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1.
J Natl Cancer Inst ; 115(1): 93-103, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36171661

ABSTRACT

BACKGROUND: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks. METHODS: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses. RESULTS: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%. CONCLUSIONS: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.


Subject(s)
Hamartoma Syndrome, Multiple , Kidney Neoplasms , Thyroid Neoplasms , Adult , Male , Humans , Female , Middle Aged , Hamartoma Syndrome, Multiple/epidemiology , Hamartoma Syndrome, Multiple/genetics , Hamartoma Syndrome, Multiple/pathology , Cohort Studies , Prospective Studies , PTEN Phosphohydrolase/genetics , Kidney Neoplasms/epidemiology , Germ-Line Mutation
2.
World Neurosurg ; 168: e67-e75, 2022 12.
Article in English | MEDLINE | ID: mdl-36126890

ABSTRACT

OBJECTIVE: Hemangioblastomas in the central nervous system are the most common manifestation of von Hippel-Lindau (VHL) disease. Because the growth rate of hemangioblastomas is unpredictable, regular follow-up is mandatory, focusing on clinical symptoms and imaging of the central nervous system. However, clinical symptoms may be subtle and nonspecific, and data about the relationship between the radiologic findings and clinical symptoms are sparse. This study aims to evaluate if and how findings of magnetic resonance imaging (MRI) regarding spinal hemangioblastomas are associated with symptoms of VHL disease, with special attention to peritumoral edema and spinal cysts. METHODS: Serial spinal MRI scans of 43 genetically or clinically established VHL patients with at least 2 years of follow-up were reevaluated to examine the volume, growth rate, and location of spinal hemangioblastomas and the presence, size, and growth rate of peritumoral edema and cysts. Findings were compared with clinical symptoms using the Fisher exact test. RESULTS: We observed a total of 77 spinal hemangioblastomas in 28 patients. Eight of the 28 patients showed peritumoral edema and spinal cysts, and 1 patient showed peritumoral edema without cyst formation; 6 of these 9 patients showed clinical symptoms. Both peritumoral edema and spinal cysts were associated with clinical symptoms (P = 0.023 and P = 0.011, respectively). CONCLUSIONS: The presence of peritumoral edema and/or spinal cysts shown on MRI in VHL patients with spinal hemangioblastomas is associated with symptoms in more than half of the patients and may alert the clinician to intensify clinical and radiologic surveillance.


Subject(s)
Cysts , Hemangioblastoma , Spinal Cord Neoplasms , von Hippel-Lindau Disease , Humans , Hemangioblastoma/diagnostic imaging , Hemangioblastoma/surgery , Hemangioblastoma/complications , von Hippel-Lindau Disease/complications , von Hippel-Lindau Disease/diagnostic imaging , Follow-Up Studies , Spinal Cord Neoplasms/diagnosis , Cysts/complications , Edema
3.
Biotechnol Adv ; 52: 107815, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34400260

ABSTRACT

Over the past few decades, the term polymer has been repeatedly used in several industries for their immense characteristics in different applications. Polymers and their composites which were prepared from chemical monomer sources turned out to be potentially harmful to the environment due to their tedious degradation process. Biopolymers are natural substitutes for synthetic polymers which can be efficiently extricated from natural sources. They are predominantly available as polymeric units as well as monomeric units that are linked covalently. These environment-friendly biopolymers and their composites can be categorized based on their numerous sources, different methods of preparation and their potential form of usage. They were found to be biocompatible and biodegradable which make them exceptionally useful in environment based applications, mainly in the process of water treatment, both potable and wastewater. Further, the biopolymer and biopolymer composites easily fit into different parts of the treatment process by acting as filtration media, adsorbents, coagulants and as flocculants. The primary focus of this review is to provide a comprehensive information of biopolymers and biopolymer composites from synthesis to their usefulness for their productive application in water treatment processes. On the whole, it can be substantiated that the biopolymers were identified to play a notable adversary to the synthetic polymers in treating waters with an indispensable need for an elaborative study in the production of the biopolymers.


Subject(s)
Water Purification , Biopolymers , Polymers , Wastewater
4.
Microb Pathog ; 159: 105133, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34390768

ABSTRACT

Zoonotic viruses originate from birds or animal sources and responsible for disease transmission from animals to people through zoonotic spill over and presents a significant global health concern due to lack of rapid diagnostics and therapeutics. The Corona viruses (CoV) were known to be transmitted in mammals. Early this year, SARS-CoV-2, a novel strain of corona virus, was identified as the causative pathogen of an outbreak of viral pneumonia in Wuhan, China. The disease later named corona virus disease 2019 (COVID-19), subsequently spread across the globe rapidly. Nano-particles and viruses are comparable in size, which serves to be a major advantage of using nano-material in clinical strategy to combat viruses. Nanotechnology provides novel solutions against zoonotic viruses by providing cheap and efficient detection methods, novel, and new effective rapid diagnostics and therapeutics. The prospective of nanotechnology in COVID 19 is exceptionally high due to their small size, large surface-to-volume ratio, susceptibility to modification, intrinsic viricidal activity. The nano-based strategies address the COVID 19 by extending their role in i) designing nano-materials for drug/vaccine delivery, ii) developing nano-based diagnostic approaches like nano-sensors iii) novel nano-based personal protection equipment to be used in prevention strategies.This review aims to bring attention to the significant contribution of nanotechnology to mitigate against zoonotic viral pandemics by prevention, faster diagnosis and medication point of view.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Animals , Humans , Nanotechnology , Prospective Studies , SARS-CoV-2
5.
Fam Cancer ; 20(4): 263-271, 2021 10.
Article in English | MEDLINE | ID: mdl-33686467

ABSTRACT

Recognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.


Subject(s)
Neoplasms , Child , Early Detection of Cancer , Humans , Mass Screening , Neoplasms/diagnosis , Neoplasms/genetics , Prospective Studies , Syndrome
6.
Carbohydr Polym ; 225: 115240, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31521287

ABSTRACT

Pectin was extracted from the waste custard apple peel using ultrasound technique and optimized the extraction process by RSM. The various significant process parameters such as liquid-solid ratio, ultra-sonication time, temperature and pH of solution were studied in the range of 10-25 mL g-1, 10-30 min, 50-80 °C, and 1-3, respectively. The maximum yield of pectin (8.93%) was attained at the optimum condition of 23.52 mL g-1 of liquid-solid ratio, 18.04  min of ultra-sonication time, 63.22 °C of temperature and 2.3 pH of solution. The extracted and commercially available fresh pectin (for comparison purposes) were characterized by various analytical techniques namely, FTIR, DSC, XRD, SEM, and NMR to evaluate their functional groups, thermal properties, crystallinities, morphological and structural characteristics, respectively. The extracted pectin was a toxic free compound as determined by its anti nutritional property study and about 20 mg/mL of antioxidant presented in it.

7.
Fam Cancer ; 18(3): 369-376, 2019 07.
Article in English | MEDLINE | ID: mdl-31087189

ABSTRACT

Von Hippel-Lindau (VHL) disease is an autosomal dominant rare tumor syndrome characterized by high penetrance. VHL mutation carriers develop numerous manifestations in multiple organs during life. The natural course of development of new and growth of existing VHL-related manifestations is still unclear. In this study we aimed to gain insight into the development of subsequent manifestations in VHL disease. We retrospectively scored each new VHL-related manifestation as detected by standard follow-up (retina, central nervous system, kidneys and pancreas, excluding adrenal and endolymfatic sac manifestations) in 75 VHL mutation carriers. The Kaplan-Meier method was used to plot the cumulative proportions of all consecutive manifestations in each organ against age. The cumulative average number of manifestations in all organs during life was calculated by summating these cumulative proportions. Poisson model parameters were used to calculate average time to the detection of consecutive VHL manifestations in each organ. Consecutive VHL-related kidney and retina manifestations during life occur linearly according to Poisson distribution model. The total number of VHL manifestations rises linearly, with an average of seven VHL-related lesions at age 60 years. The incidence of consecutive VHL-related manifestations is constant during life in VHL mutation carriers. Our data is consistent with the notion that somatic inactivation of the remaining allele (Knudson's "two-hit" hypothesis) is the determining factor in developing new VHL-related manifestations.


