Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.
In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their "anti-invadopo...
Source: Translational Oncology - September 13, 2018 Category: Cancer & Oncology Authors: Whitehead CA, Nguyen HPT, Morokoff AP, Luwor RB, Paradiso L, Kaye AH, Mantamadiotis T, Stylli SS Tags: Transl Oncol Source Type: research
Determination of Hepatocellular Carcinoma and Characterization of Hepatic Focal Lesions with Adaptive Multi-Exponential Intravoxel Incoherent Motion Model.
CONCLUSION: The adaptive multi-exponential IVIM model was useful and reliable to distinguish HCC from other hepatic lesions. PMID: 30216762 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Zhang HX, Zhang XS, Kuai ZX, Zhou Y, Sun YF, Ba ZC, He KB, Sang XQ, Yao YF, Chu CY, Zhu YM Tags: Transl Oncol Source Type: research
Sorcin a Potential Molecular Target for Cancer Therapy.
Abstract Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca2+) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as comp...
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Shabnam B, Padmavathi G, Banik K, Girisa S, Monisha J, Sethi G, Fan L, Wang L, Mao X, Kunnumakkara AB Tags: Transl Oncol Source Type: research
Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.
Abstract PURPOSE: Relapsed/refractory pediatric cancers show poor prognosis; however, their genomic patterns remain unknown. To investigate the genetic mechanisms of tumor relapse and therapy resistance, we characterized genomic alterations in diagnostic and relapsed lesions in patients with relapsed/refractory pediatric solid tumors using targeted deep sequencing. PATIENTS AND METHODS: A targeted sequencing panel covering the exons of 381 cancer genes was used to characterize 19 paired diagnostic and relapsed samples from patients with relapsed/refractory pediatric solid tumors. RESULTS: The mean covera...
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Lee B, Lee JW, Shim JH, Joung JG, Yun JW, Bae JS, Shin HT, Sung KW, Park WY Tags: Transl Oncol Source Type: research
Clinical Validation of Automatable Gaussian Normalized CBV in Brain Tumor Analysis: Superior Reproducibility and Slightly Better Association with Survival than Current Standard Manual Normal Appearing White Matter Normalization.
CONCLUSION: GN-nCBV has a slightly better association with clinical gold standard OS than conventional WM-nCBV in our glioblastoma patient cohort. This equivalent or superior validity, combined with the advantages of higher reproducibility, lower interoperator variability, and easier automation, makes GN-nCBV superior to WM-nCBV for clinical and research use in glioma patients. We recommend widespread adoption and incorporation of GN-nCBV into commercial dynamic susceptibility contrast processing software. PMID: 30216765 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Qin L, Li X, Li A, Cheng S, Qu J, Reinshagen K, Hu J, Himes N, Lu G, Young GS Tags: Transl Oncol Source Type: research
The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells.
Abstract TP53 is the most frequently mutated gene in human cancer and thus an attractive target for novel cancer therapy. Several compounds that can reactive mutant p53 protein have been identified. APR-246 is currently being tested in a phase II clinical trial in high-grade serous ovarian cancer. We have used RNA-seq analysis to study the effects of APR-246 on gene expression in human breast cancer cell lines. Although the effect of APR-246 on gene expression was largely cell line dependent, six genes were upregulated across all three cell lines studied, i.e., TRIM16, SLC7A11, TXNRD1, SRXN1, LOC344887, and SLC7A1...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Synnott NC, Madden SF, Bykov VJN, Crown J, Wiman KG, Duffy MJ Tags: Transl Oncol Source Type: research
Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma.
to MA Abstract Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. In physiological condition, autophagy funnels cytoplasmic constituents to autophagolysosomes for degradation and is an alternative way for cell-death behavior. Here, we inspected autophagy as a prosurvival mechanism essential for drug resistance in multiple myeloma (MM). Accordingly, autophagy inhibitors used in association to conventional anti-MM drugs might enforce the effect against resistant MM plasma cells and render autophagy a new therapeutic target. PMID: 30196237 [P...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Desantis V, Saltarella I, Lamanuzzi A, Mariggiò MA, Racanelli V, Vacca A, Frassanito MA Tags: Transl Oncol Source Type: research
Survival Impact of Delaying Postoperative Radiotherapy in Patients with Esophageal Cancer.
Abstract The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards mo...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Wang Y, Guan S, Bi Y, Lin S, Ma J, Xing Q, Liu C, Zhang R, Qu Z, Jiang P, Chen X, Cheng Y Tags: Transl Oncol Source Type: research
Short-Term Responders of Non-Small Cell Lung Cancer Patients to EGFR Tyrosine Kinase Inhibitors Display High Prevalence of TP53 Mutations and Primary Resistance Mechanisms.
