Aggressive recurrence of gastric cancer as a granulocyte-colony-stimulating factor-producing tumor

Kawaguchi, Masahiko; Asada, Yasuyuki; Takato, Tsuyoshi; Takehara, Akira; Munemoto, Yoshinori; Fujisawa, Katsunori; Mitsui, Toshio; Iida, Yoshiro; Miura, Shoji; Sudo, Yoshiko

doi:10.1007/s10147-010-0023-3

Cited by 34 publications

(33 citation statements)

References 13 publications

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“…Immunohistochemical staining of a tongue biopsy specimen with monoclonal anti-G-CSF antibody yielded negative results, similar to findings in many other patients with G-CSF producing tumors (5,6). Negative staining of tumor tissue may be caused by the rapid secretion of G-CSF from tumor cells (7).…”

Section: Discussionsupporting

confidence: 76%

“…G-CSF is frequently produced by poorly differentiated and undifferentiated carcinomas (5,6), and many of these G-CSF producing tumors are initially detected at advanced stage (1,(5)(6)(7)12,13). In addition, the G-CSF produced by these tumors may contribute to tumor progression by autocrine and paracrine mechanisms (18,19), as well as promoting angiogenesis and tumor growth (20).…”

Section: Discussionmentioning

confidence: 99%

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G‑CSF producing oral carcinoma with diffuse uptake of FDG in the bone marrow: A case report

et al. 2017

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Abstract.A 78-year-old male patient was referred to the Department of Oral Surgery, Hokuto Hospital (Obihiro, Japan) for painless swelling on the left neck and tongue. Histopathological examination of a biopsy specimen resulted in a diagnosis of squamous cell carcinoma of the tongue. Imaging examinations revealed cervical lymph node metastases on both sides, along with diffuse uptake of 18 F-fluorodeoxyglucose (FDG) in the bone marrow of the spine and pelvis. Hematologic tests revealed an increased white blood cell (WBC) count and serum concentrations of granulocyte colony stimulating factor (G-CSF). These findings suggested a G-CSF producing tumor, with fluctuations of WBC count, serum G-CSF concentration, and FDG uptake in the bone marrow, associated with tumor shrinkage and enlargement, an indicator of tumor status. IntroductionGranulocyte colony stimulating factor (G-CSF) is a cytokine mainly produced by macrophages, fibroblasts and endothelial cells in an inflammatory milieu. G-CSF stimulates neutrophil precursors, resulting in an increase in neutrophils, and recruits neutrophils from the bone marrow to peripheral blood. G-CSF is an important factor in infection prophylaxis, and recombinant G-CSF is universally used to treat neutropenia (1). G-CSF is also produced by non-hematologic malignancies with high leukocyte counts, consisting predominantly of neutrophils, in patients without infectious diseases. Most of these G-CSF producing tumors are present in the lungs (2), with tumors in the oral regions being rare. This report describes a patient with a tongue carcinoma producing G-CSF, as well as showing diffuse uptake of FDG in the bone marrow. Case reportIn July 2013, a 78-year-old man visited the Department of Oral Surgery, Hokuto Hospital (Obihiro, Japan) with a 2-week history of painless swelling on the left neck and tongue. The patient had no systemic complications and no significant family history. Some cervical lymph nodes on both sides were palpable (Fig. 1A). Intra-oral examination showed a tumor with induration about 40 mm in diameter on the left side of the tongue (Fig. 1B). Cytological examination of a swollen left lymph node showed atypical squamous cells, and pathological examination of a biopsy of the tongue tumor revealed a squamous cell carcinoma. A computed tomography (CT) scan with contrast demonstrated a large lateral oral tongue tumor of diameter 42 mm, without extension to the extrinsic muscles of the tongue; and some metastatic cervical lymph nodes that were enlarged, nonhomogeneously enhanced, and partially necrotic. Metastatic disease of left middle jugular lymph node was >30 mm in maximum diameter (Fig. 2). 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT showed abnormally high uptake by the tongue tumor (maximum standardized uptake value [SUVmax] 22.19) and by the four large metastatic nodes, with the large left middle jugular node having an SUVmax of 14.43 (Fig. 3A). Diffuse FDG uptake was also observed in the bone marrow of the spine and pelvis (Fig. 3B). These f...

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

G‑CSF producing oral carcinoma with diffuse uptake of FDG in the bone marrow: A case report

et al. 2017

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“…Similar to the solid cancer mouse models, in humans, elevated serum G-CSF levels (8)(9)(10)42) and extreme leukocytosis (>40,000/μL) related to a paraneoplastic leukemoid reaction have been reported for a variety of solid tumor types (43). Although initially clinically stable, the vast majority of patients with a neutrophilic predominance have poor clinical outcomes, with 76% dying within 12 wk of development of extreme leukocytosis (43).…”

Section: Discussionmentioning

confidence: 90%

“…G-CSF is also produced by various tumors and cancer cells (6), including leukemic cells of CML patients in chronic phase (7). Its concentration can be elevated in the blood of cancer patients and has been associated with poor clinical outcome (8)(9)(10). G-CSF activates neutrophils, stimulates oxidative metabolism (11), and increases agonist-induced platelet aggregation ex vivo (12).…”

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confidence: 99%

Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis

Demers

Krause

Schatzberg

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

744

752

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Cancer-associated thrombosis often lacks a clear etiology. However, it is linked to a poor prognosis and represents the second-leading cause of death in cancer patients. Recent studies have shown that chromatin released into blood, through the generation of neutrophil extracellular traps (NETs), is procoagulant and prothrombotic. Using a murine model of chronic myelogenous leukemia, we show that malignant and nonmalignant neutrophils are more prone to NET formation. This increased sensitivity toward NET generation is also observed in mammary and lung carcinoma models, suggesting that cancers, through a systemic effect on the host, can induce an increase in peripheral blood neutrophils, which are predisposed to NET formation. In addition, in the late stages of the breast carcinoma model, NETosis occurs concomitant with the appearance of venous thrombi in the lung. Moreover, simulation of a minor systemic infection in tumor-bearing, but not control, mice results in the release of large quantities of chromatin and a prothrombotic state. The increase in neutrophil count and their priming is mediated by granulocyte colony-stimulating factor (G-CSF), which accumulates in the blood of tumor-bearing mice. The prothrombotic state in cancer can be reproduced by treating mice with G-CSF combined with low-dose LPS and leads to thrombocytopenia and microthrombosis. Taken together, our results identify extracellular chromatin released through NET formation as a cause for cancer-associated thrombosis and unveil a target in the effort to decrease the incidence of thrombosis in cancer patients.

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“…G-CSF is often secreted by tumor cells [26,174,189,190,194,198,276,[352][353][354][355][356][357][358][359] and is preferentially observed in dedifferentiated or poorly differentiated tumors [360,361,354,190]. Elevated G-CSF blood concentrations in cancer patients have been associated with poor clinical outcome [174,194,198,276,352,355,356].…”

Section: Prognostic Values Of Neutrophils and Other Myeloid Subtypes mentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

336

261

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Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

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Aggressive recurrence of gastric cancer as a granulocyte-colony-stimulating factor-producing tumor

Cited by 34 publications

References 13 publications

G‑CSF producing oral carcinoma with diffuse uptake of FDG in the bone marrow: A case report

G‑CSF producing oral carcinoma with diffuse uptake of FDG in the bone marrow: A case report

Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

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