scholarly journals Tin Carboxylate Complexes of Natural Bacteriochlorin for Combined Photodynamic and Chemotherapy of Cancer è

2021 ◽  
Vol 22 (24) ◽  
pp. 13563
Author(s):  
Sergey Tikhonov ◽  
Petr Ostroverkhov ◽  
Nikita Suvorov ◽  
Andrey Mironov ◽  
Yulia Efimova ◽  
...  
Keyword(s):  
Cell Lines ◽  
Biological Tissues ◽  
Original Method ◽  
Depth Of Penetration ◽  
Small Depth ◽  
Tumor Tissues ◽  
Biological Tests ◽  
Physicochemical Methods ◽  
Combined Action

Photodynamic therapy (PDT) is currently one of the most promising methods of cancer treatment. However, this method has some limitations, including a small depth of penetration into biological tissues, the low selectivity of accumulation, and hypoxia of the tumor tissues. These disadvantages can be overcome by combining PDT with other methods of treatment, such as radiation therapy, neutron capture therapy, chemotherapy, etc. In this work, potential drugs were obtained for the first time, the molecules of which contain both photodynamic and chemotherapeutic pharmacophores. A derivative of natural bacteriochlorophyll a with a tin IV complex, which has chemotherapeutic activity, acts as an agent for PDT. This work presents an original method for obtaining agents of combined action, the structure of which is confirmed by various physicochemical methods of analysis. The method of molecular modeling was used to investigate the binding of the proposed drugs to DNA. In vitro biological tests were carried out on several lines of tumor cells: Hela, A549, S37, MCF7, and PC-3. It was shown that the proposed conjugates of binary action for some cell lines had a dark cytotoxicity that was significantly higher (8–10 times) than the corresponding metal complexes of amino acids, which was explained by the targeted chemotherapeutic action of the tin (IV) complex due to chlorin. The greatest increase in efficiency relative to the initial dipropoxy-BPI was found for the conjugate with lysine as a chelator of the tin cation relative to cell lines, with the following results: S-37 increased 3-fold, MCF-7 3-fold, and Hela 2.4-fold. The intracellular distribution of the obtained agents was also studied by confocal microscopy and showed a diffuse granular distribution with predominant accumulation in the near nuclear region.

scholarly journals MiR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction

2018 ◽  
Vol 47 (5) ◽  
pp. 2147-2158 ◽  
Author(s):  
Feiyu Chen ◽  
Na Luo ◽  
Yu Hu ◽  
Xin Li ◽  
Kejing  Zhang
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Tumor Development ◽  
Cancer Stemness ◽  
Normal Tissues ◽  
Tumor Tissues

Background/Aims: Triple negative breast cancer (TNBC) is resistant to conventional chemotherapy due to high proportions of cancer stem cells (CSCs). The aim of this study is to unravel the miR-137-mediated regulatory mechanism of B-cell lymphoma/leukemia 11A (BCL11A) in TNBC. Methods: A corhort of 34 TNBC tumor tissues and paired adjacent normal tissues, as well as 25 non-TNBC tumor tissues and paired adjacent normal tissues were collected post-operatively from patients with breast cancer. Q-PCR was performed to determine the mRNA levels of miR-137 and BCL11A in breast tissues and cell lines. Bioinformatics analysis and dual luciferase reporter assay were used to verify the direct interaction between miR-137 and BCL11A. After up-/down-regulation of BCL11A, miR-137, or DNMT1 via lentiviral transduction in TNBC cell lines SUM149 and MDA-MB-231 cells, Q-PCR and Western blot assays were used to detect the expression levels of BCL11A, DNA methyltransferases 1 (DNMT1), and Islet-1 (ISL1). Mammosphere assay was conducted to assess tumorosphere formation ability of cells, coupled with flow cytometry to determine the percentage of breast cancer stem cells. Co-immunoprecipitation assay was used to determine the interaction between BCL11A and DNMT1. Xenograft tumorigenesis assay was performed to monitor tumor formation in vivo. Results: BCL11A was highly expressed in TNBC, whereas miR-137 was significantly lower in both TNBC tissues and cell lines. miR-137 suppressed BCL11A expression at both mRNA and protein levels by directly targeting its 3’UTR. In both SUM149 and MDA-MB-231 cells, overexpression of miR-137 or knockdown of BCL11A reduced the number of tumoroshperes and the percentage of cancer stem cells in vitro, and inhibited tumor development in vivo. Furthermore, BCL11A interacted with DNMT1 in TNBC cells. Silencing of either BCL11A or DNMT1 impaired cancer stemness and tumorigenesis of TNBC via suppressing ISL1 expression both in vitro, and in vivo. Conclusions: By perturbing BCL11A-DNMT1 interaction, miR-137 impairs cancer stemness and suppresses tumor development in TNBC.

