Prediction of Avascular Necrosis of the Femoral Head by Measuring Intramedullary Oxygen Tension After Femoral Neck Fracture

Watanabe, Yoshinobu; Terashima, Yuichiro; Takenaka, Nobuyuki; Kobayashi, Makoto; Matsushita, T.

doi:10.1097/bot.0b013e318126bb56

Cited by 41 publications

(22 citation statements)

References 11 publications

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“…By relating an extensive body of literature regarding the role of hypoxia in the solid tumor setting to what is currently known about the kinetics of MM disease progression, we have formed a hypothetical model of the role of hypoxia in MM disease progression (Figure 2). In the initial stages of disease establishment, we postulate that the hypoxic BM microenvironment [108][109][110]112 supports the initial survival and growth of the MM cells. 136 As the MM PCs establish themselves within the endosteal niche of the BM, they become exposed to even greater levels of hypoxia, 137 which activates HIF-1 and/or HIF-2, and stimulates the production of angiogenic factors and angiogenesis to increase oxygen delivery to the tumor cells, thereby facilitating tumor growth.…”

Section: Discussionmentioning

confidence: 99%

The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma

et al. 2011

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Hypoxia is an imbalance between oxygen supply and demand, which deprives cells or tissues of sufficient oxygen. It is wellestablished that hypoxia triggers adaptive responses, which contribute to short-and long-term pathologies such as inflammation, cardiovascular disease and cancer. Induced by both microenvironmental hypoxia and genetic mutations, the elevated expression of the hypoxia-inducible transcription factor-1 (HIF-1) and HIF-2 is a key feature of many human cancers and has been shown to promote cellular processes, which facilitate tumor progression. In this review, we discuss the emerging role of hypoxia and the HIFs in the pathogenesis of multiple myeloma (MM), an incurable hematological malignancy of BM PCs, which reside within the hypoxic BM microenvironment. The need for current and future therapeutic interventions to target HIF-1 and HIF-2 in myeloma will also be discussed.

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Section: Discussionmentioning

confidence: 99%

The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma

et al. 2011

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“…Hypoxia is a prominent feature of the tumor microenvironment and considered an adverse prognostic factor best documented for solid tumors [9]. Hypoxia is also a physiological characteristic of the BM [10] and, as shown in mice studies, extremely hypoxic niches are essential for regulating the maintenance and functioning of hematopoietic stem cells [11], [12]. Several recent studies have demonstrated that MM displays features of hypoxia; in the 5T33M mouse MM model, myelomatous BM has been shown to be more hypoxic than normal BM.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Induced Impairment of NK Cell Cytotoxicity against Multiple Myeloma Can Be Overcome by IL-2 Activation of the NK Cells

et al. 2013

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BackgroundMultiple Myeloma (MM) is an incurable plasma cell malignancy residing within the bone marrow (BM). We aim to develop allogeneic Natural Killer (NK) cell immunotherapy for MM. As the BM contains hypoxic regions and the tumor environment can be immunosuppressive, we hypothesized that hypoxia inhibits NK cell anti-MM responses.MethodsNK cells were isolated from healthy donors by negative selection and NK cell function and phenotype were examined at oxygen levels representative of hypoxic BM using flowcytometry. Additionally, NK cells were activated with IL-2 to enhance NK cell cytotoxicity under hypoxia.ResultsHypoxia reduced NK cell killing of MM cell lines in an oxygen dependent manner. Under hypoxia, NK cells maintained their ability to degranulate in response to target cells, though, the percentage of degranulating NK cells was slightly reduced. Adaptation of NK- or MM cells to hypoxia was not required, hence, the oxygen level during the killing process was critical. Hypoxia did not alter surface expression of NK cell ligands (HLA-ABC, -E, MICA/B and ULBP1-2) and receptors (KIR, NKG2A/C, DNAM-1, NCRs and 2B4). It did, however, decrease expression of the activating NKG2D receptor and of intracellular perforin and granzyme B. Pre-activation of NK cells by IL-2 abrogated the detrimental effects of hypoxia and increased NKG2D expression. This emphasized that activated NK cells can mediate anti-MM effects, even under hypoxic conditions.ConclusionsHypoxia abolishes the killing potential of NK cells against multiple myeloma, which can be restored by IL-2 activation. Our study shows that for the design of NK cell-based immunotherapy it is necessary to study biological interactions between NK- and tumor cells also under hypoxic conditions.

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“…In contrast, other authors have suggested that invasive techniques, including arteriography, 29 , venography, 30,31 needle aspiration, 32 manometry, 33 oxymetry, 34,35 and measurement of intraosseous and intracapsular pressure, 36 are more sensitive and, therefore, possibly more appropriate diagnostic tools in the detection of vascularity of the femoral head. However, Calandruccio and Anderson 21 have suggested that, based on the accuracy of assessments of vascularity of the femoral head using these techniques, they are not sufficiently quantitative.…”

Section: Discussionmentioning

confidence: 78%