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1.
Somatic mutations of the chromatin remodeling gene ARID2 are observed in ∼7% of human lung adenocarcinomas (LUADs). However, the role of ARID2 in the pathogenesis of LUADs remains largely unknown. Here we find that ARID2 expression is decreased during the malignant progression of both human and mice LUADs. Using two KrasG12D-based genetically engineered murine models, we demonstrate that ARID2 knockout significantly promotes lung cancer malignant progression and shortens overall survival. Consistently, ARID2 knockdown significantly promotes cell proliferation in human and mice lung cancer cells. Through integrative analyses of ChIP-Seq and RNA-Seq data, we find that Hspa1a is up-regulated by Arid2 loss. Knockdown of Hspa1a specifically inhibits malignant progression of Arid2-deficient but not Arid2-wt lung cancers in both cell lines as well as animal models. Treatment with an HSPA1A inhibitor could significantly inhibit the malignant progression of lung cancer with ARID2 deficiency. Together, our findings establish ARID2 as an important tumor suppressor in LUADs with novel mechanistic insights, and further identify HSPA1A as a potential therapeutic target in ARID2-deficient LUADs.  相似文献   

2.
Matrix metalloproteinase [MMP]-2 and tissue inhibitor of metalloproteinase [TIMP]-2 are emerging as pivotal players in inflammation and carcinogenesis. The present study aimed to evaluate the role of MMP-2 (−735C > T) [rs 2285053] and TIMP-2 (−418G > C) [rs 8179090] gene polymorphisms in cervical cancer susceptibility in Indian women. We recruited 200 cervical cancer patients from North India and 200 unrelated, age-matched, cancer-free healthy female controls of similar ethnicity. Genomic DNA extraction from peripheral blood samples, collected from the study subjects, was carried out using salting-out method. MMP-2 and TIMP-2 genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism. Our findings demonstrated no significant association between MMP-2 (−735C > T) and TIMP-2 (−418G > C) gene polymorphisms and the risk of developing cervical cancer in the study population. Further stratified analysis using a case-only study approach revealed that there was no effect of MMP-2/TIMP-2 polymorphisms on early and advanced stages of cervical cancer. Further MMP-2 and TIMP-2 polymorphisms did not modulate the risk in cervical cancer patients who smoked tobacco/cigarettes. Overall, the present study demonstrated a lack of association between MMP-2 and TIMP-2 gene polymorphisms and cervical cancer susceptibility in women of Northern India.  相似文献   

3.
In human tumors, somatic mutation frequently occur in K-ras gene at codon 12, which makes the K-ras protein hyper active leading to uncontrolled signaling for cell division: one of the important hall mark of cancer. In order to correlate mutations in K-ras to cause, response to treatment, disease progression and recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) the following study was undertaken. By using PCR–RFLP method prevalence of codon 12 in K-ras gene was studied in 56 HNSCC patients. High frequency of K-ras mutation was detected in codon 12 (60.71%). The result of this study helps us in understanding the role of K-ras somatic mutations in HNSCC patients and in designing novel treatment protocols for HNSCC patients.Electronic supplementary materialThe online version of this article (10.1007/s12291-020-00882-w) contains supplementary material, which is available to authorized users.  相似文献   

4.
The purpose of this study is to find out the frequency of TP53 mutations in acute myeloid leukemia (AML) patients and correlate sensitivity of drug response with TP53 mutations. In AML more than 90 % of cases comprise of wild type TP53. 94.2 % of TP53 mutations are found within exon 5–8 of which 73 % are point mutations. TP53 mutations were analysed with high resolution melting curve analysis. We analysed 106 AML samples of which we found nine mutations which represents 8.5 % mutation rate and found one rare SNP. The effect of TP53 mutations were studied on the chemosensitivity of two new drugs AZD115 and RHPS4, an Aurora Kinase B inhibitor and Telomerase inhibitor respectively. Four mutations were found out of 17 for RHPS4 stating significant (p = 0.002) increase in sensitivity and no mutation found in AZD1152 database, but need more study to get definite conclusion.  相似文献   

