Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A transplantable murine breast carcinoma in mice was associated with marked leukemoid reaction. Within 1 week of subcutaneous implantation of tumor the leukocyte count began to increase and reached average levels of 165,000 leukocytes per cubic millimeter within 18 days. This represented an increase in mature neutrophils primarily, although other blood leukocytes were modestly increased as well. The total number of neutrophils per humerus was increased but no increase was detected in the number of myloblasts, promyelocytes, or myelocytes. The tritiated thymidine-labeling index of the latter three cells was not significantly changed during tumor growth. The number of progenitor cells forming granulocytic and mononuclear cells in vitro was decreased in the marrow during tumor growth. Colony-stimulating activity in plasma was slightly increased during the early phase of tumor growth and decreased during later phases. Emergence time of blood neutrophils was normal, as measured by labeling with tritiated thymidine, but decline in labeled cells was abnormally slow in tumor-bearing mice. There was a shift of erythropoiesis to the spleen, but total erythropoiesis appeared to be normal in most mice. Surgical excision of the tumor resulted in prompt reversal of the leukemoid reaction. In the aggregate these results are consistent with a hypothesis that the leukemoid reaction was the result of increased blood transit time of neutrophils primarily, rather than increased neutrophil production.
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PMID:Kinetic studies of a tumor-induced leukemoid reaction in mice. 29 65

Recent reports of cancers that produce colony-stimulating factors (CSF) and which are associated with leukocytosis indicate that most are granulocyte CSF-producing tumors. A 71-year-old man with metastatic chest wall tumors from large cell lung cancer with marked leukocytosis and eosinophilia was reported. His maximal leukocyte count was 48300/microliter with 37.5% eosinophils. Granulocyte-macrophage CSF (GM-CSF) activity detected by enzyme-linked immunosorbent assay (ELISA) in serum was 112 pg/ml (normal range < 2.0 pg/ml), but G-CSF was normal. Immunohistochemical detection of GM-CSF protein on a chest wall tumor sample was positive. Irradiation of the chest wall tumor was performed and the leukocyte count decreased temporally. However, he died of respiratory failure due to progressive tumor growth 56 days after admission. Based on these results it appears that autocrine production of GM-CSF is a possible cause of this leukemoid reaction.
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PMID:Production of granulocyte-macrophage colony-stimulating factor in a patient with metastatic chest wall large cell carcinoma. 979 30

A white blood cell count more than 50 x 10(9)/l, not related to bone marrow involvement, is termed leukemoid reaction. We report on the first case of an undifferentiated sarcoma of the lung associated with an intense paraneoplastic neutrophilic leukemoid reaction related to the production of granulocyte colony-stimulating factor (G-CSF). A radiography and a computed tomography scan of the chest revealed a well-limited voluminous and heterogeneous low-density mass of the left lung. The patient died of multiorgan failure related to uncontrolled progressive tumor growth after admission and two cycles of chemotherapy. The patient's G-CSF serum concentration was dramatically elevated (6,538 pg/ml) compared to serum levels observed in normal controls and patients with elevated leukocytosis (31 and 387 pg/ml, respectively). The G-CSF concentration dramatically increased after the first cycle of chemotherapy and during the subsequent neutropenia, as a result of the tumor lyses as well as of disruption of the physiological negative feedback mechanism. Adjunction of the patient's serum to CD34+ cell cultures induced a 12.3-fold increase in CD15+ cells, demonstrating the serum's capacity to induce myeloid differentiation.
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PMID:Intense paraneoplastic neutrophilic leukemoid reaction related to a G-CSF-secreting lung sarcoma. 1624 54

Cancer is associated with immune dysfunction characterized by the presence of proinflammatory and immunosuppressive cells and factors that contribute to tumor growth and progression. Here we show that mammary tumor growth is associated with defects in hematopoiesis, leading to myeloproliferative-like disease (leukemoid reaction), anemia, and disruption of the bone marrow stem/progenitor compartment. The defects we characterized included impaired erythropoiesis, leukocytosis, loss of early progenitor cells in the bone marrow, and splenic extramedullary hematopoiesis. We established an in vitro model to dissect interactions between mammary cancers and the hematopoietic system. Investigations in this model revealed that granulocyte colony-stimulating factor (G-CSF) produced by mammary tumors can synergize with FLT3L and granulocyte macrophage CSF (GM-CSF) to expand myeloid progenitors and their progeny in culture. Mammary tumor growth was associated with histone methylation changes within lineage-negative c-Kit-positive hematopoietic cells within the bone marrow of tumor-bearing mice. Similarly, parallel histone methylation patterns occurred in cultured bone marrow cells exposed to mammary tumor-conditioned cell culture media. Notably, changes in histone methylation in these cell populations correlated with dysregulated expression of genes controlling hematopoietic lineage commitment and differentiation, including Hox family genes and members of the Polycomb repressive complex 2 (PRC2) chromatin-remodeling complex. Together, our results show that mammary tumor-secreted factors induce profound perturbations in hematopoiesis and expression of key hematopoietic regulatory genes.
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PMID:Dysregulated hematopoiesis caused by mammary cancer is associated with epigenetic changes and hox gene expression in hematopoietic cells. 2391 28