The authors have no acknowledgements.

Die Daten über alle Patienten mit EBUS-geführte Cisplatin behandelt wurden überprüft. Die Institutional Review Board an der University of Florida genehmigt diese Studie (# IRB201400823). Alle Daten wurden prospektiv erhoben und retrospektiv analysiert. Verwenden Sie die folgenden Aufnahmekriterien. 1. Patientenauswahl <ol><li> Wählen Patienten im Alter zwischen 18 und 80 Jahren, die eine Biopsie bestätigt nicht-kleinzelligem Lungenkrebs (NSCLC) oder kleinzelliges Lungenkarzinom haben (SCLC) und haben eine pathologisch bestätigt Wiederholung. Einzuschreiben Patienten, die mindestens 50 Gy von Strahlung auf die hilar und mediastinalen Strukturen für 6 Monate oder länger erhalten haben. Fügen Sie Patienten mit eingeschränkter Wiederholung der hilar, mediastinalen und peribronchiale Strukturen (Lymphknoten, Knötchen und Massen) zugänglich über den EBUS und Fernmetastasen. </li><li> Präsentieren Sie alle solche Patienten zu einem multidisziplinären Board Thorax Onkologie Tumor und erhalten Konsens mit der in auf fortfahrentratumoral Cisplatin aufgrund eines Mangels an anderen lokalisierten therapeutischen Optionen. Die Entscheidung, mit EBUS-geführten ITC fortfahren sollte eine gemeinsame Empfehlung des institutionellen Brust- Onkologie Tumor Bord sein. </li></ol> 2. Endobronchial Ultraschall (EBUS) -geführte Cisplatin Injection <ol><li> Verwenden Sie eine konvex-Sonde EBUS, die einen eingebauten Ultraschallsonde auf einem flexiblen Bronchoskop hat und ermöglicht die Echtzeit-Visualisierung von hilar, mediastinalen und peribronchiale Strukturen für ITC. </li><li> Stellen Sie sicher, dass die Patienten von oralen Nahrung und Flüssigkeit für mindestens 6 h vor dem Eingriff der Stimme enthalten. </li><li> Erstellen einer wässrigen Cisplatin - Lösung bei einer Konzentration von 1 mg / ml mit einer maximalen Dosis von 40 mg pro Einheit, basierend auf zuvor veröffentlichten Literatur 9, 10. Auflösen lyophilisierten Cisplatin-Pulver in 0,9% NaCl-Lösung unmittelbar vor der Verwendung. </li><li> Gib 10 mg Dexamethason und 8 mg Ondansetron intravenös zu Beginnning des Verfahrens Übelkeit zu vermeiden. </li><li> Führen Sie das Verfahren mit Sedierung mit Midazolam und Fentanyl intravenös (IV). Verwenden topischer Anästhesie in Form von 5 ml 4% Lidocain Vernebelung vor dem Verfahren. </li><li> Beginnen Sie mit einer IV-Injektion von 2 mg Midazolam und 50 &amp; mgr; g Fentanyl. Neu beurteilen Patienten alle 1-2 min und geben zusätzlich 1 mg Midazolam und 25 ug Fentanyl-Bolus zu erreichen und aufrechtzuerhalten Analgosedierung (ein minimal gedrückt Bewusstsein, so dass der Patient in der Lage ist, kontinuierlich und unabhängig ein Atemwege halten, behalten Schutzreflexe, und bleiben in Reaktion auf verbale Befehle und körperliche Stimulation). überschreiten die maximal zulässigen Dosen von Fentanyl und Midazolam nicht, 200 ug und 10 mg. </li><li> Verwenden Sie Standard-Überwachung, einschließlich einer kontinuierlichen 3-adriges EKG-Überwachung der Herzfrequenz, kontinuierliche Pulsoxymetrie und Atemfrequenz-Messungen. Für