4 research outputs found
Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer
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
EFEK NEGATIF TERAPI REHABILITASI PADA MANTAN PENYALAH GUNA NAPZA DI PUSAT REHABILITASI YAYASAN AL-ISLAMI, PONDOK PESANTREN NURUL HAROMAEN, PONDOK REHABILITASI TETIRAH DZIKIR DAN RUMAH SAKIT JIWA GHRASIA
Background: The increase of drug abusers in Indonesia,
including Yogyakarta, has reached an alarming rate. The
implication, means of rehabilitation methods to treat
drug addiction emerge in Indonesia, and backed up by
medical or non-medical basis.
Aims: This study aims to determine the differences
between medical to non-medical approach for drug
abusers therapy in several drug addiction centers in
Special Province of Yogyakarta area.
Methods: This study uses cross-sectional method, with
samples taken from drug abusers whom currently undergo
rehabilitation therapy in Al-Islami Foundation
Rehabilitation Center, Nurul Haromaen Boarding House,
Tetirah Dzikir Rehabilitation Center and Ghrasia Mental
Hospital.
Results: The comparison between drug usage duration and
rehabilitation therapy duration (less than and more
than one year) does not show any statistical
significance. The same result found in the comparison
between the rehabilitation therapy using medical and
non-medical approach. It does not show any significant
difference statistically for kidney and liver value of
function.
Conclusion: Rehabilitation therapy using medical and
non-medical approach does not show any statistical
significance.
Keywords: rehabilitation therapy effect, drug abuser,
medical rehabilitation, non-medical rehabilitatio
Novel zebrafish patient-derived tumor xenograft methodology for evaluating efficacy of immune-stimulating bcg therapy in urinary bladder cancer
BACKGROUND: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. METHODS: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. RESULTS: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. CONCLUSIONS: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value
Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer
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