المؤلفون: Dae Seog Heo, Tae Min Kim, Sehui Kim, Jiwon Koh, Jin Ho Paik, Yoon Kyung Jeon, Cheol Lee, Jeemin Yim, Bogyeong Han

المصدر: Cancers, Vol 12, Iss 3305, p 3305 (2020)
Cancers
Volume 12
Issue 11

مصطلحات موضوعية: Cancer Research, medicine.medical_specialty, Poor prognosis, BCL2, diffuse large B-cell lymphoma, MYC, Gastroenterology, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, International Prognostic Index, immune system diseases, Internal medicine, Lactate dehydrogenase, hemic and lymphatic diseases, Medicine, Poor performance status, neoplasms, high-grade B-cell lymphoma, business.industry, lactate dehydrogenase, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Lymphoma, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, Cohort, double expression, Bone marrow, prognosis, business, Diffuse large B-cell lymphoma, 030215 immunology

الوصف: Diffuse large B-cell lymphoma (DLBCL) patients with MYC/BCL2 double expression (DE) show poor prognosis and their clinical outcomes after R-CHOP therapy vary immensely. We investigated the prognostic value of DE in aggressive B-cell lymphoma patients (n = 461), including those with DLBCL (n = 417) and high-grade B-cell lymphoma (HGBL
n = 44), in a prospectively immunoprofiled cohort. DE was observed in 27.8% of DLBCLs and 43.2% of HGBLs (P = 0.058). DE-DLBCL patients were older (P = 0.040) and more frequently exhibited elevated serum LDH levels (P = 0.002), higher international prognostic index (IPI
P = 0.042), non-germinal-center B-cell phenotype (P <
0.001), and poor response to therapy (P = 0.042) compared to non-DE-DLBCL patients. In R-CHOP-treated DLBCL patients, DE status predicted poor PFS and OS independently of IPI (P <
0.001 for both). Additionally, in DE-DLBCL patients, older age (>
60 years
P = 0.017), involvement of ³
2 extranodal sites (P = 0.021), bone marrow involvement (P = 0.001), high IPI (P = 0.017), CD10 expression (P = 0.006), poor performance status (P = 0.028), and elevated LDH levels (P <
0.001) were significantly associated with poor OS. Notably, DE-DLBCL patients with normal LDH levels exhibited similar PFS and OS to those of patients with non-DE-DLBCL. Our findings suggest that MYC/BCL2 DE predicts poor prognosis in DLBCL. Risk stratification of DE-DLBCL patients based on LDH levels may guide clinical decision-making for DE-DLBCL patients.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49b3753692166b49112983ab20b38e30Test
https://www.mdpi.com/2072-6694/12/11/3305Test

المؤلفون: Viktor Grünwald, Barbara Seliger, Iris Benz-Rüd, Arnulf Stenzl, Frederik C. Roos, Sebastian Hölters, Peter J. Goebell, Johanna Harde, Marinela Augustin, Philip Zeuschner, Anja Mueller, Kerstin Junker, Michael Staehler, Daniel C. Christoph, Fabian Brüning, Hagen S. Bachmann, Michael Stöckle, Marc-Oliver Grimm

المصدر: Cancers, Vol 13, Iss 2594, p 2594 (2021)
Cancers; Volume 13; Issue 11; Pages: 2594
Cancers

مصطلحات موضوعية: 0301 basic medicine, Oncology, second-line, Cancer Research, medicine.medical_specialty, Medizin, urologic and male genital diseases, metastatic renal cell carcinoma, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Renal cell carcinoma, Polymorphism (computer science), Lactate dehydrogenase, Internal medicine, medicine, ddc:610, RC254-282, Predictive biomarker, Everolimus, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, everolimus, Clear cell renal cell carcinoma, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biomarker, phase IV, Biomarker (medicine), business, Clear cell, medicine.drug

