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Article: Neutropenic Enterocolitis in the Treatment of Solid Tumors: A Case Report and Review of the Literature.

Cherri, Sara / Prochilo, Tiziana / Rota, Luigina / Mutti, Stefano / Garatti, Marco / Liserre, Barbara / Zaniboni, Alberto

Case reports in oncology

2020 Volume 13, Issue 1, Page(s) 442–448

Abstract: Neutropenic enterocolitis is a clinical condition characterized by inflammation of the colic mucosa, usually the caecum, associated with bowel wall thickening in patients with compromised immune system due to chemotherapy treatments. It can occur as well ...

Abstract	Neutropenic enterocolitis is a clinical condition characterized by inflammation of the colic mucosa, usually the caecum, associated with bowel wall thickening in patients with compromised immune system due to chemotherapy treatments. It can occur as well in other clinical conditions that lead to immunosuppression. Clinically, patients present with abdominal pain, fever, and neutropenia on blood tests. A number of major and minor criteria have been suggested for the clinical diagnosis of typhlitis. The most sensitive radiological investigation is represented by a computed tomography scan. There are no guidelines for treatment, but some factors may lead the clinician to medical treatments or prompt surgery as the best choice in that particular patient. The most implicated chemotherapeutic regimens are those based on taxanes. Here, we present a clinical case of a young patient with breast cancer and a review of the state of the art of knowledge regarding neutropenic enterocolitis in adult patients undergoing chemotherapy for the treatment of solid tumors.
Language	English
Publishing date	2020-04-22
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2458961-5
ISSN	1662-6575
ISSN	1662-6575
DOI	10.1159/000506896
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Article ; Online: Late intracranial metastasis from adenoid-cystic carcinoma of the parotid gland: Imaging, histologic and molecular features.

Morassi, Mauro / Scavuzzo, Alessandro / Cobelli, Milena / Liserre, Barbara / Arias, Jahard Aliaga / Biasi, Brunella Di

Current problems in cancer

2020 Volume 44, Issue 5, Page(s) 100564

Abstract: We describe the neuroradiologic, histologic, and genetic features of a very unusual intracranial dural metastasis from adenoid cystic carcinoma of the parotid gland detected 27 years after the initial diagnosis. ...

Abstract	We describe the neuroradiologic, histologic, and genetic features of a very unusual intracranial dural metastasis from adenoid cystic carcinoma of the parotid gland detected 27 years after the initial diagnosis.
MeSH term(s)	Brain Neoplasms/secondary ; Brain Neoplasms/surgery ; Carcinoma, Adenoid Cystic/pathology ; Carcinoma, Adenoid Cystic/surgery ; Humans ; Male ; Middle Aged ; Parotid Neoplasms/pathology ; Parotid Neoplasms/surgery ; Prognosis
Language	English
Publishing date	2020-03-05
Publishing country	United States
Document type	Case Reports
ZDB-ID	441816-5
ISSN	1535-6345 ; 0147-0272
ISSN (online)	1535-6345
ISSN	0147-0272
DOI	10.1016/j.currproblcancer.2020.100564
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Article ; Online: Rapid on-site evaluation improves the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for solid pancreatic lesions irrespective of technique: A single-centre experience.

Milluzzo, Sebastian Manuel / Olivari, Nicola / Rossi, Giulio / Bianchi, Denise / Liserre, Barbara / Graffeo, Massimo / Lovera, Mauro / Correale, Loredana / Hassan, Cesare / Spada, Cristiano

Cytopathology : official journal of the British Society for Clinical Cytology

2023 Volume 34, Issue 4, Page(s) 318–324

Abstract: Objective: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the first-line technique for the sampling of pancreatic lesions. Many factors can influence the diagnostic performance of this procedure, including the use of rapid on-site ... ...

