Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 16 de 16
Filter
Add more filters










Publication year range
1.
Histochem Cell Biol ; 156(2): 165-182, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34003355

ABSTRACT

Diagnosis and prognosis of breast cancer is based on disease staging identified through histopathological and molecular biology techniques. Animal models are used to gain mechanistic insights into the development of breast cancer. C(3)1-TAg is a genetically engineered mouse model that develops mammary cancer. However, carcinogenesis caused by this transgene was characterized in the Friend Virus B (FVB) background. As most genetic studies are done in mice with C57BL/6 J background, we aimed to define the histological alterations in C3(1)-TAg C57BL/6 J animals. Our results showed that C3(1)-TAg animals with C57BL/6 J background develop solid-basaloid adenoid cystic carcinomas with increased fibrosis, decreased area of adipocytes, and a high proliferative index, which are triple-negative for progesterone, estrogen, and human epidermal growth factor receptor 2 (HER2) receptors. Our results also revealed that tumor development is slower in the C57BL/6 J background when compared with the FVB strain, providing a better model to study the different stages in breast cancer progression.


Subject(s)
Antigens, Viral, Tumor/genetics , Breast Neoplasms/genetics , Carcinoma, Adenoid Cystic/genetics , Models, Genetic , Animals , Antigens, Viral, Tumor/immunology , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Carcinoma, Adenoid Cystic/immunology , Carcinoma, Adenoid Cystic/pathology , Female , Friend murine leukemia virus/immunology , Mice , Mice, Inbred C57BL , Mice, Transgenic
2.
J Cell Mol Med ; 24(17): 9574-9589, 2020 09.
Article in English | MEDLINE | ID: mdl-32691511

ABSTRACT

The tumour mass is composed not only of heterogeneous neoplastic cells, but also a variety of other components that may affect cancer cells behaviour. The lack of detailed knowledge about all the constituents of the tumour microenvironment restricts the design of effective treatments. Nerves have been reported to contribute to the growth and maintenance of numerous tissues. The effects of sensory innervations on tumour growth remain unclear. Here, by using state-of-the-art techniques, including Cre/loxP technologies, confocal microscopy, in vivo-tracing and chemical denervation, we revealed the presence of sensory nerves infiltrating within the melanoma microenvironment, and affecting cancer progression. Strikingly, melanoma growth in vivo was accelerated following genetic ablation or chemical denervation of sensory nerves. In humans, a retrospective analysis of melanoma patients revealed that increased expression of genes related to sensory nerves in tumours was associated with better clinical outcomes. These findings suggest that sensory innervations counteract melanoma progression. The emerging knowledge from this research provides a novel target in the tumour microenvironment for therapeutic benefit in cancer patients.


Subject(s)
Melanoma/pathology , Sensory Receptor Cells/pathology , Skin Neoplasms/pathology , Animals , Cell Communication/physiology , Cell Line, Tumor , Disease Progression , Humans , Mice , Mice, Inbred C57BL , Retrospective Studies , Tumor Microenvironment
3.
J Cell Mol Med ; 23(9): 5949-5955, 2019 09.
Article in English | MEDLINE | ID: mdl-31278859

ABSTRACT

Wound healing is a complex dynamic physiological process in response to cutaneous destructive stimuli that aims to restore the cutaneous' barrier role. Deciphering the underlying mechanistic details that contribute to wound healing will create novel therapeutic strategies for skin repair. Recently, by using state-of-the-art technologies, it was revealed that the cutaneous microbiota interact with skin immune cells. Strikingly, commensal Staphylococcus epidermidis-induced CD8+ T cells induce re-epithelization of the skin after injury, accelerating wound closure. From a drug development perspective, the microbiota may provide new therapeutic candidate molecules to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of the microbiota in the skin microenvironment.


