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1.
Int J Pharm ; 652: 123839, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38266944

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. METHODS: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. RESULTS: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. CONCLUSIONS: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.


Assuntos
Antineoplásicos , Doenças do Sistema Nervoso Periférico , Ratos , Masculino , Animais , Cisplatino/toxicidade , Lipossomos , Acetona , Antineoplásicos/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/patologia , Polietilenoglicóis/efeitos adversos
2.
Cancers (Basel) ; 15(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37686578

RESUMO

Introduction: Colorectal cancer (CRC) is a common cancer associated with poor outcomes, underscoring a need for the identification of novel prognostic and therapeutic targets to improve outcomes. This study aimed to identify genetic variants and differentially expressed genes (DEGs) using genome-wide DNA and RNA sequencing followed by validation in a large cohort of patients with CRC. Methods: Whole genome and gene expression profiling were used to identify DEGs and genetic alterations in 146 patients with CRC. Gene Ontology, Reactom, GSEA, and Human Disease Ontology were employed to study the biological process and pathways involved in CRC. Survival analysis on dysregulated genes in patients with CRC was conducted using Cox regression and Kaplan-Meier analysis. The STRING database was used to construct a protein-protein interaction (PPI) network. Moreover, candidate genes were subjected to ML-based analysis and the Receiver operating characteristic (ROC) curve. Subsequently, the expression of the identified genes was evaluated by Real-time PCR (RT-PCR) in another cohort of 64 patients with CRC. Gene variants affecting the regulation of candidate gene expressions were further validated followed by Whole Exome Sequencing (WES) in 15 patients with CRC. Results: A total of 3576 DEGs in the early stages of CRC and 2985 DEGs in the advanced stages of CRC were identified. ASPHD1 and ZBTB12 genes were identified as potential prognostic markers. Moreover, the combination of ASPHD and ZBTB12 genes was sensitive, and the two were considered specific markers, with an area under the curve (AUC) of 0.934, 1.00, and 0.986, respectively. The expression levels of these two genes were higher in patients with CRC. Moreover, our data identified two novel genetic variants-the rs925939730 variant in ASPHD1 and the rs1428982750 variant in ZBTB1-as being potentially involved in the regulation of gene expression. Conclusions: Our findings provide a proof of concept for the prognostic values of two novel genes-ASPHD1 and ZBTB12-and their associated variants (rs925939730 and rs1428982750) in CRC, supporting further functional analyses to evaluate the value of emerging biomarkers in colorectal cancer.

3.
Cancers (Basel) ; 15(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37568755

RESUMO

Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.

4.
Neurosci Lett ; 812: 137367, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37419304

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is an important adverse effect of treatment with oxaliplatin (OXA). We have developed PEGylated nanoliposomal oxaliplatin (OXA-LIP) and tested its activity in an animal model of CIPN. OXA-LIPs were prepared using a combination of egg yolk lecithin, cholesterol, and DSPE-mPEG2000 (at ratios 400, 80, and 27 mg). These liposomes were characterized using several different methods (e.g., polydispersity index (PDI), and zeta potential, FESEM). The in vivo study was performed in 15 male rats comprising three groups: a negative control (normal saline) OXA, and OXA-LIP. These were injected intraperitoneally at a concentration of 4 mg/kg on two consecutive days every week, for 4 weeks. After that, CIPN was assessed using the hotplate and acetonedropmethods. Oxidative stress biomarkers such as SOD, catalase, MDA, and TTG were measured in the serum samples. The functional disturbances of the liver and kidney were assessed by measuring the serum levels of ALT, AST, creatinine, urea, and bilirubin. Furthermore, hematological parameters were determined in the three groups. The OXA-LIP had an average particle size, PDI, and zeta potential of 111.2 ± 1.35 nm, 0.15 ± 0.045, and -52.4 ± 17 mV, respectively. The encapsulation efficiency of OXA-LIP was 52% with low leakage rates at 25 °C.Thermal hyperalgesia changes showed OXA has significant effects in the induction of neuropathy on days 7, 14, and 21 compared to the control group. OXA had a significantly greater sensitivity than the OXA-LIP and control groups in the thermal allodynia test (P < 0.001). OXA-LIP administration did not show significant effects on the changes of oxidative stress, biochemical factors, and cell count. Our findings provide a proof of concept on the potential application of oxaliplatin encapsulated with PEGylated nanoliposome to ameliorate the severity of neuropathy, supporting further studies in clinical phases to explore the value of this agent for Chemotherapy-induced peripheral neuropathy.