örtliche anesthesia und zusätzliches O 2 , wie erforderlich. </li><li> Rückt den Umfang durch die Stimmbänder in den Atemwegen. Ermittlung und Bewertung der Zielläsion lokalisieren. </li><li> Schalten Sie den EBUS-Prozessor und pumpen Sie den Ballon an der Spitze des Bereichs mit 1-2 ml normaler Kochsalzlösung. Biegen Sie den Rahmen über die Atemwegswand und die Läsion zu lokalisieren. Die Lage der Läsion wird auf CT / PET-Befunde ab, aber einige der häufigsten Sehenswürdigkeiten gehören die subkarinalen Bereich, die rechte und linke paratracheal Bereiche und die rechten und linken hilar Bereichen. </li><li> Bereitstellen einer 22 G EBUS Nadel, die in einer Hülle durch den Arbeitskanal des Bereichs untergebracht ist, und arretieren. Hinweis: Obwohl es keine genaue chirurgische Koordinaten für die Injektionsstelle sind, sind einige der häufigsten behandelten Stellen umfassen die subkarinalen (medial an der Kreuzung von der linken und rechten Hauptbronchien), die rechte paratracheal (seitlich am rechten Hauptbronchus, einfach oberhalb des rechten Oberlappens Öffnung), der linken paratracheal(An der Verbindung der distalen Trachea und dem linken Haupt zwischen dem Bogen der Aorta und der linken Lungenarterie), die rechte hilar (seitlich am proximalen Bronchus intermedius, unter dem rechten Oberlappen Öffnung), und die linke hilar (at die Verbindung des linken oberen Lappens und der linke untere Lappen Bronchien). </li><li> Unter Echtzeit-Ultraschallkontrolle durchstechen die tracheobronchial Wand und die Nadel in der Zielläsion platzieren. Entfernen des Stiletts in der Nadel und die Injektion Cisplatin in die Läsion 10 ml (1 mg / ml Cisplatin) zu einer Zeit. Ziehen Sie die Nadel innerhalb des Bogens. </li><li> Behandeln Sie jeden Läsion mit vier Einstiche pro Sitzung an verschiedenen Standorten in der Injektion des Medikaments zu erleichtern. Injizieren 10 mg Cisplatin pro Einstich. </li><li> Treat 01.59 Läsionen pro Sitzung. Wenn mehr als eine Läsion pro Sitzung behandelt wird, injizieren jeden Standort mit 20 mg Cisplatin, mit Gesamtdosis pro Sitzung nicht mehr als 40 mg. </li><li> Entfernen Sie die Nadel aus der working Kanal des Umfangs. </li><li> Saugen Sie zusätzliche Arzneimittel von den distalen Atemwege und das Bronchoskop zu entfernen. </li><li> Lassen Sie die Patienten pro Krankenhaus-Protokoll zu erholen und sie noch am selben Tag entlassen. </li><li> Wiederholen der Cisplatin-Injektion (Schritte 2,7-2,13) ​​einmal pro Woche für insgesamt 4 Wochen (an den Tagen 1, 8, 15 und 22). HINWEIS: Nach der Behandlung eine bestimmte Läsion sollte nie mit ITC bei zukünftigen Begegnungen für eine erneute Behandlung in Betracht gezogen werden. </li></ol> 3. Post-Injektion <ol><li> Bewerten Sie die Antwort durch ein Follow-up Brust-Computertomographie (CT) oder Positronen-Emissions-Tomographie (PET / CT) 8-12 Wochen nach der letzten Behandlung Sitzung. Definieren Sie die lokale Rezidiv als Wiederholung am Ort der Behandlung und der regionalen Rezidiv als Wiederholung im Mediastinum, hilum oder Supraklavikulargrube. </li></ol>

