Noninvasive Multimodality Imaging of the Tumor Microenvironment: Registered Dynamic Magnetic Resonance Imaging and Positron Emission Tomography Studies of a Preclinical Tumor Model of Tumor Hypoxia

Cho, HyungJoon; Ackerstaff, Ellen; Carlin, Sean; Lupu, Mihaela; Ya, Wang; Rizwan, Asif; O’Donoghue, Joseph A.; Ling, C. Clifton; Humm, John L.; Zanzonico, Pat; Koutcher, Jason A.

doi:10.1593/neo.81360

Cited by 110 publications

(112 citation statements)

References 34 publications

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“…Regarding mechanism, we speculate that focal hypoenhancement corresponds to areas of decreased vascularity and/or tumor necrosis. Consistent with this notion, animal studies have demonstrated that regions of tumor necrosis (on pathology) correlated with deceased perfusion on CMR and reduced metabolic activity on positron emission tomography 19. Studies have also indicated that tumor necrosis corresponds to chronic ischemic injury from tissue hypoxia, which would be expected to manifest as decreased contrast uptake on DE‐CMR 20, 21.…”

Section: Discussionmentioning

confidence: 80%

Pattern and Prognostic Implications of Cardiac Metastases Among Patients With Advanced Systemic Cancer Assessed With Cardiac Magnetic Resonance Imaging

Pun

Plodkowski

Matasar

et al. 2016

JAHA

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BackgroundCardiac magnetic resonance (CMR) imaging is well validated for tissue characterization of cardiac masses but has not been applied to study pattern and prognostic implications of cardiac metastases (CMETs) among patients with systemic cancer.Methods and ResultsThe population consisted of 60 patients with stage IV cancer (32 patients with CMETs, 28 diagnosis‐matched controls) undergoing CMR. CMET was defined as a discrete mass with vascular tissue properties on delayed enhancement CMR. CMET‐positive patients and controls had similar clinical characteristics, cardiac geometry, and function (P=NS). Leading cancer types associated with CMET were sarcoma, melanoma, and gastrointestinal. Patients with CMETs had similar distribution of extracardiac metastatic disease compared with controls (organs involved: 3.4±2.0 versus 2.7±1.9, P=0.17). In 94% of patients with CMETs, there were metastases involving ≥1 extracardiac organ (66% lung involvement). CMET location varied (right ventricle 44%, right atrium 19%, left ventricle 28%, left atrium 9%, pericardial 25%); 22% of cases had multichamber involvement. Right‐sided chamber involvement was common in hematologic/lymphatic spread (67%); pericardial involvement was common with direct spread (64%). Regarding tissue properties on delayed enhancement CMR, CMETs commonly (59%) demonstrated heterogeneous enhancement (41% diffuse enhancement). Heterogeneous lesions were larger and had increased border irregularity (P<0.05). Survival 6 months post‐CMR was numerically lower among patients with CMETs (56% [95% CI 39–74%]) versus stage IV cancer–matched controls (68% [95% CI 50–86%]), although differences between groups were nonsignificant (P=0.42).Conclusions CMETs vary regarding etiology, location, and tissue properties on CMR, highlighting need for comprehensive surveillance of cardiac involvement regardless of cancer origin. Prognosis remains poor with for patients with CMETs, albeit similar to that for stage IV cancer controls matched for cancer etiology.

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Section: Discussionmentioning

confidence: 80%

Pattern and Prognostic Implications of Cardiac Metastases Among Patients With Advanced Systemic Cancer Assessed With Cardiac Magnetic Resonance Imaging

Pun

Plodkowski

Matasar

et al. 2016

JAHA

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“…Bentzen et al [195] , Rasey et al [196] , Bentzen et al [197] , Troost et al [198] Bentzen et al [125] , Gagel et al [126] , Bruehlmeier et al [199] , Lawrentschuk et al [200] , O'Donoghue et al [72] , Piert et al [166] , Sørensen et al [201] , Gagel et al [202] , Carlin et al [203] , Chang et al [204] , Mortensen et al [127] Hatano et al [205] , Huang et al [206] , Huang et al [207] , Oehler et al [208] , Cho et al [209] , Troost et al [210] , Matsumoto et al [136] , Troost et al [198] , Dubois et al [211] Dubois et al [211] , Cherk et al [212] , Riesterer et al [213] , Lehmann et al [214] , Chen et al [215] , Campanile et al [216] , Cheng et al [217] , Sato et al [218] , Norikane et al [219] Cherk et al [212] , Eschmann et al [77] , Gagel et al [82] , Koh et al [87] , Rasey et al [220] , Vera et al…”

Section: F]fmisomentioning

confidence: 99%

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Verwer

Boellaard

Veldt

2014

WJCO

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Core tip:This review provides an overview of the current applications of positron emission tomography for hypoxia and perfusion imaging in lung cancer. Available PET tracers are discussed and the benefits of combined hypoxia and perfusion PET imaging are clarified. Hypoxia imaging could aid in selecting patients for hypoxia-specific treatment strategies. To achieve this, consensus about the optimal imaging protocol and quantification method is essential. Large clinical trials are needed to confirm the value of hypoxia imaging for improving patient care.Verwer EE, Boellaard R, van der Veldt AAM. Positron emission tomography to assess hypoxia and perfusion in lung cancer.

