Polyploidy in First and Second Trimester Pregnancies in Romania - a Retrospective Study.

BACKGROUND: Polyploidy is a rare lethal cytogenetic anomaly in pregnancies, generally leading to pregnancy termination. This study aims to compare first and second trimester polyploidy in pregnancies and describe the underlying mechanisms. METHODS: A retrospective study was conducted in three medical genetics laboratories, collecting cases from Eastern, Southern, and Western Romania. The period of interest was January 2008 to December 2018. Prenatal samples (chorionic villi and amniotic fluid) and miscarriage samples were tested by standard karyotyping, as well as QF-PCR or FISH as complementary or alternative techniques. RESULTS: In first trimester pregnancies, we report cytogenetic results of chorionic villi samples from miscarriages: 25 triploid cases and 13 tetraploid cases. In second trimester samples obtained by amniocentesis, cytogenetic findings were positive for 17 triploid cases. Maternal age, age of the pregnancy, and fetal gender identified by ultrasound were recorded in all cases and, additionally, data on biochemical risk and ultrasonographic findings for second trimester pregnancies. CONCLUSIONS: Cytogenetic investigations of spontaneous abortions provide valuable information on the cause of abortion. This information is crucial for genetic counseling and may also contribute to prenatal diagnosis in subsequent pregnancies.

Prenatal and postnatal findings in a 10.6 Mb interstitial deletion at 10p11.22-p12.31.

Interstitial deletion of the proximal short arm of chromosome 10 represents a rare genetic alteration. Literature review revealed that only 10 postnatal diagnosed clinical cases with deletions overlapping 10p12p11 were published until present. We report the first prenatal diagnosis and postnatal findings in a male fetus with a 10.6 Mb interstitial deletion of the short arm of chromosome 10 (10p11.22-p12.31).

IL-1RN +2018T>C polymorphism is correlated with colorectal cancer.

Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B -511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06-5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05-7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.

Cytokine promoter polymorphisms and risk of colorectal cancer.

BACKGROUND: Cytokines and chemokines are involved in cancer development and progression, but their role in colorectal tumorigenesis is still far from well defined. This study investigated the association between five cytokine promoter polymorphisms and risk, stage, and histological grade of colorectal cancer (CRC) in a hospital-based case-control study. METHODS: A total of 377 Romanian subjects were included in this study: 144 patients with sporadic colorectal cancer and 233 controls. Cytokine polymorphisms (IL-1B -31T > C, IL-4R -3223C > T, IL-8 -251T > A, IL-10 -1082A > G, and TNF-A -308G > A) were genotyped by allelic discrimination TaqMan PCR assay with specific probes. RESULTS: A significant association was observed for IL-10 -1082A > G polymorphism, the subjects carrying AG genotype were at a lower risk for CRC (OR 0.63, 95% CI: 0.40 - 0.98) when compared with the more frequent AA genotype. Furthermore, in a dominant model the carriers of G allele were protected against CRC (OR 0.64, 95% CI: 0.42 - 0.97). In a stratified analysis the only association between CRC and cytokine polymorphisms was found for carriers of IL-10 -1082G allele and was restricted to poorly differentiated cases (OR 0.36, 95% CI: 0.16 - 0.81). No association was observed for the remaining polymorphisms and CRC risk. CONCLUSIONS: This study shows that IL-10 -1082A > G polymorphism may influence CRC risk, the carriers of G allele being protected against CRC in the Romanian population.

Terminal deletion 2q37.3 in a patient with Klippel-Trenaunay-Weber syndrome.

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disorder, characterized by capillary, venous and lymphatic vascular malformations in association with bone and soft tissue hypertrophy. We report a KTWS patient with extensive hemangiomatosis of the right lower limb, trunk and upper limbs; bone and soft tissue hypertrophy of upper limbs, scapular girdle and right lower limb; and muscle atrophy on left lower limb with marked body asymmetry, scoliosis and toe malformations. These pathological features are associated with moderate mental retardation, mild renal and hepatic abnormalities. We identified by array CGH (Comparative Genomic Hybridization) a submicroscopic deletion 2q37.3 that could be related to impaired cognitive function. To our knowledge this is the first reported 2q37.3 microdeletion in a patient with KTWS.

miR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71-24.47; OR 2.30, 95% CI: 1.23-4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population.

First Trimester Ultrasound Detection of Fetal Central Nervous System Anomalies.