Abstract	Objective: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the first-line technique for the sampling of pancreatic lesions. Many factors can influence the diagnostic performance of this procedure, including the use of rapid on-site evaluation (ROSE). The primary aim of this study was to compare the adequacy, diagnostic yield, accuracy, sensitivity and specificity of EUS-FNA for solid pancreatic lesions before and after the introduction of ROSE. Methods: This retrospective single-centre study evaluated all consecutive patients who underwent EUS-FNA for suspicious, solid pancreatic masses from April 2012 to March 2015. We compared the findings of EUS-FNA procedures performed during the first and second years following the adoption of ROSE ("ROSE1" and "ROSE2", respectively) to those performed the year before ROSE introduction (the "pre-ROSE" group). Results: Ninety-one consecutive patients with a total of 93 pancreatic lesions were enrolled. For the pre-ROSE, ROSE1 and ROSE2 groups, the adequacy rates were 96.2%, 96.6% and 100%, the diagnostic yield values were 76.9%, 89.7% and 92.1% and accuracy values were 69.2%, 86.2% and 89.5% (p = NS). Sensitivity for malignancy improved from 63.7% in the pre-ROSE group to 91.7% and 91.2% in the post-ROSE groups (p < 0.05). Specificity for malignancy was 100% in all groups. Conclusions: ROSE can improve the diagnostic performance of EUS-FNA for solid pancreatic lesions, although only sensitivity reached statistical significance.
MeSH term(s)	Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/pathology ; Rapid On-site Evaluation ; Retrospective Studies ; Pancreas/pathology
Language	English
Publishing date	2023-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1034190-0
ISSN	1365-2303 ; 0956-5507 ; 1350-4037
ISSN (online)	1365-2303
ISSN	0956-5507 ; 1350-4037
DOI	10.1111/cyt.13237
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Article: Diagnosis of Mixed Adenoneuroendocrine Carcinoma (MANEC) after Neoadjuvant Chemotherapy for Pancreatic and Gastric Adenocarcinoma: Two Case Reports and a Review of the Literature.

Oneda, Ester / Liserre, Barbara / Bianchi, Denise / Rota, Luigina / Savelli, Giordano / Zorzi, Fausto / Zaniboni, Alberto

Case reports in oncology

2019 Volume 12, Issue 2, Page(s) 434–442

Abstract: Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract involving both epithelial and neuroendocrine (NE) components, each of which represents at least 30% of the tumor. Because of the low frequency of this histotype, ... ...

Abstract	Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract involving both epithelial and neuroendocrine (NE) components, each of which represents at least 30% of the tumor. Because of the low frequency of this histotype, only a few cases have been described. In this report we discuss two cases treated with neoadjuvant chemotherapy: a pancreatic adenocarcinoma and a gastric adenocarcinoma. The histopathological specimens examined after surgery showed an additional NE component with a possible indication of the MANEC histotype. We hypothesize two possible explanations: tumor NE cells are more chemo-resistant than adenocarcinoma cells, and cytotoxic injury induces NE differentiation in tumor cells. The clinical significance and prognostic value of endocrine differentiation, however, remain controversial issues.
Language	English
Publishing date	2019-06-13
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2458961-5
ISSN	1662-6575
ISSN	1662-6575
DOI	10.1159/000501200
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Article ; Online: A Multifocal Glioneuronal Tumor with RGNT-Like Morphology Occupying the Supratentorial Ventricular System and Infiltrating the Brain Parenchyma.

Morassi, Mauro / Vivaldi, Oscar / Cobelli, Milena / Liserre, Barbara / Zorzi, Fausto / Bnà, Claudio

World neurosurgery

2019 Volume 133, Page(s) 196–200

Abstract: Background: Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent ... ...

Abstract	Background: Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent evidence based on molecular data suggest that low-grade glioneuronal tumors (GNT) involving the septum pellucidum and the lateral ventricles, with either dysembryoplastic neuroepithelial tumor-like or RGNT-like features, may belong to a neuropathologic entity distinct from cortical dysembryoplastic neuroepithelial tumor and "typical" fourth ventricle RGNT, respectively. Given their rarity, the classification of these neoplasms is still uncertain and their clinicopathological and radiological aspects are only partially known. Case description: A 24-year-old male presented a GNT with RGNT-like morphological features centered in the septum pellucidum with multifocal masses occupying the lateral ventricles and the third ventricle with extraventricular infiltration of the frontal lobe. The patient underwent subtotal resection and 4 years follow-up. The clinicopathological and radiological features of the neoplasm are discussed. Conclusions: Advanced magnetic resonance imaging (magnetic resonance spectroscopy and perfusion-weighted imaging) may provide valuable information in the differential diagnosis between rare GNTs and other more frequent intraventricular neoplasms. In the present case, the enhancing remnant portion of the tumor showed remarkable contrast enhancement variability during the follow-up with slow in situ progression. However, available data suggest that spontaneous contrast enhancement "fluctuations" over time in RGNT may not represent a reliable indicator of tumor behavior.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Craniotomy ; Glioma/diagnostic imaging ; Glioma/pathology ; Glioma/surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Neurosurgical Procedures ; Septum Pellucidum/diagnostic imaging ; Septum Pellucidum/pathology ; Septum Pellucidum/surgery ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2019-10-10
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2019.10.017
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Article: Diagnosis of Mixed Adenoneuroendocrine Carcinoma (MANEC) after Neoadjuvant Chemotherapy for Pancreatic and Gastric Adenocarcinoma: Two Case Reports and a Review of the Literature