Assuntos
Antineoplásicos , Doenças do Sistema Nervoso Periférico , Masculino , Ratos , Animais , Oxaliplatina/efeitos adversos , Antineoplásicos/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Polietilenoglicóis/efeitos adversos
5.
Pathol Res Pract ; 220: 153390, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640713

RESUMO

Gastrointestinal (GIs) cancers are among the most common causes of cancer related death, and hence the importance for the identification of novel prognostic/predictive biomarkers for detection of patients at an early stage, and for using these to identify novel targeted therapies to improve the efficacy of existing chemotherapeutic regimens. Programmed cell death 1 has been reported as a potential target in several malignancies, and targeting agents are being developed, some already approved by FDA, such as: pembrolizumab, Atezolizumab, Nivolumab. Pembrolizumab that have been approved for the treatment of metastatic non-small cell lung cancer. Here we provide an overview of the mechanism of action PD-1/PD-L1, prognostic value and current progress in clinical trials using PD-1/PD-L1 inhibitors, and the resistant mechanisms at underlie the inhibitory effect of these agents in the treatment of gastrointestinal cancers.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Esofágicas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Terapia de Alvo Molecular , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Resultado do Tratamento
6.
Appl Radiat Isot ; 160: 109096, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32174459

RESUMO

European corn borer Ostrinia nubilalis Hübner is one of the polyphagous insects which causes damage to more than 200 plant species. This study evaluated the applicability of using sterile insect technique (SIT) and F1 sterility (when male parents were irradiated by sub-sterilizing doses). Accordingly, the effect of gamma radiation at doses 100-350 Gy was determined on the biological and reproductive parameters.


Assuntos
Raios gama , Infertilidade , Mariposas/efeitos da radiação , Animais , Mariposas/fisiologia , Zea mays/parasitologia
7.
J Cell Biochem ; 120(5): 6962-6971, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30672016

RESUMO

The transforming growth factor-ß (TGF-ß) signaling pathway is one of the important pathways involved in the cancer cell proliferation, invasion, migration, angiogenesis, apoptosis, as well as in metastasis by agitation or invasion of metastasis-related factors, including matrix metalloproteinase (MMP), epithelial-to-mesenchymal transition (EMT), tumor microenvironment (TME), cancer stem cells (CSCs), and cell adhesion molecules (CAMs). These data suggest its potential value as a therapeutic object in the treatment of malignancies including breast cancer. Several pharmacological approaches have been established to suppress TGF-ß pathway; such as vaccines, small molecular inhibitors, antisense oligonucleotides, and monoclonal antibodies. Some of these are now approved by the US Food and Drug Administration for targeting the TGF-ß signaling pathway. This study attempts to summarize the current data about the functions of TGF-ß in cancer cells, and their probable application in the cancer therapy with a specific emphasis on recent preclinical and clinical research in the treatment of breast cancer and its prognostic value.

8.
J Cell Physiol ; 234(2): 1230-1236, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30191971

RESUMO

Long noncoding RNAs (lncRNAs) consist of 200 nucleotide sequences that play essential roles in different processes, including cell proliferation, and differentiation. There is evidence showing that the dysregulation of lncRNAs promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) leads to the development and progression in several cancers including colorectal cancer, via p53-dependent manner. This suggests that these lncRNAs may be of value as prognostic indices and a therapeutic target, as a high expression of lncRNAs PANDAR is associated with poor prognosis. Furthermore, modulating lncRNAs PANDAR has been reported to induce apoptosis and inhibit the tumor growth through modulation of cell cycle and epithelial-mesenchymal transition (EMT) pathway. The aim of the current review was to provide an overview of the prognostic and therapeutic values of lncRNAs PANDAR in colorectal cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Humanos , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Prognóstico , RNA Longo não Codificante/metabolismo , Terapêutica com RNAi , Transdução de Sinais
9.
J Cell Physiol ; 234(2): 1289-1294, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30191988

