LIVIVO - Search results -

Search results

Result 1 - 10 of total 43

Search options

Article ; Online: Can MRI features predict clinically relevant hepatocellular carcinoma genetic subtypes?

Liu, Xiaoyang / Guo, Yang / Zhao, Lei / Misdraji, Joseph / Kapur, Tina / Abrams, Thomas A / Shyn, Paul B

2023 Volume 48, Issue 6, Page(s) 1955–1964

Abstract: Purpose: Recent studies in cancer genomics have revealed core drivers for hepatocellular carcinoma (HCC) pathogenesis. We aim to study whether MRI features can serve as non-invasive markers for the prediction of common genetic subtypes of HCC.: ... ...

Abstract	Purpose: Recent studies in cancer genomics have revealed core drivers for hepatocellular carcinoma (HCC) pathogenesis. We aim to study whether MRI features can serve as non-invasive markers for the prediction of common genetic subtypes of HCC. Methods: Sequencing of 447 cancer-implicated genes was performed on 43 pathology proven HCC from 42 patients, who underwent contrast-enhanced MRI followed by biopsy or resection. MRI features were retrospectively evaluated including tumor size, infiltrative tumor margin, diffusion restriction, arterial phase hyperenhancement, non-peripheral washout, enhancing capsule, peritumoral enhancement, tumor in vein, fat in mass, blood products in mass, cirrhosis and tumor heterogeneity. Fisher's exact test was used to correlate genetic subtypes with imaging features. Prediction performance using correlated MRI features for genetic subtype and inter-reader agreement were assessed. Results: The two most prevalent genetic mutations were TP53 (13/43, 30%) and CTNNB1 (17/43, 40%). Tumors with TP53 mutation more often demonstrated an infiltrative tumor margin on MRI (p = 0.01); inter-reader agreement was almost perfect (kappa = 0.95). The CTNNB1 mutation was associated with peritumoral enhancement on MRI (p = 0.04), inter-reader agreement was substantial (kappa = 0.74). The MRI feature of an infiltrative tumor margin correlated with the TP53 mutation with accuracy, sensitivity, and specificity of 74.4%, 61.5% and 80.0%, respectively. Peritumoral enhancement correlated with the CTNNB1 mutation with accuracy, sensitivity, and specificity of 69.8%, 47.0% and 84.6%, respectively. Conclusion: An infiltrative tumor margin on MRI correlated with TP53 mutation and peritumoral enhancement correlated with CTNNB1 mutation in HCC. Absence of these MRI features are potential negative predictors of the respective HCC genetic subtypes that have implications for prognosis and treatment response.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Retrospective Studies ; Contrast Media ; Magnetic Resonance Imaging/methods ; Sensitivity and Specificity ; Gadolinium DTPA
Chemical Substances	Contrast Media ; Gadolinium DTPA (K2I13DR72L)
Language	English
Publishing date	2023-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2839786-1
ISSN	2366-0058 ; 2366-004X
ISSN (online)	2366-0058
ISSN	2366-004X
DOI	10.1007/s00261-023-03876-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1262: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Priming of Sorafenib Prior to Radiofrequency Ablation Does Not Increase Treatment Effect in Hepatocellular Carcinoma.

Bockorny, Bruno / Bullock, Andrea J / Abrams, Thomas A / Faintuch, Salomao / Alsop, David C / Goldberg, S Nahum / Ahmed, Muneeb / Miksad, Rebecca A

Digestive diseases and sciences

2021 Volume 67, Issue 7, Page(s) 3455–3463

Abstract: Background: Preclinical studies have shown that modulation of the tumor microvasculature with anti-angiogenic agents decreases tumor perfusion and may increase the efficacy of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). ... ...