الوصف: Simple Summary: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge due to the lack of biomarkers indicating the optimal drug for each patient. This study analyzed blood samples of patients with predominant clear cell mRCC who were treated with the mTOR inhibitor everolimus after failure of one prior tumor therapy. In an exploratory approach, predictive blood biomarkers were searched. We found lower levels of the protein thrombospondin-2 (TSP-2) at the start of the therapy and higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation to be associated with therapy response. Of note, these blood biomarkers had a higher predictive value than baseline patient parameters or risk classifications. Polymorphisms in the mTOR gene appeared to be associated with therapy response, but were not significant. To conclude, it seems feasible to identify patients showing longtime responses to everolimus and possible to increase tumor therapy response rates based on biomarkers for individual therapy selection. Abstract: There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.

وصف الملف: application/pdf; application/octet-stream

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd7d53c25898776c3b4ea829371444b9Test
https://www.mdpi.com/2072-6694/13/11/2594Test

المؤلفون: Romelyn Delos Santos, Justin Delos Santos, Kayvan R. Keshari, Renuka Sriram, Hecong Qin, Robert Bok, Mark Van Criekinge, Fayyaz Ahamed, Rosalie Nolley, Z. Laura Tabatabai, Donna M. Peehl, John Kurhanewicz, Daniel B. Vigneron

المصدر: Cancers
Volume 12
Issue 3
Cancers, Vol 12, Iss 3, p 537 (2020)
Cancers, vol 12, iss 3

مصطلحات موضوعية: Urologic Diseases, 0301 basic medicine, Aging, Cancer Research, Oncology and Carcinogenesis, lactate dehydrogenase (LDH), urologic and male genital diseases, lcsh:RC254-282, Article, dynamic nuclear polarization, 03 medical and health sciences, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, dynamic nuclear polarization (DNP), Prostate, Lactate dehydrogenase, medicine, aerobic glycolysis, Cancer, biology, medicine.diagnostic_test, Prostate Cancer, hyperpolarized C-13 magnetic resonance, lactate dehydrogenase, Magnetic resonance imaging, Metabolism, hyperpolarized 13C magnetic resonance, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, prostate cancer, hyperpolarized 13C magnetic resonance (HP 13C MR), lactate efflux, 030104 developmental biology, medicine.anatomical_structure, Oncology, chemistry, Anaerobic glycolysis, 030220 oncology & carcinogenesis, Monocarboxylate transporter 4, biology.protein, Cancer research, hyperpolarized 13c magnetic resonance (hp 13c mr)

الوصف: Non-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP) 13C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-13C]pyruvate to [1-13C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP 13C MR could distinguish low-risk (Gleason score &le
3 + 4) from high-risk (Gleason score &ge
4 + 3) PCa. To test this and the ability of HP 13C MR to detect these metabolic changes, we cultured prostate tissues in an MR-compatible bioreactor under continuous perfusion. 31P spectra demonstrated good viability and dynamic HP 13C-pyruvate MR demonstrated that high-grade PCa had significantly increased lactate efflux compared to low-grade PCa and benign prostate tissue. These metabolic differences are attributed to significantly increased LDHA expression and LDH activity, as well as significantly increased monocarboxylate transporter 4 (MCT4) expression in high- versus low- grade PCa. Moreover, lactate efflux, LDH activity, and MCT4 expression were not different between low-grade PCa and benign prostate tissues, indicating that these metabolic alterations are specific for high-grade disease. These distinctive metabolic alterations can be used to differentiate high-grade PCa from low-grade PCa and benign prostate tissues using clinically translatable HP [1-13C]pyruvate MR.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eeb5dbabf63f22313427aa5c1799f8a2Test

