Search Results (81)

This review provides an updated overview of oncolytic virotherapy as a promising therapeutic strategy for colorectal cancer (CRC), focusing on six key viral platforms: adenovirus, herpes simplex virus (HSV), reovirus, vesicular stomatitis virus (VSV), vaccinia virus (VV), and measles virus (MV). These viruses exhibit tumor-selective replication and exert their effects through mechanisms such as direct oncolysis, the delivery of immunostimulatory genes (e.g., IL-12, IL-15, GM-CSF), the activation of innate and adaptive immune responses, and the remodeling of the tumor microenvironment. Preclinical and early clinical studies suggest that oncolytic viruses can enhance the efficacy of existing treatments, particularly in immunologically “cold” tumors such as microsatellite stable CRC, when used in combination with chemotherapy or immune checkpoint inhibitors. Despite encouraging results, several challenges remain, including antiviral immune clearance, tumor heterogeneity, and limitations in systemic delivery. Current research focuses on improving viral engineering, enhancing tumor targeting, and designing combinatorial strategies to overcome resistance and maximize clinical benefits. Overall, oncolytic viruses represent a versatile and evolving therapeutic class with the potential to address unmet clinical needs in CRC. Full article

Cancer remains a primary cause of mortality, with over 18.1 million new cases and 9.6 million deaths globally in 2018. Chemotherapy, which utilizes a spectrum of cytotoxic drugs targeting the rapidly dividing cancer cells, is a predominant treatment modality. However, the tendency of chemotherapeutics to induce drug resistance and exhibit non-specific cytotoxicity necessitates the development of new anticancer agents with heightened efficacy and minimized toxicity. In recent years, the discovery of safe and effective antibacterial/antiviral agents has also been a hot spot in medicinal chemistry. This paper comprehensively reviews the synthesis, anticancer/antibacterial/antiviral activity, and structure–activity relationships of natural 1,4-naphthoquinones and their derivatives. It highlights their potential as efficient and low-toxicity antitumor and anti-infectious drug candidates. Full article

Background: Immunosuppressed patients still exhibit a high mortality rate due to SARS-CoV-2 infection, up to 21%. Persistent viral load replication and protracted viral symptoms result in a high risk of developing pneumonia, a potential risk of antiviral resistance, and a subsequent delay of onco-hematological treatments. Methods: Hematological patients and kidney transplant patients with SARS-CoV-2 infection, treated at GOM Niguarda Hospital (Milan) with combined antiviral therapy (remdesivir plus nirmatrelvir/ritonavir at standard doses) between November 2022 and March 2024, were retrospectively reviewed. Results: Thirty-four patients were analyzed. Twenty-four (71%) patients had pneumonia. The median duration of SARS-CoV-2 positivity before antiviral treatment was 40 (10–34) days. The median treatment duration was 11 (10–10) days. All patients went through clinical resolution. Thirteen patients were exposed to a new immune-chemotherapy cycle early after antiviral treatment (median 13, IQR 6–12 days), while five resumed a standard immunosuppressive regimen immediately after viral clearance. No relapse or recurrence of symptoms was reported for up to 226 (106–318) days of follow-up. Antiviral therapy was well tolerated, and no adverse events were observed. The 30-day overall survival was 94%, while the 90-day survival was 88%. No patient died of SARS-CoV-2 infection. Conclusions: The administration of nirmatrelvir/ritonavir and remdesivir lead to the complete resolution of SARS-CoV-2 pneumonia with no side effects in this cohort. The combination of these two antivirals may be a safe option in immunosuppressed population at risk of severe complications and prolonged SARS-CoV-2 infection in order to treat severe clinical presentation and to avoid viral recurrence after chemotherapy. Full article