Abstract	Background: Preclinical studies have shown that modulation of the tumor microvasculature with anti-angiogenic agents decreases tumor perfusion and may increase the efficacy of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). Retrospective studies suggest that sorafenib given prior to RFA promotes an increase in the ablation zone, but prospective randomized data are lacking. Aims: We conducted a randomized, double-blind, placebo-controlled phase II trial to evaluate the efficacy of a short-course of sorafenib prior to RFA for HCC tumors sized 3.5-7 cm (NCT00813293). Methods: Treatment consisted of sorafenib 400 mg twice daily for 10 days or matching placebo, followed by RFA on day 10. The primary objectives were to assess if priming with sorafenib increased the volume and diameter of the RFA coagulation zone and to evaluate its impact on RFA thermal parameters. Secondary objectives included feasibility, safety and to explore the relationship between tumor blood flow on MRI and RFA effectiveness. Results: Twenty patients were randomized 1:1. Priming with sorafenib did not increase the size of ablation zone achieved with RFA and did not promote significant changes in thermal parameters, although it significantly decreased blood perfusion to the tumor by 27.9% (p = 0.01) as analyzed by DCE-MRI. No subject discontinued treatment owing to adverse events and no grade 4 toxicity was observed. Conclusion: Priming of sorafenib did not enhance the effect of RFA in intermediate sized HCC. Future studies should investigate whether longer duration of treatment or a different antiangiogenic strategy in the post-procedure setting would be more effective in impairing tumor perfusion and increasing RFA efficacy.
MeSH term(s)	Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/surgery ; Catheter Ablation/adverse effects ; Catheter Ablation/methods ; Humans ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/drug therapy ; Liver Neoplasms/surgery ; Niacinamide/adverse effects ; Phenylurea Compounds/adverse effects ; Prospective Studies ; Radiofrequency Ablation/adverse effects ; Radiofrequency Ablation/methods ; Retrospective Studies ; Sorafenib/therapeutic use ; Treatment Outcome
Chemical Substances	Phenylurea Compounds ; Niacinamide (25X51I8RD4) ; Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2021-07-23
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-021-07156-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ui V Zs.35: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Physical activity in older adults with metastatic gastrointestinal cancer: a pilot and feasibility study.

Brown, Justin C / Brighton, Elizabeth / Campbell, Nancy / McCleary, Nadine J / Abrams, Thomas A / Cleary, James M / Enzinger, Peter C / Ng, Kimmie / Rubinson, Douglas / Wolpin, Brian M / Yurgelun, Matthew B / Meyerhardt, Jeffrey A

BMJ open sport & exercise medicine

2022 Volume 8, Issue 2, Page(s) e001353

Abstract: Objectives: This study determined the feasibility of delivering a 12-week structured physical activity programme during chemotherapy to older adults recently diagnosed with metastatic gastrointestinal (GI) cancer.: Methods: This study used a single- ... ...

Abstract	Objectives: This study determined the feasibility of delivering a 12-week structured physical activity programme during chemotherapy to older adults recently diagnosed with metastatic gastrointestinal (GI) cancer. Methods: This study used a single-cohort design. Older adults (aged ≥65 years) diagnosed with metastatic oesophageal, gastric, pancreatic or colorectal cancer who planned to initiate chemotherapy were enrolled. The physical activity programme included a combination of aerobic, flexibility, strength and balance modalities delivered by a certified cancer exercise trainer during chemotherapy infusion appointments, then translated and sustained at home by participants. The co-primary endpoints included: (1) accrual of 20 participants in 12 months and (2) physical activity adherence of ≥50%. Results: Between March and October 2018, 29 participants were screened, and 20 were enrolled within 12 months (recruitment rate: 69% (90% CI: 55% to 83%); p<0.001), meeting the first co-primary endpoint. The median age of participants was 73.3 years (IQR: 69.3-77.2). At week 12, 67% (90% CI: 48% to 85%) of participants adhered to ≥50% of the prescribed physical activity (p=0.079 (statistically significant)), meeting the second co-primary endpoint. From baseline to week 12, accelerometer-measured light-intensity and moderate-intensity to vigorous-intensity physical activity increased by 307.4 (95% CI: 152.6 to 462.2; p<0.001) and 25.0 min per week (95% CI: 9.9 to 40.1; p=0.001), respectively. There were no serious or unexpected adverse events. The median overall survival was 16.2 months (8.4-22.4). Conclusion: These results establish the feasibility of a larger scale randomised controlled trial that enrols older adults with metastatic GI cancer and delivers a structured physical activity programme during chemotherapy. Trial registration number: NCT03331406.
Language	English
Publishing date	2022-05-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2817580-3
ISSN	2055-7647
ISSN	2055-7647
DOI	10.1136/bmjsem-2022-001353
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts.