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The authors have nothing to disclose.

<html> Unsere Handschrift konzentriert sich auf die Verwaltung von isolierten mediastinal und hilar Rezidive von Lungenkrebs für Patienten, bei denen mehr Strahlung ist keine Option. Die Inzidenz von IMHR beträgt ca. 9% 11. Verschiedene Behandlungsmöglichkeiten haben bei diesen Patienten, einschließlich palliative Chemotherapie, mehr externe Strahlentherapie oder unterstützende Pflege und Überwachung versucht worden. In unserer Institution, behandeln wir diese Patienten mit intratumorale Cis...

Lungenkrebs ist die häufigste Krebsart weltweit bei Männern und Frauen und Konten für 1 in 5 aller krebsbedingten Todesfälle. Es hat eine Letalität von 0,87 1, 2. Rezidive nach der Erstbehandlung Konten für die meisten Todesfälle bei Patienten mit Lungenkrebs. Therapeutische Optionen für wiederkehrende Lungenkrebs sind begrenzt. Recurrent Lungenkrebs führt auch zu einer erheblichen Beeinträchtigung der Lebensqualität und zu erheblichen Betreuungsperson Burnout und erfordert zusätzliche unterstützende Pflege, von denen alle verringern die Wahrscheinlichkeit der Akzeptanz und Toleranz zu weiteren Interventionen 3. Fast 30% der Patienten mit NSCLC haben lokoregionären Rezidiv nach der Bestrahlung 4. Behandlungsmöglichkeiten für diese Patienten sind begrenzt und umfassen eine systemische Chemotherapie, die eine objektive Reaktionsrate von nur 10% 5, 6.Obwohl Wiederholungs Brust Strahlung möglich ist, hat es sich für die palliative Zwecke und Linderung der Symptome untersucht in erster Linie worden und wurde für die Krankheitsremission 3 nicht verwendet. In unserer Institution, alle Patienten mit isolierten mediastinal und hilar Wiederholung (IMHR) zugänglich durch Bronchoskopie wurden mit einem endobronchiale Ultraschall (EBUS) -geführte transbronchial intratumorale Injektion von Cisplatin (ITC) behandelt. Die gleichzeitige Behandlung mit systemischer Chemotherapie und / oder einer externen Strahlentherapie (EBRT) wurde gemäß den behandelnden Onkologen Ermessensspielräume erlaubt. Dieses Manuskript unterstreicht die Sicherheit, Wirksamkeit, Durchführbarkeit und detaillierte Methoden des Protokolls an unserer Hochschule eingesetzt.

<table border="0" cellpadding="0" cellspacing="0" width="261">
	<tbody>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;width:261px;">Bronchoscope</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">22 Guage olympus EBUS needle</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">40 g of cisplatin in 40 mls of normal saline</td>
		</tr>
	</tbody>
</table>

endobronchial ultrasound-guided intratumoral injection of cisplatin for the treatment of isolated mediastinal recurrence of lung cancer

Isolierte hilar und Mediastinums Wiederholung (IMHR) im Anschluss an die externe Strahlentherapie (EBRT) bei Patienten mit Lungenkrebs ist weit verbreitet. Diese Patienten haben nicht viele Möglichkeiten der Behandlung und sind in der Regel palliative Chemotherapie oder am besten unterstützende Pflege angeboten. Endobronchial Ultraschall (EBUS) -geführte intratumorale Injektion von Cisplatin (ITC) ist ein neuartiger Ansatz für diese Patienten. Das Verfahren wird unter Sedierung durchgeführt. Die Läsion ist mit einer Bronchoskopie unter Verwendung EBUS befindet, und eine 22-Gauge-Nadel wird EBUS durch den Arbeitskanal des Umfangs vorgeschoben und in Position verriegelt. Unter Ultraschallkontrolle wird die Wand des Tracheobronchialbaumes durchstochen und die Nadel in die Zielläsion bewegt wird. Die Nadel Mandrin wird dann entfernt und Cisplatin (40 mg / 40 ml) wird in die Läsion injiziert. Ein bis zwei Standorten werden pro Sitzung behandelt. Einzelheiten des Verfahrens werden in dem Protokollabschnitt Papier beschrieben. In unserem Zentrum wurden 50 Standorte in 36 Patienten behandelt(19 Männer, 17 Frauen). Das Durchschnittsalter unserer Kohorte betrug 61,9 ± 8,5 Jahren. Wir führten endgültigen Analysen auf 35 Patienten und 41 Seiten. 24/35 (69%) hatten vollständige oder partielle Ansprechen (Responder), während 11/35 (31%) stabil oder progressive Krankheit (Non-Responder) hatte. Insgesamt Überleben in unserer Gruppe betrug 8 Monate (95% CI von 6-11 Monate), mit Patienten, die deutlich bessere Überlebenszeit als diejenigen, gefolgt seid, die nicht.