المؤلفون: Franchette W P J van den Berkmortel, Jacobus J.M. van der Hoeven, M Schouwenburg, Albert J. ten Tije, Alfons J.M. van den Eertwegh, Michiel C T van Zeijl, Wim H. J. Kruit, John B. A. G. Haanen, Alexander C.J. van Akkooi, Rutger H. T. Koornstra, Maureen J.B. Aarts, Djura Piersma, Michel W.J.M. Wouters, Karijn P M Suijkerbuijk, A Jochems, Ellen Kapiteijn, Geke A. P. Hospers, Jan Willem B. de Groot, Gerard Vreugdenhil, Rozemarijn S. van Rijn

المساهمون: Medical oncology, CCA - Cancer biology and immunology, AII - Cancer immunology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Pathology, Internal Medicine, Psychiatry, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy

المصدر: Cancers, 11(12):1940. Multidisciplinary Digital Publishing Institute (MDPI)
Cancers, 11:WOS:000507382100117. Multidisciplinary Digital Publishing Institute (MDPI)
Cancers, 11, 12
Schouwenburg, M G, Suijkerbuijk, K P M, Koornstra, R H T, Jochems, A, van Zeijl, M C T, van den Eertwegh, A J M, Haanen, J B A G, Aarts, M J, van Akkooi, A C J, van den Berkmortel, F W P J, de Groot, J W B, Hospers, G A P, Kapiteijn, E, Kruit, W H, Piersma, D, van Rijn, R S, ten Tije, A J, Vreugdenhil, G, van der Hoeven, J J M & Wouters, M W J M 2019, ' Switching to immune checkpoint inhibitors upon response to targeted therapy; the road to long-term survival in advanced melanoma patients with highly elevated serum LDH? ', Cancers, vol. 11, no. 12, 1940 . https://doi.org/10.3390/cancers11121940Test
Cancers
Cancers, 11(12). Multidisciplinary Digital Publishing Institute (MDPI)
Cancers, 11
Cancers, 11(12):1940. MDPI AG

مصطلحات موضوعية: 0301 basic medicine, Oncology, medicine.medical_specialty, Cancer Research, Immune checkpoint inhibitors, medicine.medical_treatment, Real-life data, Article, Metastasis, Targeted therapy, Elevated serum, immune checkpoint inhibitors, 03 medical and health sciences, chemistry.chemical_compound, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], 0302 clinical medicine, real-life data, Lactate dehydrogenase, Internal medicine, medicine, melanoma, metastasis, METASTATIC MELANOMA, PEMBROLIZUMAB, Advanced melanoma, LACTATE-DEHYDROGENASE, OUTCOMES, business.industry, Melanoma, Lactatedehydrogenase, IPILIMUMAB, prognostic factors, NIVOLUMAB, lactate dehydrogenase, medicine.disease, targeted therapy, DABRAFENIB, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Population study, business

الوصف: Contains fulltext : 215533.pdf (Publisher’s version ) (Open Access) The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (>/=2x upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4-5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.

وصف الملف: image/pdf; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e0f5fa3bb8e0ec9098ab93a137bfae3Test
https://cris.maastrichtuniversity.nl/en/publications/31683df4-46fd-4d12-88be-34ddbf9ea021Test

المؤلفون: Dipok Kumar Dhar, Steven W.M. Olde Damink, Massimo Malagó, Pilar Acedo, Goran Mohammad, Vessela Vassileva, Stephen P. Pereira

المساهمون: Surgery, MUMC+: MA Heelkunde (9), RS: NUTRIM - R2 - Liver and digestive health

المصدر: Cancers, 11(9):1372. Multidisciplinary Digital Publishing Institute (MDPI)
Cancers, Vol 11, Iss 9, p 1372 (2019)
Cancers
Cancers 11(9), (2019). doi:10.3390/cancers11091372
Volume 11
Issue 9

