Cathepsin D Content in Colorectal Cancer

Cathepsin D content and activity were determined in matched paired sets of colorectal tumor tissue and normal mucosa and correlated with a number of biological and clinical parameters. Significantly higher cathepsin D activity was measured in tumor cytosol compared to paired normal mucosa (p < 0.02), in Dukes’ stage A tumors compared to Dukes’ B and C (p < 0.05), in tumors < 5 cm compared to those > 5 cm, or in tumors with a low proliferation rate compared to those with a high proliferation rate (p < 0.05). Moreover, significant differences in enzyme activity between tumor tissue and paired normal mucosa were observed in node-positive and G2 tumors (p < 0.05). No significa…

Kinetics of in vivo inhibition of tissue cathepsin d by pepstatin A

1. 1. We have investigated the kinetics of inhibition of cathepsin D in heart, liver and skeletal muscle of CD-1 mice following administration of 25, 50, 100 and 200 mg/kg i.p. of pepstatin A, a specific inhibitor of this protease. 2. 2. In the liver, a significant inhibition of cathepsin D occurred up to at least 15 days, whereas, in heart and skeletal muscle, this inhibition lasted for a much shorter period of time. 3. 3. These results show that the recovery of enzyme activity to normal values is dose-dependent and that, at the same dose level, marked differences occur in the recovery of enzyme activity in these organ tissues, the liver being the most sensitive one. © 1988.

Effects of phenols of extra virgin olive oil on HL60 cell lines sensitive and reristant to anthracyclines

Modulating activity of dietary flavonols and flavan-3ols on the enzymes xanthina oxidase (XO) and mitochondrial superoxide dismutase (Mn-SOD)

Adipokines in obesity and metabolic diseases

Adipose tissue secretes many adipokines that regulate important physiological functions. Growing studies have highlighted that these bioactive molecules may contribute to the development of metabolic and cardiovascular diseases. Adipokines exert systemic metabolic effects and independent activity on numerous cells of the cardiovascular system, including cardiomyocytes and vascular cell walls. Adiponectin shows anti-inflammatory and anti-atherosclerotic activity on blood vessels. Conversely, resistin is endowed with pro-inflammatory effects and stimulates the proliferation of smooth muscle cells, thus promoting the development of atherosclerotic plaque. Leptin plays an important role in card…

Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma

With the widespread use of ultrasonography (US) and computerized tomography (CT), the usefulness of α-fetoprotein assay in the diagnosis of hepatocellular carcinoma (HCC) has decreased. The aim of our study was to evaluate the best cut-off value for serum α-fetoprotein to discriminate between liver cirrhosis (LC) and HCC and the factors influencing levels in a Sicilian population. Three hundred and seventy-two patients with LC and 197 with HCC-associated LC were studied. The etiology was: HCV in 288 cases (77.4%) of LC and 147 cases (75%) of HCC; HBV in 31 cases (8.3%) of LC and 15 cases (7.6%) of HCC; HCV/HBV in 21 cases (5.6%) of LC and 6 cases (3.0%) of HCC; non-viral in 32 cases (8.6%) …

Tumor markers in urogynaecological tumors.

Activin a and matrix metalloproteinase-2 and -9 blood levels as gauges of bone metastatic spread. In: Tumor microenvironment:Heterotypic interactions.

Different Behaviour of Plasma Antioxidant Status after Red Wine Consumption in Subjects of the Same Sex: A Preliminary Report

<p>Several studies report that the plasma antioxidant capacity (PAC) increases after a single ingestion of red wine. However, data on the different behaviour of PAC after food intake in subjects of the same sex are still lacking. On the basis of these observations some investigations were undertaken in order to evaluate the effects of red wine intake on PAC in a homogeneous groups of healthy female volunteers (n=18). Additionally, the possible correlation between increase of PAC values and increase in uric acid levels was also assessed. PAC and uric acid concentrations were determined before wine intake and 50, 120 and 240 minutes thereafter. The results obtained following these studi…