Abstract Non-small cell lung cancer (NSCLC) with activating EGFR mutations in exon 19 and 21 typically responds to EGFR tyrosine kinase inhibitors (TKI); however, for some patients, responses last only a few months. The underlying mechanisms of such short responses have not been fully elucidated. Here, we sequenced the genomes of 16 short-term responders (SR) that had progression-free survival (PFS) of less than 6 months on the first-generation EGFR TKI and compared them to 12 long-term responders (LR) that had more than 24 months of PFS. All patients were diagnosed with advanced lung adenocarcinoma and harbored E...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Xu Y, Tong X, Yan J, Wu X, Shao YW, Fan Y Tags: Transl Oncol Source Type: research
Development and Validation of Nomograms for Predicting Overall and Breast Cancer-Specific Survival in Young Women with Breast Cancer: A Population-Based Study.
The objective of current study was to develop and validate comprehensive nomograms for predicting the survival of young women with breast cancer. METHODS: Women aged
Source: Translational Oncology - September 3, 2018 Category: Cancer & Oncology Authors: Gong Y, Ji P, Sun W, Jiang YZ, Hu X, Shao ZM Tags: Transl Oncol Source Type: research
Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer.
aucler C Abstract Human cytomegalovirus (HCMV) has been detected in various types of tumors. We studied the prevalence of HCMV in ovarian cancer and its relation to clinical outcome. Paraffin-embedded tissues obtained prospectively from 45 patients with ovarian cancer and 30 patients with benign ovarian cystadenoma were analyzed for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Plasma was analyzed for HCMV serology. HCMV-IgG levels were higher in patients with ovarian cancer or benign cystadenoma than in age-matched controls (P = .002, P
Source: Translational Oncology - August 30, 2018 Category: Cancer & Oncology Authors: Rådestad AF, Estekizadeh A, Cui HL, Kostopoulou ON, Davoudi B, Hirschberg AL, Carlson J, Rahbar A, Söderberg-Naucler C Tags: Transl Oncol Source Type: research
Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation.
Abstract The current study reveals the clinicopathological association of PD-L1 in Hong Kong esophageal squamous cell carcinoma (ESCC) patients and the differential regulation of PD-L1 by standard first-line chemotherapy in ESCC. Immunohistochemical analysis of tissue microarray data from 84 Hong Kong ESCC patients shows that PD-L1 was expressed in 21% of the tumors. Positive PD-L1 staining was significantly associated with later disease stage (stages III and IV) (P value = .0379) and lymph node metastasis (P value = .0466) in the Hong Kong cohort. Furthermore, PD-L1 expression was significantly induced in ESCC ce...
Source: Translational Oncology - August 30, 2018 Category: Cancer & Oncology Authors: Ng HY, Li J, Tao L, Lam AK, Chan KW, Ko JMY, Yu VZ, Wong M, Li B, Lung ML Tags: Transl Oncol Source Type: research
Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity.
In conclusion, genomic alterations in ESCC are highly heterogeneous, impacting negatively in target therapy development. PMID: 30172240 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 29, 2018 Category: Cancer & Oncology Authors: Souza-Santos PT, Soares Lima SC, Nicolau-Neto P, Boroni M, Meireles Da Costa N, Brewer L, Menezes AN, Furtado C, Moreira MAM, Seuanez HN, de Almeida Simão T, Ribeiro Pinto LF Tags: Transl Oncol Source Type: research
Somatic TP53 Mutations Are Detectable in Circulating Tumor DNA from Children with Anaplastic Wilms Tumors.
CONCLUSION: We demonstrate for the first time that ddPCR is an effective method for detection of mutant TP53 in ctDNA from children with DAWT even when there is intratumoral somatic heterogeneity. This should be further explored in a larger cohort of patients, as early detection of circulating variant TP53 may have significant clinical impact on future risk stratification and surveillance. PMID: 30172241 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 29, 2018 Category: Cancer & Oncology Authors: Treger TD, Chagtai T, Butcher R, Cresswell GD, Al-Saadi R, Brok J, Williams RD, Roberts C, Luscombe NM, Pritchard Jones K, Mifsud W Tags: Transl Oncol Source Type: research
Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance.
g O Abstract Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with frequent post-surgical local recurrence. The combination of adjuvant chemotherapy with radiotherapy is under consideration to achieve a prolonged progression-free survival (PFS). To date, few studies have determined the proteome profiles associated with response to adjuvant chemoradiation. We herein analyzed the proteomes of primary PDAC tumors subjected to additive chemoradiation after surgical resection and achieving short PFS (median 6 months) versus prolonged PFS (median 28 months). Proteomic analysis revealed the overexpression of ...
