scholarly journals A Fractional Modeling of Tumor–Immune System Interaction Related to Lung Cancer with Real Data

2021 ◽  
Vol 137 (1) ◽  
Author(s):  
Fatma Özköse ◽  
Seçil Yılmaz ◽  
Mehmet Yavuz ◽  
İlhan Öztürk ◽  
M. Tamer Şenel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Fractional Order ◽  
Lung Tumor ◽  
Real Data ◽  
Host Cells ◽  
University Hospital ◽  
Tissue Samples ◽  
Macrophage Cells ◽  
Fractional Modeling

AbstractIn this study, we investigate a new fractional-order mathematical model which considers population dynamics among tumor cells-macrophage cells-active macrophage cells, and host cells involving the Caputo fractional derivative. Firstly, the stability of the positive steady state of the model is studied. Subsequently, the conditions for existence and uniqueness of the solutions are examined. Then, the least squares curve fitting method (LSCFM) which is one of the prominent methods for parameter estimation is used to fit the parameters of the model. It is aimed to fit the relevant parameters with the help of the tumor tissue samples which were collected from the patient with non-small cell lung cancer who had chemotherapy-naive hospitalized at Kayseri Erciyes University hospital in Turkey. A total of 12 parameters in the model are estimated using the data of lung tumor cells of this patient for 14 days. Moreover, the numerical simulations are given by considering the different fractional orders and different parameters for the model. So, it is achieved how the change in $$\alpha $$ α affects the dynamic behavior of the system. In the sequel, to point out the advantages of the fractional-order modeling, the memory trace and hereditary traits are taken into consideration. Finally, the interpretations in terms of biological science are provided in conclusion. We believe that this interdisciplinary study will open new doors for other similar studies and will shed light on the studies to be developed on the use of real data in the mathematical modeling of cancer.

scholarly journals FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽  
2021 ◽  
Author(s):  
Yan Lu ◽  
Yushuang Zheng ◽  
Yuhong Wang ◽  
Dongmei Gu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Lung Tumor ◽  
Early Stage ◽  
High Rate ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Metastasis ◽  
Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

scholarly journals Leukotriene B4 receptor-2 contributes to KRAS-driven lung tumor formation by promoting interleukin-6-mediated inflammation

2021 ◽  
Author(s):  
Jae-Hyun Jang ◽  
Donghwan Park ◽  
Guen-soo Park ◽  
Dong-Wook Kwak ◽  
JaeIn Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Interleukin 6 ◽  
Double Mutant ◽  
Lung Tumor ◽  
Leukotriene B4 ◽  
Tumor Formation ◽  
Human Lung Cancer ◽  
Specific Expression ◽  
Tissue Samples ◽  
Attractive Therapeutic Target

AbstractAlthough lung cancer is the leading cause of cancer-related deaths worldwide and KRAS is the most frequently mutated oncogene in lung cancer cases, the mechanism by which KRAS mutation drives lung cancer has not been fully elucidated. Here, we report that the expression levels of leukotriene B4 receptor-2 (BLT2) and its ligand-producing enzymes (5-LOX, 12-LOX) were highly increased by mutant KRAS and that BLT2 or 5-/12-LOX blockade attenuated KRAS-driven lung cell proliferation and production of interleukin-6 (IL-6), a principal proinflammatory mediator of lung cancer development. Next, we explored the roles of BLT2 and 5-/12-LOX in transgenic mice with lung-specific expression of mutant KRAS (KrasG12D) and observed that BLT2 or 5-/12-LOX inhibition decreased IL-6 production and tumor formation. To further determine whether BLT2 is involved in KRAS-driven lung tumor formation, we established a KrasG12D/BLT2-KO double-mutant mouse model. In the double-mutant mice, we observed significantly suppressed IL-6 production and lung tumor formation. Additionally, we observed high BLT2 expression in tissue samples from patients with KrasG12D-expressing lung adenocarcinoma, supporting the contributory role of BLT2 in KRAS-driven human lung cancer. Collectively, our results suggest that BLT2 is a potential contributor to KRAS-driven lung cancer and identify an attractive therapeutic target for KRAS-driven lung cancer.