ACTIVIN A CIRCULATING LEVELS IN PATIENTS WITH PRIMARY OSTEOPOROSIS OR BONE METASTASES FROM BREAST CANCER

Cathepsin L in Normal and Pathological Bone Remodeling

Abstract Cathepsin L is a ubiquitous lysosomal cysteine endopeptidase that is mainly involved in the metabolic turnover of intracellular proteins. However, it is now well established that this enzyme may also be implicated in the regulation of other important biological processes includ- ing bone resorption. Therefore, altered expression levels of Cathepsin L may result in disturbances of bone homeo- stasis and, eventually, in the onset of pathological condi- tions associated with altered bone turnover. These observations support the concept that Cathepsin L may be regarded as an additional target for the development of novel therapeutic options for the treatment of patients with bone disea…

Phenotyping normal kidney function in elderly patients with type 2 diabetes: a cross-sectional multicentre study

AimsType 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80years or older who presented with a fully preserved kidney function.MethodsFrom an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR>90ml/min/1.73m(2) and …

Activin A circulating levels in patients with osteoporosis or bone metastasis from breast cancer

Cathepsin D in the malignant progression of neoplastic diseases

Recent studies suggest that aspartic proteinase Cathepsin D may be implicated in the process of tumor invasion and metastasis. In fact several in vitro observations showed that this proteinase may facilitate the spread of neoplastic cells through different mechanisms related to its proteolytic activity by acting at different levels of the metastatic cascade. Cathepsin D may promote tumor cell proliferation by acting as an autocrine mitogen through the activation of latent forms of growth factors or by interacting with growth factor receptors. The enzyme was also shown to be able to degrade in vitro extracellular matrix and to activate latent precursors forms of other proteinases involved in…

Effects of phenols of extra vergin olive oil on Hl60 cell lines sensitive and resistant to anthracycline

MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone.

Background: The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. Patients and Methods: MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). Results: Activin A…

Effects of oleuropein on tumor cell growth and bone remodelling: Potential clinical implications for the prevention and treatment of malignant bone diseases

Oleuropein (Ole) is the main bioactive phenolic compound present in olive leaves, fruits and olive oil. This molecule has been shown to exert beneficial effects on several human pathological conditions. In particular, recent preclinical and observational studies have provided evidence that Ole exhibits chemo-preventive effects on different types of human tumors. Studies undertaken to elucidate the specific mechanisms underlying these effects have shown that this molecule may thwart several key steps of malignant progression, including tumor cell proliferation, survival, angiogenesis, invasion and metastasis, by modulating the expression and activity of several growth factors, cytokines, adh…

Effects of Zoledronic Acid on Cathepsin K circulating levels in patients with bone metastasis.

Cathepsin K serum levels were determinated in patients with bone metastases from breast cancer or prostate cancer in therapy with zoledronic acid or in patients or in patients with located breast or prostate cancer end in patients with non malignant diseases and in healthy blood. donors (control group). Cathepsin K serum levels were significantly more eleved in healthy subjects or in patients with peimary osteoporosis. Furthermore, the administration of Zoledronic acid to patients with metastatic bome disease from breast or prostate cancer, induced a marked increase of Cathepsin K serum levels.

Haemopoietic effects of 7 alpha, 17 beta dimethyltestosterone.

Some haematic parameters were investigated in female COBS mice treated with 7 alpha, 17 beta Dimethyltestcsterone (DMT). The drug causes an increase of circulating platelets in normal mice. Bone marrow graft from DMT-treated donors facilitates in irradiated mice repopulation of white blood cells and platelets but lowers % survival. These data are interpreted on the basis of a commitment and a loss of self-maintenance induced by DMT on CFUs compartment. © 1979 The Italian Pharmacological Society.

Cytotoxic effects of a crude extract of extra virgin olive oil on human HL60 cell lines sensitive and resistant with MDR phenotype

Lysosomal alterations in heart and liver of mice treated with doxorubicin.

This study was carried out to evaluate the influence of long-term treatment with doxorubicin (DXR) (4mg/kg IV for 5 weeks) on heart and liver lysosomes of mice. We evaluated the variations in both total and "sedimentable" enzyme activity of cathepsin D, which is the major endopeptidase of myocites and probably involved in physiologic and pathologic degradation of actomyosin and mitochondria, and that of acid phosphatase, which is more prominent in interstitial cells. Our results show that marked changes occur in both total and sedimentable enzyme activity of cathepsin D in the heart of treated animals and to a lesser extent in the liver. In contrast, no modification of either total or sedim…

Cathepsin D activity levels in colorectal cancer: Correlation with cathepsin B and L and other biological and clinical parameters

