Mitochondrial DNA and Inflammation Are Associated with Cerebral Vessel Remodeling and Early Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.

Pancreaticoduodenectomy with Anatomical Vascular Variant in Groove Pancreatitis-A Case Report.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal "C" loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, which is usually associated with long-term alcohol and tobacco misuse, and is more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66-year-old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast-enhanced computed tomography revealed the existence of chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head, and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since endoscopic retrograde cholangiopancreatography was not possible due to the local changes, we decided to perform pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Cystic Echinococcosis in Hospitalized Adult Patients from Western Romania: 2007-2022.

Cystic echinococcosis (CE) is a neglected parasitic disease caused by the tapeworm Echinococcus granulosus. The aim of this study was to assess the epidemiological features of human cystic echinococcosis in patients from Western Romania. We retrospectively investigated the medical records of patients hospitalized with CE between 1 January 2007 and 1 September 2022. A total of 366 patients (range 18-90 years) were recorded. The number of hospitalized individuals was higher in patients aged 50-59 years (83/366, 22.7%), in females (194/366, 53%), and in residents of rural areas (225/366, 61.5%). The liver was the most common localization of the cysts (302/366, 82.5%). Ninety-eight patients (26.8%) presented complications, including biliary fistula, allergies, and infection of the cyst. Patients with complications had a longer mean hospital stay (15.7 ± 8.3 days) compared to patients without complications (11.5 ± 7.3 days) (p < 0.001). The results of this study revealed that patients diagnosed with CE required hospitalization and extended medical care, indicating that this zoonotic disease remains a significant public health problem in Western Romania. Public health authorities should enhance CE surveillance by implementing control programs and mandatory notification of new cases.

Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease.

Chronic kidney disease (CKD) has emerged as one of the most progressive diseases with increased mortality and morbidity. Metabolomics offers new insights into CKD pathogenesis and the discovery of new biomarkers for the early diagnosis of CKD. The aim of this cross-sectional study was to assess metabolomic profiling of serum and urine samples obtained from CKD patients. Untargeted metabolomics followed by multivariate and univariate analysis of blood and urine samples from 88 patients with CKD, staged by estimated glomerular filtration rate (eGFR), and 20 healthy control subjects was performed using ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry. Serum levels of Oleoyl glycine, alpha-lipoic acid, Propylthiouracil, and L-cysteine correlated directly with eGFR. Negative correlations were observed between serum 5-Hydroxyindoleacetic acid, Phenylalanine, Pyridoxamine, Cysteinyl glycine, Propenoylcarnitine, Uridine, and All-trans retinoic acid levels and eGFR. In urine samples, the majority of molecules were increased in patients with advanced CKD as compared with early CKD patients and controls. Amino acids, antioxidants, uremic toxins, acylcarnitines, and tryptophane metabolites were found in all CKD stages. Their dual variations in serum and urine may explain their impact on both glomerular and tubular structures, even in the early stages of CKD. Patients with CKD display a specific metabolomic profile. Since this paper represents a pilot study, future research is needed to confirm our findings that metabolites can serve as indicators of early CKD.

Seroprevalence of Anti-Echinococcus granulosus Antibodies and Risk Factors for Infection in Blood Donors from Western Romania.

Cystic echinococcosis is a worldwide-distributed zoonotic parasitic disease. This cross-sectional study aimed to assess the seroprevalence and risk factors potentially associated with Echinococcus granulosus in healthy blood donors from Timis County, an endemic region in Western Romania. Serum samples were collected from 1347 Romanian blood donors. Serologic tests to determine the presence of anti-Echinococcus antibodies were performed using an anti-Echinococcus-ELISA immunoassay. Anti-Echinococcus antibodies were detected in 38 blood donors, indicating an overall seroprevalence of 2.8%. The seropositivity rate was 3.7% in females and 3.1% in blood donors residing in urban areas. The highest seropositivity was found in the age group of 31-40 years (3.6%). There were no significant differences between Echinococcus seropositivity and gender, area of residence, age, contact with dogs, or raising sheep. This serologic survey evaluated for the first time the presence of Echinococcus antibodies in healthy blood donors from Western Romania and the potential risk factors associated with echinococcosis. Our results suggest that this zoonotic infection might evolve asymptomatically in apparently healthy individuals. Further studies should be conducted in the general population to estimate the true extent of human echinococcosis and its risk factors.

Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin.

Chloride intracellular channel 1 (CLIC1) is involved in cell migration and metastasis. The histological growth patterns of liver metastasis are as follows: desmoplastic (d-HGP), replacement (r-HGP), pushing (p-HGP), and mixed. The aim of this study was to evaluate the relation between HGP, angiogenesis, and CLIC1 expression. Materials and Methods: A total of 40 cases of primary tumors and their LM: d-HGP (12 cases), r-HGP (13 cases), and p-HGP (15 cases), were evaluated through simple and double immunostaining. CLIC1 assessment was conducted as follows: scores of 0 (less than 10% of positive cells), 1 (10-30%), 2 (30-50%), or 3 (more than 50%) were assigned. Heterogeneous CLIC1 expression was found. CLIC1 in primary tumors correlated with grade G for all cases of LM with a p-HGP (p = 0.004). The CLIC1 score for LMs with an r-HGP correlated with grade G of the corresponding primary tumor (p = 0.027). CLIC1 and CD34+/Ki67+ vessels (p = 0.006) correlated in primary tumors. CLIC1 in primary tumors correlated with CD34+/Ki67+ vessels of LMs with a d HGP (p = 0.024). Conclusions: The CLIC1 score may have prognostic value, mainly for LMs with a p-HGP and r-HGP, and therapeutic value for LMs with a d-HGP.

Phytochemical Analysis and In Vitro Cytotoxic Activity against Colorectal Adenocarcinoma Cells of Hippophae rhamnodies L., Cymbopogon citratus (D.C.) Stapf, and Ocimum basilicum L. Essential Oils.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed cancer types with current deficient and aggressive treatment options, but various studied alternative therapies are able to efficiently contribute to its management. Essential oils (EOs) contain valuable compounds, with antibacterial, anti-inflammatory, and anticancer properties, which might serve as effective solutions in CRC prophylaxis or treatment. The aim of the present work was to evaluate the phytochemical composition and in vitro biological activity of essential oils derived from Hippophae rhamnoides (Hr_EO), Cymbopogon citratus (Cc_EO), and Ocimum basilicum (Ob_EO) species on HT-29 and Caco-2 human colorectal adenocarcinoma cell lines. The main compounds identified by GC-MS analysis were estragole (Hr_EO, Ob_EO), alpha- and beta-citral (Cc_EO). All tested EOs exerted a dose-dependent cytotoxicity on both cell lines by reducing the cell viability, especially in the case of Cc_EO, where at 75 µg/mL the viability percentages reached the values of 62.69% (Caco-2) and 64.09% (HT-29), respectively. The nuclear morphology evaluation highlighted significant dysmorphologies on both lines after their treatment with EOs at 75 µg/mL.

Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective.

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Two Antibiotics, Ampicillin and Tetracycline, Exert Different Effects in HT-29 Colorectal Adenocarcinoma Cells in Terms of Cell Viability and Migration Capacity.

Antibiotics are considered the cornerstone of modern medicine; however, currently, antibiotic resistance has become a global health issue. Antibiotics also find new uses in the treatment of other pathologies as well as cancer. The present study aimed to verify the impact of tetracycline and ampicillin in a colorectal adenocarcinoma cell line, HT-29. The effects of the two antibiotics on cell viability and nucleus were evaluated by the means of MTT assay and the Hoechst staining method, respectively. The irritant potential at vascular level of the chorioallantoic membrane was tested by the HET-CAM assay. Treatment of HT-29 cells with the two antibiotics determined different effects: (i) tetracycline induced a dose- and time-dependent cytotoxic effect characterized by decreased cell viability, changes in cells morphology, apoptotic features (nuclear fragmentation), and inhibition of cellular migration, whereas (ii) ampicillin exerted a biphasic response-cytotoxic at low doses and proliferative at high concentrations. In terms of effect on blood vessels, both antibiotics exerted a mild irritant effect. These results are promising and could be considered as starting point for further in vitro studies to define the molecular mechanisms involved in the cytotoxic/proliferative effects.

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy.

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin's (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment.

Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells.

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl2 and CuSO4 aqueous solutions on DNA methylation in HT-29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti-migratory potential of these substances. The results showed a dose-dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT-29 cell migration capacity. In addition, RT-qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT-29 cells and their capacity to induce epigenetic changes.

Urinary proteins detected using modern proteomics intervene in early type 2 diabetic kidney disease - a pilot study.

Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instrument. Raw data were searched using the SEQUEST algorithm and integrated into Proteome Discoverer platform. Results & discussion: Unique peptide sequences, resulted sequence coverage, scoring of peptide spectrum matches were reported to albuminuria and databases. Five proteins that can be associated with early DKD were found: apolipoprotein AI, neutrophil gelatinase-associated lipocalin, cytidine deaminase, S100-A8 and hemoglobin subunit delta. Conclusion: Urinary proteome analysis could be used to evaluate mechanisms of pathogenesis of DKD.

Thermosensitive Betulinic Acid-Loaded Magnetoliposomes: A Promising Antitumor Potential for Highly Aggressive Human Breast Adenocarcinoma Cells Under Hyperthermic Conditions.

PURPOSE: Breast cancer presents one of the highest rates of prevalence around the world. Despite this, the current breast cancer therapy is characterized by significant side effects and high risk of recurrence. The present work aimed to develop a new therapeutic strategy that may improve the current breast cancer therapy by developing a heat-sensitive liposomal nano-platform suitable to incorporate both anti-tumor betulinic acid (BA) compound and magnetic iron nanoparticles (MIONPs), in order to address both remote drug release and hyperthermia-inducing features. To address the above-mentioned biomedical purposes, the nanocarrier must possess specific features such as specific phase transition temperature, diameter below 200 nm, superparamagnetic properties and heating capacity. Moreover, the anti-tumor activity of the developed nanocarrier should significantly affect human breast adenocarcinoma cells. METHODS: BA-loaded magnetoliposomes and corresponding controls (BA-free liposomes and liposomes containing no magnetic payload) were obtained through the thin-layer hydration method. The quality and stability of the multifunctional platforms were physico-chemically analysed by the means of RAMAN, scanning electron microscopy-EDAX, dynamic light scattering, zeta potential and DSC analysis. Besides this, the magnetic characterization of magnetoliposomes was performed in terms of superparamagnetic behaviour and heating capacity. The biological profile of the platforms and controls was screened through multiple in vitro methods, such as MTT, LDH and scratch assays, together with immunofluorescence staining. In addition, CAM assay was performed in order to assess a possible anti-angiogenic activity induced by the test samples. RESULTS: The physico-chemical analysis revealed that BA-loaded magnetoliposomes present suitable characteristics for the purpose of this study, showing biocompatible phase transition temperature, a diameter of 198 nm, superparamagnetic features and heating capacity. In vitro results showed that hyperthermia induces enhanced anti-tumor activity when breast adenocarcinoma MDA-MB-231 cells were exposed to BA-loaded magnetoliposomes, while a low cytotoxic rate was exhibited by the non-tumorigenic breast epithelial MCF 10A cells. Moreover, the in ovo angiogenesis assay endorsed the efficacy of this multifunctional platform as a good strategy for breast cancer therapy, under hyperthermal conditions. Regarding the possible mechanism of action of this multifunctional nano-platform, the immunocytochemistry of the MCF7 and MDA-MB-231 breast carcinoma cells revealed a microtubule assembly modulatory activity, under hyperthermal conditions. CONCLUSION: Collectively, these findings indicate that BA-loaded magnetoliposomes, under hyperthermal conditions, might serve as a promising strategy for breast adenocarcinoma treatment.

Right hepatectomy extended to segments I and IVa and segmental colectomy performed in the same operative time - case presentation.

Colorectal cancer remains an important cause of morbidity and mortality worldwide. We present the case of a 58-year-old male patient admitted in Timisoara Hepato-Biliary-Pancreatic Surgical Center, Romania, with transverse colon cancer and synchronous liver metastases, who underwent a major hepatectomy and a segmental colon resection performed in the same operative time. The patient had a postoperative outcome without major complications and with no signs of local or distant recurrence at 15 months postoperatively. Conclusions: The synchronous approach of both the primary tumor and liver metastases in colorectal cancer is a possible therapeutic method, even in the case of major hepatectomies.

Left internal carotid artery agenesis associated with communicating arteries anomalies. A case report.

Agenesis, aplasia and hypoplasia of the internal carotid artery are rare congenital malformations. They are usually asymptomatic and incidentally discovered through ultrasound or imagistic tests. The aim of this study is to improve their management in our Departments. We report here the case of a 39-year-old woman addressed to our ambulatory in 2013 for benign symptoms like dizziness and headache. Imagistic findings (magnetic resonance imaging of the brain, and cervical spine, and magnetic resonance angiography of the head and neck) indicated a very rare condition: left internal carotid artery agenesis accompanied by the absence of the pre-communicant part of the left anterior cerebral artery and of the right posterior communicating artery. Internal carotid artery agenesis is an uncommon congenital anomaly and it could be misdiagnosed as stenosis/occlusion of this artery. This condition is important to be recognized due to the associated hemodynamic changes and in order to discover and evaluate other accompanying vascular malformations (aneurysms, collateral channels) and their life threatening potential risks (subarachnoid hemorrhage or ischemia). Also, it has a special importance in case of planning carotid or trans-sphenoidal hypophyseal surgery.

Replaced common hepatic artery originating from the superior mesenteric artery and prepancreatic, anterior course in a patient with cephalic pancreaticoduodenectomy - case report.

The presence of hepatic arterial variations is particularly important for patients undergoing cephalic pancreaticoduodenectomy, because it can lead to unnecessary incidents or postoperative complications. We present the case of a patient with pancreatic head neoplasm in which the cephalic pancreaticoduodenectomy was performed and the origin of common hepatic artery from superior mesenteric artery, with an anterior, prepancreatic course.

Synchronous gastric tumors - case presentation.

Synchronous gastric tumors, and, especially the presence of an adenocarcinoma and gastrointestinal stromal tumors, are less frequent. We present the case of a 75-year-old patient, with no gastrointestinal pathology in the medical history, who was admitted for marked asthenia, nausea, coffee grounds vomiting, inappetence, dizziness, weight loss and periodical epigastralgias. The clinical and imagistic examinations highlighted an ulcerative, infiltrative, bleeding tumor formation, present on the anterior side and subcardially on the small curvature. During the surgery, there was highlighted a second tumor, whitish, of about 2.5 cm, prominent under the peritoneal serous, of firm consistency and with an adherence to the stomach muscles. For removing the two tumors, there was performed total gastrectomy with esophagus-jejunal termino-lateral anastomosis, with jejunum ansa "in omega". The histopathological and immunohistochemical examinations established that the first tumor was a poorly differentiated carcinoma, and the second was a gastrointestinal stromal tumor. The patient's evolution was a good one, both clinically and biologically, the imagistic examinations performed after six and 12 months highlighting the lack of local relapses and absence of metastases.

Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

The tyrosine kinase inhibitors effects on metastatic tumor graft in the chick chorioallantoic membrane assay.

BACKGROUND: Due to its heterogeneous nature, pancreatic cancer has a higher incidence and a clinical treatment failure. In this study, we present the effects of Avastin, Rapamycin and their combination on the pancreatic liver metastatic human tumor graft in the chick chorioallantoic membrane (CAM) assay. MATERIALS AND METHODS: We conducted this study with 33 fertilized chicken eggs, incubated at 37°C, divided into three working groups: control (three eggs), first (10 eggs), second (10 eggs), and third group (10 eggs). A cell suspensions derived from human liver metastasis of pancreatic tumor were implanted on the CAM, in the ring. First group was treated with 2 µL Avastin (Bevacizumab 25 mg÷mL), the second with Rapamycin and the third with Avastin and Rapamycin combination on days 10, 12, 14 of incubation. The immunohistochemical techniques using vascular endothelial growth factor A (VEGFA), CD34, podoplanin, platelet-derived growth factor subunit A (PDGFA) and epidermal growth factor receptor (EGFR) as primaries antibodies were performed on metastatic tumor and metastatic tumor graft. RESULTS: Our results showed that the unique treatment with Avastin gave rise to metastases on CAM xenograft, due likely to inflammatory infiltrate and vascular remodeling. The lowest immunoexpression of CD34, podoplanin, PDGFA, EGFR has been noticed in the Rapamycin-treated group without important differences correlated to dosage and time. In the third group, decreased value was found for PDGFA only. The periphery of the tumor graft malignant cells intensely expressed VEGFA, podoplanin and EGFR. CONCLUSIONS: The inhibitory therapy with mechanistic target of Rapamycin (mTOR) and Avastin may favor the epithelial to mesenchymal transition by podoplanin and phosphatase and tensin homolog (PTEN) pathways in liver metastasis pancreatic graft to CAM.