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1.
Asian Pac J Cancer Prev ; 24(3): 1027-1036, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36974558

RESUMEN

INTRODUCTION: Colorectal cancer (CRC) is a major health problem Worldwide, Egypt shows a high rate of early CRC in the world as 35% of 1,600 Egyptian CRC patients were under 40 with threefold increased risk of death within 5 years. DNA methylation-based biomarkers as methylated Septin9 (mSEPT9) has a promising role for detecting CRC. As well as set of nuclear matrix proteins associated with changes in the nuclear structure/architecture. detection of these nuclear proteins resulted in identification of biomarkers that are specific for colon cancer. Particular interest has been placed on colon cancer specific antigen-2(CCSA-2). METHODS: A total of 30 newly diagnosed CRC patients, 7 colonic adenoma patients, and 15 age- and sex-matched control subjects were recruited in this study. Plasma mSEPT9was assayed by Epi procolon kit, CCSA-2 by ELISA and, Occult blood in stool by Guaiac-based fecal occult blood test. The level of Colon Cancer mSEPT9 and CCSA-2 were carried on CRC patients both preoperatively and three months postoperatively. RESULTS: mSEPT9 has 96.7% sensitivity and 95.5% specificity in differentiating colorectal cancer patients from non-malignant cases. Also, our study showed a highly statistically significant difference between the pre and three months postoperative expression of mSEPT9 in colorectal cancer as there was a dramatically decrease in the expression of mSEPT9 postoperatively (p value < 0.001). The CCSA-2 at the cutoff level of >1.43 would provide 93.3% sensitivity and 90.9% specificity in differentiation between malignant and non-malignant cases. Also, the study showed that there is a statistically significant difference between colorectal cancer patients preoperatively and postoperatively according to CCSA-2 with dramatic decrease in its level postoperatively (p value > 0.001). CONCLUSION: The plasma SEPT9 DNA methylation level and Serum CCSA-2 could be used as promising non-invasive methods for observing the CRC patients postsurgical response to predict the occurrence of complete remission or relapses.


Asunto(s)
Antígenos de Neoplasias , Neoplasias Colorrectales , Septinas , Humanos , Biomarcadores de Tumor/genética , Relevancia Clínica , Neoplasias Colorrectales/patología , Metilación de ADN , Detección Precoz del Cáncer , Recurrencia Local de Neoplasia/genética , Septinas/genética , Antígenos de Neoplasias/genética
2.
PLoS One ; 17(12): e0278282, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36480560

RESUMEN

AIM: The role of surgical castration and rosuvastatin treatment on lipid profile and lipid metabolism related markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients. METHODS: A total of 84 newly diagnosed castrated mPC patients treated with castration were recruited and divided into two groups: Group I served as control (statin non-users) while group II treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR), Caveolin-1 (CAV1), lipid profile (LDL, HDL, triglycerides (TG) and total cholesterol (TC)) and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and soluble low density lipoprotein receptor related protein 1 (SLDLRP1)) were measured at baseline, after 3 and 6 months. Overall survival (OS) was analyzed by Kaplan-Meier and COX regression for prognostic significance. RESULTS: Before castration, HMG-CoA reductase was elevated in patients <65 years (P = 0.009). Bone metastasis was associated with high PSA level (P = 0.013), but low HMGCR (P = 0.004). Patients with positive family history for prostate cancer showed high levels of EGFR, TG, TC, LDL, alkaline phosphatase (ALP), but low AKR1C4, SLDLRP1, CAV1 and ABCA-1 levels. Smokers had high CAV1 level (P = 0.017). After 6 months of castration and rosuvastatin administration, PSA, TG, LDL and TC were significantly reduced, while AKR1C4, HMGCR, SLDLRP1, CAV1 and ABCA-1 were significantly increased. Overall survival was reduced in patients with high baseline of SLDLRP1 (>3385 pg/ml, P = 0.001), PSA (>40 ng/ml, P = 0.003) and CAV1 (>4955 pg/ml, P = 0.021). CONCLUSION: Results of the current study suggest that the peripheral lipidogenic effects of rosuvastatin may have an impact on the treatment outcome and survival of castrated mPC patients. TRAIL REGISTRATION: This trial was registered at the Pan African Clinical Trial Registry with identification number PACTR202102664354163 and at ClinicalTrials.gov with identification number NCT04776889.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias de la Próstata , Rosuvastatina Cálcica , Humanos , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos , Oxidorreductasas , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Rosuvastatina Cálcica/uso terapéutico , Castración , Egipto
3.
Curr Org Synth ; 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983349

