmental barriers that affect drug delivery and immune responses. Factors in the tumor microenvironment, such as dense stroma, hypoxia, immune suppression, cancer stem cells (CSCs), and angiogenesis, can reduce drug efficacy, worsen prognosis, and increase the risk of recurrence. Research highlights impaired immune function in ovarian cancer patients as a contributor to recurrence, emphasizing the importance of immunotherapies to target tumors and restore immune function. Preclinical studies and early clinical trials found that natural killer (NK) cell-based therapies have great potential to tackle ovarian tumors. This review explores the challenges and opportunities in treating ovarian cancer, focusing on how NK cells could help overcome these obstacles. Recent findings reveal that engineered NK cells, unlike their primary NK cells, can destroy both stem-like and differentiated ovarian tumors, pointing to their ability to target diverse tumor types. Animal studies on NK cell therapies for solid cancers have shown smaller tumor sizes, tumor differentiation in vivo, recruitment of NK and T cells in the tumor environment and peripheral tissues, restored immune function, and fewer tumor-related systemic effects—suggesting a lower chance of recurrence. NK cells clinical trials in ovarian cancer patients have also shown encouraging results, and future directions include combining NK cell therapies with standard treatments to potentially boost effectiveness. Full article

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reactivating T cell-mediated anti-tumor immunity. However, this enhanced immune activity can lead to immune-related adverse events (irAEs). This narrative review focuses on endocrine irAEs, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. It also explores infectious complications and their underlying mechanisms. These mechanisms include immune dysregulation resulting directly from ICI-induced T-cell activation and indirectly from the immunosuppressive therapies used to treat irAEs. Furthermore, potential role of endocrine irAEs in predisposing patients to infectious complications is analyzed. The objective is to provide non-oncology specialists with the clinical insight necessary to recognize and manage these complex side effects. This narrative review synthesizes current literature on the diagnosis, management, and pathophysiology of endocrine irAEs and infections associated with different classes of ICIs (anti-CTLA-4, anti-PD-1, and anti-PD-L1). Endocrine irAEs are common, with incidence varying by ICI type; combination therapies pose the highest risk. Thyroid dysfunction is the most frequent, followed by hypophysitis, which often leads to permanent secondary adrenal insufficiency. ICI-induced diabetes mellitus is a rare but serious complication, frequently presenting as diabetic ketoacidosis. ICIs are believed to induce a distinct array of infections resulting from immunological dysregulation, unrelated to immunosuppressive medication. The phenomenon is increasingly called ICI therapy-induced dysregulated immunity. Moreover, evidence suggests that endocrine irAEs can compromise immune function and lead to a significantly higher risk of bacterial and fungal infections. Identifying infections that imitate irAEs is particularly important because the therapy is significantly distinct. Greater interdisciplinary awareness is crucial for the early recognition and appropriate management of both the endocrine and infectious complications, ultimately improving the safety and outcomes for patients receiving immunotherapy. Full article

The treatment of gynecological cancers is challenging because they are often diagnosed at the advanced stages. Furthermore, available chemotherapeutics increasingly imply the development of resistance in cancer patients. This necessitates the search for alternative solutions that could be used in therapy. One of the possibilities to consider is the use of pentacyclic triterpenoids. They are naturally occurring compounds characterized by a wide range of biological activities. They can also be modified to improve their pharmacological properties. Terpenoids based on oleanane, ursane, and lupane skeletons can modulate the numerous processes occurring in both normal and transformed cells. To develop effective anti-cancer therapy, it is essential to understand the processes regulating the progression and suppression of a given type of cancer. For this reason, it is necessary to assess the influence of the tested compounds on cellular processes such as the cell cycle, epithelial–mesenchymal transition, autophagy, and apoptosis. This article summarizes available information on the effects of pentacyclic triterpenoids on the PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Notch, HIF-1α, TGF-β, Wnt/β-catenin, Hippo, and Hedgehog signaling pathways in ovarian cancer cells. Full article

