13 april 2011: ik ben kanker-actueel aan het herzien en kwam in mijn zoektocht naar meer over de urinetest met o.a. het eiwit McM5 voor slokdarmkanker op het volgende. De urinetest waarover in onderstaand artikel wordt gesproken blijkt ook gebruikt te kunnen worden voor het vaststellen van beginnende of een recidief van blaaskanker. Onderaan artikel hebben we een abstract geplaatst van een studie die deze urinetest onderzocht op betrouwbaarheid bij vaststellen van blaaskanker. Als u hier klikt kunt u een volledig studierapport lezen van deze urinetest (met nadruk op MCM5 eiwit) bij vaststellen van alvleesklierkanker

Nieuwe eenvoudige test op McM5, een eiwitachtig stofje in vocht van slokdarm, geeft hoop voor vroegtijdige ontdekking van slokdarmkanker en daarmee hoop op succesvolle behandeling.

Bron: Cancer Research UK 13 augustus 2004

Engelse Onderzoekers hebben gevonden dat de aanwezige hoeveelheid van het eiwit McM5 in vocht genomen van de slokdarm bepalend is voor het ontwikkelen van slokdarmkanker. Deze test wordt simpel uitgevoerd met een buisje dat wat vocht uit de slokdarmdarm haalt en is niet pijnlijk of belastend voor de patiënt. De onderzoekers zegen dat zij, op grond van een studie bij 40 slokdarmkankerpatiënten, hiermee voor 85% kunnen voorspellen of iemand slokdarmkanker ontwikkelt of niet. Slokdarmkanker wordt heel vaak pas ontdekt als het al te ver is doorgegroeid en vaak ook uitgezaaid. slecht 8% van de slokdarmkankerpatiënten overleeft de vijf jaars grens in Engeland, wat in Nederland niet veel anders zal zijn. Wanneer tijdig slokdarmkanker kan worden gediagnosteerd is echter de kans op overleven 80%. Althans dat beweeert Cancer Research UK in dit persbericht over deze studie. De studieresultaten zijn gepubliceerd in The British Journal of Cancer van 13 augustus 2004.

McM5 wordt in het Engels als volgt omschreven: The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation.

Hieronder het volledige persbericht van Cancer Research UK d.d. 13 augustus 2004:

New test gives hope for early diagnosis of oesophageal cancer

Release date: 3 August 2004

A NEW screening test for oesophageal (food pipe) cancer could dramatically improve survival from the disease, according to research published in the British Journal of Cancer*(1) this week.
Cancer Research UK funded scientists at University College London's Wolfson Institute for Biomedical Research used a protein in fluid taken from a person's oesophagus to diagnose cancer with unprecedented accuracy.
Oesophageal cancer is often difficult to diagnose in its early stages, partly because of its lack of distinct symptoms. The potential new test would be simple and inexpensive and holds promise for improving detection of the cancer. The team now plans to investigate the test's clinical viability through a large-scale trial.
There are over 7,000 cases of oesophageal cancer in the UK each year, making it the ninth most common cancer. Incidence of the disease has risen by 27 per cent in the last 15 years*(2).
The new test works by detecting levels of a protein called Mcm5 in fluid samples taken from the oesophagus using a narrow tube. Mcm5 is one of a family of proteins called minichromosome maintenance (MCM) proteins, which are already known to be good markers of the uncontrolled cell growth that is the hallmark of cancer. The team analysed samples from 40 patients at Addenbrooke's Hospital in Cambridge to assess whether the Mcm5 test could accurately detect cancer. Approximately half of the patients in the study had oesophageal cancer and half did not. The test was able to identify cases of disease, distinguishing between patients with and without oesophageal cancer with 85 per cent accuracy.

Dr Kai Stoeber, lead researcher on the project, says: "Our team has been studying MCM proteins for a number of years to find out how they might prove useful in diagnosing cancer. Cancer Research UK Senior Clinical Research Fellow Professor Gareth Williams, who heads the research group, adds: "As oesophageal cancer is particularly difficult to diagnose early, doctors and patients would benefit greatly from a simple test to detect the condition. "Research shows that early diagnosis is the single most important factor for improving survival prospects for patients with oesophageal cancer."
Fve-year survival from oesophageal cancer in the UK is currently around eight per cent. But where the disease is diagnosed early, surgery and chemotherapy can yield survival rates in excess of 80 per cent.