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“…5,6) In contrast to established cell lines cultured under normal oxygen concentrations, tumors in the body grow under a specific internal environment characterized by much lower oxygen concentrations. Tissue factor (TF) is frequently over-expressed in human tumors and exhibits dual influences through its signaling and procoagulant activity.…”

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confidence: 99%

The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor

Sun

Lin

Zhao

et al. 2010

Biological & Pharmaceutical Bulletin

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In 2009, the most commonly diagnosed type of cancer among women in the United States was breast cancer, accounting for 27% (192370) of all new cancer cases.1) Despite improvements in detecting and treating the primary tumor, long-term survival is often compromised by the appearance of metastatic lesions in unrelated tissues such as the brain or bone.2) The metastatic dissemination of tumor cells requires the acquisition of biological properties including enhanced migratory behavior and the capacity to breach blood vessel walls and the dense collagenous matrix surrounding tumors.3,4) Currently, there is no effective therapy for this cancer in the advanced stages after metastasis, and new approaches are urgently needed to treat such a malignant disease.Hypoxia is an important factor that promotes cancer metastasis. 5,6) In contrast to established cell lines cultured under normal oxygen concentrations, tumors in the body grow under a specific internal environment characterized by much lower oxygen concentrations. Tissue factor (TF) is frequently over-expressed in human tumors and exhibits dual influences through its signaling and procoagulant activity. 7)In some cases, tumor cells were found to ectopically produce the main TF ligand, plasma protein factor VII, an observation that may suggest a cancer-specific 'autocrine' activation of the TF pathway.7) These new observations of TF suggest this unique molecule can be exploited in various ways to treat human cancer. As it is functionally involved in tumor initiation, growth and angiogenesis, TF could be a rational target for the development of agents to specifically kill tumor cells or block metastasis.8) Overall, several new findings related to TF create a fascinating prospect that this unique molecule could be explored in various ways to treat human cancer.Dwarf lilyturf tuber, a traditional Chinese medicinal (TCM) plant, is used widely in the clinics.9) The saponin monomer 13 of dwarf lilyturf tuber (DT-13), one of the saponin monomers of dwarf lilyturf tuber isolated from Ophiopogon japonicus (THUNB.) ker-Gaul, 9,10) has been found to exhibit anti-tumor effects.11) However, direct evidence for the mechanism of action of DT-13 on tumors during hypoxia is lacking. Interestingly, in our preliminary experiments, we found that DT-13 could inhibit hypoxia-induced adhesion of cancer cells. Thus, the purpose of this present study was to investigate the effects of DT-13 on human breast carcinoma metastasis in hypoxic conditions, and explore the possible mechanism of DT-13 against tumor metastases. MATERIALS AND METHODS Cell Lines and Cell CultureHuman breast carcinoma MDA-MB-435 cells were cultured as monolayers in Dulbecco's modified Eagle's medium media (DMEM, Gibco) supplemented with 10% fetal calf serum (FCS, Gibco), 100 U/ml penicillin and 100 mg/ml streptomycin. To create hypoxic conditions, 70-80% confluent cells were placed in an anaerobic chamber (HERAcell 150, Thermo) with 1% O 2 and 5% CO 2 at 37°C.Cytotoxicity Assays Inhibitory effects were determined using t...

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Noninvasive Multimodality Imaging of the Tumor Microenvironment: Registered Dynamic Magnetic Resonance Imaging and Positron Emission Tomography Studies of a Preclinical Tumor Model of Tumor Hypoxia

Cited by 110 publications

References 34 publications

Pattern and Prognostic Implications of Cardiac Metastases Among Patients With Advanced Systemic Cancer Assessed With Cardiac Magnetic Resonance Imaging

Pattern and Prognostic Implications of Cardiac Metastases Among Patients With Advanced Systemic Cancer Assessed With Cardiac Magnetic Resonance Imaging

Positron emission tomography to assess hypoxia and perfusion in lung cancer

The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor

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