Coxsackievirus B (CVB) infections, ranging from mild to severe diseases, lack specific antiviral treatments, underscoring the need for novel therapeutic strategies. Drug therapy is an important tool for controlling enterovirus infections, but clinically effective drugs do not currently exist, mainly due to the development of drug resistance. Combination therapy with two or more drugs has the potential to successfully inhibit viral infection more effectively than either drug alone as well as delay the development of resistance. This study explores the consecutive alternating administration (CAA) scheme in mice with CVB1 infection, utilizing double antiviral combinations consisting of pleconaril and MDL-860, with guanidine hydrochloride and oxoglaucine. The CAA combinations of pleconaril achieved a survival rate, in infected mice, of up to 59%, while the combinations of MDL-860 showed no significant effects. CAA reduced mortality, prolonged mean survival time (up to 5 days), and mitigated drug resistance compared to monotherapy or simultaneous administration. Monotherapeutic courses and daily administration of double combinations had no effect. Phenotypic characterization using the IC₅₀ marker of virus isolates from brain tissue of infected and treated mice was of particular importance for the evaluation of the CAA treatment scheme. The results show increased susceptibility of the virus isolates to the partner compounds in double CAA combinations. In contrast, virus isolates from the monotherapeutic groups manifested a diminished susceptibility to their respective compound, which signals the development of drug resistance. All data obtained prove the potential of the CAA scheme for the development of effective chemotherapy of enterovirus infections. Full article

Therapy resistance still constitutes a common hurdle in the treatment of many human cancers and is a major reason for treatment failure and patient relapse, concomitantly with a dismal prognosis. In addition to “intrinsic resistance”, e.g., acquired by random mutations, cancer cells typically escape from certain treatments (“acquired resistance”) by a large variety of means, including suppression of apoptosis and other cell death pathways via upregulation of anti-apoptotic factors or through inhibition of tumor-suppressive proteins. Therefore, ideally, the tumor-cell-restricted induction of apoptosis is still considered a promising avenue for the development of novel, tumor (re)sensitizing therapies. A growing body of evidence has highlighted the multifaceted role of tripartite motif 25 (TRIM25) in controlling different aspects of tumorigenesis, including chemotherapeutic drug resistance. Accordingly, overexpression of TRIM25 is observed in many tumors and frequently correlates with a poor patient survival. In addition to its originally described function in antiviral innate immune response, TRIM25 can play critical yet context-dependent roles in apoptotic- and non-apoptotic-regulated cell death pathways, including pyroposis, necroptosis, ferroptosis, and autophagy. The review summarizes current knowledge of molecular mechanisms by which TRIM25 can interfere with different cell death modalities and thereby affect the success of currently used chemotherapeutics. A better understanding of the complex repertoire of cell death modulatory effects by TRIM25 is an essential prerequisite for validating TRIM25 as a potential target for future anticancer therapy to surmount the high failure rate of currently used chemotherapies. Full article

Misshapen/NIKs-related kinase (MINK) 1 belongs to the mammalian germinal center kinase (GCK) family. It contains the N-terminal, conserved kinase domain, a coiled-coil region, a proline-rich region, and a GCK, C-terminal domain with the Citron-NIK-Homology (CNH) domain. The kinase is an essential component of cellular signaling pathways, which include Wnt signaling, JNK signaling, pathways engaging Ras proteins, the Hippo pathway, and STRIPAK complexes. It thus contributes to regulating the cell cycle, apoptosis, cytoskeleton organization, cell migration, embryogenesis, or tissue homeostasis. MINK1 plays an important role in immunological responses, inhibiting Th17 and Th1 cell differentiation and regulating NLRP3 inflammasome function. It may be considered a link between ROS and the immunological system, and a potential antiviral target for human enteroviruses. The kinase has been implicated in the pathogenesis of sepsis, rheumatoid arthritis, asthma, SLE, and more. It is also involved in tumorigenesis and drug resistance in cancer. Silencing MINK1 reduces cancer cell migration, suggesting potential for new therapeutic approaches. Targeting MINK1 could be a promising treatment strategy for patients insensitive to current chemotherapies, and could improve their prognosis. Moreover, MINK1 plays an important role in the nervous system and the cardiovascular system development and function. The modulation of MINK1 activity could influence the course of neurodegenerative diseases, including Alzheimer’s disease. Further exploration of the activity of the kinase could also help in gaining more insight into factors involved in thrombosis or congenital heart disease. This review aims to summarize the current knowledge on MINK1, highlight its therapeutic and prognostic potential, and encourage more studies in this area. Full article