Dr Stephen Middleton, who led the clinical trial at Addenbrooke's Hospital, says: "Our pilot study has shown that the Mcm5 test has many advantages over the methods doctors currently use to detect oesophageal cancer. "Current tests rely on a pathologist or technician analysing cell changes through a microscope. But as the new test is chemical in nature it could be readily automated, making it suitable for screening large numbers of people for precancerous or cancerous changes in oesophageal cells." "The test would be much less invasive than the endoscopic tests currently used to regularly check the oesophageal lining of patients who have a high risk of developing cancer. This would make it safer and more convenient for patients. "If large-scale trials prove the test's effectiveness, it could enter use within five years."
Mcm5 plays a key role in cell division. In normal cells its levels are tightly regulated so that cells only divide when they are required to do so. Cancer develops when these controls break down, leading to very high levels of Mcm5 and uncontrolled cell division. Professor Williams adds: "Testing for high levels of Mcm5 could enable doctors to pick up cancer at an early stage, as it reflects a faulty cellular process that begins long before the tumour reaches an easily detectable size." Cancer Research UK holds the patent on the Mcm5 test, and the research team are currently seeking commercial partners to develop it further.
Cancer Research UK's Director of Policy and Communications Professor Robert Souhami says: "Low survival rates for oesophageal cancer are to a great extent a result of late diagnosis. Until we have a reliable, accurate and practical test to diagnose the disease at an early stage it will be difficult to improve survival prospects. "Professor Williams and his team are making a great contribution towards this goal using the Mcm5 protein. A large-scale trial will tell us if using the test is feasible and can save lives."

*1 British Journal of Cancer Volume 91 Issue 4
*2 Incidence statistic for Great Britain
 

Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts

Bron: BMC, klik hier voor volledige studierapport

BMC Cancer. 2010 Nov 24;10:646.

Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts.

Brems-Eskildsen AS, Zieger K, Toldbod H, Holcomb C, Higuchi R, Mansilla F, Munksgaard PP, Borre M, Ørntoft TF, Dyrskjøt L.

Department of Molecular Medicine, Aarhus University Hospital, Skejby, Denmark.

Abstract

BACKGROUND: Identification of urinary biomarkers for detection of bladder cancer recurrence would be beneficial to minimize the frequency of cystoscopy. Our objective was to determine the usability of urine content of mRNA in the detection and prediction of bladder cancer recurrence.

METHODS: We analyzed 123 prospectively cross-sectional collected urine samples from 117 patients with bladder cancer (12 incident cancers and 111 control visits). We used biopsies from cystoscopies as diagnostic criteria for recurrence, and followed the patients for a median time of 28.5 months (range 0-44 months). We measured the levels of hTERT, SENP1, PPP1CA, and MCM5 mRNA in urine by q-RT- PCR.

RESULTS: We found significant differences in urinary content of hTERT (p < 0.001), SENP1 (p < 0.001), MCM5 (p < 0.001), and PPP1CA (p < 0.001) transcripts, when comparing urine samples from patients with and without tumor present in the bladder. We obtained sensitivity and specificity values for hTERT: 63/73, SENP1: 56/78, MCM5: 63/66, and PPP1CA: 69/63, respectively. Including follow-up data resulted in sensitivity and specificity values for hTERT: 62/84, SENP1:53/84, MCM5: 61/73, and PPP1CA: 65/66. Interestingly, at non-tumor visits the urinary content of especially hTERT (p = 0.0001) and MCM5 (p = 0.02) were significantly associated with subsequent tumour recurrence. Combining the markers with cytology improved the detection. The best combination was hTERT and cytology with a sensitivity of 71% and a specificity of 86% after follow-up. Further prospective validation or registration studies needs to be carried out before clinical use.

CONCLUSIONS: We could use the urinary content of hTERT, SENP1, PPP1CA, and MCM5 to detect bladder cancer recurrence. All markers showed a higher sensitivity than cytology. The detection rate improved when including cytology results, but also the combination of hTERT and MCM5 increased the detection rate. Furthermore, hTERT and MCM5 levels predicted subsequent tumor recurrences.

PMID: 21106093 [PubMed - indexed for MEDLINE]PMCID: PMC3001447


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