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1.
Cancers (Basel) ; 15(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37760581

RESUMO

The overall risk of developing cancer before the age of 75 years in the Kingdom of Saudi Arabia is 9.9%. We aimed to explore the pattern of skin cancer, specifically among the Saudi population residing in the Aseer region. We obtained data from the medical records of Aseer Central Hospital regional histopathological laboratory considering surgical pathology reports from 2011 to 2021. The 61-80-year-old age group represented most of the cases (41.4%), followed by the 41-60-year-old group at 24.1%. Men made up the majority of the cases (59.4%). Furthermore, the dataset predominantly consisted of Saudi nationals (94.3% of the sample). The percentage of cases diagnosed each year relative to the cumulative number of skin cancer cases varied each year, ranging from 1.6% in 2011 to 11.6% in 2017. The most common diagnoses were squamous cell carcinoma (SCC) with 230 cases (41.1%) and basal cell carcinoma (BCC) with 147 cases (26.3%). The majority of cases occurred in the head and neck region (55.4%), followed by the lower limb (16.6%), trunk (13.6%), upper limb (8.2%), and pelvis (2.3%). There was a significant variation in the type of skin cancer across the age groups (p < 0.001) and across different body parts (p < 0.001). The incidence of skin cancer exhibited variability throughout the study period. The predominant diagnoses observed were SSC and BCC. Among the affected areas, the head and neck region displayed the highest prevalence, followed by the lower limb, trunk, upper limb, and pelvis.

2.
Cureus ; 15(12): e51402, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38292972

RESUMO

Background and purpose The Microsporum gypseum complex is a globally distributed group of geophilic dermatophytes that primarily affect animals but can also rarely cause dermatomycoses in humans. With some regional and occupational variations, tinea corporis is the most prevalent presentation of the infection. The aim of this study was to report on the diagnosis and treatment of dermatophytosis cases among related families, and their pets, from southern Saudi Arabia. Up-to-date information on dermatophytes and dermatophytosis is needed. Methods This is a prospective case series undertaken at the Dermatology Outpatient Clinic of King Khalid University, Saudi Arabia. Six patients with suspected dermatophytosis were received at our hospital in 2022 and have been followed for recovery with or without scars. Characteristics of fungal pathogens were examined phenotypically on the basis of microscopic and growth characteristics, and laboratory data were used to initiate treatment with oral fluconazole, topical terbinafine cream, or oral itraconazole. Results Clinical features and culture results confirmed tinea capitis and tinea corporis caused by M. gypseum, which was also present in a pet cat. Tinea capitis cases (n = 4) did not respond to fluconazole and terbinafine treatment, but treatment with itraconazole resulted in a full recovery. Tinea corporis cases (n = 2) were treated with terbinafine, which resulted in a full recovery within four weeks, with no signs of scarring. Conclusions M. gypseum presents with serious persistent lesions and is extremely contagious. Treatment is durable but challenging, and breaking the transmission chain is more difficult.

3.
Oncol Res ; 29(5): 305-318, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37305163

RESUMO

Malignant melanoma is characterized by both genetic and molecular alterations that activate phosphoinositide 3-kinase (PI3K), and RAS/BRAF pathways. In this work, through diversity-based high-throughput virtual screening we identified a lead molecule that selectively targets PI3K and BRAFV600E kinases. Computational screening, Molecular dynamics simulation and MMPBSA calculations were performed. PI3K and BRAFV600E kinase inhibition was done. A375 and G-361 cells were used for in vitro cellular analysis to determine antiproliferative effects, annexin V binding, nuclear fragmentation and cell cycle analysis. Computational screening of small molecules indicates compound CB-006-3 selectively targets PI3KCG (gamma subunit), PI3KCD (delta subunit) and BRAFV600E. Molecular dynamics simulation and MMPBSA bases binding free energy calculations predict a stable binding of CB-006-3 to the active sites of PI3K and BRAFV600E. The compound effectively inhibited PI3KCG, PI3KCD and BRAFV600E kinases with respective IC50 values of 75.80, 160.10 and 70.84 nM. CB-006-3 controlled the proliferation of A375 and G-361 cells with GI50 values of 223.3 and 143.6 nM, respectively. A dose dependent increase in apoptotic cell population and sub G0/G1 phase of cell cycle were also observed with the compound treatment in addition to observed nuclear fragmentation in these cells. Furthermore, CB-006-3 inhibited BRAFV600E, PI3KCD and PI3KCG in both melanoma cells. Collectively, based on the computational modeling and in vitro validations, we propose CB-006-3 as a lead candidate for selectively targeting PI3K and mutant BRAFV600E to inhibit melanoma cell proliferation. Further experimental validations, including pharmacokinetic evaluations in mouse models will identify the druggability of the proposed lead candidate for further development as a therapeutic agent for treating melanoma.


Assuntos
Melanoma , Fosfatidilinositol 3-Quinases , Humanos , Animais , Camundongos , Fosfatidilinositol 3-Quinase , Proteínas Proto-Oncogênicas B-raf/genética , Ensaios de Triagem em Larga Escala , Melanoma/tratamento farmacológico , Melanoma/genética
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