Managing hemolysis in serum neuron-specific enolase measurements - an automated algorithm for routine practice.

Neuron-specific enolase (NSE) derived from neurons and peripheral neuroendocrine cells is a biomarker for neuroendocrine tumors and for prognostication in comatose cardiac arrest survivors. However, as platelets and erythrocytes contain NSE, hemolysis causes falsely elevated NSE. We used native serum and hemolysate derived from the same patients to make serial dilutions, and subsequently measured NSE (mNSE) and hemolytic index (HI) in each dilution.

Thyroid hypofunction in aging testicular cancer survivors.

Purpose: Thyroid hypofunction is a late effect observed in several groups of cancer survivors, but has to date not been evaluated indepth in testicular cancer survivors (TCSs). We investigated the prevalence of thyroid hypofunction in long-term TCSs and compared the findings with those of a comparison group from the general population.

Patients And Methods: Norwegian TCSs diagnosed with unilateral testicular cancer in the period 1980-1994 ( = 1,436) were grouped according to their cancer treatment (Surgery only; Radiotherapy only; Cisplatin-based chemotherapy, eventually combined with radiotherapy).

Longitudinal kidney function outcome in aging testicular cancer survivors.

Testicular cancer survivors (TCSs) have increased risk of reduced kidney function related to treatment burden, but longitudinal studies of renal outcome in aging TCSs have been lacking. This longitudinal study describes age- and treatment-related kidney function changes in TCSs compared to a comparison group from the general population. Estimated glomerular filtration rate (eGFR) was determined in blood samples from Norwegian TCSs (diagnosed 1980-1994) and surveyed median 11, 19 and 26 years since diagnosis (Survey1 [ = 1273], 2 [ = 849] and 3 [ = 670]) defining four treatment groups; Surgery only, Radiotherapy (RT) only, Cisplatin-based chemotherapy (CBCT) ≤850 mg and High CBCT/RT >850 mg cisplatin or any combination of CBCT with RT.

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

Background: Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay.

Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition.

Background: The tumor response to preoperative radiotherapy of locally advanced rectal cancer varies greatly, warranting the use of experimental models to assay the efficacy of molecular targeting agents in rectal cancer radiosensitization. Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby remodeling of chromatin structure, may override cell cycle checkpoint responses to DNA damage and amplify radiation-induced tumor cell death.

Methods: Human colorectal carcinoma cell lines were exposed to ionizing radiation and HDAC inhibitors, and cell cycle profiles and regulatory factors, as well as clonogenicity, were analyzed.

DNA damage responses in cell cycle G2 phase and mitosis--tracking and targeting.

Background: In order to determine temporal responses of cell cycle populations to DNA damage, a rational combination of cell cycle analyses is critical. Moreover, the targeting of cell cycle checkpoint responses may modify the cytotoxic effect of DNA damage.

Materials And Methods: The characteristics of cell cycle populations (DNA content, cell cycle transitioning of S phase cells and size of mitotic cell fraction within the total G2/M phase population) in HeLa cells exposed to ionizing radiation were analyzed using three individual flow cytometry-based assays.

Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death.

In breast cancer, radiation has a central role in the treatment of brain metastasis, although tumor sensitivity might be limited. The tumor cell defense response to ionizing radiation involves activation of cell cycle checkpoint signaling. Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby aberrations in the chromatin structure, may also override the DNA damage defense response and facilitate the radiation-induced mitotic cell death.

Inhibitory targeting of checkpoint kinase signaling overrides radiation-induced cell cycle gene regulation: a therapeutic strategy in tumor cell radiosensitization?

Background And Purpose: The tumor cell defense response to ionizing radiation involves a temporary arrest at the cell cycle G(2) checkpoint, which is activated by a signaling cascade initiated by the ATM kinase response to DNA damage, ultimately leading to the outcome of further cell survival if the DNA is properly repaired. The inhibitory targeting of the checkpoint kinase signaling elicited by ATM may define a biologically based strategy to override the G(2) phase delay that prevents mitotic entry after DNA damage, thereby increasing the probability of mitotic cell death following exposure to ionizing radiation.

Materials And Methods: Breast carcinoma cell lines with intact or defective function of the tumor-suppressor protein BRCA1 were exposed to ionizing radiation in the absence or presence of a specific inhibitor (UCN-01) of the checkpoint kinase CHK1, and the response profiles of cell cycle distribution and G(2) phase regulatory factors, as well as the efficiency of clonogenic regrowth, were analyzed.

Repression of mRNA for the PLK cell cycle gene after DNA damage requires BRCA1.

DNA damage activates the G2 cell cycle checkpoint to allow time for DNA repair before mitotic entry. The mechanism involves inhibition of the enzymatic activity for polo-like kinase 1 (Plk1), rendering Cdc25C with a basal phosphatase activity that is insufficient for converting Cdc2 to the fully active G2/M transition kinase. We found that cell cycle arrest at the G2/M boundary after ionizing radiation (IR) of breast carcinoma cells may involve repression of the gene for Plk1, PLK, mediated by the tumor-suppressor protein BRCA1.