Subject(s)
von Hippel-Lindau Disease/complications , Adolescent , Adult , Age Factors , Aged , Central Nervous System Neoplasms/etiology , Disease Progression , Female , Hemangioblastoma/etiology , Heterozygote , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/etiology , Male , Middle Aged , Pancreatic Neoplasms/etiology , Retinal Neoplasms/etiology , Retrospective Studies , Time Factors , Young Adult , von Hippel-Lindau Disease/genetics
8.
Cancer Epidemiol Biomarkers Prev ; 28(6): 1010-1014, 2019 06.
Article in English | MEDLINE | ID: mdl-30824524

ABSTRACT

BACKGROUND: PMS2-associated Lynch syndrome is characterized by a relatively low colorectal cancer penetrance compared with other Lynch syndromes. However, age at colorectal cancer diagnosis varies widely, and a strong genetic anticipation effect has been suggested for PMS2 families. In this study, we examined proposed genetic anticipation in a sample of 152 European PMS2 families. METHODS: The 152 families (637 family members) that were eligible for analysis were mainly clinically ascertained via clinical genetics centers. We used weighted Cox-type random effects model, adjusted by birth cohort and sex, to estimate the generational effect on the age of onset of colorectal cancer. Probands and young birth cohorts were excluded from the analyses. Weights represented mutation probabilities based on kinship coefficients, thus avoiding testing bias. RESULTS: Family data across three generations, including 123 colorectal cancers, were analyzed. When compared with the first generation, the crude HR for anticipation was 2.242 [95% confidence interval (CI), 1.162-4.328] for the second generation and 2.644 (95% CI, 1.082-6.464) for the third generation. However, after correction for birth cohort and sex, the effect vanished [HR = 1.302 (95% CI, 0.648-2.619) and HR = 1.074 (95% CI, 0.406-2.842) for second and third generations, respectively]. CONCLUSIONS: Our study did not confirm previous reports of genetic anticipation in PMS2-associated Lynch syndrome. Birth-cohort effect seems the most likely explanation for observed younger colorectal cancer diagnosis in subsequent generations, particularly because there is currently no commonly accepted biological mechanism that could explain genetic anticipation in Lynch syndrome. IMPACT: This new model for studying genetic anticipation provides a standard for rigorous analysis of families with dominantly inherited cancer predisposition.


Subject(s)
Anticipation, Genetic , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Mismatch Repair Endonuclease PMS2/genetics , Mutation , Age of Onset , Aged , Cohort Effect , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , DNA Mismatch Repair , Female , Humans , Male , Middle Aged , Models, Statistical , Netherlands/epidemiology , Pedigree , Penetrance , Proportional Hazards Models
9.
J Clin Oncol ; 36(29): 2961-2968, 2018 10 10.
Article in English | MEDLINE | ID: mdl-30161022

