RESUMO
Breast implant associated-anaplastic large cell lymphoma (BIA-ALCL) has become a hot topic in recent plastic surgery and oncology forum. Its cases have been on the rise since its first emergence more than two decades ago. This condition is less known and management guidelines are still evolving. BIA-ALCL was seen recently with a classical presentation in one of our patients, who underwent immediate reconstruction with a macro-textured silicone implant following breast cancer surgery. We want to add the first case report from India to the global information database. There are still unanswered questions in its management, and we wish to highlight the same to make way for further research. With the rise in aesthetic and reconstructive implant surgeries, the knowledge of BIA-ALCL must expand among oncologists, radiologists, and pathologists for early identification and treatment for better patient outcomes.
RESUMO
Data on skin manifestations associated with pediatric obesity are limited. We conducted a prospective study to evaluate the association of pediatric obesity with skin dermatoses and dermatologic quality of life. Our findings suggest that ongoing monitoring of skin problems is recommended for children with obesity.
Assuntos
Obesidade Infantil , Dermatopatias , Criança , Humanos , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Pele , Dermatopatias/complicações , Dermatopatias/etiologiaRESUMO
Two series of (hetero)arylamino-naphthoquinones and benzo-fused carbazolequinones were considered for study with the rationale that related structural motifs are present in numerous drugs, clinical trial agents, natural products and hTopoIIα inhibitors. Total 42 compounds were synthesized by reactions including dehydrogenative CN and Pd-catalyzed CC bond forming transformations. These compounds were screened against numerous cancer cells including highly metastatic one (MCF-7, MDA-MB-231, H-357 and HEK293T), and normal cells (MCF 10A). Some of the active compounds were evaluated for clonogenic cell survival and apoptotic effects in cancer cells (DAPI nuclear staining, Comet assay, Annexin-V-FITC/PI dual staining, flow cytometry, and western blot analysis with relevant proteins). All compounds were tested for hTopoIIα inhibitory activity. The investigated series compounds showed important properties like significant apoptotic antiproliferation in cancer cells with cell cycle arrest at S-phase and downregulation of NF- κß signaling cascade, relatively less cytotoxicity to normal cells, and hTopoIIα inhibition with more efficiency compared to an anticancer drug etoposide.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , DNA Topoisomerases Tipo II/metabolismo , Naftoquinonas/farmacologia , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Inibidores da Topoisomerase II/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Carbazóis/síntese química , Carbazóis/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Naftoquinonas/síntese química , Naftoquinonas/toxicidade , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/toxicidadeRESUMO
We present here-in the molecular design and chemical synthesis of a novel series of diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition. The in vitro cytotoxicity of the synthesized compounds was evaluated against four human cancer cell lines including DU143, HEPG2, RKO and A549 in addition to non-cancerous immortalized human embryonic kidney cells (HEK-293). Compound 11 showed significant cytotoxicity against all the four human cancer cell lines with IC50 values ranging from 4.2 to 6.59 µM. 11 was also found to display 13-fold selective cytotoxicity towards A549 cancerous cells compared to the non-cancerous cell lines (HEK-293). The decatenation, DNA relaxation and intercalation assays revealed that the investigational compounds 10 and 11 act as highly selective inhibitors of Topo-I with DNA minor groove binding ability which was also supported by the results obtained from circular dichroism (CD), UV-visible spectroscopy and viscosity studies. Apoptosis induced by the lead 11 was observed using morphological observations, AO/EB and DAPI staining procedures. Further, dose-dependent increase in the depolarization of mitochondrial membrane was also observed through JC-1 staining. Annexin V-FITC/PI assay confirmed that 11 induced early apoptosis. Additionally, cell cycle analysis indicated that the cells were arrested at sub-G1 phase. Gratifyingly, in silico studies demonstrated promising interactions of 11 with the DNA and Topo I, thus supporting their potential DNA minor groove binding property with relatively selective Topo I inhibition compared to Topo II.
Assuntos
Antineoplásicos/farmacologia , Azepinas/farmacologia , DNA Topoisomerases Tipo I/metabolismo , DNA de Neoplasias/efeitos dos fármacos , Indóis/farmacologia , Simulação de Acoplamento Molecular , Inibidores da Topoisomerase I/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Azepinas/síntese química , Azepinas/química , Sítios de Ligação/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/químicaRESUMO
Gender dysphoria (GD) and obesity share commonalities, including associations with mental health comorbidities, disordered eating, body dissatisfaction and may intensify with physical and developmental changes during adolescence. While associations of obesity and gender diversity have been identified, rates of gender diversity among adolescents with obesity remain unclear. The aim was to examine gender diversity among adolescents with obesity in a weight management programme. A single-centre cross-sectional questionnaire study was conducted. Eligible adolescents received the Gender Identity/GD Questionnaire for Adolescents and Adults (GIDYQ-AA), a validated instrument measuring gender diversity and GD. Gender identities, sexual orientations, questionnaire scores, and frequency of GD (GIDYQ-AA score <3) were determined. The relationship of GIDYQ-AA scores and BMI Z-score (BMIz) was assessed. Of 72 consenting youth, 29 assigned females (AF) and 17 assigned males (AM) completed GIDYQ-AA and demographic questions. Seventeen (59%) AF reported non-heterosexual orientations, and 6 (21%) reported non-cisgender identities. One (6%) AM reported non-cisgender identity. Two (4%) AF individuals had GD based on GIDYQ-AA scores. GIDYQ-AA scores did not correlate with BMIz. In conclusion, adolescents with obesity, particularly AF with non-heterosexual orientation, reported high rates of non-cisgender identity and GD. Routine screening for gender-related concerns in weight management settings may be warranted.