RESUMO

Cervical cancer (CC) is a common malignancy in women and a major cause of cancer-related mortality globally. Some novel biomarkers may enable the early diagnosis and monitoring of CC. MicroRNAs (miRNAs) are small noncoding RNAs that control gene translation at a posttranscriptional level. Hence the deregulation of these molecules can cause many diseases. There appears to be an association between aberrant miRNA expression and CC, but the molecular mechanisms involved in the development of CC remain unknown. The upregulation of some circulating miRNAs, for example, miRNA-20a, miRNA-203, miRNA-21, miRNA-205, miRNA-218, and miR-485-5, as well as tissue-specific miRNAs, for example, miR-7, miR-10a, miR-17-5p, miR-135b, miR-149, and miR-203 have been found in patients with CC. There is also growing evidence for the importance of miRNAs in the development of drug resistance. This review therefore highlights recently published preclinical and clinical investigation performed on tissue specific and circulating miRNAs, as potential biomarkers for the detection of patients at early stages of CC, in the prediction of prognosis, and monitoring of their response to therapy.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Exossomos/genética , Neoplasias do Colo do Útero/genética , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Tomada de Decisão Clínica , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/metabolismo , Feminino , Humanos , Medicina de Precisão , Resultado do Tratamento , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/tratamento farmacológico
10.
BMC Microbiol ; 18(Suppl 1): 143, 2018 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470191

RESUMO

BACKGROUND: The management of the tsetse species Glossina pallidipes (Diptera; Glossinidae) in Africa by the sterile insect technique (SIT) has been hindered by infections of G. pallidipes production colonies with Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; Hytrosaviridae family). This virus can significantly decrease productivity of the G. pallidipes colonies. Here, we used three highly diverged genes and two variable number tandem repeat regions (VNTRs) of the GpSGHV genome to identify the viral haplotypes in seven Glossina species obtained from 29 African locations and determine their phylogenetic relatedness. RESULTS: GpSGHV was detected in all analysed Glossina species using PCR. The highest GpSGHV prevalence was found in G. pallidipes colonized at FAO/IAEA Insect Pest Control Laboratory (IPCL) that originated from Uganda (100%) and Tanzania (88%), and a lower prevalence in G. morsitans morsitans from Tanzania (58%) and Zimbabwe (20%). Whereas GpSGHV was detected in 25-40% of G. fuscipes fuscipes in eastern Uganda, the virus was not detected in specimens of neighboring western Kenya. Most of the identified 15 haplotypes were restricted to specific Glossina species in distinct locations. Seven haplotypes were found exclusively in G. pallidipes. The reference haplotype H1 (GpSGHV-Uga; Ugandan strain) was the most widely distributed, but was not found in G. swynnertoni GpSGHV. The 15 haplotypes clustered into three distinct phylogenetic clades, the largest contained seven haplotypes, which were detected in six Glossina species. The G. pallidipes-infecting haplotypes H10, H11 and H12 (from Kenya) clustered with H7 (from Ethiopia), which presumably corresponds to the recently sequenced GpSGHV-Eth (Ethiopian) strain. These four haplotypes diverged the most from the reference H1 (GpSGHV-Uga). Haplotypes H1, H5 and H14 formed three main genealogy hubs, potentially representing the ancestors of the 15 haplotypes. CONCLUSION: These data identify G. pallidipes as a significant driver for the generation and diversity of GpSGHV variants. This information may provide control guidance when new tsetse colonies are established and hence, for improved management of the virus in tsetse rearing facilities that maintain multiple Glossina species.


Assuntos
Variação Genética , Vírus de Insetos/genética , Glândulas Salivares/virologia , Moscas Tsé-Tsé/virologia , África , Distribuição Animal , Animais , Vírus de DNA/genética , Etiópia , Evolução Molecular , Genoma Viral , Haplótipos , Repetições Minissatélites , Filogenia , Tanzânia , Uganda
11.
Environ Sci Pollut Res Int ; 25(31): 30894-30906, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30178411

