CIBA - ArtículosCentro de Investigaciones básicas y aplicadashttp://repositorio.unnoba.edu.ar/xmlui/handle/23601/902024-03-28T08:49:40Z2024-03-28T08:49:40ZA Novel MSH6 Gene Variant in a Lynch Syndrome Patient with Lipomashttp://repositorio.unnoba.edu.ar/xmlui/handle/23601/6662023-12-18T19:18:06Z2023-04-07T00:00:00ZA Novel MSH6 Gene Variant in a Lynch Syndrome Patient with Lipomas
Colorectal cancer is one of the most frequently occurring cancers today, with a large percentage
of cases having a hereditary basis. Lynch syndrome is the most common cause of hereditary
colorectal cancer. The genetic defect characteristics of this syndrome involve mutations in mismatch
repair (MMR) genes, which result in microsatellite instability. Early detection of the mutation can help
evaluate the cancer risk and, consequently, a proper course of clinical management for the person
harboring the mutation. Herein, we describe the first report of a c.1458dup (p.Glu487*) new mutation
in a 53-year-old colorectal cancer patient with diagnosed Lynch syndrome. Additionally, the existence
of lipomas in this patient and his family could be related to this syndrome. Further investigation may
provide a possible visual clue that can indicate a need for genetic screening.
2023-04-07T00:00:00ZInitial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cellshttp://repositorio.unnoba.edu.ar/xmlui/handle/23601/6372023-12-05T16:49:05Z2021-02-09T00:00:00ZInitial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells
UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved
in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of
UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast
cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast
cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The
prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells
were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis
were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined.
Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation
increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased
and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated
with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High
expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown
contributes to epirubicin resistance, which might be associated with increases in the expression,
deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as
a new prognostic marker in breast cancer, positively associated with development of epirubicin
resistance and modulation of extracellular matrix.
2021-02-09T00:00:00ZCo-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expressionhttp://repositorio.unnoba.edu.ar/xmlui/handle/23601/6362023-12-05T16:59:41Z2018-11-27T00:00:00ZCo-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
Hyaluronan, the main glycosaminoglycan of extracellular matrices, is concentrated
in tissues with high cell proliferation and migration rates. In cancer, hyaluronan
expression is altered and it becomes fragmented into low-molecular-weight forms,
affecting mechanisms associated with cell proliferation, invasion, angiogenesis and
multidrug resistance. Here, we analyzed the effect of low-molecular-weight hyaluronan
on the response of T lymphoma, osteosarcoma, and mammary adenocarcinoma cell
lines to the antineoplastic drug doxorubicin, and whether co-treatment with hyaluronan
and doxorubicin modified the behavior of endothelial cells. Our aim was to associate
the hyaluronan-doxorubicin response with angiogenic alterations in these tumors.
After hyaluronan and doxorubicin co-treatment, hyaluronan altered drug accumulation
and modulated the expression of ATP-binding cassette transporters in T-cell lymphoma
cells. In contrast, no changes in drug accumulation were observed in cells from solid
tumors, indicating that hyaluronan might not affect drug efflux. However, when we
evaluated the effect on angiogenic mechanisms, the supernatant from tumor cells
treated with doxorubicin exhibited a pro-angiogenic effect on endothelial cells.
Hyaluronan-doxorubicin co-treatment increased migration and vessel formation in
endothelial cells. This effect was independent of vascular endothelial growth factor
but related to fibroblast growth factor-2 expression. Besides, we observed a proangiogenic
effect on endothelial cells during hyaluronan and doxorubicin co-treatment
in the in vivo murine model of T-cell lymphoma. Our results demonstrate for the first
time that hyaluronan is a potential modulator of doxorubicin response by mechanisms
that involve not only drug efflux but also angiogenic processes, providing an adverse
tumor stroma during chemotherapy.
2018-11-27T00:00:00ZThe effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progressionhttp://repositorio.unnoba.edu.ar/xmlui/handle/23601/6352023-12-05T17:01:56Z2022-01-31T00:00:00ZThe effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
Hyaluronan (HA) is a component of the extracellular matrix (ECM) it is the
main non-sulfated glycosaminoglycan able to modulate cell behavior in the
healthy and tumor context. Sulfated hyaluronan (sHA) is a biomaterial derived
from chemical modifications of HA, since this molecule is not naturally sulfated.
The HA sulfation modifies several properties of the native molecule,
acquiring antitumor properties in different cancers. In this study, we evaluated
the action of sHA of 30–60 kDa with different degrees of sulfation (0.7 sHA1
and 2.5 sHA3) on tumor cells of a breast, lung, and colorectal cancer model
and its action on other cells of the tumor microenvironment, such as endothelial
and monocytes/macrophage cells. Our data showed that in breast and lung
tumor cells, sHA3 is able to modulate cell viability, cytotoxicity, and proliferation,
but no effects were observed on colorectal cancer cells. In 3D cultures of
breast and lung cancer cells, sHA3 diminished the size of the tumorsphere and
modulated total HA levels. In these tumor models, treatment of monocytes/
macrophages with sHA3 showed a downregulation of the expression of angiogenic
factors. We also observed a decrease in endothelial cell migration and
modulation of the hyaluronan-binding protein TSG-6. In the breast in vivo
xenograft model, monocytes/macrophages preincubated with sHA1 or sHA3
decreased tumor vasculature, TSG-6 and HA levels. Besides, in silico analysis
showed an association of TSG-6, HAS2, and IL-8 with biological processes
implicated in the progression of the tumor. Taken together, our data indicate that sHA in a breast and lung tumor context is able to induce an antiangiogenic action on tumor cells as well as in onocytes/macrophages (Mo/MØ) by modulation of endothelial migration, angiogenic factors, and vessel formation.
2022-01-31T00:00:00Z