5.
Oral squamous cell carcinoma is one of the most common malignancies recognized. Biomarkers which can predict presence of cancer and its progression can help in better management of these disorders. Over production of lipid peroxidation byproducts and disturbances in antioxidant defense system have been implicated in the pathogenesis of several diseases including oral cancer. Studies have shown a correlation of butyrylcholinesterase (BChE), with tumourigenesis, cell proliferation and cell differentiation. Earlier we have observed a significant elevation in plasma BChE and protein thiols in oral cancer patients which correlated well with stages of cancer. As it was not clear whether the above markers will be altered in saliva of oral cancer patients this study was undertaken. Institutional Ethics Committee gave permission to carry out this study. Total of 55 subjects comprising healthy controls (n = 30) and biopsy proven oral cancer patients (n = 25) consented to participate in this study. Salivary samples from cases were taken before any definitive treatment. Protein thiols and BChE were estimated in salivary samples using validated assay methods. Oral cancer patients had a significant increase in pre-treatment salivary BChE levels (p ≤ 0.001) and a significant decrease (p ≤ 0.001) in salivary thiols as compared to respective values in controls. Salivary protein thiols and BChE may have a role in pathophysiology of oral cancer. Saliva can be used as a potential non-invasive screening tool in oral cancer patients.  相似文献   

6.
Cystic Fibrosis Trans membrane conductance regulator (CFTR) gene is an asthma susceptibility gene. In the present study we investigated the possible association of CFTR gene mutations in Indian asthmatic children as compared to controls. The study included 250 asthmatics and 250 age and sex matched controls. Case to control ratio for sample size was 1:1. Genotyping was performed for 24 CFTR gene mutations by ARMS-PCR and PCR–RFLP method. Among 24 CFTR gene mutations, heterozygous allele of R553X mutation was found in 4 (1.6 %) asthmatic cases and 2 (0.8 %) controls. Value of FVC and FEV1/FVC ratio were significantly lower in heterozygous individuals (p value <0.05). No significant difference was observed in the genotype and allele frequency of R553X mutation (OR = 1.339, 95 % CI = 0.755–2.374, p value = 0.685). Furthermore, all wild type homozygous alleles were observed in remaining 23 CFTR gene mutations. Our data concludes that R553X mutation was not significantly associated in Indian asthmatic children.  相似文献   

7.
Nebulizers have considerable advantages over conventional inhalers for pulmonary drug administration, particularly because they do not require coordinated breath actuation to generate and deliver the aerosols. Nevertheless, besides being less amenable to miniaturization and hence portability, some nebulizers are prone to denature macromolecular drugs due to the large forces generated during aerosolization. Here, we demonstrate a novel portable acoustomicrofluidic device capable of nebulizing epidermal growth factor receptor (EGFR) monoclonal antibodies into a fine aerosol mist with a mass median aerodynamic diameter of approximately 1.1 μm, optimal for deep lung deposition via inhalation. The nebulized monoclonal antibodies were tested for their stability, immunoactivity, and pharmacological properties, which confirmed that nebulization did not cause significant degradation of the antibody. In particular, flow cytometry demonstrated that the antigen binding capability of the antibody is retained and able to reduce phosphorylation in cells overexpressing the EGFR, indicating that the aerosols generated by the device were loaded with stable and active monoclonal antibodies. The delivery of antibodies via inhalation, particularly for the treatment of lung cancer, is thus expected to enhance the efficacy of this protein therapeutic by increasing the local concentration where they are needed.  相似文献   