T-cell–inflamed gene expression profile (GEP) and PD-L1 expression in patients (pts) with esophageal cancer (EC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 26-26
Author(s):  
Torben Steiniche ◽  
Sun Young Rha ◽  
Hyun Cheol Chung ◽  
Jeanette Bæhr Georgsen ◽  
Morten Ladekarl ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Proportional Hazards ◽  
Performance Status ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Tissue Samples

26 Background: GEP and PD-L1 expression have been associated with anti–PD-1/PD-L1 therapy. In this retrospective observational study we explored the prognostic value of GEP and PD-L1 expression in pts with EC receiving standard-of-care therapy (SOC). Methods: Tumor tissue samples collected from 2005 to 2017 were procured from Yonsei Cancer Center (South Korea), Memorial Sloan Kettering Cancer Center (USA) and Aarhus University Hospital (Denmark). GEP score was derived from an 18-gene signature using extracted tumor RNA analyzed by NanoString nCounter; GEP high/intermediate (GEP-H/I) and low were defined by a cutoff of –1.540, consistent with pembrolizumab clinical trials. PD-L1 expression was assessed by PD-L1 IHC 22C3 pharmDx assay (Agilent); positive was defined as combined positive score (CPS) ≥ 10, where CPS is the the number of PD-L1–positive cells (tumor cells, lymphocytes and macrophages) divided by the total number of viable tumor cells, multiplied by 100. Associations of GEP score and PD-L1 expression with clinicopathologic variables were analyzed by chi-square test and multiple logistic regression models. Overall survival (OS) from diagnosis date to death date/last follow-up was analyzed using Cox proportional hazards models adjusting for age, sex, stage, region and ECOG performance status (PS). Results: 294 samples with both PD-L1 and GEP data were analyzed. Median age was 65 y (range 33-88); 85% were from men, 58% were stage IV, 63% were esophageal adenocarcinoma (EAC) and 37% were esophageal squamous cell carcinoma (ESCC). Overall 36% of tumors were GEP-H/I: 46% in EAC vs 18% in ESCC. GEP was not associated with OS overall (adjusted hazard ratio [aHR] –0.90; 95% CI 0.68-1.18) or in pts with EAC (aHR 0.93; 95% CI 0.68-1.27) or ESCC (aHR 0.76; 95% CI 0.40-1.44). 21% of tumors were PD-L1-CPS ≥ 10: 18% in EAC and 26% in ESCC. PD-L1 expression was associated with ECOG PS (adjusted odds ratio 0.520; 95% CI 0.309-0.875; P = 0.014) but was not associated with OS overall (aHR 0.89; 95% CI 0.64-1.24) or in pts with EAC (aHR 0.97; 95% CI 0.63-1.49) or ESCC (aHR 1.31; 95% CI 0.73-2.34). Conclusions: Our results suggest that T-cell–inflamed GEP and PD-L1 expression may not be prognostic in pts with EC who received SOC.

Abstract 1140: Characterization of a novel PDE10 inhibitor in lung tumor cells and an orthotopic mouse model of lung cancer

2017 ◽  
Author(s):  
Veronica Ramirez-Alcantara ◽  
Bing Zhu ◽  
Xi Chen ◽  
Rajkumar Savai ◽  
Prema Subbarayal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Tumor Cells ◽  
Lung Tumor ◽  
Orthotopic Mouse Model

The heterogeneity of circulating lung tumor cells from non-small cell lung cancer patients

2016 ◽  
Vol 61 ◽  
pp. S80
Author(s):  
S.L. Kong ◽  
S.J. Tan ◽  
T.K.H. Lim ◽  
H.M. Poh ◽  
T.Z.X. Yeo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Lung Tumor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

454 Oncolytic parainfluenza virus 5 vector enhances natural killer cell killing of lung tumor cells in 2D and 3D spheroid cultures

