Detection of Hypoxia and HIF in Paraffin-Embedded Tumor Tissues

Li, Fuming; Lee, Kyoung Eun; Simon, M. Celeste

doi:10.1007/978-1-4939-7665-2_24

Cited by 13 publications

(7 citation statements)

References 6 publications

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“…Paraffin embedded tissue sections were deparaffinized and stained according to previously published protocols (27). Primary antibodies HIF-1 (anti-rabbit A300-286A; 1:100; Bethyl Laboratories), HIF-2 (anti-rabbit NB100-122; 1:100; Novus Biologicals), LOX (anti-rabbit ab174316; 1:500; Abcam) and PIMO (anti-rabbit; 1:100; Hypoxyprobe) were used.…”

Section: Methodsmentioning

confidence: 99%

Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

et al. 2019

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Peritoneal metastases are the leading cause of morbidity and mortality in high-grade serous ovarian cancer (HGSOC). Accumulating evidence suggests that mesothelial cells are an important component of the metastatic microenvironment in HGSOC. However, the mechanisms by which mesothelial cells promote metastasis are unclear. Here we report that the HGSOC tumor-mesothelial niche was hypoxic and hypoxic signaling enhanced collagen I deposition by mesothelial cells. Specifically, hypoxic signaling increased expression of lysyl oxidase (LOX) in mesothelial and ovarian cancer cells to promote collagen crosslinking and tumor cell invasion. The mesothelial niche was enriched with fibrillar collagen in human and murine omental metastases. Pharmacologic inhibition of LOX reduced tumor burden and collagen remodeling in murine omental metastases. These findings highlight an important role for hypoxia and mesothelial cells in the modification of the extracellular matrix and tumor invasion in HGSOC.

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Section: Methodsmentioning

confidence: 99%

Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

et al. 2019

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“…One hour following injection, mice were sacrificed and tumors were dissected and fixed with 4% paraffin. Then, tumors were stained with the anti-Hypoxyprobe-1 antibody (1:50) according to the manufacturer's instructions [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization

Yuan

Bai

Ren

et al. 2020

Translational Oncology

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Tumor vessels play important roles in cancer development and angiogenesis has been characterized as an essential process for tumor cell tumor growth. Our previous studies found that a single-dose local intraosseous simvastatin injection rapidly and long-termly mobilized bone marrow-derived endothelial progenitor cells to peripheral blood, promoting angiogenesis and ameliorating ischemia injury. However, whether intraosseous injection of simvastatin participates in cancer progression and the role of angiogenesis enhancement in this process remain unknown. In this study, we found that intraosseous injection of simvastatin improves tumor vascular structure, along with increasing the percentage of pericyte coverage on tumor vessels, and reducing vascular permeability, tumor hypoxia and tumor necrosis. Further, we demonstrate that a single-dose local intraosseous simvastatin injection suppresses tumor growth, facilitates sensitivity of chemotherapy and prolongs survival in breast cancer-bearing mice. In addition, oral application, intravenous, subcutaneous and intraperitoneal injection of simvastatin do not show these effects. Taken together, these results demonstrate that intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization, which might be a promising strategy for cancer treatment.

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“…The expression of HIF is activated by hypoxia condition, which can be detected by monoclonal anti-HIF-1α antibodies, and is generally used to assess the tumor hypoxia. The procedures of HIF-1α staining were referenced to the study of Li et al ( 20 ). Ki-67 is a proliferation marker reflecting the degree of proliferation activity of tumor cells.…”

Section: Methodsmentioning

confidence: 99%

Evaluating the Treatment Efficacy of Nano-Drug in a Lung Cancer Model Using Advanced Functional Magnetic Resonance Imaging

Huang

Liang

et al. 2020

Front. Oncol.

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Objectives Nano-drug delivery system is an interesting field in precise cancer treatment, but few study has reported the microenvironmental changes after such treatment. This study aimed to detect the hemodynamic and microenvironmental changes in a lung cancer xenograft model after treated with doxorubicin (DOX) encapsulated by a cyclic arginine-glycine-aspartic acid polypeptide modified poly-(lactic-co-glycolic acid) nanosystem (cRGD-PLGA@DOX) using functional magnetic resonance imaging. Materials and Methods Thirty-two tumor-bearing mice were randomly divided into four groups. Group A was treated with 0.9% saline, Group B with 4 mg/kg of doxorubicin, Group C with 2 mg/kg of cRGD-PLGA@DOX, and Group D with 4 mg/kg of cRGD-PLGA@DOX. Intravoxel incoherent motion diffusion-weighed imaging (IVIM-DWI) and R2 ∗ mapping were performed, and D ∗ , f, D, and R2 ∗ values were obtained before and1, 2, and 3 weeks after treatment. They were sacrificed for pathological examination after examinations. Results The reconstructed cRGD-PLGA@DOX was homogeneous, well-dispersed, and spherical in shape, with an average size of 180 nm. Group D demonstrated the smallest tumor volume and highest tumor inhibition rate in 3 weeks. D value of Group B, C, and D manifested an upward trend in 3 weeks with the highest increase in Group D. D ∗ values shared a similar increased trends with f values in Group A, B, and C in 3 weeks, except Group D. R2 ∗ value of Group A gradually increased in 3 weeks, but the trends were reversed in the treatment groups. D value was significantly negative with Ki-67 expression ( r = −0.757, P < 0.001) but positive with TUNEL ( r = 0.621, P < 0.001), and phosphate and tension homology deleted on chromosome ten (PTEN) staining ( r = 0.57, P = 0.004). R2 ∗ value was closely correlated with HIF-1a ( r = 0.721, P < 0.001). Conclusion The nano-drug demonstrated an enhanced anti-tumor effect without the need of increased chemotherapeutic dosage. The tumor microenvironment such as cellular and perfusion changes during treatment can be non-invasively detected by two functional MRI including IVIM-DWI and R2 ∗ mapping.

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Detection of Hypoxia and HIF in Paraffin-Embedded Tumor Tissues

Cited by 13 publications

References 6 publications

Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

Collagen Remodeling in the Hypoxic Tumor-Mesothelial Niche Promotes Ovarian Cancer Metastasis

Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization

Evaluating the Treatment Efficacy of Nano-Drug in a Lung Cancer Model Using Advanced Functional Magnetic Resonance Imaging

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