8.
Increased levels of plasma DNA have frequently been noticed in the blood plasma of cancer patients. The possibility of using plasma DNA level as the indicator of tumor stage in breast cancer was investigated in plasma samples obtained from 100 breast cancer patients and 100 healthy women who were included as controls. Circulatory plasma free DNA was extracted from plasma samples and quantified by fluorometer. The median concentration of plasma DNA in the plasma samples from breast cancer patients classified by TNM staging system as stage I, II, III, IV and breast surgical patients were 0.5, 235, 422, 1,280 and 0.5 ng/ml, respectively. The level of plasma DNA in the stage II- IV group was significantly higher than those in the surgical group with breast cancer and control group (P value < 0.001). The plasma DNA concentration in stage II, III and IV of breast cancer were higher when compared with healthy group. These tumor size, TNM stage and metastasis were significantly correlated with plasma DNA. The cut point of 120 ng/ml was early screening and treatment follow up breast cancer.  相似文献   

9.
The case control study was conducted to quantify the amount of the carcinogenic tobacco specific nitrosamine in smokeless tobacco users and smokers in patients with oral leukoplakia and also to emphasize the role of tobacco-specific nitrosamine in the incidence of oral leukoplakia. The study was conducted on 30 patients. The urine samples were obtained from smokeless tobacco users with oral leukoplakia, smokers with oral leukoplakia and non-tobacco users (i.e. people who do not use tobacco in any form). The collected samples were processed by gas chromatography-mass spectrometry. A highly significant difference of NNAL[4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] in smokeless tobacco users than tobacco smokers P = 0.0002 (Table 1) was obtained. This significant difference shows smokeless tobacco is more carcinogenic than smoked tobacco. This study confirmed that NNAL is a potent biomarker for calculating the risk of occurrence of carcinoma in smokeless tobacco users and smokers, and that smokeless tobacco is more harmful than smoked tobacco.  相似文献   

10.
Nicotine, responsible for the addictive properties of tobacco, is widely used in nicotine replacement therapy for tobacco use cessation. We investigated the time-dependent effect of treatment with nicotine on the tumor suppressor, DNA repair and immune responses. Swiss Albino mice (laca strain) of both sexes received nicotine dissolved at a dose of 100 µg/ml in 2% sucrose for 24 weeks, by oral gavage, while age- and gender-matched controls received only 2% sucrose for the same period. Nicotine-treated and control mice were sacrificed 6, 16 and 24 weeks post-treatment, and their tissues evaluated for alterations in histology, oxidative stress, TNF-α levels, nitric oxide (NO) and myeloperoxidase (MPO) release, tumor suppressor response and DNA repair response. Statistical significance of results was determined using Students’ t test. The tissues of nicotine treated mice exhibited a large number of multinucleated and binucleated cells, enlarged nuclei and non-uniform distribution of cells, significant increase in expression of TNF-α gene and serum TNF-α, and time-dependent significant increase in lipid peroxidation, protein carbonylation, NO and MPO release when compared to age-and gender-matched controls. The mRNA expression of the tumor suppressor gene p53, its primary regulator Mdm2, and the DNA repair genes Brca2 and Ape1 were significantly elevated, but the corresponding protein levels remained largely unaltered. In conclusion, treatment with nicotine caused oxidative stress and inflammation which can cause widespread cellular damage from the very onset of treatment, without subverting the tumor suppressor and DNA repair responses.Electronic supplementary materialThe online version of this article (10.1007/s12291-020-00903-8) contains supplementary material, which is available to authorized users.  相似文献   

11.
We have developed a microfluidics based sampling system for tissue analytics. The proof-of-concept of the sampling system was demonstrated by extracting lipid samples from tissue biopsies. The sample collection system consists of a disposable silicon based multiport microneedle integrated with polymer microfluidics. The polymethyl methacrylate polymer microfluidic chip has a 10 μl sample reservoir and actuation membranes for liquid pumping. A special automated robotic system was developed to control the positioning of the needle and the sampling procedure on preselected spots on the tissue. Real breast cancer tissue samples were used to test the feasibility of the sampling system. We successfully measured indicative cancer biomarkers from the tissue surface. Phosphatidylcholine and phosphoethanolamine were extracted from the tissue membrane with methyl tert-butyl ether solvent and detected by mass spectrometry. In the future, this tool could be used in characterization of preoperative biopsies and tumour tissues removed during surgery.  相似文献   

