We are analyzing https://link.springer.com/article/10.1186/1479-5876-3-22.

Title:
The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice | Journal of Translational Medicine
Description:
Background Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials. Methods We have investigated the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated with Apo2L/TRAIL, gemcitabine or a combination of both therapies. Results Patient tumors grown as xenografts exhibited a spectrum of sensitivity to Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were found, as well as tumors that showed heterogeneity of response. Changes in apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was observed and correlated with inhibition of tumor growth. However, in a tumor that was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase 3 was negligible. This resistant tumor also expressed a high level of the anti-apoptotic molecule Bcl-XL that, in comparison, was not detected in a sensitive tumor. Importantly, in the majority of these tumors, addition of gemcitabine to Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used alone. Conclusion These data suggest that in a clinical setting we will see heterogeneity in the response of patients
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tumor, apoltrail, tumors, pancreatic, cancer, pubmed, article, google, scholar, combination, figure, cas, gemcitabine, mice, cells, treatment, growth, treated, patient, cell, apoptosis, resistant, scid, therapy, sensitivity, sensitive, original, effect, necrosis, lines, resistance, results, response, procaspase, patients, human, antitumor, bclxl, authors, glands, agents, control, xenografts, ligand, expression, significantly, factor, chemotherapy, model, adenocarcinoma,

Topics {✒️}

trail/apo-2l-mediated apoptosis tumour-necrosis factor superfamily trail-receptor-mediated apoptosis anti-apoptotic molecule bcl-xl tumor necrosis factor open access article patient-derived pancreatic adenocarcinomas peroxidase-conjugated secondary antibody trail-mediated cell death students unpaired t-test related subjects article download pdf apo-2 ligand bcl-xlwas differentially expressed patient-derived colon tumors scid mouse model trail-induced apoptosis anti-egfr antibody c225 tissue procurement facility apoptosis-controlling genes significant anti-tumor effect anti-tumor effect appears 500 μg/mouse- daily human pancreatic cancer mouse monoclonal antibody human pancreatic adenocarcinoma marked anti-tumor effect privacy choices/manage cookies molecule induces apoptosis apo2l/trail receptor expression patient pancreatic adenocarcinomas greater anti-tumor effect mol cancer ther pancreatic cancer reflects advanced pancreatic cancer apoptosis-regulating genes full size image cancer therapy based induced apoptosis pancreatic cell lines pancreatic carcinoma cells pancreatic cancer cells authors’ original file curr opin immunol human ovarian carcinomas anti-bcl-xl show uniform suppression nat rev cancer anti β-actin resistant pancreatic adenocarcinoma

Questions {❓}

Chu QD, Khushalani N, Javle MM, Douglass HOJ, Gibbs JF: Should adjuvant therapy remain the standard of care for patients with resected adenocarcinoma of the pancreas?

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         description:Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can validate and/or complement information obtained from cell lines and prove valuable in the design of future clinical trials. We have investigated the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated with Apo2L/TRAIL, gemcitabine or a combination of both therapies. Patient tumors grown as xenografts exhibited a spectrum of sensitivity to Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were found, as well as tumors that showed heterogeneity of response. Changes in apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was observed and correlated with inhibition of tumor growth. However, in a tumor that was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase 3 was negligible. This resistant tumor also expressed a high level of the anti-apoptotic molecule Bcl-XL that, in comparison, was not detected in a sensitive tumor. Importantly, in the majority of these tumors, addition of gemcitabine to Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used alone. These data suggest that in a clinical setting we will see heterogeneity in the response of patients' tumors to Apo2L/TRAIL, including tumors that are highly sensitive as well as those that are resistant. While much more work is needed to understand the molecular basis for this heterogeneity, it is very encouraging, that Apo2L/TRAIL in combination with gemcitabine increased therapeutic efficacy in almost every case and therefore may be a highly effective strategy for controlling human pancreatic cancer validating and expanding upon what has been reported for cell lines.
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      name:Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, USA
      name:Department of Immunology, Roswell Park Cancer Institute, Buffalo, USA

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