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11.
Alaa Mohamed Maria Mohamed El-Shebiney Ayman Mohamed El-Saka Yomna Zamzam 《Journal of the Egyptian National Cancer Institute》2018,30(2):49-55
Purpose
The purpose of this work was to assess the truncated form of human epidermal growth factor receptor 2 (HER2) such as p95-HER2 expression in HER2-positive breast cancer (BC) patients who developed metastatic disease after adjuvant treatment with a trastuzumab-containing regimen.Patients and methods
Thirty-two histologically diagnosed HER2-positive BC patients who developed distant failure after treatment with trastuzumab-based chemotherapy (CT) regimen as an adjuvant therapy were included in the study. Immunohistochemistry (IHC) method was used to analyze p95-HER2 expression in the formalin-fixed, paraffin-embedded (FFPE) blocks of the enrolled patients.Results
p95-HER2 was positive in 34.4% of the patients. The median overall survival (OS) was 22.5 and 35?months for p95-HER2 positive and negative patients, respectively (p?=?0.036) and the median time to metastases was 14 and 21?months, respectively (p?=?0.006). There was a statistically significant association between positive p95-HER2 expression and negative hormonal receptors expression (p?=?0.004), high Ki-67 expression (p?<?0.001) and development of visceral metastasis (p?=?0.034).Conclusion
Expression of p95-HER2 in HER2-positive BC patients is significantly associated with negative hormonal receptors expression, high Ki-67 expression, presence of visceral metastases and worse overall survival. A larger study is required to confirm its association with different prognostic factors and its effect on survival. 相似文献12.
Yomna I. El-Gazzar Heba R. Ghaiad Ahmed M. El Kerdawy Riham F. George Hanan H. Georgey Khairia M. Youssef Hussein I. El-Subbagh 《Archiv der Pharmazie》2023,356(1):2200417
New 2-mercapto-quinazolin-4-one analogs were synthesized and tested for their in vitro anticancer activity, dihydrofolate reductase (DHFR) inhibition, and epidermal growth factor tyrosine kinase (EGFR-TK) inhibition activities. Compound 24 , which is characterized by a 2-benzyl-thio function, showed broad-spectrum anticancer activity with high safety profile and selectivity index. The concentrations of 24 causing 50% growth inhibition (GI50) and total cell growth inhibition (TGI) and its lethal concentration 50 (LC50) were 15.1, 52.5, and 91.2 µM, respectively, using 5-fluorouracil as a positive control. Also, it showed EGFR-TK inhibitory activity with IC50 = 13.40 nM compared to gefitinib (IC50 = 18.14 nM) and DHFR inhibitory potency with 0.30 μM compared to methotrexate (MTX; IC50 = 0.08 μM). In addition, compound 24 caused cell cycle arrest and apoptosis on COLO-205 colon cancer cells. Compounds 37, 21 , and 54 showed remarkable DHFR inhibitory activity with IC50 values of 0.03, 0.08, and 0.08 μM, respectively. The inhibitory properties of these compounds are due to an electron-withdrawing group on the quinazolinone ring, except for compound 54 . In a molecular modeling study, compound 24 showed the same binding mode as gefitinib as it interacted with the amino acid Lys745 via π–π interaction. Compound 37 showed a similar binding mode as MTX through the binding interaction with Lys68, Asn64 via hydrogen bond acceptor, and Phe31 via arene–arene interaction. The obtained model and substitution pattern could be used for further development. 相似文献
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Abdelhadi M. Habeb Sarah E. Flanagan Mohamed A. Zulali Mohamed A. Abdullah Renata Pomahačová Veselin Boyadzhiev Lesby E. Colindres Guillermo V. Godoy Thiruvengadam Vasanthi Ramlah Al Saif Aria Setoodeh Amirreza Haghighi Alireza Haghighi Yomna Shaalan International Neonatal Diabetes Consortium Andrew T. Hattersley Sian Ellard Elisa De Franco 《Diabetologia》2018,61(5):1027-1036
Aims/hypothesis
Diabetes is one of the cardinal features of thiamine-responsive megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic diabetes subtype is limited. We investigated the genotype, phenotype and response to thiamine (vitamin B1) in a cohort of individuals with TRMA-related diabetes.Methods
