Targeting Liposomes to Metastatic Tumors with Antibodies Specific for VCAM-1

Metastatic cancer disease is the major cause of death in cancer patients. Because those small secondary tumors are clinically hardly detectable in their early stages, little is known about drug biodistribution and permeation into those metastatic tumors potentially contributing to insufficient clinical success against metastatic disease. Our recent studies indicated that breast cancer liver metastases may have compromised perfusion of intratumoral capillaries hindering the delivery of therapeutics for yet unknown reasons. To understand the microcirculation of small liver metastases, we have utilized computational simulations to study perfusion and oxygen concentration fields in and around the metastases smaller than 700 µm in size at the locations of portal vessels, central vein, and liver lobule acinus. Despite tumor vascularization, the results show that blood flow in those tumors can be substantially reduced indicating the presence of inadequate blood pressure gradients across tumors. A low blood pressure may contribute to the collapsed intratumoral capillary lumen limiting tumor perfusion that phenomenologically corroborates with our previously published in vivo studies. Tumors that are smaller than the liver lobule size and originating at different lobule locations may possess a different microcirculation environment and tumor perfusion. The acinus and portal vessel locations in the lobule were found to be the most beneficial to tumor growth based on tumor access to blood flow and intratumoral oxygen. These findings suggest that microcirculation states of small metastatic tumors can potentially contribute to physiological barriers preventing efficient delivery of therapeutic substances into small tumors.

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CT Simplified Radiomic Approach to Assess the Metastatic Ductal Adenocarcinoma of the Pancreas

Cancers ◽

10.3390/cancers13081843 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1843

Author(s):

Mirko D’Onofrio ◽

Riccardo De Robertis ◽

Gregorio Aluffi ◽

Camilla Cadore ◽

Alessandro Beleù ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Ductal Adenocarcinoma ◽

Newly Diagnosed ◽

Inclusion Criteria ◽

Permeability Index ◽

Metastatic Tumors ◽

Qualitative And Quantitative ◽

Portal Phase ◽

Phase Images ◽

Adenocarcinoma Of The Pancreas

The aim of this study was to perform a simplified radiomic analysis of pancreatic ductal adenocarcinoma based on qualitative and quantitative tumor features and to compare the results between metastatic and non-metastatic patients. A search of our radiological, surgical, and pathological databases identified 1218 patients with a newly diagnosed pancreatic ductal adenocarcinoma who were referred to our Institution between January 2014 and December 2018. Computed Tomography (CT) examinations were reviewed analyzing qualitative and quantitative features. Two hundred eighty-eight patients fulfilled the inclusion criteria and were included in this study. Overall, metastases were present at diagnosis in 86/288 patients, while no metastases were identified in 202/288 patients. Ill-defined margins and a hypodense appearance on portal-phase images were significantly more common among patients with metastases compared to non-metastatic patients (p < 0.05). Metastatic tumors showed a significantly larger size and significantly lower arterial index, perfusion index, and permeability index compared to non-metastatic tumors (p < 0.05). In the management of pancreatic ductal adenocarcinoma, early detection and correct staging are key elements. The study of computerized tomography characteristics of pancreatic ductal adenocarcinoma showed substantial differences, both qualitative and quantitative, between metastatic and non-metastatic disease.

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Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression

Nature Immunology ◽

10.1038/s41590-021-00930-4 ◽

2021 ◽

Author(s):

Raoul J. P. Bonnal ◽

Grazisa Rossetti ◽

Enrico Lugli ◽

Marco De Simone ◽

Paola Gruarin ◽

...

Keyword(s):

Disease Progression ◽

Metastatic Tumors

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Selectively Potentiating Hypoxia Levels by Combretastatin A4 Nanomedicine: Toward Highly Enhanced Hypoxia‐Activated Prodrug Tirapazamine Therapy for Metastatic Tumors

Advanced Materials ◽

10.1002/adma.201805955 ◽

2019 ◽

Vol 31 (11) ◽

pp. 1805955 ◽

Cited By ~ 50

Author(s):

Shengcai Yang ◽

Zhaohui Tang ◽

Chenyang Hu ◽

Dawei Zhang ◽

Na Shen ◽

...

Keyword(s):

Metastatic Tumors ◽

Combretastatin A4

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Opportunities and Challenges for Analyzing Cancer Data at the Inter- and Intra-Institutional Levels

JCO Precision Oncology ◽

10.1200/po.19.00394 ◽

2020 ◽

pp. 743-756

Author(s):

Julie Wu ◽

Jordan Bryan ◽

Samuel M. Rubinstein ◽

Lucy Wang ◽

Michele Lenoue-Newton ◽

...

Keyword(s):

Clinical Data ◽

Information Exchange ◽

Cancer Center ◽

Bipartite Network ◽

Genotypic Differences ◽

Cancer Type ◽

Sample Type ◽

Metastatic Tumors ◽

Institutional Level ◽

Cancer Data

PURPOSE Our goal was to identify the opportunities and challenges in analyzing data from the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE), a multi-institutional database derived from clinically driven genomic testing, at both the inter- and the intra-institutional level. Inter-institutionally, we identified genotypic differences between primary and metastatic tumors across the 3 most represented cancers in GENIE. Intra-institutionally, we analyzed the clinical characteristics of the Vanderbilt-Ingram Cancer Center (VICC) subset of GENIE to inform the interpretation of GENIE as a whole. METHODS We performed overall cohort matching on the basis of age, ethnicity, and sex of 13,208 patients stratified by cancer type (breast, colon, or lung) and sample site (primary or metastatic). We then determined whether detected variants, at the gene level, were associated with primary or metastatic tumors. We extracted clinical data for the VICC subset from VICC’s clinical data warehouse. Treatment exposures were mapped to a 13-class schema derived from the HemOnc ontology. RESULTS Across 756 genes, there were significant differences in all cancer types. In breast cancer, ESR1 variants were over-represented in metastatic samples (odds ratio, 5.91; q < 10−6). TP53 mutations were over-represented in metastatic samples across all cancers. VICC had a significantly different cancer type distribution than that of GENIE but patients were well matched with respect to age, sex, and sample type. Treatment data from VICC was used for a bipartite network analysis, demonstrating clusters with a mix of histologies and others being more histology specific. CONCLUSION This article demonstrates the feasibility of deriving meaningful insights from GENIE at the inter- and intra-institutional level and illuminates the opportunities and challenges of the data GENIE contains. The results should help guide future development of GENIE, with the goal of fully realizing its potential for accelerating precision medicine.

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Risk of Metastatic Ovarian Involvement in Nongynecologic Malignancies

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182332cd1 ◽

2012 ◽

Vol 22 (1) ◽

pp. 3-8 ◽

Cited By ~ 4

Author(s):

Kidong Kim ◽

Soo Youn Cho ◽

Sang-Il Park ◽

Hye Jin Kang ◽

Beob-Jong Kim ◽

...

Keyword(s):

Overall Survival ◽

Malignant Tumors ◽

Rank Test ◽

Benign Tumors ◽

Binary Logistic Regression Analysis ◽

Fisher Exact Test ◽

Tumor Type ◽

Metastatic Tumors ◽

Number Of Patients ◽

Adnexal Tumors

ObjectiveThe objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors.MethodsThe eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test.ResultsIn 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers.ConclusionOne hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

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