Publications (53)120.78 Total impact
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Article: Prognostic value of bcl-2 expression among women with breast cancer in Libya.
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ABSTRACT: We studied the association of the immunohistochemical bcl-2 expression in Libyan breast cancer with clinicopathological variables and patient outcome. Histological samples from 170 previously untreated primary Libyan breast carcinoma patients were examined. In immunohistochemistry, the NCL-L-bcl-2-486 monoclonal antibody was used. Positive expression of bcl-2 was found in 106 patients (62.4 %). The bcl-2 expression was significantly associated with estrogen receptor (p < 0.0001) and progesterone receptor positive tumors (p = 0.002), small tumor size (p < 0.0001), low tumor grade (p < 0.0001), negative axillary lymph nodes (p < 0.0001), early stages (p = 0.001), and low risk of metastasis (p < 0.0001). Positive expression was also associated with older patients (>50 years; p = 0.04). Histological subtypes and family history of breast cancer did not have significant relationship with bcl-2. Patients with positive expression of bcl-2 had lower recurrence rate than bcl-2-negative patients and better survival after median follow-up of 47 months. Patients with high bcl-2 staining were associated with the best survival. The role of bcl-2 as an independent predictor of disease-specific survival was assessed in a multivariate survival (Cox) analysis, including age, hormonal status, recurrence, histological grade, and clinical stage variables. Bcl-2 (p < 0.0001) and clinical stage (p = 0.016) were independent predicators of disease-specific survival. For analysis of disease-free survival, the same variables were entered to the model and only bcl-2 proved to be an independent predictor (p = 0.002). Patients with positive expression of bcl-2 were associated with low grade of malignancy, with lower recurrence rate, with lower rate of death, and with longer survival time. Bcl-2 is an independent predictor of breast cancer outcome, and it provides useful prognostic information in Libyan breast cancer. Thus, it could be used with classical clinicopathological factors to improve patient selection for therapy.Tumor Biology 02/2013; · 1.94 Impact Factor -
Article: Loss of MUC2 expression predicts disease recurrence and poor outcome in colorectal carcinoma.
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ABSTRACT: Clinical staging and histological grading after surgery have been the "gold standard" for predicting prognosis and planning for adjuvant therapy of colorectal cancer (CRC). With the recent development of molecular markers, it has become possible to characterize tumors at the molecular level. This is important for stage II and III CRCs, in which clinicopathological features do not accurately predict heterogeneity, e.g., in their tumor response to adjuvant therapy. In the present study, archival samples from 141 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital (Finland) were used (as microarray blocks) to analyze MUC2 expression by immunohistochemistry. Altogether, 49.7 % of all tumors were positive for MUC2. There was no significant correlation between MUC2 expression and age (P < 0.499), tumor invasion (P < 0.127), tumor staging (P < 0.470), histological grade (P < 0.706), lymph node involvement (P < 0.854), or tumor metastasis (P < 0.586). However, loss of MUC2 expression was significantly associated with disease recurrence (P < 0.031), tumor localization (P < 0.048), and with borderline significance with gender (P < 0.085). In univariate (Kaplan-Meier) survival analysis, positive MUC2 significantly predicted longer disease-free survival (DFS) and disease-specific survival (DSS) as well. However, in multivariate (Cox) survival analysis, MUC2 lost its power as an independent predictor of DFS and DSS. Our results implicate the value of MUC2 expression in predicting disease recurrence and long-term survival in CRC.Tumor Biology 11/2012; · 1.94 Impact Factor -
Article: Diagnosis delay in Libyan female breast cancer.