Oneda, Ester / Liserre, Barbara / Bianchi, Denise / Rota, Luigina / Savelli, Giordano / Zorzi, Fausto / Zaniboni, Alberto

Case Reports in Oncology

2019 Volume 12, Issue 2, Page(s) 434–442

Institution	Department of Clinical Oncology, Fondazione Poliambulanza, Brescia, Italy Department of Pathology, Fondazione Poliambulanza, Brescia, Italy Department of Nuclear Medicine, Fondazione Poliambulanza, Brescia, Italy
Abstract	Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract involving both epithelial and neuroendocrine (NE) components, each of which represents at least 30% of the tumor. Because of the low frequency of this histotype, only a few cases have been described. In this report we discuss two cases treated with neoadjuvant chemotherapy: a pancreatic adenocarcinoma and a gastric adenocarcinoma. The histopathological specimens examined after surgery showed an additional NE component with a possible indication of the MANEC histotype. We hypothesize two possible explanations: tumor NE cells are more chemo-resistant than adenocarcinoma cells, and cytotoxic injury induces NE differentiation in tumor cells. The clinical significance and prognostic value of endocrine differentiation, however, remain controversial issues.
Keywords	Mixed adenoneuroendocrine carcinoma ; Neoadjuvant chemotherapy ; Neuroendocrine differentiation
Language	English
Publishing date	2019-06-13
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Case Report ; This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC).
ZDB-ID	2458961-5
ISSN	1662-6575 ; 1662-6575
ISSN (online)	1662-6575
ISSN	1662-6575
DOI	10.1159/000501200
Database	Karger publisher's database

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Article: A Rare Complex BRAF Mutation Involving Codon V600 and K601 in Primary Cutaneous Melanoma: Case Report.

Consoli, Francesca / Barbieri, Gianluca / Picciolini, Matteo / Medicina, Daniela / Bugatti, Mattia / Tovazzi, Valeria / Liserre, Barbara / Zambelli, Claudia / Zorzi, Fausto / Berruti, Alfredo / Giurisato, Emanuele / Vermi, William

Frontiers in oncology

2020 Volume 10, Page(s) 1056

Abstract: BRAF is one of the most common mutated kinases detected in human cancer, particularly in cases of primary cutaneous melanomas (PCM). Mutations of the BRAF proto-oncogene, at the p.V600 codon, has been detected in more than 50% of primary and metastatic ... ...

Abstract	BRAF is one of the most common mutated kinases detected in human cancer, particularly in cases of primary cutaneous melanomas (PCM). Mutations of the BRAF proto-oncogene, at the p.V600 codon, has been detected in more than 50% of primary and metastatic melanoma cells in clinical samples. In addition to the most frequent BRAF p.V600E mutation, corresponding to the single base pair substitution c.1799T>A, rarer mutations, within and outside the V600 codon, have been described. Expectedly, BRAF and MEK inhibitors (or their combination) have been poorly explored as potential therapeutic strategies in metastatic melanomas harboring this rare mutation. By using a set of sequencing techniques and immunohistochemistry, this work reports the genomic and clinical features of two melanoma patients showing a rare complex mutation affecting codon V600 and K601 of the BRAF gene, leading to a V600E2; K601I change. Specifically, these two patients show a distinct clinical behavior and significantly differ in their responses to BRAF and MEK inhibitors. Indeed, although this treatment has proven to be effective and safe in both cases, the observed variability between the two patients resulted as a direct consequence of the baseline extent of brain involvement, intracranial treatment failure as well as on the PTEN status.
Language	English
Publishing date	2020-07-10
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.01056
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Article ; Online: The Day-To-Day Practice of MMR and MSI Assessment in Colorectal Adenocarcinoma: What We Know and What We Still Need to Explore.