12.
Cripto-1 (CR-1) is an oncofetal protein with its role as a key factor in early process of carcinoma has been evaluated in cases of various cancers. However, very few studies have reported its role in oral cancer, which is the sixth most common cancer around the world, particularly with high prevalence in developing countries. Oral squamous cell carcinoma (OSCC) is the most predominant (90%) of all the histological types of oral cancer. Late detection, associated with increased morbidity and mortality, is mainly attributed to non-availability of a suitable biomarker for the disease. In the present pilot study, we have evaluated the role of soluble CR-1, in serum as a potential tumor marker for OSCC. CR-1 was estimated using sandwich ELISA in serum samples of 50 biopsy proven OSCC patients (pre and post treatment) along with age and gender matched healthy controls. Immunohistochemistry was also done in corresponding tumor tissue sections to check the expression of CR-1. Pre-treatment CR-1 was found to be 2.25-fold higher in serum of OSCC patients as compared to control (p < 0.0001***), which was reduced to 1.6 folds post treatment (p = 0.0006***). CR-1 levels were comparatively higher in early stage of disease. Upon IHC 80% of the cases were found to be positive for CR-1. This study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.  相似文献   

13.
BackgroundWeedy rice (Oryza sativa L.) is a noxious form of cultivated rice (O. sativa L.) associated with intensive rice production and dry seeding. A cost-efficient strategy to control this weed is the Clearfield rice production system, which combines imidazolinone herbicides with mutant imidazolinone-resistant rice varieties. However, imidazolinone resistance mutations can be introgressed in weedy rice populations by natural outcrossing, reducing the life span of the Clearfield technology. Timely and accurate detection of imidazolinone resistance mutations in weedy rice may contribute to avoiding the multiplication and dispersion of resistant weeds and to protect the Clearfield system. Thus, highly sensitive and specific methods with high throughput and low cost are needed. KBioscience’s Allele Specific PCR (KASP) is a codominant, competitive allele-specific PCR-based genotyping method. KASP enables both alleles to be detected in a single reaction in a closed-tube format. The aim of this work is to assess the suitability and validity of the KASP method for detection in weedy rice of the three imidazolinone resistance mutations reported to date in rice.ResultsValidation was carried out by determining the analytical performance of the new method and comparing it with conventional allele-specific PCR, when genotyping sets of cultivated and weedy rice samples. The conventional technique had a specificity of 0.97 and a sensibility of 0.95, whereas for the KASP method, both parameters were 1.00.ConclusionsThe new method has equal accuracy while being more informative and saving time and resources compared with conventional methods, which make it suitable for monitoring imidazolinone-resistant weedy rice in Clearfield rice fields.  相似文献   

14.
DNA repair capacity is essential in maintaining cellular functions and homeostasis. Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. Double strand break repair pathway plays critical roles in maintaining genome stability. Present study was conducted to determine distribution of XRCC3 Exon 7 (C18067T, rs861539) and XRCC7 Intron 8 (G6721T, rs7003908) gene polymorphisms in North Indian population and compare with different populations globally. The genotype assays were performed in 224 normal healthy individuals of similar ethnicity using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Allelic frequencies of wild type were 79% (C) in XRCC3 Exon 7 C > T and 57% (G) in XRCC7 Intron 8 (G > T) 57% (G) observed. On the other hand, the variant allele frequency were 21% (T) in XRCC3 Exon 7 C > T and 43% (T) in XRCC7 Intron 8 G > T respectively. Major differences from other ethnic populations were observed. Our results suggest that frequency in these DNA repair genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.  相似文献   