Luciferase (luc) bioluminescence (BL) is the most used light-emitting protein that has been engineered to be expressed in multiple cancer cell lines, allowing for the detection of tumor nodules in vivo as it can penetrate most tissues. The goal of this study was to develop an oncolytic adenovirus (OAd)-resistant human triple-negative breast cancer (TNBC) that could express luciferase. Thus, when combining an OAd with chemotherapies or targeted therapies, we would be able to monitor the ability of these compounds to enhance OAd antitumor efficacy using BL in real time. The TNBC cell line HCC1937 was stably transfected with the plasmid pGL4.50[luc2/CMV/Hygro] (HCC1937/luc2). Once established, HCC1937/luc2 was orthotopically implanted in the 4th mammary gland fat pad of NSG (non-obese diabetic severe combined immunodeficiency disease gamma) female mice. Bioluminescence imaging (BLI) revealed that the HCC1937/luc2 cell line developed orthotopic breast tumor and lung metastasis over time. However, the integration of luc plasmid modified the HCC1937 phenotype, making HCC1937/luc2 more sensitive to OAdmCherry compared to the parental cell line and blunting the interferon (IFN) antiviral response. Testing two additional luc cell lines revealed that this was not a universal response; however, proper controls would need to be evaluated, as the integration of luciferase could affect the cells’ response to different treatments. Full article

Background: Daily clinical practice requires repeated and prolonged venous access for delivering chemotherapy, antibiotics, antivirals, parenteral nutrition, or blood transfusions. This study aimed to investigate the performance and the safety of totally implantable vascular access devices (TIVADs) over a 5-year follow-up period through a standardized well-trained surgical technique and patient management under local anesthesia. Methods: In a retrospective, observational, and monocentric study, 70 patients receiving POLYSITE^® TIVADs for chemotherapy were included. The safety endpoints focused on the rate of perioperative, short-term, and long-term complications. The performance endpoints included vein identification for device insertion and procedural success rate. Results: The study demonstrated no perioperative or short-term complications related to the TIVADs. One (1.4%) complication related to device manipulation was identified as catheter flipping, which led to catheter adjustment 56 days post-placement. Moreover, one (1.4%) infection due to usage conditions was observed, leading to TIVAD removal 3 years and 4 months post-surgery. Catheter placement occurred in cephalic veins (71.4%), subclavian veins (20%), and internal jugular veins (8.6%). The procedural success rate was 100%. Overall, the implantable ports typically remained in place for an average of 22.4 months. Conclusions: This study confirmed the TIVADs’ performance and safety, underscored by low complication rates compared to published data, thereby emphasizing its potential and compelling significance for enhancing routine clinical practice using a standardized well-trained surgical technique and patient management. Full article

Ocimum gratissimum (O. gratissimum), a medicinal herb with antifungal and antiviral activities, has been found to prevent liver injury and liver fibrosis and induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we evaluated the effect of aqueous extracts of O. gratissimum (OGE) on improving the efficacy of chemotherapeutic drugs in HCC cells. Proteomic identification and functional assays were used to uncover the critical molecules responsible for OGE-induced sensitization mechanisms. The antitumor activity of OGE in combination with a chemotherapeutic drug was evaluated in a mouse orthotopic tumor model, and serum biochemical tests were further utilized to validate liver function. OGE sensitized HCC cells to the chemotherapeutic drug cisplatin. Proteomic analysis and Western blotting validation revealed the sensitization effect of OGE, likely achieved through the inhibition of breast cancer type 1 susceptibility protein (BRCA1). Mechanically, OGE treatment resulted in BRCA1 protein instability and increased proteasomal degradation, thereby synergistically increasing cisplatin-induced DNA damage. Moreover, OGE effectively inhibited cell migration and invasion, modulated epithelial-to-mesenchymal transition (EMT), and impaired stemness properties in HCC cells. The combinatorial use of OGE enhanced the efficacy of cisplatin and potentially restored liver function in a mouse orthotopic tumor model. Our findings may provide an alternate approach to improving chemotherapy efficacy in HCC. Full article

