DPYD gene polymorphisms in patients with gastrointestinal tumors receiving chemotherapy with 5-fluorouracil.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 90-90
Author(s):  
Oleg Ivanovich Kit ◽  
Liubov Yu Vladimirova ◽  
Natalya N. Timoshkina ◽  
Anna E. Storozhakova ◽  
Natalia A. Petrusenko ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Venous Blood ◽  
Gastrointestinal Tumors ◽  
Hematological Toxicity ◽  
Malignant Neoplasms ◽  
Inclusion Criteria ◽  
Dpyd Gene ◽  
Caucasian Patients ◽  
Partial Deficiency ◽  
Caucasoid Population

90 Background: Complete or partial deficiency of the DPD enzyme due to genetic polymorphisms of the DPYD gene causes acute toxicity of fluoropyrimidines, which are widely used in combination chemotherapy regimens for various malignant neoplasms. The purpose of the study: to identify polymorphisms of the DPYD gene significant for 5-fluorouracil-induced toxicity. Methods: Venous blood samples from Caucasian patients were used to identify alleles of *2А rs3918290, 5* rs1801159, *13 rs55886062 and rs67376798 DPYD by RT-PCR and direct sequencing. Inclusion criteria were: verified diagnosis of gastrointestinal tumors, age>18 years old, fluoropyrimidine-containing regimes of treatment. Results: 104 pts were included, 54% were female. Mean age-61 years. Colorectal cancer was found in 80.7% pts, non-colorectal in 19.3% pts. Hematological and non-hematological toxicity Gd.3-4 was found in 24% pts. Allele * 5rs18011595, which causes enzyme deficiency was found in 28% of patients, (frequency was 0.281) which is significantly higher than the population frequency of the allele charactering for Caucasoid population (p <0.05). Meanwhile genotyping did not reveal the *2A, *13 alleles and rs67376798 alleles in the DPYD gene. Conclusions: *5rs1801159 allele was found as the main DPYD polymorphism associated with fluoropyrimidine toxicity in Caucasian pts with gastrointestinal tumors.

scholarly journals Study of polymorphisms of UGT1A1 and DPYD genes in chemotherapy for colorectal cancer

2019 ◽  
Vol 17 (6) ◽  
pp. 49-56
Author(s):  
N. N. Timoshkina ◽  
O. A. Bogomolova ◽  
I. A. Zhuzhelenko ◽  
S. N. Kabanov ◽  
E. A. Kalabanova ◽  
...  
Keyword(s):  
Side Effects ◽  
Venous Blood ◽  
Significant Proportion ◽  
Circulatory System ◽  
Individual Choice ◽  
Dpyd Gene ◽  
Preliminary Examination ◽  
Caucasian Patients ◽  
Personalized Approach ◽  
Toxic Reactions

Background. The personalized approach implies an individual choice of medicines and their doses for the patient, providing the most effective and safe pharmacotherapy. Objective: analysis of the frequencies of UGT1A1 and DPYD polymorphisms and comparison of genotyping data with irinotecan and 5-fluorouracil-induced toxicity, respectively.Materials and Methods. Venous blood of 94 Caucasian patients (46 men and 48 women, median age 61 years). The *6 and *28 UGT1A1 alleles were identified by pyrosequencing, and the *2А DPYD allele was identified by Real-time PCR.Results. The genotyping of 94 patients with colon cancer did not reveal the *2A SNP in the DPYD gene. The frequency rate of the *6 and *28 alleles of the UGT1A1 gene was 0.346 and 0.016, respectively. 24 % of patients receiving chemotherapy with 5-fluorouracil developed side effects associated with the circulatory system and the gastrointestinal tract. Hematological and nonhematological toxic reactions were noted in 48 % and 50 % of patients receiving irinotecan. Severe bilirubinemia was associated with the *28/*28 UGT1A1 genotype. The presence of a high-risk genotype (*28/*1, *28/*28 UGT1A1) correlated with the development of side effects (p=0.040).Conclusion. The absence of carriers of the *2А DPYD allele in the sample with a significant proportion of pronounced adverse toxic reactions to 5-fluorouracil causes the need for the inclusion of new polymorphisms of the DPYD gene in pharmacogenetic testing. The inclusion of genotyping of UGT1A1 polymorphisms into a complex of preliminary examination is advisable when planning treatment with irinotecan.