Cathepsin D, B and L activity levels were determined in colorectal cancer and correlated with a number of biological and clinical parameters. Our studies have evidenced significant higher activity levels of these lysosomal enzymes in tumor cytosol compared to paired normal mucosa as well as an evident increase of tumor specific cathepsin D activity in Dukes' stage A tumors compared to later stages (B, C and D). Furthermore, significant higher cathepsin B and L activity levels were observed in Dukes' stage A compared to Dukes' stage D tumors while significant higher cathepsin B activity levels were observed in tumors ≤5 cm than in those >5 cm as well as in moderately differentiated tumors…

Induction of differentiation by phenols crude extract of extravirgin olive oil on tumor cell lines sensitive and resistatnt to antitumor agents

Corrigendum to “Effects of Oleuropein on tumor cell growth and bone remodeling: Potential clinical implications for the prevention and treatment of malignant bone diseases” [Life Sci. 264 (2021) 118694]

Differential expression levels of urokinase-type plasminogen activator and cathepsin D in locally advanced laryngeal squamous cell carcinoma: Clinical implications

The expression levels and the prognostic impact of urokinase-type plasminogen activator (uPA) and cathepsin D (CD) were evaluated in patients with locally advanced laryngeal squamous cell carcinoma (LSCC). uPA and CD protein levels were determined by immunoluminometric or immunoenzymatic assays in the cytosol of paired sets of tumor tissues and corresponding adjacent normal mucosa (NLM) from 57 patients with stage III/IV LSCC and were correlated with a number of clinicobiological parameters of this tumor including anatomical site, tumor grade, nodal status, clinical stage, DNA ploidy, proliferation rate, and patient outcome. Median uPA levels were significantly higher in LSCC than in NLM (…

Cathepsin D: A possible biochemical marker for anthracycline cardiomyopathy

This study was carried out in an attempt to assess the pattern of cathepsin D variations induced by Doxorubicin (DXR) and to clarify the role possibly played by this endopeptidase in the onset of anthracyclines-induced cardiotoxicity. We evaluated the variations in both total and 'sedimentable' enzyme activity of cathepsin D in the heart of mice treated once a week for up to 8 weeks with DXR (4 mg/kg i.v.b.wt.) and sacrificed 12h, 3 and 6 days after 1, 4, 5 and 8 administrations. Our results show that significant but transitory changes in both total and sedimentable activity of cathepsin D occur after each administration and decline after prolonged treatments. These data do not suggest, but…

Zoledronic acid-induced variations in MMP-2, MMP-9 and uPA plasma concentrations in patients with metastatic bone disease

3,5-DIIODO-L-THYRONINE-INDUCED MODIFICATION IN PITUITARY-THYROID AXIS IN RATS FED HIGH-FAT DIET. A PRELIMINARY REPORT

Experimental observations highlight that the administration of 3,5-diiodo-L-thyronine (T2) may decrease the body weight and the plasma levels of cholesterol and triglycerides and may prevent the onset of hepatic steatosis in rats fed diets rich in lipids (HFD). On the basis of these findings we have carried out some in vivo studies to evaluate the effects of increased levels of T2 on pituitary thyroid axis function in HFD rats. Fifteeen Wistar male rats were divided in 3 groups. The first group (N) was fed with a standard diet. The second group (G) was fed with a diet high in fat (HDF), while the third group (GT2) was additionally administered intraperitoneally with T2 (70 ug/100g body weig…

Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases.

Background: The effects of the bisphosphonate derivative zoledronic acid (ZA) on the > circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 > (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in > patients with bone metastasis (BMTS) and the possible correlation with the symptomatic > response induced by this drug in these patients were evaluated. Patients and Methods: > Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the > plasma of 30 patients with painful bone metastases from breast or prostate cancer > undergoing multiple treatment with ZA (4 mg i.v., every 4 weeks). Healthy subjects > (HS) of…

Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications.

