Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Am J Case Rep ; 20: 1648-1651, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31704906

RESUMO

BACKGROUND Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is one of the treatment options in low-grade appendiceal mucinous neoplasm with peritoneal dissemination. The minimal invasive surgery approach was introduced to the field after years of traditional open technique. Multi-port laparoscopic and robotic techniques were reported with good short-term outcomes in very selected patients with low PCI scores. We describe here the first single-port laparoscopic approach of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. CASE REPORT We present a case of low-grade appendiceal mucinous neoplasm with peritoneal dissemination, in which single-port laparoscopic approach of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was completed through a 5.5-cm incision. A 35-year-old man with no medical illness underwent laparoscopic appendectomy for acute appendicitis 3 months earlier. Postoperative surgical pathology reported a low-grade appendiceal mucinous neoplasm with positive margin. After complete assessment and Tumor Board discussion, the patient was scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. A single gel port access was inserted through a 5.5-cm peri-umbilical incision. The Peritoneal Cancer Index score was 4, and the decision was made to proceed with partial cecectomy, omentectomy, peritonectomy, and hyperthermic intraperitoneal chemotherapy with the Sugarbaker mitomycin C-based regimen. Postoperative care was carried out following the Enhanced Recovery After Surgery protocol. The patient was discharged on day 3 without any complications. CONCLUSIONS A single-port laparoscopic approach in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is safe and feasible in very selected patients, and has the advantage of direct visualization and palpation through the incision to determine more accurate Peritoneal Cancer Index assessment in comparison to other MIS approaches. Nevertheless, additional prospective studies are needed.

2.
Int J Mol Med ; 44(4): 1552-1562, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364730

RESUMO

The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease­free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol­based derivative of sulfonamide. The compound's inhibitory effect on cell proliferation was determined using the MTT assay and the xCelligence RTDP machine. Alternations in the expression of Bcl­2 and inhibitor of apoptosis protein families were detected by western blotting. Apoptotic marker protein expression, including cytochrome c and cleaved poly(ADP­ribose)polymerase was measured in the cytosolic extract of cells. Apoptosis and necrosis were detected by flow cytometry and immunofluorescence. Reactive oxygen species (ROS), and activation of caspase­3 and caspase­7 were measured using flow cytometry. Activation of the JNK pathway was detected by western blotting. We investigated the molecular mechanism of action of the sulfonamide derivative on colorectal cancer cells and found that the compound possesses a potent anticancer effect, which is primarily exerted by inducing apoptosis and necrosis. Interestingly, this compound exhibited little antiproliferative effect against the normal colonic epithelial cell line FHC. Furthermore, our results showed that the compound could significantly increase ROS production. Apoptosis induction could be attenuated by the free oxygen radical scavenger N­acetyl cysteine (NAC), indicating that the antiproliferative effect of this compound on colorectal cancer cells is at least partially dependent on the redox balance. In addition, JNK signaling was activated by treatment with this derivative, which led to the induction of apoptosis. On the contrary, a JNK inhibitor could suppress the cell death induced by this compound. Our findings thus suggested a novel anticancer mechanism of a benzo(1,3)dioxol­based derivative of sulfonamide for colorectal cancer cells and may have therapeutic potential for the treatment of colorectal cancer; however, further investigation is required.

3.
Int J Surg Case Rep ; 60: 224-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31247520

RESUMO

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a feared complication of appendicular mucocele perforation. Although a rare disease, its major sequel mandates recognition and early intervention. Intestinal malrotation is mostly asymptomatic in adults. Its significance arises when it complicates another coinciding condition by confusing the presentation, leading to delay in diagnosis and treatment. PMP and incidental finding of gut malrotation in adults are two rare events, and the chance of both occurring in the same patient is very slim. This can complicate the clinical picture and lead to devastating outcomes. PRESENTATION OF THE CASE: We present a case of PMP in a patient with gut malrotation, managed with cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). DISCUSSION: Management with CRS/HIPEC has been found to improve outcomes for patients with PMP. However, the extensive disease and abnormal anatomy of the patient in our report proposed unique intraoperative challenges. Preserving part of the colon was possible with an improvised surgical technique that we used which proved to be safe and effective. CONCLUSION: Early recognition and consideration of uncommon but serious surgical conditions are essential for improved patient outcomes. To our knowledge, this is the first report in the English literature that describes the use of CRS/HIPEC for PMP in a case of intestinal malrotation. This improvised surgical technique was found to be safe and can provide a surgical solution for preserving part of the colon in selected patients.

