Prognostic significance of HIF-2.ALPHA. expression on tumor infiltrating macrophages in patients with uterine cervical cancer undergoing radiotherapy

Kawanaka, Takashi; Kubo, Akiko; Ikushima, Hitoshi; Sendo, Toshiaki; Takegawa, Yoshihiro; Nishitani, Hiromu

doi:10.2152/jmi.55.78

Cited by 39 publications

(16 citation statements)

References 30 publications

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“…However, under these conditions, they express higher levels of HIF-1α as compared to HIF-2α, and consistent with these findings, the levels of HIF-1α are higher in TAMs infiltrating breast and ovarian carcinomas (23). HIF-2α is expressed in human cancers and correlates with poor prognosis (25–27). Murine myeloid specific knockouts of both HIF-1α and HIF-2α show distinct activities in regulating the immune response.…”

Section: Tumor-associated Macrophagesmentioning

confidence: 99%

Orchestration of Angiogenesis by Immune Cells

et al. 2014

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It is widely accepted that the tumor microenvironment (TUMIC) plays a major role in cancer and is indispensable for tumor progression. The TUMIC involves many “players” going well beyond the malignant-transformed cells, including stromal, immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can “orchestrate” the “symphony” of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy. Considerable attention within the context of tumor angiogenesis should focus not only on the ECs, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here, we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation, and angiogenesis to tumor progression. Here, we review the data in the literature and seek to identify the “conductors” of this “orchestra.” We also suggest that interrupting the immune → inflammation → angiogenesis → tumor progression process can delay or prevent tumor insurgence and malignant disease.

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Section: Tumor-associated Macrophagesmentioning

confidence: 99%

Orchestration of Angiogenesis by Immune Cells

et al. 2014

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“…Kawanaka et al [17] suggested the ratio of the HIF-2α positive cell in tumor infiltrative macrophages may be a new predictive indicator for prognosis. Our study also solidified that HIF-2α staining may be a key in radioresistance in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the same results regarding HIF-2α have been released showing that HIF-2α expression is associated with prognosis in patients with cervical cancer undergoing radiotherapy [17]. …”

Section: Introductionmentioning

confidence: 97%

Clinical significance of HIF-2α immunostaining area in radioresistant cervical cancer

Kim

Sung

et al. 2011

J Gynecol Oncol

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ObjectiveHypoxia has been established as a key factor influencing the pathophysiology of malignant growth. Hypoxia-induced changes in gene expression are coordinated primarily by hypoxia inducible factor-1 alpha (HIF-1α) and HIF-2α. The purpose of this study was to determine whether or not HIF-2α expression is associated with survival and response to radiation in patients with cervical cancer.MethodsAfter reviewing the medical records of 119 patients treated in our institution by primary therapy for stage IIB-IVA cervical cancer, we performed a case-control study. Cases (n=12) were selected from patients with local recurrence or radiation failure after primary radiation therapy with or without concurrent chemoradiation. For each case, we selected two controls from patients who had no evidence of local recurrence. Using pre-treatment paraffin-embedded tissues, we evaluated the expression of HIF-2α by immunohistochemistry. Staining was scored based on intensity (intensity score [IS], 0-3) and proportion (proportion score [PS], 0-100). The results were analyzed by the Student t-test, Mann-Whitney U test, Fisher's exact test, and Cox proportional hazards regression model.ResultsCytoplasmic expression of HIF-2α, representing the degree of hypoxia, had a relationship with poor response to radiotherapy. The hazard ratio of recurrence was 1.71 for the HIF-2α IS (p=0.110) and 1.04 for the HIF-2α PS (p<0.001), indicating that the HIF-2α staining area correlates weakly with the risk for recurrence.ConclusionThe HIF-2α expression area may have an important role in radioresistance in patients with locally advanced cervical cancer. We conclude that a wider area of hypoxia predicts an increased probability of radioresistance.

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“…Whereas angiogenesis-promoting genes might be preferentially up-regulated in small tumors, proapoptotic genes might be induced in large tumors. Similarly, recent data suggested that the ratio of the HIF-2alpha positive cell in tumor infiltrative macrophages may be a new predictive indicator for prognosis before RT for uterine cervical cancer [45].…”

Section: Introductionmentioning

confidence: 94%

Molecular profiling of uterine cervix carcinoma: an overview with a special focus on rationally designed target-based anticancer agents

Magné

Chargari

Deutsch

et al. 2008

Cancer Metastasis Rev

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Although conventional multimodality approaches allowed improvement in the prognosis of patients with cervix cancer, several tumors do not respond similarly to standard approaches. Recent advances in basic research and genomics have improved our understanding of the biologic basis of the tumor development and progression. Tumor profiling allows for more selective therapeutic strategies leading to the identification of biomarkers or indicators of treatment response and to increased clinical efficacy through development of targeted therapies. Several markers have been identified, that are involved in cellular proliferation, interaction with angiogenesis, extracellular matrice adhesion/invasion, apoptosis, cell cycle pathways and DNA repair mechanisms. In this report, molecular profiling of uterine cervix carcinoma were reviewed with a special focus on rationally designed target-based anticancer agents, in order to clarify and to summary the present state of art in these particular promising area in cervix cancer management.

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Prognostic significance of HIF-2.ALPHA. expression on tumor infiltrating macrophages in patients with uterine cervical cancer undergoing radiotherapy

Cited by 39 publications

References 30 publications

Orchestration of Angiogenesis by Immune Cells

Orchestration of Angiogenesis by Immune Cells

Clinical significance of HIF-2α immunostaining area in radioresistant cervical cancer

Molecular profiling of uterine cervix carcinoma: an overview with a special focus on rationally designed target-based anticancer agents

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