We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire.Results
We identified 24 different mutations, of which nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years (median 6 months [interquartile range, IQR 3–24]) and median age at diabetes onset was 10 months (IQR 5–27). At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Follow-up data was available for 15 individuals treated with thiamine for a median 4.7 years (IQR 3–10). Four patients were able to stop insulin and seven achieved better glycaemic control on lower insulin doses. These 11 patients were significantly younger at diabetes diagnosis (p?=?0.042), at genetic testing (p?=?0.01) and when starting thiamine (p?=?0.007) compared with the rest of the cohort. All patients treated with thiamine became transfusion-independent and adolescents achieved normal puberty. There were no additional benefits of thiamine doses >150 mg/day and no reported side effects up to 300 mg/day.Conclusions/interpretation
In TRMA syndrome, diabetes can be asymptomatic and present before the appearance of other features. Prompt recognition is essential as early treatment with thiamine can result in improved glycaemic control, with some individuals becoming insulin-independent.Data availability
SLC19A2 mutation details have been deposited in the Decipher database (https://decipher.sanger.ac.uk/).17.
Ayman Taher Dalia Farouk Mohamed Mahmoud Mohamed Kotb Nevein Kamal Ghamry Khaled Kholaif Ahmed A. Mageed A. Allah Ahmed Said Ali Omneya M. Osman Hala Nabil Yomna Islam Mohamed Sobhy Bakry Bassem Aly Islam Mahmoud Alalfy Salma Ashraf Nassar Almandouh H. Bosilah Ashraf A. Ghanem Nansy Mohamed Ali Rund Rania Refaat Sherif Sameh Zaki 《Fertility and sterility》2021,115(3):793-801
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Yomna I. Mahmoud 《Ultrastructural pathology》2018,42(1):23-31
Hypogonadism is a well-known complication in males with chronic liver diseases. However, the consequences of chronic hepatopathies on female reproductive capacities have received relatively little attention. The present study evaluates the effect of chronic obstructive jaundice on the ovary of adult cycling rats. Estrous cyclicity was monitored to check the functional status of the hypothalamic–pituitary–ovarian axis. Ovarian changes were assessed using histomorphometric, immunohistochemical, and ultrastructural techniques. Chronic cholestasis was associated with estrous cycle irregularities, diminished ovarian weight, primordial follicle loss, atretic follicle prevalence, marked stromal fibrosis, and diminished immunoexpression of proliferation marker and estrogen receptors, in addition to many ultrastructural alterations in theca, granulosa cells, and oocytes of antral follicles. The results establish that chronic cholestasis causes hypogonadism and premature ovarian insufficiency in adult cycling female rats. 相似文献
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Testicular atrophy and testesterone insufficiency have been commonly reported associated with chronic liver diseases. Though testosterone dependent, the epididymal changes induced by liver disease have never been studied before. Thus, this study aimed to assess the ultrastructural events in the epididymis of rats with chronic obstructive jaundice. Chronic cholestasis induced many epididymal structural alterations manifested by the reduced tubular diameters, thickening of the tubular basement membrane, and regression of the principal cells. This was accompanied with reduction of principal cell organelles, cytoplasmic vacuolations, nuclear alterations, and stereovilli loss. The results establish that chronic cholestasis causes epididymal structural changes due to androgen deficiency. 相似文献
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Marzouk Huda Farag Yomna El-Hanafi Hadeel M. Ibrahim Eman 《Clinical rheumatology》2018,37(12):3397-3403
Clinical Rheumatology - Familial Mediterranean fever (FMF) is an autoinflammatory disorder. It is caused by mutations in the MEFV gene encoding the pyrin protein, which regulates the innate... 相似文献