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Article ; Online: Pancreatic Enzyme Replacement and Nutritional Support With nab-Paclitaxel-based First-Line Chemotherapy Regimens in Metastatic Pancreatic Cancer.

Giordano, Guido / Cincione, Raffaele Ivan / Losavio, Francesca / Senia, Tiziano / Aquilini Mummolo, Arianna / Pacilli, Mario / Lizzi, Vincenzo / Bruno, Giuseppina / Piscazzi, Annamaria / Conteduca, Vincenza / Landriscina, Matteo

The oncologist

2023 Volume 28, Issue 9, Page(s) e793–e800

Abstract: Background: At diagnosis, more than 80% of patients with pancreatic cancer (PC) suffer from significant weight loss due to malnutrition which is a major concern for patient management, and this may negatively impact treatment outcomes and patient ... ...

Abstract	Background: At diagnosis, more than 80% of patients with pancreatic cancer (PC) suffer from significant weight loss due to malnutrition which is a major concern for patient management, and this may negatively impact treatment outcomes and patient prognosis. Patients and methods: We performed an observational, retrospective study on patients with metastatic PC (mPC) undergoing first-line chemotherapy with nab-Paclitaxel containing schedules and receiving or not receiving nutritional support (NS) and pancreatic enzyme replacement therapy (PERT) to investigate their relevance in this setting. Results: We observed that PERT and ancillary dietary interventions are related to longer overall survival (OS; median: 16.5 vs. 7.5 months, P < .001) and have a significant, independent, prognostic impact for better outcomes (P = .013), independently from the therapeutic regimen. Furthermore, PERT and NS prevented weight loss during chemotherapy and obtained an improvement of nutritional parameters such as phase angle and free-fat mass index, after 3 months of anticancer treatment. Consistently, the positive impact on OS correlated also with the prevention of Karnofsky performance status deterioration and a lower incidence of maldigestion-related symptoms. Conclusions: Our data suggest that an early and well-conducted NS in patients with mPC may impact on survival and preserve performance status, thus improving quality of life.
MeSH term(s)	Humans ; Gemcitabine ; Deoxycytidine ; Retrospective Studies ; Quality of Life ; Pancreatic Neoplasms/pathology ; Nutritional Support ; Paclitaxel/adverse effects ; Weight Loss ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Albumins
Chemical Substances	Gemcitabine ; Deoxycytidine (0W860991D6) ; Paclitaxel (P88XT4IS4D) ; Albumins
Language	English
Publishing date	2023-05-06
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyad101
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 494: Show issues

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Article: Obstructive Sleep Apnea Worsens Progression-Free and Overall Survival in Human Metastatic Colorectal Carcinoma.

Lacedonia, Donato / Landriscina, Matteo / Scioscia, Giulia / Tondo, Pasquale / Caccavo, Incoronata / Bruno, Giuseppina / Giordano, Guido / Piscazzi, Annamaria / Foschino Barbaro, Maria Pia

Journal of oncology

2021 Volume 2021, Page(s) 5528303

Abstract: Sleep disorders have emerged as highly prevalent conditions, and along with improved understanding of such disorders, increased attention has gained the evidence that perturbation in sleep architecture and continuity may initiate, exacerbate, or modulate ...

Abstract	Sleep disorders have emerged as highly prevalent conditions, and along with improved understanding of such disorders, increased attention has gained the evidence that perturbation in sleep architecture and continuity may initiate, exacerbate, or modulate the phenotypic expression of multiple diseases including cancer. Furthermore, obstructive sleep apnea (OSA) has recently been implicated in increased incidence and more adverse prognosis of cancer in humans. This study was designed to confirm the high prevalence of OSA in human malignancies and assess its prognostic relevance in metastatic colorectal carcinomas (mCRCs). A prospective cohort of 52 subjects, affected by solid histologically confirmed metastatic malignancies, was analyzed, and among them, 29 mCRCs were studied for the prognostic role of OSA. OSA was diagnosed in 34.6% (18/52) of patients with a statistically significant difference in apnea-hyponea index between OSA and non-OSA subgroups (14.2 ± 12.2 vs. 2.1 ± 1.5,
Language	English
Publishing date	2021-04-02
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2461349-6
ISSN	1687-8469 ; 1687-8450
ISSN (online)	1687-8469
ISSN	1687-8450
DOI	10.1155/2021/5528303
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Article ; Online: Differential and divergent activity of insulin-like growth factor binding protein 6 in platinum-sensitive versus platinum-resistant high-grade serous ovarian carcinoma cell lines.

