Publications by authors named "Maria Licari"

11 Publications

  • Page 1 of 1

Overall survival in mCPRC patients treated with Radium-223 in association with bone health agents: a national multicenter study.

Int J Radiat Biol 2020 Dec 3;96(12):1608-1613. Epub 2020 Nov 3.

Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.

Purpose: Radium-223 has demonstrated efficacy in improving overall survival (OS) and in delaying symptomatic skeletal-related events (SREs). Bone Health Agents (BHA), i.e. RANK ligand inhibitor (Denosumab) and bisphosphonate such as zoledronic acid, are indicated to prevent SREs without a clear survival benefit. SREs on patient health have a high impact and it is, therefore, important to consider the role of new therapies with BHA to better understand the involvement of combination therapy. The primary aim of this multicentric study is to assess OS in mCRPC patients treated with Radium-223 in combination with BHA.

Materials And Methods: 430 consecutive patients treated with Radium-223 alone or in combination with BHA, affected by mCRPC, from January 2015 to July 2019 in six Italian Nuclear Medicine Units, were included. Furthermore, data were collected at baseline, after every Radium-223 administration, and during follow-up, at 3 and 6 months and 1 year after the 6th cycle. Clinical data have been evaluated before starting treatment with Radium-223 and at the end of treatment and/or at progression. Patients who received target bone therapy with BHA before Radium-223 treatment together with patients who did not receive this therapy at all (NO BHA GROUP), were compared to patients treated with concomitant Radium-223 and BHA (BHA GROUP).

Results: In univariate models ( < .05) several clinical aspects have an impact on OS: concomitant BHA ( = .018), BMI ( .001), ECOG PS ( = .000), Baseline Hb ( = .000), Baseline PSA ( = .000), Baseline tALP ( = .000), Baseline LDH ( = .000), and Baseline neutrophils ( = .009). Baseline Hb, Baseline tALP, and Baseline LDH have been confirmed as statistically significant parameters in multivariate models. Indeed, concomitant BHA has not a significant impact on OS ( = .244) in multivariate models.

Conclusions: At univariate analysis, our data showed that NO BHA GROUP and BHA GROUP differ in OS by 7 months (95%CI: (1-16.4),  = .02). This is not confirmed at multivariate analysis where after adjusting for other baseline factors, BHA is not significant anymore. This is clearly explained as bias by indication: patients with the same levels of tALP, Hb, and LDH receiving or not receiving BHA are expected to have a similar survival. Our results support and confirm the role of Radium-223 therapy on OS and, furthermore, appear to confirm that BHA treatment has not a survival benefit.
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http://dx.doi.org/10.1080/09553002.2020.1838655DOI Listing
December 2020

Milk thistle seed cold press oil attenuates markers of the metabolic syndrome in a mouse model of dietary-induced obesity.

J Food Biochem 2020 12 12;44(12):e13522. Epub 2020 Oct 12.

Department of Medicine, New York Medical College, Valhalla, NY, USA.

Milk thistle cold press oil (MTO) is an herbal remedy derived from Silybum marianum which contains a low level of silymarin and mixture of polyphenols and flavonoids. The effect of MTO on the cardiovascular and metabolic complications of obesity was studied in mice that were fed a high-fat diet (HFD) for 20 weeks and treated with MTO for the final 8 weeks of the diet. MTO treatment attenuated HFD-induced obesity, fasting hyperglycemia, hypertension, and induced markers of mitochondrial fusion and browning of white adipose. Markers of inflammation were also attenuated in both adipose and the liver of MTO-treated mice. In addition, MTO resulted in the improvement of liver fibrosis. These results demonstrate that MTO has beneficial actions to attenuate dietary obesity-induced weight gain, hyperglycemia, hypertension, inflammation, and suggest that MTO supplementation may prove beneficial to patients exhibiting symptoms of metabolic syndrome. PRACTICAL APPLICATIONS: Natural supplements are increasingly being considered as potential therapies for many chronic cardiovascular and metabolic diseases. Milk thistle cold press oil (MTO) is derived from Silybum marianum which is used as a dietary supplement in different parts of the world. The results of the present study demonstrate that MTO supplementation normalizes several metabolic and cardiovascular complications arising from dietary-induced obesity. MTO supplementation also had anti-inflammatory actions in the adipose as well as the liver. These results suggest that supplementation of MTO into the diet of obese individuals may afford protection against the worsening of cardiovascular and metabolic disease and improve inflammation and liver fibrosis.
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http://dx.doi.org/10.1111/jfbc.13522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770619PMC
December 2020