Compound heterozygous CNGA3 mutations (R436W, L633P) in a Japanese patient with congenital achromatopsia

2006 ◽  
Vol 23 (3-4) ◽  
pp. 395-402 ◽  
Author(s):  
SATOSHI GOTO-OMOTO ◽  
TAKAAKI HAYASHI ◽  
TAMAKI GEKKA ◽  
AKIKO KUBO ◽  
TOMOKAZU TAKEUCHI ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Direct Sequencing ◽  
Mutation Screening ◽  
Venous Blood ◽  
Japanese Patients ◽  
White Background ◽  
Compound Heterozygous ◽  
Polymorphism Analysis ◽  
Missense Mutations ◽  
Α Subunit

Congenital achromatopsia is a stationary retinal disorder with autosomal recessive inheritance that is characterized by loss of color discrimination, low visual acuity, photophobia, and nystagmus. This disorder has been shown to be associated with CNGA3, CNGB3, and GNAT2 mutations, and the frequency of mutations in the CNGA3 gene (encoding α subunit of the cone-specific cGMP-gated cation channel) was 23–33% in European populations. The aim of this study was to test the hypothesis that CNGA3 mutations are also responsible for congenital achromatopsia in Japanese patients. DNA from venous blood samples from a total of 14 patients from 13 Japanese pedigrees was prepared. Mutation screening of the CNGA3 gene was performed using direct sequencing and PCR-single-strand conformation polymorphism analysis. Compound heterozygous missense mutations (p.R436W and p.L633P, the latter of which was novel) were identified in one patient only, a 22-year-old female. Neither of these two mutations was found in 150 Japanese control individuals. The patient's parents and sister carried one of these mutations each but were not affected. No mutations in the CNGB3 or GNAT2 genes were identified in the patient. Clinically, best-corrected visual acuity was 0.1 in both eyes. No specific findings were obtained in funduscopy. Optical coherence topography revealed a normal foveal thickness but a 20% decrease in parafoveal thickness. Ganzfeld full-field electroretinograms (ERGs) showed normal responses in rod and mixed rod-plus-cone ERGs but no response in cone or 30-Hz flicker ERGs. Spectral sensitivity on a white background revealed a curve with only one peak at around 500 nm, which fits the absorption spectrum of human rhodopsin. L633, conserved among vertebrate orthologs of human CNGA3, is a hydrophobic residue forming part of the carboxy-terminal leucine zipper (CLZ) domain, which is functionally important in the mediation of intracellular interactions. To our knowledge, this is the first report of a Japanese complete achromat with CNGA3 mutations, and of any patient with a missense mutation within the CLZ domain. The outcome suggests low frequency (7%, 1/14) of CNGA3 mutations in Japanese patients.

scholarly journals Direct Oral Anticoagulant (DOAC) to Warfarin Transitions in a Pharmacist-led Anticoagulation Clinic

2019 ◽  
Vol 66 (1) ◽  
pp. 48-51
Author(s):  
Ashley Woodhouse ◽  
Madeline Burke ◽  
Anne Misher
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulant ◽  
Warfarin Therapy ◽  
Bridge To Surgery ◽  
Direct Oral Anticoagulant ◽  
Inclusion Criteria ◽  
Practice Recommendations ◽  
Clinical Trial Evidence ◽  
Caucasian Patients ◽  
Trial Evidence