Luo, Xiao / Yang, Wanshui / Joshi, Amit D / Wu, Kana / Simon, Tracey G / Yuan, Chen / Jin, Lina / Long, Lu / Kim, Mi Na / Lo, Chun-Han / Liu, Xing / Abrams, Thomas A / Wolpin, Brian M / Chan, Andrew T / Giovannucci, Edward L / Zhang, Xuehong

British journal of cancer

2022 Volume 127, Issue 6, Page(s) 1069–1075

Abstract: Background: Gallstones may result in inflammation, altered bile flow, and changes in metabolic hormone levels, thereby increasing cancer risk. However, previous studies for gallstones and cancers of the liver, biliary tract and pancreas in the U.S. were ...

Abstract	Background: Gallstones may result in inflammation, altered bile flow, and changes in metabolic hormone levels, thereby increasing cancer risk. However, previous studies for gallstones and cancers of the liver, biliary tract and pancreas in the U.S. were relatively limited. Methods: We followed 115,036 women from the Nurses' Health Study (1982-2012) and 49,729 men from the Health Professionals Follow-up Study (1986-2012). History of gallstones, including with or without performed cholecystectomy, was reported at baseline and updated through biennial questionnaires. The Cox proportional hazard regression model was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: During up to 30-year follow-up, we identified 204 incidents of liver cancer, 225 biliary tract cancer and 1147 pancreatic cancer cases. Compared to those without gallstones diagnosis, the multivariable HRs for individuals with gallstones (untreated or with cholecystectomy) were 1.60 for liver cancer (95% CI: 1.14-2.26), 4.79 for biliary tract cancer (95% CI: 3.02-7.58), and 1.13 for pancreatic cancer (95% CI: 0.96-1.32). The multivariable HRs for individuals with cholecystectomy were 1.33 for liver cancer (95% CI: 0.90-1.95) and 1.15 for pancreatic cancer (95% CI: 0.98-1.36). Conclusions: Gallstones were associated with a higher risk of cancers of the liver, biliary tract and possibly pancreas.
MeSH term(s)	Biliary Tract ; Biliary Tract Neoplasms/epidemiology ; Female ; Follow-Up Studies ; Gallstones/complications ; Gallstones/epidemiology ; Humans ; Liver Neoplasms ; Male ; Pancreas ; Pancreatic Neoplasms/epidemiology ; Prospective Studies ; Risk Factors ; Pancreatic Neoplasms
Language	English
Publishing date	2022-06-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-022-01877-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uh III Zs.142: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: PD-1 Blockade Induces Reactivation of Nonproductive T-Cell Responses Characterized by NF-κB Signaling in Patients with Pancreatic Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 30, Issue 3, Page(s) 542–553

Abstract: Purpose: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease in which bulky tumor burden and limited time to develop antitumor T cells may have contributed to poor clinical ... ...

Abstract	Purpose: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease in which bulky tumor burden and limited time to develop antitumor T cells may have contributed to poor clinical efficacy. Here, we evaluated peripheral blood and tumor T cells from patients with PDAC receiving neoadjuvant chemoradiation plus anti-PD-1 (pembrolizumab) versus chemoradiation alone. We analyzed whether PD-1 blockade successfully reactivated T cells in the blood and/or tumor to determine whether lack of clinical benefit could be explained by lack of reactivated T cells versus other factors. Experimental design: We used single-cell transcriptional profiling and TCR clonotype tracking to identify TCR clonotypes from blood that match clonotypes in the tumor. Results: PD-1 blockade increases the flux of TCR clonotypes entering cell cycle and induces an IFNγ signature like that seen in patients with other GI malignancies who respond to PD-1 blockade. However, these reactivated T cells have a robust signature of NF-κB signaling not seen in cases of PD-1 antibody response. Among paired samples between blood and tumor, several of the newly cycling clonotypes matched activated T-cell clonotypes observed in the tumor. Conclusions: Cytotoxic T cells in the blood of patients with PDAC remain sensitive to reinvigoration by PD-1 blockade, and some have tumor-recognizing potential. Although these T cells proliferate and have a signature of IFN exposure, they also upregulate NF-κB signaling, which potentially counteracts the beneficial effects of anti-PD-1 reinvigoration and marks these T cells as non-productive contributors to antitumor immunity. See related commentary by Lander and DeNardo, p. 474.
MeSH term(s)	Humans ; NF-kappa B ; Programmed Cell Death 1 Receptor ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; T-Lymphocytes, Cytotoxic/metabolism ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Receptors, Antigen, T-Cell/genetics ; CD8-Positive T-Lymphocytes
Chemical Substances	NF-kappa B ; Programmed Cell Death 1 Receptor ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-1444
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Patterns of Chemotherapy Use in a U.S.-Based Cohort of Patients with Metastatic Pancreatic Cancer.