OBJECTIVE: To evaluate the potential of the first-trimester ultrasound (US) features for the detection of central nervous system (CNS) anomalies. Methods/Methodology: This is a prospective one-center three-year study. Unselected singleton pregnant women were examined using an extended first-trimester anomaly scan (FTAS) that included the CNS assessment: the calvaria shape, the septum (falx cerebri), the aspect of the lateral ventricles, the presence of the third ventricle and aqueduct of Sylvius (AS) and the posterior brain morphometry: the fourth ventricle, namely intracranial translucency (IT), brain stem/brain stem-occipital bone ratio (BS/BSOB) and cisterna magna (CM). The spine and underlying skin were also evaluated. The cases were also followed during the second and third trimesters of pregnancy and at delivery. FTAS efficiency to detect major CNS abnormalities was calculated. RESULTS: We detected 17 cases with CNS major abnormalities in a population of 1943 first-trimester (FT) fetuses, including spina bifida with myelomeningocele, exencephaly-anencephaly, holoprosencephaly, hydrocephaly, cephalocele and Dandy-Walker malformation. The CNS features in the abnormal group are presented. In the second trimester (ST), we further diagnosed cases of corpus callosum agenesis, cerebellar hypoplasia, vein of Galen aneurysm and fetal infection features (ventriculomegaly, intraventricular bands, intraventricular cyst and hyperechoic foci), all declared normal at the FTAS. During the third trimester (TT) scan we identified a massive fetal cerebral haemorrhage absent at previous investigations. We report a detection rate of 72.7% of fetal brain anomalies in the FT using the proposed CNS parameters. The sensitivity of the examination protocol was 72.7%, and the specificity was 100%. CONCLUSION: A detailed FT CNS scan is feasible and efficient. The majority of cases of major CNS abnormalities can be detected early in pregnancy. The visualization rates of the CNS parameters in the FT are great with short, if any, additional investigation time. FT cerebral disorders such as haemorrhage or infections were missed in the FT even when an extended evaluation protocol was used.

Interleukin-4 receptor -3223T→C polymorphism is associated with increased gastric adenocarcinoma risk.

BACKGROUND: Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations. OBJECTIVE: To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1b -511C→T [rs16944], IL-4 receptor [IL-4R] -3223C→T [rs2057768], IL-8 -251T→A [rs4073], IL-10 -1082A→G [rs1800896] and tumour necrosis factor-alpha -308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population. METHODS: A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the chi squared test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI. RESULTS: A significant association between the IL-4R -3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R -3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R -3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms. CONCLUSION: The results suggest that the IL-4R -3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.

Pathogenic Copy Number Variations Involved in the Genetic Etiology of Syndromic and Non-Syndromic Intellectual Disability-Data from a Romanian Cohort.

The investigation of unexplained global developmental delay (GDD)/intellectual disability (ID) is challenging. In low resource settings, patients may not follow a standardized diagnostic process that makes use of the benefits of advanced technologies. Our study aims to explore the contribution of chromosome microarray analysis (CMA) in identifying the genetic etiology of GDD/ID. A total of 371 Romanian patients with syndromic or non-syndromic GDD/ID, without epilepsy, were routinely evaluated in tertiary clinics. A total of 234 males (63.07%) and 137 (36.93%) females, with ages ranging from 6 months to 40 years (median age of 5.5 years), were referred for genetic diagnosis between 2015 and 2022; testing options included CMA and/or karyotyping. Agilent Technologies and Oxford Gene Technology CMA workflows were used. Pathogenic/likely pathogenic copy number variations (pCNVs) were identified in 79 patients (21.29%). Diagnosis yield was comparable between mild ID (17.05%, 22/129) and moderate/severe ID 23.55% (57/242). Higher rates were found in cases where facial dysmorphism (22.97%, 71/309), autism spectrum disorder (ASD) (19.11%, 26/136) and finger anomalies (20%, 27/96) were associated with GDD/ID. GDD/ID plus multiple congenital anomalies (MCA) account for the highest detection rates at 27.42% (17/62). pCNVs represent a significant proportion of the genetic causes of GDD/ID. Our study confirms the utility of CMA in assessing GDD/ID with an uncertain etiology, especially in patients with associated comorbidities.

Cytogenetic Analysis of Sporadic First-Trimester Miscarriage Specimens Using Karyotyping and QF-PCR: A Retrospective Romanian Cohort Study.