Cathepsin D is a lysosomal acid proteinase which is involved in the malignant progression of breast cancer and other gynecological tumors. Clinical investigations have shown that in breast cancer patients cathepsin D overexpression was significantly correlated with a shorter free-time disease and overall survival, whereas in patients with ovarian or endometrial cancer this phenomenon was associated with tumor aggressiveness and a degree of chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate the role and the prognostic value of cathepsin D also in other solid neoplasms. However, conf…

Influence of flavonoids on the transmembrane electron transport:study ex-vivo

The oxidative stress results from a change in the physiological balancebetween oxidant and antioxidant species. This condition induces an chemical change in the redox state of cells.. The function of t-PMET is to cooperate with intracellular redox pairs, like piruvate and lactate, to maintain thecytoplasmatic NAD+/NADH balance. The t-PMET is correlated with the modulation of internal pH and redox homeostasis, as it is able to activate proton release. Thus, t-PMET causes external and internal pH modification, as well as development of an inside negative membrane potential. The aim of this work was evaluate the erythrocytes redox status in a group of health volunteers and then to study whethe…

Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications.

The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as comp…

Stefin A and cathepsin B and L circulating serum levels in patients with malignant or non-malignant liver diseases: A preliminary report

Experimental and clinical studies have recently shown a significant correlation between increased activity levels of lysosomal proteinases Cathepsin B, L in tumor tissues and malignant progression. On the basis of these findings we have undertaken some preliminary studies to evaluate the clinical impact of these enzymes and their intracellular inhibitor Stefin A in patients with malignant and non malignant liver diseases. The serum levels of Cathepsin B, L and Stefin A resulted significantly increased (mean 7 folds) in patients with liver diseases as compared to healthy subjects . these findings suggest that Cathepsin B, Cathepsin L, and Stefin A serum levels may be potentially useful as pr…

Flavonols and flavan-3-ols as modulators of xanthine oxidase and manganese superoxide dismutase activity.

Experiments were performed to assess the dose-dependent effects of quercetin, kaempferol, (+) catechin, and (-) epicatechin on superoxide radical production through the modulation of manganese superoxide dismutase and xanthine oxidase activities. The experiments were carried out at flavanoid concentrations ranging from 1 µM to 100 µM. This investigation highlighted that flavonols induced opposite effects on superoxide radical production at different doses, i.e. pro-oxidant at the highest concentration (100 µM) and anti-oxidant at the lowest concentration (1 µM). Similar behaviors were observed for xanthine oxidase with flavan-3ols. The diastereoisomer (the catechin) acted as a stronger radi…

On the role of cystatin C in cancer progression

Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases, which has been shown to play a role in several normal and pathological processes. Interestingly, a growing number of experimental and clinical studies suggest that this inhibitor also appears to be implicated in the malignant progression of various human tumors. However, the role of Cyst C in malignant diseases is still controversial as these studies have highlighted that this protein may function either as tumor suppressor or tumor promoter. The specific mechanisms underlying these opposing effects at present remain murky and are the subject of many current investigations. On the other hand, a complete knowle…

Vitamin D in cancer chemoprevention

Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Results and conclus…

The Role of Vitamin K in Bone Remodeling and Osteoporosis

Vitamin K is an essential fat soluble vitamin involved in the regulation of normal coagulation. However, growing evidence highlights that this molecule appears to be also implicated in the regulation of other important biological functions such as bone mineralization, calcium homeostasis, apoptosis, cell growth and signal transduction. In particular, many studies have focused their attention on the protective effects of vitamin K on bone tissue in the outlook of its use in the prevention and treatment of osteoporosis in post-menopausal women. The objective of the present paper is to review data of the literature regarding the metabolic effects of Vitamin K in bone tissue and its clinical ro…

Induction of differentiation by phenols crude extract of extavirgin olive oil on tumor cell lines sensitive and resistant to anticancer drugs

Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines

Subcutaneous recombinant human erythropoietin prevents chemotherapy-related anemia in patients with advanced cancer.

Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C.

The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst C), an endogenous inhibitor of cysteine proteinase cathepsin K, was investigated by immunoassays in patients with bone metastasis from breast cancer (BCa) or prostate cancer (PCa). Additional studies were also performed in these patients to assess the effects of zoledronic acid (ZA) administration on the circulating levels of these molecules. Mean IL-6 and Cyst C serum concentrations were signifi- cantly increased in BCa patients and in patients with primary osteoporosis (PU) compared to healthy subjects (HS). However, Cyst C, but not IL-6, resulted significantly more elevated in BCa patients t…

Circulating cathepsin K and cystatin C in patients with cancer related bone disease: clinical and therapeutic implications.