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ABSTRACT: BACKGROUND: To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya METHODS: 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008--2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time) was categorized into 3 periods: <3 months, 3--6 months, and >6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay). Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire) during an interview with each patient and from medical records. RESULTS: The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3--6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer) was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s) that did not include a lump (p < 0.0001), with women who did not report monthly self examination (p < 0.0001), with old age (p = 0.004), with illiteracy (p = 0.009), with history of benign fibrocystic disease (p = 0.029) and with women who had used oral contraceptive pills longer than 5 years (p = 0.043). At the time of diagnosis, the clinical stage distribution was as follows: 9.0% stage I, 25.5% stage II, 54.0% stage III and 11.5% stage IV.Diagnosis delay was associated with bigger tumour size (p <0.0001), with positive lymph nodes (N2, N3; p < 0.0001), with high incidence of late clinical stages (p < 0.0001), and with metastatic disease (p < 0.0001). CONCLUSIONS: Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing detectable of tumors are necessary.BMC Research Notes 08/2012; 5(1):452. -
Article: Prognostic significance of DNA image cytometry in Libyan breast cancer.
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ABSTRACT: We evaluated the relation of nuclear DNA content and clinicopathological features and prognosis in primary breast cancer of female Libyan patients with variable stage and grade and different treatment regimes. Histological samples from 104 patients of breast carcinoma were retrospectively studied by computerized nuclear DNA cytometry. Isolated nuclei from paraffin sections were stained with Feulgen stain and DNA was measured using a computer-assisted image analysis cytometry system. In each case, 200 nuclei were measured and the DNA histograms, S phase fraction (SPF) and number of cells above 5c and 9c were determined. We applied different approaches in the analysis of DNA to compare the DNA histograms with different clinicopathological features and survival. The mean of DNA ploidy mode for all tumors was 3.43; 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF was 3.5% for DNA diploid and 13.5% for DNA aneuploid tumors. DNA aneuploid tumors and high SPF were associated with advanced stage, distant metastasis, high histological grade and lymph node involvement. The SPF was also associated with large tumor size and with younger patients (<50 years). In the overall population (median follow-up 51 months), patients with aneuploid DNA histograms and high SPF values had shorter survival times than those with diploid DNA histograms and low SPF values (p = 0.001, p < 0.0001, respectively). Also, short survival was associated with a multiploid DNA histogram and with DNA aneuploid cells ≥5 cells (p < 0.0001, p = 0.001, respectively). In a Cox multivariate analysis, DNA ploidy (p = 0.010), age (p = 0.038) and clinical stage (p = 0.001) were independent predictors of overall survival, and DNA ploidy (p = 0.018) and clinical stage (p = 0.001) also proved to be independent predictors of disease-specific survival. The SPF cutoff point of 11% might be applied to separate patients into good and poor prognosis groups. DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in Libyan breast cancer, with potential clinical implications in patient management, particularly in predicting the patients at high risk for metastasis and recurrence who should be considered as candidates for combined adjuvant therapy.Oncology 08/2012; 83(3):165-76. · 2.27 Impact Factor -
Article: Main effects and interactions of carbonic anhydrase IX, hypoxia-inducible factor-1α, ezrin and glucose transporter-1 in multivariate analysis for disease outcome in rectal cancer.
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ABSTRACT: Strong expression of carbonic anhydrase IX (CA IX), hypoxia-inducible factor-1α (HIF-1α), ezrin and glucose transporter-1 (GLUT-1) were previously shown to be interrelated and to affect clinicopathological prognostic factors. In the current study, operative samples from 178 rectal cancer patients, 77 treated with short-course, 47 with long-course preoperative radiotherapy (RT), and 54 with no preoperative treatment, as well as 80 preoperative biopsies from the RT group were analysed using multivariate modelling in order to assess the role of these markers as predictors of disease outcome. Multivariate survival analysis revealed several sets of panels with the potential ability to identify patients at increased or decreased risk of dying from their disease or disease recurrence. The most remarkable panel, consisting of moderate/strong expression of CA IX, positive HIF-1α expression and negative/weak GLUT-1 expression in operative samples and negative/weak ezrin expression in preoperative biopsies was associated with 47.5-fold risk of death from this disease. These results should, however, be interpreted with caution due to the heterogeneity of the patient population in this retrospective study.Anticancer research 08/2012; 32(8):3299-303. · 1.73 Impact Factor -
Article: Loss of E-cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma.