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A481-A481
Author(s):  
Namita Varudkar ◽  
Jeremiah Oyer ◽  
Alicja Copik ◽  
Griffith Parks
Keyword(s):  
Lung Cancer ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Immune Cells ◽  
Nk Cell ◽  
Lung Tumor ◽  
A549 Cells ◽  
Live Cell ◽  
Parainfluenza Virus

BackgroundNatural killer (NK) cells are innate immune cells with natural cytotoxicity towards both tumor cells and virus infected cells. We have developed a particle-based method for in vitro specific expansion of NK cells that yields highly cytotoxic NK cells (PM21-NK cells). There is intense interest in the use of novel oncolytic viruses with the potential to synergize with immune cells to kill tumor cells. Here we have tested the hypothesis that infection with a tumor-selective cytopathic Parainfluenza virus 5 (PIV5-P/V) vector will enhance PM21-NK cell-mediated killing of lung cancer cells in both 2-dimensional (2D) and 3-dimensional (3D) cultures.MethodsIn 2D cultures, live cell time-lapse imaging, flow cytometry and luminescence-based methods were used to assess the killing efficiency of PM21-NK cells against A549 lung tumor cells infected with PIV5-P/V. Blocking antibodies were used to evaluate different NK cell activating receptors involved in recognition of infected tumor cells. IncuCyte live cell imaging system was used to assess real time killing of 3D lung spheroids by a combination of NK cells and PIV5-P/V virus. Z-stack spheroid images were captured using Keyence microscope.ResultsIn 2D cultures, PM21 NK cells efficiently kill A549 cells that have been infected with P/V CPI- virus and enhance the overall rate of killing compared to uninfected cell targets. Antibody blocking showed that the viral Hemagglutinin-Neuraminidase (HN) glycoprotein and NK cell receptors NKp30, NKp46 and NKG2D were involved in PM21-NK cell recognition of PIV5-P/V infected A549 cells. In 3D cultures of A549 tumor spheroids, PIV5-P/V infection was limited to the outer layer of the spheroid, with restricted spread of the infection to inner compartments. However, addition of PM21-NK cells to PIV5-P/V-infected spheroids resulted in killing of not only the infected surface of the spheroid but continued to the uninfected cells located at the center of the spheroid.ConclusionsOur data support the potential of combining oncolytic virotherapy along with PM21-NK cell adoptive therapy against lung cancer.

scholarly journals Effects of conditioned media from murine lung cancer cells and human tumor cells on cultured myotubes

2020 ◽  
Vol 318 (1) ◽  
pp. E22-E32 ◽  
Author(s):  
Blas A. Guigni ◽  
Jos van der Velden ◽  
C. Matthew Kinsey ◽  
James A. Carson ◽  
Michael J. Toth
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Lung Tumor ◽  
Control Cell ◽  
Human Tumor ◽  
Human Lung Tumor ◽  
Primary Cell Lines ◽  
Cultured Myotubes

Factors secreted from tumors/tumor cells are hypothesized to cause skeletal muscle wasting in cancer patients. We examined whether cancer cells secrete factors to promote atrophy by evaluating the effects of conditioned media (CM) from murine lung cancer cells and primary cultures of human lung tumor cells on cultured myotubes. We evaluated murine Lewis lung carcinoma (LLC) and KRASG12D cells, and primary cell lines derived from tumor biopsies from patients with lung cancer (hTCM; n = 6). In all experiments, serum content was matched across treatment groups. We hypothesized that CM from murine and human tumor cells would reduce myotube myosin content, decrease mitochondrial content, and increase mitochondrial reactive oxygen species (ROS) production. Treatment of myotubes differentiated for 7 days with CM from LLC and KRASG12D cells did not alter any of these variables. Effects of murine tumor cell CM were observed when myotubes differentiated for 4 days were treated with tumor cell CM and compared with undiluted differentiation media. However, these effects were not apparent if tumor cell CM treatments were compared with control cell CM or dilution controls. Finally, CM from human lung tumor primary cell lines did not modify myosin content or mitochondrial content or ROS production compared with either undiluted differentiated media, control cell CM, or dilution controls. Our results do not support the hypothesis that factors released from cultured lung cancer/tumor cells promote myotube wasting or mitochondrial abnormalities, but we cannot dismiss the possibility that these cells could secrete such factors in vivo within the native tumor microenvironment.