Abstract The clinical significance of serum cathepsin K and cystatin C was assessed in patients with breast cancer (BCa) or prostate cancer (PCa) with confined disease (M0) or bone metastasis (BM). Cathepsin K and cystatin C circulating levels were determined by ELISAs in 63 cancer patients, in 35 patients with nonmalignant diseases and in 42 healthy blood donors (control group). In BCa patients, cathepsin K serum levels were significantly lower than in sex matched control group (HS; p  = 0.0008) or in patients with primary osteoporosis (OP; p  = 0.0009). On the contrary, cystatin C levels were significantly higher in BCa patients than in HS ( p  = 0.0001) or OP ( p  = 0.017). In PCa patien…

Biological characterization of laryngeal squamous-cell carcinoma

The traditional prognostic factors, including stage of disease and tumour grade, have shown a limited prognostic significance and an inability to predict clinical response to specific treatment in patients with laryngeal squamous-cell carcinoma. More recent data suggest that cell kinetics indices, DNA-ploidy, lysosomal cysteine proteinase expression and genetic changes of both tumour suppressor genes and proto-oncogenes may be considered as reliable and reproducible indicators of biological aggressiveness in these patients. Moreover, the frequency of different genetic alterations suggests that several pathways are involved in the genesis of these neoplasias and, in particular, it is very pr…

The potential of cystatin C as a predictive biomarker in breast cancer

Breast cancer (BCa) is the leading cause of cancer-related deaths among women. Numerous efforts are being directed toward identifying novel tissue and/or circulating molecular markers that may help clinicians in detecting early-stage BCa patients and in providing an accurate estimation of the prognosis and prediction of response to clinical treatments. In this setting, emerging evidence has indicated Cystatin C (Cyst C), as the most potent endogenous inhibitor of cysteine cathepsins, as a possible useful marker in the clinical management of BCa patients.This review analyzes the results of emerging studies underpinning a potential clinical role of Cyst C, as additional marker in BCa.Cyst C e…

Bioactive effects of citrus flavonoids and role in the prevention of atherosclerosis and cancer

Citrus fruits are the main fruits of the Mediterranean diet and have been long recognized for their beneficial effects on human health. Observational studies have shown a significant association between dietary flavonoid intake and reduced risk of cardiovascular and malignant diseases. The beneficial effects of citrus fruits on human health appear to be due to their high content in vitamins, minerals and fibers. In particular, the antioxidant and anti-inflammatory activities have been indicated as some of the mechanisms through which citrus fruits may thwart the development of chronic degenerative diseases such as atherosclerosis and cancer. This review would critically examine the results …

Clinical significance of Activin A serum levels in patients with primary osteoporosis: a preliminary report

The role of histamine in doxorubicin and teniposide-induced cardiotoxicity in dog and mouse.

In previous studies we reported that teniposide (VM26) induced acute cardiac effects in dogs seem to be related to a release of histamine and that a prior treatment with chlorpheniramine, an H, histamine blocker, prevents the onset of this phenomenon. Since histamine and other vasoactive substances also seem to be involved in doxorubicin (DXR)-induced acute cardiac effects, experiments were undertaken in the aim to prevent, as in the case of VM26, the onset of this phenomenon by administering chlorpheniramine. Since DXR-induced chronic cardiomyopathy also seems to be related to the same mechanisms involved in the onset of acute cardiac effects induced by this drug, additional studies were …

Activin A and matrix metalloproteinase -2 and -9 blood levels as gauges of bone metastatic spread

The use of zoledronic acid in patients with bone metastases from prostate carcinoma: Effect on analgesic response and bone metabolism biomarkers

Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers. Eligibility for this study required prostate cancer patients with metastatic bone disease and pain not controlled by analgesics. Patients were excluded from the study if they were receiving cytotoxic chemotherapy or radiation therapy within three months. Eighteen patients (75%) were considered responder to acid zoledronic, only 6 patient…

Effects of amsacrine (m-AMSA), a new aminoacridine antitumor drug, on the rabbit heart.

