scholarly journals Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models

2016 ◽  
Vol 241 (3) ◽  
pp. 362-374 ◽  
Author(s):  
Victoria L Bridgeman ◽  
Peter B Vermeulen ◽  
Shane Foo ◽  
Agnes Bilecz ◽  
Frances Daley ◽  
...  
Keyword(s):  
Lung Metastasis ◽  
Human Lung ◽  
Lung Metastases ◽  
Angiogenic Therapy ◽  
Metastasis Models

scholarly journals Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Tong Shen ◽  
Jing-Lin Liu ◽  
Chu-Yi Wang ◽  
Youlutuziayi Rixiati ◽  
Shi Li ◽  
...  
Keyword(s):  
B Cells ◽  
Lung Metastasis ◽  
Lung Metastases ◽  
Pdz Domain ◽  
Clinical Samples ◽  
Key Factors ◽  
Combined Use ◽  
Iga Production

AbstractThe mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear. Here, using clinical samples from lung metastases of CRC patients, we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC. Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin, one member of the leucine-rich repeat and PDZ domain (LAP) family, was involved in the lung metastases. Erbin deletion in B cells suppressed lung metastasis of CRC in vivo. And, deletion of Erbin in B cells enhanced the killing effects of CD8+ T cells on tumor cells. Mechanistically, Erbin knockout attenuated TGFβ-mediated suppression of migration of CXCR5+ IgA+ cells and STAT6-mediated PD1 expression. Our study uncovered a key role of Erbin in regulating PD1+ IgA+ B cells in lung metastasis of CRC. Targeting Erbin as well as combined use of neutralizing B cells and antibodies neutralizing PD1 suppresses lung metastasis of CRC in mice, suggesting the potential option for treatment of lung metastasis of CRC.

scholarly journals Risk Analysis for Pulmonary Metastasis of Chondrosarcoma and Establishment and Validation of Novel Clinical Prediction Models: a Clinical Study Based on the SEER Database

2020 ◽  
Author(s):  
Wenle LI ◽  
WANG Hao-sheng ◽  
NING Li-Jun ◽  
GAO Sen ◽  
ZHANG Wen-shi ◽  
...  
Keyword(s):  
Lung Metastasis ◽  
Prediction Models ◽  
Lung Metastases ◽  
Training Group ◽  
Clinical Impact ◽  
Individual Risk ◽  
Seer Database ◽  
Validation Group ◽  
Decision Curve Analysis ◽  
The Individual

Abstract Objective: Lung metastasis of chondrosarcoma is associated with poor prognosis. The purpose of this study was to develop and validate the nomogram to predict the risk of lung metastasis in patients with chondrosarcoma, thus contributing to clinical diagnosis and treatment.Methods: Data on chondrosarcoma patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016 were then screened by univariate and multivariate Logistic regression to construct a Nomogram predicting lung metastasis risk. Nomogram model discrimination was assessed by calibration charts, while prediction accuracy and clinical values were measured by decision curve analysis (DCA) and clinical impact charts. In addition, the predicted Nomogram were validated in the internal test set. Results: A total of 944 patients were enrolled and randomly divided into the training group (n=664) and the validation group (n=280) in a ratio of 7 to 3.After logistics regression analysis, significant variables were gender, age, marital status, tumor volume and lymphatic metastasis. Calibration curves show consistency between Nomogram predictions and actual observations, while DCA and clinical impact diagrams show the clinical utility of Nomogram. In addition, ROC also showed good discrimination and calibration in the training group (AUC = 0.789, 95%CI 0.789 -- 0.808) and the validation group (AUC = 0.796, 95%CI 0.744 -- 0.841).Conclusions: Nomogram for lung metastases in chondrosarcoma can effectively predict the individual risk of lung metastases and provide clinicians with enlightening information to optimize treatment.

Cavitation of Lung Metastases from Bladder Cancer. Report of two Cases

1993 ◽  
Vol 79 (2) ◽  
pp. 141-143 ◽  
Author(s):  
Javier C. Angulo ◽  
José I. Lopez ◽  
Nicolas Flores
Keyword(s):  
Bladder Cancer ◽  
Differential Diagnosis ◽  
Lung Metastasis ◽  
Pulmonary Nodule ◽  
Lung Metastases

We describe 2 cases of cavitary lung metastasis from bladder cancer and retrospectively analyze the frequency of such an event in our environment. Although rare, this finding is not exceptional and should be taken into account when clinicians and oncologists face the differential diagnosis of pulmonary cavitation. Moreover, a cavitary pulmonary nodule may also be the presenting sign of bladder cancer.

scholarly journals Erythrocyte leveraged chemotherapy (ELeCt): Nanoparticle assembly on erythrocyte surface to combat lung metastasis