RESUMO

Recently, the exposure to heavy metals through the consumption of vegetables has become a global concern. In this regard, the current study was aimed to measure the concentrations of lead (Pb) and cadmium (Cd) in the collected onion bulb samples as well as the surrounded soil using a flame atomic absorption spectrometer (FAAS). Additionally, the target hazard quotient (THQ) for males and females in all age groups of consumers were estimated by using Monte Carlo Simulation (MCS) method. Furthermore, the soil threshold values (STVs) were evaluated to investigate the heavy metal contents in the soil based on the established standard limits. In this context, 45 onion bulbs (HashtBandi region, 25 and Ravang region, 20) and 41 soil (HashtBandi region, 21 and Ravang region, 20) samples were collected (March-May of 2016). The average concentrations of Pb in the onions from HashtBandi and Ravang regions were determined as 0.0052 ± 0.0011 and 0.0061 ± 0.0022 mg/kg, and for Cd were 0.0095 ± 0.0024 and 0.0011 ± 0.0035 mg/kg, respectively. The average concentration of Pb in the soil from HashtBandi and Ravang regions were measured as 3.99 ± 3.77 and 2.03 ± 0.69 mg/kg, and for Cd, the corresponding values were determined as 2.21 ± 3.17 and 2.22 ± 0.92 mg/kg, respectively. The average concentration of Pb and Cd in both investigated onion bulb and soil were lower than Iranian national (onion bulb: Pb = 0.1 mg/kg, Cd = 0.05 mg/kg) and FAO/WHO (onion bulb: Pb = 0.3 mg/kg, Cd = 0.1 mg/kg; soil: Pb = 50 mg/kg, Cd = 0.3 mg/kg) standard limits. Moreover, the THQ and total target hazard quotient (TTHQ) for males and females in all age groups were less than 1 value. Therefore, no risk of the exposure to Pb and Cd as result of onion bulb consumption was reported. STVs for Pb and Cd in the HashtBandi region were calculated as 3.99 and 2.21 mg/kg, and Ravang as 2.03 and 2.22 mg/kg, respectively. Due to the higher calculated STVs for Cd while compared with the established standard limit for the soil, the further revisions regarding the heavy metal standard limits in the soil were recommended.


Assuntos
Cádmio/análise , Contaminação de Alimentos/análise , Chumbo/análise , Cebolas , Raízes de Plantas/química , Poluentes do Solo/análise , Adolescente , Adulto , Monitoramento Ambiental , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Medição de Risco , Espectrofotometria Atômica , Adulto Jovem
12.
Curr Pharm Des ; 24(23): 2701-2709, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30062956

RESUMO

Colorectal Cancer (CRC) is one of the most common cancers with a high rate of morbidity and mortality worldwide. It has been demonstrated that epigenetic alterations which may cause changes in the expression of microRNA, DNA methylation and histone acetylation that results in inheritable modifications in gene expression in colorectal epithelial cells, plays a crucial role in the development of CRC. Recently, targeting epigenetic modification has emerged as a potentially important treatment approach in CRC. The US Food and Drug Association has approved the use of some epigenetic drugs that may be able to inhibit or reverse these alterations and also enhance sensitivity to chemotherapeutic agents and radiotherapy in CRC. In this review we have summarized the recent pre-clinical and clinical trial studies investigating the therapeutic value of using epigenetic drugs as novel therapeutic approach in CRC treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Epigênese Genética/efeitos dos fármacos , Neoplasias Colorretais/radioterapia , Epigênese Genética/genética , Humanos
13.
Appl Radiat Isot ; 139: 279-284, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29879533

RESUMO

Bactrocera oleae is one of the most hazardous pests threatening olive orchards in Iran. SIT is an environment-friendly system of pest control based on releasing sterile males able to compete with wild males to mate with wild females. To determine sterile doses of radiation, pupae were irradiated to the doses of 0-160 Gy. Doses of 90-100 Gy were found optimal providing the necessary sterilization without severely impairing the competitiveness of the irradiated males in mating.


Assuntos
Controle Biológico de Vetores/métodos , Tephritidae/patogenicidade , Tephritidae/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Estudos de Viabilidade , Feminino , Fertilidade/efeitos da radiação , Raios gama , Irã (Geográfico) , Larva/crescimento & desenvolvimento , Larva/efeitos da radiação , Masculino , Olea/parasitologia , Comportamento Sexual Animal/efeitos da radiação , Tephritidae/fisiologia
14.
Pharmacogenomics ; 19(5): 463-474, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29629612

