ABSTRACT
Triple-negative breast tumours (TNBTs) make up 15-20% of all breast tumours. There is no treatment for them, and the role that cancer stem cells (CSCs) have in carcinogenesis is still unclear, so finding markers and therapeutic targets in CSC exosomes requires these cells to exist as a homogeneous cell population. The objective of this work was to determine differences in ultrastructural morphology, proliferative capacity, and mouse-xenotransplantation characteristics of the MDA-MB-231 and MDA-MB-436 TNBT cell lines with the CD44 high /CD24 low phenotype in order to study their exosomes. The results show that the CD44 high /CD24 low MBA-MB-231 cells had a population doubling time of 41.56 h, compared to 44.79 h in the MDA-MB-436 cell line. After magnetic immunoseparation, 18.75% and 14.56% of the stem cell population of the MDA-MB-231 and MDA-MB-436 cell lines, respectively, were of the CD44 high /CD24 low phenotype, which were expanded to reach purities of 80.4% and 87.6%. The same expanded lineage in both cell lines was shown to possess the pluripotency markers Nanog and Oct4. Under a scanning electron microscope, the CD44 high /CD24 low lineage of the MBA-MD-231 cell line formed groups of more interconnected cells than this lineage of the MBA-MD-436 line. A total of 16% of the mice inoculated with the CD44 high /CD24 low lineage of either cell line presented tumours of the breast, lung, and submandibular ganglia, in whose tissues variable numbers of inoculated cells were found 30 days post-inoculation. By magnetic immunoselection, it was possible to isolate in similar quantities and characterize, expand, and xenotransplant the CD44 high /CD24 low lineage of the MDA-MB-231 and MDA-MB-436 cell lines. The former cell line has greater proliferative capacity, the two lines differ under scanning electron microscopy in how they intercommunicate, and both cell lines induce new tumours in mice and persist at least 30 days post-inoculation in the transplanted animal so their exosomes would also be different.
ABSTRACT
Objetivos. Evaluar la frecuencia y factores asociados al compromiso parametrial (CP) en pacientes con cáncer de cérvix IB-1 sometidas a histerectomía radical (HR) en el Instituto Nacional de Enfermedades Neoplásicas del Perú. Materiales y métodos. Estudio transversal analítico en 214 pacientes con cáncer de cérvix IB-1 sometidas a HR con linfadenectomía pélvica entre el 2007 y 2012. Se comparó la población con y sin CP según variables clinicopatológicas como edad, tamaño tumoral, profundidad de infiltración, grado histológico y afectación ganglionar pélvica. Resultados. Diez pacientes (4,6%) presentaron CP. El análisis multivariable mostró que la profundidad de la invasión (OR 8,37, IC 95%: 1,24-56,41, p=0,029) y el compromiso de ganglios pélvicos (OR 18,03, IC 95%: 3,30-98,44, p=0,001) resultaron ser predictores independientes del CP. La presencia de tamaño tumoral ≤ 2 cm, invasión ≤ 10 mm, ausencia de permeación linfovascular y ausencia de compromiso ganglionar permitió identificar 97 pacientes de bajo riesgo de CP, de los cuales ninguno tuvo CP en patología. Conclusiones. Confirmamos la baja frecuencia del CP en el subgrupo de cáncer de cervix IB-1 y su asociación con la profundidad de la invasión y con el compromiso ganglionar linfático sugeridos en estudios previos. Esta información permitirá identificar un subgrupo de pacientes con bajo riesgo de CP candidatas a una cirugía menos radical en nuestra institución. (AU)
Objectives. To assess the frequency and factors associated with parametrial involvement (PI) in patients with cervical cancer IB1 who underwent radical hysterectomy (RH) at the National Institute of Neoplastic Diseases in Peru. Materials and methods. Cross-sectional study of 214 patients with cervical cancer IB1 undergoing RH with pelvic lymphadenectomy between 2007 and 2012. The population was compared with and without clinicopathological variables associated with PI such as age, tumor size, depth of infiltration, histological grade and pelvic lymph node involvement. Results. Ten patients (4.6%) had PI. Multivariate analysis showed that the depth of invasion (OR 8.37, 95% CI 1.24- 56.41, p=0.029) and pelvic node involvement (OR 18.03; 95% CI 3.30-98.44, p=0.001) were all independent predictors of PI. The presence of tumor size ≤ 2 cm, invasion ≤ 10 mm, absence of lymphovascular permeation and absence of nodal involvement identified 97 patients at low risk of PI, none of whom had PI pathology. Conclusions. We confirmed the low frequency of PI in the cervical cancer IB1 subgroup and its association with the depth of invasion and lymph node involvement suggested in previous studies. This information will allow the identification of a subgroup of patients at low risk of PI for less radical surgery in our institution. (AU)