RESUMEN

BACKGROUND: A series of new pyrimidines and thiazoles containing camphor moiety were synthesized under both conventional and microwave irradiation techniques. METHODS: The condensation of camphor either with aminoguanidine or thiosemicarbazide gives the camphor hydrazine carboximidiamide 2 and the camphor thiosemicarbazone 3, respectively. Refluxing of 3 with chloroacetonitrile afforded the camphor thiazol-4-imine 4. Compounds 2 and 4 were used as precursors for the synthesis of target products. RESULTS: The reaction of 2 with different species such as arylidene malononitrile, acetylacetone, and ethyl acetoacetate gave the corresponding camphor pyrimidine derivatives 5a,b-7 while refluxing of compound 4 with different reagents e.g. aldehydes, isatin, ninhydrin, acetic anhydride, benzene sulphonyl chloride, and p-nitro-benzoyl chloride afforded the camphor thiazole derivatives 8a-d-13, respectively. CONCLUSION: A comparison between the conventional way and the eco-friendly microwave irradiation method occurred in the synthesis of the same compounds, which the latter was more efficient. The elemental analysis, FT-IR, 1H NMR, 13C NMR, and Mass spectra confirm the structures of the obtained new compounds. The potential use of some selected derivatives as antimicrobial agents was investigated and gave promising results.

4.
Int J Immunopathol Pharmacol ; 35: 20587384211008332, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33832346

RESUMEN

This study monitored the changes in the expression of inflammatory IL-6 and IL-1ß during the treatment period of Fluoropyrimidine (FP) based therapy. RNA was extracted from the peripheral blood of 102 CRC patients before treatment with FP therapy, and from 48 and 32 patients after 3 and 6 months of treatment, respectively. The genetic transcription of IL-6 and IL-1ß was determined by real time PCR. Patients were stratified according to their levels of IL-6 and IL-1ß genes expression for subgroup and survival analyses. Baseline CRC patients showed overexpression of IL-6 and IL-1ß compared to healthy control. FP therapy significantly induced IL-6 and IL-1ß expression. Subgroup analysis showed that patients with right colon tumors had significant elevation in both IL-6 and IL-1ß with FP therapy. FP therapy significantly induced IL-1ß expression in patients ⩽45 years, smokers, with high baseline level of CA19.9, right colon tumors, low grade pathology, T3 tumors and positive lymph nodes. Survival analysis showed that baseline levels of interleukins expression had insignificant effect on overall survival and event free survival. FP therapy has an impact on the level of interleukins expression declared in certain clinicopathological subgroups of CRC patients, but without a prognostic significance on patients' survival.


Asunto(s)
Antineoplásicos/farmacología , Capecitabina/farmacología , Neoplasias Colorrectales/genética , Interleucina-1beta/genética , Interleucina-6/genética , Oxaliplatino/farmacología , Adulto , Anciano , Antineoplásicos/uso terapéutico , Capecitabina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oxaliplatino/uso terapéutico , Adulto Joven
5.
Onco Targets Ther ; 14: 1937-1951, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33758513

