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- Ali, Zaheer, et al.
(författare)
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Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer
- 2022
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BMC. - 1756-9966. ; 41:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days. Methods Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients. Results The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days. Conclusions We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.
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| 2. |
- Ujan, Zaheer Ahmed, et al.
(författare)
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The Crystal Disorder into ZnO with Addition of Bromine and Its Outperform Role in the Photodegradation of Methylene Blue
- 2022
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Ingår i: Journal of cluster science. - : SPRINGER/PLENUM PUBLISHERS. - 1040-7278 .- 1572-8862. ; 33:1, s. 281-291
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Tidskriftsartikel (refereegranskat)abstract
- In this research work, bromine (Br) is successfully doped into ZnO nanostructures using solvothermal method. The morphology, crystalline features, and composition of Br doped ZnO nanostructures were studied by scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X ray spectroscopy (EDX) respectively. These newly prepared nanostructured materials were tested as photocatalysts for the photodegradation of methylene blue (MB) in aqueous solution under UV light. The kinetic rate constants were observed in the order (20% Br/ZnO > 15% Br/ZnO > 10% Br/ZnO > 5% Br/ZnO >pristine ZnO), thus they are indicating that the increasing Br dopant level has linear effect on the photodegradation of MB. The photocatalytic degradation efficiency of 60% was achieved for the pristine ZnO during the irradiation of UV light for 5 h, however 20% Br doped ZnO nanostructures has shown enhanced degradation efficiency of 97.63% during the irradiation of UV light for short interval of time of 2.2 h. The 20% Br/ZnO describes the highest rate constant value of (24.13 x 10(-3) min(-1)), for time period of 2.2 h and this values is about 8 and 4 times higher than the pristine ZnO (3.72 x 10(-3) min(-1)) and 5% Br/ZnO (6.13 x 10(-3) min(-1)), respectively. The obtained results of 20% Br doped ZnO sample are superior or equal in performance than the recently reported works. The catalytic mechanism is also proposed and it indicates the role of electrons coming from the bromine ion might act as radical for the degradation of MB. The present approach is simpler, environment friendly, scalable and could be of great consideration for the diverse energy and environment related applications. Graphic
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