There is emerging clinical evidence that amsacrine (m-AMSA) administration may be associated with cardiotoxic effects such as severe, even fatal, ventricular arrhythmias and impairment of the inotropic performance of the heart. Information on the cardiac effects of m-AMSA in animals is scanty. Studies on mice, dogs, and monkeys have not evidenced the cardiotoxicity of the compound. The data presented in this paper show that m-AMSA causes acute ECG alterations in normal rabbits and a dose-related negative inotropic effect on the isolated rabbit heart, suggesting that this species may be a useful model for the study of the cardiac actions of this antiblastic.

Lenograstim in preventing chemotherapy-induced febrile neutropenia in patients with soft tissue sarcoma

Background: Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in chemotherapeutic regimens for soft tissue sarcoma. Prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN). The correct timing of G-CSF administration should be considered in order to optimize the prophylactic treatment. Patients and Methods: Patients (≥18 years old) affected by soft tissue sarcoma and treated with epirubicin and ifosfamide, underwent prophylactic treatment with G-CSF (lenograstim at 263 μg) from day 5 to day 9. The proportion of patients experiencing FN and G4 neutropenia was considered. Results: A total of 36 patient…

Serum follistatin in patients with prostate cancer metastatic to the bone

The clinical significance of circulating fol- listatin (FLST), an inhibitor of the multifunctional cytokine activin A (Act A), was investigated in patients with prostate cancer (PCa). The serum concentrations of this molecule were determined by an enzyme-linked immunosorbent assay (ELISA) in PCa patients with (M?) or without (M0) bone metastases, in patients with benign prostate hyperplasia (BPH) and in healthy sub- jects (HS). The effectiveness of FLST in detecting PCa patients with skeletal metastases was determined by the receiver operating characteristic (ROC) curve analysis. Serum FLST was significantly higher in PCa patients than in BPH patients (P = 0.001) or HS (P = 0.011). Converse…

Selenium and Autoimmune Thyroiditis

The essential mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system. An elevated selenium intake may be associated with reduced cancer risk

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF w…

Activin A and bone metastasis

Activin A, is a multifunctional cytokine of the transforming growth factor-b superfamily of growth factors. This molecule has been shown to be implicated in the regulation of a broad range of important biological functions including bone remodelling. Therefore, a deregulation in the activin signalling pathway may result in disturbances of normal bone metabolism and, eventually, in the onset of severe pathological conditions associated with an altered bone resorption. These observations support the concept that Act A might also be implicated in the pathogenesis of bone metastasis. This review provides insight into the most recent advances in understanding the role of this growth factor in th…

Cytotoxic effects of polyphenols from waste-water of extra virgin olive oil on human HL60 and K562 cell lines.

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy b…

New potential circulating markers for the therapeutic monitoring of metastatic bone disease.

Effects of extra virgin olive oil phenols on HL60 cell lines sensitve and resistant to anthracycline

Lysosomal aspartic and cysteine proteinases serum levels in patients with pancreatic cancer or pancreatitis

Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in patients with ductal pancreatic carcinoma (DPC) and correlated with some biological and clinical parameters of this tumor. CB serum concentrations significantly higher than those measured in healthy subjects (NS) were observed in CHP, AP, and DPC patients (p < 0.01). However, no significant difference was noted among these groups. Increased CL serum levels were evident only in cancer patients compared to NS, AP, or CHP groups (p < 0.05), while no difference was observed among these groups. Elevated CD serum values were observed i…

Membrane gangliosides and immuno-mediated cytolysis in drug sensitive and treatment-induced multidrug resistant human ovarian cancer cells

The pattern of cytoplasmic membrane gangliosides and two cellular features which have been reported to be related to the expression of different membrane gangliosides, namely adhesion to solid substrates and susceptibility to the lytic activity of immune effector cells, have been investigated in drug sensitive A2780 human ovarian cancer cells and in two treatment-induced multidrug resistant sublines (A2780-DX1 and A2780-DX3). The total membrane gangliosides content of A2780 sensitive cells was comparable to that of the two multidrug resistant (MDR) sublines, but the acquisition of the MDR phenotype was characterized by an increased expression of the polysialylated gangliosides (particularly…

Flow cytometric DNA analysis and lysosomal cathepsins b and l in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance

Background. The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. Methods. Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC. Lysosomal cathepsin B and L activity levels were determined biochemically in match…

Antimetastatic activity of adriamycin in combinations with proteinase inhibitors in mice

