The authors have no acknowledgements.

נתונים על כלל החולים שטופלו עם ציספלטין EBUS המונחה נסקרו. דירקטוריון הסקירה המוסדי באונ&#39; פלורידה אשר במחקר זה (# IRB201400823). כל הנתונים נאספו באופן פרוספקטיבי ונותחו למפרע. השתמש קריטריוני ההרשמה הבאות. 1. בחירת חולים <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> חולים בחר בין הגילאים 18 ו 80 שנים שיש להם סרטן ריאות מסוג תאים ביופסיה-אישר שאינם קטנים (NSCLC) או סרטן ריאות תאים קטנים (SCLC) ויש הישנות פתולוגית-אושר. הרשם מטופלים שקיבלו לפחות 50 GY של קרינה אל hilar ומבנים mediastinal במשך 6 חודשים או יותר. כלול חולים עם הישנות מוגבלת hilar, mediastinal, ומבני peribronchial (בלוטות לימפה, גושים, והמוני) נגישים באמצעות EBUS ו גרורות מרוחקות. </li><li style=";text-align:right;direction:rtl"> להציג את כל לחולים כאלה קרשו אונקולוגיה גידול החזי רב-תחומי להשיג קונסנסוס על שתמשיך בציספלטין tratumoral בשל חוסר אפשרויות טיפוליות מקומיות אחרות. ההחלטה להמשיך עם ITC EBUS מונחה צריכה להיות המלצה משותפת של לוח גידול אונקולוגיה החזי המוסדי. </li></ol> 2. Endobronchial אולטראסאונד (EBUS) -guided הזרקת ציספלטין <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> השתמש EBUS קמור-בדיקה, אשר יש לו בדיקה מובנה אולטרסאונד על ברונכוסקופ גמישה ומאפשרת ויזואליזציה בזמן אמת של hilar, mediastinal, ומבנים peribronchial עבור המרכז לטניס בישראל. </li><li style=";text-align:right;direction:rtl"> ודא כי חולים להתנזר מזון ונוזלים דרך הפה במשך לפחות 6 שעות לפני ההליך. </li><li style=";text-align:right;direction:rtl"> צור פתרון ציספלטין מימי בריכוז של 1 מ&quot;ג / מיליליטר עם מינון מקסימאלי של 40 מ&quot;ג בכל הפעלה, המבוסס על ספרות בעבר בהוצאה 9, 10. ממסי אבקת ציספלטין lyophilized בתמיסת NaCl 0.9% רק לפני השימוש. </li><li style=";text-align:right;direction:rtl"> תן 10 מ&quot;ג של dexamethasone ו -8 מ&quot;ג אונדאנסטרון לווריד במרכז בגיןנינג של נוהל למניעת בחילות. </li><li style=";text-align:right;direction:rtl"> בצע את ההליך עם סדציה מודע באמצעות midazolam ו פנטניל לווריד (IV). השתמש הרדמה מקומית בצורת 5 מ&quot;ל של לידוקאין עִרפּוּל 4% לפני ההליך. </li><li style=";text-align:right;direction:rtl"> להתחיל עם זריקה IV של 2 מ&quot;ג של midazolam ו -50 מיקרוגרם של פנטניל. להעריך מחדש את החולה כל 1-2 דקות ולתת midazolam נוסף 1 מ&quot;ג ו -25 מיקרוגרם פנטניל בולוס להשיג ולשמר סדציה הכרתית (תודעה מדוכאת מינימאלי כך החולה אינו מסוגל באופן רציף ועצמאי לשמור על דרך נשימת פטנט, לשמור על רפלקסים מגן, ולהישאר תגובה לפקודות מילוליות גירוי פיזי). אין לעבור את המינון המקסימאלי המותר של פנטניל ו midazolam, 200 מיקרוגרם ו -10 מ&quot;ג, בהתאמה. </li><li style=";text-align:right;direction:rtl"> השתמש ניטור סטנדרטי, כולל רל רציף 3 להוביל ניטור קצב הלב, oximetry הדופק הרציף, ומדידות קצב נשימה. ספק anest המקומיhesia ונוסף O 2 כנדרש. </li><li style=";text-align:right;direction:rtl"> לקדם את היקף דרך מיתרי הקול בדרכי הנשימה. לזהות ולאתר את נגע היעד. </li><li style=";text-align:right;direction:rtl"> הפעילו את מעבד EBUS לנפח את הבלון בקצה היקף באמצעות 1-2 מ&quot;ל של תמיסת מלח רגיל. להגמיש את ההיקף על הקיר דרכי הנשימה ולאתר את הנגע. המיקום של הנגע יהיה תלוי ממצאי CT / PET, אך כמה מן האתרים הנפוצים כוללים את אזור subcarinal, ימינה ושמאלה באזורי paratracheal, וזכות ואזורי hilar עזבו. </li><li style=";text-align:right;direction:rtl"> פרוס מחט 22 G EBUS כי שוכן בתוך נרתיק דרך תעלת העבודה של היקף ולנעול אותו במקומו. הערה: למרות שאין קואורדינטות כירורגית מדויקות עבור הזריקה, חלק מהאתרים שטופלו בדרך כלל כולל את subcarinal (מדיאלית בצומת של הסמפונות העיקרי על ימין ועל שמאל), את paratracheal התקין (רוחבית על הסמפונות הזכות העיקריות, רק מעל פתח האונה הימנית העליונה), את paratracheal עזב(בצומת של קנה הנשימה דיסטלי ואת השמאלי הראשי בין קשת אבי העורקים והעורק הריאתי משמאל), hilar תקין (רוחבית על intermedius הסמפונות הפרוקסימלי, מתחת לפתח האונה הימנית העליונה), ואת hilar שמאלה (ב בצומת של האונה השמאלית העליונה ואת הסמפונות האונה השמאלית התחתונה). </li><li style=";text-align:right;direction:rtl"> בהנחיית אולטרסאונד בזמן האמת, לנקב את קיר tracheobronchial ומניח את מחט נגע היעד. הסר את stylet בתוך המחט ולהזריק ציספלטין לתוך 10 מ&quot;ל הנגע (1 מ&quot;ג / מ&quot;ל ​​של ציספלטין) בכל פעם. לחזור בו מחט בתוך הגיליון. </li><li style=";text-align:right;direction:rtl"> פנק את כל נגע עם ארבע דקירות בכל הפעלה במקומות שונים כדי להקל על הזרקת התרופה לאורך כל דרך. להזריק 10 מ&quot;ג של ציספלטין לכל לנקב. </li><li style=";text-align:right;direction:rtl"> נוהג אחד כדי שני נגעים בכל הפעלה. אם יותר נגע אחד מטופל בכל הפעלה, להזריק כל אתר עם 20 מ&quot;ג של ציספלטין, עם מינון הכולל בכל הפעלה שלא יעלה על 40 מ&quot;ג. </li><li style=";text-align:right;direction:rtl"> הסר את המחט מן working ערוץ של ההיקף. </li><li style=";text-align:right;direction:rtl"> יניקה כל תרופה נוספת מן דרכי הנשימה דיסטלי ולהסיר את ברונכוסקופ. </li><li style=";text-align:right;direction:rtl"> שתוכל החולים להתאושש לפי פרוטוקול חולים ולפרוק אותם באותו היום. </li><li style=";text-align:right;direction:rtl"> חזור על זריקת ציספלטין (שלבי 2.7-2.13) פעם בשבוע עבור סכום כולל של 4 שבועות (בימים 1, 8, 15, ו -22). הערה: לאחר שטופל, נגע מסוים לא היה אמור להיכלל עבור retreatment עם ITC על המפגשים הבאים. </li></ol> 3. לאחר הזרקה <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> להעריך את התגובה על ידי טומוגרפיה ממוחשבת בחזה מעקב (CT) או טומוגרפיה פליטת פוזיטרונים (PET / CT) סריקה 8-12 שבועות לאחר פגישת הטיפול האחרונה. הגדר את הישנות מקומית כמו הישנות באתר של הטיפול ואת הישנות אזורית כמו הישנות mediastinum, hilum, או fossa supraclavicular. </li></ol>