Die Reaktion wurde durch Follow-up-Bildgebung 8-12 Wochen nach der Therapie gemessen. Die Antwort wurde als eine komplette Remission (CR) eingestuft, eine partielle Remission (PR), eine stabile Erkrankung (SD), progressive Krankheit (PD), oder nicht in der Lage Antwort zu beurteilen , basierend auf RECIST 1.1 Kriterien 8. Patienten mit CR und PR wurden als positiv gewertet, und die anderen wurden als Non-Responder eingestuft. Sekundäre Endpunkte waren die Antwort...

Watch this Scientific Journal Video about Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer at JoVE.com

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field.

Endobronchial intratumorale Injektion von Cisplatin zur Behandlung von isolierten Mediastinale Recurrence von Lungenkrebs Ultraschall-gesteuerte

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients ...

endobronchial-ultrasound-guided-intratumoral-injection-cisplatin-for

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Cancer Research

10.4K Aufrufe.  University of Florida College of Medicine. The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field. 

Serie: Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Operating Procedures of the Electrochemotherapy for Treatment of Tumor in Dogs and Cats

Electrochemotherapy (ECT) is a local approach which is used for treating solid tumors of different histologies. Its mechanism is based on cell membrane permeabilization by means of &#34;electroporation&#34;. To achieve the &#34;electroporation&#34; of the cells, electric pulses are generated by a generator and delivered to the target tissue by the use of electrodes. Electroporation is a physical method which is used to introduce molecules, like cytostatic drugs, into the cells that could not pass the cell membrane on their own. In electrochemotherapy, currently, cisplatin and bleomycin are clinically used. Electrochemotherapy antitumor effectiveness is high, for example up to 100% complete response of canine mast cell tumors smaller than 2 cm3 was achieved. Additionally, electrochemotherapy can be used for the treatment of inoperable tumors. One of the important characteristics of electrochemotherapy is that it can be effective as a one-time treatment only. However, in the case of failure or partial tumor response it can be repeated several times with equal or improved effectiveness. Electrochemotherapy is already a standard treatment for cutaneous and subcutaneous tumors of various histologies in human and veterinary oncology. Furthermore, several clinical studies exploiting electrochemotherapy for deep-seated tumors are on-going.

Electrochemotherapy is the local treatment of solid tumors. The main mechanism is electroporation-mediated permeabilization of the tumor cells' membrane which enables increased internalization of cytostatics like bleomycin and cisplatin. Thus, antitumor effectiveness is potentiated at the site of the application of electric pulses to the tumors.

Die Arbeitsverfahren der Elektrochemotherapie zur Behandlung von Tumor bei Hunden und Katzen

Electrochemotherapy (ECT) is a local approach which is used for treating solid tumors of different histologies. Its mechanism is based on cell membrane ...

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Krebsforschung

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by CTCs critically contributes to early lung metastatic processes, has been vigorously investigated. As such, animal models are the only approach that captures the full systemic process of metastasis. Given that problems occur in previous experimental designs for examining the contributions of CTCs to blood vessel extravasation, we established an in vivo lung colonization assay in which a long-term-fluorescence cell-tracer, carboxyfluorescein succinimidyl ester (CFSE), was used to label suspended tumor cells and lung perfusion was performed to clear non-specifically trapped CTCs prior to lung removal, confocal imaging, and quantification. Polymeric fibronectin (polyFN) assembled on CTC surfaces has been found to mediate lung colonization in the final establishment of metastatic tumor tissues. Here, to specifically test the requirement of polyFN assembly on CTCs for lung colonization and extravasation, we performed short term lung colonization assays in which suspended Lewis lung carcinoma cells (LLCs) stably expressing FN-shRNA (shFN) or scramble-shRNA (shScr) and pre-labeled with 20 &#956;M of CFSE were intravenously inoculated into C57BL/6 mice. We successfully demonstrated that the abilities of shFN LLC cells to colonize the mouse lungs were significantly diminished in comparison to shScr LLC cells. Therefore, this short-term methodology may be widely applied to specifically demonstrate the ability of CTCs within the circulation to colonize the lungs.

An animal model is needed to decipher the role of circulating tumor cells (CTCs) in promoting lung colonization during cancer metastasis. Here, we established and successfully performed an in vivo assay to specifically test the requirement of polymeric fibronectin (polyFN) assembly on CTCs for lung colonization.

