Biosynthesis of hormone immunoreactive proteins by non-small cell lung tumor cells in vitro

Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP) to assess tryptophan transporters using an automated synthesizer.Methods. Tosylpropoxytryptophan (Ts-TP) was reacted with K18F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses.In vitrocellular uptake of18F-FTP and18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with18F-FTP and18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv).Results. Radio-TLC and HPLC analyses of18F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of18F-FTP and18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that18F-FTP had less tumor uptake than18F-FDG in prostate cancer model. However,18F-FTP had more uptake than18F-FDG in small cell lung cancer model.Conclusion.18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

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

European Journal of Cancer ◽

10.1016/s0959-8049(16)61277-7 ◽

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

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Comparative intracellular uptake of adriamycin and 4′-deoxydoxorubicin by non-small cell lung tumor cells in culture and its relationship to cell survival

Lung Cancer ◽

10.1016/s0169-5002(87)80099-5 ◽

1987 ◽

Vol 3 (2) ◽

pp. 99-100

Keyword(s):

Cell Survival ◽

Tumor Cells ◽

Lung Tumor ◽

Small Cell ◽

Intracellular Uptake ◽

Small Cell Lung ◽

Cells In Culture

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Dynamic BH3 profiling identifies active BH3 mimetic combinations in non-small cell lung cancer

Cell Death and Disease ◽

10.1038/s41419-021-04029-4 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Danielle S. Potter ◽

Ruochen Du ◽

Patrick Bhola ◽

Raphael Bueno ◽

Anthony Letai

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Tumor Burden ◽

Small Cell ◽

Targeted Agents ◽

Small Cell Lung ◽

Conventional Chemotherapy ◽

Bh3 Mimetic

AbstractConventional chemotherapy is still of great utility in oncology and rationally constructing combinations with it remains a top priority. Drug-induced mitochondrial apoptotic priming, measured by dynamic BH3 profiling (DBP), has been shown in multiple cancers to identify drugs that promote apoptosis in vivo. We therefore hypothesized that we could use DBP to identify drugs that would render cancers more sensitive to conventional chemotherapy. We found that targeted agents that increased priming of non-small cell lung cancer (NSCLC) tumor cells resulted in increased sensitivity to chemotherapy in vitro. To assess whether targeted agents that increase priming might enhance the efficacy of cytotoxic agents in vivo as well, we carried out an efficacy study in a PC9 xenograft mouse model. The BH3 mimetic navitoclax, which antagonizes BCL-xL, BCL-w, and BCL-2, consistently primed NSCLC tumors in vitro and in vivo. The BH3 mimetic venetoclax, which electively antagonizes BCL-2, did not. Combining navitoclax with etoposide significantly reduced tumor burden compared to either single agent, while adding venetoclax to etoposide had no effect on tumor burden. Next, we assessed priming of primary patient NSCLC tumor cells on drugs from a clinically relevant oncology combination screen (CROCS). Results confirmed for the first time the utility of BCL-xL inhibition by navitoclax in priming primary NSCLC tumor cells and identified combinations that primed further. This is a demonstration of the principle that DBP can be used as a functional precision medicine tool to rationally construct combination drug regimens that include BH3 mimetics in solid tumors like NSCLC.

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The prognostic roles of circulating ALDH1+ tumor cell in the patients with non-small cell lung cancer

Bioscience Reports ◽

10.1042/bsr20180914 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 1

Author(s):

Shuang Tian ◽

Ya-Nan Xing ◽

Pu Xia

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Tumor Cells ◽

Cell Lung Cancer ◽

Small Cell ◽

Stem Cell Marker ◽

Small Cell Lung ◽

Nsclc Patients

Circulating tumor cells can provide important diagnostic and prognostic information of the patients with non-small cell lung cancer (NSCLC). Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, has been used in various tumors, including NSCLC. In the present study, we isolated the circulating ALDH1+ tumor cells from the NSCLC patients using ALDH1 as a potential marker. Higher percentage of ALDH1+ tumor cells was identified in blood samples from the NSCLC patients compared with normal controls. ALDH1+ cells were correlated with the poor prognosis of these patients by using Kaplan–Meier analysis. In the last, the tumorigenic properties of ALDH1+ tumor cells were determined in vitro and in vivo by using sphere assay and xenograft tumor mouse models. Our in vitro and in vivo experiments demonstrated that ALDH1 could drive the stemness of circulating NSCLC cells. Circulating ALDH1+ cells could be used as a prognostic marker for NSCLC.

