Photofrin Uptake as a Function of Tumor Size and the Detection of Microscopic Nests of Tumor Cells by Photofrin Fluorescence

1996 ◽  
pp. 123-128
Author(s):  
W. R. Potter ◽  
D. A. Bellnier
Keyword(s):  
Tumor Cells ◽  
Tumor Size

P13.15 Pre-clinical trial of T601 oncolytic virus for high grade glima via intra-tumoral injection

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii35-ii36
Author(s):  
Z He ◽  
Z Meng ◽  
P Liang ◽  
L Xing ◽  
X Zheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Viability ◽  
Tumor Cells ◽  
Tumor Size ◽  
Side Effect ◽  
Combined Treatment ◽  
Nucleotide Metabolism ◽  
Cell Counting ◽  
High Grade ◽  
Acceptable Side

Abstract BACKGROUND An effective therapeutic method still hasn’t been devised for lethal high grade glioma. Thus, a method with high anti-tumoral efficiency, tumoral targeting, and acceptable side effect needs to be designed. Oncolytic virotherapy which can specifically lyse tumor cells via mass replication and deleting nucleotide metabolism related gene, like TK, required in viral replication and overexpressed in tumor cells, provides hope for patients. However, the virus only contained TK deletion is unable to show sufficient specificity of anti-tumoral response in tumor cells. Here, the adapted strain of vaccinia virus with high tumoral specificity due to TK and RR deletion and FUC1 insertion, named T601, is chosen in this project. In clinical application, intra-tumoral injection showed improved anti-tumoral efficiency and acceptable side effect. However, intra-tumoral viral injection in orthotropic glioma model is rare. In this project, various biosafety and antitumoral efficiency parameter would be tested for confirming the biosafety and reliability of intra-tumoral T601 viral injection for future clinical trials. MATERIAL AND METHODS For measuring the IC50 of T601, 10 different amounts of virus was tested in vitro via calculating cell viability with CCK-8(cell counting kit-8). For measuring the further antitumoral response of FCU1, different concentration of the 5-FC was added into the medium with IC50 viral amount. To ensure the biosafety of T601, MTD (maximum tolerance dose) was measured. Based on the MTD result, for evaluating the anti-tumoral efficiency, 106 pfu,105 pfu,104 pfu of virus was intra-tumoral injected in orthotopic GBM bearing mice. Tumor size was measured once a week through in vivo bioimaging system. RESULTS 0.022 MOI, the IC50 of T601, showed high cytotoxicity of T601. Moreover, the significantly decreased cell viability under the combined treatment of 5-FC and 0.22MOI T601 showed intact anti-tumoral function. In MTD assay, except for 107 group, no significant weight loss was found. However, in 107 pfu group, mean body weight decreased around 10% and animal fatality happened on day 9. According to the MTD result, certain amount of virus was intra-tumorally injected. In all treatment group, the tumor size was significantly shrined. At the same time, the survival rate of mice under viral treatment was significantly extended. CONCLUSION In summary, T601 exhibited efficient anti-tumoral function and acceptable side effect. T601 treatment prolonged the survival period of GBM mice with acceptable neurotoxicity, demonstrating that T601 contains necessary criterial for intra-tumoral injection. Ultimately, this project provided basic reference information of dose for future clinical trial.

Immediate post-thermal ablation biopsy of colorectal liver metastases to predict oncologic outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4602-4602
Author(s):  
Nikiforos Vasiniotis Kamarinos ◽  
Efsevia Vakiani ◽  
Mithat Gonen ◽  
Nancy E. Kemeny ◽  
Anne M. Covey ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Cells ◽  
Tumor Size ◽  
Thermal Ablation ◽  
Colorectal Liver Metastases ◽  
Univariate Analysis ◽  
Contrast Material ◽  
Maximum Diameter ◽  
Minimal Risk ◽  
Viable Tumor