Subject(s)
Cellular Microenvironment/physiology , Skin/growth & development , Skin/microbiology , Staphylococcus epidermidis/physiology , Wound Healing/physiology , Animals , CD8-Positive T-Lymphocytes/immunology , Cellular Microenvironment/immunology , Humans , Mice , Microbiota/immunology , Skin/immunology , Skin Neoplasms/pathology , Skin Physiological Phenomena , Staphylococcus epidermidis/immunology
4.
Cancer Metastasis Rev ; 37(4): 779-790, 2018 12.
Article in English | MEDLINE | ID: mdl-30203108

ABSTRACT

Lung cancer is the leading cause of cancer mortality around the world. The lack of detailed understanding of the cellular and molecular mechanisms participating in the lung tumor progression restrains the development of efficient treatments. Recently, by using state-of-the-art technologies, including in vivo sophisticated Cre/loxP technologies in combination with lung tumor models, it was revealed that osteoblasts activate neutrophils that promote tumor growth in the lung. Strikingly, genetic ablation of osteoblasts abolished lung tumor progression via interruption of SiglecFhigh-expressing neutrophils supply to the tumor microenvironment. Interestingly, SiglecFhigh neutrophil signature was associated with worse lung adenocarcinoma patients outcome. This study identifies novel cellular targets for lung cancer treatment. Here, we summarize and evaluate recent advances in our understanding of lung tumor microenvironment.


Subject(s)
Cell Communication/physiology , Lung Neoplasms/pathology , Neutrophils/pathology , Osteoblasts/pathology , Animals , Humans , Tumor Microenvironment
5.
Wound Repair Regen ; 26(5): 392-397, 2018 09.
Article in English | MEDLINE | ID: mdl-30098299

ABSTRACT

Dermal wound healing is the process of repairing and remodeling skin following injury. Delayed or aberrant cutaneous healing poses a challenge for the health care system. The lack of detailed understanding of cellular and molecular mechanisms involved in this process hampers the development of effective targeted treatments. In a recent study, Parfejevs et al.-using state-of-the-art technologies, including in vivo sophisticated Cre/loxP techniques in combination with a mouse model of excisional cutaneous wounding-reveal that Schwann cells induce adult dermal wound healing. Strikingly, genetic ablation of Schwann cells delays wound contraction and closure, decreases myofibroblast formation, and impairs skin re-epithelization after injury. From a drug development perspective, Schwann cells are a new cellular candidate to be activated to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of Schwann cells roles in the skin microenvironment.


Subject(s)
Schwann Cells/physiology , Skin/injuries , Wound Healing/physiology , Wounds and Injuries/pathology , Animals , Cell Differentiation/physiology , Cells, Cultured , Disease Models, Animal , Mice , Receptor Cross-Talk , Skin/pathology
6.
Angiogenesis ; 21(4): 667-675, 2018 11.
Article in English | MEDLINE | ID: mdl-29761249

ABSTRACT

Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.


Subject(s)
Blood-Brain Barrier/metabolism , Brain Neoplasms/drug therapy , Drug Delivery Systems/methods , Glioblastoma/drug therapy , Pericytes/metabolism , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adenine/analogs & derivatives , Animals , Blood-Brain Barrier/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Glioblastoma/metabolism , Glioblastoma/pathology , Mice , Pericytes/pathology , Piperidines , Tumor Microenvironment/drug effects , Xenograft Model Antitumor Assays
7.
Cancer Res ; 78(11): 2779-2786, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29789421

ABSTRACT

The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779-86. ©2018 AACR.


Subject(s)
Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Pericytes/pathology , Animals , Humans , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/genetics , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology
8.
Cancer Med ; 7(4): 1232-1239, 2018 04.
Article in English | MEDLINE | ID: mdl-29479841

ABSTRACT

Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.


Subject(s)
Brain Neoplasms/immunology , Brain Neoplasms/pathology , Glioblastoma/immunology , Glioblastoma/pathology , Immunomodulation , Pericytes/immunology , Animals , Biomarkers , Brain Neoplasms/therapy , Glioblastoma/therapy , Humans , Immune Tolerance , Pericytes/metabolism , Phenotype , Signal Transduction , Tumor Escape/immunology , Tumor Microenvironment/immunology
9.
Neuroscientist ; 24(5): 440-447, 2018 10.
Article in English | MEDLINE | ID: mdl-29283016

ABSTRACT

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.