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Caspase-3 Silencing Attenuates Tumor Repopulation Via Impairing Radiation-Induced DNA Damage Response and Downstream Pathway in Non-Small-Cell Lung Cancer

10.21203/rs.3.rs-27514/v1 ◽

2020 ◽

Author(s):

Minghui Zhao ◽

Yiwei Wang ◽

Yucui Zhao ◽

Sijia He ◽

Ruyi Zhao ◽

...

Keyword(s):

Tumor Cells ◽

Caspase 3 ◽

Small Cell ◽

Wild Type ◽

Small Cell Lung ◽

Promoting Effect ◽

Damage Response ◽

Radiation Induced ◽

Growth Promoting

Abstract Background: Radiotherapy is an effective treatment on non-small-cell lung cancer (NSCLC). However, radiation-induced dying tumor cells are postulated to generate potent growth signals to stimulate the repopulation of adjacent surviving tumor cells, which may promote tumor recurrence. We investigated the role of caspase-3-centered molecular mechanism in NSCLC repopulation after radiotherapy.Methods: The stable caspase-3 knockout (Casp3 KO) NSCLC cells were compared with wild-type cells for growth-promoting effect after radiotherapy using in vitro repopulation model. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay and luciferase reporter assay were used to identify the possible molecules and pathway. To elucidate the function of caspase-3 in tumor repopulation, a series of in vitro assays were performed with Casp3 KO NSCLC cells. Finally, tumor cell growth rate of Casp3 KO and wild-type tumor cells in vivo was tested using xenograft tumor assay and key proteins were further confirmed in tumor tissues with or without radiotherapy.Results: We found that radiation induced DNA damage response (DDR) and caspase-3 activation, as well as promoted tumor repopulation in NSCLC cells. Unexpectedly, depleting caspase-3 significantly attenuated ataxia-telangiectasia mutated kinase (ATM)/p53-mediated DDR via attenuating endonuclease G (EndoG) nuclear migration, thus decreasing the growth-promoting effect of irradiated dying cells. Moreover, we identified p53 as a regulator of the Cox-2/PGE2 axis, which was probably involved in caspase-3-centered tumor repopulation after radiotherapy. Additionally, depleting caspase-3 in NSCLC cells showed impaired tumor growth in nude mice model.Conclusions: Our findings demonstrated that caspase-3 was implicated in tumor repopulation and that was accompanied by promoting DDR and downstream Cox-2/PGE2 axis activation in NSCLC cells. This hitherto undescribed signaling pathway mediated by caspase-3 may deepen insight into the radiobiology and provide therapeutic targets to reduce NSCLC recurrence after radiotherapy.

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Investigation of in vitro Activities of Cu2ZnSnS4 Nanoparticles in Human Non-Small Cell Lung Cancer

Materials Today Communications ◽

10.1016/j.mtcomm.2021.102304 ◽

2021 ◽

pp. 102304

Author(s):

Suleyman Gokhan Colak ◽

Canan Vejselova Sezer ◽

Ruken Esra Demirdogen ◽

Mine Ince ◽

Fatih Mehmet Emen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

Communications Biology ◽

10.1038/s42003-021-02136-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Katrina Kildey ◽

Neha S. Gandhi ◽

Katherine B. Sahin ◽

Esha T. Shah ◽

Eric Boittier ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Genome Instability ◽

Small Cell ◽

Small Cell Lung ◽

Protein Levels ◽

Platinum Based Chemotherapy ◽

Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

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