Abrams, Thomas A / Meyer, Gary / Meyerhardt, Jeffrey A / Wolpin, Brian M / Schrag, Deborah / Fuchs, Charles S

The oncologist

2017 Volume 22, Issue 8, Page(s) 925–933

Abstract: Purpose: Few population studies have examined patterns of systemic therapy administration in metastatic pancreatic cancer (MPC) or the predictors associated with specific treatment choices.: Patients and methods: We assessed 4,011 consecutive MPC ... ...

Abstract	Purpose: Few population studies have examined patterns of systemic therapy administration in metastatic pancreatic cancer (MPC) or the predictors associated with specific treatment choices. Patients and methods: We assessed 4,011 consecutive MPC patients who received chemotherapy between January 2005 and December 2015 at academic, private, and community-based oncology practices subscribing to a U.S.-wide chemotherapy order entry system capturing disease, patient, provider, and treatment data. Multivariate analyses of these prospectively recorded characteristics identified significant predictors of specific therapeutic choices. Results: Overall, 100 different regimens were used in first-line treatment of MPC. First-line gemcitabine monotherapy usage fell steadily from 72% in 2006 to 16% in 2015. This steep decline mirrored increases in first-line usage of both 5 fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine + nab-paclitaxel. Younger male patients were more likely to receive FOLFIRINOX as first-line treatment, whereas patients treated at community practices and by oncologists with lower MPC patient volume were more likely to receive gemcitabine plus nab-paclitaxel (all Conclusion: This population-based study provides insight into treatment patterns of MPC in the U.S. Usage patterns varied greatly according to patient and provider characteristics. Implications for practice: This study examined real world metastatic pancreatic cancer treatment patterns in the United States with the goals of understanding changes in chemotherapy treatment frequencies over time and determining the individual predictors that underlie the chemotherapy choices oncologists make for their patients. Our data set is unique in that it captured not only patient-level data, but also oncologist-level data. It also captured data from private and community practices as well as academic centers. To our knowledge, this is the only data set that can give this degree of insight into oncologist decision making practices.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/epidemiology ; Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Albumins/administration & dosage ; Albumins/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Camptothecin/administration & dosage ; Camptothecin/adverse effects ; Camptothecin/analogs & derivatives ; Decision Making ; Deoxycytidine/administration & dosage ; Deoxycytidine/adverse effects ; Deoxycytidine/analogs & derivatives ; Female ; Fluorouracil/administration & dosage ; Fluorouracil/adverse effects ; Humans ; Leucovorin/administration & dosage ; Leucovorin/adverse effects ; Male ; Middle Aged ; Neoplasm Metastasis ; Organoplatinum Compounds/administration & dosage ; Organoplatinum Compounds/adverse effects ; Paclitaxel/administration & dosage ; Paclitaxel/adverse effects ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/epidemiology ; Pancreatic Neoplasms/pathology ; United States/epidemiology
Chemical Substances	130-nm albumin-bound paclitaxel ; Albumins ; Organoplatinum Compounds ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R) ; Paclitaxel (P88XT4IS4D) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2017-05-05
Publishing country	United States
Document type	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	10.1634/theoncologist.2016-0447
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Targeted therapy for dermatofibrosarcoma protuberans.