ABSTRACT

PURPOSE: Lynch syndrome due to pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, and MSH6 is predominantly associated with colorectal and endometrial cancer, although extracolonic cancers have been described within the Lynch tumor spectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 variants. METHODS: A modified segregation analysis was conducted that incorporated both genotyped and nongenotyped relatives, with conditioning for ascertainment to estimates corrected for bias. Hazard ratios (HRs) and corresponding 95% CIs were estimated for each cancer site for mutation carriers compared with the general population, followed by estimation of penetrance. RESULTS: In total, 284 families consisting of 4,878 first- and second-degree family members were included in the analysis. PMS2 mutation carriers were at increased risk for colorectal cancer (cumulative risk to age 80 years of 13% [95% CI, 7.9% to 22%] for males and 12% [95% CI, 6.7% to 21%] for females) and endometrial cancer (13% [95% CI, 7.0%-24%]), compared with the general population (6.6%, 4.7%, and 2.4%, respectively). There was no clear evidence of an increased risk of ovarian, gastric, hepatobiliary, bladder, renal, brain, breast, prostate, or small bowel cancer. CONCLUSION: Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer. This finding justifies that PMS2-specific screening protocols could be restricted to colonoscopies. The role of risk-reducing hysterectomy and bilateral salpingo-oophorectomy for PMS2 mutation carriers needs further discussion.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Mismatch Repair Endonuclease PMS2/genetics , Neoplasms/epidemiology , Neoplasms/genetics , Penetrance , Adult , Aged , Female , Heterozygote , Humans , Male , Middle Aged , Mutation
10.
Gastroenterology ; 155(3): 844-851, 2018 09.
Article in English | MEDLINE | ID: mdl-29758216

ABSTRACT

BACKGROUND & AIMS: Germline variants in mismatch repair genes MLH1, MSH2 (EPCAM), MSH6, or PMS2 cause Lynch syndrome. Patients with these variants have an increased risk of developing colorectal cancers (CRCs) that differ from sporadic CRCs in genetic and histologic features. It has been a challenge to study CRCs associated with PMS2 variants (PMS2-associated CRCs) because these develop less frequently and in older patients than CRCs with variants in other mismatch repair genes. METHODS: We analyzed 20 CRCs associated with germline variants in PMS2, 22 sporadic CRCs, 18 CRCs with germline variants in MSH2, and 24 CRCs from patients with germline variants in MLH1. Tumor tissue blocks were collected from Dutch pathology departments in 2017. After extraction of tumor DNA, we used a platform designed to detect approximately 3,000 somatic hotspot variants in 55 genes (including KRAS, APC, CTNNB1, and TP53). Somatic variant frequencies were compared using the Fisher exact test. RESULTS: None of the PMS2-associated CRCs contained any somatic variants in the catenin-ß1 gene (CTNNB1), which encodes ß-catenin, whereas 14 of 24 MLH1-associated CRCs (58%) contained variants in CTNNB1. Half the PMS2-associated CRCs contained KRAS variants, but only 20% of these were in hotspots that encoded G12D or G13D. These hotspot variants occurred more frequently in CRCs associated with variants in MLH1 (37.5%; P = .44) and MSH2 (71.4%; P = .035) than in those associated with variants in PMS2. CONCLUSIONS: In a genetic analysis of 84 colorectal tumors, we found tumors from patients with PMS2-associated Lynch syndrome to be distinct from colorectal tumors associated with defects in other mismatch repair genes. This might account for differences in development and less frequent occurrence.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/genetics , Germ-Line Mutation , Mismatch Repair Endonuclease PMS2/genetics , Adult , Aged , DNA Mismatch Repair , DNA-Binding Proteins/genetics , Epithelial Cell Adhesion Molecule/genetics , Female , Humans , Male , Middle Aged , MutL Protein Homolog 1/genetics , beta Catenin/genetics
11.
Clin Cancer Res ; 24(7): 1594-1603, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29351919

ABSTRACT

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer.Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome.Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein-Taybi syndrome, ARID1A-based Coffin-Siris syndrome, ACTB-based Baraitser-Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition.Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. Clin Cancer Res; 24(7); 1594-603. ©2018 AACR.


