Dessa 2 forskare som 2018 skapade uppmärksamhet genom att utropa “We believe we’ve found the Holy Grail”. Från mitt inlägg klistrar jag in den text man då kommunicerade ut.
2018-05-14
- Associate Professor Derek Richard, at Queensland University of Technology in Australia, has, with help from HoloMonitor M4, found a way to turn back time and make old cells young again.
Watch the video and learn why “this could change the way we live and when we die” and how the research could change the way we treat heart disease, cholesterol, Arthritis, Alzheimer’s, and cancer and even replace chemotherapy when treating cancer (Seven News Australia, 2018).
Men till forskningsrapporten som publiceras idag (2 tim sen) på förstasidan hos ansedda Nature.Japp återigen en studie HoloMonitor varit inblandad i som får äran att omnämnas i denna högst rankade vetenskapliga publikation.
Latest Research
Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer
Abstract
Non-small cell lung cancers (NSCLC) account for 85–90% of all lung cancers. As drug resistance critically impairs chemotherapy effectiveness, there is great need to identify new therapeutic targets. The aims of this study were to investigate the prognostic and therapeutic potential of the copper-metabolism-domain-protein, COMMD4, in NSCLC.
Background
Lung cancer is the most commonly diagnosed cancer worldwide and additionally the most common cause of death from cancer.1,2,3
In 2018, there were ~2.1 million new lung cancer cases diagnosed and
1.8 million deaths worldwide resulting from lung cancer, accounting for
11.6% of the total cancer burden.4
Non-small cell lung cancers (NSCLC) account for 85–90% of lung cancers and can be further classified into adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinomas (LCC) which account for ~40%, 30% and 10%, respectively, of all lung cancers.5,6
At present, surgery is the best option for patients with stage I–II NSCLC, with the 5-year survival rate reaching 80–90% for stage IA and 73%, 65% and 56% for stage IB, IIA and IIB, respectively.7 Nevertheless, most NSCLC cases present at advanced stage IIIB or IV, which is incurable, and in some patients, relapse after surgery is observed. Although platinum-based chemotherapy remains commonly used for the majority of NSCLC patients,8 acquired resistance and relapse pose a significant challenge in the long-term treatment of NSCLC.9
For early-stage NSCLC patients who are not suitable for surgery, radiotherapy remains an important frontline treatment option10 and at present, there are several promising clinical trials combining radiotherapy with immune checkpoint inhibitors.11 Despite advances in immunotherapy and targeted therapies, the global 5-year survival rate for NSCLC remains low at 4–17%, depending on the stage and regional differences.3,7,12
Thus, the identification of novel therapeutic targets and cancer therapies are needed to improve patient outcome and the quality of life of NSCLC sufferers.
A family of copper metabolism gene MURR1 domain (COMMD) proteins, have shown promise as potential therapeutic targets in several cancers.13,14 COMMD proteins are a family of ten evolutionarily conserved proteins, characterised by the presence of a highly conserved carboxy-terminal COMM domain.
COMMD proteins regulate many biological processes including copper homoeostasis, activity of the NF-κB transcription factor, cell proliferation and protein trafficking.15,16
Interestingly, NF-κB has been implicated in the survival of cancer cells and activated NF-κB has been implicated in cisplatin resistance.17 COMMD1 expression has been shown to be downregulated in several cancers, with lower expression associated with a more invasive tumour phenotype. COMMD1 inhibits tumour invasion by disrupting the dimerisation of the hypoxia-inducible factor, HIF-1α/β, a transcription factor that regulates oxygen homoeostasis.13
Interestingly, CIGB-552, an anti-tumour peptide, was shown to increase COMMD1 expression levels in cells, induce apoptosis and inhibit the growth of human lung cancer cells.14
Knockdown of COMMD7 was shown to suppress cell proliferation, migration and invasion and led to apoptosis in hepatocellular carcinoma stem cell models, suggesting COMMD7 as therapeutic target in hepatocellular carcinoma,18 while COMMD10 was shown to possibly function as a tumour suppressor in clear cell renal carcinoma.19
Interestingly, COMMD9 expression was shown to be upregulated in NSCLC cells and tissues and siRNA-mediated silencing of COMMD9 resulted in the inhibition of cell migration and proliferation, arrested cells at the G1/S phase of the cell cycle and induced autophagy of the NSCLC cells.