RESUMEN

BACKGROUND: Microsatellite instability (MSI) and circulating tumor cells (CTCs) play important roles in the diagnosis, prognosis and management of colorectal cancer (CRC) patients. METHODS: CTCs and MSI were assessed in the blood and representative tumor tissues of 100 CRC patients by flow cytometry (FCM) and PCR amplification. The data were correlated to relevant clinicopathological features of the patients, progression-free survival (PFS) and overall survival (OS) rates. RESULTS: MSI-high was detected in 44 (44.0%) patients, MSI-low in 37 (37%), and microsatellite stable (MSS) in 19 (19.0%) patients (P=0.007). The baseline CTCs count (<4 cells/7mL blood) was reported in 39% of the patients, and CTCs ≥4 cells/7mL blood in 61% of the patients (P=0.028). Improved PFS and OS rates were associated significantly with MSI-high (P<0.001), decreased CTC levels during the course of treatment (P<0.001) and post-treatment CTCs (P=0.008). There was no significant association between MSI-high and PFS or OS in early-stage patients (P=0.187 and P=0.187; respectively); however, it was associated significantly with better PFS and OS in late-stage patients (P<0.001). Multivariate analysis showed that only a change in serial CTC levels is considered an independent prognostic factor for OS (P<0.012). Post-treatment CTCs level, serial CTCs level changes during the course of treatment, lymph nodes and distant metastasis were independent prognostic factors for PFS (P<0.001, P= 0.047, P=0.001 and P<0.001; respectively). CONCLUSION: MSI and CTCs could be used as accurate, reliable and sensitive diagnostic and prognostic biomarkers for CRC patients' survival rates and outcomes.

6.
RSC Adv ; 11(25): 15184-15194, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35424040

RESUMEN

Water desalination via solar-driven interfacial evaporation is one of the most essential technologies to limit the problem of global freshwater scarcity. Searching for a highly efficient, stable, eco-friendly, and cost-effective solar-absorber material that can collect the full solar spectrum is critically important for solar steam generation. This study reports the development of a new solar thermal evaporation system based on plasmonic copper oxide/reduced graphene oxide (rGO). The silver nanoparticles in the composite exhibit a very strong solar absorption. Also, rGO and CuO nanoparticles offer excellent thermal absorptivity. Polyurethane was used as the support and as a thermal insulator. Moreover, filter paper was used for fast water delivery to the surface of the solar absorber. Ag/CuO-rGO nanocomposite is manifested to be one of the most efficient solar-absorbers reported to date for solar desalination which exhibits an average 2.6 kg m-2 h-1 evaporation rate with solar thermal efficiency up to 92.5% under 1 sun irradiation. Furthermore, the composite has excellent stability and durability as it displays stable evaporation rates for more than 10 repeated cycles in use, with no significant decrease in the activity. Besides, the successful removal of various organic dyes from contaminated water is also revealed, resulting in the production of clean condensed freshwater. Finally, this work commences a new avenue of synthesizing cost-effective thermal absorbers based on metal oxides.

7.
Hematol Oncol Stem Cell Ther ; 14(3): 206-213, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32758485

RESUMEN

OBJECTIVE/BACKGROUND: The purpose of this study was to evaluate serum cardiac troponin I and serum N-terminal (NT) pro-brain natriuretic peptide (pro-BNP) levels and the utility of tissue Doppler imaging in assessing cardiovascular changes following left ventricular (LV) dysfunction in children with beta-thalassemia major (ß-TM). In children with ß-TM who depend on regular blood transfusion, cardiac iron toxicity is a common serious complication. The most common cause of death among these patients is congestive heart failure. METHODS: This is a cross-sectional study which included 50 patients with ß-TM and 50 healthy controls. Tissue Doppler imaging was performed and levels of serum ferritin, cardiac troponin I, and NT pro-BNP were estimated for all included patients. RESULTS: Serum NT pro-BNP and cardiac troponin (cTnI) showed a significant increase in patients with ß-TM (p < .001). In patients with ß-TM, LV dimensions (LV end systolic diameter) and (LV end diastolic diameter) were large (p < .01); LV mass (p < .01), E wave, and E/A ratio (p < .01) were high (p < .05); and deceleration time was short (p < .05). Besides, transmitral ratio (E/Em) (p < .05) and tricuspid valve velocity were higher (p < .05), and early diastolic velocity (Em) (p < .05) and systolic wave velocity (Sm) were lower in patients with ß-TM (p < .05). A significant positive correlation was detected between the pro-BNP and E wave (r = 0.558, p < .001), E/A ratio (r = 0.403, p < .001), E/Em ratio (r = 0.576, p < .001), and ferritin (r = 0.545, p < .001). CONCLUSION: Pulsed wave tissue Doppler imaging and NT pro-BNP had a significant role in the estimation of ventricular dysfunction in children with ß-TM.