4.
J Enzyme Inhib Med Chem ; 34(1): 672-683, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30821525

RESUMO

Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC50 values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j, 8d/15a/15e, 5b, and 8f displayed lowered IC50 values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA2, and AmPLA2. In addition, 8d, 8h, 8j, 15a, 15b, 15e, and 15f showed better anti-α-amylase than quercetin, whereas 8g, 8h, and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Síndrome Metabólica/tratamento farmacológico , Peptídeo Hidrolases/metabolismo , Fosfolipases/antagonistas & inibidores , Quinazolinonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células HT29 , Humanos , Síndrome Metabólica/metabolismo , Estrutura Molecular , Fosfolipases/metabolismo , Quinazolinonas/síntese química , Quinazolinonas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
5.
Cancer Manag Res ; 10: 2653-2661, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233234

RESUMO

Background: IL-17 expressed by Th17 cells play a crucial role in tissue inflammation by induction of proinflammatory and neutrophil mobilizing cytokines, and IL-17 polymorphisms are associated with colorectal cancer (CRC). Objective: We investigated the expression of IL-17 and the association of IL-17 gene polymorphisms with CRC susceptibility in a Middle East population. Materials and methods: The study included 117 diagnosed CRC patients and 100 age- and gender-matched healthy controls. IL-17A rs2275913 (G197A) and IL-17F rs763780 (T7488C) single nucleotide polymorphisms, mRNA, and protein levels of IL-17A were assessed. Results: We observed significant association between rs2275913 in IL-17A and susceptibility to CRC (p = 0.016228). The AG and AA genotypes conferred 2-fold and 2.8-fold, respectively, higher risk of developing CRC compared with individuals having GG genotype. Stratification of the data based on gender and age revealed very strong association of CRC with IL17A rs2275913 only in males and "AG" genotype in patients ≤57 years of age at the time of disease diagnosis. The rs763780 in IL-17F was not linked with CRCs in our cohort. Furthermore, IL-17A mRNA expression in CRCs was significantly elevated compared to adjacent normal tissues, particularly in early stages of disease (p = 0.0005). Strong immunoreactivity to IL-17A protein was observed in 70% of early stage relative to 30% of late-stage tumors. Conclusion: The IL-17A G197A variant may be utilized as a genetic screening marker in assessing CRC risk, and its expression can be used as a biomarker for early detection of CRC in the Saudi population.

6.
Onco Targets Ther ; 11: 3313-3322, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29892198

RESUMO

Introduction: Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rate. Developments in screening, prevention, biomarker, personalized therapies and chemotherapy have improved detection and treatment. However, despite these advances, many patients with advanced metastatic tumors still succumb to the disease. New anticancer agents are needed for treating advanced stage CRC as most of the deaths occur due to cancer metastasis. A recently developed novel sulfonamide derivative 4-((2-(4-(dimethylamino) phenyl)quinazolin-4-yl)amino)benzenesulfonamide (3D) has shown potent antitumor effect; however, the mechanism underlying the antitumor effect remains unknown. Materials and methods: 3D-mediated inhibition on cell viability was evaluated by MTT and real-time cell proliferation was measured by xCelligence RTDP instrument. Western blotting was used to measure pro-apoptotic, anti-apoptotic proteins and JAK2-STAT3 phosphorylation. Flow cytometry was used to measure ROS production and apoptosis. Results: Our study revealed that 3D treatment significantly reduced the viability of human CRC cells HT-29 and SW620. Furthermore, 3D treatment induced the generation of reactive oxygen species (ROS) in human CRC cells. Confirming our observation, N-acetylcysteine significantly inhibited apoptosis. This is further evidenced by the induction of p53 and Bax; release of cytochrome c; activation of caspase-9, caspase-7 and caspase-3; and cleavage of PARP in 3D-treated cells. This compound was found to have a significant effect on the inhibition of antiapoptotic proteins Bcl2 and BclxL. The results further demonstrate that 3D inhibits JAK2-STAT3 pathway by decreasing the constitutive and IL-6-induced phosphorylation of STAT3. 3D also decreases STAT3 target genes such as cyclin D1 and survivin. Furthermore, a combination study of 3D with doxorubicin (Dox) also showed more potent effects than single treatment of Dox in the inhibition of cell viability. Conclusion: Taken together, these findings indicate that 3D induces ROS-mediated apoptosis and inhibits JAK2-STAT3 signaling in CRC.

