Oncology reports
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The aim of the present study was to determine whether the cAMP response element binding protein (CREB) contributes to neuropathic pain during development stage. Adult (7-8 weeks old) male C57BL/6 mice weighing 20-25 g were used. Intrathecal catheter implantation and chronic constriction of the sciatic nerve of the animals were performed. ⋯ The increase of NR1 and NR2B subunits of the NMDAR was significantly diminished by intrathecal administration of the CREB antisense oligonucleotide against CREB and pCREB. Additionally, nociceptive behavior induced by CCI was attenuated by intrathecal administration of the CREB antisense oligonucleotide during the period of injection, and the above effects of relieving pain lasted at least 12 days following the last injection. Our results suggested that central functional pCREB may contribute to the development of neuropathic pain and regulate the expression of the NR1 and NR2B subunits of the NMDAR in the process.
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Paclitaxel-containing treatment regimens are standard chemotherapy schemes for breast cancer patients. The use of oncolytic herpes simplex virus (oHSV) vectors has been shown to be a safe and effective therapeutic approach for different types of cancer. We hypothesized that paclitaxel in combination with an oHSV vector would present an enhanced killing effect when used against breast cancer cells. ⋯ Combination therapy resulted in no morbidity in vivo. Our data demonstrated that G47Δ and paclitaxel combination therapy had synergistic effects in the treatment of breast cancer. This combination therapy may be promising for breast cancer patients.
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Core binding factor (CBF) acute myeloid leukaemia (AML) represents 5-8% of all AMLs and has a relatively favourable prognosis. However, activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. To verify the incidence and prognostic value of c-KIT mutations in CBF AML, we retrospectively analysed bone marrow samples of 23 consecutive adult patients with de novo CBF AML [14 inv(16) and 9 t(8;21)] treated at a single institution from 2000 to 2011. ⋯ Our results confirm a better prognosis for CBF AML than all other AML categories, and for inv(16) than t(8;21) AML. However, no prognostic value for c-KIT mutational status was found in our series. The association between LDH levels and c-KIT mutation would indicate a more active proliferation for mutated CBF AML.
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Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-20% of breast cancer patients and is associated with an aggressive tumor and a poor prognosis. Currently, patients are selected for adjuvant HER2-targeted therapy based on HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). In this study, we assessed the clinical significance of tissue HER2 status determined by a quantitative immunoassay using ADVIA Centaur. ⋯ The quantitative Centaur assay defined a greater number of patients (100 patients, 26.4%) as HER2-positive than IHC/FISH (63 patients, 16.6%) (P<0.0001). No significant difference in IDFS (P=0.159) and OS (P=0.150) was observed among the four groups of patients. However, in the IHC/FISH-positive group without adjuvant HER2-targeted therapy (group 2), a significantly greater number of events was found compared to the Centaur-positive group without adjuvant HER2-targeted therapy (group 3) for both IDFS (P=0.025) and OS (P=0.020). Quantitative HER2 determination by Centaur did not define a new group of patients eligible for HER2-targeted therapy. Currently, tissue HER2 status defined by IHC/FISH analysis remains the gold standard.
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The urokinase plasminogen activator system, which consists of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), plays an important role in tumor invasion and metastasis, and it may be a potential diagnostic biomarker and therapeutic target in cancer. It has been found that the expression of uPA and PAI-1 in ovarian cancer is related to clinical pathologies, while their effects on the biological behavior of tumor cells and their clinical significance are still unknown. In this study, 100 tissue samples (60 samples from malignant tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49 samples each from patients with malignant tumors, benign tumors and control group, respectively) were analyzed. The positive expression levels of uPA and PAI-1 in the malignant tumor samples and their serum concentrations in the malignant group were all significantly higher than these levels in the benign tumors and controls. ⋯ The Cox model analysis showed that expression of uPA at the transcription level had significant associations with prognosis. In addition, uPA greatly enhanced the abilities of cell invasion, migration and adhesion through its overexpression in SKOV3 cells. Collectively, our results showed that uPA and PAI-1 play important roles in ovarian cancer development; therefore, their expression in tissues and their concentrations in serum would greatly assist the diagnosis and prediction of the prognosis in ovarian cancer.