The authors additionally demonstrated that COMMD9 attenuated p53 signalling and through its interaction with TFDP1, COMMD9 promoted TFDP1/E2F1 activation in NSCLC.20
Here, we have investigated the role of COMMD4 in NSCLC. COMMD4 has been shown to control NF-κB activity21 and regulate the activity of cullin-RING E3 ubiquitin ligases.22
We demonstrate that COMMD4 expression is upregulated in NSCLC and high COMMD4 expression is prognostic for ADC patient outcome. We further show that siRNA-mediated depletion of COMMD4 markedly reduces cell proliferation and viability after exposure to double-strand DNA breaks induced by ionising radiation and camptothecin. COMMD4 depletion ultimately leads to apoptosis induced by mitotic catastrophe in NSCLC cells, suggesting COMMD4 as a promising therapeutic target in NSCLC.
Som vanligt klistrar jag enbart in HoloMonitor-relevant info.
Methods
Four regions per well were imaged every 1 h over a period of 96 h using the HoloMonitorM4 (Phase Holographic Imaging).
The captured images were analysed using HStudio software (Phase Holographic Imaging).
We additionally analysed cell proliferation using the HoloMonitorM4
holographic imaging microscope. Similar to our observations using the
Incucyte S3, we noticed substantial retardation in cell growth in the
NSCLC cells representing each subtype, after depletion of COMMD4 with
siRNA #2 and #3 and observed no significant reduction in cell growth in
the HBEC3-KT control cell line depleted of COMMD4 (Fig. 3f–i).
Min kommentar
Att som forskare få sina studier publicerade i Nature är naturligtvis höjden av ära.
Nu får våra Australienska vänner internationell uppmärksamhet genom denna artikel.Det är de värda mtp den forskning som ligger bakom dessa nya insikter,och förhoppningsvis till glädje (snart) för lungcancerdrabbade världen över.Naturligtvis spiller lite av äran ut över de instrument som bidragit till att komma fram till resultaten.
Att HoloMonitor återigen figurerar i dessa högst komplexa studier visar på instrumentets kvaliteter.
Det är ju förvisso ingen nyhet för oss phi,are som följt HoloMonitors framfart i de publikationer vi tagit del av.
Nu får även omvärlden ånyo se hur bra instrumentet är.Kanske denna studie tar ner den eventuella skepsis forskarna haft tidigare? Och kollar i sina egna försäljningskanaler om det går att inhandla.
Vilket det troligtvis inte gör,men förhoppningsvis skapar det ett tryck hos bjässarna som idag dominerar/äger införsäljningen av instrument till forskningsmiljön.
Detta är studie nr 153 där HoloMonitor ingår. (bloggen leder med 2 😎,se fg inlägg)
Tillägg.
Värt att veta: Detta är 4e gången bara i år HoloMonitor figurerar i en studie publicerad i någon av Natures editioner.Sammanlagt återfinns HoloMonitor i 20 studier hos detta ansedda organ.
Mvh the99
Non-small cell lung cancers (NSCLC) account for 85–90% of lung cancers and can be further classified into adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinomas (LCC) which account for ~40%, 30% and 10%, respectively, of all lung cancers.5,6
At present, surgery is the best option for patients with stage I–II NSCLC, with the 5-year survival rate reaching 80–90% for stage IA and 73%, 65% and 56% for stage IB, IIA and IIB, respectively.7 Nevertheless, most NSCLC cases present at advanced stage IIIB or IV, which is incurable, and in some patients, relapse after surgery is observed. Although platinum-based chemotherapy remains commonly used for the majority of NSCLC patients,8 acquired resistance and relapse pose a significant challenge in the long-term treatment of NSCLC.9
For early-stage NSCLC patients who are not suitable for surgery, radiotherapy remains an important frontline treatment option10 and at present, there are several promising clinical trials combining radiotherapy with immune checkpoint inhibitors.11 Despite advances in immunotherapy and targeted therapies, the global 5-year survival rate for NSCLC remains low at 4–17%, depending on the stage and regional differences.3,7,12
Thus, the identification of novel therapeutic targets and cancer therapies are needed to improve patient outcome and the quality of life of NSCLC sufferers.
A family of copper metabolism gene MURR1 domain (COMMD) proteins, have shown promise as potential therapeutic targets in several cancers.13,14 COMMD proteins are a family of ten evolutionarily conserved proteins, characterised by the presence of a highly conserved carboxy-terminal COMM domain.
