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Pia Vihinen

Publications and source records attributed to Pia Vihinen.

9 recordsLinked to original sources
PubMed2006

Association between high collagenase-3 expression levels and poor prognosis in patients with head and neck cancer.

BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) is a common cancer type. The ability for curative treatment with surgery and radiotherapy (RT) is usually highly dependent on tumor stage at the time of diagnosis. METHODS: The purpose of this study was to determine whether the expression of a cancer-specific proteinase, collagenase-3 (matrix metalloproteinase-13 [MMP-13]), is associated with survival parameters in patients with HNSCC. We studied MMP-13 expression in tumors of 81 patients with stage I-IV HNSCC treated with surgery alone or in combination with radiotherapy. RESULTS: We found a subgroup of patients with high MMP-13 expression level in their tumors (>/=90% MMP-13-positive tumor cells) associated with unfavorable prognosis (median overall survival [OS], 11.8 vs 19.6 months, p = .032). In addition, the median disease-specific survival (DSS) time was markedly reduced in this subgroup (13.8 months vs 40.7 months, p = .062). When the subgroup of patients treated with a curative intent was studied, the same association was found in OS (13.8 vs 24.6 months, p = .023) and DSS (p = .004). In addition, there was a trend for association between >/=90% MMP-13 positivity and a recurrent tumor (p = .078) in curatively treated patients. CONCLUSIONS: The short survival time associated with high MMP-13 expression levels could not be predicted by tumor size or local lymph node invasion. These results show that a high MMP-13 expression level is associated with aggressiveness of HNSCC and may have prognostic value in patient evaluation.

Aged↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

High serum levels of matrix metalloproteinase-9 and matrix metalloproteinase-1 are associated with rapid progression in patients with metastatic melanoma.

PURPOSE: Matrix metalloproteinases (MMP) are proteolytic enzymes that play an important role in various aspects of cancer progression. In the present work, we have studied the prognostic significance of serum levels of gelatinase B (MMP-9), collagenase-1 (MMP-1), and collagenase-3 (MMP-13) in patients with advanced melanoma. EXPERIMENTAL DESIGN: Total pretreatment serum levels of MMP-9 in 71 patients and MMP-1 and MMP-13 in 48 patients were determined by an assay system based on ELISA. Total MMP levels were also assessed in eight healthy controls. The active and latent forms of MMPs were defined by using Western blot analysis and gelatin zymography. RESULTS: Patients with high serum levels of MMP-9 (> or = 376.6 ng/mL; n = 19) had significantly poorer overall survival (OS) than patients with lower serum MMP-9 levels (n = 52; median OS, 29.1 versus 45.2 months; P = 0.033). High MMP-9 levels were also associated with visceral or bone metastasis (P = 0.027), elevated serum alkaline phosphatase level (P = 0.0009), and presence of liver metastases (P = 0.032). Serum levels of MMP-1 and MMP-13 did not correlate with OS. MMP-1 and MMP-9 were found mainly in latent forms in serum, whereas the majority of MMP-13 in serum was active (48 kDa) form. MMP-13 was found more often in active form in patients (mean, 99% of the total MMP-13 level) than in controls (mean, 84% of the total MMP-13 level; P < 0.0001). After initiating the therapy, patients with elevated levels of MMP-1 (> or = 29.8 ng/mL, n = 10) progressed more rapidly than patients with lower levels (median, 1.9 versus 3.5 months; P = 0.023). Serum levels of MMP-9 and MMP-13 did not correlate with the time to progression (TTP). In multivariate analysis with age and gender, MMP-9 or MMP-1 turned out to be independent prognostic factors for OS [P = 0.039; hazard ratio (HR), 1.8; 95% confidence interval (95% CI), 1.03-3.3] or TTP (P = 0.023; HR, 2.7; 95% CI, 1.15-6.4), respectively. CONCLUSIONS: Our findings provide evidence that MMP-1, MMP-9, and MMP-13 play important roles at different phases of metastatic melanoma spread and that serum MMP-9, in particular, could have clinical value in identifying patients at high risk for melanoma progression.

Adult↗
PubMed2005

Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme.

BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent with demonstrated efficacy as therapy for glioblastoma multiforme (GBM) and anaplastic astrocytoma. TMZ has widely replaced the procarbazine, lomustine plus vincristine (PCV) combination for the treatment of malignant brain tumours as a result of its oral administration and favourable toxicity profile. OBJECTIVES: This study had three related aims. First, the cost effectiveness of TMZ (from the Finnish healthcare payer perspective) was compared with PCV in patients with GBM that had relapsed after primary treatment with surgery and radiotherapy. Second, the probability that TMZ is cost effective, compared with PCV, was estimated at different societal willingness-to-pay levels. Third, the value of new information for reducing the uncertainty related to the choice of treatment between TMZ and PCV was evaluated. METHODS: The cost effectiveness of TMZ and PCV was evaluated using a decision-modelling approach. Incremental cost-effectiveness ratios (ICERs) for cost per gained life-month, progression-free life-month and QALY were calculated. Various information sources were used to acquire parameter values for the model. The efficacy information of both treatments was derived from the medical literature, quality-of-life (QOL) estimates were gathered from Finnish neuro-oncologists using visual analogue scale methods, and data on the use of healthcare resources were collected from hospital databases. The exact prices for resource use were gained from the list of Finnish health service unit costs (year 2001 prices). The model was analysed using second-order Monte Carlo simulation. The value of new information on reducing uncertainty was analysed using the expected value of perfect information (EVPI) approach. RESULTS: According to the derived ICERs, 1 extra life-month gained with TMZ costs euro2367, 1 extra progression-free life-month costs euro2165, and 1 extra QALY costs euro32 471, compared with PCV, in the treatment of GBM. The probability of TMZ being the most cost-effective choice of treatment was >60% for all levels of willingness to pay >euro5000 per gained life-month. The respective probabilities were >75% for all levels of willingness to pay >euro10 000 per gained progression-free life-month and about 85% for all levels of willingness to pay >euro20 000 per gained quality-adjusted life-month. According to EVPI analysis, future research would potentially be cost effective if the costs of research were euro4.1 million (maximum). CONCLUSIONS: On the basis of this Finnish analysis, TMZ has a high probability of being more cost effective than PCV for patients with GBM. The addition of QOL aspects to the prolonging of survival increases the probability further.

Antineoplastic Agents, Alkylating↗
PubMed2005

Matrix metalloproteinases as therapeutic targets in cancer.

Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumor tissue or serum of patients with advanced cancer, and their role as prognostic indicators in cancer has been widely examined. In addition, therapeutic intervention in tumor growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors (MMPIs) are in clinical cancer trials. Even though results of the first clinical trials in advanced cancer have been mostly disappointing, there are also positive results. Recent observations show, that certain MMPs limit tumor growth. Therefore, identification of proper MMPs for therapeutic intervention with array-based molecular classifications of tumors and targeting these with more specific MMPIs in combination with conventional chemotherapy is expected to provide a feasible approach for cancer therapy. MMPIs represent a totally different therapeutic modality from proven anti-cancer drugs and thus traditional approaches to evaluate drug efficiency cannot be used without modification. In this review, we discuss the current view on the feasibility of MMPs as targets for therapeutic intervention in cancer.

Animals↗
PubMed2004

Integrin chains beta1 and alphav as prognostic factors in human metastatic melanoma.

The expression pattern of integrin-type cell adhesion receptors is often changed during malignant transformation. In the present work, we studied the prognostic significance of beta1 and alphav integrin chains for survival of patients with metastatic melanoma. The expression levels of beta1 integrin were also compared with those of Bcl-2, an anti-apoptotic protein, the presence of which is associated with treatment response and survival in melanoma. The expression of beta1 and alphav integrins in 68 melanoma metastases obtained from 55 patients treated with combined chemoimmunotherapy was studied by immunohistochemistry using anti-beta1 and anti-alphav antibodies. The patients were divided into two groups (using a cut-off point of >/= 81%) for beta1 integrin expression levels and into three categories (negative/low, median, high) for alphav integrin expression levels. All tumours were positive for beta1 integrin, and the tumours (n = 6) which had the highest alphav score were also strongly positive for beta1 (94%; P = 0.0055). Patients (n = 43) with 80% or less beta1 integrin-positive tumour cells in their samples had a median disease-free survival (DFS) of 17.0 months, and patients (n = 12) with 81% or more beta1 integrin-positive tumour cells had a DFS of only 5.7 months (P = 0.0001). Patients (n = 32) with low alphav integrin expression levels had shorter DFS (median 12.3 months; P = 0.0146) than patients (n = 20) with median expression levels (median 16.7 months; P = 0.0146). However, three patients who had a very strong alphav expression in their tumours had a median DFS of only 1.8 months (P = 0.0146). Median level expression of beta1 integrin was associated with the presence of Bcl-2 in tumour cells (P = 0.0033). Our results suggest that beta1 and alphav integrin chains are independently expressed in metastatic melanoma and may have an effect on the metastatic potential of melanoma cells.

Adult↗
PubMed2002

Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets.

Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer.

Biomarkers, Tumor↗
PubMed2002

High expression levels of collagenase-1 and stromelysin-1 correlate with shorter disease-free survival in human metastatic melanoma.

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. We studied the expression of collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and collagenase-3 (MMP-13) in 70 melanoma metastases obtained from 56 patients treated with combined chemoimmunotherapy. The patients were divided into 2 groups using a cut-off point of 0% for MMP-1 expression and 20% for MMP-3 expression. We found that patients with MMP-1 positive metastases (n = 38) had significantly shorter disease-free survival compared to patients with MMP-1 negative metastases (n = 18) (median 11.2 vs. 17.0 months, p = 0.0383). The disease-free survival of patients with high levels of MMP-3 expression in their metastases (> or = 20% positive tumor cells, n = 14) was also significantly shorter compared to patients with lower levels of expression (n = 42) (median 5.1 vs. 14.0 months, p = 0.0294). The expression of MMP-13 did not correlate to survival parameters. We also found that the presence of melanin, a pigment produced by melanocytes, correlated with high expression levels of MMP-1 (p = 0.0002), MMP-3 (p < 0.0001) and MMP-13 (p = 0.0009). The high expression levels of MMP-13 were also associated with the presence of visceral metastases (p = 0.0284). Our findings suggest that MMP-1 and -3 may have a special role in melanoma metastasis formation and thus they could be used to measure the biological activity of the disease.

Adult↗