Comparative localization of glioma-reactive monoclonal antibodies in vivo in an athymic mouse human glioma xenograft model

1987 ◽  
Vol 15 (1) ◽  
pp. 37-56 ◽  
Author(s):  
C.J. Wikstrand ◽  
R.E. McLendon ◽  
S. Carrel ◽  
J.T. Kemshead ◽  
J.-P. Mach ◽  
...  
PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11583 ◽  
Author(s):  
Krishna Kumar Veeravalli ◽  
Chandramu Chetty ◽  
Shivani Ponnala ◽  
Christopher S. Gondi ◽  
Sajani S. Lakka ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 543 ◽  
Author(s):  
Hui-Yun Hwang ◽  
Yoon Sun Cho ◽  
Jin Young Kim ◽  
Ki Na Yun ◽  
Jong Shin Yoo ◽  
...  

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors are shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets, we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC–MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.


2000 ◽  
Vol 12 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Zhong-ping Chen ◽  
Jun Pan ◽  
Qiang Huang ◽  
Zhi-fang Sun ◽  
Li-ying Zhou ◽  
...  

Author(s):  
Hui-Yun Hwang ◽  
Yoon Sun Cho ◽  
Jin Young Kim ◽  
Ki Na Yun ◽  
Jong Shin Yoo ◽  
...  

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.


Author(s):  
Heather Keen ◽  
Sally‐Ann Ricketts ◽  
Juliana Bales ◽  
Aoife Shannon ◽  
Armelle Logie ◽  
...  

Hybridoma ◽  
1997 ◽  
Vol 16 (1) ◽  
pp. 93-100 ◽  
Author(s):  
JACQUELINE G. EMRICH ◽  
CHRISTOPHER M. HAND ◽  
THOMAS J. DILLING ◽  
REINER CLASS ◽  
HANS BENDER ◽  
...  

1986 ◽  
Vol 64 (2) ◽  
pp. 257-262 ◽  
Author(s):  
Dennis E. Bullard ◽  
Carol J. Adams ◽  
R. Edward Coleman ◽  
Darell D. Bigner

✓ Current diagnostic and therapeutic modalities for malignant human gliomas are largely nonspecific. The development of monoclonal antibodies (MA's) with their high degree of specificity may allow precise tumor imaging and selective administration of therapeutic agents. However, the ability of these antibodies to specifically localize tumor tissue in vivo remains speculative. This study compares the localization and imaging properties of two MA's: a specific human glioma-associated extracellular matrix glycoprotein MA, 81C6, and a nonspecific control MA, 45.6, against a human glioma cell line, D-54 MG, intracranially inoculated into athymic rats. Forty-one animals received MA's labeled with iodine-131 (131I) or 125I and underwent imaging with a gamma camera. The images were independently evaluated and compared to tissue radioactivity levels. Radiolabeled antiglioma MA 81C6 specifically localized in intracranial xenografts. The percent of injected dose per gram of tissue for tumor was 1.707 ± 0.405/gm for 81C6 and 0.118 ± 0.056/gm for 45.6. All other organs had equivalent levels of specific and nonspecific MA's. For brain, these were 0.004 ± 0.002/gm and 0.005 ± 0.005/gm, respectively, and for the other organs, the range was from 0.053 to 0.284/gm. Statistically, 45.6 achieved levels in tumor that were significantly higher than normal brain (p < 0.05) but significantly less than that achieved with 81C6 (p < 0.005). With 81C6, the degree of localization was high enough to allow imaging of intracranial tumors at sizes as small as 20 mg. Intracranial tumors were imaged with 45.6 only when they achieved sizes greater than 300 mg. In this imaging study, radiolabeled 81C6, a specific antiglioma MA, proved to be significantly better for imaging small and intermediate-sized tumors than the control MA's. Large tumors were visualized by both MA's, although higher quality scans were obtained earlier and more frequently with specific MA's than with nonspecific immunoglobulin G. These data suggest that specific MA's have a role to play in both the diagnosis and treatment of primary intracranial human tumors.


2018 ◽  
Vol 47 (3) ◽  
pp. 1108-1121 ◽  
Author(s):  
Fei Peng ◽  
Xiaoxiong Wang ◽  
Mengting Shu ◽  
Mingfei Yang ◽  
Ligang Wang ◽  
...  

Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.


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