Piscazzi, Annamaria / Condelli, Valentina / Crispo, Fabiana / Coda, Anna Rita Daniela / Calice, Giovanni / Bruno, Giuseppina / Venuto, Santina / Tibullo, Daniele / Giordano, Guido / Pietrafesa, Michele / Liso, Arcangelo / Landriscina, Matteo

Oncology letters

2022 Volume 23, Issue 6, Page(s) 185

Abstract: Insulin-like growth factor binding protein 6 (IGFBP6) is a secreted protein with a controversial role in human malignancies, being downregulated in most types of human cancer, but upregulated in selected tumors. Ovarian cancer (OC) is a human malignancy ... ...

Abstract	Insulin-like growth factor binding protein 6 (IGFBP6) is a secreted protein with a controversial role in human malignancies, being downregulated in most types of human cancer, but upregulated in selected tumors. Ovarian cancer (OC) is a human malignancy characterized by IGFBP6 downregulation; however, the significance of its low expression during ovarian carcinogenesis is still poorly understood. In the present study, IGFBP6 expression and activation of its associated signaling pathway were evaluated in two matched OC cell lines derived from a high-grade serous OC before and after platinum resistance (PEA1 and PEA2 cells, respectively). A whole genome gene expression analysis was comparatively performed in both cell lines upon IGFBP6 stimulation using Illumina technology. IGFBP6 gene expression data from human OC cases were obtained from public datasets. Gene expression data from public datasets confirmed the downregulation of IGFBP6 in primary and metastatic OC tissues compared with in normal ovarian tissues. The comparative analysis of platinum-sensitive (PEA1) and platinum-resistant (PEA2) cell lines showed quantitative and qualitative differences in the activation of IGFBP6 signaling. Notably, IGFBP6 enhanced ERK1/2 phosphorylation only in PEA1 cells, and induced more evident and significant gene expression reprogramming in PEA1 cells compared with in PEA2 cells. Furthermore, the analysis of selected genes modulated by IGFBP6 (i.e.,
Language	English
Publishing date	2022-04-21
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2573196-8
ISSN	1792-1082 ; 1792-1074
ISSN (online)	1792-1082
ISSN	1792-1074
DOI	10.3892/ol.2022.13305
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Article ; Online: TRAP1 regulates the response of colorectal cancer cells to hypoxia and inhibits ribosome biogenesis under conditions of oxygen deprivation.

Bruno, Giuseppina / Li Bergolis, Valeria / Piscazzi, Annamaria / Crispo, Fabiana / Condelli, Valentina / Zoppoli, Pietro / Maddalena, Francesca / Pietrafesa, Michele / Giordano, Guido / Matassa, Danilo Swann / Esposito, Franca / Landriscina, Matteo

International journal of oncology

2022 Volume 60, Issue 6

Abstract: Metabolic rewiring fuels rapid cancer cell proliferation by promoting adjustments in energetic resources, and increasing glucose uptake and its conversion into lactate, even in the presence of oxygen. Furthermore, solid tumors often contain hypoxic areas ...

Abstract	Metabolic rewiring fuels rapid cancer cell proliferation by promoting adjustments in energetic resources, and increasing glucose uptake and its conversion into lactate, even in the presence of oxygen. Furthermore, solid tumors often contain hypoxic areas and can rapidly adapt to low oxygen conditions by activating hypoxia inducible factor (HIF)‑1α and several downstream pathways, thus sustaining cell survival and metabolic reprogramming. Since TNF receptor‑associated protein 1 (TRAP1) is a HSP90 molecular chaperone upregulated in several human malignancies and is involved in cancer cell adaptation to unfavorable environments and metabolic reprogramming, in the present study, its role was investigated in the adaptive response to hypoxia in human colorectal cancer (CRC) cells and organoids. In the present study, glucose uptake, lactate production and the expression of key metabolic genes were evaluated in TRAP1‑silenced CRC cell models under conditions of hypoxia/normoxia. Whole genome gene expression profiling was performed in TRAP1‑silenced HCT116 cells exposed to hypoxia to establish the role of TRAP1 in adaptive responses to oxygen deprivation. The results revealed that TRAP1 was involved in regulating hypoxia‑induced HIF‑1α stabilization and glycolytic metabolism and that glucose transporter 1 expression, glucose uptake and lactate production were partially impaired in TRAP1‑silenced CRC cells under hypoxic conditions. At the transcriptional level, the gene expression reprogramming of cancer cells driven by HIF‑1α was partially inhibited in TRAP1‑silenced CRC cells and organoids exposed to hypoxia. Moreover, Gene Set Enrichment Analysis of TRAP1‑silenced HCT116 cells exposed to hypoxia demonstrated that TRAP1 was involved in the regulation of ribosome biogenesis and this occurred with the inhibition of the mTOR pathway. Therefore, as demonstrated herein, TRAP1 is a key factor in maintaining HIF‑1α‑induced genetic/metabolic program under hypoxic conditions and may represent a promising target for novel metabolic therapies.
MeSH term(s)	Cell Hypoxia ; Colorectal Neoplasms/pathology ; Glucose/metabolism ; Glycolysis ; HSP90 Heat-Shock Proteins/genetics ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lactates ; Oxygen/metabolism ; Ribosomes/genetics ; Ribosomes/metabolism ; Ribosomes/pathology ; TNF Receptor-Associated Factor 1/metabolism
Chemical Substances	HSP90 Heat-Shock Proteins ; Hypoxia-Inducible Factor 1, alpha Subunit ; Lactates ; TNF Receptor-Associated Factor 1 ; TRAP1 protein, human ; Glucose (IY9XDZ35W2) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-05-11
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2022.5369
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Zs.A 3690: Show issues