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ABSTRACT: The traditional staging system is currently inadequate for identifying those patients with colorectal carcinoma (CRC) who carry a high risk for poor outcome. In this study, the expression of E-cadherin was evaluated in CRC to determine its correlation with clinico-pathological variables, and association with disease outcome in patients with long-term follow-up. The present series consisted of tissue samples obtained from 230 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital. Archival paraffin-embedded samples were used to build up tissue microarray blocks, and E-cadherin expression was assessed by immunohistochemistry using an automated staining system. Different grading systems were tested for expression of E-cadherin. Fifty-nine percent of all tumors were positive for E-Cadherin. There was no significant correlation between E-cadherin expression and gender (p < 0.83), localization (p < 0.45), tumor invasion (p < 0.32), or histologic grade (p < 0.41). However, loss of E-cadherin expression was significantly associated with older age (p < 0.03) and lymph node involvement (p < 0.02), and with borderline significance with advanced stage (p < 0.09) and tumor metastasis (p < 0.09). In univariate (Kaplan-Meier) survival analysis, positive E-cadherin significantly (p = 0.009) predicted longer disease-free survival (DFS), and the same was true with disease-specific survival (DSS) as well (p = 0.007). In multivariate (Cox) survival analysis, E-cadherin retained its significance as independent predictor of DFS (HR = 1.56; 95% CI 1.01-2.42, p = 0.043), but not DSS. A sub-group analysis revealed that E-cadherin expression also predicts DFS (p < 0.01) and DSS (p < 0.04) in stage II CRC. Our results implicate the usefulness of E-cadherin expression in predicting disease recurrence and long-term survival in CRC.Apmis 07/2012; 120(7):539-48. · 1.99 Impact Factor -
Article: Previous pregnancy is a favourable prognostic factor in women with localised cutaneous melanoma.
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ABSTRACT: The influence of pregnancy on survival in melanoma has been a controversial issue. In this retrospective study we investigated whether pregnancy (overall or temporally melanoma-related) has any effect on melanoma progression or patient outcome. Patient data were collected from Turku University Hospital records concerning all women in fertile age (15-45 years) and diagnosed with melanoma between January 1, 1990 and December 31, 2009. We collected data on melanoma characteristics, treatment, pregnancies and patient outcomes. Of the 334 patients, 248 (74%) had been pregnant in some point during their life while 55 (17%) were nulliparous. The history of pregnancies could not be verified in 31 women (9%). Progression of melanoma to advanced stage was found in 58 (17%) of these women. Altogether, 35 women (14%) with at least one pregnancy had disease progression in contrast to 14 women (26%) with no pregnancies (p =0.049). Women with at least one pregnancy had a 94% probability to survive from melanoma compared to nulliparous women of whom only 83% survived (p =0.041). In Multivariate (COX) analysis pregnancy was a favourable factor for disease-specific survival (DSS) (HR 3.75; 95% CI 1.24-11.34; p =0.019) when adjusted for age (HR 1.064; 95% CI 1.00-1.13; p =0.50), localisation and stage (p =0.040), and Breslow (HR 1.32; 95% CI 1.10-1.58; p =0.002). However, when ulceration of the primary tumour was included in the multivariate model, Breslow remained as the only independent predictor of DSS (HR 1.58; 95% CI 1.34-1.86; p =0.0001) and pregnancy was dropped from the stepwise backward model in the step preceding the last one (p =0.081). Pregnancy is not a risk factor for disease recurrence or progression in melanoma patients, but instead can exert some favourable influence on prognosis.Acta oncologica (Stockholm, Sweden) 04/2012; 51(5):662-8. · 2.27 Impact Factor -
Article: Prognostic value of proliferation markers: immunohistochemical ki-67 expression and cytometric s-phase fraction of women with breast cancer in libya.
