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2.
Am J Ther ; 23(2): e594-6, 2016.
Article in English | MEDLINE | ID: mdl-24413370

ABSTRACT

The antitumor agent actinomycin D has been used in the treatment of Wilms tumor for the past 40 years. Actinomycin D-induced hepatopathy-thrombocytopenia syndrome (HTS) is characterized as a rare syndrome. The mechanism underlying HTS may differ with individual multidrug resistance protein-1 (MDR1) genotype. The relationship between actinomycin D-related HTS and MDR1 gene mutations is presented in this case study of a pediatric patient with Wilms tumor. Our findings revealed that the girl had (-)1G>A, 1236C>T, 2677G>T, 3435C>T, and 61A>G MDR1 gene mutations. Understanding the function of genetic variants of MDR1 is an important aim for personalized cancer management.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Dactinomycin/adverse effects , Kidney Neoplasms/drug therapy , Polymorphism, Genetic , Thrombocytopenia/chemically induced , Wilms Tumor/drug therapy , ATP Binding Cassette Transporter, Subfamily B/genetics , Child, Preschool , Female , Humans
3.
Proc Natl Acad Sci U S A ; 112(28): E3661-8, 2015 Jul 14.
Article in English | MEDLINE | ID: mdl-26124131

ABSTRACT

Several cellular events cause permanent or transient changes in inherent magnetic and density properties of cells. Characterizing these changes in cell populations is crucial to understand cellular heterogeneity in cancer, immune response, infectious diseases, drug resistance, and evolution. Although magnetic levitation has previously been used for macroscale objects, its use in life sciences has been hindered by the inability to levitate microscale objects and by the toxicity of metal salts previously applied for levitation. Here, we use magnetic levitation principles for biological characterization and monitoring of cells and cellular events. We demonstrate that each cell type (i.e., cancer, blood, bacteria, and yeast) has a characteristic levitation profile, which we distinguish at an unprecedented resolution of 1 × 10(-4) g ⋅ mL(-1). We have identified unique differences in levitation and density blueprints between breast, esophageal, colorectal, and nonsmall cell lung cancer cell lines, as well as heterogeneity within these seemingly homogenous cell populations. Furthermore, we demonstrate that changes in cellular density and levitation profiles can be monitored in real time at single-cell resolution, allowing quantification of heterogeneous temporal responses of each cell to environmental stressors. These data establish density as a powerful biomarker for investigating living systems and their responses. Thereby, our method enables rapid, density-based imaging and profiling of single cells with intriguing applications, such as label-free identification and monitoring of heterogeneous biological changes under various physiological conditions, including antibiotic or cancer treatment in personalized medicine.


Subject(s)
Magnetics , Single-Cell Analysis , Anti-Infective Agents/pharmacology , Bacteria/cytology , Bacteria/drug effects , Cell Line, Tumor , Culture Media , Erythrocytes/cytology , Humans , Leukocytes/cytology , Models, Theoretical , Yeasts/cytology , Yeasts/drug effects
4.
Am J Ther ; 22(2): e36-9, 2015.
Article in English | MEDLINE | ID: mdl-24434920

ABSTRACT

5-Fluorouracil (5-FU), the mainstay of solid tumor chemotherapy over the past 40 years, induces grade III-IV toxicities in up to 15% of patients with polymorphisms in the dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) genes. These toxicities include mucositis, neutropenia, nausea, diarrhea, myelosuppression, hand-foot syndrome, and rare ocular adverse effects. Here, we present the case of a female patient with rectal cancer who received 5-FU-based chemotherapy and developed grade III hand-foot syndrome and rare acute ocular adverse effects. Genetic analysis revealed that the patient had an 85T>C mutation in the DPYD gene resulting in a DPYD*9A allele. The clinical and molecular observations indicate that DPYD deficiency may be responsible for the severe ocular adverse effects observed in 5-FU-treated patients. Application of personalized therapy based on molecular testing should help clinicians provide the most effective chemotherapy agents and dose modifications for each patient, although further population-based pharmacogenetic trials for the 5-FU metabolism-related genes are necessary to minimize adverse effects and enhance clinical outcomes.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Dihydrouracil Dehydrogenase (NADP)/genetics , Eye Diseases/chemically induced , Fluorouracil/adverse effects , Alleles , Antimetabolites, Antineoplastic/adverse effects , Eye Diseases/genetics , Female , Fluorouracil/therapeutic use , Hand-Foot Syndrome/etiology , Humans , Middle Aged , Mutation , Pharmacogenetics , Rectal Neoplasms/drug therapy , Rectal Neoplasms/etiology
5.
BMC Hematol ; 14(1): 17, 2014.
Article in English | MEDLINE | ID: mdl-25264491