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Article ; Online: IDH1

Crispo, Fabiana / Pietrafesa, Michele / Condelli, Valentina / Maddalena, Francesca / Bruno, Giuseppina / Piscazzi, Annamaria / Sgambato, Alessandro / Esposito, Franca / Landriscina, Matteo

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 16

Abstract: Cholangiocarcinoma is a primary malignancy of the biliary tract characterized by late and unspecific symptoms, unfavorable prognosis, and few treatment options. The advent of next-generation sequencing has revealed potential targetable or actionable ... ...

Abstract	Cholangiocarcinoma is a primary malignancy of the biliary tract characterized by late and unspecific symptoms, unfavorable prognosis, and few treatment options. The advent of next-generation sequencing has revealed potential targetable or actionable molecular alterations in biliary tumors. Among several identified genetic alterations, the
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/pathology ; Cholangiocarcinoma/drug therapy ; Cholangiocarcinoma/metabolism ; Cholangiocarcinoma/pathology ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.)
Language	English
Publishing date	2020-08-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25163754
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Article ; Online: Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era.

Giordano, Guido / Parcesepe, Pietro / Bruno, Giuseppina / Piscazzi, Annamaria / Lizzi, Vincenzo / Remo, Andrea / Pancione, Massimo / D'Andrea, Mario Rosario / De Santis, Elena / Coppola, Luigi / Pietrafesa, Michele / Fersini, Alberto / Ambrosi, Antonio / Landriscina, Matteo

International journal of molecular sciences

2021 Volume 22, Issue 14

Abstract: Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such ...

Abstract	Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Pharmacological/chemistry ; Biomarkers, Pharmacological/metabolism ; Clinical Trials, Phase III as Topic ; Colorectal Neoplasms/enzymology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Humans ; Mutation ; Precision Medicine/methods ; Randomized Controlled Trials as Topic ; ras Proteins/genetics ; ras Proteins/metabolism
Chemical Substances	Biomarkers, Pharmacological ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2021-07-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22147717
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Article ; Online: Cyclin-dependent kinase 1 targeting improves sensitivity to radiation in BRAF V600E colorectal carcinoma cells.

Spagnoletti, Girolamo / Li Bergolis, Valeria / Piscazzi, Annamaria / Giannelli, Francesca / Condelli, Valentina / Sisinni, Lorenza / Bove, Giuseppe / Storto, Giovanni / Landriscina, Matteo

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

2018 Volume 40, Issue 4, Page(s) 1010428318770957

Abstract: Objectives: Preoperative chemoradiation is currently the standard of care in locally advanced rectal carcinoma, even though a subset of rectal tumors does not achieve major clinically meaningful responses upon neoadjuvant chemoradiation. At present, no ... ...

