STEM-03. NOVEL METASTATIC BRAIN TUMOR TARGETS ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS

Abstract To effectively target metastatic brain tumors (MBTs), the paradigm of treating MBTs after visualization on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-population, which may form as a result from activation of epithelial-mesenchymal transition, may allow for more effective means of isolating and targeting brain metastasis. In order to isolate BMICs, we have harvested cells from patient derived MBTs originating from lung cancer and cultured the cells using serum-free media conditions. In vivo phage display biopanning was used to isolate 12-amino acid length peptides that specifically target BMICs. Of the peptides recovered, one peptide, LBM4, was tested for specificity of binding to MBTs through in vitro and in vivo binding assays. When comparing patient derived metastatic brain tumors cells against brain metastasis cell lines, we found that both types of cells demonstrated similar morphology when grown in serum media conditions, but when grown in serum-free media, both demonstrated a tumor sphere morphology, similar to a stem cell-like state. LBM4 demonstrated specific binding to MBT cells over primary lung cancer cells in vitro through flow cytometry analysis and immunocytochemistry. Fluorescent tagged LBM4 intravenously injected into mice harboring intracranial BM demonstrated peptide localization to the tumor within the intracranial cavity visualized with live animal imaging. In vivo phage display biopanning is an effective tool that is able to isolate cell specific targeting peptides. MBT targeting peptides can potentially result in a shifting of the clinical treatment paradigm of brain metastases, through the development of more effective targeted therapeutics aimed at BMICs, as well as improving detection of MBT cells which may result in earlier tumor visualization as well as delineation of tumor recurrence versus radiation effects.

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STEM-23. METASTATIC BRAIN TUMOR IMAGING THROUGH TARGETED PEPTIDES ISOLATED VIA PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS

Neuro-Oncology ◽

10.1093/neuonc/noz175.996 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi238-vi238

Author(s):

JongMyung Kim ◽

James Liu

Keyword(s):

Lung Cancer ◽

Brain Metastasis ◽

Brain Metastases ◽

Phage Display ◽

Tumor Imaging ◽

Mesenchymal Transition ◽

Phage Display Biopanning ◽

In Vivo Phage Display

Abstract To effectively target metastatic brain tumors (MBTs), the paradigm of initiating treatment against MBTs following detection on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-population, which may form as a result of activation of the epithelial-mesenchymal transition, may allow for more effective means of understanding and targeting brain metastases. In order to isolate BMICs, we have harvested cells from patient derived MBTs originating from lung cancer and cultured the cells using stem cell media conditions. We then performed in vitro and in vivo phage display biopanning to isolate 12-amino acid length peptides that specifically target BMICs. Several peptides were isolated from both in vitro and in vivo biopanning strategies. Of the peptides recovered, one peptide, LBM4, demonstrated specific binding to MBT cells over primary lung cancer cells in vitro through flow cytometry analysis and immunocytochemistry. Fluorescent tagged LBM4 intravenously injected into mice harboring intracranial brain metastases demonstrated peptide localization to the tumor within the intracranial cavity visualized with live animal imaging. Peptide imaging of tumor corresponded to MRI imaging confirming that the peptides could serve as an alternative to tumor imaging, with the potential for greater sensitivity resulting from the cellular targeting of MBTs. Our results demonstrate that we can use a combination of in vitro and in vivo phage display biopanning to isolate cell specific targeting peptides. MBT targeting peptides can potentially result in a shifting of the clinical treatment paradigm of brain metastases, through the development of more effective targeted therapeutics aimed at BMICs, as well as improving detection of MBT cells which may result in earlier tumor visualization, as well as delineation of tumor recurrence versus radiation effects.

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Clinicopathological Factors Related to the Prognosis of Metastatic Breast Cancer Patients after Development of Brain Metastasis

Breast Care ◽

10.1159/000442192 ◽

2015 ◽

Vol 10 (6) ◽

pp. 387-392 ◽

Cited By ~ 3

Author(s):

Jun Yamamura ◽

Norikazu Masuda ◽

Hiroyuki Yasojima ◽

Makiko Mizutani ◽

Keiko Kuriyama ◽

...

