The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer

Kawano, Mahiru; Mabuchi, Seiji; Matsumoto, Yoshihisa; Sasano, Tomoyuki; Takahashi, Ryoko; Kozasa, Katsumi; Hashimoto, Kae; Isobe, Aki; Sawada, Kenjiro; Hamasaki, Toshimitsu; Morii, Eiichi; Kimura, Tadashi

doi:10.1038/srep18217

Cited by 126 publications

(144 citation statements)

References 37 publications

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“…Tumor-related leukocytosis, which is occasionally encountered in patients with malignant tumors, is a paraneoplastic syndrome involving high leukocyte counts without underlying infection, bone marrow metastasis, or corticosteroid administration (1,2). Tumor-related leukocytosis is observed in 10% of patients with solid tumors and is associated with poor clinical outcome (3).…”

Section: Introductionmentioning

confidence: 99%

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review

et al. 2018

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Abstract. The current study presents the case of a 72-year-old woman with a rapidly enlarged liver metastasis from esophagogastric junction (EGJ) cancer, accompanied by progressive leukocytosis (47,680/µl) and elevated serum granulocyte colony-stimulating factor (G-CSF; 779 pg/ml). The patient underwent right hemihepatectomy 26 months after a total gastrectomy. On the seventh post-operative day the patient's leukocyte count and serum G-CSF level decreased to 4,280/µl and ≤19.5 pg/ml, respectively. Histologically, the lesion was a well to moderately differentiated adenocarcinoma similar to the primary lesion. Therefore, this tumor was clinically diagnosed as a G-CSF-producing liver metastasis from EGJ cancer, although immunohistochemical staining for G-CSF was negative. A right pulmonary nodule detected simultaneously with the hepatic mass was resected four months following the hepatectomy and was diagnosed as a pulmonary metastasis. The patient's leukocyte count was normal at the time of her initial surgery for EGJ cancer, and her clinical course varied for different metastatic sites. The liver metastasis was accompanied by progressive leukocytosis and elevated serum G-CSF and demonstrated rapid tumor growth during a six-month period, whereas the non-G-CSF-producing pulmonary metastasis grew slowly during the same period. In addition 21 reported cases of G-CSF-producing upper gastrointestinal tract cancer were reviewed to elucidate the clinicopathological features of this disease.

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Section: Introductionmentioning

confidence: 99%

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review

et al. 2018

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“…In 2012, there were an estimated 527,600 novel cervical cancer cases and 265,700 mortalities worldwide (1). Although the majority of patients can be cured with treatments based on surgery and radiotherapy, a significant number eventually develop recurrent disease, with the the risk of recurrence being 10-20% for patients with stage IB-IIA [International Federation of Gynecology and Obstetrics (FIGO) stage] and 50-70% for those in stages IIB-IVA2 (2,3). With advances in the development of molecular-targeted drugs, novel diagnostic and therapeutic molecular targets may enable the development of novel therapies for cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Similarity in the functions of HIF‑1α and HIF‑2α proteins in cervical cancer cells

Jiang

Shi

et al. 2017

Oncol Lett

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Abstract. Hypoxia is a common feature of many solid tumours, including cervical cancer. Aggressive tumour progression is mostly associated with hypoxia. Furthermore, hypoxic conditions in tumours are also associated with resistance to chemotherapy and radiation, and with poor prognosis. Hypoxia inducible factor (HIF)-1, composed of a constitutively expressed β-subunit (HIF-β/ARNT) and one of the three known oxygen-regulated α-subunits, HIF-1α, HIF-2α, or HIF-3α, mediates the tumour cell response to hypoxia. The distinction between the roles of HIF-1α and HIF-2α in tumorigenesis is not clearly delineated. Therefore, the aim of the present study was to investigate the effect of HIF-2α on the characteristics of a cervical cancer cell line and to compare the functions of HIF-1α and HIF-2α. The present study demonstrated that the levels of HIF-1α and HIF-2α expression increased under hypoxic exposure compared with normoxia. The major difference was the temporal expression of HIF-1α and HIF-2α, with expression of the two proteins peaking at different time-points. In addition, HIF-1α and HIF-2α had similar effects on proliferation, cell cycle and apoptosis. Suppression of expression of HIF-1α or HIF-2α inhibited proliferation, induced G1-phase arrest and promoted apoptosis in the cervical cancer cell line CaSki. However, the effects of HIF-1α and HIF-2α on invasion and cell autophagy were different. The inhibitory effect of HIF-1α on cell invasion was stronger compared with HIF-2α, while the inhibitory effect of HIF-1α on cell autophagy was weaker compared with HIF-2α.Together, these results demonstrate that HIF-1α and HIF-2α have similar effects on the characteristics of a cervical cancer cell line. The major difference that the authors observed between the effects exerted by the two proteins on the cervical cancer cell line studied is the extent of their effect on invasion and autophagy.

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“…It was revealed that tumor-induced granulocyte colony-stimulating factor (G-CSF) is one of those factors (Waight et al 2011;Abrams and Waight 2012;Luyckx et al 2012;Kawano et al 2015). Our recent study also showed that the serum G-CSF level is associated with the inhibition of expansion and differentiation of G-MDSCs in tumor-bearing adiponectin knockout mice (Han et al 2013).…”

Section: The Subsets Of Mdscsmentioning

confidence: 91%

Phenotypic and functional dissection of myeloid-derived suppressor cells

Han

Yang

2016

Appl Biol Chem

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Myeloid-derived suppressor cells (MDSCs) are originated and differentiated population from common hematopoietic progenitor cells. Generally, in the late stage of inflammation, MDSCs differentiation and expansion are promoted to suppress the over-activated immune system so that the immune system can maintain the homeostasis. Recently, it has been revealed that MDSCs accumulate in cancer patients and tumor-bearing experimental animals, and these tumor-derived MDSCs suppress anti-tumor immunity by secreting immunosuppressive cytokines including reactive oxygen species and inducible nitric oxide synthase. This fact prompts scientists to shed light on MDSCs as significant targets for anti-cancer immunotherapy. However, due to morphological, phenotypic, and functional heterogeneities of MDSCs, it is not easy to develop therapeutic strategies targeting MDSCs. In this review, we will summarize recent progress on defined subsets of MDSCs and their strategies to suppress T cellmediated anti-tumor immunity.

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The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer

Cited by 126 publications

References 37 publications

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review

Similarity in the functions of HIF‑1α and HIF‑2α proteins in cervical cancer cells

Phenotypic and functional dissection of myeloid-derived suppressor cells

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