Abstract	Objectives: Preoperative chemoradiation is currently the standard of care in locally advanced rectal carcinoma, even though a subset of rectal tumors does not achieve major clinically meaningful responses upon neoadjuvant chemoradiation. At present, no molecular biomarkers are available to predict response to neoadjuvant chemoradiation and select resistant tumors willing more intense therapeutic strategies. Thus, BRAF mutational status was investigated for its role in favoring resistance to radiation in colorectal carcinoma cell lines and cyclin-dependent kinase 1 as a target to improve radiosensitivity in BRAF V600E colorectal tumor cells. Methods: Colony-forming assay and apoptotic rates were evaluated to compare the sensitivity of different colon carcinoma cell lines to ionizing radiation and their radiosensitivity upon exposure to BRAF and/or cyclin-dependent kinase 1 inhibitory/silencing strategies. Cyclin-dependent kinase 1 expression/subcellular distribution was studied by immunoblot analysis. Results: Colon carcinoma BRAF V600E HT29 cells exhibited poor response to radiation compared to BRAF wild-type COLO320 and HCT116 cells. Interestingly, neither radiosensitizing doses of 5-fluoruracil nor BRAF inhibition/silencing significantly improved radiosensitivity in HT29 cells. Of note, poor response to radiation correlated with upregulation/relocation of cyclin-dependent kinase 1 in mitochondria. Consistently, cyclin-dependent kinase 1 inhibition/silencing as well as its targeting, through inhibition of HSP90 quality control pathway, significantly inhibited the clonogenic ability and increased apoptotic rates in HT29 cells upon exposure to radiation. Conclusion: These data suggest that BRAF V600E colorectal carcinoma cells are poorly responsive to radiation, and cyclin-dependent kinase 1 represents a target to improve radiosensitivity in BRAF V600E colorectal tumor cells.
MeSH term(s)	CDC2 Protein Kinase/antagonists & inhibitors ; CDC2 Protein Kinase/biosynthesis ; CDC2 Protein Kinase/genetics ; Cell Line, Tumor ; Chemoradiotherapy/methods ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/radiotherapy ; Fluorouracil/pharmacology ; HCT116 Cells ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HT29 Cells ; Humans ; Mitochondria/metabolism ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Radiation Tolerance/drug effects ; Radiation Tolerance/genetics ; Radiation, Ionizing ; Radiation-Sensitizing Agents/pharmacology
Chemical Substances	HSP90 Heat-Shock Proteins ; Radiation-Sensitizing Agents ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; CDC2 Protein Kinase (EC 2.7.11.22) ; CDK1 protein, human (EC 2.7.11.22) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2018-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	605825-5
ISSN	1423-0380 ; 0289-5447 ; 1010-4283
ISSN (online)	1423-0380
ISSN	0289-5447 ; 1010-4283
DOI	10.1177/1010428318770957
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Zs.A 1598: Show issues

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Article ; Online: Comparative Gene Expression Profiling of Tobacco-Associated HPV-Positive versus Negative Oral Squamous Carcinoma Cell Lines.

Lepore, Silvia / Lettini, Giacomo / Condelli, Valentina / Sisinni, Lorenza / Piscazzi, Annamaria / Simeon, Vittorio / Zoppoli, Pietro / Pedicillo, Maria Carmela / Natalicchio, Maria Iole / Pietrafesa, Michele / Landriscina, Matteo

International journal of medical sciences

2020 Volume 17, Issue 1, Page(s) 112–124

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Aged ; Antigens, CD/genetics ; Axin Protein/genetics ; Cadherins/genetics ; Cell Line, Tumor ; Cyclin D1/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Human papillomavirus 16/genetics ; Human papillomavirus 16/pathogenicity ; Humans ; Hyaluronan Receptors/genetics ; Male ; MicroRNAs/genetics ; Middle Aged ; Papillomavirus Infections/complications ; Papillomavirus Infections/genetics ; Papillomavirus Infections/virology ; Proto-Oncogene Proteins c-myc/genetics ; Squamous Cell Carcinoma of Head and Neck/chemically induced ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/pathology ; Squamous Cell Carcinoma of Head and Neck/virology ; Nicotiana/adverse effects ; Wnt Signaling Pathway/genetics
Chemical Substances	AXIN2 protein, human ; Antigens, CD ; Axin Protein ; CD44 protein, human ; CDH1 protein, human ; CDKN2A protein, human ; Cadherins ; Cyclin-Dependent Kinase Inhibitor p16 ; HNF1A protein, human ; Hepatocyte Nuclear Factor 1-alpha ; Hyaluronan Receptors ; MYC protein, human ; MicroRNAs ; Proto-Oncogene Proteins c-myc ; mirnlet7 microRNA, human ; Cyclin D1 (136601-57-5)
Language	English
Publishing date	2020-01-01
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2151424-0
ISSN	1449-1907 ; 1449-1907
ISSN (online)	1449-1907
ISSN	1449-1907
DOI	10.7150/ijms.35133
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Article ; Online: TRAP1 enhances Warburg metabolism through modulation of PFK1 expression/activity and favors resistance to EGFR inhibitors in human colorectal carcinomas.