Subject(s)
Genetic Predisposition to Disease/genetics , Germ-Line Mutation/genetics , Neoplasms/genetics , Abnormalities, Multiple/genetics , Adolescent , Child , Child, Preschool , Congenital Hypothyroidism/genetics , Craniofacial Abnormalities/genetics , Exome/genetics , Face/abnormalities , Female , Genotype , Hand Deformities, Congenital/genetics , Humans , Infant , Intellectual Disability/genetics , Male , Micrognathism/genetics , Neck/abnormalities , Phenotype , Rubinstein-Taybi Syndrome/genetics , Exome Sequencing/methods
12.
Fam Cancer ; 17(4): 507-515, 2018 10.
Article in English | MEDLINE | ID: mdl-29147930

ABSTRACT

Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2-3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5-4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/genetics , Mismatch Repair Endonuclease PMS2/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 8 , Colorectal Neoplasms/mortality , Colorectal Neoplasms, Hereditary Nonpolyposis/mortality , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Heterozygote , Humans , Kaplan-Meier Estimate , Male , Middle Aged
13.
Carbohydr Polym ; 173: 707-713, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28732917

ABSTRACT

The main aim of this current work is to extract pectin from waste heads of Helianthus annus by ultrasound and optimize the process variables (ultrasound power (USP), pH, time of sonication (TS) and ratio of solid to liquid (RSL) on maximal recovery of pectin using central composite statistical experimental design. In addition to that, extracted pectin at optimal condition was characterized and compared with commercial pectin. The optimal extraction process condition was USP of 375w, pH of 3.2, TS of 32min and RSL of 1:15g/ml. Mean experimental pectin yield of 8.89±0.024% was well accord with predicted pectin yield (8.91%). Analysis of chemical composition and Fourier transform infrared spectroscopy of extracted pectin did not show any significant difference with commercial pectin. XRD analysis illustrated a similar crystalline profile in both extracted and commercial pectin. Morphological analysis was performed on fresh and extracted samples using scanning electron microscopy.


Subject(s)
Helianthus/chemistry , Pectins/isolation & purification , Sonication , Ultrasonography
14.
Eur J Cancer ; 80: 48-54, 2017 07.
Article in English | MEDLINE | ID: mdl-28544908

ABSTRACT

INTRODUCTION: Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a child for genetic consultation. METHODS: We performed a PubMed search to review the incidence of TPSs in children for 85 tumour types listed in the International Classification of Childhood Cancer third edition (ICCC-3). The results were discussed during a national consensus meeting with representative clinical geneticists from all six academic paediatric oncology centres in The Netherlands. A TPS incidence of 5% or more was considered a high probability and therefore in itself a reason for referral to a clinical geneticist. RESULTS: The literature search resulted in data on the incidence of a TPS in 26 tumours. For 23/26 tumour types, a TPS incidence of 5% or higher was reported. In addition, during the consensus meeting the experts agreed that children with any carcinoma should always be referred for clinical genetic consultation as well, as it may point to a TPS. CONCLUSION: We present an overview of 23 paediatric tumours with a high probability of a TPS; this will facilitate paediatric oncologists to decide which patients should be referred for genetic consultation merely based on type of tumour.


Subject(s)
Genetic Counseling , Genetic Predisposition to Disease , Neoplastic Syndromes, Hereditary/epidemiology , Child , Humans , Incidence , Referral and Consultation
15.
Ultrason Sonochem ; 35(Pt A): 204-209, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27707645

ABSTRACT

The objectives of the present work are to extract pectin from industrial waste of Musa balbisiana by ultrasound assisted citric acid mediated extraction method and optimization was done through central composite statistical experimental design under response surface methodology. The outcomes of this study exhibited that, process variables (ultrasound power, pH and extraction time) had considerable influence on the pectin extraction. Second order mathematical equation was constructed to predict the data through regression analysis. The optimal extraction process condition was ultrasound power of 323w, pH of 3.2, extraction time of 27min and SL (solid-liquid) ratio of 1:15g/ml. The mean experimental yield of pectin (8.99±0.018%) was fine accord among predicted yield of pectin (9.02%).