Radiotherapy remains a central component of cancer therapy that induces DNA damage and cancer cell death. Beyond its cytotoxic effects, radiotherapy acts as a potent immunomodulator by releasing immunogenic molecules, inflammatory mediators, and neoantigens that shape anti-tumor immunity. Radiation-induced immune responses can have opposing effects, including immune activation or immunosuppression that dictate local tumor responses. Increasing evidence suggests these immunologic effects are not confined to the site of irradiation, as radiation exposure to surrounding normal tissue can trigger systemic immune signaling that affects local tumor progression as well as metastatic spread. This review examines radiotherapy-induced immune responses across three interconnected contexts: (i) tumor-intrinsic signaling during radiation; (ii) tumor microenvironmental changes where innate and adaptive immune responses alter local outcomes; and (iii) systemic and off-target effects contributing to broader immune remodeling. A comprehensive understanding of radiotherapy-induced immune responses will guide therapeutic strategies to enhance its immunological potential while minimizing unintended immune and off-target effects. Full article

Colorectal carcinoma (CRC) represents the third most common cancer worldwide. Approximately 20% of patients present with metastatic disease at diagnosis, and 30–50% experience disease recurrence over time. For metastatic CRC (mCRC), the standard treatment consists of chemotherapy combined with a targeted agent based on molecular profile, such as RAS, BRAF, and MSI status. Anti-angiogenic drugs, which inhibit the formation of new blood vessels, have an established role in the management of mCRC. Mounting evidence highlights the critical interplay among angiogenesis, hypoxia, and the immune response in tumor progression. These insights have paved the way for testing novel combinations and molecules to control cancer progression. In particular, combining anti-angiogenic agents with immune checkpoint inhibitors has shown promise in improving outcomes for mCRC patients. Among emerging therapies, the novel anti-angiogenic agent fruquintinib has recently demonstrated clinical efficacy in the treatment of mCRC. Based on the data discussed in the present narrative review, the therapeutic landscape of mCRC appears poised for significant evolution in the near future. While numerous challenges and unanswered questions remain, the emergence of innovative therapeutic combinations and agents provides a promising opportunity for improving patient outcomes in mCRC. Full article

Selective gene delivery to defined cell populations remains one of the key challenges in lentiviral vector-based gene therapy. The vesicular stomatitis virus glycoprotein (VSV-G) confers high infectivity but lacks cell-type specificity because of the ubiquitous expression of its receptor, LDLR. To enable modular, receptor-specific targeting while retaining the production efficiency of VSV-G-pseudotyped vectors, we designed a bispecific adapter, 929-B6, comprising a VSV-G-binding nanobody and an ERBB2-binding DARPin 9.29. Anti-VSV-G nanobodies were isolated from an alpaca immune library and screened in cell-based pseudoreceptor assays to identify the optimal binder (VSVG-B6). The resulting adapter was evaluated with receptor-ablated (VSV-G_mut) and wild-type VSV-G-pseudotyped LVs across ERBB2-positive and -negative cell lines and in a mouse xenograft model. 929-B6 enabled efficient, receptor-specific transduction of ERBB2-expressing cells without increasing infection of ERBB2-negative controls. Pre-incubation of VSV-G_mut-pseudotyped LVs with 1–2 µg/mL 929-B6 increased transduction up to eight-fold in ERBB2⁺ cells, with similar but smaller effects for VSV-G and VSV-G_mut + 929R pseudotypes. Across breast cancer lines, transduction enhancement correlated with ERBB2 surface density, and co-culture experiments confirmed selective entry into ERBB2⁺ populations. In vivo imaging of ERBB2⁺ tumors revealed a visible tumor-localized luminescent signal following administration of 929-B6-treated vectors. The 929-B6 adapter provides a rapid, scalable means to retarget standard LV stocks toward chosen receptors without re-engineering the envelope or co-packaging pseudoreceptor plasmids. Its modularity suggests a generalizable platform for both gene therapy and oncolytic applications requiring flexible, receptor-defined tropism. Full article

