text:
1–10 of 499 records found matching your query:
< Back 1 2 3 4 5 6 7 8 9 10 Next > >>
< Back 1 2 3 4 5 6 7 8 9 10 Next > >> List View | Details
A. Signore; S. J. Mather;G. Piaggio, G. Malviya; R. A. Dierckx
Molecular Imaging of Inflammation/Infection: Nuclear Medicine and Optical Imaging Agents and Methods
molecular imaging; inflammatory diseases; optical imaging; nuclear medicine imaging; SPECT; hybrid imaging; in vivo imaging
PKI @ sarah.piper @
New symmetrically esterified m-bromobenzyl non-aminobisphosphonates inhibited breast cancer growth and metastases
Antineoplastic Agents; Bioware; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Diphosphonates; Esterification; Female; Humans; Hydrophobic and Hydrophilic Interactions; MDA-MB-231-D3H2LN cells; Neoplasm Metastasis; Structure-Activity Relationship
BACKGROUND Although there was growing evidence in the potential use of Bisphosphonates (BPs) in cancer therapy, their strong osseous affinities that contrast their poor soft tissue uptake limited their use. Here, we developed a new strategy to overcome BPs hydrophilicity by masking the phosphonic acid through organic protecting groups and introducing hydrophobic functions in the side chain. METHODOLOGY/PRINCIPAL FINDINGS We synthesized non-nitrogen BPs (non N-BPs) containing bromobenzyl group (BP7033Br) in their side chain that were symmetrically esterified with hydrophobic 4-methoxphenyl (BP7033BrALK) and assessed their effects on breast cancer estrogen-responsive cells (T47D, MCF-7) as well as on non responsive ones (SKBR3, MDA-MB-231 and its highly metastatic derived D3H2LN subclone). BP7033Br ALK was more efficient in inhibiting tumor cell proliferation, migration and survival when compared to BP7033Br. Although both compounds inhibited tumor growth without side effects, only BP7033Br ALK abrogated tumor angiogenesis and D3H2LN cells-induced metastases formation. CONCLUSION/SIGNIFICANCE Taken together these data suggest the potential therapeutic use of this new class of esterified Bisphosphonates (BPs) in the treatment of tumor progression and metastasis without toxic adverse effects.
Abdelwahab, M. G.; Fenton, K. E.; Preul, M. C.; Rho, J. M.; Lynch, A.; Stafford, P.; Scheck, A. C.
The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma
Bioware cell linesIVIS Imaging Systems
GL261-luc2, IVIS, 3-Hydroxybutyric Acid/metabolism; Animals; Blood Glucose/metabolism; Brain/metabolism/pathology; Combined Modality Therapy; Disease Models, Animal; Glioma/*diet therapy/*radiotherapy; Humans; Kaplan-Meier Estimate; *Ketogenic Diet; Ketones/blood; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Time Factors
INTRODUCTION: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal(R) (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2x4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of beta-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.
Abdelwahab, M. G.; Sankar, T.; Preul, M. C.; Scheck, A. C.
Intracranial Implantation with Subsequent 3D In Vivo Bioluminescent Imaging of Murine Gliomas
J Vis Exp
GL261-luc2, IVIS, Glioma, Biolumninescence imaging
The mouse glioma 261 (GL261) is recognized as an in vivo model system that recapitulates many of the features of human glioblastoma multiforme (GBM). The cell line was originally induced by intracranial injection of 3-methyl-cholantrene into a C57BL/6 syngeneic mouse strain (1); therefore, immunologically competent C57BL/6 mice can be used. While we use GL261, the following protocol can be used for the implantation and monitoring of any intracranial mouse tumor model. GL261 cells were engineered to stably express firefly luciferase (GL261-luc). We also created the brighter GL261-luc2 cell line by stable transfection of the luc2 gene expressed from the CMV promoter. C57BL/6-cBrd/cBrd/Cr mice (albino variant of C57BL/6) from the National Cancer Institute, Frederick, MD were used to eliminate the light attenuation caused by black skin and fur. With the use of albino C57BL/6 mice; in vivo imaging using the IVIS Spectrum in vivo imaging system is possible from the day of implantation (Caliper Life Sciences, Hopkinton, MA). The GL261-luc and GL261-luc2 cell lines showed the same in vivo behavior as the parental GL261 cells. Some of the shared histological features present in human GBMs and this mouse model include: tumor necrosis, pseudopalisades, neovascularization, invasion, hypercellularity, and inflammation (1). Prior to implantation animals were anesthetized by an intraperitoneal injection of ketamine (50 mg/kg), xylazine (5 mg/kg) and buprenorphine (0.05 mg/kg), placed in a stereotactic apparatus and an incision was made with a scalpel over the cranial midline. A burrhole was made 0.1mm posterior to the bregma and 2.3mm to the right of the midline. A needle was inserted to a depth of 3mm and withdrawn 0.4mm to a depth of 2.6mm. Two mul of GL261-luc or GL261-luc2 cells (10(7) cells/ml) were infused over the course of 3 minutes. The burrhole was closed with bonewax and the incision was sutured. Following stereotactic implantation the bioluminescent cells are detectable from the day of implantation and the tumor can be analyzed using the 3D image reconstruction feature of the IVIS Spectrum instrument. Animals receive a subcutaneous injection of 150mug luciferin /kg body weight 20 min prior to imaging. Tumor burden is quantified using mean tumor bioluminescence over time. Tumor-bearing mice were observed daily to assess morbidity and were euthanized when one or more of the following symptoms are present: lethargy, failure to ambulate, hunched posture, failure to groom, anorexia resulting in >10% loss of weight. Tumors were evident in all of the animals on necropsy.