RESUMO

Colorectal cancer (CRC) is a major cause of cancer-related-death worldwide. Despite extensive efforts to identify valid biomarkers for the risk stratification of CRC patients, there are few of proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to CRC. Recent genome-wide association studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CRC. Several genetic polymorphisms have been identified in this region that are associated with CRC. Three genes are located at this locus; CDKN2B(encoding-p15ink4b), CDKN2A (encoding-p16ink4a/p14ARF) and 3' end of CDKN2BAS (termed-antisense-noncoding-RNA in the INK4-locus [ANRIL]). ANRIL has a post-transcriptional modulatory activity, which has been shown to perturb the expression of nearby genes. It also plays an important role in coordinating tissue remodeling through regulation of cell proliferation, apoptosis, aging, extra-cellular matrix remodeling and inflammatory response. However, the role of ANRIL is not well understood in CRC. Hypermethylation of the p14ARF and p16INK4a genes is often found in some tumors, including CRC. However, further studies are necessary to explore the clinical utility of these putative markers in risk stratification, and in the assessment of prognosis. In this review, we have summarized the prognostic and therapeutic potential of the p14ARF and p16INK4a genes in patients with colorectal cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Marcadores Genéticos/genética , Cromossomos Humanos Par 9 , Inibidor de Quinase Dependente de Ciclina p15/genética , Humanos , Prognóstico
15.
Clin Nutr ; 37(6 Pt A): 2122-2126, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29128340

RESUMO

BACKGROUND: The high prevalence of cardiovascular disease (CVD) globally is attributable to an interaction between environmental and genetic factors. Gene × diet interaction studies aim to explore how a modifiable factor interacts with genetic predispositions. Here we have explored the interaction of a heat shock protein (HSP70) gene polymorphism (+1267A > G) with dietary intake and their possible association with serum C-reactive protein (CRP), an inflammatory marker, that is a major component of CVD risk. METHODS: HSP70 genotype was determined using a TaqMan real time PCR based method.Dietary intake was assessed using a dietary questionnaire. Serum high sensitivity (Hs) CRP and other cardiovascular risk factors were assessed by routine methods. This included coronary angioplasty to determine the presence of coronary artery stenosis. RESULTS: There were significant differences between serum lipid profile and Hs-CRP across the genotypes for Hsp70. The carriers of G allele had higher serum hs-CRP concentrations, compared with the AA homozygotes, with the wild genotype. Interaction analysis showed the association was modulated by total energy intake; the interaction of high energy intake with GG genotype: RERI = 0.77, AP = 0.26, S = 1.6. CONCLUSION: We have found a significant association between the +1267A > G variant of the HSP70 gene with cardiovascular risk factors and serum hs-CRP concentrations. It is possible that a low energy diet could ameliorate the unfavorable effects of G allele of HSP70.


Assuntos
Doenças Cardiovasculares , Dieta/estatística & dados numéricos , Proteínas de Choque Térmico HSP70/genética , Inflamação , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doença Crônica/epidemiologia , Comportamento Alimentar , Feminino , Predisposição Genética para Doença , Humanos , Inflamação/epidemiologia , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
J Cell Physiol ; 233(4): 2882-2888, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28542793

RESUMO

Mutations in the Wilm's tumor 1 (WT1) gene are associated with a wide spectrum of renal manifestations, ultimately leading to end-stage kidney failure. There is an inadequate understanding of the molecular functions of WT1 in renal development, and this has limited the potential for therapeutic interventions in WT1-related diseases. In this review, we discuss the existing data on the genetic and epigenetic abnormalities that have been described in WTs and their potential utility as biomarkers for risk stratification, prediction and prognosis in patients with WTs.


Assuntos
Predisposição Genética para Doença , Tumor de Wilms/diagnóstico , Tumor de Wilms/genética , Biomarcadores Tumorais/genética , Epigênese Genética , Humanos , Prognóstico
17.
J Cell Physiol ; 233(3): 1929-1939, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28542881

RESUMO

Cervical cancer (CC) is the third most common malignancy in women globally, and persistent infection with the oncogenic human papillomaviruses (HPV) is recognized as the major risk factor. The pathogenesis of CC relies on the interplay between the tumorigenic properties of the HPV and host factors. Host-related genetic factors, including the presence of susceptibility loci for cervix tumor is substantial importance. Preclinical and genome-wide association studies (GWAS) have reported the associations of genetic variations in several susceptibility loci for the development of cervical cancer. However, many of these reports are inconsistent. In this review, we discuss the findings to date of candidate gene association studies, and GWAS in cervical cancer. The associations between these genetic variations with response to chemotherapy are also discussed.


