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Journal of Experimental & Clinical... Jan 2009To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall... (Meta-Analysis)
Meta-Analysis
PURPOSE
To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment.
METHODS
A meta-analysis of randomized controlled trials (RCT) was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently.
RESULTS
A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84-1.25, p = 0.77). Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 - 1.03) and brain tumor progression (OR = 1.11, 95% CI 0.9 - 1.3) when the two arms were compared.
CONCLUSION
Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide), have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast) to have positive action in lung and breast carcinoma brain metastases in association with WBRT.
Topics: Adult; Brain Neoplasms; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Dose Fractionation, Radiation; Humans; Radiation-Sensitizing Agents; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19126230
DOI: 10.1186/1756-9966-28-1 -
Oncology (Williston Park, N.Y.) May 2006Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain... (Review)
Review
Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
Topics: Brain Neoplasms; Carcinoma, Renal Cell; Dacarbazine; Humans; Kidney Neoplasms; Metalloporphyrins; Neoplasm Metastasis; Radiation Oncology; Radiation-Sensitizing Agents; Radiosurgery; Temozolomide
PubMed: 16773845
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Oct 1999That hypoxic tissues are more resistant to the effects of radiation than well-oxygenated tissues has been known for many decades, and repeated in vitro demonstrations... (Review)
Review
That hypoxic tissues are more resistant to the effects of radiation than well-oxygenated tissues has been known for many decades, and repeated in vitro demonstrations have confirmed that to achieve the same degree of cytotoxicity, hypoxic cells require about three times the radiation dose that well-oxygenated cells need. Hypoxic cell sensitizers enhance the tissue response to standard radiation, generally by mimicking the effects of oxygen, which induces the formation and stabilization of toxic DNA radicals. Although many hypoxic cell sensitizers like the nitroimidazoles have been evaluated in combination with radiation, these agents have had no or only minimal therapeutic impact due to either their limited potency or their toxicity at biologically relevant concentrations. This article reviews several new modalities that either increase oxygen delivery or sensitize hypoxic tissues. These modalities, all currently in early clinical evaluations, include: (1) tirapazamine, a bioreductive agent; (2) gadolinium texaphyrin, a hypoxic cell sensitizer with biolocalization properties using magnetic resonance imaging; (3) RSR13, an allosteric modifier of hemoglobin; and (4) bovine hemoglobin modified by the attachment of polyethylene glycol polymers.
Topics: Animals; Antineoplastic Agents; Cell Hypoxia; Clinical Trials as Topic; Combined Modality Therapy; DNA Damage; Hemoglobins; Humans; Metalloporphyrins; Neoplasms; Radiation-Sensitizing Agents; Tirapazamine; Triazines
PubMed: 10550828
DOI: No ID Found -
PloS One 2012Recent research has revealed various molecular markers in lung cancer. However, the organizational principles underlying their genetic regulatory networks still await...
Recent research has revealed various molecular markers in lung cancer. However, the organizational principles underlying their genetic regulatory networks still await investigation. Here we performed Network Component Analysis (NCA) and Pathway Crosstalk Analysis (PCA) to construct a regulatory network in human lung cancer (A549) cells which were treated with 50 uM motexafin gadolinium (MGd), a metal cation-containing chemotherapeutic drug for 4, 12, and 24 hours. We identified a set of key TFs, known target genes for these TFs, and signaling pathways involved in regulatory networks. Our work showed that putative interactions between these TFs (such as ESR1/Sp1, E2F1/Sp1, c-MYC-ESR, Smad3/c-Myc, and NFKB1/RELA), between TFs and their target genes (such as BMP41/Est1, TSC2/Myc, APE1/Sp1/p53, RARA/HOXA1, and SP1/USF2), and between signaling pathways (such as PPAR signaling pathway and Adipocytokines signaling pathway). These results will provide insights into the regulatory mechanism of MGd-treated human lung cancer cells.
Topics: Antineoplastic Agents; Cell Line, Tumor; Computational Biology; Gene Regulatory Networks; Humans; Lung Neoplasms; Metalloporphyrins; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 22693540
DOI: 10.1371/journal.pone.0031984 -
Discover Oncology Apr 2024Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled...