Keyword(s):

Breast Cancer ◽

Brain Tumor ◽

Brain Metastasis ◽

Cancer Patients ◽

Breast Cancer Subtype ◽

Performance Status ◽

Metastatic Breast ◽

Metastatic Brain Tumor ◽

Clinicopathological Factors ◽

Breast Cancer Patients

Background: The prognosis of breast cancer patients with brain metastasis (BM) is extremely poor, and the survival after development of BM is very short. We aimed to investigate clinicopathological factors related to significant effects on the prognosis after BM development. Patients and Methods: This is a retrospective study of 75 early breast cancer patients who received the standard of care and subsequently developed BM. Results: Breast cancer subtype was one of the significant predictors for prognosis after BM diagnosis. Luminal HER2 patients had the most favorable prognosis after BM diagnosis (p = 0.011). Favorable performance status (PS) at BM diagnosis (p < 0.001) and a single metastatic brain tumor (p = 0.032) were significantly associated with good prognosis after BM diagnosis. Metastatic time courses of the patients was found not to be significantly associated with survival after BM diagnosis. Univariate and multivariate analysis indicated that luminal HER2 cancer, favorable PS at BM diagnosis, and a single metastatic brain tumor were the independent prognostic factors for survival after BM development, making a decisive influence on local or systemic control. Conclusion: Appropriate treatments for tumor subtypes and to improve the general condition of patients would result in improved outcomes for the patients with BM.

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MET-04 A case of Brain Metastases with repeated bleeding from Esophageal carcinoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.082 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii19-ii19

Author(s):

Masataka Mikai ◽

Mitsuyoshi Abe ◽

Yo watanabe ◽

Chie Nakada ◽

Yutaka Huchinoue ◽

...

Keyword(s):

Brain Tumor ◽

Brain Metastases ◽

Esophageal Carcinoma ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Cerebral Hemorrhage ◽

Small Cell ◽

The Body ◽

Metastatic Brain Tumor ◽

Carcinoma Of The Esophagus

Abstract Brain metastases from esophageal cancer is rare and the incidence has been reported at approximately 5%. We report a case of brain metastases with repeated bleeding from Esophageal carcinoma. The case is a 76-year-old man. Three years ago he was diagnosed with small cell carcinoma of the esophagus by endoscopic biopsy. Metastasis was found only in the cervical lymph node, but the condition was stable by chemoradiotherapy and no metastases were found throughout the body before 1 month. He was admitted to the hospital because of a sudden convulsion, and CT scan revealed cerebral hemorrhage in the right frontal lobe. We performed conservative treatment, but rebleeding was observed from the same site repeatedly after 1 month and 2 months. Due to the influence of bleeding, it was difficult to distinguish cerebral hemorrhage from brain tumor by contrast MRI. After surgery, the cause of bleeding was diagnosed as metastatic brain tumor of esophageal small cell carcinoma. Postoperative radiation therapy was performed in another hospital, but rebleeding was observed 3 months after the operation. A reoperation was performed at another hospital, and a recurrence of metastatic brain tumor was diagnosed. In the case of highly malignant metastatic brain tumors, it was considered necessary to frequently follow the images.

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Treatment of Metastatic Brain Tumor from Esophageal Carcinoma

Neurologia medico-chirurgica ◽

10.2176/nmc.31.518 ◽

1991 ◽

Vol 31 (8) ◽

pp. 518-522 ◽

Cited By ~ 12

Author(s):

Hisashi KOGA ◽

Jiro MUKAWA ◽

Koichi MIYAGI ◽

Susumu NAKASONE ◽

Toshihiko KINJO ◽

...

Keyword(s):

Brain Tumor ◽

Esophageal Carcinoma ◽

Metastatic Brain Tumor

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The isolation and characterisation of novel antibodies against the murine beta common receptor using two methods of phage display biopanning

10.14264/978415a ◽

2021 ◽

Author(s):

◽

Nadya Panagides

Keyword(s):

Phage Display ◽

Common Receptor ◽

Phage Display Biopanning

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Changes in the Peritumoral Hypoperfusion Area immediately after Radiosurgery for Metastatic Brain Tumor : Analysis using 3D-SPECT

Japanese Journal of Neurosurgery ◽

10.7887/jcns.10.604 ◽

2001 ◽

Vol 10 (9) ◽

pp. 604-611

Author(s):

Masaaki Nemoto

Keyword(s):

Brain Tumor ◽

Metastatic Brain Tumor

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Cerebellar hemorrhage due to dural arteriovenous fistula mimicking a hemorrhagic metastatic brain tumor: a case report

Nosotchu ◽

10.3995/jstroke.10584 ◽

2018 ◽

Vol 40 (6) ◽

pp. 427-431

Author(s):

Yoichi Yoshida ◽

Yoshinori Higuchi ◽

Ryota Nomura ◽

Shiro Ikegami ◽

Toshimasa Shin ◽

...

Keyword(s):

Brain Tumor ◽

Case Report ◽

Arteriovenous Fistula ◽

Dural Arteriovenous Fistula ◽

Metastatic Brain Tumor ◽

Cerebellar Hemorrhage

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Preparation and Culture of Organotypic Hippocampal Slices for the Analysis of Brain Metastasis and Primary Brain Tumor Growth

Methods in Molecular Biology - Metastasis ◽

10.1007/978-1-0716-1350-4_5 ◽

2021 ◽

pp. 59-77

Author(s):

Ellina Schulz ◽

Tim Hohmann ◽

Urszula Hohmann ◽

Ralf-Ingo Ernestus ◽

Mario Löhr ◽

...

Keyword(s):

Brain Tumor ◽

Brain Metastasis ◽

Tumor Growth ◽

Hippocampal Slices ◽

Primary Brain Tumor

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A Liquid Biopsy to Assess Brain Tumor Recurrence: Presence of Circulating Mo-MDSC and CD14+ VNN2+ Myeloid Cells as Biomarkers That Distinguish Brain Metastasis From Radiation Necrosis Following Stereotactic Radiosurgery

Neurosurgery ◽

10.1093/neuros/nyaa334 ◽

2020 ◽

Vol 88 (1) ◽

pp. E67-E72

Author(s):

David C Soler ◽

Amber Kerstetter-Fogle ◽

Theresa Elder ◽

Alankrita Raghavan ◽

Jill S Barnholtz-Sloan ◽

...

Keyword(s):

Brain Tumor ◽

Brain Metastasis ◽

Stereotactic Radiosurgery ◽

Peripheral Blood ◽

Radiation Necrosis ◽

Surrogate Marker ◽

Suppressor Cells ◽

Surgical Biopsy ◽

Hla Dr ◽

The Us

Abstract BACKGROUND Brain metastases (BM) are the most common type of brain tumor malignancy in the US. They are also the most common indication for stereotactic radiosurgery (SRS). However, the incidence of both local recurrence and radiation necrosis (RN) is increasing as treatments improve. MRI imagery often fails to differentiate BM from RN; thus, patients must often undergo surgical biopsy or resection to obtain a definitive diagnosis. OBJECTIVE To hypothesize that a marker of immunosuppression might serve as a surrogate marker to differentiate patients with active vs inactive cancer—including RN. METHODS We thus purified and quantified Monocytic Myeloid-Derived Suppressor Cells (Mo-MDSC) by flow cytometry in patients proven by biopsy to represent BM or RN. RESULTS We report the utility of the previously reported HLA-Dr-Vnn2 Index or DVI to discriminate recurrent BM from RN using peripheral blood. The presence of CD14+ HLA-DRneg/low Mo-MDSC is significantly increased in the peripheral blood of patients with brain metastasis recurrence compared to RN (Average 61.5% vs 7%, n = 10 and n = 12, respectively, P < .0001). In contrast, expression of VNN2 on circulating CD14+ monocytes is decreased in BM patients compared to patients with RN (5.5% vs 26.5%, n = 10 and n = 12, respectively, P = .0008). In patients with biopsy confirmed recurrence of brain metastasis, the average DVI was 11.65, whereas the average DVI for RN patients was consistently <1 (Avg. of 0.17). CONCLUSION These results suggest that DVI could be a useful diagnostic tool to differentiate recurrent BM from RN using a minimally invasive blood sample.

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