COMMD proteins regulate many biological processes including copper homoeostasis, activity of the NF-κB transcription factor, cell proliferation and protein trafficking.15,16
Interestingly, NF-κB has been implicated in the survival of cancer cells and activated NF-κB has been implicated in cisplatin resistance.17 COMMD1 expression has been shown to be downregulated in several cancers, with lower expression associated with a more invasive tumour phenotype. COMMD1 inhibits tumour invasion by disrupting the dimerisation of the hypoxia-inducible factor, HIF-1α/β, a transcription factor that regulates oxygen homoeostasis.13
Interestingly, CIGB-552, an anti-tumour peptide, was shown to increase COMMD1 expression levels in cells, induce apoptosis and inhibit the growth of human lung cancer cells.14
Knockdown of COMMD7 was shown to suppress cell proliferation, migration and invasion and led to apoptosis in hepatocellular carcinoma stem cell models, suggesting COMMD7 as therapeutic target in hepatocellular carcinoma,18 while COMMD10 was shown to possibly function as a tumour suppressor in clear cell renal carcinoma.19
Interestingly, COMMD9 expression was shown to be upregulated in NSCLC cells and tissues and siRNA-mediated silencing of COMMD9 resulted in the inhibition of cell migration and proliferation, arrested cells at the G1/S phase of the cell cycle and induced autophagy of the NSCLC cells.
The authors additionally demonstrated that COMMD9 attenuated p53 signalling and through its interaction with TFDP1, COMMD9 promoted TFDP1/E2F1 activation in NSCLC.20
Here, we have investigated the role of COMMD4 in NSCLC. COMMD4 has been shown to control NF-κB activity21 and regulate the activity of cullin-RING E3 ubiquitin ligases.22
We demonstrate that COMMD4 expression is upregulated in NSCLC and high COMMD4 expression is prognostic for ADC patient outcome. We further show that siRNA-mediated depletion of COMMD4 markedly reduces cell proliferation and viability after exposure to double-strand DNA breaks induced by ionising radiation and camptothecin. COMMD4 depletion ultimately leads to apoptosis induced by mitotic catastrophe in NSCLC cells, suggesting COMMD4 as a promising therapeutic target in NSCLC.
Som vanligt klistrar jag enbart in HoloMonitor-relevant info.
Methods
Cell proliferation and apoptosis using digital holographic imaging
For proliferation and apoptosis, 3 × 103 cells were seeded into lumox 96-well plates (Sarstedt).Four regions per well were imaged every 1 h over a period of 96 h using the HoloMonitorM4 (Phase Holographic Imaging).
The captured images were analysed using HStudio software (Phase Holographic Imaging).
 |
| a Immunoblot showing the depletion of COMMD4 using control siRNA or COMMD4 siRNA #2 or #3 across HBEC3-KT and three NSCLC cell lines. β-actin shows the loading. b–e Proliferation analysis of HBEC3-KT, H460, H1975 and CRL5889 cells depleted of COMMD4 with control or siRNA #2 or #3 and analysed using the Incucyte S3 live imaging system. f–i Proliferation analysis of HBEC3-KT, H460, H1975 and CRL5889 cells depleted of COMMD4 with control or siRNA #2 or #3 and analysed using the HoloMonitor M4 live imaging system. Asterix (*) denotes p < 0.05. n.s, not significant. Error bars represent mean ± SD from three independent experiments. |
Min kommentar
Att som forskare få sina studier publicerade i Nature är naturligtvis höjden av ära.
Nu får våra Australienska vänner internationell uppmärksamhet genom denna artikel.Det är de värda mtp den forskning som ligger bakom dessa nya insikter,och förhoppningsvis till glädje (snart) för lungcancerdrabbade världen över.Naturligtvis spiller lite av äran ut över de instrument som bidragit till att komma fram till resultaten.
Att HoloMonitor återigen figurerar i dessa högst komplexa studier visar på instrumentets kvaliteter.
Det är ju förvisso ingen nyhet för oss phi,are som följt HoloMonitors framfart i de publikationer vi tagit del av.
Nu får även omvärlden ånyo se hur bra instrumentet är.Kanske denna studie tar ner den eventuella skepsis forskarna haft tidigare? Och kollar i sina egna försäljningskanaler om det går att inhandla.
Vilket det troligtvis inte gör,men förhoppningsvis skapar det ett tryck hos bjässarna som idag dominerar/äger införsäljningen av instrument till forskningsmiljön.
Detta är studie nr 153 där HoloMonitor ingår. (bloggen leder med 2 😎,se fg inlägg)
Tillägg.
Värt att veta: Detta är 4e gången bara i år HoloMonitor figurerar i en studie publicerad i någon av Natures editioner.Sammanlagt återfinns HoloMonitor i 20 studier hos detta ansedda organ.
Mvh the99
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