Cold Press Pomegranate Seed Oil Attenuates Dietary-Obesity Induced Hepatic Steatosis and Fibrosis through Antioxidant and Mitochondrial Pathways in Obese Mice.

Int J Mol Sci 2020 Jul 31;21(15). Epub 2020 Jul 31.

Departments of Medicine and Pharmacology, New York Medical College, Valhalla, NY 10595, USA.

Aim: Obesity is associated with metabolic syndrome, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. In this study, we investigated whether the dietary supplementation of pomegranate seed oil (PSO) exerted a protective effect on liver lipid uptake, fibrosis, and mitochondrial function in a mouse model of obesity and insulin resistance.

Method: In this in vivo study, eight-week-old C57BL/6J male mice were fed with a high fat diet (HFD) for 24 weeks and then were divided into three groups as follows: group (1) Lean; group ( = 6) (2) HF diet; group ( = 6) (3) HF diet treated with PSO (40 mL/kg food) ( = 6) for eight additional weeks starting at 24 weeks. Physiological parameters, lipid droplet accumulation, inflammatory biomarkers, antioxidant biomarkers, mitochondrial biogenesis, insulin sensitivity, and hepatic fibrosis were determined to examine whether PSO intervention prevents obesity-associated metabolic syndrome.

Results: The PSO group displayed an increase in oxygen consumption, as well as a decrease in fasting glucose and blood pressure ( < 0.05) when compared to the HFD-fed mice group. PSO increased both the activity and expression of hepatic HO-1, downregulated inflammatory adipokines, and decreased hepatic fibrosis. PSO increased the levels of thermogenic genes, mitochondrial signaling, and lipid metabolism through increases in Mfn2, OPA-1, PRDM 16, and PGC1α. Furthermore, PSO upregulated obesity-mediated hepatic insulin receptor phosphorylation Tyr-, p-IRB tyr, and pAMPK, thereby decreasing insulin resistance.

Conclusions: These results indicated that PSO decreased obesity-mediated insulin resistance and the progression of hepatic fibrosis through an improved liver signaling, as manifested by increased insulin receptor phosphorylation and thermogenic genes. Furthermore, our findings indicate a potential therapeutic role for PSO in the prevention of obesity-associated NAFLD, NASH, and other metabolic disorders.
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http://dx.doi.org/10.3390/ijms21155469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432301PMC
July 2020

Validation of the 3-variable prognostic score (3-PS) in mCRPC patients treated with Radium-dichloride: a national multicenter study.

Ann Nucl Med 2020 Oct 11;34(10):772-780. Epub 2020 Jul 11.

Department of Radiological Sciences, Oncology and Anatomical Pathology, "Sapienza" University of Rome, Rome, Italy.

Objective: Radium-223 (Ra) has been approved for treatment in patients with metastatic castration-resistant prostatic cancer (mCRPC) and bone metastasis. This α-emitting radionuclide has a beneficial effect on pain and is also capable to increase overall survival (OS). Several studies evaluated the prognostic value of different biomarkers at baseline, such as serum values, imaging parameters or pain. To date, however, clinicians lack a validated and simple system to assess which patients will most likely benefit from Ra treatment. The 3-variable prognostic score (3-PS), proposed in a single-center study in 2017 classifies patients in five prognostic groups with a specific OS. This study aims to validate the 3-PS in a larger multicenter population.