Subject(s)
Chemical Fractionation/methods , Citric Acid/chemistry , Industrial Waste , Musa/chemistry , Pectins/isolation & purification , Ultrasonic Waves , Hydrogen-Ion Concentration , Pectins/chemistry , Time Factors
16.
Ultrason Sonochem ; 34: 525-530, 2017 01.
Article in English | MEDLINE | ID: mdl-27773278

ABSTRACT

Four factors three level face centered central composite response surface design was employed in this study to investigate and optimize the effect of process variables (liquid-solid (LS) ratio (10:1-20:1ml/g), pH (1-2), sonication time (15-30min) and extraction temperature (50-70°C)) on the maximum extraction yield of pectin from waste Artocarpus heterophyllus (Jackfruit) peel by ultrasound assisted extraction method. Numerical optimization method was adapted in this study and the following optimal condition was obtained as follows: Liquid-solid ratio of 15:1ml/g, pH of 1.6, sonication time of 24min and temperature of 60°C. The optimal condition was validated through experiments and the observed value was interrelated with predicted value.


Subject(s)
Artocarpus/chemistry , Chemical Fractionation/methods , Fruit/chemistry , Pectins/isolation & purification , Ultrasonic Waves , Waste Products/analysis , Hydrogen-Ion Concentration , Temperature , Time Factors
18.
Hum Mutat ; 37(11): 1162-1179, 2016 11.
Article in English | MEDLINE | ID: mdl-27435373

ABSTRACT

Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/MSI (immunohistochemistry/microsatellite instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro mismatch repair assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor prescreening methods will however miss some PMS2 germline mutation carriers.


Subject(s)
Brain Neoplasms/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/genetics , DNA Mutational Analysis/methods , Mismatch Repair Endonuclease PMS2/genetics , Neoplastic Syndromes, Hereditary/genetics , Brain Neoplasms/metabolism , Cohort Studies , Colorectal Neoplasms/metabolism , Colorectal Neoplasms, Hereditary Nonpolyposis/metabolism , Genetic Predisposition to Disease , Genetic Variation , Germ-Line Mutation , Humans , Microsatellite Instability , Mismatch Repair Endonuclease PMS2/metabolism , Neoplastic Syndromes, Hereditary/metabolism , Netherlands
19.
Int J Biol Macromol ; 86: 857-64, 2016 May.
Article in English | MEDLINE | ID: mdl-26827756

ABSTRACT

The present study investigates the effect of independent variables such as extraction temperature (35-55 °C), time (1-5h) and solid-liquid ratio (1:5-1:25 g/ml) over the extraction yield of polysaccharide from Gossypium arboreum L. seeds was investigated and optimized. Aqueous extraction method was opted for the extraction of polysaccharide. Central composite response surface design was utilized for developing the experimental design. A second order polynomial mathematical model was developed from the obtained results. From the results, Significance of process variables over the extraction process can be clearly depicted. At the extraction temperature of 45 °C, extraction time of 3h and solid-liquid ratio of 1:15 g/ml maximum yield of polysaccharide (8.67%) from Gossypium arboreum L. seed was obtained. Characteristics of the extracted polysaccharide are analyzed through physico-chemical property analysis and Fourier Transform Infrared Spectroscopy (FTIR).


Subject(s)
Chemical Fractionation/methods , Gossypium/chemistry , Models, Theoretical , Polysaccharides/isolation & purification , Seeds/chemistry , Chemical Phenomena , Polysaccharides/chemistry , Temperature , Time Factors
20.
J Food Sci Technol ; 53(1): 792-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26788000

ABSTRACT

In this study, ultrasound-assisted extraction (UAE) of natural pigment extraction from waste red beet stalks were optimized under four factors (extraction temperature, ultrasonic power, extraction time and solid-liquid ratio) by using three level Box-Behnken response surface design. Extraction temperature, ultrasonic power and solid-liquid ratio were significantly influenced the extraction yield of pigments. Extraction temperature of 53 °C, ultrasonic power of 89 w, extraction time of 35 min and SL ratio of 1:19 g/ml was identified as the optimal condition. Under this condition, the actual yield of (betacyanin of 1.28 ± 0.02 and betaxanthin of 5.31 ± 0.09 mg/g) pigments was well correlated with predicted values (betacyanin was 1.29 mg/g and betaxanthin was 5.32 mg/g).

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