Source: Translational Oncology - August 29, 2018 Category: Cancer & Oncology Authors: Oria VO, Bronsert P, Thomsen AR, Föll MC, Zamboglou C, Hannibal L, Behringer S, Biniossek ML, Schreiber C, Grosu AL, Bolm L, Rades D, Keck T, Werner M, Wellner UF, Schilling O Tags: Transl Oncol Source Type: research
Aminopeptidase N (CD13): Expression, Prognostic Impact, and Use as Therapeutic Target for Tissue Factor Induced Tumor Vascular Infarction in Soft Tissue Sarcoma.
emann C Abstract Aminopeptidase N (CD13) is expressed on tumor vasculature and tumor cells. It represents a candidate for targeted therapy, e.g., by truncated tissue factor (tTF)-NGR, binding to CD13, and causing tumor vascular thrombosis. We analyzed CD13 expression by immunohistochemistry in 97 patients with STS who were treated by wide resection and uniform chemo-radio-chemotherapy. Using a semiquantitative score with four intensity levels, CD13 was expressed by tumor vasculature, or tumor cells, or both (composite value, intensity scores 1-3) in 93.9% of the STS. In 49.5% tumor cells, in 48.5% vascular/perivas...
Source: Translational Oncology - August 17, 2018 Category: Cancer & Oncology Authors: Kessler T, Baumeier A, Brand C, Grau M, Angenendt L, Harrach S, Stalmann U, Schmidt LH, Gosheger G, Hardes J, Andreou D, Dreischalück J, Lenz G, Wardelmann E, Mesters RM, Schwöppe C, Berdel WE, Hartmann W, Schliemann C Tags: Transl Oncol Source Type: research
Inhibitor of DNA Binding 2 Inhibits Epithelial-Mesenchymal Transition via Up-Regulation of Notch3 in Breast Cancer.
Abstract Breast cancer is the second leading cause of cancer death in women worldwide. Incurable metastatic breast disease presents a major clinical challenge and is the main cause of breast cancer-related death. The epithelial-mesenchymal transition (EMT) is a critical early promoter of metastasis. In the present study, we identified a novel role for the inhibitor of DNA binding 2 (Id2), a member of the basic helix-loop-helix protein family, during the EMT of breast cancer. Expression of Id2 was positively correlated with Notch3 in breast cancer cells. Low expression of Id2 and Notch3 was associated with worse di...
Source: Translational Oncology - August 14, 2018 Category: Cancer & Oncology Authors: Wen XF, Chen M, Wu Y, Chen MN, Glogowska A, Klonisch T, Zhang GJ Tags: Transl Oncol Source Type: research
Establishment and Characterization of Paired Primary and Peritoneal Seeding Human Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic Potential.
Abstract Peritoneal metastasis is one of the major patterns of unresectability in colorectal cancer (CRC) and a cause of death in advanced CRC. Identification of distinct gene expressions between primary CRC and peritoneal seeding metastasis is to predict the metastatic potential of primary human CRC. Three pairs of primary CRC (SNU-2335A, SNU-2404A, and SNU-2414A) and corresponding peritoneal seeding (SNU-2335D, SNU-2404B, and SNU-2414B) cell lines were established to determine the different gene expressions and resulting aberrated signaling pathways in peritoneal metastasis tumor using whole exome sequencing and...
Source: Translational Oncology - August 13, 2018 Category: Cancer & Oncology Authors: Kim SC, Hong CW, Jang SG, Kim YA, Yoo BC, Shin YK, Jeong SY, Ku JL, Park JG Tags: Transl Oncol Source Type: research
Overexpression of miRNA 4451 is Associated With a Poor Survival of Patients With Hypopharyngeal Cancer After Surgery With Postoperative Radiotherapy.
Abstract Hypopharyngeal cancer (HC) is the most common subset of head and neck cancers. These tumors often have an aggressive clinical outcome characterized by local invasion and regional nodal metastasis. Upregulated miRNAs might be useful as biomarkers for prognosis and molecular targets for these tumors. We determined tumor expression of candidate miRNAs using microarray in 8 HC patients and validated in 372 HC patients. We also used paired tumorous and mucosal tissue to verify the miRNA expression. Log-rank test and Cox model were used to evaluate the survival; and Harrell's C-index was used to compare concord...
Source: Translational Oncology - August 10, 2018 Category: Cancer & Oncology Authors: Xu X, Liu H, Gross N, Wei D, Qian Y, Li W, Wei P, Li G, Zhang F, Yang Z, Lei D, Pan X Tags: Transl Oncol Source Type: research
Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography.
Abstract PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO2) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO2 upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for tr...
