Preparation and <i>in vitro</i> tumor growth inhibitory effect of oligo (L-lactate) nanoparticles

In multiple myeloma (MM), the cell surface protein, CD19, is specifically lost while it continues to be expressed on normal plasma cells. To examine the biological significance of loss of CD19 in human myeloma, we have generated CD19 transfectants of a tumorigenic human myeloma cell line (KMS-5). The CD19 transfectants showed slower growth rate in vitro than that of control transfectants. They also showed a lower capability for colony formation as evaluated by anchorage-independent growth in soft agar assay. The CD19 transfectants also had reduced tumorigenicity in vivo when subcutaneously implanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hIL-6) transgenic mice. The growth-inhibitory effect was CD19-specific and probably due to CD19 signaling because this effect was not observed in cells transfected with a truncated form of CD19 that lacks the cytoplasmic signaling domain. The in vitro growth-inhibitory effect was confirmed in a nontumorigenic human myeloma cell line (U-266). However, introduction of the CD19 gene into a human erythroleukemia cell line (K-562) also induced growth inhibition, suggesting that this effect is CD19-specific, but not restricted to myeloma cells. These data suggest that the specific and generalized loss of CD19 in human myeloma cells could be an important factor contributing to the proliferation of the malignant plasma cell clones in this disease.

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Growth inhibitory effect on glioma cells of adenovirus-mediated p16/INK4a gene transfer in vitro and in vivo.

International Journal of Molecular Medicine ◽

10.3892/ijmm.6.5.559 ◽

2000 ◽

Cited By ~ 2

Author(s):

S H Lee ◽

M S Kim ◽

H C Kwon ◽

I C Park ◽

M J Park ◽

...

Keyword(s):

Gene Transfer ◽

Glioma Cells ◽

Inhibitory Effect ◽

Growth Inhibitory Effect ◽

Growth Inhibitory ◽

P16 Ink4a

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BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

Molecules ◽

10.3390/molecules26237139 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7139

Author(s):

Pedro Novais ◽

Patrícia M. A. Silva ◽

Joana Moreira ◽

Andreia Palmeira ◽

Isabel Amorim ◽

...

Keyword(s):

Cancer Cells ◽

Spindle Assembly Checkpoint ◽

Human Cancer ◽

Antitumor Agent ◽

Inhibitory Effect ◽

Growth Inhibitory Effect ◽

Human Cancer Cells ◽

Antimitotic Activity ◽

Growth Inhibitory

Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

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NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers

Frontiers in Oncology ◽

10.3389/fonc.2021.669667 ◽

2021 ◽

Vol 11 ◽

Author(s):

Atsushi Takatori ◽

Shamim Hossain ◽

Atsushi Ogura ◽

Jesmin Akter ◽

Yohko Nakamura ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Inhibitory Effect ◽

Tumor Cell Proliferation ◽

Growth Inhibitory Effect ◽

Extracellular Domains ◽

Growth Inhibitory ◽

Fniii Domain

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.

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