Die Einrichtung eines Lunge Kolonisation Assays für zirkulierenden Tumor Zelle Visualisierung im Lungengewebe

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by ...

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard subcutaneous flank models include procedural ease and the ability to monitor tumor progression and response without invasive imaging. Such models are often inconsistent in translational clinical trials and have limited biologically relevant characteristics with low proclivity to produce metastasis, as there is a lack of a native microenvironment. In comparison, orthotopic xenograft models at native tumor sites have been shown to mimic the tumor microenvironment and replicate important disease characteristics such as distant metastatic spread. These models often require tedious surgical procedures with prolonged anesthetic time and recovery periods. To address this, cancer researchers have recently utilized ultrasound-guided injection techniques to establish cancer xenograft models for preclinical experiments, which allows for rapid and reliable establishment of tissue-directed murine models. Ultrasound visualization also provides a noninvasive method for longitudinal assessment of tumor engraftment and growth. Here, we describe the method for ultrasound-guided injection of cancer cells, utilizing the adrenal gland for NB and renal sub capsule for ES. This minimally invasive approach overcomes tedious open surgery implantation of cancer cells in tissue-specific locations for growth and metastasis, and abates morbid recovery periods. We describe the utilization of both established cell lines and patient derived cell lines for orthotopic injection. Pre-made commercial kits are available for tumor dissociation and luciferase tagging of cells. Injection of cell suspension using image-guidance provides a minimally invasive and reproducible platform for the creation of preclinical models. This method is utilized to create reliable preclinical models for other cancers such as bladder, liver and pancreas exemplifying its untapped potential for numerous cancer models.

Here, we present a protocol to utilize ultrasound-guided injection of neuroblastoma (NB) and Ewing's sarcoma (ES) cells (established cell lines and patient-derived tumor cells) at biologically relevant sites to create reliable preclinical models for cancer research.

Nutzung von Ultraschall geführte Gewebe gerichtet zellulären Implantation für die Einrichtung der biologisch relevanten metastasiertem Tumor Xenografts

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard ...

Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% of patients. Surgery has been widely used in association with radiofrequency, cryotherapy, or microwaves to expand the number of treatments performed with a curative intent. Nevertheless, several limitations have been documented when using these techniques (i.e., a traumatic puncture of the parenchyma, a limited size of lesions, and an inability to monitor the treatment in real-time).High-intensity focused ultrasound (HIFU) technology can achieve precise ablations of biological tissues without incisions or radiation. Current HIFU devices are based on an extracorporeal approach with limited access to the liver. We have developed a HIFU device designed for intraoperative use. The use of a toroidal transducer enables an ablation rate (10 cm3&#183;min-1) higher than any other treatment and is independent of perfusion.
The feasibility, safety, and accuracy of intraoperative HIFU ablation were evaluated during an ablate-and-resect prospective study. This clinical phase I and IIa study was performed in patients undergoing hepatectomy for liver metastases. The HIFU treatment was performed on healthy tissue scheduled for resection.Liver metastases measuring less than 20 mm will be targeted during phase IIb (currently ongoing). This set-up allows the real-time evaluation of HIFU ablation while protecting participating patients from any adverse effects related to this new technique.
Fifteen patients were included in phase I&#8211;IIa and 30 HIFU ablations were safely created within 40 s and with a precision of 1&#8211;2 mm. The average dimensions of the HIFU ablations were 27.5 x 21.0 mm2, corresponding to a volume of approximately 7.5 cm3. The aim of the ongoing phase IIb is to ablate metastases of less than 20 mm in diameter with a 5 mm margin.

Here, we present an ablate-and-resect prospective study to evaluate the feasibility, safety, and accuracy of intraoperative high-intensity focused ultrasound ablation in patients undergoing hepatectomy for liver metastases.

Bewertung der Machbarkeit, Sicherheit und Genauigkeit einer intraoperativen hochintensive fokussiert Ultraschall-Gerät zur Behandlung von Lebermetastasen

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% ...