Maddalena, Francesca / Condelli, Valentina / Matassa, Danilo Swann / Pacelli, Consiglia / Scrima, Rosella / Lettini, Giacomo / Li Bergolis, Valeria / Pietrafesa, Michele / Crispo, Fabiana / Piscazzi, Annamaria / Storto, Giovanni / Capitanio, Nazzareno / Esposito, Franca / Landriscina, Matteo

Molecular oncology

2020 Volume 14, Issue 12, Page(s) 3030–3047

Abstract: Metabolic rewiring is a mechanism of adaptation to unfavorable environmental conditions and tumor progression. TRAP1 is an HSP90 molecular chaperone upregulated in human colorectal carcinomas (CRCs) and responsible for downregulation of oxidative ... ...

Abstract	Metabolic rewiring is a mechanism of adaptation to unfavorable environmental conditions and tumor progression. TRAP1 is an HSP90 molecular chaperone upregulated in human colorectal carcinomas (CRCs) and responsible for downregulation of oxidative phosphorylation (OXPHOS) and adaptation to metabolic stress. The mechanism by which TRAP1 regulates glycolytic metabolism and the relevance of this regulation in resistance to EGFR inhibitors were investigated in patient-derived CRC spheres, human CRC cells, samples, and patients. A linear correlation was observed between TRAP1 levels and
MeSH term(s)	Cell Line, Tumor ; Cell Respiration/drug effects ; Cetuximab/pharmacology ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Drug Resistance, Neoplasm/drug effects ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Enzyme Stability/drug effects ; ErbB Receptors/metabolism ; Fluorodeoxyglucose F18/metabolism ; Glucose Transporter Type 1/metabolism ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Oxidation-Reduction ; Phenotype ; Phosphofructokinase-1/metabolism ; Protein Binding/drug effects ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/metabolism ; Warburg Effect, Oncologic/drug effects
Chemical Substances	Glucose Transporter Type 1 ; HSP90 Heat-Shock Proteins ; Protein Kinase Inhibitors ; TRAP1 protein, human ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Phosphofructokinase-1 (EC 2.7.1.11) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Cetuximab (PQX0D8J21J)
Language	English
Publishing date	2020-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.12814
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Article ; Online: DAAs Rapidly Reduce Inflammation but Increase Serum VEGF Level: A Rationale for Tumor Risk during Anti-HCV Treatment.

Villani, Rosanna / Facciorusso, Antonio / Bellanti, Francesco / Tamborra, Rosanna / Piscazzi, Annamaria / Landriscina, Matteo / Vendemiale, Gianluigi / Serviddio, Gaetano

PloS one

2016 Volume 11, Issue 12, Page(s) e0167934

Abstract: Background: Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has ... ...

Abstract	Background: Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has been reported within weeks of starting treatment, but the mechanism is not known. Methods: We monitored the serum level of vascular endothelial growth factor (VEGF) and changes in the pattern of circulating interleukins in 103 chronic hepatitis C patients during antiviral treatment with DAA-regimens. VEGF, epidermal growth factor (EGF), and several interleukins were assessed at baseline, during treatment, and after treatment. The biological effect of DAA-treated patient serum on human umbilical vein endothelial cell (HUVEC) proliferation was also confirmed. Results: After 4 weeks of therapy, VEGF increased approximately 4-fold compared to baseline, remained elevated up to the end of treatment, and returned to the pre-treatment level after the end of therapy. In contrast, interleukin-10 and tumor necrosis factor-alpha significantly decreased during therapy, which was coincident with HCV clearance. The levels of both remained low after treatment. The addition of serum from patients collected during therapy induced HUVEC proliferation; however, this disappeared after the end of therapy. Conclusions: DAA administration induces an early increase in serum VEGF and a change in the inflammatory pattern, coinciding with HCV clearance. This may alter the balance between inflammatory and anti-inflammatory processes and modify the antitumor surveillance of the host. Fortunately, such modifications return reverse to normal after the end of treatment.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/administration & dosage ; Antiviral Agents/adverse effects ; Cell Proliferation/drug effects ; Epidermal Growth Factor/blood ; Female ; Hepacivirus/metabolism ; Hepatitis C/blood ; Hepatitis C/drug therapy ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Inflammation/blood ; Inflammation/drug therapy ; Interleukin-10/blood ; Male ; Middle Aged ; Neoplasms ; Tumor Necrosis Factor-alpha/blood ; Vascular Endothelial Growth Factor A/blood
Chemical Substances	Antiviral Agents ; IL10 protein, human ; Tumor Necrosis Factor-alpha ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Interleukin-10 (130068-27-8) ; Epidermal Growth Factor (62229-50-9)
Language	English
Publishing date	2016-12-20
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0167934
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