scholarly journals Tryptophan metabolism induced by TDO2 promotes prostatic cancer chemotherapy resistance in a AhR/c-Myc dependent manner

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Li ◽  
Zhenyu Zhao ◽  
Zongbiao Zhang ◽  
Yan Zhang ◽  
Wei Guan
Keyword(s):  
Cancer Treatment ◽  
Cell Lines ◽  
Prostatic Cancer ◽  
Nuclear Translocation ◽  
Metabolic Reprogramming ◽  
Dependent Manner ◽  
Cell Bank ◽  
Slc Transporters ◽  
Tumor Tissues

Abstract Background Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood. Materials and methods Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6 ~ 8 weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments. Result Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2, 3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-κB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp/TDO2/Kyn/AhR/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment. Conclusion Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.

scholarly journals Rapid transport of germ-mimetic nanoparticles with dual conformational polyethylene glycol chains in biological tissues

2020 ◽  
Vol 6 (6) ◽  
pp. eaay9937
Author(s):  
Yiwei Yang ◽  
Falin Tian ◽  
Di Nie ◽  
Yuan Liu ◽  
Kun Qian ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Rational Design ◽  
Biological Tissues ◽  
Polymer Conformation ◽  
Tumor Tissues ◽  
Rapid Transport ◽  
Adhesive Interactions ◽  
Crystalline Drugs

Polyethylene glycols (PEGs) can improve the diffusivity of nanoparticles (NPs) in biological hydrogels, while extended PEG chains severely impede cellular uptake of NPs. Inspired by invasive germs with flagellum-driven mucus-penetrating and fimbriae-mediated epithelium-adhering abilities, we developed germ-mimetic NPs (GMNPs) to overcome multiple barriers in mucosal and tumor tissues. In vitro studies and computational simulations revealed that the tip-specific extended PEG chains on GMNP functioned similarly to flagella, facilitating GMNP diffusion (up to 83.0-fold faster than their counterparts). Meanwhile, the packed PEG chains on the bodies of GMNP mediated strong adhesive interactions with cells similarly to the fimbriae, preserving cellular uptake efficiency. The in vivo results proved the superior tumor permeability and improved oral bioavailability provided by the GMNP (21.9-fold over administration of crystalline drugs). These findings offer useful guidelines for the rational design of NPs by manipulating surface polymer conformation to realize multiple functions and to enhance delivery efficacy.

In Vitro Cultivation of Human Tumor Tissues II. Morphological and Virological Characterization of Three Cell Lines

Oncology ◽  
1978 ◽  
Vol 35 (6) ◽  
pp. 246-252 ◽  
Author(s):  
H. Heremans ◽  
A. Billiau ◽  
J.J. Cassiman ◽  
J.C. Mulier ◽  
P. de Somer
Keyword(s):  
Cell Lines ◽  
Human Tumor ◽  
In Vitro Cultivation ◽  
Tumor Tissues

scholarly journals SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Hao Ji ◽  
Juan Wang ◽  
Binbin Lu ◽  
Juan Li ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Mrna Degradation ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Long Non Coding Rna ◽  
Regulate Gene

Abstract Background LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration. Methods We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1. Results AGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA. Conclusions We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.

scholarly journals CRISPR-CasRx Targeting LncRNA LINC00341 Inhibits Tumor Cell Growth in vitro and in vivo

2021 ◽  
Vol 8 ◽  
Author(s):  
Chunjing Li ◽  
Yu Cao ◽  
Li Zhang ◽  
Jierong Li ◽  
Jianfeng Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Low Grade ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Tumor Tissues ◽  
E Cadherin

CRISPR-CasRx technology provides a new and powerful method for studying cellular RNA in human cancer. Herein, the pattern of expression of long noncoding RNA 00341 (LINC00341) as well as its biological function in bladder cancer were studied using CRISPR-CasRx. qRT-PCR was employed to quantify the levels of expression of LINC00341 in tumor tissues along with the matched non-tumor tissues. sgRNA targeting LINC00341 or the sgRNA negative control were transiently transfected into the T24 as well as 5,637 human bladder cancer cell lines. CCK-8, ELISA as well as wound healing methods were employed to explore cell proliferation, apoptosis and migration, respectively. The tumorigenicity experiment in nude mice also performed to detect cell proliferation. The expression of p21, Bax as well as E-cadherin were assayed using western blot. The results demonstrated that LINC00341 was overexpressed in bladder cancer in contrast with the healthy tissues. The LINC00341 expression level in high-grade tumors was higher in contrast with that in low-grade tumors. The expression of linc00341 was higher relative to that of non-invasive tumors. In T24 as well as 5637-cell lines harboring LINC00341-sgRNA, inhibition of cell proliferation (in vitro and in vivo), elevated apoptosis rate and diminished migration ability. Moreover, silencing LINC00341 upregulated the expressions of p21, Bax as well as E-cadherin. Knockout of these genes could eliminate the phenotypic changes caused by sgRNA targeting LINC00341. Our data demonstrate that LINC00341 has a carcinogenic role in human bladder cancer.

scholarly journals miR-4324 functions as a tumor suppressor in colorectal cancer by targeting HOXB2

2019 ◽  
Vol 48 (3) ◽  
pp. 030006051988373 ◽  
Author(s):  
Hailin Li ◽  
Guiling Zhu ◽  
Yanwei Xing ◽  
Yuekun Zhu ◽  
Daxun Piao
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Quantitative Polymerase Chain Reaction ◽  
Malignant Cell ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Cell Behaviors ◽  
Tumor Tissues

Objective MicroRNAs (miRNAs) are reported to have crucial roles in human cancers; however, their role in colorectal cancer (CRC) remains largely unknown. Methods In this study, we analyzed the expression of miR-4324 in CRC cell lines using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We also examined miR-4324 expression in CRC tumor tissues using a miRNA expression dataset obtained from the Gene Expression Omnibus. We validated the connection between miR-4324 and homeobox B2 (HOXB2) using a luciferase activity reporter assay and western blotting. The effects of miR-4324 and HOXB2 on CRC cell malignant behaviors in vitro were further investigated. Results miR-4324 expression was significantly decreased in both CRC tumor tissues and cell lines. Overexpression of miR-4324 suppressed CRC cell proliferation, migration, and invasion. In contrast, overexpression of HOXB2 promoted CRC malignant cell behaviors. Furthermore, we validated HOXB2 as a direct target of miR-4324. Conclusions miR-4324 expression was decreased in CRC. miR-4324 regulates CRC cell proliferation, migration, and invasion by targeting HOXB2.

scholarly journals CYTOKINESIS-BLOCK MICRONUCLEUS ASSAY IN HUMAN GLIOMA CELLS EXPOSED TO RADIATION

2011 ◽  
Vol 23 (3) ◽  
pp. 159 ◽  
Author(s):  
Jerzy Slowinski ◽  
Grazyna Bierzynska-Macyszyn ◽  
Urszula Mazurek ◽  
Maria Widel ◽  
Malgorzata Latocha ◽  
...  
Keyword(s):  
Cell Lines ◽  
Phase Contrast ◽  
Dose Range ◽  
Micronucleus Assay ◽  
Human Glioma Cells ◽  
Biological Tests ◽  
Genomic Damage ◽  
Gamma Irradiated ◽  
Methodological Aspects