Parente, Paola / Grillo, Federica / Vanoli, Alessandro / Macciomei, Maria Cristina / Ambrosio, Maria Raffaella / Scibetta, Nunzia / Filippi, Emanuela / Cataldo, Ivana / Baron, Luigi / Ingravallo, Giuseppe / Cazzato, Gerardo / Melocchi, Laura / Liserre, Barbara / Giordano, Carla / Arborea, Graziana / Pilozzi, Emanuela / Scapinello, Antonio / Aquilano, Maria Costanza / Gafà, Roberta /

Battista, Serena / Dal Santo, Luca / Campora, Michela / Carbone, Francesco Giuseppe / Sartori, Chiara / Lazzi, Stefano / Hanspeter, Ester / Angerilli, Valentina / Mastracci, Luca / Fassan, Matteo

Digestive diseases (Basel, Switzerland)

2023 Volume 41, Issue 5, Page(s) 746–756

Abstract: Background: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using ... ...

Abstract	Background: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using immunohistochemistry. Deficit in one or more MMR proteins, configuring deficient MMR status (dMMR), leads to frameshift mutations particularly clustered in microsatellite repeats. Thus, microsatellite instability (MSI) is the epiphenomenon of dMMR. In colorectal cancer (CRC), MMR/MSI status is a biomarker with prognostic and predictive value of resistance to 5-fluorouracil and response to immune checkpoint inhibitor therapy. Summary: In this Review, we describe the challenges the practicing pathologist may face in relation to the assessment of MMR/MSI status and any open issues which still need to be addressed, focusing on pre-analytic issues, pitfalls in the interpretation, and technical aspects of the different assays. Key messages: The current methods of detecting dMMR/MSI status have been optimized for CRCs, and whether these techniques can be applied to all tumor and specimen types is still not fully understood. Following the Food and Drug Administration (FDA), tissue/site agnostic drug approval of pembrolizumab for advanced/metastatic MSI tumors, MMR/MSI status in gastrointestinal tract is a common request from the oncologist. In this setting, several issues still need to be addressed, including criteria for sample adequacy.
MeSH term(s)	Humans ; Microsatellite Instability ; DNA Mismatch Repair/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Adenocarcinoma
Language	English
Publishing date	2023-05-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	632798-9
ISSN	1421-9875 ; 0257-2753
ISSN (online)	1421-9875
ISSN	0257-2753
DOI	10.1159/000531003
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Article: Helicobacter pylori infection in patients with celiac disease.

Villanacci, Vincenzo / Bassotti, Gabrio / Liserre, Barbara / Lanzini, Alberto / Lanzarotto, Francesco / Genta, Robert M

The American journal of gastroenterology

2006 Volume 101, Issue 8, Page(s) 1880–1885

Abstract: Background and aims: Patients with Helicobacter pylori gastritis are more likely to have increased duodenal intraepithelial lymphocytes (IEL); this can be reversed by H. pylori eradication. We hypothesized that: (1) H. pylori-infected celiac disease (CD) ...

Abstract	Background and aims: Patients with Helicobacter pylori gastritis are more likely to have increased duodenal intraepithelial lymphocytes (IEL); this can be reversed by H. pylori eradication. We hypothesized that: (1) H. pylori-infected celiac disease (CD) patients could have different clinicopathological features from noninfected subjects; and (2) the histopathological responses to a gluten-free diet could be different in H. pylori-infected and noninfected patients. Methods: Duodenal and gastric biopsies obtained from 80 adults with histologically and serologically confirmed CD before and after 12-18 months of a gluten-free diet were retrospectively evaluated. Gastritis was classified and scored according to the Updated Sydney System; duodenal biopsies were classified using both the Marsh-Oberhuber and a simplified classification proposed by our group. Results: At baseline, 30 patients had H. pylori infection and 50 did not; at follow-up five new infections were detected. Fifteen patients (3 H. pylori-positive and 12 negative) had lymphocytic gastritis. At baseline, a greater proportion of H. pylori-negative patients had severe villous atrophy (p < 0.01), but milder forms were more prevalent in H. pylori-positive patients (p < 0.01). After a gluten-free diet, significant improvement occurred in all duodenal features (p < 0.001), irrespective of H. pylori status; gastric variables did not change, except for lymphocytic, which resolved in 2 infected and 10 noninfected patients. Conclusions: The clinical features of CD patients are unrelated to H. pylori gastritis, and a gluten-free diet is equally effective in infected as in uninfected patients. The higher prevalence of milder duodenal lesions in CD patients with H. pylori infection suggests that lymphocytosis induced by H. pylori gastric infection becomes less obvious as profound inflammatory and structural changes alter the mucosal architecture. This study also provides further support for a pathogenetic relationship between CD and lymphocytic gastritis.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biopsy ; Celiac Disease/pathology ; Chi-Square Distribution ; Female ; Helicobacter Infections/pathology ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Retrospective Studies
Language	English
Publishing date	2006-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.1111/j.1572-0241.2006.00621.x
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Article ; Online: EGFR amplified and overexpressing glioblastomas and association with better response to adjuvant metronomic temozolomide.

Cominelli, Manuela / Grisanti, Salvatore / Mazzoleni, Stefania / Branca, Caterina / Buttolo, Luciano / Furlan, Daniela / Liserre, Barbara / Bonetti, Maria Fausta / Medicina, Daniela / Pellegrini, Vilma / Buglione, Michela / Liserre, Roberto / Pellegatta, Serena / Finocchiaro, Gaetano / Dalerba, Piero / Facchetti, Fabio / Pizzi, Marina / Galli, Rossella / Poliani, Pietro Luigi

Journal of the National Cancer Institute

2015 Volume 107, Issue 5

Abstract: Background: Lack of robust predictive biomarkers, other than MGMT promoter methylation, makes temozolomide responsiveness in newly diagnosed glioblastoma (GBM) patients difficult to predict. However, we identified patients with long-term survival (≥35 ... ...

Abstract	Background: Lack of robust predictive biomarkers, other than MGMT promoter methylation, makes temozolomide responsiveness in newly diagnosed glioblastoma (GBM) patients difficult to predict. However, we identified patients with long-term survival (≥35 months) within a group of newly diagnosed GBM patients treated with standard or metronomic adjuvant temozolomide schedules. We thus investigated possible molecular profiles associated with longer survival following temozolomide treatment. Methods: We investigated the association of molecular features with progression-free (PFS) and overall survival (OS). Human-derived GBM cancer stem cells (CSCs) were used to investigate in vitro molecular mechanisms associated with temozolomide responsiveness. Surgically removed recurrences allowed investigation of molecular changes occurring during therapy in vivo. Statistical analyses included one- and two-way analysis of variance, Student's t test, Cox proportional hazards, and the Kaplan-Meier method. All statistical tests were two-sided. Results: No association was found between survival and gene classifiers associated with different molecular GBM subtypes in the standard-treated group, while in metronomic-treated patients robust association was found between EGFR amplification/overexpression and PFS and OS (OS, EGFR-high vs low: hazard ratiodeath = 0.22, 95% confidence interval = 0.09 to 0.55, P = .001). The result for OS remained statistically significant after Bonferroni correction (P interaction < .0005). Long-term survival following metronomic temozolomide was independent from MGMT and EGFRvIII status and was more pronounced in EGFR-overexpressing GBM patients with PTEN loss. In vitro findings confirmed a selective dose- and time-dependent decrease in survival of temozolomide-treated EGFR+ human-derived glioblastoma CSCs, which occurred through inhibition of NF-κB transcriptional activity. In addition, reduction in EGFR-amplified cells, along with a statistically significant decrease in NF-κB/p65 expression, were observed in specimens from recurrent metronomic-treated EGFR-overexpressing GBM patients. Conclusions: EGFR-amplified/overexpressing glioblastomas strongly benefit from metronomic temozolomide-based therapies.
MeSH term(s)	Administration, Metronomic ; Adult ; Analysis of Variance ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Agents, Alkylating/therapeutic use ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/surgery ; Chemotherapy, Adjuvant ; Dacarbazine/administration & dosage ; Dacarbazine/analogs & derivatives ; Dacarbazine/therapeutic use ; Disease-Free Survival ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/surgery ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplastic Stem Cells/drug effects ; Odds Ratio ; Proportional Hazards Models ; Receptor, Epidermal Growth Factor/genetics ; Up-Regulation
Chemical Substances	Antineoplastic Agents, Alkylating ; Dacarbazine (7GR28W0FJI) ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; temozolomide (YF1K15M17Y)
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djv041
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