15.
Genetic sequence and hyper-methylation profile information from the promoter regions of tumor suppressor genes are important for cancer disease investigation. Since hyper-methylated DNA (hm-DNA) is typically present in ultra-low concentrations in biological samples, such as stool, urine, and saliva, sample enrichment and amplification is typically required before detection. We present a rapid microfluidic solid phase extraction (μSPE) system for the capture and elution of low concentrations of hm-DNA (≤1 ng ml−1), based on a protein-DNA capture surface, into small volumes using a passive microfluidic lab-on-a-chip platform. All assay steps have been qualitatively characterized using a real-time surface plasmon resonance (SPR) biosensor, and quantitatively characterized using fluorescence spectroscopy. The hm-DNA capture/elution process requires less than 5 min with an efficiency of 71% using a 25 μl elution volume and 92% efficiency using a 100 μl elution volume.  相似文献   

16.
Reactive oxygen species (ROS) are cytotoxic at higher concentration resulting in cell death, mutations, chromosomal aberrations or carcinogenesis. In this study DNA was modified by singlet oxygen and superoxide anion radicals generated by illumination of riboflavin under 365 nm UV-light. The modified DNA induced high titre antibodies in experimental animals. In enzyme immunoassay, serum antibodies from cancer patients (n = 34) showed a higher recognition of the modified DNA, as compared to the native form. This was further confirmed by the gel-shift assay. Immune IgG were used as a probe to detect oxidative lesions in the DNA of cancer patients. DNA isolated from lymphocytes of cancer patients proved to be an appreciable inhibitor of the experimentally induced antibodies against the ROS-DNA. This indicates the presence of oxidative lesions in the DNA obtained from cancer patients. The results show that ROS induced oxidative damage to DNA in cancer patients generate neo-epitopes that are alien for the immune system, resulting in autoantibody formation.  相似文献   

17.
Methionine synthase reductase (MTRR) is an important enzyme of the folate/homocysteine pathway. It is responsible for regulation of methionine enzyme by reductive methylation. A common variant A66G is reported in the FMN-binding domain of the MTRR gene, which leads to substitution of isoleucine by methionine (I22M) in MTRR enzyme with reduced activity. Reduced catalytic activity of enzyme leads to high homocysteine concentration in blood and increases risk for numerous diseases. The frequency of A66G polymorphism varies in different ethnic groups. The present study has been designed to evaluate the frequency of MTRR A66G gene polymorphism in the Eastern UP population by PCR–RFLP method. Along with this we also performed a meta-analysis to evaluate the global prevalence of this polymorphism. Databases were screened to identified the eligible studies. The prevalence of the G allele and GG genotype was determined by the use of prevalence proportion with 95% CI. Open meta-analyst software was used for the meta-analysis. Total 1000 blood samples were analyzed, the frequencies of A and G alleles were 0.35 and 0.65 respectively. Meta-analysis results revealed that the prevalence of G allele and GG genotype were 49.4% (95% CI 40.6–58.1, p ≤ 0.001) and 24.3% (95% CI 17.8–30.9, p ≤ 0.001) respectively. In sub-group meta-analysis, the lowest frequency of G allele was found in South America (32.7%; 95% CI 14.1–51.3, p ≤ 0.001), and highest in Asia (56.4%; 95% CI 39.5–73.3, p ≤ 0.001). The results of the meta-analysis showed that the Asian population has the highest frequency of G allele and highest frequency of the GG genotype was found in the European population.  相似文献   

18.
2D nanomaterials generally exhibit enhanced physiochemical and biological functions in biomedical applications due to their high surface-to-volume ratio and surface charge. Conventional cancer chemotherapy based on nanomaterials has been hindered by their low drug loading and poor penetration in tumor tissue. To overcome these difficulties, novel materials systems are urgently needed. Hereby, the lanthanide-based porphyrin metal–organic framework (MOF) nanosheets (NSs) with promising cancer imaging/chemotherapy capacities are fabricated, which display superior performance in the drug loading and tumor tissue penetration. The biodegradable PPF-Gd NSs deliver an ultrahigh drug loading (>1500%) and demonstrate the stable and highly sensitive stimuli-responsive degradation/release for multimodal tumor imaging and cancer chemotherapy. Meanwhile, PPF-Gd NSs also exhibit excellent fluorescence and magnetic resonance imaging capability in vitro and in vivo. Compared to the traditional doxorubicin (DOX) chemotherapy, the in vivo results confirm the evident suppression of the tumor growth by the PPF-Gd/DOX drug delivery system with negligible side effects. This work further supports the potential of lanthanide-based MOF nanomaterials as biodegradable systems to promote the cancer theranostics technology development in the future.  相似文献   