The antimetastatic activity of adriamycin in combination with proteinase inhibitors was investigated in mice bearing the metastatic tumors L1210 leukemia, Lewis lung carcinoma or M5076 sarcoma. Leupeptin, a cathepsin B inhibitor, when administered as a single agent was devoid of antimetastatic activity but some therapeutic activity was noted in mice with Lewis lung carcinoma when the agent was administered in combination with adriamysin. Pepstatin A, a cathepsin D inhibitor, had no effect as a single agent in mice with L1210 leukemia but displayed some antimetastatic activity in mice with Lewis lung carcinoma. In mice with M5076 sarcoma the combination of pepstatin A and adriamycin resulted…

Effects of E-64 (cysteine-proteinase inhibitor) and pepstatin (aspartyl-proteinase inhibitor) on metastasis formation in mice with mammary and ovarian tumors.

The effects of E-64 (Cathepsin B and L inhibitor) and Pepstatin A (Cathepsin D inhibitor) on spontaneous and experimental metastasis formation were investigated in mice with MCa mammary carcinoma, M5076 ovarian sarcoma and L1210 leukemia. Pepstatin induced a marked decrease in the number of spontaneous metastasis in MCa or M5076 tumor bearing mice. This phenomenon was also noted with E-64 but only in M5076 tumor bearing mice. On the other hand, both these agents were unable to prevent the formation of experimental metastasis in mice injected i.v. with L1210, MCa or M5076 tumor cells or with tumor cells in which Cathepsin B, L and D activities were inhibited by a 24 hour continuous exposure …

Clinical Impact of Cystatin C/Cathepsin L and Follistatin/Activin A Systems in Breast Cancer Progression: A Preliminary Report.

This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively. Therefore, these proteins may have a clinical role as circulating biomarkers in the diagnosis and therapeutic monitoring of breast cancer patients.

Cardiac lysosomes in doxorubicin cardiotoxicity: An ultrastructural study

Effect of extra virgin olive oli phenols on HL60 cell lines sensitive and resistant to anthracyclines

Activin A circulating levels in Patients with primary osteoporosis or bone metastases from brest cancer

LIVELLI CIRCOLANTI DI ACTIVINA A IN PAZIENTI CON OSTEOPOROSI PRIMITIVA O METASTASI OSSEE DA CARCINOMA MAMMARIO

Cathepsin D serum mass concentrations in patients with hepatocellular carcinoma and/or liver cirrhosis

Cathepsin D serum mass concentrations were determined by enzyme immunoassay in patients with hepatocellular carcinoma (n = 51) and/or liver cirrhosis (n = 92) or benign steatosis (n = 16) and correlated with some biochemical and clinical properties of these diseases. Increased cathepsin D serum mass concentrations (P < 0.001) were observed in all these groups of patients as compared to normal subjects (n = 98). However, patients with steatosis had serum mass concentrations of this enzyme significantly lower (mean 2—3 fold) than those measured in cancer patients (P < 0.05) or cirrhotic patients (P < 0.001). Interestingly, significantly higher cathepsin D serum mass concentrations (m…

Current status and future directions in the treatment of bone metastases from breast cancer

The clinical treatment of bone metastasis from breast cancer is currently based on the systemic administration of antiresorptive agents, radiopharmaceuticals, and/or local treatments such as radiation therapy, radiofrequency ablation and surgery. However, these therapeutic options are merely palliative and do not show to have a significant positive impact on patients' survival. In addition, the systemic administration of antiresorptive drugs and/or antitumour agents and/or radiopharmaceuticals may negatively affect normal bone metabolism with detrimental consequences for cancer patients. Hence, the need to identify alternative therapeutic strategies that, based on the hallmarks of bone meta…

Follistatin as potential therapeutic target in prostate cancer

Follistatin is a single-chain glycosylated protein whose primary function consists in binding and neutralizing some members of the transforming growth factor-β superfamily such as activin and bone morphogenic proteins. Emerging evidence indicates that this molecule may also play a role in the malignant progression of several human tumors including prostate cancer. In particular, recent findings suggest that, in this tumor, follistatin may also contribute to the formation of bone metastasis through multiple mechanisms, some of which are not related to its specific activin or bone morphogenic proteins' inhibitory activity. This review provides insight into the most recent advances in understa…

Cathepsin L in metastatic bone disease: therapeutic implications

AbstractCathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests that this endopeptidase might also be implicated in the regulation of other important biological functions, including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodeling processes, could contribute to facilitate bone metastasis formation. In support of this hypothesis, recent studies indicate that cathepsin L can foster this process by triggering multiple mechanisms which, in part, differ from those of t…

Effects of eztra virgin olive oil phenols on HL60 cell line sensitive and resistant to anthracycline.