Ackermann, M.; Carvajal, I.M.; Morse, B.A.; Moreta, M.; O'Neil, S.; Kossodo, S.; Peterson, J.D.; Delventhal, V.; Marsh, H.N.; Furfine, E.S.; Konerding, M.A.
Adnectin CT-322 inhibits tumor growth and affects microvascular architecture and function in Colo205 tumor xenografts
International Journal of Oncology
AngioSense
AngioSense 680; anti-angiogenic; anti-tumorigenic; Cancer; FMT1 (VisEn); FMT-Solaris; In vivo imaging (VisEn); intraperitoneal injection; mice
Antiangiogenesis has become a promising pillar in modern cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin[TM], CT-322, in a murine Colo-205 xenograft tumor model. CT-322 specifically binds to and blocks vascular endothelial growth factor receptor (VEGFR-2). Adnectins are a novel class of targeted biologics engineered from the 10th domain of human fibronectin. CT-322 treated tumors exhibited a significant reduction in tumor growth of 69%, a 2.8 times lower tumor surface area and fewer necrotic areas. Control tumors showed a 2.36-fold higher microvessel density (MVD) and a 2.42 times higher vessel volume in corrosion casts. The vascular architecture in CT-322-treated tumors was characterized by a strong normalization of vasculature. This was quantified in corrosion casts of CT-322 treated tumors in which the intervascular distance (a reciprocal parameter indicative of vessel density) and the distance between two consecutive branchings were assessed, with these distances being 2.21 times and 2.37 times greater than in controls, respectively. Fluorescence molecular tomography (FMT) equally affirmed the inhibitory effects of CT-322 on tumor vasculature as indicated by a 60% reduction of the vascular probe, AngioSense, accumulating in tumor tissue, as a measurement of vascular permeability. Moreover, AngioSense accumulation was reduced as early as 24 h after starting treatment. The sum of these effects on tumor vasculature illustrates the anti-angiogenic mechanism underlying the antitumor activity of CT-322 and provides support for further evaluation of this Adnectin in combinatorial strategies with standard of care therapies.
PKI @ user @ 8449
Agarwal, A.; Mackey, M. A.; El-Sayed, M. A.; Bellamkonda, R. V.
Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods
Annexin VivoIVIS Imaging Systems
Annexin Vivo, Annexin-Vivo, IVIS, Animals; Antineoplastic Agents/*administration & dosage; Apoptosis; Cell Line, Tumor; Doxorubicin/*administration & dosage; Drug Carriers; Drug Delivery Systems; Female; Glioblastoma/drug therapy; Gold/chemistry; Humans; Liposomes/*chemistry; Metal Nanoparticles/chemistry; Mice; Mice, Nude; Nanostructures/chemistry; Neoplasms/*drug therapy; Polyethylene Glycols/chemistry
Delivery of chemotherapeutic agents after encapsulation in nanocarriers such as liposomes diminishes side-effects, as PEGylated nanocarrier pharmacokinetics decrease dosing to healthy tissues and accumulate in tumors due to the enhanced permeability and retention effect. Once in the tumor, however, dosing of the chemotherapeutic to tumor cells is limited potentially by the rate of release from the carriers and the size-constrained, poor diffusivity of nanocarriers in tumor interstitium. Here, we report the design and fabrication of a thermosensitive liposomal nanocarrier that maintains its encapsulation stability with a high concentration of doxorubicin payload, thereby minimizing "leak" and attendant toxicity. When used synergistically with PEGylated gold nanorods and near-infrared stimulation, remote triggered release of doxorubicin from thermosensitive liposomes was achieved in a mouse tumor model of human glioblastoma (U87), resulting in a significant increase in efficacy when compared to nontriggered or nonthermosensitive PEGylated liposomes. This enhancement in efficacy is attributed to increase in tumor-site apoptosis, as was evident from noninvasive apoptosis imaging using Annexin-Vivo 750 probe. This strategy affords remotely triggered control of tumor dosing of nanocarrier-encapsulated doxorubicin without sacrificing the ability to differentially dose drugs to tumors via the enhanced permeation and retention effect.