Background/Objective: Cannabidiol (CBD) has gained increasing interest due to its multifaceted anticancer properties and favourable safety profile. Glioblastoma multiforme (GBM), a highly aggressive brain tumour with limited treatment options, represents a compelling target for CBD-based therapies. In this study, we report the rational design of two distinct formulations of lipid nanocapsules (LNCs) co-encapsulating CBD and a chemotherapeutic agent, tailored for intracranial and systemic administration. Methods: The cytotoxicity of various CBD–chemotherapeutic combinations, including temozolomide, carmustine, doxorubicin, and paclitaxel (PTX), were screened in vitro in U-87 MG and U-373 MG human GBM cell lines and analyzed for chemical compatibility. Moreover, the efficacy and the anti-migratory effect of the selected combination was further assessed in ovo and in vitro, respectively. Lastly, two LNC formulations coloaded with the selected combination were prepared in two different sizes via the phase inversion temperature method. Results: First, CBD in solution exhibited potent cytotoxicity and significantly inhibited cell migration in both GBM cell lines. Among the CBD–chemotherapeutic combinations tested, only CBD + PTX demonstrated both additive/synergistic interaction and favourable chemical compatibility. Second, this enhanced effect was confirmed in ovo. Third, the CBD + PTX combination also exhibited anti-migratory effect. Finally, two co-loaded LNC formulations—51.2 ± 0.9 nm and 25.9 ± 0.3 nm in size—were developed for intracranial and systemic delivery, respectively. Both formulations exhibited high monodispersity, a slightly negative ζ-potential, and consistently maintained a 7.5:1 CBD:PTX mass encapsulation ratio across both particle sizes. Conclusions: CBD + PTX co-loaded LNCs represent a promising and versatile nanomedicine platform for GBM therapy. Full article

Previous studies have shown that AtMP1 and AtMP2, antimicrobial peptides found in the climbing perch (Anabas testudineus), possess antibacterial and anticancer properties. This study aimed to determine whether modified forms of the AtMP2 peptide could enhance its antimicrobial activity. In the research study, the epidermal mucus of Anabas testudineus was extracted and tested to contain antibacterial and anticancer properties. Two peptides were initially extracted from the freshwater fish Anabas testudineus; however, the focus was placed on AtMP2 to evaluate its potential for enhanced antibacterial activity. Systematic-directed evolution was used to generate AtMP2 varieties. The AtMP2 varieties were characterized using APD3, CAMP, and AMPFun. Based on the characterization, two peptides, AtMP2-1 and AtMP2-2, were selected for synthesis. AtMP2-1 and AtMP2-2 demonstrated higher antimicrobial activity against Gram-positive than Gram-negative bacteria compared to the AtMP2 peptide, based on Minimum Inhibitory Concentration (MIC) determination and Kirby–Bauer Disk Diffusion analysis. For the SRB cytotoxicity analysis using the HS-27 and Vero cell lines, both AtMP2-1 and AtMP2-2 are safe for human use at 20 μg/mL. ZDOCK and HPEPDOCK servers were used to evaluate the binding affinity between AtMP2-1 and AtMP2-2 peptides and proteins involved in the bacterial cell death cycle. The results showed varying docking scores, with more negative values indicating stronger binding interactions, particularly with proteins such as SecA, RpoB, GyrA, ClpP, and MetG. The study concluded that modified peptides derived from Anabas testudineus show enhanced antibacterial properties and minimal cytotoxicity, making them potential alternatives to traditional antibiotics. Future research should investigate the specific biochemical pathways affected by these AMPs to understand their mechanisms of action better and explore their potential as therapeutic agents, particularly in the treatment of bacterial infections, wound healing, and cancer therapy. Full article

Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, exhibits potent anticancer properties; however, its poor solubility and bioavailability limit its therapeutic application. To overcome these challenges and facilitate molecular target identification, a set of biotin-conjugated UA derivatives (5a–d) was synthesized through selective C-28 alkylation and biotinylation. The use of microwave-assisted synthesis significantly enhanced both reaction efficiency and product purity. Among the derivatives, compound 5c exhibited increased cytotoxicity and selectivity against bladder cancer cell lines, surpassing UA in its ability to induce apoptosis, generate reactive oxygen species (ROS), and halt cell cycle progression at the G1 phase. Proteomic profiling revealed that 5c interacts with proteins involved in ER stress, RNA processing, cytoskeletal remodeling, and metabolic regulation. These findings underscore the potential of biotinylated UA derivatives as multifunctional chemical probes for mechanistic studies in the development of targeted therapies for cancer. Full article

Background: Hypochlorous acid (HOCl) is an integral component of the human innate immune system. It possesses antimicrobial properties and is available in solution, dermal spray, and scar gel forms. Objectives/Methods: This review presents data from studies on the clinical use of HOCl in various specialties, including dermatology, surgery, dentistry, ophthalmology, and rhinology. Results: Due to its anti-inflammatory/antimicrobial/immunomodulatory and healing properties, HOCl is advantageous in treating various skin disorders: ulcus cruris (and wound care), diabetic ulcers, atopic dermatitis, seborrheic dermatitis, pruritus, acne vulgaris, etc. Also, the application of a HOCl spray/gel after surgical procedures may prevent infection, reduce inflammation, and accelerate healing. HOCl is also effective and safe for the prevention and treatment of hypertrophic and keloid scars. Growing evidence shows a broader role for HOCl in limiting cancer cell survival and slowing tumor growth. It is also important in treating various viral infections like SARS-CoV-2 (coronavirus), influenza, and herpes, thereby helping to prevent the spread of aerosols. In addition, since HOCl is an endogenous compound naturally present in mammals with a high safety profile, it may be an effective bacterial disinfectant in dental waterlines. In ophthalmology, adjuvant treatment with HOCl ophthalmic spray can reduce the duration of antibiotic/corticosteroid use, even in severe blepharitis. To fully harness the protective/therapeutic properties of HOCl, future advancements will rely on the development of new chemical compounds and sophisticated pharmaceutical formulations. Conclusions: The majority of clinical studies have confirmed that HOC1 is useful in therapy, although the results are not entirely consistent. Further research is essential to optimize HOCl dosing and to develop controlled-release systems aimed at maximizing its anti-inflammatory and photoprotective effects while minimizing tissue irritation and damage. Full article

We aimed to develop and internally validate a nomogram to estimate axillary pathological complete response (pCR, ypN0) after neoadjuvant systemic therapy (NAST) in clinically node-positive (cN1–2) breast cancer. In a single-center retrospective cohort of 144 consecutive patients treated with NAST (anti-HER2 as indicated), all underwent standardized pre- and post-NAST 18F-FDG PET/CT and axillary staging (sentinel lymph node biopsy [SLNB], targeted axillary dissection [TAD], or axillary lymph node dissection [ALND]). Axillary pCR occurred in 51.4% (74/144). In a multivariable analysis, independent positive determinants of ypN0 included the triple-negative subtype, Modified PERCIST (SUVmax-based) reduction ≥ 80.70%, pre-NAST tumor-to-axilla SUVmax ratio ≥ 1.21, and residual breast tumor size < 0.5 mm; conversely, conglomerate/matted nodal morphology at diagnosis was inversely associated. The model showed good internal discrimination (AUC 0.857, 95% CI 0.797–0.917) and acceptable calibration (Hosmer–Lemeshow p = 0.425). Exploratory, subtype-restricted signals were observed for inflammatory indices within Luminal B (HER2+) but were not retained in the final model. The resulting nomogram—combining tumor biology, PET/CT response, and pre-NAST nodal features—may support risk stratification for axillary de-escalation after NAST; however, prospective external validation—ideally embedded in ongoing de-escalation frameworks—remains essential before clinical implementation, and the tool should currently be regarded as hypothesis-generating rather than a stand-alone decision aid for routine practice. Full article