scholarly journals Ferri–Liposomes: Preformulation and Selective Cytotoxicity against A549 Lung Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 712
Author(s):  
Marina Guedes Fonseca de Souza ◽  
Fabrícia Nunes de Jesus Guedes ◽  
Marli Luiza Tebaldi ◽  
Éverton do Nascimento Alencar ◽  
Lucas Amaral-Machado ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Iron Oxide ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Lung Tumor ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Clinical Practices ◽  
Stealth Liposomes

Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri–liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri–liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri–liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential.

Registry of Primary Lung Tumours in Ain Shams Hospitals

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Yasser Moustafa Mohamed ◽  
Tamer Mohamed Ali ◽  
Mai Mohamed Ali EzzEldin ◽  
Fatma Emad Soliman
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Delay Time ◽  
Lung Tumor ◽  
Small Cell ◽  
University Hospital ◽  
Fibreoptic Bronchoscopy ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Abstract Background Bronchogenic carcinoma is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. This growth can spread beyond the lung by the process of metastasis into nearby tissue or other parts of the body. Most cancers that start in the lung, known as primary lung cancers, are carcinomas, The two main types are small-cell lung carcinoma (SCLC) and non- small-cell lung carcinoma (NSCLC). Aim of the Study Register cases of primary lung tumors presented to Ain shams university hospital during period from June 2018 to June 2019 and to follow up their response to different lines of treatment and to assess delay time between diagnosis and start of treatment. Patients and Methods This study is an observational, analytical and retrospective study, conducted upon 95 cases of primary lung tumor cases presented to Ain Shams University Hospital _oncology chest clinic. Results The main age of our studied population ranging from 17 to 66 years old in cases diagnosed as small cell lung cancer (SCLC), from 30 to 81 years old in cases diagnosed as non small cell lung cancer(NSCLC), eight out of nine cases diagnosed as SCLC were males, sixty six out of 86 NSCLC cases were males, about 66.7% of SCLC cases & 57% of NSCLC were smokers, forty four percent of SCLC presented with performance score 2, while 48.8% of NSCLC presented with performance score 1, Out of 86 cases of non small cell lung cancer 54 were adenocarcinoma, 27 were squamous cell carcinoma, 4 cases were large cell lung cancer and 1 case was mucoepidermoid carcinoma. Dyspnea was the main symptom in SCLC cases (6 cases out of 8). Fibreoptic bronchoscopy was the diagnostic tool in 33.3% of SCLC cases, 29.1% of NSCLC cases. In non small cell lung cancer, US guided biopsy took the second hand after fibreoptic bronchoscopy by 25.6%, Most of cases were stage 4, 77.8% in small cell carcinoma, 80.2% in non small cell lung cancer. SCLC received Gemcitabine/carboplatin in 33.3% of cases, 22.2% of cases received palliative radiotherapy as first line treatment.11.1% of them received definitive radiotherapy as second line treatment.In NSCLC, 25.6% of cases treated with Gemcitabine/carboplatin, 17.4% received palliative radiotherapy.In NSCLC 36% of cases presented with dyspnea then chest pain 22%.The relation between delay time and prognosis as regard disease progression is non significant similar to the relation between delay time from definitive diagnosis to start of treatment)and stage at time of diagnosis. Unlikely, the inverse relation between delay time and ECOG(Eastern Cooperative Oncology Group Performance status) in both small and non small cell lung cancer. Conclusion The relation between delay time and prognosis is non significant similar to the relation between delay time and stage at time of diagnosis. Unlikely, the inverse relation between delay time and ECOG in both small and non small cell lung cancer.

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