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ABSTRACT: Background: We evaluated the association of the immunohistochemical Ki-67 expression, and S-phase fraction with clinicopathological variables and patient outcome.Patients and methods: Histological samples from 100 primary Libyan breast carcinoma patients were retrospectively studied with monoclonal antibody to Ki-67. S-phase fraction was determined by DNA image cytometry.Results: The median Ki-67 percentage for all tumors was 27.5%, ranging from 1 to 80% and the median S-phase fraction (SPF) was 11%, ranging from 0 to 62 %. Tumors with high Ki-67 expression were found in 76% of patients and with high SPF values in 56%. Ki-67 expression was more frequent in tumors with high SPF than low SPF. High Ki-67 and high SPF were associated with advanced stages, poor differentiation of tumors, positive lymph nodes, and distant metastasis. The Ki-67 was associated with hormone receptor negative tumors. The SPF was higher in young patients (<50 years) than in older patients. In the overall population (median follow-up 49 months), patients with high Ki-67 and high SPF had shorter survival time and predicted recurrence than patients with low Ki-67 and low SPF. In a Cox multivariate analysis, high SPF (p= 0.007), hormonal status (p= 0.001) and clinical stage (p=0.005) were independent predictors of disease-specific survival. The Ki-67 (p=0.065) in borderline significance proved to be independent predictor of disease-free survival. The SPF showed more statistically significance with a high grade of malignancy and survival time than Ki-67.Conclusions: The SPF value is useful cell proliferation marker to assess tumor prognosis. These markers may reflect the aggressive behavior of Libyan breast cancer and predict of the recurrence. It is therefore important to take these markers into consideration to select a high risk subgroup of the patients for intensive treatment.Journal of Cancer. 01/2012; 3:421-31. -
Article: Melanoma-Associated Cancer-Testis Antigen 16 (CT16) Regulates the Expression of Apoptotic and Antiapoptotic Genes and Promotes Cell Survival.
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ABSTRACT: Cancer-testis (CT) antigens are predominantly expressed in testis or placenta, but absent in most adult tissues. During malignant transformation CT genes are often activated. CT antigen 16 (CT16, PAGE5) is frequently expressed in advanced melanoma but its biological function has been unknown. To examine the role of CT16 in cell survival we knocked it down in A2058 melanoma cells using specific siRNAs and exposed the cells to cancer drug cisplatin known to induce apoptosis. As a result, cell survival was markedly decreased. To study the effects of CT16 on cell survival in more detail, the cellular gene expression profiles were investigated after CT16 silencing in CT16 positive A2058 melanoma cells, as well as after CT16 overexpression in CT16 negative WM-266-4 melanoma cells. Among the 11 genes both upregulated by CT16 silencing and downregulated by CT16 overexpression or vice versa, 4 genes were potentially apoptotic or antiapoptotic genes. CT16 was recognized as a positive regulator of antiapoptotic metallothionein 2A and interleukin 8 genes, whereas it inhibited the expression of apoptosis inducing dickkopf 1 (DKK1) gene. In addition CT16 enhanced the expression of fatty acid binding protein 7, a known promoter of melanoma progression. The effect of CT16 on DKK1 expression was p53 independent. Furthermore, CT16 did not regulate apoptotic genes via DNA methylation. In twenty melanoma metastasis tissue samples average DKK1 mRNA level was shown to be significantly (p<0.05) lower in high CT16 expressing tumors (n = 3) when compared to the tumors with low CT16 expression (n = 17). Thus, our results indicate that CT16 promotes the survival of melanoma cells and is therefore a potential target for future drug development.PLoS ONE 01/2012; 7(9):e45382. · 4.09 Impact Factor -
Article: Carbonic anhydrase IX, hypoxia-inducible factor-1α, ezrin and glucose transporter-1 as predictors of disease outcome in rectal cancer: multivariate Cox survival models following data reduction by principal component analysis of the clinicopathological predictors.