Elastic Staining on Paraffin-embedded Slides of pT3N0M0 Gastric Cancer Tissue

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and eosin (H&amp;E) staining but can be visualized through elastic staining. One of the important benefits of elastic staining is that it makes it easy to determine whether tumor cells have invaded beyond the elastic lamina. This helps in examining the extent of peritoneal surface invasion, thereby distinguishing the pT3 and pT4 stages in gastrointestinal cancer. In this study, we present a protocol to identify elastic fibers in the formalin-fixed, paraffin-embedded pT3N0M0 gastric cancer tissue sections. We prepare 5-&#181;m paraffin sections fixed on slides, and then all the slides are deparaffinated and rehydrated during the staining procedure. Subsequently, all the sections are oxidized by potassium permanganate, bleached by oxalic acid, stained by elastic staining, and counterstained by Van Gieson's. Finally, we examine the effect of staining; elastic lamina is stained blue-black and collagen fibers are stained red, while the cancer cells are stained in varying shades of yellow. We also describe in detail the methods used for determining the positional relationship between cancer cells and elastic lamina. This method is simple, low-cost, and widely applicable in the identification of peritoneal surface invasion in gastrointestinal cancer because of its outstanding selectivity for elastic fibers and authentic results.

Here, we present a protocol of elastic staining to identify elastic fibers in pT3N0M0 gastric cancer tissues on formalin-fixed, paraffin-embedded sections. Subsequently, we describe a method to determine whether tumor cells invade beyond the elastic lamina.

Elastische Färbung auf Paraffin-eingebetteten Dias von pT3N0M0 Magenkrebsgewebe

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the limitations of current treatments, as the majority of patients do not respond to immunotherapy. Development of accurate preclinical models to quickly identify novel and effective therapeutic combinations are critical to address this unmet clinical need. Pancreatic ductal adenocarcinoma (PDA) is a canonical example of an immune checkpoint blockade resistant tumor with only 2% of patients responding to immunotherapy. The genetically engineered KrasG12D+/-;Trp53R172H+/-;Pdx-1 Cre (KPC) mouse model of PDA recapitulates human disease and is a valuable tool for assessing therapies for immunotherapy resistant in the preclinical setting, but time to tumor onset is highly variable. Surgical orthotopic tumor implantation models of PDA maintain the immunobiological hallmarks of the KPC tissue-specific tumor microenvironment (TME) but require a time-intensive procedure and introduce aberrant inflammation. Here, we use an ultrasound-guided orthotopic tumor implantation model (UG-OTIM) to non-invasively inject KPC-derived PDA cell lines directly into the mouse pancreas. UG-OTIM tumors grow in the endogenous tissue site, faithfully recapitulate histological features of the PDA TME, and reach enrollment-sized tumors for preclinical studies by four weeks after injection with minimal seeding on the peritoneal wall. The UG-OTIM system described here is a rapid and reproducible tumor model that may allow for high throughput analysis of novel therapeutic combinations in the murine PDA TME.

We describe a protocol for the ultrasound guided implantation of murine-derived pancreatic ductal adenocarcinoma cell lines directly into the native tumor site. This approach resulted in pancreatic tumors detectable by ultrasound scanning within 2-4 weeks of injection, and significantly reduced the proportion tumor cell seeding on the peritoneal wall as compared to surgical orthotopic implantation.

Ultraschallgeführte orthotopische Implantation von murine Pankreas-Ductalsocarcinom

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

Perfusion and Inflation of the Mouse Lung for Tumor Histology

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform necropsies rapidly and efficiently from studies without sacrificing the quality of the tissues procured. The goal of this protocol is to present a method to rapidly perfuse, inflate, and fix mouse lungs for downstream histological analysis. This method does not standardize lung inflation; thus, it does not require any special procedures or equipment and instead simply instills fixative directly through the trachea following perfusion through the heart. This allows for sufficient estimation of tumor size, histology, and scoring. This also allows for the collection of frozen tissue prior to lung tissue fixation. This method is limited in that it does not allow for later morphometric quantification of the lung; however, it is more than sufficient for lung tumor analysis from genetically engineered mouse models (GEMMs), syngeneic models, as well as xenograft tumor and metastasis studies.

The purpose of this method is to present a simple and efficient method for the perfusion, inflation, and fixation of mouse lungs for the examination of lung tumor pathology and evaluation of metastases to the lung.

