The Role of Fluoropirimidines in Gastrointestinal Tumours: from the Bench to the Bed

2017 ◽  
Vol 48 (2) ◽  
pp. 135-147 ◽  
Author(s):  
Jorge Hernando-Cubero ◽  
Ignacio Matos-García ◽  
Vicente Alonso-Orduña ◽  
Jaume Capdevila
2006 ◽  
Vol 20 (4) ◽  
pp. 457-460 ◽  
Author(s):  
Gian Luigi Adani ◽  
Umberto Baccarani ◽  
Dario Lorenzin ◽  
Maria Gropuzzo ◽  
Patrizia Tulissi ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13587-13587
Author(s):  
R. Bendardaf ◽  
A. Elzagheld ◽  
R. Ristamäki ◽  
K. Syrjänen ◽  
S. Pyrhonen

13587 Objective: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides required for DNA synthesis and is a critical target for fluoropyrimidines, which are widely used in the treatment of gastrointestinal tumours. Tumour TS expression was analysed in a series of 39 patients diagnosed and treated for Duke’s B, C and D colorectal cancer between January 1996 and August 2003 to investigate the role of TS in the development of metastatic phenotype in CRC. Methods: TS expression was determined immunohistochemically in 39 paraffin-embedded primary and metastatic tumour sections and the overall staining index was calculated according to the intensity of the cytoplasmic staining (0, 1, 2, 3) and the fraction of the corresponding tumour cells in the sample. Results: Tumours were classified as showing either lower or higher TS expression, i.e. below- or above the mean. In 29/39 (74.3%) pairs, the primary tumours and their metastases are concordant. In 10 out of 39 (25.7%) discordant pairs, TS expression was high in the primary tumours and low in the metastasis in 9/10 cases, and opposite in the remaining one case. Using the absolute staining index values, TS expression in the primary tumours and in the metastases was also significantly correlated (Pearson R=0.501, p=0.001). Conclusion: Between the paired primary tumours and distant metastatic lesion, the TS expression is in the majority higher in primary tumours compared to the metastasis and more concordant cases showed compared to discordant cases and in 9/10 discordant cases, TS expression in the primary tumours was above the mean and below the mean in their corresponding metastases compare to only one case showing the opposite pattern. No significant financial relationships to disclose.


2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
S. Mendis ◽  
S. Gill

Immunotherapy has been described as the “fourth pillar” of oncology treatment, in conjunction with surgery, chemotherapy, and radiotherapy. However, the role of immunotherapy in gastrointestinal tumours is still evolving. Data for checkpoint inhibition in esophagogastric, hepatocellular, colorectal, and anal squamous cell carcinomas are expanding. In phase iii trials in the second-line setting, PD-1 inhibitors have demonstrated positive results for the subset of esophageal cancers that are positive for PD-L1 at a combined positive score of 10 or more. Based on results of phase ii trials, PD-1 inhibitors were approved in North America for use in PD-L1–positive chemorefractory gastric cancers, in hepatocellular carcinoma after sorafenib exposure, and in treatment refractory deficient mismatch repair (dmmr) or high microsatellite instability (msi-h) tumours, regardless of tissue site. Combination use of PD-1 and ctla-4 inhibitors has been approved by the U.S. Food and Drug Administration for chemorefractory dmmr or msi-h colorectal cancer. Responses to checkpoint inhibition are durable, particularly in the dmmr or msi-h colorectal cancer cohort. As trials of combination immunotherapy, immunotherapy in combination with other systemic therapies, and immunotherapy in combination with other treatment modalities move forward in multiple tumour sites, cautious optimism is called for. The treatment landscape is continually changing, and expanded indications are likely to be just around the corner.


1991 ◽  
Vol 6 (5) ◽  
pp. 423-441 ◽  
Author(s):  
I. IHSE ◽  
R. N. GIBSON ◽  
H. W. BOYCE ◽  
W. R. LEES ◽  
E. VANSONNENBERG

2020 ◽  
Vol 3 (1) ◽  
pp. 1-22
Author(s):  
Csongor G. Lengyel ◽  
Baker Habeeb ◽  
Shah Z. Khan ◽  
Khalid El Bairi ◽  
Sara C. Altuna ◽  
...  

Gastrointestinal (GI) tumors account for a quarter of all the cancer burden and a third of the global cancer-related mortality. Among them, some cancers retain a dismal prognosis; therefore, newer and innovative therapies are urgently needed in priority disease areas of high-unmet medical need. In this context, HER2 could be a relevant prognostic and predictive biomarker acting as a target for specific drugs. However, if the role of HER2 has been object of investigation for several years in gastric cancer, it is not well established in other GI malignancies. The aim of this narrative review was to portray the current landscape of the potential role of HER2 as a predictive biomarker for GI tumors beyond gastric cancer. In colon cancer, the benefit from anti-HER2 therapies is less clear than in gastric neoplasms for the lack of controlled studies. Pancreatic, biliary tract adenocarcinomas and hepatocarcinoma may derive a less clear clinical benefit by using anti-HER2 agents in HER2 positive tumors. Overall, the results are promising and seem to suggest that the integration of multiple modalities of therapies can optimize the cancer care. However, further prospective trials are needed to validate the use of personalized targeted therapies in this field.


JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.


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