Asunto(s)
Ecocardiografía Doppler en Color , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Troponina I/sangre , Disfunción Ventricular Izquierda , Talasemia beta , Niño , Estudios Transversales , Egipto , Femenino , Humanos , Masculino , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/diagnóstico por imagen , Talasemia beta/sangre , Talasemia beta/diagnóstico por imagen , Talasemia beta/fisiopatología
8.
Front Mol Biosci ; 8: 775013, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35111810

RESUMEN

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (-11.5 and -8.5 Kcal/mol) as compared to the standard drug ampicillin (-8.0 and -8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

9.
J Inflamm Res ; 13: 1245-1259, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33408498

RESUMEN

AIM: The change in the levels of peripheral inflammatory markers together with EGFR in relation to 5- fluorouracil (5-FU) therapy was evaluated for their prognostic significance in colorectal cancer (CRC) patients. PATIENTS AND METHODS: Expression levels of COX2, IL6, IL1ß, EGFR, IL10, and TNFα were determined with quantitative real-time PCR (qPCR) in the peripheral blood of 90 CRC patients. The inflammatory response was correlated with patients' clinical features, disease-free survival (DFS), and overall survival (OS). RESULTS: After 6 months of 5-FU therapy, increased inflammatory response was found to be associated with smoking, T3 or T4 tumors, performance status (PS) III, positive lymph nodes, distant metastasis, and gastrointestinal (GIT) toxicity. The combination of COX2 with interleukins in a predictive equation for DFS was significant in patients with over-expression of EGFR. DFS and OS rates were reduced in patients with increased COX2, IL6, IL10, and TNFα expression with 5-FU therapy. Significant hazard of disease progression was associated with smoking (HR=1.27, P=0.004), 5-FU induction of COX2, and IL6 expression (HR=1.35, P=0.001 and HR=1.27, P=0.004, respectively). Moreover, smoking, 5-FU induction of IL6, TNFα, and IL10 expression are found to be independent prognostic factors for OS (P=0.003, 0.003, 0.002, and 0.002, respectively). CONCLUSION: The peripheral effects of 5-FU therapy have shown a significant impact on the treatment outcome of CRC patients.

10.
Egypt J Occup Med ; 43(3): 331-343, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32194314

RESUMEN

BACKGROUND: Adolescent females living in agricultural areas where crops are routinely sprayed by pesticides are expected to be environmentally exposed to pesticides' health hazards partially as those occupationally exposed. OBJECTIVE: to assess menstrual and neurobehavioral disorders among adolescent females environmentally exposed to pesticides. METHODS: This was a cross-sectional study conducted on 100 pesticide exposed adolescent females who had one or more of family members are pesticides' seasonal applicators and 50 non- exposed adolescent females matched for age and education, served as controls at Menoufia governorate, Egypt during the period of pesticide application season of cotton crop from the first days of May to the end of September 2017. A self-administered and a series of neurobehavioral tests were administered and serum Acetylcholinesterase (AChE) activity was assessed. RESULTS: A significant lower AChE activity levels were found in the exposed group than controls (Mean±SD=238.49± 23.83 vs 303.35±78.54 IU/L; respectively). There were significant higher mean scores of trail making test (parts 1 and 2) and significant lower mean scores of (similarities test, Benton visual retention test, block design test, Santa Ana dexterity test (dominant and non-dominant hands) and Beery visuo-motor imitation test in the exposed group than the controls (P<0.05). Also, the exposed group reported more prevalent irregular menstrual cycle (26.8%) and intermenstrual bleeding (28.2%) compared to the control participants (8.1% and 8.1%; respectively). CONCLUSION: Adolescent females living in agricultural areas and from families whose one or more members are pesticides' applicators have significantly lower neurobehavioral performance, report more prevalent menstrual irregularities and have lower levels of serum AChE compared to a control group. The neurobehavioral deficits demonstrated a dose-response relationship AChE levels in the exposed participants. This necessitates the need for implementation of health education programs to prevent or reduce health effects associated with pesticide exposure to adolescent females.