4602 Background: Thermal ablation (TA) is used as a local cure for selected colorectal liver metastases (CLM) with minimal risk. A critical limitation of TA has been early local tumor progression (LTP). The goal of this study is to establish the role of ablation zone (AZ) biopsy in predicting LTP. Methods: This institutional review board-approved prospective study included patients with CLM of 5cm or less in maximum diameter, with confined liver disease or stable, limited extrahepatic disease. Both radiofrequency(RF) and microwave(MW) ablation modalities were used. A biopsy of the center and margin of the AZ was performed immediately after ablation. The applicators were also examined for the presence of viable tumor cells. All samples containing morphologically identified tumor cells were further interrogated with immunohistochemistry to determine the proliferative and viability potential of the detected tumor cells. Ablation margin size was evaluated on the first CT scan performed 4–8 weeks after ablation and was confirmed by 3D assessment with Ablation Confirmation Software (Neuwave™). Variables were evaluated as predictors of time to LTP with the competing-risks model (uni- and multivariate analyses). Results: Between November 2009 and February 2019, 102 patients with 182 CLMs were enrolled. Mean tumor size was 2.0 cm (range, 0.6–4.8 cm). MW was used in 95/182 (52%) tumors and RF in 87/182 (48%). Median follow-up was 19 months. Technical effectiveness was evident in 178/182 (97%) ablated tumors on the first contrast material–enhanced CT at 4–8-weeks post-ablation. The cumulative incidence of LTP at 12 months was 19% (95% confidence interval [CI]: 14, 27). Samples from 64 (35%) of the 178 technically successful cases contained viable tumor. At univariate analysis, tumor size, minimal margin size, and biopsy results were significant in predicting LTP. In a multivariate model, margin size of less than 5 mm (P < .001; hazard ratio [HR], 4.3), and positive biopsy results (P = .02; HR, 1.8) remained significant. LTP within 12 months after TA was noted in 3% (95% CI: 1, 6) of tumor-negative biopsy CLMs with margins of at least 5 mm. Conclusions: Biopsy and pathologic examination of the AZ predicts LTP regardless of TA modality used. This can optimize ablation as a potential local cure for patients with limited CLM.

scholarly journals Assessment of the Efficient Strategies for Applying Antitumor Viral Vaccine Therapy Based On Mathematical Modeling

2019 ◽  
Vol 14 (1) ◽  
pp. 34-53 ◽  
Author(s):  
N.A. Babushkina ◽  
E.A. Kuzina ◽  
A.A. Loos ◽  
E.V. Belyaeva
Keyword(s):  
Mathematical Model ◽  
Immune Response ◽  
Tumor Cells ◽  
Tumor Size ◽  
Single Shot ◽  
Complete Elimination ◽  
Antitumor Therapy ◽  
Viral Vaccine ◽  
Two Stages ◽  
The Mathematical Model

The paper presents the mathematical description of the two stages of tumor cells’ death as a result of immune response after antitumor viral vaccine introduction. This mathematical description is presented by the system of nonlinear equations implemented in the MatLab-Simulink system. As a result of the computing experiment, two strategies for effective application of the antitumor viral vaccine were identified. The first strategy leads to complete elimination of the tumor cells after a single-shot administration of the vaccine. The second strategy makes it possible to stabilize tumor size through the recurrent introductions of the vaccine. Using the mathematical model of antitumor therapy, appropriate dosages were identified based on the number of tumor cells that die at the two stages of immune response. Dynamics of tumor growth for the two strategies of the viral vaccine application was forecasted based on the mathematical model of antitumor therapy with discontinuous trajectories of tumor growth. The computing experiments made it possible to identify initial tumor size at the start of the therapy and the dosages that allow complete elimination of the tumor cells after the single-shot introduction. For the second strategy, dosages and intervals between recurrent vaccine introductions required to stabilize tumor size at the initial level were also identified. The proposed approach to exploring the effectiveness of vaccine therapy may be applied to different types of experimental tumors and antitumor vaccines.