ABSTRACT

BACKGROUND: Mast cell leukemia (MCL) is rare type of neoplasia with an incidence of 1% in a large series of 342 adult patients with systemic mastocytosis (SM). Chronic basophilic leukemia (CBL) is an extremely rare type of leukemia with appearance of 7 cases in the literature. CASE PRESENTATION: A 73 year-old female patient who presented with weaknes, had a prolonged duration of hematologic remission after treatment of her CBL by hydroxyurea (HU). Evolution of SM occurring as a second neoplasia concurrently with relapse of de novo CBL was demonstrated by mast cells (MCs) infiltration in the bone marrow (BM) biopsy and smear and increase in tryptase level. Transformation to MCL with simultaneous occurrance of accelerated phase of CBL were documented by the appearance of MCs in both BM and peripheral blood (PB) smears, antigen expressions detected by flow cytometry and spesific stains. Sequence analysis of c-kit gene revealed c-kit exon 11 K550N mutation. Undefined associations of MCL with different mast cell morphology, increase in IL-6 level and accelerated phase of de novo CBL was described. CONCLUSION: Elevations in CRP and IL-6 levels occurring with increases in basophil counts to high levels revealed that febrile episodes with abdominal pain seen in our patient were induced by increase in IL-6 levels released from neoplastic basophils. Neoplastic basophils with diffuse and coarse basophilic granules possibly mimic neutrophils with toxic granules and cause wrong characterization of neoplastic basophils as neutrophils by the automated blood cell counters and misleaded physicians.

6.
J Gastrointest Oncol ; 5(4): 265-9, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25083299

ABSTRACT

BACKGROUND: Colorectal cancer has a heterogeneous nature that is influenced by the tumour site. Many improvements have been made in identifying and characterizing the genetic alterations between colon and rectal cancers. However, there is not enough information about KRAS mutational differences between rectosigmoid and colon cancers arising elsewhere in the large bowel. The aim of this study was to determine the differences in the frequency of KRAS genetic alterations between rectosigmoid cancers and colon cancers. METHODS: Eighty-four patients diagnosed with colorectal cancer were included in this study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumour tissue sections. KRAS mutation analysis which was designed to detect the seven most common KRAS gene mutations (Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp) was performed. Chi-square test was used to test the association between mutation status and other variables. RESULTS: This study represents the first KRAS mutational results from Turkish rectosigmoid cancer patients. The KRAS mutation frequency of rectosigmoid tumours is higher (34.3%, 12/35) than that of colon-localized tumours (30.6%, 15/49). However, there is no significant correlation between the KRAS mutation status and tumour location (rectosigmoid and colon). CONCLUSIONS: KRAS mutation analysis has a predictive and prognostic value in identifying tumours that may be resistant to treatment. Our study shows that differences in the biological behaviour of rectosigmoid and colon cancers should be considered. This finding highlights the importance of personalized cancer management, which could be assisted by cancer genotyping tools.

7.
Appl Immunohistochem Mol Morphol ; 22(1): 37-45, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23455185

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT gene mutations have great importance for GISTs. This study evaluated the relationship between KIT mutations and GIST clinicopathologic features to define region-specific and population-specific differences. Genomic DNA was extracted from 60 GISTs, and polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17. Polymerase chain reaction amplicons were sequenced in both directions. This study represents the first mutation data of the KIT gene in GISTs from a Turkish population and reports novel mutations. The mutation rate in exon 11 (46.7%) was remarkably higher than those of the other exons (8.3% for exon 9; 11.7% for exon 13; 1.7% for exon 17). There was an association between malignancy potential and the presence of KIT mutations (odds ratio=3.18). Cases with mutations in codons W557-K558 in exon 11 had 11-fold greater risk of malignancy when compared with those without a mutation in this exon (odds ratio=11). We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.


Subject(s)
Gastrointestinal Stromal Tumors/genetics , Mutation , Proto-Oncogene Proteins c-kit/genetics , Base Sequence , DNA Primers , Humans , Polymerase Chain Reaction
8.
Asian Pac J Cancer Prev ; 14(6): 3705-9, 2013.
Article in English | MEDLINE | ID: mdl-23886169

ABSTRACT

BACKGROUND: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non- small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. MATERIALS AND METHODS: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. RESULTS: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild- type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. CONCLUSIONS: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Large Cell/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/genetics , ErbB Receptors/genetics , Lung Neoplasms/genetics , Mutation/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Large Cell/mortality , Carcinoma, Large Cell/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Survival Rate , Turkey
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