Purpose Patients with non-valvular atrial fibrillation or venous thromboembolism have historically been treated with vitamin-k antagonist therapy; however, due to well-documented limitations, direct oral anticoagulant (DOAC) use has been increasing.(1)(2) The convenience and clinical utility of DOACs is not applicable to all patients, and some must be transitioned to warfarin therapy. Despite practice recommendations, suggestions from package inserts, and clinical trial evidence, there remains a lack of literature describing real-word examples of patient transition from DOACs to warfarin.(3–11) Summary All patients who were transitioned from a DOAC to warfarin from January to December 2016 and were managed by the clinic were included. Patients were excluded if the transition to warfarin did not include ≥ 2 days of DOAC overlap or if DOAC therapy was used as a bridge to surgery or procedure. St. Joseph's/Candler Health System IRB granted expedited approval and waived informed consent. Four elderly, Caucasian patients met the inclusion criteria. Four patients were successfully transitioned from a DOAC to warfarin for their atrial fibrillation, 3 were transitioned from apixaban and 1 was transitioned from rivaroxaban. Conclusion Overall the purpose of this retrospective, observational study was to highlight real-world management of the transition of DOACs to warfarin in an outpatient, pharmacist-led clinic.

Correlation of single nucleotide polymorphisms in NER pathway genes with toxicity in advanced non-small cell lung cancer patients treated with chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18115-e18115
Author(s):  
Ling Zhang
Keyword(s):  
Advanced Nsclc ◽  
Venous Blood ◽  
Stage Iv ◽  
Hematological Toxicity ◽  
Nucleotide Polymorphisms ◽  
Lung Cancer Patients ◽  
New Therapeutic Approaches ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps ◽  
Predictive Effect

e18115 Background: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. We assessed whether polymorphisms in genes of NER pathway, such as ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in advanced NSCLC pts. Methods: Eligible pts had histological or cytological confirmed stage IV or IIIB (with malignant pleural effusion) chemo-naïve NSCLC, ECOG PS of 0 to 2 and adequate organ function. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2 on day 1 and 8, or docetaxel 75 mg/m2 or taxel 175 mg/m2 on day 1 plus cisplatin 75 mg/m2 or carboplatin AUC=5 on day 1, every 21 days per cycle, for a maximum of six cycles, unless disease progression or unacceptable toxicity occurred. Hematology and biochemistry analyses were repeated every cycle or before chemotherapy for d8 treatment. Toxicity was classified according to CTC AE 3.0. Venous blood was collected and genomic DNA was isolated. Polymorphisms were assessed. SNPs in ERCC6 (A/G 1413, A/G 1213 and A/G 1097), XPC (T/C 500 and A/C 940), ERCC5 (G/C 1104), RRM1 (−37C/A), CCNH (T/C 270) and MMS19L (G811A) were assessed. Results: Totally 388 pts were included prospectively from Oct 2005 to Mar 2009. Median age was 61 years; 68.8% were male, 36.2% were ECOG PS 1, 33.2% had stage IIIB. The median follow-up time was 18 months (range 8–66 months). Hematological toxicity was the most common AE. SNPs of MMS19L and ERCC6 can predict the AE of chemotherapy in NSCLC,leucopenia (P=0.020), jaundice (P=0.039) by MMS19L. In terms of grade 3-4 AE, SNPs of MMS19L and RRM1 -37C/A have much more predictive effect. SNPs of MMS19L were good at total AE (P=0.042), thrombopenia (P=0.035), SNPs of RRM1 -37C/A were for vomiting (P=0.046) and jaundice (P=0.014). Conclusions: Polymorphisms in ERCC6, MMS19L, RRM1, can predict the tolerability of platinum-based chemotherapy in advanced NSCLC patients. Polymorphisms in other genes of NER pathway, such as ERCC5, CCNH, XPC, have no predictive effect.

scholarly journals Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li-Yun Jia ◽  
Kai Ma
Keyword(s):  
Disease Gene ◽  
Direct Sequencing ◽  
Venous Blood ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Control Group ◽  
Coding Region ◽  
Exon 2 ◽  
Norrie Disease ◽  
Familial Exudative Vitreoretinopathy

