Douglas M Noonan

• Ph.D.
• Professor (Associate) at University of Insubria

Curcumin (CUR), a polyphenol obtained from Curcuma longa L., possesses promising properties for prostate cancer (PCa) treatment. The use of polymeric nanoparticles containing the surfactant D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) can improve the aqueous solubility and low bioavailability of CUR, in addition to increasing the drug/n...

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, and anti-ageing effects to protect normal tissues, and it can exert anti-angiogenic and pro-apoptotic effects on cancer ce...

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, anti-ageing effects to protect normal tissues and can exert anti-angiogenic, and pro-apoptotic effects on cancer cells. Me...

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. Since this concept was established in the Seventies, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies...

Introduction: Extra virgin olive oil is a basic component of the Mediterranean diet; it contains several molecules with antioxidant, anti-inflammatory, anti-angiogenic and pro-apoptotic properties against a variety of cancers and influencing cellular metabolism too. Olive mill waste water (OMWW), a liquid residue produced in vast amounts during oli...

Introduction: Natural bioactive pigments are of great interest for human health. Marine organisms are underexplored as source of useful metabolites. Diatoms produce diatoxantin (diatox), a xanthophyll with several properties (chemo-preventive, anti-inflammatory, antioxidant, photoprotective, immunomodulatory), that may have beneficial effects. Doxo...

Since antiquity, numerous advantages of olive oil and its by-products have been recognized in various domains, including cooking, skincare, and healthcare. Extra virgin olive oil is a crucial component of the Mediterranean diet; several of its compounds exert antioxidant, anti-proliferative, anti-angiogenic and pro-apoptotic effects against a varie...

Introduction: Several diet-derived compounds have been reported to exert anti-oxidant, anti-proliferative, anti-angiogenic and pro-apoptotic effects. Furthermore, they can target cancer cells and the tumor microenvironment though their metabolic derangements as well. Extra virgin olive oil represents an important constituent of the Mediterranean d...

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a fundamental role in modulating inflammation and in maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have im...

Knowledge of aging biology needs to be expanded due to the continuously growing number of elderly people worldwide. Aging induces changes that affect all systems of the body. The risk of cardiovascular disease and cancer increases with age. In particular, the age-induced adaptation of the immune system causes a greater susceptibility to infections...

Coronavirus 19 disease (COVID-19) may be complicated by thrombotic events, particularly venous thromboembolism (VTE), which have been reported both in critically ill hospitalized patients and in individuals with mild symptoms. It is known that the chronic use of oral contraceptive pills (OCPs) is associated with higher risk of VTE. To date, there a...

Background: Research and production of natural anti-oxidants is growing and is developed both in experimental laboratories and in nutraceuticals and pharmaceutical industries. Marine microorganisms represent underestimated sources of bioactive compounds endowed with anti-oxidant, anti-inflammatory, cardiovascular protective and anti-angiogenic prop...

The exploration of natural preventive molecules for nutraceutical and pharmaceutical use has recently increased. In this scenario, marine microorganisms represent an underestimated source of bioactive products endowed with beneficial effects on health that include anti-oxidant, anti-inflammatory, differentiating, anti-tumor, and anti-angiogenic act...

Xanthophylls, a group of carotenoids, have attracted attention as human health benefit compounds thanks to their functionality and bioavailability. The great antioxidant and anti-inflammatory abilities of diatoxanthin (Dt), a photoprotective xanthophyll synthetized by diatoms, were recently documented. This study investigates the capacity of Dt to...

Objective Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform. Methods Two cohorts wer...

Purpose To investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period. Methods All consecutive hospitalized laboratory‐confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physic...

Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an overall 5-year survival rate, being locked in the 25–30% range in the last decade. Cancer immunotherapy is currently one of the most intensively investigated and promising therapeutic strategy and as such, is expected to provide in the incoming years signif...

Contact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is characterized by a strong inflammatory response define...