مصطلحات موضوعية: 0301 basic medicine, EXPRESSION, Cancer Research, Lactate dehydrogenase A, pancreatic cancer, lactate dehydrogenase A, HYPOXIA, PROGRESSION, PKM2, METABOLISM, lcsh:RC254-282, Article, combination therapy, 03 medical and health sciences, 0302 clinical medicine, In vivo, Pancreatic cancer, medicine, 1112 Oncology and Carcinogenesis, education, chemistry.chemical_classification, education.field_of_study, Science & Technology, Activator (genetics), Chemistry, TUMOR-GROWTH, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, Enzyme, Oncology, GEMCITABINE, Anaerobic glycolysis, 030220 oncology & carcinogenesis, CELLS, Cancer research, OVEREXPRESSION, pyruvate kinase M2, glycolytic enzymes, INHIBITORS, Life Sciences & Biomedicine, Pyruvate kinase

الوصف: Reprogrammed glucose metabolism is one of the hallmarks of cancer, and increased expression of key glycolytic enzymes, such as pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA), has been associated with poor prognosis in various malignancies. Targeting these enzymes could attenuate aerobic glycolysis and inhibit tumor proliferation. We investigated whether the PKM2 activator, TEPP-46, and the LDHA inhibitor, FX-11, can be combined to inhibit in vitro and in vivo tumor growth in preclinical models of pancreatic cancer. We assessed PKM2 and LDHA expression, enzyme activity, and cell proliferation rate after treatment with TEPP-46, FX-11, or a combination of both. Efficacy was validated in vivo by evaluating tumor growth, PK and LDHA activity in plasma and tumors, and PKM2, LDHA, and Ki-67 expression in tumor tissues following treatment. Dual therapy synergistically inhibited pancreatic cancer cell proliferation and significantly delayed tumor growth in vivo without apparent toxicity. Treatment with TEPP-46 and FX-11 resulted in increased PK and reduced LDHA enzyme activity in plasma and tumor tissues and decreased PKM2 and LDHA expression in tumors, which was reflected by a decrease in tumor volume and proliferation. The targeting of glycolytic enzymes such as PKM2 and LDHA represents a promising therapeutic approach for the treatment of pancreatic cancer.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f5638e3710116a9939277f39dd34aa7Test
https://cris.maastrichtuniversity.nl/en/publications/42d81cce-3271-4d74-b73d-b8f5729e0440Test

المؤلفون: Francesco Curcio, Lorenzo Gerratana, Silvia Zago, Valentina Fanotto, Maria Grazia Vitale, Alessandro Marco Minisini, L. Bortot, Giacomo Pelizzari, C. Lisanti, Marta Bonotto, Serena Barban, Fabio Puglisi, Marika Cinausero, Debora Basile, Mauro Mansutti, Michele Bartoletti, Gianpiero Fasola

المصدر: Cancers, Vol 11, Iss 9, p 1243 (2019)
Cancers
Volume 11
Issue 9

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, Prognostic factor, medicine.medical_specialty, LDH, lcsh:RC254-282, Article, Treatment experienced, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, Internal medicine, Medicine, Elevated ldh, monitoring metastatic breast cancer, skin and connective tissue diseases, lactate dehydrogenase, metastatic breast cancer, serum biomarker, business.industry, Proportional hazards model, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, First line treatment, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Biomarker (medicine), business

الوصف: Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40&ndash
5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16&ndash
5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00&ndash
7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d08c0494437c8a17c57a67f335e0bfe3Test
https://www.mdpi.com/2072-6694/11/9/1243Test

المؤلفون: Matteo S. Carlino, Richard A. Scolyer, Natalie Byrne, Russell J. Diefenbach, Helen Rizos, Elin S. Gray, John J. Park, Georgina V. Long

المصدر: Cancers, Vol 13, Iss 1740, p 1740 (2021)
Cancers
Volume 13
Issue 7

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Phases of clinical research, PKC inhibitor, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, Internal medicine, medicine, melanoma, Liquid biopsy, circulating tumor DNA, next generation sequencing, Adaptive clinical trial, response, Receiver operating characteristic, liquid biopsy, treatment, business.industry, Melanoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Confidence interval, Clinical trial, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, uveal melanoma, business