Source: Translational Oncology - August 10, 2018 Category: Cancer & Oncology Authors: Balasundaram G, Ding L, Li X, Attia ABE, Dean-Ben XL, Ho CJH, Chandrasekharan P, Tay HC, Lim HQ, Ong CB, Mason RP, Razansky D, Olivo M Tags: Transl Oncol Source Type: research
A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer.
The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer-associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls. In the development cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and RMRP) displayed a considerably high plasma level in lung cancer patients vs. cancer-free controls (all P
Source: Translational Oncology - August 8, 2018 Category: Cancer & Oncology Authors: Lin Y, Leng Q, Zhan M, Jiang F Tags: Transl Oncol Source Type: research
Measuring KRAS Mutations in Circulating Tumor DNA by Droplet Digital PCR and Next-Generation Sequencing.
Abstract Measuring total cell-free DNA (cfDNA) or cancer-specific mutations herein has presented as new tools in aiding the treatment of cancer patients. Studies show that total cfDNA bears prognostic value in metastatic colorectal cancer (mCRC) and that measuring cancer-specific mutations could supplement biopsies. However, limited information is available on the performance of different methods. Blood samples from 28 patients with mCRC and known KRAS mutation status were included. cfDNA was extracted and quantified with droplet digital polymerase chain reaction (ddPCR) measuring Beta-2 Microglobulin. KRAS mutati...
Source: Translational Oncology - August 4, 2018 Category: Cancer & Oncology Authors: Demuth C, Spindler KG, Johansen JS, Pallisgaard N, Nielsen D, Hogdall E, Vittrup B, Sorensen BS Tags: Transl Oncol Source Type: research
Dll1 Marks Cells of Origin of Ras-Induced Cancer in Mouse Squamous Epithelia.
Abstract The Notch signaling pathway has been implicated in homeostasis and disease, including cancer, in various tissues. Moreover, it has been involved both in stem cell maintenance and differentiation, in a context-dependent manner. Stem/progenitor cells, on the other hand, have long been suspected to be the cells of origin in various malignancies. In order to gain insight in the role of the Notch ligand Dll1 in mouse development, we generated a knock-in line expressing an inducible Cre recombinase. We have employed in vivo approaches in mice to genetically mark rare subpopulations of cells expressing Dll1 in v...
Source: Translational Oncology - August 3, 2018 Category: Cancer & Oncology Authors: Vasilaki E, Kanaki Z, Stravopodis DJ, Klinakis A Tags: Transl Oncol Source Type: research
Prognostic Significance of CSN2, CD8, and MMR Status-Associated Nomograms in Patients with Colorectal Cancer.
CONCLUSIONS: CSN2, CD8+ TILs, and MMR status were independent prognostic factors. The nomograms could be used to generate individualized predictions for DFS and OS. PMID: 30075461 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 31, 2018 Category: Cancer & Oncology Authors: Zhu B, Zhang P, Liu M, Jiang C, Liu H, Fu J Tags: Transl Oncol Source Type: research
Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis.
CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment. PMID: 30071442 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 30, 2018 Category: Cancer & Oncology Authors: Advani SM, Advani P, DeSantis SM, Brown D, VonVille HM, Lam M, Loree JM, Sarshekeh AM, Bressler J, Lopez DS, Daniel CR, Swartz MD, Kopetz S Tags: Transl Oncol Source Type: research
Immunogenomics Analysis Reveals that TP53 Mutations Inhibit Tumor Immunity in Gastric Cancer.
Abstract Although immunotherapy continues to demonstrate efficacy in a variety of refractory cancers, currently, no any immunotherapeutic strategy is clinically used for gastric cancer (GC) except its microsatellite instable subtype. Thus, it is important to identify molecular biomarkers for predicting the responders to GC immunotherapy. TP53 mutations frequently occur in GC and are associated with unfavorable clinical outcomes in GC. We performed a comprehensive characterization of the associations between TP53 mutations and immune activities in GC based on two large-scale GC cancer genomics data. We compared exp...
Source: Translational Oncology - July 27, 2018 Category: Cancer & Oncology Authors: Jiang Z, Liu Z, Li M, Chen C, Wang X Tags: Transl Oncol Source Type: research
Safety and Efficacy of Apatinib Combined with Temozolomide in Advanced Melanoma Patients after Conventional Treatment Failure.
CONCLUSIONS: In conclusion, apatinib combined with temozolomide was well tolerated and has demonstrated efficacy in advanced melanoma patients. PMID: 30056366 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 26, 2018 Category: Cancer & Oncology Authors: Cui C, Zhou L, Lian B, Si L, Sheng X, Chi Z, Kong Y, Wang X, Tang B, Mao L, Li S, Dai J, Yan X, Bai X, Guo J Tags: Transl Oncol Source Type: research
Expression Analysis of Platinum Sensitive and Resistant Epithelial Ovarian Cancer Patient Samples Reveals New Candidates for Targeted Therapies.
The objective of this study was to identify mechanisms of therapy resistance and potential biomarkers by analyzing mRNA and protein expression from samples derived from patients with platinum-sensitive and -resistant ovarian cancer (total cohort n = 53). The data revealed new candidates for targeted therapies, such as GREB1 and ROR2. We showed that the development of platinum resistance correlated with upregulation of ROR2, whereas GREB1 was downregulated. Moreover, we demonstrated that high levels of ROR2 in platinum-resistant samples were associated with upregulation of Wnt5a, STAT3 and NF-kB levels, suggesting that ...
Source: Translational Oncology - July 26, 2018 Category: Cancer & Oncology Authors: Veskimäe K, Scaravilli M, Niininen W, Karvonen H, Jaatinen S, Nykter M, Visakorpi T, Mäenpää J, Ungureanu D, Staff S Tags: Transl Oncol Source Type: research
Variable Responses of MYC Translocation Positive Lymphoma Cell Lines To Different Combinations of Novel Agents: Impact of BCL2 Family Protein Expression.
Abstract Several newly developed drugs including JQ1 (BET inhibitor), ABT199 (BCL2 inhibitor), and bortezomib (proteasome inhibitor) may offer novel therapeutic strategies for aggressive diffuse large B-cell lymphoma (DLBCL). We tested these drugs together with doxorubicin in a series of combinations in 16 DLBCL cell lines including 4 ABC-DLBCL (OCI-Ly3, OCI-Ly10, SUDHL2, RIVA) and 12 GCB-DLBCL lines (OCI-Ly4, OCI-Ly18, BJAB, SUDHL4, SUDHL6, SUDHL10, DB, PR1, VAL, SC1, Karpas-231, Karpas-422). Among these cell lines, ABT199 and doxorubicin, and to a lesser extent JQ1 and bortezomib, showed high variations in their...
Source: Translational Oncology - July 25, 2018 Category: Cancer & Oncology Authors: Deng W, Clipson A, Liu H, Huang Y, Dobson R, Wang M, Johnson P, Du MQ Tags: Transl Oncol Source Type: research
A Preliminary Proteomic Investigation of Circulating Exosomes and Discovery of Biomarkers Associated with the Progression of Osteosarcoma in a Clinical Model of Spontaneous Disease.
Abstract Circulating cancer exosomes are microvesicles which originate from malignant cells and other organs influenced by the disease and can be found in blood. The exosomal proteomic cargo can often be traced to the cells from which they originated, reflecting the physiological status of these cells. The similarities between cancer exosomes and the tumor cells they originate from exhibit the potential of these vesicles as an invaluable target for liquid biopsies. Exosomes were isolated from the serum of eight osteosarcoma-bearing dogs, five healthy dogs, and five dogs with traumatic fractures. We also characteri...
Source: Translational Oncology - July 24, 2018 Category: Cancer & Oncology Authors: Brady JV, Troyer RM, Ramsey SA, Leeper H, Yang L, Maier CS, Goodall CP, Ruby CE, Albarqi HAM, Taratula O, Bracha S Tags: Transl Oncol Source Type: research
Diffusion-Weighted MRI Is Insensitive to Changes in the Tumor Microenvironment Induced by Antiangiogenic Therapy.
Abstract Antiangiogenic treatment (AAT) used in combination with radiation therapy or chemotherapy is a promising strategy for the treatment of several cancer diseases. The vascularity and oxygenation of tumors may be changed significantly by AAT, and consequently, a noninvasive method for monitoring AAT-induced changes in these microenvironmental parameters is needed. The purpose of this study was to evaluate the potential usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI). DW-MRI was conducted with a Bruker Biospec 7.05-T scanner using four diffusion weightings and diffusion sensitization gradi...
Source: Translational Oncology - July 20, 2018 Category: Cancer & Oncology Authors: Hauge A, Wegner CS, Gaustad JV, Simonsen TG, Andersen LMK, Rofstad EK Tags: Transl Oncol Source Type: research
Efficacy and Safety of Radiotherapy Plus EGFR-TKIs in NSCLC Patients with Brain Metastases: A Meta-Analysis of Published Data.
CONCLUSION: RT plus EGFR-TKIs had higher response rate, longer OS and I-PFS than monotherapy in NSCLC patients with BM. Asian LAC patients with EGFR mutation had a better prognosis with concurrent treatment. The AEs of RT plus EGFR-TKIs were tolerated. PMID: 30032006 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 19, 2018 Category: Cancer & Oncology Authors: Wang X, Xu Y, Tang W, Liu L Tags: Transl Oncol Source Type: research
CBX1 Indicates Poor Outcomes and Exerts Oncogenic Activity in Hepatocellular Carcinoma.
Abstract Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vasc...
Source: Translational Oncology - July 18, 2018 Category: Cancer & Oncology Authors: Yang YF, Pan YH, Tian QH, Wu DC, Su SG Tags: Transl Oncol Source Type: research
PET-based Treatment Response Assessment for Neoadjuvant Chemoradiation in Pancreatic Adenocarcinoma: An Exploratory Study.
CONCLUSIONS: PERCIST1.0 appears to increase the chance of detecting patients with progressive disease compared to the conventional anatomical-based assessment of RECIST1.1. The integration of these additional radiographic metrics in assessing treatment response to nCR for pancreatic adenocarcinoma may provide a promising strategy to better select patients that are most suitable for therapeutic intensification. PMID: 30015263 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 13, 2018 Category: Cancer & Oncology Authors: Dalah E, Tai A, Oshima K, Hall WA, Erickson B, Li XA Tags: Transl Oncol Source Type: research
Development and Validation of a Nomogram for Predicting Overall Survival in Pancreatic NeuroendocrineTumors.
CONCLUSIONS: The nomogram which could predict 3- and 5-year OS were established in this study. Our nomogram showed a good performance, suggesting that it could be served as an effective tool for prognostic evaluation of patients with PNETs. PMID: 30015262 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 12, 2018 Category: Cancer & Oncology Authors: Miao DL, Song W, Qian J, Zhu ZG, Wu Q, Lv CG, Chen L Tags: Transl Oncol Source Type: research
Importance of RIP140 and LCoR Sub-Cellular Localization for Their Association With Breast Cancer Aggressiveness and Patient Survival.
In this study, we investigated RIP140 and LCoR localization (cytoplasm vs nucleus) in BC samples from a well-characterized cohort of patients (n = 320). RIP140 and LCoR were expressed in more than 80% of tumors, (predominantly in the cytoplasm), and the two markers were highly correlated. Expression of RIP140 and LCoR in the nucleus was negatively correlated with tumor size. Conversely, RIP140 and LCoR cytoplasmic expression strongly correlated with expression of two tumor aggressiveness markers: N-cadherin and CD133 (epithelial mesenchymal transition and cancer stem cell markers, respectively). Finally, high RIP140 nu...
Source: Translational Oncology - July 11, 2018 Category: Cancer & Oncology Authors: Sixou S, Müller K, Jalaguier S, Kuhn C, Harbeck N, Mayr D, Engel J, Jeschke U, Ditsch N, Cavaillès V Tags: Transl Oncol Source Type: research
Histogram Analysis Parameters Apparent Diffusion Coefficient for Distinguishing High and Low-Grade Meningiomas: A Multicenter Study.
Abstract Low grade meningiomas have better prognosis than high grade meningiomas. The aim of this study was to measure apparent diffusion coefficient (ADC) histogram analysis parameters in different meningiomas in a large multicenter sample and to analyze the possibility of several parameters for predicting tumor grade and proliferation potential. Overall, 148 meningiomas from 7 institutions were evaluated in this retrospective study. Grade 1 lesions were diagnosed in 101 (68.2%) cases, grade 2 in 41 (27.7%) patients, and grade 3 in 6 (4.1%) patients. All tumors were investigated by MRI (1.5 T scanner) by using di...
Source: Translational Oncology - July 10, 2018 Category: Cancer & Oncology Authors: Surov A, Ginat DT, Lim T, Cabada T, Baskan O, Schob S, Meyer HJ, Gihr GA, Horvath-Rizea D, Hamerla G, Hoffmann KT, Wienke A Tags: Transl Oncol Source Type: research
Characterization of long non-coding RNAs and MEF2C-AS1 identified as a novel biomarker in diffuse gastric cancer.
In this study, we provide a valuable resource of lncRNAs which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer. PMID: 30005210 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 10, 2018 Category: Cancer & Oncology Authors: Luo T, Zhao J, Lu Z, Bi J, Pang T, Cui H, Yang B, Li W, Wang Y, Wu S, Xue X Tags: Transl Oncol Source Type: research
Molecular Imaging of Pancreatic Duct Adenocarcinoma Using a Type 2 Cannabinoid Receptor-Targeted Near-Infrared Fluorescent Probe.
In conclusion, NIR760-XLP6 exhibits promising characteristics for imaging PDAC, and CB2R appears to be an attractive target for PDAC imaging. PMID: 30005208 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 9, 2018 Category: Cancer & Oncology Authors: Guo X, Ling X, Du F, Wang Q, Huang W, Wang Z, Ding X, Bai M, Wu Z Tags: Transl Oncol Source Type: research
PSP1, a Phosphatidylserine-Recognizing Peptide, Is Useful for Visualizing Radiation-Induced Apoptosis in Colorectal Cancer In Vitro and In Vivo.