PURPOSE
Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled with the need to consider the tolerance of normal tissues and the potential effects on neurocognitive function, impose constraints on the amount of RT that can be safely delivered. A strategy for augmenting the effectiveness of RT involves the utilization of radiation sensitizers (RS). Directly implanting RS-loaded fibrin glue (FG) into the tumor resection cavity would by-pass the blood brain barrier, potentially enhancing the impact of RT on tumor recurrence. This study investigated the ability of FG to incorporate and release, in non-degraded form, the radiation sensitizers 5-Fluorouracil (5FU) and Motexafin gadolinium (MGd).
METHODS
FG layers were created in a 24-well plate by combining thrombin, fibrinogen, and 5FU or MGd. Supernatants from these layers were collected at various intervals and added to F98 glioma spheroid cultures in 96-well plates. Radiation was applied either before or after RS application as single or fractionated dosages. Spheroid growth was monitored for 14 days.
RESULTS
Combined treatment of FG-released 5FU and RT significantly inhibited spheroid growth compared to RS or RT as a single treatment. As a free drug, MGd demonstrated its efficacy in reducing spheroid volume, but had diminished potency as a released RS. Fractionated radiation was more effective than single dose radiation.
CONCLUSION
Non-degraded RS was released from the FG for up to 72 h. FG-released 5FU greatly increased the efficacy of radiation therapy.
PubMed: 38573401
DOI: 10.1007/s12672-024-00953-x -
PloS One 2013Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal...
BACKGROUND
Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS.
METHODOLOGY
Human umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation.
PRINCIPAL FINDINGS
In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.
CONCLUSION
Results of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd functions as a potential therapeutic agent to inhibit the proliferation of SMCs, which may open alternative avenues to improve the long-term patency of TIPS.
Topics: Animals; Cells, Cultured; Contrast Media; Magnetic Resonance Imaging; Metalloporphyrins; Swine
PubMed: 23468986
DOI: 10.1371/journal.pone.0057419 -
PloS One 2020COVID-19 is a critical pandemic that has affected human communities worldwide, and there is an urgent need to develop effective drugs. Although there are a large number...
BACKGROUND
COVID-19 is a critical pandemic that has affected human communities worldwide, and there is an urgent need to develop effective drugs. Although there are a large number of candidate drug compounds that may be useful for treating COVID-19, the evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary.
METHOD
In this study, we applied the recently proposed method tensor decomposition (TD)-based unsupervised feature extraction (FE) to gene expression profiles of multiple lung cancer cell lines infected with severe acute respiratory syndrome coronavirus 2. We identified drug candidate compounds that significantly altered the expression of the 163 genes selected by TD-based unsupervised FE.
RESULTS
Numerous drugs were successfully screened, including many known antiviral drug compounds such as C646, chelerythrine chloride, canertinib, BX-795, sorafenib, sorafenib, QL-X-138, radicicol, A-443654, CGP-60474, alvocidib, mitoxantrone, QL-XII-47, geldanamycin, fluticasone, atorvastatin, quercetin, motexafin gadolinium, trovafloxacin, doxycycline, meloxicam, gentamicin, and dibromochloromethane. The screen also identified ivermectin, which was first identified as an anti-parasite drug and recently the drug was included in clinical trials for SARS-CoV-2.
CONCLUSIONS
The drugs screened using our strategy may be effective candidates for treating patients with COVID-19.
Topics: A549 Cells; Antiviral Agents; Betacoronavirus; Drug Discovery; Humans; SARS-CoV-2; Unsupervised Machine Learning
PubMed: 32915876
DOI: 10.1371/journal.pone.0238907 -
NMR in Biomedicine Jun 2015The purpose of this study was to investigate the feasibility of interventional MRI-guided local agent delivery into pig common bile duct (CBD) walls using a newly...
The purpose of this study was to investigate the feasibility of interventional MRI-guided local agent delivery into pig common bile duct (CBD) walls using a newly designed MR-compatible, needle-integrated balloon catheter system. We first designed a needle-integrated balloon catheter system that comprised of a 22 G MR-compatible Chiba biopsy needle and a conventional 12 mm × 2 cm balloon catheter. Under fluoroscopy guidance, a custom needle-balloon system was positioned in the target CBD via a transcholecystic access. T1-weighted MRI was used to localize and reposition the needle-balloon system in the target. A 0.5 mL mixture of motexafin gadolinium (MGd) and trypan blue dye as well as 5-fluorouracil was delivered into the CBD wall through the needle-balloon system. Post-infusion T1-weighted MRI was obtained and contrast-to-noise ratios (CNRs) of CBD walls of pre- and post-MGd-blue infusions were compared by a paired t-test. In addition, post-infusion x-ray cholangiography was achieved to evaluate the potential injuries of CBDs by the needle-balloon system. Subsequent histologic analysis was performed to correlate and confirm the imaging findings. A post-infusion cholangiogram did not show any extravasation of contrast agent, indicating no procedure-related damage to the CBDs. MRI demonstrated clear enhancement of the target bile duct walls infused with MGd-trypan blue dye with average penetration depth of 4.7 ± 1.2 mm and an average MGd perfusion length of 21 ± 1.5 mm in the bile ducts and their surrounding tissues. The average CNR of the post-infusion bile ducts was significant higher than that of the pre-infusion bile ducts (110.6 ± 22 versus 5.7 ± 2.8, p < 0.0001). Histology depicted the blue dye staining and red fluorescence of MGd through the target CBD walls, which was well correlated with the imaging findings. It is feasible to use the new MR-compatible, needle-integrated balloon catheter system for intrabiliary local agent delivery into CBD walls under MRI guidance, which may open new avenues for efficient management of pancreatobiliary malignancies using MR-guided interventional oncology.
Topics: Animals; Antineoplastic Agents; Bile Ducts; Catheters; Cholangiopancreatography, Magnetic Resonance; Equipment Design; Equipment Failure Analysis; Infusions, Parenteral; Magnetic Resonance Imaging, Interventional; Needles; Swine; Systems Integration
PubMed: 25900480
DOI: 10.1002/nbm.3308 -
Dalton Transactions (Cambridge, England... Dec 2009The synthesis of a new PEG-solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH(3))(2) moiety is described. The effect of the tumor...
The synthesis of a new PEG-solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH(3))(2) moiety is described. The effect of the tumor localizing Gd-Tex macrocycle on platinum activity was evaluated in cell culture. The malonate moiety, analogous to that present in carboplatin, is expected to release an aquated Pt(NH(3))(2) species under physiological conditions. The half-life in phosphate-buffered saline was found to be ca. 3 days at room temperature, and the hydrolytic product released from the conjugate was collected and confirmed as Pt-based by flameless atomic absorption spectrophotometry. Anti-proliferative activity was tested using A549 human lung cancer and A2780 human ovarian cancer cell lines. In both cell lines, the activity of the Gd-Tex conjugate was found to be similar to that of carboplatin. Efficacy against a Pt-resistant ovarian cell line greater than that displayed by carboplatin was also observed.
Topics: Antineoplastic Agents; Carboplatin; Cell Line, Tumor; Coordination Complexes; Drug Resistance, Neoplasm; Humans; Metalloporphyrins; Platinum
PubMed: 20023913
DOI: 10.1039/b912089k -
Journal of Porphyrins and... Jul 2011The synthesis and characterization of two 18-crown-6 functionalized analogues of an extensively studied gadolinium texaphyrin derivative, motexafin gadolinium (1, MGd),...
The synthesis and characterization of two 18-crown-6 functionalized analogues of an extensively studied gadolinium texaphyrin derivative, motexafin gadolinium (1, MGd), are reported. These are the monomeric and dimeric species, compounds 2 and 3, respectively. Both crown ether functionalized species proved to be stable at physiological pH and revealed distinct shifts in the UV spectrum when treated with sodium-, potassium-, ammonium- or zinc(II)-salts. Zinc(II) is believed to play a major role regulating apoptosis mechanisms in cancerous cells. Therefore, cytotoxicity studies of 2 and 3 were carried out using Ramos cell lines in the presence and absence of zinc(II).
PubMed: 22025887
DOI: 10.1142/S108842461100315X