Abrams, Thomas A / Schuetze, Scott M

Current oncology reports

2007 Volume 8, Issue 4, Page(s) 291–296

Abstract: Dermatofibrosarcoma protuberans (DFSP) is a rare, cutaneous tumor characterized by aggressive local invasion. Local recurrence after excision is common, especially when negative margins are not achieved. DFSP frequently exhibits translocation of ... ...

Abstract	Dermatofibrosarcoma protuberans (DFSP) is a rare, cutaneous tumor characterized by aggressive local invasion. Local recurrence after excision is common, especially when negative margins are not achieved. DFSP frequently exhibits translocation of chromosomes 17 and 22, t(17;22). This rearrangement fuses the collagen type Ialpha1 (COL1A1) gene to the platelet-derived growth factor B-chain (PDGFB) gene. The resultant chimeric gene causes unregulated expression of platelet-derived growth factor leading to abnormal activation of the platelet-derived growth factor receptor (PDGFR) beta tyrosine kinase through an autocrine loop. This is believed to be the critical event in DFSP tumorigenesis. Imatinib mesylate is a potent inhibitor of several protein tyrosine kinases, including the PDGFRs. Clinical evidence suggests that imatinib mesylate is a safe and effective treatment in DFSP, especially in cases of recurrent or metastatic disease. Three phase II, multicenter clinical trials are open to further investigate the role of imatinib mesylate in DFSP.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Dermatofibrosarcoma/drug therapy ; Dermatofibrosarcoma/metabolism ; Humans ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Skin Neoplasms/drug therapy ; Skin Neoplasms/metabolism
Chemical Substances	Antineoplastic Agents ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2007-01-22
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057359-5
ISSN	1523-3790
ISSN	1523-3790
DOI	10.1007/s11912-006-0035-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5521: 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)

Order via subito

Details ▾

Article ; Online: G-CSF rescue of FOLFIRINOX-induced neutropenia leads to systemic immune suppression in mice and humans.

Cardot-Ruffino, Victoire / Bollenrucher, Naima / Delius, Luisa / Wang, S Jennifer / Brais, Lauren K / Remland, Joshua / Keheler, C Elizabeth / Sullivan, Keri M / Abrams, Thomas A / Biller, Leah H / Enzinger, Peter C / McCleary, Nadine J / Patel, Anuj K / Rubinson, Douglas A / Schlechter, Benjamin / Slater, Sarah / Yurgelun, Matthew B / Cleary, James M / Perez, Kimberly /

Dougan, Michael / Ng, Kimmie / Wolpin, Brian M / Singh, Harshabad / Dougan, Stephanie K

Journal for immunotherapy of cancer

2023 Volume 11, Issue 6

Abstract: Background: Recombinant granulocyte colony-stimulating factor (G-CSF) is routinely administered for prophylaxis or treatment of chemotherapy-induced neutropenia. Chronic myelopoiesis and granulopoiesis in patients with cancer has been shown to induce ... ...