11.
Exp Mol Pathol ; 106: 90-101, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30578762

RESUMEN

PURPOSE: We assessed CTCs counts in NMCRC patients using four different techniques. METHODS: CTCs were detected in 63 NMCRC patients, 40 benign bowel diseases (BBD) and 40 normal controls (NC) using, flow-cytometry (FCM), CellSearch (CS), cytomorphology and quantitative real time (qPCR) for CK19, MUC1, CD44, CD133, ALDH1 expression. Results were correlated to progression free (PFS) and overall (OS). RESULTS: Positive CTCs (≥4 cells /7.5 mL blood) were detected in 50.8% (32/63) NMCRC by FCM and 7.5% (3/40) BBD (p < .001). CTCs were detected in 34/63 (54%) NMCRC, 4/40 (10%) BBD (p < .001) by CS. CK19, MUC1, CD44, CD133 and ALDH1 were expressed in 35 (55.6%), 29 (46.0%), 28 (44.4%), 26 (41.3%) and 25 (41.3%) cases of NMCRC. In BBD 4/40 (10%) cases expressed CK19, MUC1 and CD44, while 2/40 (5%) expressed CD133. Cytomorphology showed the lowest sensitivity (47.6%) and specificity (90%) for CTCs detection. The combined use of FCM or CS with CTCs-mRNA markers improved the sensitivity and specificity to 68.3%, and 95.0%; respectively. Positive CTCs and mRNA markers expression were significantly associated with shorter 5-yr PFS and OS. In multivariate analysis, CTCs mRNA markers were independent prognostic factors for PFS and OS. CONCLUSIONS: Enumeration of CTCs by FCM and RNA expression for specific colon cancer markers are comparable to CS regarding sensitivity and specificity. CTCs also represent novel therapeutic targets for NMCRC cases.


Asunto(s)
Adenocarcinoma/patología , Recuento de Células Sanguíneas/métodos , Neoplasias Colorrectales/patología , Citometría de Flujo/métodos , Técnica del Anticuerpo Fluorescente Directa/métodos , Separación Inmunomagnética/métodos , Células Neoplásicas Circulantes/patología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Coloración y Etiquetado/métodos , Adenocarcinoma/sangre , Adenocarcinoma/epidemiología , Adenocarcinoma/mortalidad , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Egipto/epidemiología , Femenino , Humanos , Enfermedades Intestinales/sangre , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes/metabolismo , Pronóstico , Supervivencia sin Progresión , Estudios Prospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , ARN Mensajero/sangre , ARN Neoplásico/sangre , Sensibilidad y Especificidad , Análisis de Supervivencia , Adulto Joven
12.
Telemed J E Health ; 25(6): 462-470, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30048216

RESUMEN

Background:Adherence and safety challenges aroused with the use of oral chemotherapeutic agents, such as capecitabine, necessitated implementation of a more focused follow-up for patients receiving these agents.Patients and Methods:This prospective, randomized open-label study explored the usefulness of weekly telephone-based follow-up in Egyptian patients with metastatic colorectal or gastric cancer treated with capecitabine-based chemotherapy regimens at the National Cancer Institute, Egypt, compared with a standard care group. Patients' adherence, safety, efficacy, and health service utilization were assessed and compared in 82 eligible patients; control group (n = 38) and intervention group (n = 44).Results:The intervention group showed statistically better tolerability to certain adverse effects in certain cycles with nonsignificantly higher patients' adherence and overall survival (OS), along with statistically higher passive call duration.Conclusion:These results suggested that pharmacist-led telephone follow-up (TFU) could help in building a close trusting rapport between the patient and caregiving pharmacist. They also demonstrated the potential usefulness of the TFU on patients' tolerability, adherence, and OS; however, further trials with a larger sample size should be encouraged to explore more pronounced results. Otherwise, the provided standard care could be considered good enough for these patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Capecitabina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Neoplasias Gástricas/tratamiento farmacológico , Teléfono , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Egipto , Femenino , Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Aceptación de la Atención de Salud/estadística & datos numéricos , Farmacéuticos/organización & administración , Estudios Prospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología
13.
Front Pharmacol ; 9: 1173, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30405408