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The authors have nothing to disclose.

<html> כתב היד שלנו מתמקדת בניהול הישנויות mediastinal ו hilar המבודדים של סרטן הריאות בחולים שאצלם יותר קרינה היא לא אופציה. תחולת IMHR היא כ -9% 11. אפשרויות טיפול שונות נסות בחולים אלו, כוללים כימותרפיה פליאטיבי, הקרנות קרן חיצונית יותר, או טיפול ומעקב תומך. במוסד שלנו...

סרטן הריאות הוא הסרטן הנפוץ בעולם בשני הגברים ונשים והחשבונות עבור 1 ב 5 מכלל מקרי המוות הקשורה לסרטן. יש לו שיעור תמותה של 0.87 1, 2. הישנות לאחר טיפול ראשוני ואחראית למרבית מקרי מוות בחולים עם סרטן ריאות. אפשרויות טיפוליות לסרטן ריאות חוזרות מוגבלות. סרטן הריאות חוזר מוביל גם ירידת ערך משמעותי באיכות חיים לשחיקה מטפלת משמעותית ומחייב טיפול תומך נוסף, שכולן להקטין את הסבירות של קבלה וסובלנות כדי התערבויות נוספות 3. קרוב ל -30% מחולים עם NSCLC יש ישנות locoregional לאחר קרינת 4. אפשרויות טיפול בחולים אלה מוגבלות וכוללות כימותרפיה מערכתית, אשר יש שיעור תגובה אובייקטיבי של 10% בלבד 5, 6.למרות קרינת חזה חוזרת אינה ריאלית, זה נחקר בעיקר למטרות פליאטיבי והקלת סימפטום ולא שמש במשך פוגה במחלה 3. במוסד שלנו, כל החולים עם הישנות mediastinal ומבודד hilar (IMHR) נגיש באמצעות ברונכוסקופיה טופלו אולטרסאונד endobronchial (EBUS) -guided הזרקת intratumoral transbronchial של ציספלטין (ITC). טיפול במקביל כימותרפיה מערכתית ו / או הקרנות קרן חיצונית (EBRT) הותר על פי &#39;discretions אונקולוגים בטיפול. כתב יד זה מדגיש את הבטיחות, יעילות, היתכנות, ושיטות מפורטות של הפרוטוקול המשמש במוסד שלנו.