7.
Sci Technol Adv Mater ; 18(1): 364-373, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28634498

RESUMO

Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed. Here, we have carried out a systematic study to characterize CeO2-NCs phase purity (X-ray diffraction), morphology (electron microscopy), and optical features (optical absorption, Raman scattering, and photoluminescence) to better establish their potential as anticancer drugs. Our study revealed anticancer effects of CeO2-NCs in HT29 and SW620 colorectal cancer cell lines with half-maximal inhibitory concentration (IC50) values of 2.26 and 121.18 µg ml-1, respectively. Reductions in cell viability indicated the cytotoxic potential of CeO2-NCs in HT29 cells based on inverted and florescence microscopy assessments. The mechanism of cytotoxicity confirmed by estimating possible changes in the expression levels of Bcl2, BclxL, Bax, PARP, cytochrome c, and ß-actin (control) proteins in HT29 cells. Down-regulation of Bcl2 and BclxL and up-regulation of Bax, PARP, and cytochrome c proteins suggested the significant involvement of CeO2-NCs exposure in the induction of apoptosis. Furthermore, biocompatibility assay showed minimum effect of CeO2-NCs on human red blood cells.

8.
Oncol Rep ; 37(6): 3175-3180, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28440429

RESUMO

Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population. Serum CTSB levels were evaluated in 70 patients and 20 healthy control subjects using enzyme-linked immunosorbant assay (ELISA) technique. CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal colonic tissue using quantitative PCR for mRNA levels. Detection of CTSB protein expression in tissues was carried out using both immunohistochemistry and western blotting techniques. ELISA analysis showed that in sera obtained from CRC patients, the CTSB concentration was significantly higher in late stage patients with lymph node metastases when compared to early stage patients with values of 2.9 and 0.33 ng/ml, respectively (P=0.001). The majority of tumors studied had detectable CTSB protein expression with significant increased positive staining in tumors cells when compared with matched normal colon subjects (P=0.006). The mRNA expression in early stage CRC compared to late stage CRC was 0.04±0.01 and 0.07±0.02, respectively. Increased mRNA expression was more frequently observed in the advanced cancer stages with lymph node metastases when compared with the control (P=0.002). Mann-Whitney test and paired t-test were used to compare serum CTSB and mRNA levels in early and late tumor stage. A subset of four paired tissue extracts were analyzed by western blotting. The result confirmed a consistent increase in the CTSB protein expression level in tumor tissues compared with that noted in the adjacent normal mucosal cells. These findings indicate that CTSB may be an important prognostic biomarker for late stage CRC and cases with lymph node metastases in the Middle Eastern population. Monitoring serum CTSB in CRC patients may predict and/or diagnose cases with lymph node metastases.


Assuntos
Biomarcadores Tumorais/sangue , Catepsina B/sangue , Neoplasias Colorretais/sangue , Prognóstico , Adulto , Idoso , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia
9.
Colloids Surf B Biointerfaces ; 153: 320-326, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28285257

RESUMO

Copper oxide nanoparticles (CuO-NPs) were synthesized using a urea-based thermal decomposition technique, and characterized using different techniques. X-ray diffraction (XRD) and Raman spectroscopy confirmed the phase purity and crystalline structure of CuO-NPs. The size of CuO-NPs was investigated using XRD and was confirmed via dynamic light scattering analysis. CuO-NPs showed an average diameter of ∼20nm. The possible cytotoxicity of CuO-NPs was evaluated in HT-29 and SW620 cancer cell lines. The median inhibitory concentration of CuO-NPs in HT-29 and SW-620 cells was 4.99 and 3.75µg/mL, respectively. The underlying mechanism responsible for apoptosis in colon cancer cells after CuO-NP exposure has not been well understood. In this study, we investigated the possible mechanisms of induction of apoptosis via analysis of the expression of Bcl-2 and Bcl-xL proteins in HT-29 human colon cancer cells after CuO-NP exposure. Western blot assay showed downregulation of Bcl-2 and Bcl-xL protein expression after CuO-NP exposure. Our findings may aid in the understanding of the potential mechanisms responsible for induction of apoptosis owing to inhibition of Bcl-2 and Bcl-xL protein expression. Furthermore, the antibacterial activity assay showed that the synthesized CuO-NPs did not exert significant inhibitory effects against different gram-positive and gram-negative bacteria in vitro.


Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Cobre/farmacologia , Nanopartículas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Relação Estrutura-Atividade
10.
BMC Cancer ; 17(1): 4, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-28049506

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. METHODS: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. RESULTS: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFß-induced phosphorylation of Smad2 and Samd3. CONCLUSIONS: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfanílicos/química , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Citocromos c/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Células Tumorais Cultivadas , Cicatrização/efeitos dos fármacos
11.
PLoS One ; 11(6): e0155236, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27309378

RESUMO

BACKGROUND: Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer. OBJECTIVE: To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population. METHODS: The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited. RESULTS: We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the 'C' allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations. CONCLUSION: Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Desoxirribonucleases de Sítio Específico do Tipo II/química , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Arábia Saudita , Análise de Sequência de DNA
12.
Oncol Lett ; 12(1): 393-400, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27347157

RESUMO

Mucin overexpression has been implicated in the tumorigenesis and progression of colorectal carcinoma (CRC). However, data obtained on the prognostic importance of mucin expression in CRC is inconsistent. Due to lack of data on mucin expression and the increase in CRC incidence in Saudi Arabia, the aim of the present study was to analyze the mucin expression profile in patients with CRC in this ethnic group. The present study consisted of 22 patients that underwent surgery for CRC. Histopathological and immunohistochemical staining was performed on CRC tumor and adjacent normal tissues. A tissue microarray was prepared from the tumor and normal adjacent samples to investigate the mucin expression profile using immunohistochemistry. Formalin-fixed paraffin-embedded human colorectal cancer tissues were immunostained with mucin 1 (MUC1), mucin 2 (MUC2) and mucin 5AC (MUC5AC) antibodies. Associations between mucin expression and histopathological variables were evaluated. The present study indicated that MUC1 was highly expressed in early (stage I and II; P=0.0016) and late (stage III and IV; P<0.0001) stage CRC tissues compared to normal adjacent tissues. However, MUC2 expression was observed to be downregulated in early and late stage CRC tissues compared to normal and adjacent tissues. Furthermore, serum MUC1 levels were observed to be increased in early and late stage CRC. The present findings indicate that MUC1 expression was significantly higher in early and late stage CRC tissues and MUC2 was downregulated in CRC tissues compared with normal adjacent tissues, and serum MUC1 protein was significantly higher in CRC patients compared to control serum. In conclusion, during colorectal tumorigenesis the pattern of MUC1 and MUC2 expression is altered in Saudi Arabian patients with CRC compared with normal. A higher expression of MUC1 may be used as an independent biomarker in various stages of CRC tumors, which would aid in the early detection of CRC.

13.
Oncol Lett ; 11(2): 1406-1412, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893751

RESUMO

MicroRNAs (miRNAs or miRs) have been advocated as potentially robust and highly stable biomarkers of diverse disease conditions including cancer. The primary aim of this study was two-fold: i) to profile the expression levels of selected mature miRNA signature genes, such as miR-145, miR-195, miR-29 and miR-92, in a paired-study design of 20 colorectal cancer (CRC) tissues from patients versus adjacent neoplasm-free mucosal tissues employing reverse transcription-quantitative polymerase chain reaction; and ii) to examine their expression level in the plasma of the same CRC patients in relation to the age-matched plasma of healthy controls. Statistically significant (P<0.01) increases in miR-29 (2.5) and miR-92 (2.6) were observed in CRC tissues compared with adjacent neoplasm-free mucosal tissues. Profiling of CRC plasma samples showed that the expression levels of circulating miR-29 and miR-92 were significantly higher (P<0.01) than in the age-matched normal plasma. By contrast, miR-145 and miR-195 exhibited significant (P<0.05) decreases in their mean expression levels in CRC tissue samples in relation to the normal tissues. The mean expression levels of miR-145 and miR-195 were significantly lower (P<0.05) in CRC plasma than the healthy controls. Distinct stage-dependent changes in the expression level of the four miRNA gene profiles were observed between stages II and IV plasma of CRC patients relative to the control plasma. Taken together, the results clearly reflect a similar trend for the four miRNA expression levels in tissue and plasma as well as the positive correlation in the levels of miRNAs in tissues and plasma. These findings may be useful to clarify the molecular mechanisms underlying colorectal carcinogenesis and to underscore the potential of the investigated miRNAs as novel early diagnostic biomarkers of CRC.

