ABSTRACT
INTRODUCTION: Breast cancer (BC) is the most common cancer in women, and the incidence of brain metastasis (BM) from BC ranges from 20% to 30%, with a median survival of 10 to 15 months. Previous reports have shown that the presence of obesity or diabetes negatively impacts survival. The present study investigates the association between obesity or diabetes mellitus (DM) and overall survival of patients with BC with BM. MATERIALS AND METHODS: A database from 2 referral centers for the period of July 2014 to February 2018 was analyzed. The inclusion criteria were as follows: patients who had a confirmed diagnosis of BC with BM were followed and treated at these centers. Demographic data, body weight and height, clinical and oncologic history, functional status, prognostic scales, and prognoses were examined. RESULTS: A total of 228 patients were included. The median age at BM was 50 years; the median survival after diagnosis was 12.1 months; 108 patients had a body mass index (BMI) ≥ 25, and 40 (17%) patients had DM. The association between survival and the presence of BMI > 25 exhibited a P value of 0.3. DISCUSSION: We found no association between overweight, obesity, or DM and survival in patients with BC with BM. The role of obesity in cancer is a robust research topic, as there are many questions to be answered. CONCLUSION: Obesity as a prognostic indicator should be further studied, because we found no association between overall survival and either patients with BM from BC with a BMI > 25 or those with normal weight.
Subject(s)
Brain Neoplasms/epidemiology , Brain Neoplasms/secondary , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Overweight/epidemiology , Adult , Aged , Body Mass Index , Comorbidity , Diabetes Mellitus/epidemiology , Female , Humans , Incidence , Kaplan-Meier Estimate , Mexico/epidemiology , Middle Aged , Obesity/epidemiology , PrognosisABSTRACT
BACKGROUND: Prolonged mitotic arrest in response to anti-cancer chemotherapeutics, such as DNA-damaging agents, induces apoptosis, mitotic catastrophe, and senescence. Disruptions in mitotic checkpoints contribute resistance to DNA-damaging agents in cancer. MAD2 has been associated with checkpoint failure and chemotherapy response. In this study, a novel splice variant of MAD2, designated MAD2γ, was identified, and its association with the DNA damage response was investigated. METHODS: Endogenous expression of MAD2γ and full-length MAD2 (MAD2α) was measured using RT-PCR in cancer cell lines, normal foreskin fibroblasts, and tumor samples collected from patients with testicular germ cell tumors (TGCTs). A plasmid expressing MAD2γ was transfected into HCT116 cells, and its intracellular localization and checkpoint function were evaluated according to immunofluorescence and mitotic index. RESULTS: MAD2γ was expressed in several cancer cell lines and non-cancerous fibroblasts. Ectopically expressed MAD2γ localized to the nucleus and reduced the mitotic index, suggesting checkpoint impairment. In patients with TGCTs, the overexpression of endogenous MAD2γ, but not MAD2α, was associated with resistance to cisplatin-based chemotherapy. Likewise, cisplatin induced the overexpression of endogenous MAD2γ, but not MAD2α, in HCT116 cells. CONCLUSIONS: Overexpression of MAD2γ may play a role in checkpoint disruption and is associated with resistance to cisplatin-based chemotherapy in TGCTs.
Subject(s)
Drug Resistance, Neoplasm , M Phase Cell Cycle Checkpoints , Mad2 Proteins/metabolism , Neoplasms, Germ Cell and Embryonal/metabolism , Neoplasms, Germ Cell and Embryonal/pathology , Testicular Neoplasms/metabolism , Testicular Neoplasms/pathology , Adult , Amino Acid Motifs , Amino Acid Sequence , Base Sequence , Cell Line, Tumor , Cisplatin/pharmacology , Computer Simulation , Drug Resistance, Neoplasm/drug effects , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Foreskin/pathology , Humans , M Phase Cell Cycle Checkpoints/drug effects , Mad2 Proteins/chemistry , Mad2 Proteins/genetics , Male , Protein Domains , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Subcellular Fractions/metabolism , Young AdultABSTRACT
OBJECTIVE: To estimate the prevalence of cognitive impairment (CI) among patients recently diagnosed with type 2 diabetes (RDD) and to identify any relationships between CI and RDD comorbidities. METHODS: One thousand seven hundred twelve patients with RDD participated in a cross-sectional study. The patients' sociodemographic and clinical data were registered. RESULTS: The sample population had an average age of 51 ± 11 years, and 63.26% of the patients were female. CI was diagnosed in 38 patients (2.2%) and was more common among both females (2.8% vs. 1.3%, p = 0.063) and the elderly (0% at an age ≤ 30 years vs. 10.4% at an age > 70 years, p = 0.0001). Rheumatoid arthritis (present in 15.8% vs. absent in 2.1%) and asthma (13% vs. 2.1%) correlated significantly with CI based on the results of our logistic regression analysis. CONCLUSION: Age, female gender, rheumatoid arthritis and asthma are risk factors for CI in the setting of RDD.