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			<td colspan="2" height="20" style="height:20px;width:261px;">Bronchoscope</td>
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			<td colspan="2" height="20" style="height:20px;">22 Guage olympus EBUS needle</td>
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			<td colspan="2" height="20" style="height:20px;">40 g of cisplatin in 40 mls of normal saline</td>
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endobronchial ultrasound-guided intratumoral injection of cisplatin for the treatment of isolated mediastinal recurrence of lung cancer

hilar מבודד והישנות mediastinal (IMHR) לאחר טיפול קרינה קרן חיצונית (EBRT) בחולים עם סרטן ריאות היא תופעה שכיחה. חולים אלה אין אפשרויות טיפול רבות מוצעות בדרך כלל כימותרפיה פליאטיבי או טיפול תומך הטוב ביותר. אולטרסאונד Endobronchial (EBUS) -guided הזרקת intratumoral של ציספלטין (ITC) היא גישה חדשנית עבור חולים אלה. ההליך מבוצע תחת הרדמה מודעת. הנגע ממוקם עם ברונכוסקופיה באמצעות EBUS, ומחט EBUS 22-מד היא מתקדמת דרך תעלת העבודה של היקף ונעל בעמדה. בהנחיית אולטרסאונד, קיר עץ tracheobronchial הוא נקב ואת המחט מועברת לתוך נגע היעד. את stylet מחט מוסר מכן ו- cisplatin (40 מ&quot;ג / 40 מ&quot;ל) מוזרק לתוך הנגע. אחת לשני אתרי מטופלים בכל הפעלה. פרטי הנוהל מתוארים בסעיף הפרוטוקול של נייר. במרכז שלנו, 50 אתרים טופלו 36 חולים(19 גברים, 17 נשים). הגיל הממוצע של המחזור שלנו היה 61.9 ± 8.5 שנים. בצענו ניתוחים סופיים על 35 חולים ו -41 אתרים. 24/35 (69%) היה תגובה מלאה או חלקית (המשיבים) ואילו 11/35 (31%) אובחנו עם מחלה יציבה או מתקדמת (שלא הגיבו לטיפול). בסך הכל, הישרדות בקבוצה שלנו הייתה 8 חודשים (95% CI של 6-11 חודשים), עם חולים שהגיבו שיש הישרדות טובה יותר באופן משמעותי מאלו שלא.

<html> התגובה נמדדה על ידי הדמית מעקב 8-12 שבועות לאחר הטיפול. התגובה סווגה הפוגה מלאה (CR), הפוגה חלקית (PR), מחלה יציבה (SD), מחלה מתקדמת (PD), או לא מסוגל להעריך את התגובה מבוסס על RECIST 1.1 קריטריונים 8. חולים עם CR ויחסי הציבור הגיבו לטיפול, והאחרים סוו?...

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 אולטראסאונד מונחה הזרקת intratumoral של ציספלטין לטיפול ישן Mediastinal הבודדה של סרטן הריאות

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

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Cancer Research

10.3K Views.  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. 

Video: 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.

נוהלי עבודה של Electrochemotherapy לטיפול גידול בכלבים וחתולים

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

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.

הקמת Assay קולוניזציה הריאה עבור מחזור הגידול ויזואליזציה תאים ברקמות הריאה

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.

ניצול של אולטרסאונד מודרכת מכוון רקמות השרשה הסלולר להקמתה של גידול גרורתי רלוונטי מבחינה ביולוגית 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.

הערכה של כדאיות, בטיחות, דיוק בעצימות גבוהה פוסט מרוכז מכשיר אולטרסאונד לטיפול גרורות בכבד

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.

מכתים אלסטי על פרפין-שקופיות מוטבעות של רקמת סרטן pT3N0M0 קיבה

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.

אולטרה סאונד-הדרכה אורתודפית של הלבלב מורלין אדנוקרצינומה

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.

זלוף ואינפלציה של ריאת העכבר עבור היסטולוגיה גידול

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.

ניתוח פתולוגי של גרורות ריאות בעקבות הזרקת וריד זנב לרוחב של תאים סרטניים

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.

מידול גרורות מוח באמצעות הזרקה תוך גולגולתית והדמיית תהודה מגנטית

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.

מידול גרורות במוח באמצעות הזרקת ורידים בזנב של תאי סרטן שד דלקתיים

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 ...