Background: In cancer patients receiving chemotherapeutic agents, cardiovascular toxicities still remains one of the most undesirable side effects. One of the best known cardiotoxic agents is doxorubicin, a very powerful chemotherapeutic molecules for breast cancer. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with...

Background: Tissue inhibitors of metalloproteases (TIMPs) have been reported to exert dual roles in cancer, based on the different cancer type and interactions with the tumor microenvironments. As inhibitors of Matrix metalloproteases (MMP) they downregulate invasion, metastasis and angiogenesis. However, TIMP1 levels have been found increased in p...

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatments over the last 10 years, with even increasing indications in many neoplasms. Non-small cell lung cancer (NSCLC) is considered highly immunogenic, and ICIs have found a wide set of applications in this area, in both early and advanced lines of treatment, significantly changing...

Cardiovascular toxicity in cancer patients receiving chemotherapy remains one of the most undesirable side effects, limiting the choice of the most efficient therapeutic regimen, including combinations of different anticancer agents. Anthracyclines (doxorubicin) and antimetabolites (5-fluorouracil (5-FU), capecitabine) are among the most known agen...

Reliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the “gray zone” (PSA 4–10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between 4 and 16 ng/ml, using the SANIST-Cloud Ion Mobilit...

A two-dose regimen of Pfizer–BioNTech COVID-19 vaccination confers 95% protection against COronaVIrus Disease 19 (COVID-19) and the safety profile is adequate. To the submission date, there were no reports in literature of acute pericarditis after BNT162b2 vaccination. However, pericarditis has been reported as a rare event associated with COVID-19...

Natural Killer (NK) cells have been found to be anergic, exhausted and pro-angiogenic in cancers. NK cell from healthy donors, exposed to TGFβ, acquire the CD56brightCD9+CD49a+ decidual-like-phenotype, together with decreased levels of NKG2D activation marker, increased levels of TIM-3 exhaustion marker, similar to cancer-associated NK cells. Tissu...

Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry and is expressed on the surface of several pulmonary and non-pulmonary cell types, with induction of a “cytokine storm” upon binding. Other cell types present the receptor and can be infected, including cardiac, renal, intest...

Cardiovascular toxicity remains one of the most adverse side effects in cancer patients receiving chemotherapy. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, anti-oxidant activities which could exert protective effects on heart cells. One very interesting derivative of EVOO preparation is rep...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptor on vascular cells. As a consequence, patients with COVID-19 have an increased incidence of thromboembolic complications of the SARS-CoV-2 infection and subsequent endothelial cell damage with consequence of development...

Tissue inhibitors of metalloproteases (TIMPs) have been reported to exert dual roles in cancer, based on the different cancer type and interactions with the tumor microenvironments. As inhibitors of Matrix metalloproteases (MMP) they downregulate invasion, metastasis and angiogenesis. However, TIMP1 levels have been found increased in patients with...

Photochemoprevention can be a valuable approach to counteract the damaging effects of environmental stressors (e.g., UV radiations) on the skin. Pigments are bioactive molecules, greatly attractive for biotechnological purposes, and with promising applications for human health. In this context, marine microalgae are a valuable alternative and eco-s...

BACKGROUND The novel coronavirus has a high mortality rate (over 1% for patients older than 50). This could be only partially ascribed to other comorbidities. Possible explanation could be something which assures the ability to prompt response to SARS-CoV-2 in younger people independently from the novelty of the virus itself. Something stimulated t...

Background: The novel coronavirus has a high mortality rate (over 1% for patients older than 50). This could be only partially ascribed to other comorbidities. Possible explanation could be something which assures the ability to prompt response to SARS-CoV-2 in younger people independently from the novelty of the virus itself. Something stimulated...

Background Cardiovascular toxicities still remain one of the most undesirable side effects in cancer patients receiving chemotherapy, and cardiotoxicity has been detected associated with many therapeutic regimens. A number of mechanisms are reported for these effects, some of which are related to inflammation, oxygen radical generation, mitochondri...

Angiogenesis has been shown to play a crucial role in prostate cancer (PCa) progression in several preclinical models, in the clinic, pro-angiogenic factors have been shown to correlate with, Gleason score, metastasis and prognosis in PCa. Plasma levels of VEGF were shown to be higher in patients with metastatic PCa than those with localized diseas...

Phenolic compounds (PCs) are a family of secondary metabolites with recognized biological activities making them attractive for the biomedical “red” biotechnology. The development of the eco-sustainable production of natural bioactive metabolites requires using easy cultivable organisms, such as microalgae, which represents one of the most promisin...

Natural killer (NK) cells, effector lymphocytes of the innate immunity, have been shown to be altered in several cancers, both at tissue and peripheral levels. We have shown that in Non-Small Cell Lung Cancer (NSCLC) and colon cancer, tumour associated circulating NK (TA-NK) and tumour infiltrating NK (TI-NK) exhibit pro-angiogenic phenotype/functi...

Regulated cell death (RCD) has always been considered a tolerogenic event. Immunogenic cell death (ICD) occurs as a consequence of tumour cell death accompanied by the release of damage-associated molecular patterns (DAMPs), triggering an immune response. ICD plays a major role in stimulating the function of the immune system in cancer during chemo...

Marine organisms with fast growth rates and great biological adaptive capacity might have biotechnological interests, since ecological competitiveness might rely on enhanced physiological or biochemical processes’ capability promoting protection, defense, or repair intracellular damages. The invasive seagrass Halophila stipulacea, a non-indigenous...

Natural killer (NK) cells accumulate at the fetal-maternal interface and represent 70% of immune cells in the decidua (dNK) at first-trimester pregnancy; they are immune-tolerant toward the semiallogenic fetus and are "nurturing" and nonkilling NK cells. A subset of NK cells in patients with cancer have features in common with dNK, which include ex...

Growing interest in hypertension—one of the main factors characterizing the cardiometabolic syndrome (CMS)—and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin- Angiotensin-...

Marine biotechnology is promising to provide new solutions to society and humans, such as for health protection or natural treatments against diseases. In this framework, different strategies are explored to select marine organisms to initiate the pipeline, hopefully ended by the product development. Organisms with fast growth rates and great biolo...

Lung cancer is the leading cause of cancer-related death worldwide and the only curative treatment remains surgery. Recurrence rates in resected patients remain high: from 30% for stage I to 80% for stage III. We previously demonstrated the role of 24 microRNAs in the pathogenesis and aggressiveness of lung tumors. Natural Killer (NK) cells, cellul...

Prostate cancer (PCa) remains the second most common cancer worldwide in men. Angiogenesis has been shown to play a crucial role in PCa progression in several preclinical models. Production of pro-angiogenic factors have been shown to correlate with metastasis, Gleason score and prognosis in PCa and plasma levels of VEGF were shown to be higher in...

The olive mill wastewater polyphenol extracts exhibit chemopreventive properties in lung cancer cell lines, acting on the CXCR4/CXCL12 axis. Lung cancer still is a leading cause of cancer death worldwide. Although avoidance of tobacco use and smoking cessation will have the greatest impact on lung cancer development, (chemo)prevention could prove t...

The exploration of natural antioxidants for nutraceuticals and pharmaceuticals industries has recently increased. In this scenario, marine microorganisms, represent underestimated sources of bioactive products endowed with beneficial effects on health, that include anti-oxidant, anti-tumor and anti-angiogenic activities. Here, we tested the potenti...

Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk of severe disease and fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19), there is now emerging evidence that overweight and obesity predispose to severe symptoms and negative prognosis. Remarkably,...

Background. Natural killer (NK) cells are effector lymphocytes of the innate immunity. Two major subsets of NK cells are mostly present in the peripheral blood (pNKs): the cytotoxic CD56dimCd16+ NK cell subset (90-95% of pNKs), and the low cytotoxic, highly cytokine-producing CD56brightCD16-/low NK cell subset (5-10% of pNKs). It has been demonstra...

This study assessed the relationship between the ability of Natural Killer (NK) cells to activate antibody-dependent cellular cytotoxicity against human HT29 colorectal cancer cells exposed to cetuximab and the body mass index of the human subjects from whom the NK cells had been obtained. NK cells obtained from 73 human donors were co-incubated wi...

e17544 Background: Prostate cancer (PCa) represents the second most common cancer worldwide in men. Angiogenesis has been shown to play a crucial role in PCa progression in several preclinical models. Production of pro-angiogenic factors can correlate with metastasis, Gleason score and prognosis in PCa and plasma levels of VEGF were shown to be hig...

SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected...

As the COVID-19 epidemic expands in the world, and with the previous SARS epidemic, avian flu, Ebola and AIDS serving as a warning, biomedical and biotechnological research has the task to find solutions to counteract viral entry and pathogenesis. A novel approach can come from marine chemodiversity, recognized as a relevant source for developing a...

Ovarian cancer (OvCA) accounts for one of the leading causes of death from gynecologic malignancy. Despite progress in therapy improvements in OvCA, most patients develop a recurrence after first-line treatments, dependent on the tumor and non-tumor complexity/heterogeneity of the neoplasm and its surrounding tumor microenvironment (TME). The TME h...

Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. Here, we...

Human RNASET2 acts as a powerful oncosuppressor protein in in vivo xenograft-based murine models of human cancer. Secretion of RNASET2 in the tumor microenvironment seems involved in tumor suppression, following recruitment of M1-polarized macrophages. Here, we report a murine Rnaset2-based syngeneic in vivo assay. BALB/c mice were injected with pa...

The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal–fetal interface. The biological and immunological processes behind the maternal–fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, tho...

Background: Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, re...

The link between cancer development or progression and immune system dysregulation has long been established. Virtually every cell type belonging to both the innate and adaptive immune system has been reported to be involved in a complex interplay that might culminate into either a pro- or anti-tumorigenic response. Among the cellular components of...

The main role of vitamin D is to control mineral homeostasis. However, recent studies suggested the existence of a number of extraskeletal effects. Among the latter, preclinical studies provided consistent data on the involvement of vitamin D in innate and adaptive immunity and autoimmunity. Molecular biology studies showed that both vitamin D rece...

Background: The published circulating miRNA signatures proposed for early-stage non-small cell lung cancer (NSCLC) detection are inconsistent and difficult to replicate. Reproducibility and validation of an miRNA simple signature of NSCLC are prerequisites for translation to clinical application. Methods: The serum level of miR-223 and miR-29c,...

World Health Organization (WHO) report from 2014 documented that non-communicable so-called civilization diseases such as cardiovascular disease, chronic respiratory diseases, cancer or type 2 diabetes are responsible for over 50% of all premature deaths in the world. Research carried out over past 20 years has provided data suggesting that diet is...

Prostate cancer (PCa) represents the second cause of male cancer death worldwide. Immune cells can acquire pro-tumor phenotype and functions as consequence of their plasticity. Natural killer (NK) cells are cellular mediators of the innate immunity, primarily involved in tumor recognition and elimination. Altered NK phenotype and functions have bee...

Epidemiological studies are providing strong evidence on beneficial health effects from dietary measures, leading scientists to actively investigate which foods and which specific agents in the diet can prevent diseases. Public health officers and medical experts should collaborate toward the design of disease prevention diets for nutritional inter...

Myeloid-derived suppressor cells (MDSCs) contribute to the induction of an immune suppressive/anergic, tumor permissive environment. MDSCs act as immunosuppression orchestrators also by interacting with several components of both innate and adaptive immunity. Natural killer (NK) cells are innate lymphoid cells functioning as primary effector of imm...

Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of a waste material, termed ‘olive mill w...

The RNASET2 gene encodes for a highly conserved extracellular ribonuclease which has recently been shown to carry out a marked oncosuppressive role by means of modification of the tumor microenvironment. In particular, focusing on two independent ovarian cancer cell models, we recently reported that RNASET2-mediated tumor suppression in vivo involv...

Macrophages represent key inflammatory cellular effectors of the innate immune response. Despite being widely acknowledged as professional phagocytes, the functional roles played by these cells have been progressively widened over the years to encompass regulation of the adaptive immune system, stimulation or suppression of cancer cell growth and t...

Background Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epidermal growth factor receptor (E...

Natural Killer (NK) cells are effector lymphocytes involved in tumor immunosurveillance. In solid malignancies, tumor associated (TANK; peripheral blood) and tumor infiltrating (TINK) NK cells have compromised functions. We functionally and molecularly characterize TINK and TANKs from blood and tissue samples of colorectal cancer (CRC) patients, a...

NK cells are effector lymphocytes involved in tumor immunosurveillance; however, in patients with solidmalignancies,NKcells have compromised functions.Wehave previously reported that lung tumor-associated NKcells (TANKs; peripheralblood) andtumor-infiltratingNKcells (TINKs) showproangiogenic,decidualNK-like (dNK) phenotype. In this study, we functi...

Background Serum steroids are crucial molecules altered in prostate cancer (PCa). Mass spectrometry (MS) is currently the elected technology for the analysis of steroids in diverse biological samples. Steroids have complex biological pathways and stoichiometry and it is important to evaluate their quantitative ratio. MS applications to patient horm...

The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs) and stromal cells. TAL...

The calibrate analyte concentrations and the calculated concentrations of both known and unknown samples.

Two steroid relationship ratios that can selectively discriminate patients with prostate carcinoma from benign prostate hyperplasia and healthy controls, together with the associated enzyme (P450C17).

Schematic representation for steroid synthesis starting from the precursor cholesterol and the enzymes involved.

Scheme of singular absolute concentration match and the steroids ratio concentration match models.

The internal standard concentrations.

Carnitines play an important role in the energy exchange in cells, involved in the transport of fatty acids across the inner mitochondrial membrane. L-Acetylcarnitine (ALCAR) is an acetic acid ester of carnitine that has higher bioavailability than carnitine and is considered a fat-burning energizer supplement. We previously found that in serum sam...

Natural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from peripheral blood (PB) and pleural effusions of patien...

Supplemental Figure 1: evaluation of the CD9, activatory, and inhibitory receptor expression on total NK cell. Flow cytometric analysis on NK cells in samples from healthy individuals (hPB), peripheral blood (iPB) and pleural effusion (iPE) from patients with inflammatory disease, peripheral blood (ptPB) and pleural effusion (ptPE) from patients wi...

Cancer chemoprevention is the use of synthetic, natural or biological agents to prevent or delay the development or progression of malignancies. Intriguingly, many phytochemicals with anti-inflammatory and anti-angiogenic effects, recently proposed as chemoprevention strategies, are inhibitors of Cytochrome P450 family 1B1 (CYP1B1), an enzyme overe...

Cancer chemotherapy has made remarkable advances in the treatment of both solid and hematologic malignancies, and significant progress has been achieved in the reduction of recurrences. However, many anticancer agents, while successuful in their anti-tumor activities, are often associated with side effects affecting the cardiovascular compartment,...

Selected circulating microRNAs (miRNAs) have been suggested for non-invasive screening of non-small cell lung cancer (NSCLC), however the numerous proposed miRNA signatures are inconsistent. Aiming to identify miRNAs suitable specifically for stage I-II NSCLC screening in serum/plasma samples, we searched the databases “Pubmed”, “Medline”, “Scopus”...