الوصف: The prognosis for patients with UM is poor, and recent clinical trials have failed to prolong overall survival (OS) of these patients. Over 95% of UM harbor activating driver mutations, and this allows for the investigation of ctDNA. In this study, we investigated the value of ctDNA for adaptive clinical trial design in metastatic UM. Longitudinal plasma samples were analyzed for ctDNA in 17 metastatic UM patients treated with PKCi-based therapy in a phase 1 clinical trial setting. Plasma ctDNA was assessed using digital droplet PCR (ddPCR) and a custom melanoma gene panel for targeted next generation sequencing (NGS). Baseline ctDNA strongly correlated with baseline lactate dehydrogenase (LDH) (p <
0.001) and baseline disease burden (p = 0.002). Early during treatment (EDT) ctDNA accurately predicted patients with clinical benefit to PKCi using receiver operator characteristic (ROC) curves (AUC 0.84, [95% confidence interval 0.65–1.0, p = 0.026]). Longitudinal ctDNA assessment was informative for establishing clinical benefit and detecting disease progression with 7/8 (88%) of patients showing a rise in ctDNA and targeted NGS of ctDNA revealed putative resistance mechanisms prior to radiological progression. The inclusion of longitudinal ctDNA monitoring in metastatic UM can advance adaptive clinical trial design.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68adbd715b022bb91e9ad152b9dd152fTest
https://www.mdpi.com/2072-6694/13/7/1740Test

المؤلفون: Rebecca Gross, Negin Rahimzadeh, Stacey L. Stern, Linh T Tran, Hunter Cole, Ling Takeshima, Dave S.B. Hoon, Steven J. O'Day, Matias A. Bustos, Kevin Tran

المصدر: Cancers, Vol 12, Iss 3361, p 3361 (2020)
Cancers
Volume 12
Issue 11

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, lcsh:RC254-282, Article, immune checkpoint inhibitors, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, Internal medicine, microRNA, Medicine, Stage (cooking), neoplasms, plasma, miRNA, business.industry, Melanoma, Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Circulating MicroRNA, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, serum LDH, circulating microRNA, immunotherapy, blood biomarker, business, Progressive disease, metastatic melanoma

الوصف: Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients&rsquo
disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients&rsquo
responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA
2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients&rsquo
and 73 normal donors&rsquo
plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors&rsquo
plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36f4dd98399f8dea7db6fdd0d1f3486cTest
https://www.mdpi.com/2072-6694/12/11/3361Test

المؤلفون: András Jeney, Regina Raffay, Janina Kulka, Gábor Petővári, Anna Sebestyén, Ildikó Krencz, Krisztina Németh, Anna-Mária Tőkés, Titanilla Dankó, Krisztina Vellai-Takács, Dániel Sztankovics, Melinda Hajdu, Enikő Vetlényi

المصدر: Cancers
Volume 12
Issue 9
Cancers, Vol 12, Iss 2492, p 2492 (2020)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Anabolism, Lactate dehydrogenase A, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, metabolic characterisation, Medicine, mTOR activity, education, PI3K/AKT/mTOR pathway, education.field_of_study, business.industry, Catabolism, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, metabolic plasticity, 030104 developmental biology, Oncology, Drug development, 030220 oncology & carcinogenesis, Cancer research, Immunohistochemistry, business, metabolism