RESUMEN

Background: Global DNA methylation has an impact in cancer pathogenesis and progression. This study aimed at investigating the impact of global DNA methylation in treatment outcome of Colorectal Cancer (CRC). Patients and Methods: Global DNA methylation was measured by LC/MS/MS in peripheral blood leucocytes of 102, 48, and 32 Egyptian CRC patients at baseline and after 3 and 6 months of Fluoropyrimidine (FP) therapy respectively, in addition to 32 normal healthy matched in age and sex. The genetic expressions of DNA methyl transferases (DNMTs) were determined and correlated with patients' survival using univariate and multivariate methods of analyses. Results: Egyptian CRC patients had significant global hypomethylation of 5mC level and 5mC % with overexpression of DNMT3A and DNMT3B. Significant higher 5mC levels were shown in patients > 45 years, male gender, T2 tumors, stage II, negative lymph nodes, and absence of metastasis. FP therapy significantly reduced DNA methylation particularly in the subgroups of patients with high DNA methylation level at baseline and good prognostic features. After 3 years of follow up, patients with 5mC % > 8.02% had significant poor overall survival (OS) while, significant better event-free survival (EFS) was found in patients with 5mC level > 0.55. High initial CEA level and presence of metastasis were significantly associated with hazards of disease progression and death. Conclusion: Global DNA methylation has a significant impact on the treatment outcome and survival of Egyptian CRC patients treated with FP- based therapy.

14.
Mol Biol Rep ; 45(6): 2025-2035, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30229477

RESUMEN

The aim of the current study was to assess the prognostic value of circulating tumor cells (CTCs) and their related markers at different points of chemotherapy regimens in metastatic breast cancer (MBC) patients. The impact of CTCs on progression free survival (PFS) and overall survival (OS) rates were also assessed. Peripheral blood samples were obtained from 66 female patients with MBC at different time intervals for evaluation of CTCs by flow cytometry (FC). cytokeratin 19 (CK19), mammaglobin, prolactin inducible peptide (PIP), aldehyde dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) were also assessed by qRT-PCR. Analysis of different CTC levels (at 4, 5, and 6 cells/7 ml), showed statistically significant values at 4 cells/7 ml blood. The presence of baseline CTCs < 4 cells/7 ml, associated significantly with higher PFS (P value = 0.03). Patients showing a decrease in the CTCs level after treatment had significantly prolonged median PFS and OS rates compared to those whose CTCs level increased (P = 0.007 and P = 0.014; respectively). Mammaglobin, CK19, PIP, ALDH1 and hCG expression did not affect PFS or OS. However, patients with CTCs ≥ 4 at diagnosis had higher rates of progression compared to those with CTCs < 4 (1.9 times, P = 0.07), and who metastasized before 4 years showed a worse decrease outcomes (they were 2.4 time more progressed than those who metastasized after 4 years; P = 0.029). CTCs could be an independent prognostic and predictive biomarker for MBC patients' outcomes. Although none of the assessed genes (mammaglobin, CK19, PIP, ALDH1 and hCG) showed correlation with PFS or OS rates, further studies on a larger number of patients are required to validate the current results.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/patología , Adulto , Familia de Aldehído Deshidrogenasa 1 , Biomarcadores de Tumor , Neoplasias de la Mama/mortalidad , Proteínas Portadoras/análisis , Gonadotropina Coriónica/análisis , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Glicoproteínas/análisis , Humanos , Isoenzimas/análisis , Queratina-19/análisis , Mamoglobina A/análisis , Proteínas de Transporte de Membrana , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Pronóstico , Supervivencia sin Progresión , Retinal-Deshidrogenasa/análisis
15.
Exp Mol Pathol ; 105(3): 260-271, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30213464