Perfusion und Inflation der Mauslunge für Tumorhistologie

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform ...

Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection of suitable cell lines is a mainstay of metastasis research. When cancer cells are injected into the lateral tail-vein, the lung is their preferred site of colonization. A potential limitation of this technique is the accurate quantification of the metastatic lung tumor burden. While some investigators count macrometastases of a pre-defined size and/or include micrometastases following sectioning of tissue, others determine the area of metastatic lesions relative to normal tissue area. Both of these quantification methods can be exceedingly difficult when the metastatic burden is high. Herein, we demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor burden using image analysis software. This process allows for investigation of multiple end-point parameters, including average metastasis size, total number of metastases, and total metastasis area, to provide a comprehensive analysis. Furthermore, this method has been reviewed by a veterinary pathologist board-certified by the American College of Veterinary Pathologists (SEK) to ensure accuracy.

Intravenous injection of cancer cells is often used in metastasis research, but the metastatic tumor burden can be difficult to analyze. Herein, we demonstrate a tail-vein injection model of metastasis and include a novel approach to analyze the resulting metastatic lung tumor burden.

Pathologische Analyse der Lungenmetastasierung nach lateraler Schwanzveneninjektion von Tumorzellen

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous ...

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are particularly devastating, difficult to treat, and confer a poor prognosis. While the precise incidence of brain metastases in the United States remains hard to estimate, it is likely to increase as extracranial therapies continue to become more efficacious in treating cancer. Thus, it is necessary to identify and develop novel therapeutic approaches to treat metastasis at this site. To this end, intracranial injection of cancer cells has become a well-established method in which to model brain metastasis. Previously, the inability to directly measure tumor growth has been a technical hindrance to this model; however, increasing availability and quality of small animal imaging modalities, such as magnetic resonance imaging (MRI), are vastly improving the ability to monitor tumor growth over time and infer changes within the brain during the experimental period. Herein, intracranial injection of murine mammary tumor cells into immunocompetent mice followed by MRI is demonstrated. The presented injection approach utilizes isoflurane anesthesia and a stereotactic setup with a digitally controlled, automated drill and needle injection to enhance precision, and reduce technical error. MRI is measured over time using a 9.4 Tesla instrument in The Ohio State University James Comprehensive Cancer Center Small Animal Imaging Shared Resource. Tumor volume measurements are demonstrated at each time point through use of ImageJ. Overall, this intracranial injection approach allows for precise injection, day-to-day monitoring, and accurate tumor volume measurements, which combined greatly enhance the utility of this model system to test novel hypotheses on the drivers of brain metastases.

Intracranial brain metastasis modeling is complicated by an inability to monitor tumor size and response to treatment with precise and timely methods. The presented methodology couples intracranial tumor injection with magnetic resonance imaging analysis, which when combined, cultivates precise and consistent injections, enhanced animal monitoring, and accurate tumor volume measurements.

Modellierung von Hirnmetastasen durch intrakranielle Injektion und Magnetresonanztomographie

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are ...

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are diagnosed with brain metastases each year. Significant progress has been made in improving survival outcomes for patients with primary breast cancer and systemic malignancies; however, the dismal prognosis for patients with clinical brain metastases highlights the urgent need to develop novel therapeutic agents and strategies against this deadly disease. The lack of suitable experimental models has been one of the major hurdles impeding advancement of our understanding of brain metastasis biology and treatment. Herein, we describe a xenograft mouse model of brain metastasis generated via tail-vein injection of an endogenously HER2-amplified cell line derived from inflammatory breast cancer (IBC), a rare and aggressive form of breast cancer. Cells were labeled with firefly luciferase and green fluorescence protein to monitor brain metastasis, and quantified metastatic burden by bioluminescence imaging, fluorescent stereomicroscopy, and histologic evaluation. Mice robustly and consistently develop brain metastases, allowing investigation of key mediators in the metastatic process and the development of preclinical testing of new treatment strategies.

We describe a xenograft mouse model of breast cancer brain metastasis generated via tail-vein injection of an endogenously HER2-amplified inflammatory breast cancer cell line.

Modellierung der Hirnmetastasierung durch Injektion von entzündlichen Brustkrebszellen in die Schwanzvene

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are ...