2019 ◽  
Vol 5 (11) ◽  
pp. eaax9250 ◽  
Author(s):  
Zongmin Zhao ◽  
Anvay Ukidve ◽  
Yongsheng Gao ◽  
Jayoung Kim ◽  
Samir Mitragotri
Keyword(s):  
Lung Metastasis ◽  
Late Stage ◽  
Chemotherapeutic Drugs ◽  
Drug Nanoparticles ◽  
Limited Efficacy ◽  
Erythrocyte Surface ◽  
Substantial Inhibition ◽  
Metastasis Models ◽  
Inhibition Of Tumor Growth ◽  
Tumor Accumulation

Despite being the mainstay of cancer treatment, chemotherapy has shown limited efficacy for the treatment of lung metastasis due to ineffective targeting and poor tumor accumulation. Here, we report a highly effective erythrocyte leveraged chemotherapy (ELeCt) platform, consisting of biodegradable drug nanoparticles assembled onto the surface of erythrocytes, to enable chemotherapy for lung metastasis treatment. The ELeCt platform significantly extended the circulation time of the drug nanoparticles and delivered 10-fold higher drug content to the lung compared with the free nanoparticles. In both the early- and late-stage melanoma lung metastasis models, the ELeCt platform enabled substantial inhibition of tumor growth that resulted in significant improvement of survival. Further, the ELeCt platform can be used to deliver numerous approved chemotherapeutic drugs. Together, the findings suggest that the ELeCt platform offers a versatile strategy to enable chemotherapy for effective lung metastasis treatment.

Percutaneous radiofrequency ablation of inoperable pulmonary metastases from colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3502-3502
Author(s):  
T. D. Yan ◽  
J. King ◽  
D. Glenn ◽  
K. Steinke ◽  
D. L. Morris
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Radiofrequency Ablation ◽  
Lung Metastasis ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Prognostic Parameters ◽  
Percutaneous Radiofrequency Ablation

3502 Background: This current study was an open, prospective and nonrandomized phase II study, which critically evaluated the prognostic parameters for local disease-free survival (DFS) and overall survival (OS) in patients who underwent percutaneous radiofrequency ablation (RFA) for inoperable colorectal pulmonary metastases (CRPM). Methods: The inclusion criteria were patients who had inoperable CRPM, due to number, distribution, poor performance status or patients’ refusal to accept surgery. The exclusion criteria were lesions > 6 per hemithorax; diameter of metastases > 5 cm; bleeding diathesis; and/or significantly compromised lung function. All patients underwent percutaneous RFA with a radiological clear margin of at least 2 cm. The end-points of this study were local DFS and OS, determined from the time of RFA intervention. Ten clinical and six treatment-related prognostic parameters were assessed in univariate and multivariate analyses. All patients were reviewed at one week, one month and every three months thereafter with chest CT. Fifty-five patients entered into the study. The follow-up was complete and the median follow-up was 24 months (6 to 40). Results: The median local DFS was not reached and 2-year local DFS was 57%. Univariate analysis demonstrated that largest size of lung metastasis, location of lung metastases, post-RFA CEA at 1 month and 3 months were significant for local DFS. In multivariate analysis, largest size of lung metastasis of ≤ 3 cm and post-RFA CEA of ≤ 5 ng/ml at 1 month were independently associated with an improved local DFS. The median OS was 33 months (4 to 40), with 1-, 2-, and 3-year survival of 85%, 64% and 46%, respectively. Univariate analysis demonstrated that interval between the diagnoses of colorectal cancer and pulmonary metastasis; largest size of lung metastasis and location of lung metastases were significant for OS. In multivariate analysis, only size of lung metastasis of ≤ 3 cm was independently associated with an improved OS. Conclusions: Percutaneous RFA of inoperable CRPM may have a useful role in patients with a lesion of ≤ 3 cm. No significant financial relationships to disclose.

scholarly journals Characterization of human follicular thyroid cancer cell lines in preclinical mouse models

2016 ◽  
Vol 5 (2) ◽  
pp. 47-54 ◽  
Author(s):  
Ashley N Reeb ◽  
Andrea Ziegler ◽  
Reigh-Yi Lin
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Lung Metastasis ◽  
Lung Metastases ◽  
Metastatic Potential ◽  
Follicular Thyroid Cancer ◽  
Tail Vein ◽  
Tail Vein Injection ◽  
Injection Model

Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

R413 – KITENIN Enhances Invasion and Metastasis in FOM Cancer Model

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P181-P182
Author(s):  
Joon Kyoo Lee
Keyword(s):  
Squamous Cell Carcinoma ◽  
Salivary Gland ◽  
Cell Carcinoma ◽  
Lung Metastasis ◽  
Squamous Cell ◽  
Tumor Invasion ◽  
Lung Metastases ◽  
Cancer Model ◽  
Floor Of Mouth ◽  
Diffuse Lung

Problem KAI1 is a metastatic suppressor gene. The expression of KAI1 in cancer cells results in reduced cell motility and invasiveness. A cDNA clone of VANGL1, a member of the tetraspanin protein family that specifically interacts with the COOH-terminal cytoplasm domain of KAI1, was isolated and renamed KITENIN (KAI1 COOH-terminal interacting tetraspanin). KITENIN is reported to promote metastasis in a mouse colon cancer model. The purpose of this study was to investigate tumor invasiveness and early lung metastasis by KITENIN in murine floor of mouth cancer model. Methods The cDNA of KITENIN and the vector only were transfected into the SCC VII (mouse squamous cell carcinoma cell line) cells. The transfections were performed using the FuGENE 6 transfection reagent. The suspension of 5 × 105/? viable KITENIN- or vector-transfected SCC VII cells were injected into the floor of mouth of C3H/HeJ syngeneic mice deep to the mylohyoid muscle via an intra-oral approach. From the 1st week to 6th week after injection, tumor, lung, liver, and brain tissues were obtained from six mice each group every week and were evaluated under the light microscope. Results On each group, the tumor invaded to superficial musculature of floor of mouth, deep musculature of floor of mouth, salivary gland, perineural tissue, bone, and skin sequentially. Lung metastases started from peripheral and localized region and moved to central and diffuse lung tissues. Earlier and more aggressive tumor invasion to deep floor of mouth musculature, salivary gland, perineural tissue, bone, and skin was observed in KITENIN-transfected group than in vector group. Earlier and more diffuse lung metastasis was observed in KITENIN group. Conclusion KITENIN enhanced tumor invasion and lung metastasis in murine floor of mouth squamous carcinoma model. Significance An antisense KITENIN strategy could be used to inhibit distant metastasis and progression in head and neck squamous cell carcinoma. Support This study was supported by a grant CUHRICM-CRI07038-1.

scholarly journals Amelioration of B16F10 melanoma lung metastasis in mice by a combination therapy with indomethacin and interleukin 2.

1987 ◽  
Vol 165 (1) ◽  
pp. 14-28 ◽  
Author(s):  
R S Parhar ◽  
P K Lala
Keyword(s):  
Combination Therapy ◽  
Lung Metastasis ◽  
Lung Metastases ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Cell Phenotype ◽  
B16f10 Melanoma ◽  
Killer Activity ◽  
Tumor Bearing

Our earlier work revealed that PGE-mediated inactivation of NK cells in tumor-bearing mice by host macrophages promoted spontaneous lung metastasis that could be prevented or ameliorated by chronic indomethacin therapy. Since PGE was found to suppress the in vitro development and/or activation of a family of tumoricidal lymphocytes such as CTL, NK, and LAK cells by one or both of two mechanisms, that is to say, a down regulation of IL-2-R and an inhibition of IL-2 production, the present study tested whether a combined therapy with indomethacin and IL-2 was more effective than one with indomethacin or IL-2 alone in ameliorating established experimental lung metastasis. B6 mice injected intravenously with 10(6) highly metastatic B16F10 melanoma cells showed profuse micrometastases in the lungs by day 5, and macrometastases by day 10 which were confluent on day 21. Chronic indomethacin therapy by the oral route (14 micrograms/ml in drinking water) starting on day 0 or day 5, or a single round of IL-2 therapy (25,000 U rIL-2, every 8 h for 5 d on days 10-14) reduced the number of metastatic nodules by two-thirds (from a median of 473 in control mice receiving vehicles alone) by day 21. A single round of IL-2 as above, combined with either protocol of indomethacin therapy, completely or nearly completely irradicated the lung metastases, corroborated by a histological examination. An evaluation of splenic killer cell activity measured with a 4-h 51Cr-release assay against NK-sensitive YAC-1 lymphoma and B16F10 melanoma or NK-resistant thymic lymphoma 9705 targets revealed negligible activity in control tumor-bearing mice, and a good restoration of activity against NK-sensitive targets with either protocols of indomethacin therapy. IL-2 alone or a combination of IL-2 and indomethacin given by either protocol generated strong killer activity against all these targets, most marked with the combination therapy. Splenic killer cell phenotype in normal as well as all treated animals was ASGM1+, Thy-1-, and Lyt-2-. The combination therapy resulted in the strongest mononuclear cell infiltration in the lungs, with areas of young granulation tissue suggestive of repair sites of original metastases.

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