14.
Eur J Med Chem ; 109: 247-53, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26774930

RESUMO

Carbonic anhydrases (CA I, II, IX and XII) are known to be highly expressed in various human malignancies. CA IX is overexpressed in colorectal cancer specifically in hereditary nonpolyposis colorectal cancer. Inhibition of CA activity by small molecular CA inhibitor like sulphonamides, sulphonamide derivative (SU.D2) or HIF1a inhibitor Chetomin leads to inhibition of tumorigenesis. Eighteen new quinazolin-4-sulfonamide derivatives were prepared and characterized by means of IR, NMR and mass spectra. Certain selected derivatives were tested for their ability to inhibit four isoforms of the metalloemzyme CA, namely, CA I, CA II, CA IX and CA XII. Compound 3c was found to be highly effective in inhibiting the cancer cell proliferation. 3c decreased cell viability of human HT-29 cells in dose and time dependent manner and with IC50 of 5.45 µM. Moreover, it was tested on metastatic colon cancer cell SW-620 where it was found to be equally effective on human SW-620 cells. This novel compound inhibited the CA IX and CA XII protein expression in HT-29 cells without affecting CA I and CA II expression. These findings indicate that 3c inhibits cellular proliferation in two human colon cancer cells by specifically targeting the CA IX and CA XII expression.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Anidrases Carbônicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/enzimologia , Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Células HT29 , Humanos , Quinazolinas/química , Quinazolinas/farmacologia
15.
Oncol Rep ; 35(3): 1281-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26675982

RESUMO

The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (p<0.01) and stage III (p<0.05) when compared to adjacent normal tissue. Immunohistochemical studies revealed that TIGAR expression was increased in colorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (p<0.05) and late stage (stage III and IV) CRC (p<0.01). TIGAR protein was also found to be highly expressed in stage II and III colorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer.


Assuntos
Apoptose/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
16.
Saudi J Gastroenterol ; 20(4): 262-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25038213

RESUMO

Lymphangiomas are rare tumors affecting the gastrointestinal tract, and may be seen in the bowel, gall bladder, and pancreas. They resemble hemangiomas, but consist of spaces of variable sizes containing lymph. In this report, we describe the case of a 53-year-old male who presented with abdominal pain and constipation. Computerized tomography (CT) scan showed a polypoidal lesion at the ileocecal valve which was thought to be a gastrointestinal stromal tumor. Resected specimen did, however, show a lymphangioma. We also describe the clinicopathologic features of gastrointestinal lymphangiomas with a literature review.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Neoplasias do Íleo/diagnóstico , Valva Ileocecal , Linfangioma/diagnóstico , Humanos , Neoplasias do Íleo/diagnóstico por imagem , Neoplasias do Íleo/cirurgia , Valva Ileocecal/diagnóstico por imagem , Linfangioma/diagnóstico por imagem , Linfangioma/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
17.
Saudi J Gastroenterol ; 20(2): 134-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24705152

RESUMO

BACKGROUND/AIMS: In Saudi Arabia, colorectal cancers (CRCs) are registered as the second most common cancers. However, no data has been reported about correlation of the severity of the anemia and pretreatment platelets level with clinicopathological features of CRCs. We aimed to evaluate the association between pretreatment hemoglobin and platelets level and the clinicopathological features of CRC patients in Saudi Arabia. MATERIALS AND METHODS: Between September 2005 and November 2011, One hundred and fifty-four confirmed CRC patients underwent thorough physical examination, blood investigations, endoscopic ultrasonography (EUS), and computed tomography (CT) for staging before surgery. Findings of physical assessment, EUS, CT, and pathological specimens were correlated with pretreatment hemoglobin and platelets levels the Pearson-Kendall tau correlative coefficients. RESULTS: The mean age of cohort was 56.6 years (range: 26-89). Left-sided CRC were predominant (97 patients; 63%). Mean size of primary tumor was 6 cms (1-18) SD ± 3.55. Mean values of hemoglobin, red blood cells, hematocrit, white blood cells, and platelets were 11.9 SD ± 2.3, 35.5 SD ± 5.7, 4.43 × 10 6 /mL SD ± 0.6, 7.67 10 6 /mL SD ± 2.44, and 343 × 10 3 /mL SD ± 164.4, respectively. Pretreatment hemoglobin was inversely correlated with primary tumor size (R: 0.71, R2: 1.55, P = 0.0001) and nodal status (R: 0.02, R2: 0.05, P = 0.01). Right-sided CRC had significantly low pretreatment hemoglobin levels ( P = 0.001). Interestingly, pretreatment thrombocytosis was seen only in right-sided CRC (P = 0.0001). CONCLUSION: Pretreatment anemia and thrombocytosis were found mainly in right-sided CRCs and advanced primary and nodal stages. Pretreatment hemoglobin and thrombocytosis can be considered as useful prognostic markers in CRC patients.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Hemoglobinas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos , Arábia Saudita , Trombocitose/epidemiologia
18.
World J Gastroenterol ; 20(48): 18390-6, 2014 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-25561807