Abstract	Background: Recombinant granulocyte colony-stimulating factor (G-CSF) is routinely administered for prophylaxis or treatment of chemotherapy-induced neutropenia. Chronic myelopoiesis and granulopoiesis in patients with cancer has been shown to induce immature monocytes and neutrophils that contribute to both systemic and local immunosuppression in the tumor microenvironment. The effect of recombinant G-CSF (pegfilgrastim or filgrastim) on the production of myeloid-derived suppressive cells is unknown. Here we examined patients with pancreatic cancer, a disease known to induce myeloid-derived suppressor cells (MDSCs), and for which pegfilgrastim is routinely administered concurrently with FOLFIRINOX but not with gemcitabine-based chemotherapy regimens. Methods: Serial blood was collected from patients with pancreatic ductal adenocarcinoma newly starting on FOLFIRINOX or gemcitabine/n(ab)paclitaxel combination chemotherapy regimens. Neutrophil and monocyte frequencies were determined by flow cytometry from whole blood and peripheral blood mononuclear cell fractions. Serum cytokines were evaluated pretreatment and on-treatment. Patient serum was used in vitro to differentiate healthy donor monocytes to MDSCs as measured by downregulation of major histocompatibility complex II (HLA-DR) and the ability to suppress T-cell proliferation in vitro. C57BL/6 female mice with pancreatic tumors were treated with FOLFIRINOX with or without recombinant G-CSF to directly assess the role of G-CSF on induction of immunosuppressive neutrophils. Results: Patients receiving FOLFIRINOX with pegfilgrastim had increased serum G-CSF that correlated with an induction of granulocytic MDSCs. This increase was not observed in patients receiving gemcitabine/n(ab)paclitaxel without pegfilgrastim. Interleukin-18 also significantly increased in serum on FOLFIRINOX treatment. Patient serum could induce MDSCs as determined by in vitro functional assays, and this suppressive effect increased with on-treatment serum. Induction of MDSCs in vitro could be recapitulated by addition of recombinant G-CSF to healthy serum, indicating that G-CSF is sufficient for MDSC differentiation. In mice, neutrophils isolated from spleen of G-CSF-treated mice were significantly more capable of suppressing T-cell proliferation. Conclusions: Pegfilgrastim use contributes to immune suppression in both humans and mice with pancreatic cancer. These results suggest that use of recombinant G-CSF as supportive care, while critically important for mitigating neutropenia, may complicate efforts to induce antitumor immunity.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Gemcitabine ; Granulocyte Colony-Stimulating Factor/pharmacology ; Immunosuppression Therapy ; Leukocytes, Mononuclear ; Mice, Inbred C57BL ; Neutropenia/chemically induced ; Neutropenia/drug therapy ; Neutropenia/prevention & control ; Paclitaxel/pharmacology ; Pancreatic Neoplasms/drug therapy ; Recombinant Proteins ; Tumor Microenvironment
Chemical Substances	folfirinox ; Gemcitabine ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Paclitaxel (P88XT4IS4D) ; Recombinant Proteins
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-006589
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A Phase I Expansion Cohort Study Evaluating the Safety and Efficacy of the CHK1 Inhibitor LY2880070 with Low-dose Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma.

Huffman, Brandon M / Feng, Hanrong / Parmar, Kalindi / Wang, Junning / Kapner, Kevin S / Kochupurakkal, Bose / Martignetti, David B / Sadatrezaei, Golbahar / Abrams, Thomas A / Biller, Leah H / Giannakis, Marios / Ng, Kimmie / Patel, Anuj K / Perez, Kimberly J / Singh, Harshabad / Rubinson, Douglas A / Schlechter, Benjamin L / Andrews, Elizabeth / Hannigan, Alison M /

Dunwell, Stanley / Getchell, Zoe / Raghavan, Srivatsan / Wolpin, Brian M / Fortier, Caroline / D'Andrea, Alan D / Aguirre, Andrew J / Shapiro, Geoffrey I / Cleary, James M

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 24, Page(s) 5047–5056

Abstract: Purpose: Combining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine ... ...

Abstract	Purpose: Combining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine combined with the CHK1 inhibitor LY2880070 in patients with previously treated advanced PDAC. Patients and methods: Patients with metastatic PDAC were treated with gemcitabine intravenously at 100 mg/m2 on days 1, 8, and 15, and LY2880070 50 mg orally twice daily on days 2-6, 9-13, and 16-20 of each 21-day cycle. Pretreatment tumor biopsies were obtained from each patient for correlative studies and generation of organoid cultures for drug sensitivity testing and biomarker analyses. Results: Eleven patients with PDAC were enrolled in the expansion cohort between August 27, 2020 and July 30, 2021. Four patients (36%) experienced drug-related grade 3 adverse events. No objective radiologic responses were observed, and all patients discontinued the trial by 3.2 months. In contrast to the lack of efficacy observed in patients, organoid cultures derived from biopsies procured from two patients demonstrated strong sensitivity to the gemcitabine/LY2880070 combination and showed treatment-induced upregulation of replication stress and DNA damage biomarkers, including pKAP1, pRPA32, and γH2AX, as well as induction of replication fork instability. Conclusions: No evidence of clinical activity was observed for combined low-dose gemcitabine and LY2880070 in this treatment-refractory PDAC cohort. However, the gemcitabine/LY2880070 combination showed in vitro efficacy, suggesting that drug sensitivity for this combination in organoid cultures may not predict clinical benefit in patients.
MeSH term(s)	Humans ; Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/pathology ; Checkpoint Kinase 1/antagonists & inhibitors ; Cohort Studies ; Deoxycytidine ; Gemcitabine ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use
Chemical Substances	Checkpoint Kinase 1 (EC 2.7.11.1) ; Deoxycytidine (0W860991D6) ; Gemcitabine ; Protein Kinase Inhibitors ; Antineoplastic Agents
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-2005
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Chemotherapy usage patterns in a US-wide cohort of patients with metastatic colorectal cancer.