Aki Hanyu; Kiyotsugu Kojima; Kiyohiko Hatake; Kimie Nomura; Hironori Murayama; Yuichi Ishikawa; Satoshi Miyata; Masaru Ushijima; Masaaki Matsuura; Etsuro Ogata; Keiji Miyazawa;Takeshi Imamura
Functional in vivo optical imaging of tumor angiogenesis, growth, and metastasis prevented by administration of anti-human VEGF antibody in xenograft model of human fibrosarcoma HT1080 cells
Angiogenesis; metastasis; in vivo imaging; fluorescence imaging
Angiogenesis plays a crucial role in cancer progression and metastasis. Thus, blocking tumor angiogenesis is potentially a universal approach to prevent tumor establishment and metastasis. In this study, we used in vivo and ex vivo fluorescence imaging to show that an antihuman vascular endothelial growth factor (VEGF) antibody represses angiogenesis and the growth of primary tumors of human fibrosarcoma HT1080 cells in implanted nude mice. Interestingly, administering the antihuman VEGF antibody reduced the development of new blood vessels and normalized pre-existing tumor vasculature in HT1080 cell tumors. In addition, antihuman VEGF antibody treatment decreased lung metastasis from the primary tumor, whereas it failed to block lung metastasis in a lung colonization experiment in which tumor cells were injected into the tail vein. These results suggest that VEGF produced by primary HT1080 cell tumors has a crucial effect on lung metastasis. The present study indicates that the in vivo fluorescent microscopy system will be useful to investigate the biology of angiogenesis and test the effectiveness of angiogenesis inhibitors.
http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2009.01305.x/full
Akudugu, J. M.; Azzam, E. I.; Howell, R. W.
Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype
Int J Radiat Biol
MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer
Abstract Purpose: This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with (125)I-labeled 5-iodo-2 -deoxyuridine ((125)IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods: In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix carbon scaffold. Cultures were pulse-labeled for 3 h with (125)IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2'-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT((R)) EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with (125)IdU/EdU. Additional aliquots were used to determine the mean (125)I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results: Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions: These studies demonstrate the capacity of (125)IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype.
Al Marzouqi, N.; Iratni, R.; Nemmar, A.; Arafat, K.; Ahmed Al Sultan, M.; Yasin, J.; Collin, P.; Mester, J.; Adrian, T. E.; Attoub, S.
Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts
Eur J Pharmacol
MDA-MB-231-luc2, IVIS, Breast Cancer, Bioware
Breast cancer is a major challenge for pharmacologists to develop new drugs to improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in vivo. We investigated the impact of Frondoside A on human breast cancer cell survival, migration and invasion in vitro, and on tumor growth in nude mice, using the human estrogen receptor-negative breast cancer cell line MDA-MB-231. The non-tumorigenic MCF10-A cell line derived from normal human mammary epithelium was used as control. Frondoside A (0.01-5muM) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5muM at 24h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5muM at 24h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1 (apoptotic) cell fraction through the activation of p53, and subsequently the caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In vivo, Frondoside A (100mug/kg/dayi.p. for 24days) strongly decreased the growth of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side-effects. Moreover, we found that Frondoside A could enhance the killing of breast cancer cells induced by the chemotherapeutic agent paclitaxel. These findings identify Frondoside A as a promising novel therapeutic agent for breast cancer.


Some movies have a way of sticking in the minds of their viewers; from The Exorcist in the early 70's to Ghost in the 90's, movies can stay with viewers for a lifetime. But it is always a true masterpiece of filmography that has a way of entwining its way into the soul of a viewer, and such a movie for me is 2003's OldBoy.
Cover of Volume.1 of the manga OldBoy from which the original movie was adapted.
Loosely based on a manga of the same name, OldBoy from the time of its release quickly became a firm favourite not only amongst fans of Asian cinema but general movie goers also. It was indeed such a well-made and critically acclaimed film that in 2004 it won the Grand Prix at the Cannes Film Festival, as well as high praise from the President of the Jury, director Quentin Tarantino. Often voted one of the best movies ever made, OldBoy was once described as "A powerful film not because of what it depicts, but because of the depths of the human heart which it strips bare" by film critic Roger Ebert.
If you were to outline the plot of the movie this statement as a whole rings true: Oh Dae-Su, a somewhat average man, is kidnapped and imprisoned in a cell without explanation on the eve of his young daughter's birthday. Exactly 15 years later he is released and given money, a mobile phone and clothes, yet no reason as to why he was imprisoned. As he works to explain his imprisonment and get his revenge on his kidnapper, he soon finds that there is a greater plan behind his imprisonment and led down a path of great pain and suffering, whilst falling in love with the innocent Mi-Do. Simple enough right? Wrong!
You see the hard-hitting and gripping story viewers were treated to in the movie was an entirely different one from what was depicted in the manga. From the personalities of the characters, the period of imprisonment and the reasons given for it, changes of all kinds were made. But to me it's these changes that made OldBoy the film that it was. People who might have read the manga were on a level viewing field as those who had not heard of it before. They were treated to an entirely new story which would grip and shock them in all the right ways without ever having to feel that they knew what was bound to come along next. It was shocking and extreme but mostly a flyaway success. So it comes to me to beg the question, why has Hollywood decided to take this movie (like others previously) and re-make it?
During this time Mandate Pictures released a press statement saying that a remake of the film was being taken on by them with Spike Lee taking over as director and the screenplay being written by Protosevich. The cast is definitely one that will make fans take notice: Josh Brolin, Elizabeth Olsen and Samuel L. Jackson being amongst a few. So why do so many still lack interest towards the film?
With that in mind, we go back to my initial question: why has Hollywood decided to remake the movie? One reason that is easy to pick up on is the profitable aspects of the movie. Having seen the success the initial success the movie made with Asian cinema goers upon its release, it is easy to see why DreamWorks would want to remake it for a western audience to attempt repeat the same profitable success. We have to remember also that such profit outlasted the movie's time in the cinema with the film being released by Tartan Asia Extreme several times in different editions, including a single-disc edition, featuring the film and a small amount of special features.
Scene from the original movie, one that could well be missed out in the Hollywood remake.
Another reason which could be key to the reasoning behind this remake is problems with cultural identity. The western audience simply may not be able to relate to the Korean version of the movie, therefore the idea of making the film relatable to a wider audience is appealing to film companies. Are we not as humans more able to empathise with characters and stories we can relate to? This also ties in with the language barrier. It is well-known that the majority of film fans would much rather miss a film, no matter how well reviewed or popular it is, if it were to have subtitles. Most people simply prefer to be able to watch a movie without having to read throughout it. But this to me has been one of the most disappointing things about this project, discovering that, as a fan of foreign movies. I am not part of the majority but of the minority.
However this could well be the remake's downfall. Yes the Korean film was different from the initial manga but that is what made the movie so good. They did not try to replace it but changed the entire outline, a move that could well have been a hindrance but instead made it stand out amongst other films. Another problem that could arise with this Hollywood remake is the very fact that it is a remake. Over the past decade Hollywood seems to have lost its originality and spark when it comes to creating memorable movies for the viewing public, often losing money on big investments or simply producing 'one hit wonders'. But with remakes, and especially popular ones, they at least have the certainty of being on to a sure thing. Who could possibly fail to make a profit with an idea that has already been so profitable and popular?
New poster for Spike Lee's Hollywood remake of OldBoy.
But they could well fail to hit the right mark with fans of the original. Outcry came after it was announced that plans would go ahead with the movie again and this has yet to die down, even after the release of a first trailer of the movie and movie posters (both in the last week). Whilst some have argued that the movie trailer appears to show an entirely new concept of the movie and brings hope that it may not be a complete lost cause, others have been less than forgiving, commenting that the trailer cheapens the movie and the tone of the posting being 'too surreal' and not fitting to the image of OldBoy. An image that set the tone of the entire film, which is something the recent poster fails to do.
Whatever it comes down to there is bound to be countless issues within the next few months leading up to the Hollywood version of OldBoy. Whether you are a fan not willing to give the remake a chance or someone who has not yet had the chance to experience what in my opinion is clearly an unbeatable adaption of a wonderful manga, the movie producers seem to have gotten one thing correct. The movie will be on the lips and in the minds of many a film fan up until its October release.
So what are your views towards the remake of OldBoy; do you look forward to seeing how Hollywood has adapted the storyline or do you wish they would learn when to leave a good thing alone? Let us know.
Lover of Korean hip-hop and indie music...and Unicorns.
Even those who say they're against Hollywood remakes would have to say that the trailer makes them at least a little curious to see the finished film. Besides, considering that the Korean film is itself an adaption, the whole 'remakes are a sign of a lack of creativity' argument seems invalid.
I can understand that people think the original film should be respected, but remakes can be respectable works of art in their own right. What I find the most saddening out of all this isn't that Hollywood is so fond of remakes but people's unwillingness to watch subtitled movies.
Even those who say they're against Hollywood remakes would have to say that the trailer makes them at least a little curious to see the finished film. Besides, considering that the Korean film is itself an adaption, the whole 'remakes are a sign of a lack of creativity' argument seems invalid. I can understand that people think the original film should be respected, but remakes can be respectable works of art in their own right. What I find the most saddening out of all this isn't that Hollywood is so fond of remakes but people's unwillingness to watch subtitled movies.