Methods: Four hundred and thirty mCRPC patients treated with Ra from six different centers were analyzed. The 3-PS score consists of the collection of baseline hemoglobin, prostatic specific antigen and Eastern cooperative oncology group performance status and was initially applied to the whole population (total group). The score was then validated on the 338 patient's subgroup (clean group) obtained by subtracting the 92 patients enrolled for the original study of the 3-PS score. This purified group served as further validation evidence.

Results: Statistical analysis showed that the 3-PS score was valid on the total group as well as in the clean group as the AUC estimated (0.74) falls within the CI of the AUC calculated on the validation sample (95% CI 0.66-0.82).

Conclusion: This study confirms the validity of the 3-PS score for mCRPC patients. This score is simple, noninvasive and affordable and can be easily used to select patients that will most probably complete Ra treatment. In addition, this tool provides an exact estimate of life expectancy in terms of OS.
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http://dx.doi.org/10.1007/s12149-020-01501-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515961PMC
October 2020

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study.

Clin Genitourin Cancer 2020 06 16;18(3):185-191. Epub 2019 Oct 16.

Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.

Background: We investigated, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy [RP] or external beam radiotherapy [EBRT]) on overall survival for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra).

Materials And Methods: In the present multicenter retrospective study, we enrolled 275 consecutive patients. The demographic and clinical data and mCRPC characteristics were recorded and evaluated at baseline and at the end of treatment or progression. Ra was administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: those who had undergone primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and those who had not received previous primary treatment (NO).

Results: Of the 275 patients, 128 (46.5%) were alive and undergoing monitoring at the last follow-up examination, 103 (37.4%) had stopped treatment because of disease progression or the onset of comorbidities, and 147 (53.5%) had died during the study period. Of the 275 patients, 132 were in the RP/EBRT group (48%), of whom 93 had undergone RP and 76 had undergone ablative EBRT, and 143 patients were in the NO group (52%). The data showed a clear advantage for the patients in the RP/EBRT group compared with those in the NO group, with an estimated median survival of 18 versus 11 months, respectively (P < .001). The results from the multivariate analysis corroborated this trend, with a hazard ratio of 0.7 (P = .0443), confirming the better outcome for the RP/EBRT group.

Conclusions: Previous radical treatment provides a protective role for patients with mCRPC undergoing Ra treatment.
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http://dx.doi.org/10.1016/j.clgc.2019.10.009DOI Listing
June 2020

Radium-223 treatment in castration resistant bone metastatic prostate cancer. Should be the primary tumor always treated?

Urol Oncol 2019 12 7;37(12):964-969. Epub 2019 Oct 7.

GSTU Foundation, Statistics, Palermo, Italy.

Introduction: Radium-223 (223Ra) improves symptoms and survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC).

Study Aim: To evaluate the impact of a previous radical prostatectomy (RP) on the outcome of 223Ra therapy in mCRPC patients. The primary prostate tumor left untreated could progress during 223Ra treatment.

Materials And Methods: mCRPC symptomatic patients treated with 223Ra were enrolled. Luteinizing Hormone-Releasing Hormone analogue was maintained. No other anticancer therapy was given. 223Ra was administered i.v. at the dose of 55 kBq/kg every 4 weeks for 6 cycles. Patients were stratified according to previous RP or not. Hematological toxicity was monitored. Statistical analysis of 223Ra discontinuations, progressions, and deaths were performed.

Results: Forty-four patients were enrolled, 16 (36.4%) previously received RP, 5 (11.3%) prostate radiotherapy and 23 (52.3%) maintained the primary prostate tumor after local treatment. All patients presented only bone metastases, 24 patients (54.5%) had more than 20. Twenty-six (59.1%) patients were treated after first or second line systemic chemotherapy. Treatment interruptions occurred in 14 patients (50%) with prostate and in 4 (25%) without (P = 0.04). After a median follow-up of 18 months (6-30 months), 15 (53.6%), and 7 (43.7%) progressions (P = 0.34) and 13 and 1 (6.2%) deaths (P = 0.04) occurred in patients with and without prostate respectively.