Abrams, Thomas A / Meyer, Gary / Schrag, Deborah / Meyerhardt, Jeffrey A / Moloney, Julie / Fuchs, Charles S

Journal of the National Cancer Institute

2014 Volume 106, Issue 2, Page(s) djt371

Abstract: Background: Since the introduction of biologic therapies for the treatment of metastatic colorectal cancer (mCRC), few studies have examined patterns of care or predictors of specific treatment approaches.: Methods: We assessed 4877 mCRC patients who ...

Abstract	Background: Since the introduction of biologic therapies for the treatment of metastatic colorectal cancer (mCRC), few studies have examined patterns of care or predictors of specific treatment approaches. Methods: We assessed 4877 mCRC patients who received chemotherapy between January 2004 and March 2011 at academic, private, and community-based oncology practices subscribing to a US-wide chemotherapy order entry (system capturing disease, patient, provider, and treatment data. Multivariable analyses of these prospectively recorded characteristics were used to identify independent predictors of specific therapeutic choices. All statistical tests were two-sided. Results: Throughout the study period, fluoropyrimidine/oxaliplatin combination was the most commonly used first-line chemotherapy regimen, representing 71% of first-line therapy by 2007. First-line bevacizumab use averaged 51%, peaking at 55% in 2006. Of those who received first-line bevacizumab, 34% continued to receive bevacizumab in the second-line. Only 26% of patients in our cohort ever received an anti-EGFR monoclonal antibody (cetuximab = 22%; panitumumab = 6%) at some point in their treatment course. Patients treated at academic centers, with longer duration of first-line therapy, and at sites in the western United States were statistically more likely to receive an anti-EGFR antibody. Anti-EGFR antibody use fell by 18% after the US Food and Drug Administration limited its use to patients with KRAS wild-type tumors in June 2009. Conclusions: Analysis of this US-wide mCRC cohort demonstrates that bevacizumab has been more consistently integrated into treatment regimens than anti-EGFR antibody therapies, particularly in first-line therapy. However, treatment choices vary substantially according to specific patient, practice, and provider characteristics.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab ; Camptothecin/administration & dosage ; Camptothecin/analogs & derivatives ; Cancer Care Facilities ; Cetuximab ; Chemotherapy, Adjuvant/statistics & numerical data ; Cohort Studies ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Databases, Factual ; Female ; Fluorouracil/administration & dosage ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/methods ; Molecular Targeted Therapy/statistics & numerical data ; Mutation ; Organoplatinum Compounds/administration & dosage ; Phenylurea Compounds/administration & dosage ; Practice Patterns, Physicians' ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Pyridines/administration & dosage ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/administration & dosage ; Recombinant Fusion Proteins/administration & dosage ; Retrospective Studies ; United States ; ras Proteins/genetics
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; KRAS protein, human ; Organoplatinum Compounds ; Phenylurea Compounds ; Proto-Oncogene Proteins ; Pyridines ; Recombinant Fusion Proteins ; oxaliplatin (04ZR38536J) ; aflibercept (15C2VL427D) ; regorafenib (24T2A1DOYB) ; Bevacizumab (2S9ZZM9Q9V) ; panitumumab (6A901E312A) ; irinotecan (7673326042) ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2) ; Cetuximab (PQX0D8J21J) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2014-02
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; 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/djt371
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.131: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito