F-FDOPA PET for the non-invasive prediction of glioma molecular parameters: a radiomics study
Purpose: The assessment of gliomas by 18F-FDOPA PET imaging in adjunct to MRI showed high performance by combining static and dynamic features to non-invasively predict the isocitrate dehydrogenase (IDH) mutations and the 1p/19q co-deletion, which the World Health Organization classified as significant parameters in 2016.
The current study evaluates whether other 18F-FDOPA PET radiomics features further improve performance and the contributions of each of these features to performance.
Methods: Our study included seventy-two, retrospectively selected, newly diagnosed, glioma patients with F-FDOPA PET dynamic acquisitions. A set of 114 features, including conventional static features and dynamic features as well as other radiomics features were extracted and machine-learning models trained to predict IDH mutations and the 1p/19q co-deletion.
Models were based on a machine-learning algorithm built from stable, relevant, and uncorrelated features selected by hierarchical clustering followed by a bootstrapped feature selection process. Models were assessed by comparing area under the curve (AUC) using a nested cross-validation approach. Feature importance was assessed using SHapley Additive exPlanations (SHAP) values.
Results: The best models were able to predict IDH mutations (logistic regression with L2 regularization) and the 1p/19q co-deletion (support vector machine with radial basis function kernel) with an AUC of 0.831[0.790;0.873] and 0.724[0.669;0.782] respectively.
For the prediction of IDH mutations, dynamic features were the most important features in the model (TTP: 35.5%). In contrast, other radiomics features were the most useful for predicting the 1p/19q co-deletion (up to 14.5% of importance for the small zone low grey level emphasis).
Conclusion: F-FDOPA PET is an effective tool for the non-invasive prediction of glioma molecular parameters using a full set of amino-acid PET radiomics features. The contribution of each feature set shows the importance of systematically integrating dynamic acquisition for the prediction of the IDH mutations as well as developing the use of radiomics features in routine practice for the prediction the 1p/19q co-deletion.
Combined Omic Analyzes of Cerebral Thrombi: A New Molecular Approach to Identify Cardioembolic Stroke Origin
Background and purpose: The diagnosis of cardioembolic stroke can be challenging for patient management in secondary stroke prevention, particularly in the case of covert paroxysmal atrial fibrillation.
The molecular composition of a cerebral thrombus is related to its origin. Therefore, proteomic and metabolomic analyses of the retrieved thrombotic material should allow the identification of biomarkers or signatures to improve the etiological diagnosis of stroke.
Methods: In this pilot study, the proteome and metabolome of cerebral thrombi from atherothrombotic and cardioembolic stroke patients were studied according to ASCOD phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes; D: dissection), with the highest causality grade, from the ThrombiOMIC cohort (consecutive patients with stroke recanalized by mechanical thrombectomy in an acute phase).
Proteomic and metabolomic results were used separately or combined, and the obtained omic signatures were compared with classical cardioembolic stroke predictors using pairwise comparisons of the area under receiver operating characteristics.
Results: Among 59 patients of the ThrombiOMIC cohort, 34 patients with stroke showed a cardioembolic phenotype and 7 had an atherothrombotic phenotype.
Two thousand four hundred fifty-six proteins and 5019 molecular features of the cerebral thrombi were identified using untargeted proteomic and metabolomic approaches, respectively.
Area under receiver operating characteristics to predict the cardioembolic origin of stroke were calculated using the proteomic results (0.945 [95% CI, 0.871-1]), the metabolomic results (0.836 [95% CI, 0.714-0.958]), and combined signatures (0.996 [95% CI, 0.984-1]).
The diagnostic performance of the combined signatures was significantly higher than that of classical predictors such as the plasmatic BNP (B-type natriuretic peptide) level (area under receiver operating characteristics, 0.803 [95% CI, 0.629-0.976]).
Conclusions: The combined proteomic and metabolomic analyses of retrieved cerebral thrombi is a very promising molecular approach to predict the cardioembolic cause of stroke and to improve secondary stroke prevention strategies.