scholarly journals MODERN METHODS OF DIAGNOSIS OF MAMMARY TUMOR AND TUMOR-LIKE LESIONS IN CATS

THE BULLETIN ◽  
2021 ◽  
Vol 3 (391) ◽  
pp. 33-39
Author(s):  
G.P. Dyulger ◽  
P.G. Dyulger ◽  
O. Alikhanov ◽  
E.S. Latynina ◽  
D.A. Baimukanov
Keyword(s):  
Prognostic Factors ◽  
Growth Factor ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Tumor Size ◽  
Clinical Stage ◽  
Distant Metastases ◽  
Regional Lymph Nodes ◽  
Tnm System ◽  
High Level

The paper provides an overview of the classification and diagnosis of feline mammary tumors (FMT) in cats. The clinical stage of neoplastic process is one of the driving prognostic factors. In accordance with the WHO recommendations 1980, it is determined by the TNM system: the size of neoplasm, the state of regional lymph nodes and the presence/absence of distant metastases. The clinical stage of the disease is defined based on the obtained data during the examination, surgery and study of the postoperative material (excised tumor, the edges of the resection and regional lymph nodes). It was found that tumors larger than 3 cm have a significantly worse prognosis than tumors smaller than 3 cm. The median survival with a tumor size of less than 3 cm is 1.75 times greater (21 months versus 12 months) than with a tumor size of more than 3 cm. The most significant morphological prognostic factor is the histological type of malignant tumor and the histological gradation of tumor tissue. Among carcinomas, the most invasive are micropapillary, solid and cribriform carcinomas, the most unaggressive is carcinoma in situ. Adverse prognostic factors of mammary cancer in cats are a high Ki67 index of proliferative activity, hyperexpression of Her-2 epidermal growth factor, cyclooxygenase-2, absence or low level of expression of receptors to estrogen and/or progesterone by tumor cells (less than 10%), as well as a high level of expression by tumor cells of VEGF (vascular endothelial growth factor).

scholarly journals Detection of Circulating Tumor Cells in Renal Cell Carcinoma: Disease Stage Correlation and Molecular Characterization

2020 ◽  
Vol 9 (5) ◽  
pp. 1372
Author(s):  
Petr Klezl ◽  
Eliska Pospisilova ◽  
Katarina Kolostova ◽  
Jindrich Sonsky ◽  
Ondrej Maly ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Renal Cell Cancer ◽  
Tumor Size ◽  
Renal Cell ◽  
Cell Cancer ◽  
Functional Characterization ◽  
Disease Stage ◽  
Mitochondrial Activity ◽  
Size Based Separation

The presence of circulating tumor cells (CTCs) in patients with solid tumors is associated with poor prognosis. However, there are limited data concerning the detection of CTCs in renal cell cancer (RCC). The aim of this study is to evaluate the presence of CTCs in peripheral blood of patients with RCC undergoing surgery (n = 186). CTCs were tested before and after surgery as well as during the follow-up period afterwards. In total 495 CTC testing in duplicates were provided. To enrich CTCs, a size-based separation protocol and tube MetaCell® was used. CTCs presence was evaluated by single cell cytomorphology based on vital fluorescence microscopy. Additionally, to standardly applied fluorescence stains, CTCs viability was controlled by mitochondrial activity. CTCs were detected independently on the sampling order in up to 86.7% of the tested blood samples in patients undergoing RCC surgery. There is higher probability of CTC detection with growing tumor size, especially in clear cell renal cell cancer (ccRCC) cases. Similarly, the tumor size corresponds with metastasis presence and lymph node positivity and CTC detection. This paper describes for the first-time successful analysis of viable CTCs and their mitochondria as a part of the functional characterization of CTCs in RCC.

scholarly journals Hmgb1-IL-23-IL-17-IL-6-Stat3 Axis Promotes Tumor Growth in Murine Models of Melanoma

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Qiu Tang ◽  
Jian Li ◽  
Hongfei Zhu ◽  
Pan Li ◽  
Zhenwei Zou ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Tumor Size ◽  
Immune Surveillance ◽  
Tumor Development ◽  
Murine Models ◽  
Wild Type ◽  
Proliferating Cells ◽  
Melanoma Tumor ◽  
Tumor Bearing

In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, IL-17 deficiency results in reduced melanoma tumor size, diminished numbers of proliferating cells and blood vessels, and decreased percentage of CD11b+Gr-1+MDSCs in tumor tissues. IL-17 promotes IL-6 induction and Stat3 activation. Treatment of Stat3 inhibitor WP1066 in B16-F10 tumor cells inoculated wild-type mice inhibits tumor growth. Additional administration of recombinant IL-6 into B16-F10 tumor-bearing IL-17−/−mice results in markedly increased tumor size and p-Stat3 expression, whereas additional recombinant IL-17 administration into B16-F10 tumor-bearing wild-type mice treated with anti-IL-6 mAb does not significantly alter the tumor growth and p-Stat3 expression. In our further study, blockade of Hmgb1-RAGE pathway inhibits melanoma tumor growth and reduces production of IL-23 and IL-17. All these data suggest that Hmgb1-IL-23-IL-17-IL-6-Stat3 axis plays a pivotal role in tumor development in murine models of melanoma, and blocking any portion of this axis will attenuate melanoma tumor growth.

scholarly journals SAT-555 Can Histology Predict the Presence of KCNJ5 Somatic Mutation in Aldosterone-Producing Adenomas?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yuto Yamazaki ◽  
Xin Gao ◽  
Yuta Tezuka ◽  
Kei Omata ◽  
Yoshikiyo Ono ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Somatic Mutation ◽  
Tumor Size ◽  
Scoring System ◽  
Quantitative Methods ◽  
Clear Cell ◽  
Intratumoral Heterogeneity ◽  
Driver Gene ◽  
Wild Type ◽  
Large Tumor

Abstract Aldosterone-producing adenoma (APA) is well known to harbor marked intratumoral heterogeneity in terms of morphology and CYP11B2 (aldosterone synthase) localization. In histology, APA is generally characterized by two distinct cell subtypes, namely “clear cells” and “compact cells”. Clear tumor cells harbor abundant lipid droplets in their cytoplasms and compact tumor cells generally featuring small round shape have abundant intracytoplasmic organelles including mitochondria. Relatively close correlation between these histological characteristics (morphology and CYP11B2 immunohistochemistry) and genotypes of aldosterone-driver gene somatic mutation has been reported. Among them, KCNJ5-mutated APAs have been reported to harbor clear cell predominant features, while APAs with other rare somatic mutations including ATP1A1, ATP2B3 and CACNA1D harbor heterogenous or relatively compact cell predominant morphometry. However, these previous evaluation were based on eyeball analysis with relatively low reproducibility. Therefore, we developed the more quantitative methods using digital image software in order to analyze the widespread area, which can reflect intratumoral heterogeneity, with high reproducibility to analyze the further detailed correlation between histopathological characteristics and genotype in APA. We explored the utility of immunohistochemistry including CYP11B2 and KCNJ5. We further attempted to propose histopathological scoring system to predict the presence of KCNJ5 somatic mutation in APAs. Results of our present study revealed that KCNJ5 was predominantly immunolocalized in zona glomerulosa among adrenal cortex (vs. ZF, P=0.0002, vs. ZR, P=0.0002), furthermore, predominantly in APCCs than in non-APCCs (P=0.0019). Among the tumors, KCNJ5 immunoreactivity was significantly higher in KCNJ5-wild type APAs than in mutated ones (P=0.0037). KCNJ5-mutated APAs had significantly lower nuclear / cytoplasm ratio and abundant clear cell components than those with wild type, harboring large tumor size. In conclusion, we firstly proposed a novel histopathological predicting scoring system for the presence of KCNJ5 somatic mutation, including the following histopathological findings; N/C ratio, clear cell (%), tumor size, CYP11B2 immunoreactivity and KCNJ5 immunoreactivity. It is true that no single histological factors above could precisely predict the presence of KCNJ5 somatic mutation but this newly developed combined histopathological predicting scoring system could provide relatively high accuracy to predict KCNJ5 somatic mutation in APAs (AUC=96%, sensitivity:100%, specificity:90%, 4 points or more). However, further prospective validation by large number of cases is required for clarification.

