ABSTRACT
Breast cancer remains one of the leading cancers among women. Cancer stem cells (CSCs) are tumor-initiating cells which drive progression, metastasis, and reoccurrence of the disease. CSCs are resistant to conventional chemo- and radio-therapies and their ability to survive such treatment enables tumor reestablishment. Metastasis is the main cause of mortality in women with breast cancer, thus advances in treatment will depend on therapeutic strategies targeting CSCs. Salinomycin (SAL) is a naturally occurring polyether ionophore antibiotic known for its anticancer activity towards several types of tumor cells. In the present work, a library of 17 C1-single and C1/C20-double modified SAL analogs was screened to identify compounds with improved activity against breast CSCs. Six single- and two double-modified analogs were more potent (IC50 range of 1.1 ± 0.1-1.4 ± 0.2 µM) toward the breast cancer cell line MDA-MB-231 compared to SAL (IC50 of 4.9 ± 1.6 µM). Double-modified compound 17 was found to be more efficacious than SAL against the majority of cancer cell lines in the NCI-60 Human Tumor Cell Line Panel. Compound 17 was more potent than SAL in inhibiting cell migration and cell renewal properties of MDA-MB-231 cells, as well as inducing selective loss of the CD44+/CD24/low stem-cell-like subpopulation in both monolayer (2D) and organoid (3D) culture. The present findings highlight the therapeutic potential of SAL analogs towards breast CSCs and identify select compounds that merit further study and clinical development.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Breast Neoplasms/drug therapy , Neoplastic Stem Cells/drug effects , Pyrans/pharmacology , Antibiotics, Antineoplastic/chemical synthesis , CD24 Antigen , Cell Division/drug effects , Cell Line, Tumor , Cell Movement , Drug Discovery , Drug Screening Assays, Antitumor , Female , Humans , Hyaluronan Receptors/metabolism , MCF-7 Cells , Pyrans/chemical synthesisSubject(s)
Breast Neoplasms , Effect Modifier, Epidemiologic , Health Literacy , Attitude to Health , Breast Neoplasms/epidemiology , Breast Neoplasms/prevention & control , Breast Neoplasms/psychology , Female , Humans , Illinois/epidemiology , Middle Aged , Needs Assessment , Risk Factors , Social Perception , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
Juvenile fibroadenoma is the most common breast mass in adolescents accounting for 0.5-4% of all cases of fibroadenomas. Giant fibroadenomas are well-circumscribed, firm breast masses characterized by proliferation of epithelial and connective tissue. They are defined as being larger than 5 cm or weighing more than 500 g. The peak age has been reported between the ages of 17 and 20, with less than 5% of these in patients less than 18-years-old.We present a 9-year-old, pre-menstrual, Nigerian female with no known family history of breast masses or cancers who developed spontaneous giant fibroadenoma measuring approximately 13 cm × 13 cm. Rapid growth of a breast mass can be of great concern to such young patients whose breasts are in the early formative stages. It is important to promptly rule out malignant processes or phyllodes tumor, and educate young patients and their families on treatment options that fit their unique concerns and circumstances.
Subject(s)
Breast Neoplasms/pathology , Fibroadenoma/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Child , Female , Fibroadenoma/diagnosis , Fibroadenoma/surgery , HumansSubject(s)
Alopecia/pathology , Choristoma/pathology , Corneal Diseases/pathology , Eye Diseases/diagnosis , Limbus Corneae , Lipomatosis/diagnosis , Neurocutaneous Syndromes/diagnosis , Alopecia/etiology , Choristoma/complications , Corneal Diseases/etiology , Eye Diseases/complications , Eye Diseases/pathology , Female , Humans , Infant, Newborn , Lipomatosis/complications , Lipomatosis/pathology , Neurocutaneous Syndromes/complications , Neurocutaneous Syndromes/pathology , Scalp/pathologyABSTRACT
OBJECTIVES: The male reproductive axis is responsive to energetic deficits, including multiday fasts, but little is known about brief periods of fasting (<24 hours). Reduced testosterone in low-energy balance situations is hypothesized to reflect redirection of resources from reproduction to survival. This study tests the hypothesis that testosterone levels decrease during a minor caloric deficiency by assessing the effects of a single missed (evening) meal on morning testosterone in 23 healthy male participants, age 19-36. METHODS: Participants provided daily saliva and urine samples for two baseline days and the morning following an evening fast (water only after 4 PM). Testosterone, cortisol, and luteinizing hormone were measured with enzyme immunoassays. RESULTS: Fasting specimens had significantly lower overnight urinary luteinizing hormone (P = 0.045) and morning salivary testosterone than baseline (P = 0.037). In contrast to morning salivary testosterone, there was a significant increase in overnight urinary testosterone (P = 0.000) following the evening fast, suggesting an increase in urinary clearance rates. There was a marginal increase in overnight urinary cortisol (P = 0.100), but not morning salivary cortisol (P = 0.589). CONCLUSION: These results suggest the male reproductive axis may react more quickly to energetic imbalances than has been previously appreciated.