RESUMO

AIM: To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. METHODS: Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. RESULTS: The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. CONCLUSION: High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/química , Fator de Necrose Tumoral alfa/análise , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Hospitais Universitários , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Arábia Saudita , Análise Serial de Tecidos , Fator de Necrose Tumoral alfa/genética , Regulação para Cima
19.
PLoS One ; 8(11): e79281, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24260185

RESUMO

BACKGROUND: Trypanosome-derived lymphocyte triggering factor (TLTF) is a molecule released by African trypanosomes that interacts with the host immune system, resulting in increased levels of IFN-γ production. METHODOLOGY/PRINCIPAL FINDINGS: TLTF and anti-TLTF antibodies were assessed in sera and cerebrospinal fluid (CSF) from patients infected with Trypanosoma brucei gambiense (T. b. gambiense) in an attempt to identify alternative markers for diagnosis and stage determination of human African trypanosomiasis or sleeping sickness. Seventy-four serum and sixty-one CSF samples from patients with parasitologically confirmed infection and known disease stage along with 13 sera and CSF from uninfected controls were tested. In serum the levels of anti-TLTF antibodies were unrelated to the disease stage. In contrast, levels of anti-TLTF antibodies in CSF were higher in intermediate/late stages than in early stage disease patients. Specificity of the detected antibodies was assessed by inhibition of TLTF bioactivity as represented by its ability to induce IFN-γ production. Additionally, TLTF was detected in CSF from late stage patients by Western blotting with the anti-TLTF specific monoclonal antibody MO3. CONCLUSIONS/SIGNIFICANCE: These findings suggest a new possibility for disease diagnosis with focus on involvement of the CNS through detection of TLTF and anti-TLTF antibodies in the CSF.


Assuntos
Anticorpos Antiprotozoários/líquido cefalorraquidiano , Proteínas de Protozoários/líquido cefalorraquidiano , Trypanosoma brucei gambiense , Tripanossomíase Africana/líquido cefalorraquidiano , Tripanossomíase Africana/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
20.
PLoS One ; 7(8): e43913, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22952808

RESUMO

Human African trypanosomiasis or sleeping sickness is a vector-borne parasitic disease that has a major impact on human health and welfare in sub-Saharan countries. Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days to weeks later by entry into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly cross human brain microvascular endothelial cells in vitro and appear to be able to enter the murine brain without inflicting cerebral injury. Using a murine model and intravital brain imaging, we show that bloodstream forms of T. b. brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a significant level of microvascular inflammation is detectable. Extravascular bloodstream forms were viable as indicated by motility and cell division, and remained detectable for at least 3 days post infection suggesting the potential for parasite survival in the brain parenchyma. Vascular inflammation, as reflected by leukocyte recruitment and emigration from cortical microvessels, became apparent only with increasing parasitemia at later stages of the infection, but was not associated with neurological signs. Extravascular trypanosomes were predominantly associated with postcapillary venules suggesting that early brain infection occurs by parasite passage across the neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine brain parenchyma during the early stages of the disease before meningoencephalitis is fully established. Whether individual trypanosomes can act alone or require the interaction from a quorum of parasites remains to be shown. The significance of these findings for disease development is now testable.


Assuntos
Encéfalo/parasitologia , Trypanosoma brucei brucei/fisiologia , Animais , Sangue/parasitologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/parasitologia , Encéfalo/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Especificidade da Espécie , Fatores de Tempo , Trypanosoma brucei brucei/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA