The effect of monoclonal antibody cetuximab (C225) in combination with tyrosine kinase inhibitor gefitinib (ZD1839) on colon cancer cell lines

Pathology ◽  
2012 ◽  
Vol 44 (6) ◽  
pp. 547-551 ◽  
Author(s):  
Heng-heng Yuan ◽  
Yu Han ◽  
Wei-xin Bian ◽  
Lei Liu ◽  
Yu-xian Bai
1999 ◽  
Vol 277 (6) ◽  
pp. C1142-C1148 ◽  
Author(s):  
Richard Jaszewski ◽  
Ahmed Khan ◽  
Fazlul H. Sarkar ◽  
Omer Kucuk ◽  
Martin Tobi ◽  
...  

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 μg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 μg/ml) completely abrogated transforming growth factor-α (TGF-α)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-α. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process.


mAbs ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 1038-1050 ◽  
Author(s):  
Kaja Lund ◽  
Monica Bostad ◽  
Ellen Skarpen ◽  
Michael Braunagel ◽  
Sergej Kiprijanov ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Hae Dong Kim ◽  
Eun Jung Park ◽  
Eun Kyoung Choi ◽  
Seuk Young Song ◽  
Kwang-Lae Hoe ◽  
...  

G-749 is an FLT3 kinase inhibitor that was originally developed as a treatment for acute myeloid leukemia. Some FLT3 kinase inhibitors are dual kinase inhibitors that inhibit the TAM (Tyro3, Axl, Mer) receptor tyrosine kinase family and are used to treat solid cancers such as non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). AXL promotes metastasis, suppression of immune response, and drug resistance in NSCLC and TNBC. G-749, a potential TAM receptor tyrosine kinase inhibitor, and its derivative SKI-G-801, effectively inhibits the phosphorylation of AXL at nanomolar concentration (IC50 = 20 nM). This study aimed to investigate the anticancer effects of G-749 targeting the TAM receptor tyrosine kinase in colon cancer. Here, we demonstrate the potential of G-749 to effectively inhibit tumorigenesis by degrading TYRO3 via regulated intramembrane proteolysis both in vitro and in vivo. In addition, we demonstrated that G-749 inhibits the signaling pathway associated with cell proliferation in colon cancer cell lines HCT15 and SW620, as well as tumor xenograft mouse models. We propose G-749 as a new therapeutic agent for the treatment of colon cancer caused by abnormal TYRO3 expression or activity.


2019 ◽  
Vol 9 (4) ◽  
pp. 341-348 ◽  
Author(s):  
Ibrahim Awad Mohammed ◽  
Muhammad Nadeem Akhtar ◽  
Foo Jhi Biau ◽  
Yin Sim Tor ◽  
Seema Zareen ◽  
...  

<P>Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. </P><P> Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. </P><P> Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. </P><P> Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62&#177;0.61 and 4.44&#177;0.66 &#181;g/mL) and pinostrobin chalcone (2), (IC50 = 20.42&#177;2.23 and 22.51&#177;0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. </P><P> Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.</P>


1993 ◽  
Vol 11 (5-6) ◽  
pp. 225-237
Author(s):  
Udo Schumacher ◽  
Dhia Mukthar ◽  
Thomas Schenker

A panel of monoclonal antibodies (n=72 including controls) directed against lung cancer antigens was screened immunohistochemically against a panel of seven human lung cancer cell lines (including small cell carcinoma, squamous cell carcinoma, adenocarcinoma and mesothelioma), six human breast cancer cell lines and one human colon cancer cell line, The majority of the antibodies (n=42) reacted also with antigens present on breast and colon cancer cell lines, This cross reactivity especially between lung and breast cancer cell lines is not altogether unexpected since antigens common to breast and lung tissue including their neoplasms such as MUC1 antigen have been described, Our results indicate that epitopes shared by lung and breast cancers are probably more common than previously thought. The relevance for prognosis and therapy of these shared antigens, especially as disease markers in breast cancer, has to be investigated.


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