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ABSTRACT: Strong expression of carbonic anhydrase IX (CAIX), hypoxia-inducible factor-1α (HIF-1α), ezrin and glucose transporter-1 (GLUT-1) was previously shown to be related to adverse disease outcome in rectal cancer. In this study, operative samples of 178 rectal cancer patients 77 treated with short-course and 47 with long-course preoperative radiotherapy (RT), and 54 with no preoperative treatment, as well as 80 preoperative biopsies from the RT group patients were analyzed for these markers. For data reduction, principal component analysis (PCA) was used to extract a set of factors from the original clinicopathological variables that would explain as much as possible of their variance. After extraction and promax rotation, this set of five first-order factors (F1-F5) was used in multivariate (Cox) modeling together with the four biomarkers. In model 1 (biomarkers in operative samples), F1 was the only independent determinant of disease-free (DFS) (p=0.043) and disease-specific survival (DSS) (p=0.029). In model 2 (biomarkers in preoperative biopsies), none of the five factors or biomarkers were significantly associated with DFS. However, HIF-1α (p=0.024), ezrin (p=0.034), F1 (p=0.011), and F3 (p=0.001) were significant independent predictors of DSS. Similarly, in model 3 (ezrin in preoperative biopsies and others in operative samples), none of the factors or biomarkers were significant predictors of DFS. However, CAIX (p=0.028), and F1 (p= 0.017) were significantly associated with DSS. Preoperative RT markedly modifies the expression of these four biomarkers and also interferes with the original clinicopathological prognosticators (loaded to F1-F5), emphasizing the complexity of prognostication in rectal cancer.Anticancer research 12/2011; 31(12):4529-35. · 1.73 Impact Factor -
Article: Circulating levels of VEGFR-1 and VEGFR-2 in patients with metastatic melanoma treated with chemoimmunotherapy alone or combined with bevacizumab.
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ABSTRACT: There are no identified biomarkers that could predict response to antiangiogenic or traditional chemoimmunotherapy in metastatic melanoma. We hypothesized that soluble angiogenic factor receptors might help us to identify patients responsive to treatment. A series of 48 patients with stage IV melanoma participating in two phase II clinical trials were included. The trials included treatment with carboplatin, vinorelbine, and subcutaneous interleukin-2 (n=22) or treatment with bevacizumab, dacarbazine, and low-dose interferon-α2a (n=26).Serum samples were prospectively collected and soluble vascular endothelial growth factor receptor 1 (s-VEGFR-1) and 2 (s-VEGFR-2) were measured before starting the trial treatment and during response evaluation.There was a trend toward longer overall survival among patients with higher-than-median serum VEGFR-1 levels (21.3 months) compared with 12.3 months in patients with low pretreatment s-VEGFR-1 levels (P=0.146). Pretreatment s-VEGFR-2 levels did not correlate to survival. Serum VEGFR-2 levels decreased during therapy in 44% of the patients and increased in 56% of the patients. VEGFR-2 increased in 78% (14 of 18) of the patients who progressed during therapy (P=0.017). VEGFR-2 decrease was associated with clinical benefit in 65% of the patients (11 of 17) and with progression in only four patients (P=0.016).High pretreatment levels of s-VEGFR-1 are associated with improved prognosis among patients with metastatic melanoma independently on therapy, whereas increased VEGFR-2 levels during therapy are associated with disease progression. These markers might be useful in selecting patients responsive to antiangiogenic therapy.Melanoma research 07/2011; 21(5):431-7. · 2.06 Impact Factor -
Article: NCT01110291: induction of CYP3A activity and lowered exposure to docetaxel in patients with primary breast cancer.
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ABSTRACT: To study the CYP3A activity before and after docetaxel administration. Furthermore, it was investigated whether peroral midazolam could predict docetaxel exposure and adverse events. Twenty patients with primary high risk breast cancer were given docetaxel as a 1-h infusion 80 mg/m(2) in a 21-day cycle in 3 cycles followed by 3 cycles of cyclophosphamide, epirubicin and fluorouracil. CYP3A activity was assessed a day before and a day after docetaxel by 7.5 mg oral midazolam. All patients were given peroral dexamethasone a total dose of 45 mg, of which 15 mg was given before docetaxel infusion and 30 mg before the latter assessment of CYP3A activity. All except one patient were given 11-19 mg of intravenous dexamethasone before docetaxel infusion. CYP3A activity was clearly induced when assessed a day after docetaxel administration as shown by lower midazolam AUC (P < 0.0001) and higher AUC ratio (1-OH-midazolam/midazolam, P = 0.018). The mean docetaxel AUC was about a half of that previously reported in the literature. Incidence of febrile neutropenia was smaller (15%) than reported in literature with comparable docetaxel doses and seemed to associate with slower metabolism. No correlation between pharmacokinetics of midazolam and docetaxel was found at baseline. We show here a markedly reduced docetaxel exposure followed by CYP3A induction by, most likely, dexamethasone. Peroral midazolam seemed not to predict docetaxel exposure. Slow CYP3A-mediated metabolism might predispose patients to adverse events of docetaxel.Cancer Chemotherapy and Pharmacology 06/2011; 67(6):1353-62. · 2.83 Impact Factor -
Article: Detection of melanoma-derived cancer-testis antigen CT16 in patient sera by a novel immunoassay.