In this study, we investigated the potential of phosphatidylserine-recognizing peptide 1 (PSP1) as an apoptosis-targeting probe, which identifies phosphatidylserine on cell surfaces. We first screened colon cancer cell lines for their sensitivity to radiation and selected two cell lines: HCT116 and HT29. Cell binding assay using fluorescence-activated cell sorting and optical imaging showed that HCT116 cells had better binding to PSP1 than HT29 cells. Thus, mouse xenograft model using HCT116 cells was generated and was topically irradiated with either single or fractionated dose of radiation followed by systemic administra...
Source: Translational Oncology - July 4, 2018 Category: Cancer & Oncology Authors: Bae SM, Park SJ, Choi M, Song M, Cho YE, Do EJ, Ryu YM, Park S, Lee BH, Lee SW, Hwang SW, Park SH, Yang DH, Ye BD, Byeon JS, Yang SK, Joo J, Kim SY, Myung SJ Tags: Transl Oncol Source Type: research
Small Molecules Identified from a Quantitative Drug Combinational Screen Resensitize Cisplatin's Response in Drug-Resistant Ovarian Cancer Cells.
Abstract Drug resistance to chemotherapy occurs in many ovarian cancer patients resulting in failure of treatment. Exploration of drug resistance mechanisms and identification of new therapeutics that overcome the drug resistance can improve patient prognosis. Following a quantitative combination screen of 6060 approved drugs and bioactive compounds in a cisplatin-resistant A2780-cis ovarian cancer cell line, 38 active compounds with IC50s under 1 μM suppressed the growth of cisplatin-resistant ovarian cancer cells. Among these confirmed compounds, CUDC-101, OSU-03012, oligomycin A, VE-821, or Torin2 in a combi...
Source: Translational Oncology - July 4, 2018 Category: Cancer & Oncology Authors: Sima N, Sun W, Gorshkov K, Shen M, Huang W, Zhu W, Xie X, Zheng W, Cheng X Tags: Transl Oncol Source Type: research
Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients.
CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China. PMID: 29982100 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 3, 2018 Category: Cancer & Oncology Authors: Zheng K, Tan JX, Li F, Li HY, Zeng XH, Ma BL, Ou JH, Li H, Yang SS, Jiang AM, Ni Q, Liu JL, Liu JP, Zheng H, Yue-Yang, Ling R, He JJ, Li ZG, Zeng J, Zou TN, Jiang J, Song ZJ, Liu QL, Ren GS Tags: Transl Oncol Source Type: research
Plasma Protein Profiling Reveal Osteoprotegerin as a Marker of Prognostic Impact for Colorectal Cancer.
CONCLUSIONS: Of the 92 analyzed plasma proteins, osteoprotegerin showed the strongest prognostic impact in patients with colorectal cancer, and therefore osteoprotegerin is a potential predictive marker, and it also could be a target for treatments. PMID: 29982101 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 3, 2018 Category: Cancer & Oncology Authors: Birgisson H, Tsimogiannis K, Freyhult E, Kamali-Moghaddam M Tags: Transl Oncol Source Type: research
Dose Escalation of Lobaplatin Concurrent with IMRT for the Treatment of Stage III-IVb NPC: A Phase I Clinical Trial.
Abstract The maximum tolerated dose (MTD) of lobaplatin as a single agent chemotherapy concurrent with intensity-modulated radiotherapy (IMRT) in Asian population with nasopharyngeal carcinoma (NPC) remains unclear. From June 2016 to December 2017, 17 patients diagnosed with stage III-IVb NPC from an Asian population were prospectively enrolled. Patients were administered lobaplatin with 25-50 mg/m2 escalation of dosage on day 1. Every 21 days (days 1, 22, and 43) during radiotherapy, cycles were repeated. We administered radiotherapy as 2.12-2.27 Gy per fraction with five daily fractions each week for 6 to 7 ...
Source: Translational Oncology - June 29, 2018 Category: Cancer & Oncology Authors: Wang SY, Xu XW, Yao JJ, Peng PJ, Zhou B, Liu QD, Huang XP, Lin Z Tags: Transl Oncol Source Type: research
Biphasic Alteration of Butyrylcholinesterase (BChE) During Prostate Cancer Development.