Conclusion: The presence of the primary prostate tumor seems to play a detrimental role in mCRPC patients undergoing 223Ra treatment in absence of other concomitant anticancer therapy. On the other hand a previous RP might play a protective role.
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http://dx.doi.org/10.1016/j.urolonc.2019.08.009DOI Listing
December 2019

Can radium 223 be a conservative non-surgical management of medication-related osteonecrosis of the jaw?

World J Nucl Med 2019 Jul-Sep;18(3):307-309

Internal Medicine, Biomedical Department of Internal and Specialist Medicine, University of Palermo, Italy.

Osteonecrosis of the jaw (ONJ) is a rare and severe necrotic bone disease reflecting a compromise in the body's osseous healing mechanisms and unique to the craniofacial region. Radium 223 dichloride (Ra223) is the only targeted alpha therapy able to extend survival in patients with bone metastases from prostate cancer. Mechanism of action and data currently available focused mainly on osteoblastic metastases from prostate cancer. In 2018, a Caucasian 54-year-old woman presented to our institution for a breast cancer with bone metastases. Since the patient refused any treatment and taking into account the bone disease, our multidisciplinary team evaluated a supplementary strategy with radium 223. A total of six treatments were planned with a dose of 50 KBq/kg every 4 weeks according to Phase 2 data. Four days after the second cycle administration, the patient presented for examination with a self-extracted necrotic bone fragment. Oroantral communication remained in the absence of algic symptomatology or suppuration. The multidisciplinary approach between oncologists, nuclear physicians, and dental health teams is crucial throughout the treatment process to avoid unnecessary suffering in patients at risk. More prospective studies are needed; however, considering the limitation of the present case, radio 223 may play an adjuvant role in the medical treatment of cancer patients with active ONJ.
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http://dx.doi.org/10.4103/wjnm.WJNM_7_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714154PMC
September 2019

Inhibition of Heme Oxygenase Antioxidant Activity Exacerbates Hepatic Steatosis and Fibrosis .

Antioxidants (Basel) 2019 Aug 5;8(8). Epub 2019 Aug 5.

Department of Drug Science, Biochemistry Section, University of Catania, 95125 Catania, Italy.

The progression of non-alcoholic fatty liver disease (NAFLD) and the development of hepatic fibrosis is caused by changes in redox balance, leading to an increase of reactive oxygen species (ROS) levels. NAFLD patients are at risk of progressing to non-alcoholic steatohepatitis (NASH), associated to cardiovascular diseases (CVD), coronary heart disease and stroke. Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. The present work was directed to determine whether use of an inhibitor of HO-1 activity affects lipid metabolism and fibrosis process in hepatic cells. Oil Red assay and mRNA analysis were used to evaluate the triglycerides content and the lipid metabolism pathway in HepG2 cells. ROS measurement, RT-PCR and Soluble collagen assay were used to assess the intracellular oxidant, the fibrosis pathway and the soluble collagen in LX2 cells. The activity of HO-1 was inhibited using Tin Mesoporphyrin IX (SnMP). Our study demonstrates that a non-functional HO system results in an increased lipid storage and collagen release in hepatocytes. Consequently, an increase of HO-1 levels may provide a therapeutic approach to address the metabolic alterations associated with NAFLD and its progression to NASH.
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http://dx.doi.org/10.3390/antiox8080277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719023PMC
August 2019

Hematologic toxicity of radium-223 in elderly patients with metastatic Castration Resistant Prostate Cancer: a real-life experience.

Prostate Int 2019 Mar 10;7(1):25-29. Epub 2018 Sep 10.

Division of Oncology, "Umberto I" Hospital - RAO, Siracusa, Italy.

Background: Treatment with radium-223 has been shown to increase survival and to delay skeletal events related to bone metastases of patients with metastatic Castration Resistant Prostate Cancer (mCRPC). This treatment has also proved to be well tolerated, and hematological toxicity, in particular anemia, represents the most represented adverse event.

Materials And Methods: We evaluated the hematologic toxicity of Ra-223 treatment in a real-life experience of 38 patients from two Italian cancer centers, with bone metastases from mCRPC. The main endpoint of the study was the evaluation of the efficacy and tolerability of treatment with radium-223, with greater reference to hematological toxicity (especially anemia) as the cause of interruption of treatment, specifically in the elderly patient.

Results: From August 2016 to October 2017, a total of 38 consecutive nonselected patients, 20 of them aged >75 years, with mCRPC symptomatic bone metastases, were enrolled for radium-223 at standard doses. Hematologic adverse events were recorded more frequently (72.4% with AE), and 36.8% had anemia. The most frequent cause of treatment discontinuation due to AEs was anemia [8/10 patients (80%)], followed by thrombocytopenia (2 patients) and neutropenia (1 patient). Hematologic AEs were more represented in elderly patients with greater disease burden and previously treated with docetaxel.

Conclusions: Anemia is the most represented AE related to radium-223 treatment in elderly patients with greater disease burden and previously treated with docetaxel, besides representing the main reason for interruption of treatment. Correct patient selection, appropriate timing, and adequate supportive care are elements that could facilitate successful treatment with radium-223, preventing premature interruption of the same. The results of this experience support the opportunity to propose treatment with radium-223 mostly in patients in the earliest stages.
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http://dx.doi.org/10.1016/j.prnil.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424691PMC
March 2019

N-Acetylcysteine (NAC) Ameliorates Lipid-Related Metabolic Dysfunction in Bone Marrow Stromal Cells-Derived Adipocytes.

Evid Based Complement Alternat Med 2018 17;2018:5310961. Epub 2018 Oct 17.

Department of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

Recent experimental data suggest that fatty acids and lipotoxicity could play a role in the initiation and evolution of metabolic bone diseases such as osteoporosis. A functional bone marrow adipose tissue (BMAT) may provide support to surrounding cells and tissues or may serve as a lipid reservoir that protects skeletal osteoblasts from lipotoxicity. The present study examined the effect of N-acetylcysteine (NAC), a powerful antioxidant and precursor of glutathione, commonly used to treat chronic obstructive pulmonary disease, on triglycerides accumulation in bone marrow stromal cells-derived adipocytes. Quantification of Oil Red O stained cells showed that lipid droplets decreased following NAC treatment. Additionally, exposure of bone marrow stromal cells (HS-5) to NAC increased adiponectin, PPAR, HO-1, and SIRT-1 and increased beta-oxidation markers such as PPAR and PPAR mRNA levels. As there is now substantial interest in alternative medicine, the observed therapeutic value of NAC should be taken into consideration in diabetic patients.
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http://dx.doi.org/10.1155/2018/5310961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207898PMC
October 2018

Cross-sectional evaluation of kidney function in hospitalized patients: estimated GFR versus renal scintigraphy.

Kidney Blood Press Res 2014 19;39(6):668-76. Epub 2014 Dec 19.

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Background/aims: Accurate staging of chronic kidney disease (CKD) is very important. We tried to identify difference in GFR evaluation between CKD-EPI and Gates method with renal scintigraphy and which variables are associated with these differences.

Methods: We retrospectively reviewed the records of 341 patients who underwent dynamic renal scintigraphy in the last 5 years. Patients were categorized according to KDIGO staging I to V, using the eGFR calculated with the CKD-EPI equation. Secondarily, we stratified patients according to treatment with renin-angiotensin system (RAS) inhibitors.

Results: Gates method tends to underestimate GFR especially in CKD stage I (mean -22.2 ml/min) and II (mean -12.5 ml/min). The division in quartiles of ages showed an underestimation of GFR only in the first quartile of age (< 50 years old). Gates method underestimation of GFR was more pronounced in stage I patients treated with RAS inhibitors (mean -34.6 ml/min). The same occurs in stage II, even though to a lesser extent.

Conclusion: The assessment of GFR by the Gates method must be carefully considered in the early stages of CKD, especially in younger patients. Moreover, the difference is more pronounced in patients treated with RAS inhibitors. Longitudinal studies will prove which method better predicts cardiovascular or renal events.
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http://dx.doi.org/10.1159/000355813DOI Listing
September 2015