Assuntos
Biomarcadores Tumorais/genética , Genes Supressores de Tumor , Predisposição Genética para Doença/genética , Antígenos HLA/genética , Neoplasias do Colo do Útero/patologia , Feminino , Humanos , Papillomaviridae/patogenicidade , Polimorfismo de Nucleotídeo Único/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
18.
J Cell Biochem ; 119(1): 28-33, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28543993

RESUMO

Hirschsprung's disease (HSCR) is a congenital disorder, defined by partial or complete loss of the neuronal ganglion cells in the intestinal tract, which is caused by the failure of neural crest cells to migrate completely during intestinal development during fetal life. HSCR has a multifactorial etiology, and genetic factors play a key role in its pathogenesis; these include mutations within several gene loci. These have been identified by screening candidate genes, or by conducting genome wide association (GWAS) studies. However, only a small portion of them have been proposed as major genetic risk factors for the HSCR. In this review, we focus on those genes that have been identified as either low penetrant or high penetrant variants that determine the risk of Hirschsprung's disease. J. Cell. Biochem. 119: 28-33, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Doença de Hirschsprung/genética , Predisposição Genética para Doença , Variação Genética , Síndrome
19.
Appl Radiat Isot ; 101: 135-140, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25898238

RESUMO

The effects of gamma radiation on mortality and micronucleus formation in Tribolium castaneum Herbst, Callosobruchus maculatus (F.) and Sitophilus oryzae (L.) genital cells were evaluated. Two groups of healthy and active adult insects 1-3 and 8-10 days old were irradiated with various doses (50-200 Gy) gamma ray. Seven days post-irradiation; mortality rates and micronucleus formation were assessed in genital cells of the irradiated insects. The results show that with increasing gamma doses, the mortality rate of each species increased and T. castaneum and S. oryzae showed the low and high sensitivity respectively. It was shown that the micronucleus appearance in the tested insects had correlation with amount and intensity of radiation doses. Moreover our results indicate different levels in the genotoxicity of gamma radiation among the insects' genital cells under study. The frequency of micronuclei in genital cells of 1-3 days old insects exposed to 50 and 200 Gy were 12.6 and 38.8 Mn/1000 cells in T. castaneum, 20.8 and 46.8 Mn/1000 cells in C. maculatus and 16.8 and 57.2 Mn/1000 cells in S. oryzae respectively. A high sensitivity of the genital cells to irradiation exposure was seen in S. oryzae correlated with its high mortality rate compared with the other two species. These results might be indicative of inflicting chromosomal damage expressed as micronucleus in high mortality rates observed in the pest population; an indication of genotoxic effects of radiation on the studied species.


Assuntos
Controle de Insetos/métodos , Tribolium/efeitos da radiação , Gorgulhos/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Raios gama , Testes para Micronúcleos , Tolerância a Radiação , Especificidade da Espécie , Tribolium/genética , Gorgulhos/genética
20.
Appl Radiat Isot ; 78: 16-20, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23632647

RESUMO

Effectiveness of management of insect infestation of stored products with essential oils as viable alternatives to synthetic insecticides can be enhanced with gamma radiation. We studied effects of sublethal doses of essential oils from Rosmarinus officinalis (L.) and Perovskia atriplicifolia (Benth) (safe natural insecticides) in combination with gamma radiation on mortality of adults of Tribolium castaneum (Herbst). The insects were subjected to two radiation doses and two concentrations of the essential oils in the air. This combined treatment increased the mortality, which was also 3-6 times higher than could be expected from the sum of the effects of each of the treatments. The synergistic effect was more pronounced in the case of R. officinalis (L.) than in the case of P. atriplicifolia (Benth). The experiments have shown that the known insecticidal effectiveness of the essential oils can be enhanced by preliminary irradiation. Possible approaches to implementation of the combined treatment are discussed.


Assuntos
Desinfecção/métodos , Raios gama , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , Plantas Medicinais/química , Tribolium/efeitos dos fármacos , Tribolium/efeitos da radiação , Animais , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Armazenamento de Alimentos/métodos , Tolerância a Radiação/efeitos dos fármacos , Taxa de Sobrevida , Tribolium/fisiologia
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