“…Other upregulated genes include SPAG1, which is a cancer antigen 24,25 . Actin beta 2 like is downregulated in two of the palladium arms, and this gene has recently been shown to be upregulated in colon cancer 26 .Figure 7Microarray analysis of RNA expression in LM36R xenograft tumor reveal consistency of gene profile changes. Gene array results were tabulated in a visual heat map based on RNA expression level fold changes between +3 and −3.…”
IGF1R and CD44 are overexpressed in most advanced melanomas so we designed chemotherapeutic nanoparticles to target those receptors. Tris(dibenzylideneacetone)dipalladium (Tris DBA-Pd) is a novel inhibitor of
N
-myristoyltransferase 1 (NMT-1) and has proven
in vivo
activity against melanoma. However, poor solubility impairs its effectiveness. To improve its therapeutic efficacy and overcome drug resistance in advanced melanomas, we synthesized Tris DBA-Pd hyaluronic acid nanoparticles (Tris DBA-Pd HANP) and evaluated them against
in vivo
xenografts of LM36R, an aggressive BRAF mutant human melanoma resistant to BRAF inhibitors. We treated xenografted mice in four arms: empty HANPs, free Tris DBA-Pd, Tris DBA-Pd HANPs, and Tris DBA-Pd HANPs with IGF1R antibody. The Tris DBA-Pd HANP group was the most responsive to treatment and showed the greatest depletion of CD44-positive cells on IHC. Surprisingly, the HANP containing IGF1R antibody was less effective than particles without antibody, possibly due to steric hindrance of IGF1R and CD44 binding. Tris DBA-Pd nanoparticles are an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.
“…Other upregulated genes include SPAG1, which is a cancer antigen 24,25 . Actin beta 2 like is downregulated in two of the palladium arms, and this gene has recently been shown to be upregulated in colon cancer 26 .Figure 7Microarray analysis of RNA expression in LM36R xenograft tumor reveal consistency of gene profile changes. Gene array results were tabulated in a visual heat map based on RNA expression level fold changes between +3 and −3.…”
IGF1R and CD44 are overexpressed in most advanced melanomas so we designed chemotherapeutic nanoparticles to target those receptors. Tris(dibenzylideneacetone)dipalladium (Tris DBA-Pd) is a novel inhibitor of
N
-myristoyltransferase 1 (NMT-1) and has proven
in vivo
activity against melanoma. However, poor solubility impairs its effectiveness. To improve its therapeutic efficacy and overcome drug resistance in advanced melanomas, we synthesized Tris DBA-Pd hyaluronic acid nanoparticles (Tris DBA-Pd HANP) and evaluated them against
in vivo
xenografts of LM36R, an aggressive BRAF mutant human melanoma resistant to BRAF inhibitors. We treated xenografted mice in four arms: empty HANPs, free Tris DBA-Pd, Tris DBA-Pd HANPs, and Tris DBA-Pd HANPs with IGF1R antibody. The Tris DBA-Pd HANP group was the most responsive to treatment and showed the greatest depletion of CD44-positive cells on IHC. Surprisingly, the HANP containing IGF1R antibody was less effective than particles without antibody, possibly due to steric hindrance of IGF1R and CD44 binding. Tris DBA-Pd nanoparticles are an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.