Description: A Monoclonal antibody against Human ER alpha monoclonal. The antibodies are raised in Mouse. This antibody is applicable in WB, IC, E, IP, GS
Description: A Monoclonal antibody against Human CST3 (monoclonal). The antibodies are raised in Mouse and are from clone 1H4. This antibody is applicable in WB
Description: A Monoclonal antibody against Human TNFSF18 (monoclonal). The antibodies are raised in mouse and are from clone 2E11. This antibody is applicable in WB, E
Description: A Monoclonal antibody against Human FTL (monoclonal). The antibodies are raised in Mouse and are from clone 4G7. This antibody is applicable in WB, E
Description: A polyclonal antibody for detection of HSC70 from Human, Mouse, Rat. This HSC70 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human HSC 70
Description: A polyclonal antibody for detection of HSC70 from Human, Mouse, Rat. This HSC70 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human HSC 70
Description: A polyclonal antibody for detection of HSC70 from Human, Mouse, Rat. This HSC70 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human HSC 70
Description: A polyclonal antibody for detection of HSC70 from Human, Mouse, Rat. This HSC70 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human HSC 70
Description: A polyclonal antibody for detection of HSC70 from Human, Mouse, Rat. This HSC70 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human HSC 70
Description: A polyclonal antibody for detection of HSC70 from Human, Mouse, Rat. This HSC70 antibody is for WB, IHC-P, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human HSC 70
Description: A polyclonal antibody for detection of MEK2 from Human, Mouse, Rat. This MEK2 antibody is for WB, IHC-P, IP, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human MEK-2 around the non-phosphorylation site of T394
Description: A polyclonal antibody for detection of MEK2 from Human, Mouse, Rat. This MEK2 antibody is for WB, IHC-P, IP, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human MEK-2 around the non-phosphorylation site of T394
Description: A polyclonal antibody for detection of MEK2 from Human, Mouse, Rat. This MEK2 antibody is for WB, IHC-P, IP, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human MEK-2 around the non-phosphorylation site of T394
Description: A polyclonal antibody for detection of MEK2 from Human, Mouse, Rat. This MEK2 antibody is for WB, IHC-P, IP, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human MEK-2 around the non-phosphorylation site of T394
Description: A polyclonal antibody for detection of MEK2 from Human, Mouse, Rat. This MEK2 antibody is for WB, IHC-P, IP, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human MEK-2 around the non-phosphorylation site of T394
Description: A polyclonal antibody for detection of MEK2 from Human, Mouse, Rat. This MEK2 antibody is for WB, IHC-P, IP, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human MEK-2 around the non-phosphorylation site of T394
Description: A Mouse Monoclonal antibody against GAPDH from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Pig/ Sheep/ Insect/ Yeast. This antibody is tested and validated for WB, ELISA, IHC, IF
Description: A Mouse Monoclonal antibody against GAPDH from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Pig/ Sheep/ Insect/ Yeast. This antibody is tested and validated for WB, ELISA, IHC, IF
Description: A Mouse Monoclonal antibody against ?-Tubulin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/Sheep/ Insect/ Yeast. This antibody is tested and validated for WB, ELISA, IHC, IF
Description: A Mouse Monoclonal antibody against ?-Tubulin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/Sheep/ Insect/ Yeast. This antibody is tested and validated for WB, ELISA, IHC, IF
Description: A Mouse Monoclonal antibody against ?-actin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Pig/ Sheep. This antibody is tested and validated for WB, ELISA, IHC, IF
Description: A Mouse Monoclonal antibody against ?-actin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Pig/ Sheep. This antibody is tested and validated for WB, ELISA, IHC, IF
Description: A Mouse Monoclonal antibody against ?-actin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Insect. This antibody is tested and validated for WB, ELISA
Description: A Mouse Monoclonal antibody against ?-actin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Insect. This antibody is tested and validated for WB, ELISA
Description: A Mouse Monoclonal antibody against GAPDH from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Pig/ Sheep/ Insect/ Yeast. This antibody is tested and validated for WB, ELISA
Description: A Mouse Monoclonal antibody against GAPDH from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Pig/ Sheep/ Insect/ Yeast. This antibody is tested and validated for WB, ELISA
Description: A Mouse Monoclonal antibody against ?-tubulin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Sheep/ Insect/ Yeast . This antibody is tested and validated for WB, ELISA, IHC
Description: A Mouse Monoclonal antibody against ?-tubulin from Human/ Rat/ Mouse/ Monkey/ Dog/ Chicken/ Hamster/ Rabbit/ Sheep/ Insect/ Yeast . This antibody is tested and validated for WB, ELISA, IHC
Description: A Mouse Monoclonal antibody against Desmin from Human/ Rat/ Mouse. This antibody is tested and validated for IHC
×
Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with 177 Lu-PSMA-617 for metastatic Castration-reSISTant Prostate Cancer (RESIST-PC): Efficacy results of the UCLA cohort
Objective: To determine prospectively the efficacy profile of 2 activity regimens of Lu-PSMA therapy in patients with progressive metastatic castrate resistant prostate cancer (mCRPC): 6.0 vs 7.4 GBq.
Methods: RESIST-PC (NCT03042312) was a prospective multicenter phase 2 trial. Patients with progressive mCRPC after ≥1 novel androgen-axis drug, either chemotherapy naïve or post-chemotherapy, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA expression by PSMA PET were eligible.
Patients were randomized (1:1) into two activity groups (6.0 or 7.4 GBq) and received up to 4 cycles every 8 weeks. The primary endpoint was the efficacy of Lu-PSMA measured by the PSA response rate (RR) after 2 cycles (≥50% decline from baseline). Secondary endpoints included the PSA-RR (≥50% decline) at any time (best response), and overall survival (OS).
Results: The study was closed at enrollment of 71/200 planned patients because of sponsorship transfer. We report here the efficacy UCLA cohort results only (n = 43). The PSARRs after 2 cycles and at any time were 11/40 (28%, 95%CI 15-44), 6/13 (46%, 95%CI 19-75), 5/27 (19%, 95%CI 6-38), and 16/43 (37%, 95%CI 23-53), 7/14 (50%, 95%CI 23-77), 9/29 (31%, 95%CI 15-51) in the whole cohort, the 6.0 GBq and the 7.4 GBq groups, respectively (P = 0.12 and P = 0.31).
The median OS was 14.0 months (95%CI 10.1-17.9), 15.8 (95%CI 11.8-19.4), 13.5 (95%CI 10.0-17.0) in the whole cohort, the 6.0 GBq and the 7.4 GBq groups, respectively (P = 0.87). OS was longer in patients who experienced a PSA decline ≥50% at any time than those who did not: median: 20.8 vs. 10.8 months (P = 0.005).
Conclusion: In this prospective phase 2 trial of Lu-PSMA for mCRPC the median OS was 14 months. Despite the heterogeneous study population and the premature study termination, the efficacy profile of Lu-PSMA appeared to be favorable and comparable with both activity regimens (6.0 GBq vs. 7.4 GBq).
Results justify confirmation with real world data matched pair analysis and further clinical trials to refine and optimize the LuPSMA therapy administration scheme to improve tumor radiation dose delivery and efficacy.
Advances in understanding the molecular pathology of gynecological malignancies: the role and potential of RNA sequencing
For many years technological limitations restricted the progress of identifying the underlying genetic causes of gynecologicalcancers. However, during the past decade, high-throughput next-generation sequencing technologies have revolutionized cancer research. RNA sequencing has arisen as a very useful technique in expanding our understanding of genome changes in cancer.
Cancer is characterized by the accumulation of genetic alterations affecting genes, including substitutions, insertions, deletions, translocations, gene fusions, and alternative splicing. If these aberrant genes become transcribed, aberrations can be detected by RNA sequencing, which will also provide information on the transcript abundance revealing the expression levels of the aberrant genes.
RNA sequencing is considered the technique of choice when studying gene expression and identifying new RNA species. This is due to the quantitative and qualitative improvement that it has brought to transcriptome analysis, offering a resolution that allows research into different layers of transcriptome complexity.
It has also been successful in identifying biomarkers, fusion genes, tumor suppressors, and uncovering new targets responsible for drug resistance in gynecological cancers. To illustrate that we here review the role of RNA sequencing in studies that enhanced our understanding of the molecular pathology of gynecological cancers.
Description: A sandwich quantitative ELISA assay kit for detection of Human Cystatin 3 (CST3) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Human Cystatin 3 (CST3) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Cystatin 3 (CST3) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Cystatin 3 (CST3) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Cystatin 3 (CST3) in samples from serum, plasma, urine or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Porcine Cystatin 3 (CST3) in samples from serum, plasma, urine or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Cystatin 3 (CST3) in samples from serum, plasma, urine or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Cystatin 3 (CST3) in samples from serum, plasma, urine or other biological fluids.
Description: A polyclonal antibody against CST3. Recognizes CST3 from Human, Mouse, Rat, Monkey. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/40000
Description: A polyclonal antibody against CST3. Recognizes CST3 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;ELISA:1:2000-1:10000, WB:1:1000-1:5000, IHC:1:50-1:200
Description: A polyclonal antibody against CST3. Recognizes CST3 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:1000-1:5000, IHC:1:20-1:200
Description: A polyclonal antibody against CST3. Recognizes CST3 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:1000-1:5000, IHC:1:20-1:200
Description: A polyclonal antibody against CST3. Recognizes CST3 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;ELISA:1:1000-1:5000, WB:1:200-1:1000, IHC:1:25-1:100
Description: A polyclonal antibody against CST3. Recognizes CST3 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC
Description: The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes the most abundant extracellular inhibitor of cysteine proteases, which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy. Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease. In addition, this protein has been shown to have an antimicrobial function, inhibiting the replication of herpes simplex virus. Alternative splicing results in multiple transcript variants encoding a single protein.
Description: The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes the most abundant extracellular inhibitor of cysteine proteases, which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy. Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease. In addition, this protein has been shown to have an antimicrobial function, inhibiting the replication of herpes simplex virus. Alternative splicing results in multiple transcript variants encoding a single protein.