scholarly journals Antibody-mediated suppression of grafted lymphoma. IV. Influence of time of tumor residency in vivo and tumor size upon the effectiveness of suppression by syngeneic antibody.

1976 ◽  
Vol 144 (5) ◽  
pp. 1274-1283 ◽  
Author(s):  
H S Shin ◽  
J S Economou ◽  
G R Pasternack ◽  
R J Johnson ◽  
M L Hayden
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Size ◽  
Cell Numbers ◽  
Established Tumor ◽  
Mouse Lymphoma

In the suppression of the growth of a mouse lymphoma 6C3HED by antibody, the effectiveness of antibody in suppressing growing or established tumor cells and comparable number of freshly injected tumor cells is quantitatively similar. The effectiveness of antibody diminishes markedly when the number of tumor cells per mouse reaches the level of 10(6) due to the development of a macrophage shortage. At the 10(5) tumor cells level, antibody-mediated suppression takes place in an optimal manner and between 10(5) and 10(4) tumor cell numbers, the amount of antibody required to suppress 50% of the tumor cells is directly proportional to the number of tumor cells suppressed.

Tumor kinetic modeling and identification of predictive factors for tumor response to durvalumab in patients with non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11555-11555
Author(s):  
Yanan Zheng ◽  
Rajesh Narwal ◽  
Chaoyu Jin ◽  
Bing Wang ◽  
Xiaoping Jin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Kinetic Modeling ◽  
Predictive Factors ◽  
Tumor Size ◽  
Tumor Response ◽  
Tumor Killing ◽  
Nsclc Patients

11555 Background: Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80. The primary objectives of this analysis were to describe the longitudinal tumor size profiles and identify the key factors predicting tumor growth and regression following durvalumab. Methods: Longitudinal tumor size data obtained from NSCLC patients in study 1108 (all lines of therapy) and ATLANTIC (third line and beyond) following durvalumab treatment were modeled using nonlinear mixed effect modeling. Tumor kinetics were described by four key parameters: tumor growth and killing rate constants, fraction of durvalumab-sensitive tumor cells, and delay time for tumor killing. Potential predictive factors for tumor growth and regression were evaluated in a multi-variable covariate analysis. The model was used to simulate response rates at different tumor PD-L1 expression cutoffs. Results: Tumor kinetic modeling accurately described the longitudinal tumor response profiles from NSCLC patients in both studies. The factors associated with more rapid tumor growth were liver metastases, ECOG score > 0, high neutrophil-to-lymphocyte ratio and EGFR/ALK mutation. Tumor cell PD-L1 expression, baseline tumor size and smoking history were identified as significant predictive factors for tumor killing or the fraction of sensitive tumor cells. Simulations using the tumor kinetic model showed increased response rates in patients with higher tumor cell PD-L1 expression (increased by 9-11% and 10-14% with 25% and 50% cutoff, respectively), patients receiving durvalumab as first-line therapy (increased by 12% vs. 2nd line/above), and patients with smoking histories (increased by 4-5% vs. non-smokers). Conclusions: Tumor kinetic modeling identified factors that predict tumor progression and response following durvalumab in NSCLC patients. The multivariate analysis accounts for various predictive factors within predictive biomarker strata, allowing better interpretation of different biomarker cutoffs. The modeling technique can potentially guide patient selection/enrichment, clinical trial design strategies and tumor biology. Clinical trial information: NCT02087423 and NCT01693562.

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