Abstract Purpose This study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features. Methods Thirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments. Results Four novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5’UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100). Conclusions Our results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

scholarly journals Efficacy of beta-blockers in the treatment of sepsis

2021 ◽  
Vol 16 (1) ◽  
pp. 1-18
Author(s):  
Peng Jin ◽  
Tao Zhao ◽  
Yueyue Wei ◽  
Fang Zhao
Keyword(s):  
Heart Rate ◽  
Beta Blocker ◽  
Troponin I ◽  
Beta Blockers ◽  
Meta Analysis ◽  
Venous Blood ◽  
Inclusion Criteria ◽  
Blood Oxygen Saturation ◽  
Factor Α ◽  
Necrosis Factor

This meta-analysis is to systematically evaluate the efficacy and safety of beta-blockers in the treatment of sepsis. A total of 17 articles that met the inclusion criteria were included, and 10,385 cases were obtained. The meta-analysis results showed that patients with sepsis with beta-blocker usage had a significantly lower 28-day mortality. The heart rate decreased over time in patients with sepsis using beta-blocker. Moreover, central venous blood oxygen saturation increased after 24, 48, 72 hours of treatment; lactic acid and cardiac troponin I decreased after 48, 72 hours of treatment; and tumor necrosis factor-α, interleukin-1β levels decreased significantly after 12, 24, 48, 72 hours of treatment (p<0.05).  In conclusion, beta-blockers reduce 28-day mortality and heart rate.

Mutational Screening of FGFR1, CER1, and CDON in a Large Cohort of Trigonocephalic Patients

2006 ◽  
Vol 43 (2) ◽  
pp. 148-151 ◽  
Author(s):  
Fernanda Sarquis Jehee ◽  
Luis G. Alonso ◽  
Denise P. Cavalcanti ◽  
Chong Kim ◽  
Steven A. Wall ◽  
...  
Keyword(s):  
High Performance ◽  
Direct Sequencing ◽  
Nucleotide Polymorphisms ◽  
Related Gene ◽  
Inclusion Criteria ◽  
Coding Region ◽  
Single Nucleotide ◽  
Metopic Synostosis ◽  
Mutational Screening ◽  
Johns Hopkins University

Objective Screen the known craniosynostotic related gene, FGFR1 (exon 7), and two new identified potential candidates, CER1 and CDON, in patients with syndromic and nonsyndromic metopic craniosynostosis to determine if they might be causative genes. Design Using single-strand conformational polymorphisms (SSCPs), denaturing high-performance liquid chromatography, and/or direct sequencing, we analyzed a total of 81 patients for FGFR1 (exon 7), 70 for CER1, and 44 for CDON. Patients Patients were ascertained in the Centro de Estudos do Genoma Humano in São Paulo, Brazil (n = 39), the Craniofacial Unit, Oxford, U.K. (n = 23), and the Johns Hopkins University, Baltimore, Maryland (n = 31). Clinical inclusion criteria included a triangular head and/or forehead, with or without a metopic ridge, and a radiographic documentation of metopic synostosis. Both syndromic and nonsyndromic patients were studied. Results No sequence alterations were found for FGFR1 (exon 7). Different patterns of SSCP migration for CER1 compatible with the segregation of single nucleotide polymorphisms reported in the region were identified. Seventeen sequence alterations were detected in the coding region of CDON, seven of which are new, but segregation analysis in parents and homology studies did not indicate a pathological role. Conclusions: FGFR1 (exon 7), CER1, and CDON are not related to trigonocephaly in our sample and should not be considered as causative genes for metopic synostosis. Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients.

S227 – Investigation of the Prion Protein in Subjects with Tinnitus

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P151-P151 ◽  
Author(s):  
Tobias Kleinjung ◽  
Berthold Langguth ◽  
Vielsmeier Veronika ◽  
Michael Landgrebe ◽  
Philipp Sand
Keyword(s):  
Prion Protein ◽  
Venous Blood ◽  
Auditory Pathway ◽  
Cellular Adhesion ◽  
Response To Treatment ◽  
Tinnitus Questionnaire ◽  
History Of ◽  
Caucasian Patients ◽  
Moderate Difference ◽  
Nervous Excitability