We report here the biphasic changes of BChE expression in PC. In vitro, BChE expression was decreased in more tumorigenic PC stem-like cells (PCSLCs), DU145, and PC3 cells compared to less tumorigenic non-stem PCs and LNCaP cells. On the other hand, BChE was expressed at a higher level in LNCaP cells than immortalized but non-tumorigenic prostate epithelial BPH-1 cells. In vivo, BChE expression was up-regulated in DU145 xenografts compared to LNCaP xenografts; DU145 cell-derived lung metastases displayed comparable levels of BChE as subcutaneous tumors. Furthermore, LNCaP xenografts produced in castrated mice exhibited a s...
Source: Translational Oncology - June 29, 2018 Category: Cancer & Oncology Authors: Gu Y, Chow MJ, Kapoor A, Mei W, Jiang Y, Yan J, De Melo J, Seliman M, Yang H, Cutz JC, Bonert M, Major P, Tang D Tags: Transl Oncol Source Type: research
Increased CYFRA 21-1, CEA and NSE are Prognostic of Poor Outcome for Locally Advanced Squamous Cell Carcinoma in Lung: A Nomogram and Recursive Partitioning Risk Stratification Analysis.
CONCLUSIONS: Baseline tumor marker panel including CYFRA 21-1, CEA and NSE can be prognostic of outcome for LA-SCCL receiving definitive radiotherapy. The RPA identified four prognostic subgroups, which could assist personalized therapy and clinical trial design in LA-SCCL. PMID: 29958123 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 26, 2018 Category: Cancer & Oncology Authors: Wang J, Jiang W, Zhang T, Liu L, Bi N, Wang X, Hui Z, Liang J, Lv J, Zhou Z, Xiao Z, Feng Q, Chen D, Yin W, Wang L Tags: Transl Oncol Source Type: research
The Prognostic Value of Tumor-Infiltrating lymphocytes in Stage II Colon Cancer. A Nationwide Population-Based Study.
CONCLUSION: Low CD3+ and CD8+ TILs in the invasive area are both related to inferior prognosis of stage II CC, and we recommend either of these parameters to be considered as additional high-risk factor. PMID: 29940413 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 21, 2018 Category: Cancer & Oncology Authors: Eriksen AC, Sørensen FB, Lindebjerg J, Hager H, dePont Christensen R, Kjær-Frifeldt S, Hansen TF Tags: Transl Oncol Source Type: research
Activating Transcription Factor 3 as a Novel Regulator of Chemotherapy Response in Breast Cancer.
Abstract Anthracyclines, such as doxorubicin, are used as first-line chemotherapeutics, usually in combination therapies, for the treatment of advanced breast cancer. While these drugs have been successful therapeutic options, their use is limited due to serious drug related toxicities and acquired tumor resistance. Uncovering the molecular mechanisms that mediate doxorubicin's cytotoxic effect will lead to the identification of novel more efficacious combination therapies and allow for reduced doses of doxorubicin to be administered while maintaining efficacy. In our study, we demonstrate that activating transcri...
Source: Translational Oncology - June 21, 2018 Category: Cancer & Oncology Authors: Hasim MS, Nessim C, Villeneuve PJ, Vanderhyden BC, Dimitroulakos J Tags: Transl Oncol Source Type: research
Differential Sensitivity of Human Hepatocellular Carcinoma Xenografts to an IGF-II Neutralizing Antibody May Involve Activated STAT3.
Abstract Hepatocellular carcinoma (HCC) is highly refractory to current therapeutics used in the clinic. DX-2647, a recombinant human antibody, potently neutralizes the action of insulin-like growth factor-II (IGF-II), a ligand for three cell-surface receptors (IGF-IR, insulin receptor A and B isoforms, and the cation-independent mannose-6-phosphate receptor) which is overexpressed in primary human HCC. DX-2647 impaired the growth of tumor xenografts of the HCC cell line, Hep3B; however, xenografts of the HCC cell line, HepG2, were largely unresponsive to DX-2647 treatment. Analysis of a number of aspects of the I...
Source: Translational Oncology - June 18, 2018 Category: Cancer & Oncology Authors: Greenall SA, Donoghue J, Johns TG, Adams TE Tags: Transl Oncol Source Type: research
Molecular Characterization and Putative Pathogenic Pathways of Tuberous Sclerosis Complex-Associated Renal Cell Carcinoma.
In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry. The mutational spectrum of both TSC-RCCs was evaluated by whole exome sequencing (WES), and pathogenic pathways were analyzed. Differentially expressed genes were analyzed by NanoString Technologies nCounter platform. The mTOR pathway activation and the germline mutations of TSC2 were identified in both TSC-RCC case...
Source: Translational Oncology - June 17, 2018 Category: Cancer & Oncology Authors: Park JH, Lee C, Chang MS, Kim K, Choi S, Lee H, Lee HS, Moon KC Tags: Transl Oncol Source Type: research