Prostate cancer biomarkers, the story

My name is Firas Al-Ubaidi, a consultant urological surgeon working as a part time clinician in my urologic clinic in Västerås and a part time researcher as a PhD student. In my daily clinic, I am dealing mostly with patients having different types of urological cancers, especially those having prostate cancer. At the Helleday Laboratory I work together with Niklas Schultz who is a senior researcher and a co-supervisor to this project.

Generally, the goal for treating non-metastatic prostate cancer is to cure the patient, and extend survival. Full dose radiotherapy in combination with hormonal therapy (castration) is standard treatment for localized or locally advanced prostate cancer.  However, the results are sometimes inadequate and like in all treatment modalities for prostate cancer, there is a risk of side effects, which tend to reduce the quality of life.

It is well known that is an additive effect between castration and radiotherapy, however the underlining mechanism is not fully understood. An understanding of what happens at the cellular and molecular level in prostate cancer cells, while reducing their access to androgens and then exposing them to ionizing radiation, would give us an opportunity to optimize the treatment and may also inspire novel therapeutic approaches.

The idea behind this project is to find out the underlining mechanism behind one of the most excellent way of treating an early stage prostate cancer.

We started the project in 2008 and in the first study we enrolled 20 patients with advanced prostate cancer who were treated with either surgical or pharmacological castration. Several biopsies were taken for different molecular analysis. In two published studies we were first to show that castration have a negative impact on the DNA repair pathways that are essential for the survival of cancer cells after radiotherapy. In the following study, we enrolled 50 patients with localized, non-metastasized prostate cancer who were candidates for curable measures and who were therefore treated with pharmacological castration in combination with radiotherapy. Like in the previous study, we took several biopsies from these patients before and after castration as well as radiotherapy for different molecular analysis which are still ongoing.

In the picture: Needle biopsy from the prostate of a patient with prostate cancer, Blue DNA, Red, Androgen receptor, Green KU70 (NHEJ repair protein)/ns

In the picture: Needle biopsy from the prostate of a patient with prostate cancer, Blue DNA, Red, Androgen receptor, Green KU70 (NHEJ repair protein)/ns

In the picture: Determination of Ku70 in prostate tumors

In the picture: Determination of Ku70 in prostate tumors. A, top left, an immunohistofluorescence-stained section of a prostate biopsy before castration. The 3 squares outlined in the middle of the image mark the area chosen for intensity measurement. Ku70 is stained with a mouse-monoclonal antibody (green) and the DNA is costained with TO-PRO-3 (blue). Top right, a corresponding area from an adjacent section stained with hematoxylin and eosin. The 3 panels below are close-ups of the 3 areas depicted for intensity measurements. B, as in A, but the biopsy is taken after castration, but from the same patient.

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