Subject(s)
Neurovascular Coupling/physiology , Pericytes/pathology , Pericytes/physiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/therapy , Animals , Humans
10.
J Cell Physiol ; 233(8): 5523-5529, 2018 08.
Article in English | MEDLINE | ID: mdl-29215724

ABSTRACT

Multiple sclerosis is a highly prevalent chronic demyelinating disease of the central nervous system. Remyelination is the major therapeutic goal for this disorder. The lack of detailed knowledge about the cellular and molecular mechanisms involved in myelination restricts the design of effective treatments. A recent study by using [De La Fuente et al. (2017) Cell Reports, 20(8): 1755-1764] by using state-of-the-art techniques, including pericyte-deficient mice in combination with induced demyelination, reveal that pericytes participate in central nervous system regeneration. Strikingly, pericytes presence is essential for oligodendrocyte progenitors differentiation and myelin formation during remyelination in the brain. The emerging knowledge from this research will be important for the treatment of multiple sclerosis.


Subject(s)
Central Nervous System/physiology , Myelin Sheath/physiology , Pericytes/cytology , Animals , Cell Differentiation/physiology , Cells, Cultured , Demyelinating Diseases/physiopathology , Mice , Multiple Sclerosis/physiopathology , Nerve Regeneration/physiology , Oligodendroglia/cytology
11.
Cytometry A ; 93(2): 167-171, 2018 02.
Article in English | MEDLINE | ID: mdl-29236351

ABSTRACT

Adipocyte infiltration in the bone marrow follows chemotherapy or irradiation. Previous studies indicate that bone marrow fat cells inhibit hematopoietic stem cell function. Recently, Zhou et al. (2017) using state-of-the-art techniques, including sophisticated Cre/loxP technologies, confocal microscopy, in vivo lineage-tracing, flow cytometry, and bone marrow transplantation, reveal that adipocytes promote hematopoietic recovery after irradiation. This study challenges the current view of adipocytes as negative regulators of the hematopoietic stem cells niche, and reopens the discussion about adipocytes' roles in the bone marrow. Strikingly, genetic deletion of stem cell factor specifically from adipocytes leads to deficiency in hematopoietic stem cells, and reduces animal survival after myeloablation, The emerging knowledge from this research will be important for the treatment of multiple hematologic disorders. © 2017 International Society for Advancement of Cytometry.


Subject(s)
Adipocytes/physiology , Bone Marrow Cells/physiology , Bone Marrow Transplantation , Adipocytes/transplantation , Animals , Bone Marrow/physiology , Bone Marrow Transplantation/trends , Hematopoietic Stem Cells/physiology , Humans
12.
Genes (Basel) ; 8(12)2017 Nov 29.
Article in English | MEDLINE | ID: mdl-29186038

ABSTRACT

Leber congenital amaurosis (LCA) is a severe disease that leads to complete blindness in children, typically before the first year of life. Due to the clinical and genetic heterogeneity among LCA and other retinal diseases, providing patients with a molecular diagnosis is essential to assigning an accurate clinical diagnosis. Using our gene panel that targets 300 genes that are known to cause retinal disease, including 24 genes reported to cause LCA, we sequenced 43 unrelated probands with Brazilian ancestry. We identified 42 unique variants and were able to assign a molecular diagnosis to 30/43 (70%) Brazilian patients. Among these, 30 patients were initially diagnosed with LCA or a form of early-onset retinal dystrophy, 17 patients harbored mutations in LCA-associated genes, while 13 patients had mutations in genes that were reported to cause other diseases involving the retina.

13.
Cell Cycle ; 16(21): 2018-2022, 2017.
Article in English | MEDLINE | ID: mdl-28976809

ABSTRACT

Bone marrow fibrosis is a reactive process, and a central pathological feature of primary myelofibrosis. Revealing the origin of fibroblastic cells in the bone marrow is crucial, as these cells are considered an ideal, and essential target for anti-fibrotic therapy. In 2 recent studies, Decker et al. (2017) and Schneider et al. (2017), by using state-of-the-art techniques including in vivo lineage-tracing, provide evidence that leptin receptor (LepR)-expressing and Gli1-expressing cells are responsible for fibrotic tissue deposition in the bone marrow. However, what is the relationship between these 2 bone marrow cell populations, and what are their relative contributions to bone marrow fibrosis remain unclear. From a drug development perspective, these works bring new cellular targets for bone marrow fibrosis.


Subject(s)
Bone Marrow Cells/pathology , Bone Marrow/pathology , Fibroblasts/pathology , Primary Myelofibrosis/metabolism , Receptors, Leptin/metabolism , Animals , Dissent and Disputes , Humans
14.
Neoplasia ; 19(11): 928-931, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28957694

ABSTRACT

Prostate cancer cells metastasize to the bones, causing ectopic bone formation, which results in fractures and pain. The cellular mechanisms underlying new bone production are unknown. In a recent study, Lin and colleagues, by using state-of-the-art techniques, including prostate cancer mouse models in combination with sophisticated in vivo lineage-tracing technologies, revealed that endothelial cells form osteoblasts induced by prostate cancer metastasis in the bone. Strikingly, genetic deletion of osteorix protein from endothelial cells affected prostate cancer-induced osteogenesis in vivo. Deciphering the osteoblasts origin in the bone microenvironment may result in the development of promising new molecular targets for prostate cancer therapy.


Subject(s)
Bone Neoplasms/pathology , Bone Neoplasms/secondary , Endothelial Cells/pathology , Osteoblasts/pathology , Osteogenesis/physiology , Prostatic Neoplasms/pathology , Animals , Bone Neoplasms/metabolism , Endothelial Cells/metabolism , Humans , Male , Osteoblasts/metabolism , Prostatic Neoplasms/metabolism , Tumor Microenvironment/physiology
15.
Neuroscience ; 363: 62-65, 2017 11 05.
Article in English | MEDLINE | ID: mdl-28893649

ABSTRACT

Niches are specialized microenvironments that regulate stem cells' activity. The neural stem cell (NSC) niche defines a zone in which NSCs are retained and produce new cells of the nervous system throughout life. Understanding the signaling mechanisms by which the niche controls the NSC fate is crucial for the success of clinical applications. In a recent study, Sato and colleagues, by using state-of-the-art techniques, including sophisticated in vivo lineage-tracing technologies, provide evidence that endothelial amyloid precursor protein (APP) is an important component of the NSC niche. Strikingly, depletion of APP increased NSC proliferation in the subventricular zone, indicating that endothelial cells negatively regulate NSCs' growth. The emerging knowledge from this research will be important for the treatment of several neurological diseases.


Subject(s)
Adult Stem Cells , Neural Stem Cells , Adult , Brain , Endothelial Cells , Humans , Stem Cell Niche
16.
Exp Hematol ; 54: 12-16, 2017 10.
Article in English | MEDLINE | ID: mdl-28690072

ABSTRACT

Bone marrow fibrosis is a critical component of primary myelofibrosis in which normal bone marrow tissue and blood-forming cells are gradually replaced with scar tissue. The specific cellular and molecular mechanisms that cause bone marrow fibrosis are not understood. A recent study using state-of-the-art techniques, including in vivo lineage tracing, provides evidence that Gli1+ cells are the cells responsible for fibrotic disease in the bone marrow. Strikingly, genetic depletion of Gli1+ cells rescues bone marrow failure and abolishes myelofibrosis. This work introduces a new central cellular target for bone marrow fibrosis. The knowledge that emerges from this research will be important for the treatment of several malignant and nonmalignant disorders.


Subject(s)
Bone Marrow Cells/drug effects , Molecular Targeted Therapy , Platelet Factor 4/genetics , Primary Myelofibrosis/drug therapy , Pyridines/pharmacology , Pyrimidines/pharmacology , Zinc Finger Protein GLI1/genetics , Animals , Bone Marrow/drug effects , Bone Marrow/metabolism , Bone Marrow/pathology , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Cell Proliferation , Disease Models, Animal , Gene Expression , Humans , Mice , Mice, Transgenic , Platelet Factor 4/metabolism , Primary Myelofibrosis/genetics , Primary Myelofibrosis/metabolism , Primary Myelofibrosis/pathology , Zinc Finger Protein GLI1/antagonists & inhibitors , Zinc Finger Protein GLI1/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL