Treatment of leptomeningeal metastases in a rat model using a recombinant adenovirus containing the HSV-tk gene

✓ The authors constructed recombinant adenoviral vectors to investigate their potential for gene therapy treatment of leptomeningeal metastases. Several human cell lines that were derived from tumors occurring as leptomeningeal metastases and that were infected in vitro with major late promoter recombinant adenovirus containing the luciferase (luc) gene (IG.Ad.MLP.luc.) showed high levels of expression. When these human tumor cell lines were infected in vitro with recombinant adenovirus harboring the herpes simplex virus—thymidine kinase (HSV-tk) gene (IG.Ad.MLP.TK), they were highly sensitive to the killing effects of ganciclovir (GCV). Transduction efficiency of leptomeningeal tumor cells in vivo was assessed by injecting 9-L rat brain tumor cells into the cerebrospinal fluid of Fischer rats via the cisterna magna. After 3 days, recombinant adenovirus containing the lacZ reporter gene (IG.Ad.MLP.lacZ) was injected via the same route. Six days after tumor cell injection, expression of the reporter gene was observed in tumor cells along the total neural axis. Subsequently, rats with leptomeningeal metastases were treated 3 days after tumor cell injection with HSV-tk. Beginning on the next day, GCV was injected intraperitoneally for 10 days. The rats that developed neurological symptoms were killed immediately. The symptom-free latency of every rat was determined. The rats treated with HSV-tk and subsequent GCV had significantly longer (p < 0.01) symptom-free latency than all control groups. This study demonstrates the feasibility and efficacy of this therapeutic approach in a rat model. Clinically, it should be used in the palliative treatment of patients with leptomeningeal metastases.

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Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665296 ◽

1983 ◽

Vol 50 (03) ◽

pp. 726-730 ◽

Cited By ~ 11

Author(s):

Hamid Al-Mondhiry ◽

Virginia McGarvey ◽

Kim Leitzel

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Cell Lines ◽

Human Tumor ◽

Human Platelets ◽

Factor Vii ◽

Coagulation System ◽

Breast Adenocarcinoma ◽

Activate Factor ◽

Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

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Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190730164952 ◽

2020 ◽

Vol 17 (4) ◽

pp. 512-517

Author(s):

Ognyan Ivanov Petrov ◽

Yordanka Borisova Ivanova ◽

Mariana Stefanova Gerova ◽

Georgi Tsvetanov Momekov

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Biological Activities ◽

Human Tumor ◽

Mannich Bases ◽

In Vitro Cytotoxicity ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

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Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽

10.3390/biomedicines9010092 ◽

2021 ◽

Vol 9 (1) ◽

pp. 92

Author(s):

Bashir Lawal ◽

Yen-Lin Liu ◽

Ntlotlang Mokgautsi ◽

Harshita Khedkar ◽

Maryam Rachmawati Sumitra ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Cancer Cell ◽

Human Tumor ◽

Cancer Cell Lines ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

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Synthesis and Characterization of New Palladium(II) Complexes with Ligands Derived from Furan-2-carbaldehyde and Benzaldehyde Thiosemicarbazone and their in vitro Cytotoxic Activities against Various Human Tumor Cell Lines

Zeitschrift für Naturforschung B ◽

10.1515/znb-2010-1015 ◽

2010 ◽

Vol 65 (10) ◽

pp. 1271-1278 ◽

Cited By ~ 4

Author(s):

Wilfredo Hernández ◽

Juan Paz ◽

Fernando Carrasco ◽

Abraham Vaisberg ◽

Jorge Manzur ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Myelogenous Leukemia ◽

Cytotoxic Activities ◽

Spectroscopic Techniques ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

With the ligands 4-phenyl-1-(furan-2-carbaldehyde)thiosemicarbazone, HTSC1, (1), 4-phenyl-1- (5´-phenyl-furan-2-carbaldehyde)thiosemicarbazone, HTSC2 (2), o-methoxy-benzaldehydethiosemicarbazone, HTSC3 (3), and o-cyano-benzaldehydethiosemicarbazone, HTSC4 (4), the corresponding palladium(II) complexes, Pd(TSC1)2 (5), Pd(TSC2)2 (6), Pd(TSC3)2 (7), and Pd(TSC4)2 (8) were synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structure of Pd(TSC3)2 (7) was determined by single-crystal X-ray diffraction. Complex 7 shows a squareplanar geometry, where two deprotonated ligands are coordinated to the PdII center through the nitrogen and sulfur atoms in a trans arrangement. In vitro antitumor studies against different human tumor cell lines have revealed that the palladium(II) complexes 5- 8 are more cytotoxic (IC50 values in the range of 0.21 - 3.79 μM) than their corresponding ligands (1 - 4) (> 60 μM). These results indicate that the antiproliferative activity is enhanced when thiosemicarbazone ligands are coordinated to the metal. Among the studied palladium(II) complexes, 8 exhibits high antitumor activity on K562 chronic myelogenous leukemia cells with a low value of the inhibitory concentration (IC50 = 0.21 μM).

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Cytogenetics of 52 human tumor cell lines grown in vitro

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(86)90399-7 ◽

1986 ◽

Vol 19 (1-2) ◽

pp. 185

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

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Breast Tumor Cell Lines From Pleural Effusions2

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/53.3.661 ◽

1974 ◽

Vol 53 (3) ◽

pp. 661-674 ◽

Cited By ~ 562

Author(s):

R. Cailleau ◽

R. Young ◽

M. Olivé ◽

W. J. Reeves

Keyword(s):

Chromosome Number ◽

Tumor Cell ◽

Tumor Cells ◽

Cell Lines ◽

Breast Tumor ◽

Tumor Cell Lines ◽

Breast Cancer Patients ◽

Pleural Effusions ◽

Epithelial Tumor

Summary During 1973, 4 new epithelial tumor cell lines were isolated from pleural effusions from breast cancer patients. We describe 3 of these lines: MDA-MB-134, with a mean chromosome number of 43; MDA-MB-175, with a mean chromosome number of 49; and MDA-MB-231, with a mean chromosome number between 65 and 69. We isolated the same cell type from 4 of 10 effusions from MDA-MB-134 and from 6 of 8 effusions from MDA-MB-175. We found that pleural effusions as a source of breast tumor cells to be cultured and studied in vitro have the following advantages: 1) large amounts of material and the possibility of obtaining sequential samples from the same patient; 2) high viability of tumor cells; 3) scarcity or absence of fibroblasts; and 4) the possibility of separating the tumor cells from other “contaminating” cell types by differences in their speed or degree of attachment to the flask. All lines from different patients differed, as seen grossly and microscopically. All lines from sequential pleural effusions from the same patient were apparently alike. No viruses or mycoplasmas were detected in any line.

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Interaction Of Platelets And Tumor Cells: Differentiation Between Nine Human Tumor Cell Lines Based On Aggregation And Effects Of Apyrase, Hirudin And Phospholipase D

10.1055/s-0038-1653311 ◽

1981 ◽

Author(s):

G A Jamieson ◽

Eva Bastida ◽

Antonio Ordinas

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Cell Lines ◽

Phospholipase D ◽

Lung Carcinoma ◽

Platelet Rich Plasma ◽

Human Tumor ◽

Clotting System ◽

Cell Lung Carcinoma ◽

Aggregation Pattern

Aggregation mechanisms have been examined in a homologous system using heparinized human platelet-rich plasma with cell lines derived from human tumors. The A549 (epithelial lung carcinoma) and Hut23 (adenocarcinoma) did not aggregate platelets at 107 cells/ml. Other cell lines could not be classified by aggregation pattern alone since all gave biphasic or quasibiphasic patterns. HT 29 (adenocarcinoma) , SKBR3 (adenocarcinoma), HT 144 (melanoma) and Hut 20 (large cell lung carcinoma) were inhibited by apyrase and phospholipase D but not by hirudin: aggregation induced by this group is probably primarily dependent on ADP. Aggregation by SKNMC (mesothelioma) and Hut 28 (mesothelioma) was inhibited by hirudin and phospholipase D but not by apyrase. Aggregation by this second group probably involves activation of the clotting system in the early stages but can be differentiated from a similar mechanism with U87MG since thq latter is not inhibited by phospholipase D. Phospholipase C had no effect on any cell line and phospholipase A2 inhibited all cell lines, as did its hydrolytic product, lysolecthin. Platelet aggregating material (PAM) could not be isolated by urea extraction of any of these human tumor cells. These results suggest that various inhibitors are necessary to allow classification of mechanisms of tumor cell-induced platelet aggregation.

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