RESUMO
Endometrial cancer (EC) is a common gynecological cancer worldwide. Treatment has been improved in recent years; however, in advanced stages, therapeutic options are still limited. The expression of galectins is increased in several tumor types and that they are involved in important cell processes. Large studies on endometrial cancer are still pending; Specimens of 225 patients with EC were immunohistochemically stained with antibodies for Gal-8 and Gal-9. Expression was correlated with histopathological variables. The cytosolic expression of both galectins is associated with grading and survival. Cytosolic Galectin-8 expression is a positive prognostic factor for overall survival (OS) and progression-free survival (PFS), while nuclear Gal-8 expression correlates only to OS. The cytosolic presence of Galectin-9 is correlated with a better prognosis regarding OS. Our results suggest that expression of both galectins is associated with OS and PFS in EC. Further studies are needed to understand the underlying molecular mechanisms.
Assuntos
Neoplasias do Endométrio , Galectinas , Humanos , Galectinas/metabolismo , Galectinas/genética , Feminino , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Biomarcadores Tumorais/metabolismo , Adulto , Idoso de 80 Anos ou mais , Imuno-HistoquímicaRESUMO
While the establishment of an ovarian cancer biobank from patient-derived organoids along with their clinical background information promises advances in research and patient care, standardization remains a challenge due to the heterogeneity of this lethal malignancy, combined with the inherent complexity of organoid technology. This adaptable protocol provides a systematic framework to realize the full potential of ovarian cancer organoids considering a patient-specific variability of progenitors. By implementing a structured experimental workflow to select optimal culture conditions and seeding methods, with parallel testing of direct 3D seeding versus a 2D/3D route, we obtain, in most cases, robust long-term expanding lines suitable for a broad range of downstream applications. Notably, the protocol has been tested and proven efficient in a great number of cases (N = 120) of highly heterogeneous starting material, including high-grade and low-grade ovarian cancer and stages of the disease with primary debulking, recurrent disease, and post-neoadjuvant surgical specimens. Within a low Wnt, high BMP exogenous signaling environment, we observed progenitors being differently susceptible to the activation of the Heregulin 1 ß (HERß-1)-pathway, with HERß-1 promoting organoid formation in some while inhibiting it in others. For a subset of the patient's samples, optimal organoid formation and long-term growth necessitate the addition of fibroblast growth factor 10 and R-Spondin 1 to the medium. Further, we highlight the critical steps of tissue digestion and progenitor isolation and point to examples where brief cultivation in 2D on plastic is beneficial for subsequent organoid formation in the Basement Membrane Extract type 2 matrix. Overall, optimal biobanking requires systematic testing of all main conditions in parallel to identify an adequate growth environment for individual lines. The protocol also describes the handling procedure for efficient embedding, sectioning, and staining to obtain high-resolution images of organoids, which is required for comprehensive phenotyping.
Assuntos
Bancos de Espécimes Biológicos , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Organoides/metabolismoRESUMO
OBJECTIVES: Gestational diabetes mellitus (GDM) is a growing health concern. Since members of the galectin-family are identified to play a role in the pathogenesis of GDM, we determined galectin-12 as an essential protein due to its influence in lipolysis and inflammation processes. This study investigates the expression of galectin-12 in the placentas of women with GDM. STUDY DESIGN: The study population includes 40 expectant women suffering from GDM and 40 healthy controls. The expression of galectin-12 in the syncytiotrophoblast (SCT) and the extra villous trophoblast (EVT) of the placenta was analyzed by immunohistological staining and double immunofluorescence. Immunoreactivity Score (IRS) was used for evaluation. RESULTS: The results demonstrate a significant overexpression of galectin-12 in the nucleus of the SCT and the EVT of placentas with GDM compared to the healthy control group. Additionally, double immunofluorescence visualizes corresponding results with an overexpression of galectin-12 in the extra villous trophoblast of GDM placentas representing maternal cells. CONCLUSION: This study identifies galectin-12 to be associated with the process of gestational diabetes mellitus. These findings are in correspondence with the involvement of galectin-12 in inflammatory processes. Maternal BMI and male sex seem to be confounder for the expression of galectin-12 in the nuclear syncytiotrophoblast, but not in other parts of the investigated placental areas. Further investigations are necessary to verify the correlation between gestational diabetes mellitus and the expression of galectin-12 in the placenta and to further elucidate its distinct role.