RESUMEN

AIM: To assess the role of aberrant miRNAs expressions in stage II CRC patients from Egypt. METHODS: Tumor tissue samples were obtained from 124 CRC stage II patients compared to 100 healthy controls for assessing miRNAs expression using; 1) a cataloged 84-miRNAs PCR array panel, and 2) another five miRNAs (miR-21, miR-137, miR-145, miR-320 and miR-498) that have been reported in previous studies to have a role in CRC, by quantitative real time PCR (qPCR). The results were correlated to patients' characteristics, response to treatment and survival. RESULTS: There were 17 out of 84 miRNAs differentially expressed in the CRC patients. Twenty six miRNAs were significantly differentially expressed in the female CRC patients, while 16 miRNAs were significantly differentially expressed in the male CRC patients. Only, five miRNAs (miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p) were significantly common deregulated in CRC patients regardless gender. miR-21 was overexpressed in 48.4% of the patients and it was significantly downregulated in females and over expressed in males. In univariate analysis; performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS whereas in multivariate analysis; miR-498 and miR-320 were independent prognostic factors for DFS and miR-21 was independent prognostic factors for OS. CONCLUSION: miRNAs expression differs significantly between male and female stage II CRC patients, miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p could be used as common diagnostic biomarkers for CRC. On the other hand, a three miRNAs panel (miR-21, miR-498 and miR-320) can predict recurrence and survival in those patients.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , MicroARNs/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/análisis , Estudios de Casos y Controles , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Egipto , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , MicroARNs/análisis , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto Joven
16.
RSC Adv ; 8(37): 20517-20533, 2018 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-35542380

RESUMEN

Typical highly porous metal-organic framework (MOFs) materials based on chromium benzenedicarboxylates (Cr-BDC) were prepared through a one-pot hydrothermal synthesis, and were then modified by loading the appropriate ratio of sulfamic acid (SA) using a simple impregnation technique. Pure and modified MIL-101 was characterized by XRD, TEM, SEM and FT-IR measurements. TEM and SEM measurements confirmed that the MIL-101 particles preserved their regular octahedral structure after loading with different weight contents of sulfamic acid. The total number of acid sites and Brønsted to Lewis acid sites ratio (B/L) were examined using potentiometric titration and pyridine adsorption. The acid strength and surface acidity of SA/MIL-101 gradually increased after the modification of Cr-MIL-101 by sulfamic acid crystals up to 55 wt%, then decreased again. The catalytic performance of the solid catalysts was confirmed in the synthesis of 14-phenyl-14H-dibenzo [a,j] xanthene and 7-hydroxy-4-methyl coumarin. In the two reactions, the sample with 55% sulfamic acid loaded on MIL-101 displayed the highest catalytic activity and acidity. The adsorption behaviors of sulfamic acid loaded on MIL-101 materials for methyl orange (MO) as an anionic dye were studied, and were exceptionally suitable for the Langmuir adsorption isotherm. All loaded adsorbents showed high adsorption capacity for methyl orange at 25 °C. The results indicate that the adsorption capacity was modified by changing the amount of sulfamic acid loaded on MIL-101.

17.
Andrologia ; 49(1)2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27136444

RESUMEN

To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)-induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C-reactive protein, monocyte chemoattractant proteins-1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels.


Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Antioxidantes/farmacología , Doxorrubicina/toxicidad , Estrés Oxidativo/efectos de los fármacos , Ozono/farmacología , Sustancias Protectoras/farmacología , Rutina/farmacología , Testículo/efectos de los fármacos , Animales , Hormona Folículo Estimulante/metabolismo , Hormona Luteinizante/metabolismo , Masculino , Ratas , Ratas Wistar , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/metabolismo
18.
J Infect Public Health ; 10(1): 22-30, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-26965455

RESUMEN

BK and JC polyomaviruses (PyV) have been demonstrated to be associated with the pathogenesis of various human cancers. We aimed to investigate the impact of BK and JC polyomavirus infections on several clinical parameters in different human cancers. A total of 150 cancer patients were included in the study (51 patients with solid tumors, 48 patients with lymphomas and 51 patients with leukemias). Amplification of PyV DNA was performed using a semi-nested version of Polymerase chain reaction targeting the T genomic region of PyV. The polyomavirus load was determined using real-time PCR assay. The clinical data were collected. Polyomavirus DNA could be detected in 84 (56%) of 150 of all cancerous patients. The solid tumors had the lowest proportion of JCV (6 (11.8%) of 51), whereas had the highest proportion of JCV (200copies/µl). JCV was more frequent among NHL patients (30%) and absent in HL patients (0%). During follow-up, PyV positivity decreased significantly (p=0.004) in lymphoma patients (n=28). Although PyV positivity decreased significantly from 39% to 7% in 28 of 48 lymphoma patients after treatment, it significantly persisted in leukemic patients after treatment (from 22% to 38%). JC was more frequent among leukemic patients with leukopenia. The presence of JC polyomavirus was more frequent among leukemic patients without any significant impact on their overall survival.