Nutrition, obesity and hormones

Obesity is a chronic pathological condition with a multifactorial aetiology, characterised by an excessive body fat accumulation with multiple organ-specific consequences. Emerging evidence highlights that obesity appears to be associated with multiple alterations in the endocrine system. However, the mechanisms underlying the interactions between obesity and this system remain still controversial. This review discusses the impact of obesity on various endocrine systems and, in particular, would provide a general overview on the biochemical changes that may occur in each of these axes in association with obesity.

Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines

The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance). Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At …

Pepstatins: Aspartic proteinase inhibitors having potential therapeutic applications

Cathepsin D (EC 3.4.23.5) is a lysomal aspartie proteinase that is involved, under normal phusiologycal conditions, ...

Effects of 3,5-diiodo-L-thyronine on the liver of high fat diet fed rats

Experimental studies have highlighted that the administration of 3,5-diiodo-L-thyronine (T2) to rats fed diets rich in lipids induces a decrease of cholesterol and triglycerides plasma levels and body weight (BW) without inducing liver steatosis. On the basis of these observations we carried out some experimental <em>in vivo</em> studies to assess the effects of multiple high doses of T2 on the pituitary thyroid axis of rats fed diet rich in lipids. Fifteen male Wistar rats were divided into three groups of five animals each. The first group (N group) received standard diet, the second group was fed with a high fat diet (HFD group), while the third group (HFDT2 group) was additi…

ERYTHROCYTE CATALASE ACTIVITY IN EVER-SMOKERS AND NO-SMOKERS HEALTHY SUBJECTS: INFLUENCE OF FLAVONOIDS (QUERCETIN AND LUTEOLIN)

ERYTHROCYTE CATALASE ACTIVITY IN EVER-SMOKERS AND NO-SMOKERS HEALTHY SUBJECTS: INFLUENCE OF FLAVONOIDS(QUERCETIN AND LUTEOLIN) Background. Oxygen free radicals are highly reactive species that can cause cell damage including lipid peroxidation, enzyme inactivation and DNA damage. Inactivation and removal of highly reactive species depend by the antioxidant defence systems. The catalase (CAT) belongs to the primary antioxidant defence system of the cell which catalyses the decomposition of hydrogen peroxide to water and molecular oxygen. Flavonoids are a group of polyphenolic compounds with different chemical structure and properties. They are widely distributed in fruits, vegetables, nuts, …

TP53 mutations and S-Phase fraction are independent prognostic indicators in locally advanced laryngeal squamous cell carcinoma

Larynx tumor is a rare neoplasia that represent only the 2% of all human tumor. In particular, the 90% of tumor that occur in this organ correspond to the laryngeal squamous cell carcinoma (LSCC). From the biomolecular point of view, it was shown that the TP53 gene mutations are the most common events observed in the early phases of LSCC carcinogenesis. However, them prognostic significance remains controversial. Besides, the prognostic significance of DNA ploidy has been well established for other solid tumors, but its role in LSCC is still controversial. The aim of this study was, therefore, to prospectively evaluate the prognostic significance of TP53 mutations, DNA-ploidy and S-phase fr…

Studio del pattern di distribuzione dell'Activina A nel siero di pazienti con metastasi ossee da carcinoma prostatico in trattamento con acido zoledronico

Effects of Oleuropein on colon cancer progression in vitro. A preliminary report

Introduction. Accumulating evidence highlights that Oleuropein (OLE), one of the main bioactive phenolic compound present in olives, olive oil and olive leaves, appears to exert chemo-preventive effects against several human malignancies including gastrointestinal tumors. As the cellular mechanisms underlying this phenomenon are still not fully elucidated, we have undertaken some in vitro studies to examine the effects of OLE on the growth, adhesion and invasion of HTC116 and SW480 human colon cancer cells and the influence of this molecule on the production of certain proteins that appear to be relevant to cancer progression namely, matrix metalloproteinase-2 (MMP-2), matrix metalloprotein…