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective. Full article

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and Paxlovid^TM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2. Full article

This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific therapeutics are described in alphabetical order including classic antiviral drugs, such as acyclovir, abacavir, adefovir, amantadine, didanosine, entecavir, ganciclovir, interferon, lamivudine, penciclovir, famciclovir, oseltamivir, ribavirin, and zidovudine, repurposed drugs, such as ivermectin and nitazoxanide, which were originally used as antiparasitic drugs, and some others substances showing antiviral activity, such as ampligen, azo derivates, docosanol, fluoroarabinosylpyrimidine nucleosides, and novel peptides. Most of them have only been used for research purposes and are not widely used in clinical practice because of a lack of essential pharmacokinetic and safety data. Suggested future research directions are also highlighted. Full article

Polyphenolic compounds, encompassing flavonoids (e.g., quercetin, rutin, and cyanidin) and non-flavonoids (e.g., gallic acid, resveratrol, and curcumin), show several health-related beneficial effects, which include antioxidant, anti-inflammatory, hepatoprotective, antiviral, and anticarcinogenic properties, as well as the prevention of coronary heart diseases. Polyphenols have also been investigated for their counteraction against the adverse effects of common anticancer chemotherapeutics. This review evaluates the outcomes of clinical studies (and related preclinical data) over the last ten years, with a focus on the use of polyphenols in chemotherapy as auxiliary agents acting against oxidative stress toxicity induced by antitumor drugs. While further clinical studies are needed to establish adequate doses and optimal delivery systems, the improvement in polyphenols’ metabolic stability and bioavailability, through the implementation of nanotechnologies that are currently being investigated, could improve therapeutic applications of their pharmaceutical or nutraceutical preparations in tumor chemotherapy. Full article

Licorice is a remarkable traditional Chinese medicine obtained from the dried root and rhizomes of the Glycyrrhiza genus, and t has been utilized in China for many centuries. It consists of more than 300 compounds that are mainly divided into triterpene saponins, flavonoids, polysaccharides, and phenolic components. The active compounds of licorice have been found to possess multiple biological activities, including antitumor, anti-inflammatory, antiviral, antimicrobial, immunoregulatory, cardioprotective, and neuroprotective functions. In addition to providing a brief overview of licorice’s adjuvant properties, this review describes and analyzes the pharmacological mechanisms by which licorice components function to treat gastric cancer. Furthermore, licorice compounds are also found to be potent adjuvant chemotherapy agents, as they can improve the quality of life of cancer patients and alleviate chemotherapy-induced adverse effects. Full article

Natural compounds with pharmacological activity, flavonoids have been the subject of an exponential increase in studies in the field of scientific research focused on therapeutic purposes due to their bioactive properties, such as antioxidant, anti-inflammatory, anti-aging, antibacterial, antiviral, neuroprotective, radioprotective, and antitumor activities. The biological potential of flavonoids, added to their bioavailability, cost-effectiveness, and minimal side effects, direct them as promising cytotoxic anticancer compounds in the optimization of therapies and the search for new drugs in the treatment of cancer, since some extensively antineoplastic therapeutic approaches have become less effective due to tumor resistance to drugs commonly used in chemotherapy. In this review, we emphasize the antitumor properties of tangeretin, a flavonoid found in citrus fruits that has shown activity against some hallmarks of cancer in several types of cancerous cell lines, such as antiproliferative, apoptotic, anti-inflammatory, anti-metastatic, anti-angiogenic, antioxidant, regulatory expression of tumor-suppressor genes, and epigenetic modulation. Full article