Biological tests are efficient in reflecting the biological influences of several types of generally harmful exposures. The micronucleus assay is widely used in genotoxicity studies or studies on genomic damage in general. We present methodological aspects of cytokinesis-block micronucleus assay performed in human gliomas irradiated in vitro. Eight human glioblastoma cell lines obtained from DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Germany) were gamma-irradiated (60Co) over a dose range of 0-10 Gy. Cytokinesis-block micronucleus assay was performed to quantitate cytogenetic damage. The cells were fixed directly on dishes, stained with fluorochrome DAPI and evaluated under fluorescent and phase contrast microscope. The micronucleus frequency was expressed as a micronuclei (MN) per binucleated cell (BNC) ratio, calculated after scoring at least 100 BNC per dish. The frequency of spontaneous MN ranged from 0.17 to 0.613 (mean: 0.29 ± 0.14). After irradiation increase of MN frequency in the range of 0.312 - 2.241 (mean: 0.98 ± 0.68) was found at 10 Gy. Gliomas are extremely heterogenous in regard to cytogenetic effects of irradiation, as shown in this study by cytokinesis-block micronucleus assay. This test is easily performed on irradiated glioma cell lines and can assist in determining their radiosensitivity. However, in order to obtain reliable and reproducible results, precise criteria for MN scoring must be strictly followed. Simultaneous use of fluorescent and phase contrast equipment improves imaging of morphological details and can further optimize MN scoring.

NPC-1C: A novel, therapeutic antibody to treat pancreas and colorectal cancers.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 235-235 ◽  
Author(s):  
L. A. Diaz ◽  
N. S. Azad ◽  
D. Laheru ◽  
D. T. Le ◽  
C. E. Devoe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Monoclonal Antibody ◽  
Cell Lines ◽  
Pancreatic Tumor ◽  
Human Colon ◽  
Colorectal Cancers ◽  
Tumor Tissues

235 Background: NPC-1C (ensituximab) is a chimeric monoclonal antibody being developed as a novel biologic treatment for pancreatic and colorectal cancers. This antibody was selected from a panel of hybridomas generated from mice immunized with semi-purified membrane-associated proteins derived from biologically screened, pooled human allogeneic colon cancer tissues. The NPC-1C epitope appears to be expressed specifically by human colon and pancreatic tumor tissues and cell lines. Methods: Antitumor activity was established in vitro by measuring ADCC with a standard 4-hour 111-Indium release assay on pancreatic and colorectal cancer cell lines. In vivo antitumor efficacy of NPC-1C was tested using pre-established subcutaneous human pancreatic tumor xenograft models. Results: In vitro, the NPC-1C antibody exhibits ADCC activity specifically against human colon and pancreatic tumor cells, but not against control tumor cell lines. The in vivo data showed significant, and reproducible, antitumor action, including some complete tumor regressions. The clinical application for this antibody was bolstered by several examples of human tumor tissues stained with biotin-conjugated NPC-1C that showed a strong correlation of NPC-1C staining against pancreatic and colon tumors. Approximately 45% of tumors stained strongly positive. The staining pattern was typical of elaborated mucin expression, but also showed cytoplasmic and cell membrane staining. Conclusions: A phase I open label, multicenter dose escalation clinical trial with NPC-1C is currently accruing patients with advanced pancreatic and colorectal cancer who are refractory to standard therapy. The primary objectives of the phase I clinical trial are to determine the safety and tolerability of escalating doses of NPC-1C monoclonal antibody therapy and to assess pharmacokinetics and select immune responses to the antibody at each dose level. Secondary objectives are to evaluate evidence of clinical benefit and to explore the immunologic correlates associated with administration of NPC-1C. Results from this trial will determine the minimum standard dosage levels to be used in further trials. [Table: see text]

scholarly journals Tryptophan Metabolism Induced by TDO2 Promotes Prostatic Cancer Chemotherapy Resistance in a Ahr/C-Myc Dependent Manner

2021 ◽  
Author(s):  
Fan Li ◽  
ZHENYU Zhao ◽  
ZONGBIAO Zhang ◽  
YAN ZHANG ◽  
WEI GUAN
Keyword(s):  
Cancer Treatment ◽  
Cell Lines ◽  
Prostatic Cancer ◽  
Nuclear Translocation ◽  
Metabolic Reprogramming ◽  
Dependent Manner ◽  
Cell Bank ◽  
Slc Transporters ◽  
Tumor Tissues

Abstract Background: Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood.Materials and methods: Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6~8 weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments.Result: Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2，3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-κB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp/TDO2/Kyn/AhR/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment. Conclusion：Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document