Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB14837 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR420933.fastq.gz | Fastqsanger.gz | |||
| DRR420934.fastq.gz | Fastqsanger.gz | |||
| DRR420935.fastq.gz | Fastqsanger.gz | |||
| DRR420936.fastq.gz | Fastqsanger.gz | |||
| DRR420937.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
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Project description:Expression data from adult mice breast cancer cell 4T1
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Project description:Effects of 4T1 breast cancer on normal organ gene expressions
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Project description:Immature B cells in the bone marrow emigrate into the spleen during adult lymphopoiesis. Here, we report that emigration is shifted to earlier B-cell stages in mice with orthotopic breast cancer, spontaneous ovarian cancer, and possibly in human breast carcinoma. Using mouse and human bone marrow aspirates and mouse models challenged with highly metastatic 4T1 breast cancer cells, we demonstrated that this was the result of secretion of thymic stromal lymphopoietin (TSLP) by cancer cells. First, TSLP downregulated surface expression of bone marrow (BM) retention receptors CXCR4 and VLA4 in B-cell precursors, increasing their motility and, presumably, emigration. Then, TSLP supported peripheral survival and proliferation of BM B-cell precursors such as pre-B–like cells. 4T1 cancer cells used the increased pool of circulating pre-B–like cells to generate metastasis-supporting regulatory B cells. As such, the loss of TSLP expression in cancer cells alone or TSLPR deficiency in B cells blocked both accumulation of pre-B–like cells in circulation and cancer metastasis, implying that the pre-B cell–TSLP axis can be an attractive therapeutic target. Significance: Cancer cells induce premature emigration of B-cell precursors from the bone marrow to generate regulatory B cells.
2021-01-17 | GSE164955 | GEO
Project description:Tumor-associated macrophages (TAMs) are closely related to poor prognosis in triple-negative breast cancer (TNBC). Thus, gaining insight into how TAMs support cancer progression could contribute to effective therapies. We utilized the 4T1 murine TNBC cell line and murine bone marrow-derived macrophages to assess TAMs mediated pro-proliferative effects in vivo and in vitro. Further, Transcriptional analysis was performed to identify pathways activated in TAMs stimulated 4T1 cells. To simulate tumor microenvironment, M2 macrophages and 4T1 cells were plated into upper and lower chambers of Transwell co-culture systems respectively. we performed RNA-sequencing analysis of 4T1 cells incubated with vehicle control or M2 macrophages.
2019-07-25 | GSE134787 | GEO
Project description:Current therapies for metastatic colorectal cancer only prolong life for approximately 2 years. A more innovative therapy that prolongs life significantly or even cures is needed. Bone marrow transplantation is a curative therapy for patients with leukemias and lymphomas. Tumor eradication in the case of transplantation of the patient’s own marrow (autologous transplantation) is based on the intensive chemotherapy and/or radiotherapy used for conditioning. Tumor eradication in the case of transplantation using the marrow of a normal donor is based on both tumor reduction from conditioning and the immune elimination of tumor cells by T cells in the donor transplant that recognize the foreign tissue antigens expressed by the tumor cells and kill these cells. The use of bone marrow transplantation to treat tumors other than leukemia and lymphoma has been limited, and studies of transplantation of the patient’s own marrow for the treatment of advanced /metastatic breast cancer have not conclusively shown benefit beyond conventional therapy.
Recently, the Strober lab developed a preclinical model that effectively treated colon cancer in mice by combining immunotherapy and autologous bone marrow transplantation in order to markedly augment the anti-tumor potency of immunotherapy. They used the CT26 colon cancer as the therapeutic target either as a single subcutaneous tumor nodule, as a disseminated tumor in the lungs and peritoneum, or as a metastatic tumor in the liver depending on the route of administration of the tumor cells in BALB/c mice. Mice were vaccinated mice with established primary tumors or disseminated/ metastatic disease with irradiated tumor cells mixed with the adjuvant CpG, and found that vaccination alone had no effect on tumor growth. Similarly radiation conditioning of tumor bearing hosts followed by transplantation of bone marrow and spleen cells or purified T cells and hematopoietic stem cells from unvaccinated donors of the same strain had no effect. In contrast, radiation conditioning of mice followed by transplantation of hematopoietic and immune cells from donors of the same strain vaccinated with tumor cells and CpG cured almost all subcutaneous primary as well as disseminated and metastatic tumors in the hosts. A similar result was obtained after autologous transplantation of hematopoietic and immune cells from tumor bearing mice that had been vaccinated after tumor establishment. Investigation of tumor infiltrating cells showed that the injected donor T cells do not accumulate in the tumors unless the host has been irradiated before injection.
Based on this model, we have assembled a team of Stanford University faculty members with expertise in gastrointestinal cancers, immunotherapy, radiation oncology, and bone marrow transplantation in the Departments of Medicine and Pathology to translate the preclinical findings into a Phase I safety and feasibility clinical study for the treatment of 10 patients with metastatic colorectal cancer. Resected tumor cells will be irradiated and mixed with CpG to create a vaccine. Patients will receive subcutaneous vaccination at weeks 1 and 2 after resection. Six weeks later, immune T cells and then G-CSF "mobilized" purified blood progenitor cells will be harvested from the blood and cryopreserved. If needed patients will receive chemotherapy for tumor reduction. When disease is controlled off chemotherapy, patients will receive a conditioning regimen of fludarabine (30mg/m2 daily x 3 days) followed by intensive fractionated total body irradiation. The dose of fTBI will be escalated using a 3+3 design to ensure safety and will range from 400 to 800 gray. The patient will then undergo hematopoietic and immune cell rescue. They will undergo a third vaccination within 7-14 days after transplant. Thereafter, serial monitoring of tumor burden will continue.
Immune monitoring will occur before and after vaccination as well as after transplantation. Tests will include in vitro anti-tumor immune responses of T cells (proliferation, cytotoxicity, cytokine secretion etc.) to stimulation with whole tumor cells and tumor cell lysates pulsed on to antigen presenting cells, anti-tumor antibody responses, and immune reconstitution after transplantation.
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Project description:Aged hematopoietic stem cells (HSCs) display myeloid-biased differentiation and reduced regenerative potential. In this study, we uncover that P-selectin (Selp) marks a subset of aged HSCs with reduced repopulation capacity. This population of HSCs expresses a prominent aging transcriptome. Overexpression of Selp in young HSCs impaired long-term reconstitution potential and repressed erythropoiesis. We show that IL-1β is elevated in aged bone marrow and administration of IL-1β induces expression of Selp and other aging-associated genes in HSCs. Finally, we demonstrate that transplantation of aged HSCs into young recipients restores a young-like transcriptome, specifically by repressing pro-inflammatory pathways, highlighting the important role of the bone marrow microenvironment in HSC aging.
2023-01-02 | GSE194273 | GEO
Project description:Recently, cancer immunotherapy has been paid much attention because of its improved efficacy and low frequency of adverse effects. A mouse breast cancer cell line, 4T1, has been known as poorly immunogeneic and highly metastatic cell line. In this study, we have identified a sub cell line of 4T1, designated as 4T1-Sapporo (4T1-S), which could induce a strong immune response against the same line. When 4T1-S was subcutaneously injected, striking enlargement of draining lymph nodes and increase of activated T cells were observed. The strong immune responses could not be observed when 4T1-S was injected to nude mice, indicating that this phenomenon is mediated by T cell response. Identification of 4T1-S characteristics may help to improve immunotherapy against breast cancer. 4T1-A1, 4T1-A2, 4T1-S1, 4T1-S2
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