“…1.0 g of the control and/or the malignant tissue sample was homogenized with liquid nitrogen in a mortar with pestle, suspended in chilled modified lysis buffer, vortexed for 1 h and then centrifuged at 14 000 rpm for 90 min at 4 °C (Eppendorf Centrifuge, 5417R), as described previously . Resulting supernatant was aliquot and stored at −80 °C.…”
Section: Methodsmentioning
confidence: 99%
“…2‐DE was performed to obtain proteome profile of tissue lysate samples by mixing in appropriate volume of the rehydration buffer; a total of 320 µL containing ≈800 µg total protein loaded onto 17 cm, pH 3–10 linear IPG strips (Serva Electrophoresis, Heidelberg, Germany) followed by processing and focusing as described previously . After IEF, IPG strips were equilibrated in the equilibration buffers, followed by SDS‐PAGE analysis, colloidal Coomassie G‐250 staining, destaining, scanning of gels, and comparative profiling of gel images by ImageMaster 2D Platinum 7.0 (GE Healthcare Amersham Biosciences) software in terms of each spot pI and MW investigation, with subsequent matching and quantification as described . Non‐parametric Mann–Whitney U test was applied on the same protein's multiple spots intensities and false discovery rate (FDR) was determined as mentioned …”
Section: Methodsmentioning
confidence: 99%
“…More specifically, identification of proteins differentially represented in OC tissues compared to normal ovarian tissues can provide potential diagnostic, prognostic, and therapeutic biomarkers and thus, may facilitate in deciding the available treatment choice(s) . Amongst the various proteomic approaches used for biomarker identification, 2D gel electrophoresis (2‐DE) followed by mass spectrometric (MS) identification of the differentially regulated molecules, has customarily been utilized in numerous malignancies …”
Purpose
An early and accurate diagnosis of ovarian carcinoma (OC) may reduce morbidity and mortality of the patients. To improve the clinical outcome in OC patients, the present study is aimed at identifying robust biomarkers for early OC diagnosis.
Experimental Design
In order to look for early‐stage protein markers, a systematic protein profiling approach involving 2‐dimensional electrophoresis coupled with mass spectrometric analyses of human malignant and non‐malignant ovarian biopsy samples, is performed.
Results
Six 2D gel spots, corresponding to five proteins, display statistically significant differential expression in the tumor tissues compared to benign controls (FDR ≤ 0.05; PMF score ≥ 79). Ingenuity pathway analysis predicts two proteins, that is, Ca2+‐dependent membrane‐binding protein annexin A6 (AnxA6) and the metabolic enzyme l‐lactate dehydrogenase A chain, as potential predictive biomarkers. Increased expression of AnxA6 is further ascertained by Western blot and enzyme linked immunosorbent assay in the resected tissues and the plasma samples. The expression is found markedly increasing particularly in the advanced stage tumors.
Conclusions and Clinical Relevance
The significant upregulation of AnxA6 in OC, reported for the first time, is likely to provide insight into the mechanism of OC progression, which may lead to the design of potential diagnostic and therapeutic strategies.
“…Many proteomic approaches have been used in the search for potential diagnostic biomarkers. Ghazanfar et al (36) performed two-dimensional gel electrophoresis coupled with mass spectrometry for the expression profiling of proteins extracted from freshly frozen human colorectal cancer tissue specimens (12 patients) and neighboring non-tumor tissue, and they demonstrated the upregulation of some proteins, such as actin beta-like 2 (ACTBL2), in colorectal cancer. Hao et al (37) used high-resolution Fourier transform mass spectrometry to evaluate 22 pairs of cancerous and adjacent normal tissue specimens that were gathered from 22 individuals and revealed an overexpression of dipeptidase 1 (DPEP1) in colorectal tumor tissue.…”
Colorectal cancer is one of the most common cancers in the world, and it is one of the leading causes of cancer-related death. Despite recent progress in the development of screening programs and in the management of patients with colorectal cancer, there are still many gaps to fill, ranging from the prevention and early diagnosis to the determination of prognosis factors and treatment of metastatic disease, to establish a personalized approach. The genetic profile approach has been increasingly used in the decision-making process, especially in the choice of targeted therapies and in the prediction of drug response, but there are still few validated biomarkers of colorectal cancer for clinical practice. The discovery of non-invasive, sensitive, and specific biomarkers is an urgent need, and translational proteomics play a key role in this process, as they enable better comprehension of colorectal carcinogenesis, identification of potential markers, and subsequent validation. This review provides an overview of recent advances in the search for colorectal cancer biomarkers through proteomics studies according to biomarker function and clinical application.
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