Asunto(s)
Virus BK/aislamiento & purificación , Virus JC/aislamiento & purificación , Neoplasias/complicaciones , Infecciones por Polyomavirus/epidemiología , Adolescente , Adulto , Anciano , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Infecciones por Polyomavirus/patología , Prevalencia , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Supervivencia , Carga Viral , Adulto Joven
19.
Appl. cancer res ; 37: 1-13, 2017. tab, ilus
Artículo en Inglés | LILACS, Inca | ID: biblio-913815

RESUMEN

Background: Patients with stage II CRC have a varying survival outcome. Therefore, it is critical to identify prognostic biomarkers that can define more aggressive forms of the disease. We assessed the expression levels of five miRNAs that have been previously addressed in relation to the development and progression of solid and hematological tumors. Methods: We measured the expression levels of miR-21, miR-137, miR-145, miR-320 and miR-498in stage II CRC patients from Egypt (124 tissues and 41 blood samples) by quantitative real time PCR (qPCR). The results were correlated with relevant clinicopathological factors, response to treatment and survival rates of the patients. Results: miR-137, miR-145 and miR-320 were significantly reduced in 39.5%, 48.4% and 52.4%; respectively whereas miR-21 and miR-498 were significantly overexpressed in 48.4% and 40.3% of the CRC tissues compared to the control group. In patients' blood, miR-137, miR-145 and miR-320 were significantly reduced in 46.3%, 46.3% and 51. 2%; respectively whereas mir-21 and miR-498 were significantly overexpressed in 46.3% and 43.9% of the cases, respectively. The concordance between tissue and blood was weak for miR-320 and miR-145 (kappa 40-65%), intermediate for miR-498 and miR-137 (kappa 65-75%) and strong for miR-21 (kappa 75-85%). In univariate analysis performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS. However, in multivariate analysis, miR-498 and miR-320 were independent prognostic factors for DFS whereas miR-21 was independent prognostic factors for OS. Conclusions: miRNAs play an important role in the development and progression of stage II CRC. A five markers panel (miR-21, miR-498, miR-137, miR-145 and miR-320) can predict recurrence and survival in stage II CRC patients from Egypt (AU)


Asunto(s)
Humanos , Masculino , Femenino , Pronóstico , Sobrevida , Biomarcadores , Neoplasias Colorrectales/clasificación , Neoplasias Hematológicas/genética , MicroARNs
20.
Actas Urol Esp ; 40(4): 258-62, 2016 May.
Artículo en Inglés, Español | MEDLINE | ID: mdl-26781549

RESUMEN

OBJECTIVE: Further evaluation of the cosmetic and functional results of approximated de-epithelized glanuloplasty in different degree of hypospadias. MATERIAL AND METHODS: This study included 96 male patients (DPH=68 & MPH=28). Patients selected for repair with glans approximation should have wide urethral plate & grooved glans. All cases were repaired with the classic TIP and glans approximation technique. Follow up was for one year by clinical examination of the meatal shape, size & site, glans shape, skin covering, suture line, urethral catheter, edema & fistula in addition to parent satisfaction. RESULTS: Mean operative time was 49±9minutes. As regards the functional and cosmetic outcomes, success was reported in 95.8%, while failure was in 4.16% in the form of glanular disruption in two patients and subcoronal urethrocutaneous fistula in another two patients. CONCLUSION: Glans approximation has many advantages, good cosmetic and functional results, short operative time, less blood loss, no need for tourniquet. Study of a large number of cases and comparing glans approximation with the classic TIP technique.


Asunto(s)
Hipospadias/cirugía , Pene/cirugía , Adolescente , Niño , Preescolar , Humanos , Lactante , Masculino , Procedimientos Quirúrgicos Urológicos Masculinos/métodos
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