It is well known that first-trimester miscarriages are associated with chromosome abnormalities, with numerical chromosome abnormalities being the ones most commonly detected. Conventional karyotyping is still considered the gold standard in the analysis of products of conception, despite the extended use of molecular genetic techniques. However, conventional karyotyping is a laborious and time-consuming method, with a limited resolution of 5-10 Mb and hampered by maternal cell contamination and culture failure. The aim of our study was to assess the type and frequency of chromosomal abnormalities detected by conventional karyotyping in specimens of sporadic first-trimester miscarriages in a Romanian cohort, using QF-PCR to exclude maternal cell contamination. Long-term cultures were established and standard protocols were applied for cell harvesting, slide preparation, and GTG banding. All samples with 46,XX karyotype were tested for maternal cell contamination by QF-PCR, comparing multiple microsatellite markers in maternal blood with cell culture and tissue samples. Out of the initial 311 specimens collected from patients with sporadic first-trimester miscarriages, a total of 230 samples were successfully analyzed after the exclusion of 81 specimens based on unsuitable sampling, culture failure, or QF-PCR-proven maternal cell contamination. Chromosome abnormalities were detected in 135 cases (58.7%), with the most common type being single autosomal trisomy (71/135-52.6%), followed by monosomy (monosomy X being the only one detected, 24/135-17.8%), and polyploidy (23/135-17.0%). The subgroup analysis based on maternal age showed a statistically significant higher rate of single trisomy for women aged 35 years or older (40.3%) compared to the young maternal age group (26.1%) (p = 0.029). In conclusion, the combination of conventional karyotyping and QF-PCR can lead to an increased chromosome abnormality detection rate in first-trimester miscarriages. Our study provides reliable information for the genetic counseling of patients with first-trimester miscarriages, and further large-scale studies using different genetic techniques are required.

Prenatal diagnosis of a pure 15q distal trisomy derived from a maternal pericentric inversion: A case report.

Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.

A Novel Nutraceutical Formulation Can Improve Motor Activity and Decrease the Stress Level in a Murine Model of Middle-Age Animals.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

Phenotype Heterogeneity in 3q29 Microduplication Syndrome.

3q29 microduplication syndrome is characterized by widely variable clinical presentation, but generally mild features. Developmental delay, particularly speech, and intellectual disability, eye abnormalities and heart defects are more frequently seen in affected individuals, although it is difficult to delineate a recognisable pattern. We describe a clinical case with a 1.65Mb duplication at 3q29 (chr3:195,979,518-197,638,922, GRCh37) identified by aCGH. The uncharacteristically late onset of the 34 years-old woman is marked by mild intellectual disability, progressive cortical atrophy and recurrent mucosal infections with Candida albicans. The gene content of the duplicated region-29 genes, including PAK2, DLG1, BDH1, FBXO45 and TFRC-seems closely linked to neuronal development and synaptic function, explaining brain and eye development related findings. We speculate on the possible involvement of genes like RNF168 in the aetiology of immunodeficiency. In-depth studies are needed to understand the pathophysiological mechanisms leading to the traits seen in this very rare syndrome.

Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model.

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.

Association of cytokine gene polymorphisms with osteoarthritis susceptibility.

Osteoarthritis (OA) is a multifactorial disease characterized by low-grade inflammatory processes that are mediated initially by the cells and factors of the innate immune system. In addition to their key role in inflammation, cytokines contribute to the pathogenesis of OA through angiogenesis and chemotaxis. The purpose of the present case-control study was to investigate a possible association of four cytokine single nucleotide polymorphisms (SNPs), IL-4R -3223C>T (rs2057768), IL-8 -251T>A (rs4073), IL-10 -1082A>G (rs1800896) and TNF -A-308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from blood samples collected from 305 Romanian subjects (90 patients with OA and 215 controls) and the genotyping of the SNPs was performed by TaqMan allelic discrimination polymerase chain reaction using predesigned assays. Our data indicated a significant association for IL-4R rs2057768 C>T SNP. The subjects that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21-3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI, 1.17-3.17; P=0.009) in a dominant model. The association remained significant only for knee OA in the subgroups analysis. No correlations were observed between the other remaining SNPs and OA. The results suggested that the IL-4R rs2057768 SNP could contribute to OA susceptibility in the Romanian population, providing novel evidence for the involvement of IL-4/IL-4R pair in the pathogenesis of OA.

Association of microRNA Polymorphisms with the Risk of Gastric Cancer in a Romanian Population.

BACKGROUND AND AIMS: MicroRNAs (miRNAs) play an important role in the occurrence and progression of human cancers, including gastric cancer. Our hospital-based case-control study aimed to investigate whether four commonly studied single nucleotide polymorphisms (SNPs) have effects on susceptibility to gastric cancer in a Romanian population. METHOD: We genotyped the miR-27a rs895819, miR-146a rs2910164, miR-196a2 rs11614913 and miR-499 rs3746444 SNPs by real-time PCR using predesignated TaqMan assays in 430 individuals (142 gastric cancer patients and 288 age and gender matched cancer-free controls). The associations between the investigated miRNA SNPs and gastric cancer risk were assessed by odds ratio (OR) with 95% confidence interval (CI) using logistic regression analysis. RESULTS: A higher frequency of the miR-27a rs895819 CC genotype (OR 1.98, 95% CI: 1.05-3.73, p=0.036) was found in the patients with gastric cancer compared with the controls. Similar results were observed in a recessive model, the CC genotype was correlated with gastric cancer susceptibility (OR 1.95, 95% CI: 1.07-3.55, p=0.032). In the stratified analysis, the association between miR-27a rs895819 SNP and gastric cancer risk was limited to noncardia (OR 2.08, 95% CI: 1.10-3.94, p=0.027) and intestinal (OR 2.27, 95% CI: 1.05-4.92, p=0.042) subgroups. However, after Bonferroni correction, all associations described above lost statistical significance. No correlation was observed for the remaining SNPs and risk of gastric cancer in any genetic model studied. CONCLUSION: This study showed no association of the investigated miRNA SNPs with the risk of gastric cancer in a Romanian population.

miR-149 rs2292832 C>T polymorphism and risk of gastric cancer.

Accumulating evidence that microRNA (miRNA) genes are involved in different processes associated with gastric carcinogenesis. The polymorphisms located on miRNA sequences may affect the interaction with their target messenger RNAs (mRNAs) and, consequently, genetic susceptibility to disease. The aim of our study was to investigate the association of miR-149 rs2292832 C>T polymorphism and gastric cancer susceptibility in Romanian patients. A total of 142 patients with gastric adenocarcinoma and 288 healthy controls were included in this study. The miR-149 rs2292832 allelic variants were genotyped by real-time polymerase chain reaction (RT-PCR) using specific TaqMan predesigned probes. The association between polymorphism and gastric cancer risk was estimated by odds ratio (OR) and 95% confidence interval (CI). The miR-149 rs2292832 C>T was not associated with susceptibility to gastric cancer, when TT genotype was compared with the more frequent AA genotype (OR 0.98, 95% CI 0.55-1.77, p=0.96) or when we used dominant and recessive models. Also, we compared allele frequencies and no correlation was found (OR 0.92, 95% CI 0.68-1.24, p=0.57). The sub-classification of gastric cancer into non-cardia and cardia or intestinal and diffuse type did not reveal any statistically significant difference for investigated polymorphism.

Magnetic nanoparticles-based therapy for malignant mesothelioma.

This work was aimed to analyze the versatility of the chick embryo chorioallantoic membrane (CAM) as in vivo model for the study of the malignant pleural mesothelioma (MPM) and the therapeutic potential of Fe3O4÷salicylic acid magnetic nanoparticles (SaMNPs) on MPM cells. The antitumor effects of SaMNPs were studied by in vitro and in vivo tests on CARM-L12 TG3 rat malignant mesothelioma cells and human MPM xenografts implanted on CAMs. In order to assess the human MPM xenograft growth characteristics, calretinin, HBME-1 (Hector Battifora mesothelial epitope-1), and cytokeratins immunohistochemical stainings were performed. The human MPM xenografts continue to develop on the CAMs and xenograft MPM cells showed highly metastatic features and a particular pattern of metastasis. The SaMNPs had a specific uptake by the MPM cells and an antiproliferative effect at therapeutic doses greater than 100 µg÷mL. The results confirmed the possibility to use the CAM as in vivo model to study the biology of MPM and to evaluate the antitumor potential of new therapeutic agents. They highlighted a strong antitumor effect of the SaMNPs on the rat and human MPM cells and open new perspectives in the treatment of MPM.

ATG16L1 T300A Polymorphism is Correlated with Gastric Cancer Susceptibility.

Gastric cancer is a major leading cause of cancer-related death in both sexes in Europe. The role of autophagy process in carcinogenesis remains unclear and there is increasing evidence that Helicobacter pylori is a key player in modulating autophagy in gastric carcinogenesis. The aim of this study was to assess the potential association of ATG16L1 T300A polymorphism with susceptibility of gastric cancer, and further to analyze the expression profile of ATG16L1 gene in paired tumoral and peritumoral gastric tissue. A total of 108 patients diagnosed with gastric cancer and 242 healthy controls were enrolled. ATG16L1 T300A polymorphism was detected using TaqMan genotyping assay containing primers and specific probes for A and G allele, respectively. ATG16L1 mRNA level was evaluated in 34 paired tumoral and peritumoral tissues using qRT-PCR. We found a significant association for both carriers of AG (OR 0.52, 95% CI: 0.30-0.91, p = 0.02) and GG genotype (OR 0.53, 95% CI: 0.28-0.98, p = 0.043), these were at a lower risk for gastric cancer when compared with the wild-type AA genotype. The strongest association was observed in a dominant model, the carriers of G allele were protected against gastric cancer (OR 0.52, 95% CI: 0.13-0.88, p = 0.013). In a stratified analyse, the association was limited to non-cardia type and intestinal type. ATG16L1 gene expression was detected in both tumor and peritumoral tissues, with the mRNA-ATG16L1 levels significantly higher in tumor sample. Our results suggest that ATG16L1 T300A polymorphism may be associated with gastric carcinogenesis.

Autophagy in colorectal cancer: An important switch from physiology to pathology.

Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of autophagy-related genes and modulators in colorectal carcinogenesis, and to develop potential beneficial agents for the prognosis and treatment of CRC.