19.
X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. Several studies have reported contradictory results for XRCC1 exon 6 C>T (rs1799782) gene polymorphism and cancer risk in Indian population has provided inconsistent results. Therefore, we have performed this meta-analysis to evaluate the relationship between XRCC1 exon 6 C>T gene polymorphism and risk of cancer by published studies. We searched PubMed and Google scholar web databases to cover all studies published on association between XRCC1 exon 6 C>T gene polymorphism and cancer risk. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. In order to derive a more precise estimation of the association, A total of 3197 confirmed cancer cases and 3819 controls were included from eligible seventeen case-controls studies. Results from overall pooled analysis demonstrated suggested that that variant allele (T vs. C: OR 1.301, 95% CI 1.003–1.688, p = 0.047) was associated with the risk of overall cancer. Other genetic models; heterozygous (TC vs. CC: OR 1.108, 95% CI 0.827–1.485, p = 0.491), homozygous (TT vs. CC: OR 1.479, 95% CI 0.877–2.493, p = 0.142), dominant (TT+TC vs. CC: OR 1.228, 95% CI 0.899–1.677, p = 0.196) and recessive (TT vs. TC+CC: OR 1.436, 95% CI 0.970–2.125, p = 0.071) did not reveal statistical association. Publication bias observation was also considered and none was detected during the analysis. The present meta-analysis suggested that the variant allele T of XRCC1 exon 6 gene polymorphism was associated with the risk of cancer. It is therefore pertinent to confirm this finding in a large sample size to divulge the mechanism of this polymorphism and cancer risk in Indian population.  相似文献   

20.
BackgroundPiercing/sucking insect pests in the order Hemiptera causes substantial crop losses by removing photoassimilates and transmitting viruses to their host plants. Cloning and heterologous expression of plant-derived insect resistance genes is a promising approach to control aphids and other sap-sucking insect pests. While expression from the constitutive 35S promoter provides broad protection, the phloem-specific rolC promoter provides better defense against sap sucking insects. The selection of plant-derived insect resistance genes for expression in crop species will minimize bio-safety concerns.ResultsPinellia ternata leaf agglutinin gene (pta), encodes an insecticidal lectin, was isolated and cloned under the 35S and rolC promoters in the pGA482 plant transformation vector for Agrobacterium-mediated tobacco transformation. Integration and expression of the transgene was validated by Southern blotting and qRT-PCR, respectively. Insect bioassays data of transgenic tobacco plants showed that expression of pta under rolC promoter caused 100% aphid mortality and reduced aphid fecundity up to 70% in transgenic tobacco line LRP-9. These results highlight the better effectivity of pta under rolC promoter to control phloem feeders, aphids.ConclusionsThese findings suggested the potential of PTA against aphids and other sap sucking insect pests. Evaluation of gene in tobacco under two different promoters; 35S constitutive promoter and rolC phloem-specific promoter could be successfully use for other crop plants particularly in cotton. Development of transgenic cotton plants using plant-derived insecticidal, PTA, would be key step towards commercialization of environmentally safe insect-resistant crops.How to citeUmer N, Naqvi RZ, Rauf I, et al. Expression of Pinellia ternata leaf agglutinin under rolC promoter confers resistance against a phytophagous sap sucking aphid, Myzus persicae. Electron J Biotechnol 2020;47. https://doi.org/10.1016/j.ejbt.2020.07.004.  相似文献   

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