Objectives The prion protein (PrP) plays a major role in central nervous excitability, cellular adhesion, and neurite outgrowth. We hypothesized that PrP variants may act as a modulator of chronic tinnitus, a condition frequently associated with states of overexcitability in the auditory pathway. Methods 139 Caucasian patients who presented with tinnitus lasting more than 6 months were recruited from a tinnitus clinic, underwent detailed neuro-otological examinations and donated venous blood for the extraction of genomic DNA from lymphocytes. Subjects with a history of vestibular schwannoma, Meniere's disease, or pathological middle ear conditions were excluded. Tinnitus severity was graded using the Tinnitus Questionnaire (TQ). A polymorphism encoding residue 117 of PrP was genotyped by PCR-based RFLP. Results When carriers of the minor PrP allele were compared to the remaining subjects, we noted only a moderate difference in mean TQ scores (33.4 ± 4.9 vs. 37.4 ± 1.5, p > 0.05). Conclusions The present results thus do not support a significant effect of PrP variant rs8124214 on subjective ratings of tinnitus. However, functional PrP variants may act on additional outcome parameters, e.g., on the response to treatment. Future studies will need to address the interplay of these variants, and their effects on specific subgroups.

scholarly journals The importance of the prevention of treatment induced neutropenia in patients with malignant neoplasms of the head and neck

2021 ◽  
Vol 23 (2) ◽  
pp. 356-360
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck ◽  
Primary Prophylaxis ◽  
Infectious Complications ◽  
Hematological Toxicity ◽  
Malignant Neoplasms ◽  
Common Complication ◽  
Cost Of Treatment ◽  
Risk Of Death ◽  
The Cost

Hematological toxicity is the most common complication of chemotherapy. The most dangerous manifestation of hematological toxicity is febrile neutropenia (FN). FN reduces survival, increases the risk of death, the frequency of infectious complications, hospitalizations, the cost of treatment. The risk of FN should be assessed before the beginning of the therapy, using the general algorithm from the protocol to prevent FN applying the granulocyte colony-stimulating factors (G-CSF). G-CSF for the prevention is required throughout all cycles of myelosuppressive therapy. For the prevention of FN, the most effective is the use of PEGylated G-CSF. Patients with head and neck squamous cell carcinoma, receiving the TPF or DCF regimen, combined with docetaxel and cisplatin, are included in the group of routine primary prophylaxis for neutropenia. In case of developing 34 grade FN in these patients, the use of PEGylated G-CSF (empegfilgrastim) is preferable.

scholarly journals Hyponatremia among Psychiatric Patients Using Antipsychotic Medication in a Tertiary Hospital in South-South, Nigeria

2018 ◽  
Vol 04 ◽  
pp. 28
Author(s):  
Emmanuel O. Olose ◽  
Donald C. Chukwujekwu ◽  
Monday N. Igwe ◽  
Miriam C. Aguocha ◽  
Cecilia O. Busari ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Serum Sodium ◽  
Psychiatric Patients ◽  
Venous Blood ◽  
Tertiary Hospital ◽  
Typical Antipsychotic ◽  
Inclusion Criteria ◽  
Interview Schedule ◽  
Antipsychotic Medications ◽  
Atypical Antipsychotic Medications

The aim of this study was to determine the prevalence of hyponatremia among psychiatric patients taking antipsychotics, to determine the correlation between serum sodium levels and dosage of medications as well as to determine the association between class of antipsychotic medication and serum sodium levels among patients taking antipsychotic medications. This is a longitudinal study. From 92 consenting antipsychotic na�ve patients who met the inclusion criteria, sociodermographic interview schedule was administered. Thereafter, a single venous blood sample was obtained for serum electrolyte analysis and repeated after 6 weeks. Prevalence of hyponatremia was 19.4%, there was a correlation between hyponatremia and dose of antipsychotic in chlorpromazine equivalent (r = −0.354; p = 0.01), and there is an association between typical antipsychotic use and hyponatremia. The use of both typical and atypical antipsychotic medications can lead to hyponatremia. This is in keeping with previous reports.

Sign in / Sign up

Export Citation Format

Share Document