الوصف: In spite of tremendous developments in breast cancer treatment, the relatively high incidence of relapsing cases indicates a great need to find new therapeutic strategies in recurrent, metastatic and advanced cases. The bioenergetic needs of growing tumours at the primary site or in metastases&mdash
accumulating genomic alterations and further heterogeneity&mdash
are supported by metabolic rewiring, an important hallmark of cancer. Adaptation mechanisms as well as altered anabolic and catabolic processes balance according to available nutrients, energy, oxygen demand and overgrowth or therapeutic resistance. Mammalian target of rapamycin (mTOR) hyperactivity may contribute to this metabolic plasticity and progression in breast carcinomas. We set out to assess the metabolic complexity in breast cancer cell lines and primary breast cancer cases. Cellular metabolism and mTOR-related protein expression were characterised in ten cell lines, along with their sensitivity to specific mTOR and other metabolic inhibitors. Selected immunohistochemical reactions were performed on ~100 surgically removed breast cancer specimens. The obtained protein expression scores were correlated with survival and other clinicopathological data. Metabolic and mTOR inhibitor mono-treatments had moderate antiproliferative effects in the studied cell lines in a subtype-independent manner, revealing their high adaptive capacity and survival/growth potential. Immunohistochemical analysis of p-S6, Rictor, lactate dehydrogenase A, glutaminase, fatty acid synthase and carnitine palmitoyltransferase 1A in human samples identified high mTOR activity and potential metabolic plasticity as negative prognostic factors for breast cancer patients, even in subtypes generally considered as low-risk. According to our results, breast cancer is characterised by considerable metabolic diversity, which can be targeted by combining antimetabolic treatments and recent therapies. Alterations in these pathways may provide novel targets for future drug development in breast cancer. We also propose a set of immunostainings for scoring metabolic heterogeneity in individual cases in order to select patients who may benefit from more accurate follow-up and specific therapies.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b645b55ca77b8a1d08a0379c78a3578Test

المؤلفون: Jérôme Solassol, Géraldine Chauchard, Vincent Ducros, Pauline Blateau, Estelle M.N. Laurent, Benoît Béganton, Etienne Coyaud, Julie A. Vendrell

المساهمون: INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, Département Pathologie et Onco-biologie [CHU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), SALZET, Michel, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

المصدر: Cancers, Vol 12, Iss 2224, p 2224 (2020)
Cancers
Cancers, 2020, 12 (8), pp.2224. ⟨10.3390/cancers12082224⟩
Cancers, MDPI, 2020, 12 (8), pp.2224. ⟨10.3390/cancers12082224⟩
Volume 12
Issue 8

مصطلحات موضوعية: 0301 basic medicine, MAPK/ERK pathway, Cancer Research, BRAF V600, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], melanoma, Medicine, Clinical significance, prognosis factor, Protein kinase A, Genotyping, neoplasms, BRAFV600, Mutation, business.industry, Melanoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, targeted therapies, 3. Good health, 030104 developmental biology, Oncology, chemistry, TERT promoter, 030220 oncology & carcinogenesis, Cancer research, co-occurring mutation, business, Brain metastasis

الوصف: Although the development of mitogen-activated protein kinase (MAPK) inhibitors has greatly improved the prognosis of BRAFV600 cutaneous melanomas, the identification of molecular indicators for mutated patients at risk of early progression remains a major issue. Using an amplicon-based next-generation-sequencing (NGS) assay that targets cancer-related genes, we investigated co-occurring alterations in 89 melanoma samples. We analyzed both their association with clinicopathological variables and clinical significance in terms of progression-free survival (PFS) and overall survival (OS) according to BRAF genotyping. Among co-occurring mutations, TERT promoter was the most frequently mutated gene. Although no significant difference in PFS was observed in the presence or absence of co-occurring alterations to BRAFV600, there was a trend of longer PFS for patients harboring TERT c.-124C>
T mutation. Of most interest, this mutation is an independent marker of good prognosis in subgroups of patients with poor prognosis (presence of brain metastasis and elevated level of lactate dehydrogenase, LDH). Moreover, combination of elevated LDH level, presence of brain metastasis, and TERT c.-124C>
T mutation was identified as the best fit model for predicting clinical outcome. Our work revealed the potential interest of c.-124C>
T status determination in order to refine the prognosis of BRAFV600 melanoma under mitogen-activated protein kinase (MAPK) inhibitors.

وصف الملف: application/rdf+xml; charset=utf-8; application/octet-stream; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85e5d962992b865ffc352cbd7d465048Test
https://www.mdpi.com/2072-6694/12/8/2224Test