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ABSTRACT: Cancer-testis antigens (CTAs) are expressed mainly in various cancer tissues and in testis or placenta. Because of their restricted expression pattern, the CTAs can be potentially used for vaccine development and diagnostic applications. CTA CT16 has been found to be expressed in lung and renal cancers as well as in melanomas. Detection of CT16 protein directly from patient serum could facilitate monitoring of tumor growth and response to therapy in CT16-positive patients. A highly sensitive time-resolved fluorescence-based immunoassay measuring CTA CT16 in serum was developed. Generally, CTAs have not been measured directly from body fluids. CT16 level was detectable in 14 of 23 (61%) patients with metastatic melanoma, whereas none of the nine healthy volunteers collected by us had measurable CT16 level. For an unknown reason, 1 of 20 commercial control serum samples gave a positive result. The Wilcoxon-Mann-Whitney exact test showed statistically significant difference when patients with metastatic melanoma were compared to our control group (p = 0.006) or to the commercial set (p < 0.001). Four melanoma patients had exceptionally high serum CT16 level. CT16 did not correlate either with S100B, a recognized marker of progressing melanoma, or with unspecific serum marker lactate dehydrogenase. Elevation of CT16 titers preceded or followed the clinical diagnosis of disease progression in four patients with metastatic melanoma. As a conclusion, our results show that CT16 protein can be measured directly from patient serum, and the developed assay has a potential for clinical use.International Journal of Cancer 05/2011; 128(10):2382-92. · 5.44 Impact Factor -
Article: Preoperative radiotherapy modulates ezrin expression and its value as a predictive marker in patients with rectal cancer.
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ABSTRACT: The purpose of this study was to assess the value of ezrin expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Operative samples from 176 rectal cancer patients and 76 diagnostic preoperative biopsies from the same cohort were analyzed for ezrin expression using immunohistochemistry. The patients had received short- (n = 76) or long-course radiotherapy with (n = 36) or without chemotherapy (n = 10) or no treatment preoperatively (n = 54). The direct effect of radiation on ezrin expression was studied in cultured cells by Western blot analysis. The biopsies and respective operative samples were significantly different (κ = -0.010 for 4-tier scoring and κ = 0.028 for dichotomized scoring) in their ezrin expression. Most preoperative biopsies (61/76, 80%) had negative/weak ezrin expression compared with 56% (43/76) of the corresponding operative samples. After preoperative treatment, negative expression in the biopsies of 18 (82%) of 22 patients turned positive, whereas positive expression in 6 (11%) of 54 biopsies turned negative in the operative samples. In univariate analysis, disease-free survival and disease-specific survival were significantly longer (P = .027 and P = .002) when ezrin expression in the preoperative biopsy was negative/weak compared with moderate/strong expression. Such prognostic association was lost in the radiated operative specimens. In multivariate regression model, ezrin was not a predictor of disease-free survival. No direct effect of radiation on ezrin expression was seen in vitro. In conclusion, radiotherapy increases ezrin expression in rectal cancer. In pretreatment biopsies, negative/weak ezrin expression correlates with favorable disease outcome, suggesting that ezrin expression modulates tumor aggressiveness and/or response to treatment.Human pathology 03/2011; 42(3):384-92. · 3.03 Impact Factor -
Article: The expression and distribution of group IIA phospholipase A2 in human colorectal tumours.
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ABSTRACT: Secretory phospholipase A2 group IIA (IIA PLA2) is a protein shown to be increased in various human malignancies. The expression profile of this protein, however, is controversial in colorectal carcinoma. The aim of this study was to examine the distribution and expression of IIA PLA2 protein in benign, premalignant and malignant colorectal tumours as well as in peritumoural mucosa. Seven hyperplastic polyps, 24 adenomas and 83 colorectal carcinomas were stained with immunohistochemistry (IHC) for IIA PLA2. Four hyperplastic polyps, 12 adenomas and nine carcinomas were also evaluated for the sites of IIA PLA2 expression using mRNA in situ hybridisation (ISH). There was no immunoreactivity for IIA PLA2 in hyperplastic polyps. A total of 79% of adenomas and 31% of carcinomas showed IIA PLA2-immunopositive tumour cells in IHC, and the expression was localised to epithelial cells with ISH. In carcinomas, IIA PLA2-immunopositive apoptotic cells and necrosis were also found. The epithelial cells in the peritumoural mucosa showed immunopositivity for IIA PLA2 in 96% of cases, with considerably stronger intensity adjacent to carcinoma than in the more distal mucosa. Moreover, IIA PLA2-immunopositive malignant epithelial cells were found in 44% of cases in the invasive front of carcinomas. Our results suggest that the IIA PLA2 protein content is dramatically decreased in malignant colorectal tumours as compared with adenomas. The protein is also found in the apoptotic cells, necrosis, peritumoural mucosa and in the invasive front of carcinomas.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2010; 457(6):659-67. · 2.49 Impact Factor -
Article: A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-alpha2a as first line treatment in metastatic melanoma.
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ABSTRACT: Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon alpha-2a (IFN-alpha2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m days 1-5 every 4 weeks) and IFN-alpha2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab+/-IFN-alpha2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23% (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed > or =3 months after the last bevacizumab-DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.Melanoma research 04/2010; 20(4):318-25. · 2.06 Impact Factor -
Article: [Are immunological treatments beneficial for malignant melanoma of the skin?].
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ABSTRACT: Treatment results of metastatic malignant melanoma of the skin have failed to exhibit significant improvement for 30 years. Owing to the poor efficiency of cytotoxic therapies, attention has focused on the patient's own immune system and its strengthening or "teaching" to counteract the melanoma tissue. The most significant forms of immunotherapy currently include the interferons, interleukin-2 and antibody therapy directed against a specific T-lymphocyte associated antigen (CTLA-4). So far, therapeutic vaccines for melanoma have not ended up into routine clinical use.Duodecim; lääketieteellinen aikakauskirja 01/2010; 126(14):1701-10. -
Article: MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients.
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ABSTRACT: Extracellular matrix degradation is required for invasion and metastasis formation in colorectal carcinoma (CRC), therefore, we have examined matrix metalloproteinases MMP-9 expression in tumors from patients with CRC. The study comprises of 360 patients who underwent bowel resection for stage II, III, IV tumors. Paraffin-embedded CRC tissue samples were used for immunohistochemical staining. Negative MMP-9 expression levels correlated with longer survival time as evaluated by disease-free survival and disease-specific survival (p =.023, p =.006). In multivariate survival (Cox) analysis, MMP9 was a significant independent predictor of DFS (p =.014), but not of DSS, which was independently predicted by disease recurrence, stage and localization. The detection of MMP-9 expression may be valuable in finding patients who are at high risk of developing disease recurrence.Cancer Investigation 01/2010; 28(1):38-43. · 1.85 Impact Factor -
Article: Prognostic significance of matrix metalloproteinase-9 (MMP-9) in stage II colorectal carcinoma.
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ABSTRACT: Approximately 30% of all colorectal cancer patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well-established that a subgroup of patients with stage II is at high risk for recurrence within their life time and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of matrix metalloproteinase-9 (MMP-9) as a predictor of disease outcome in a series of 202 stage II colorectal cancer (CRC) patients with long-term follow-up. The present study comprises a series of 202 patients who underwent bowel resection for stage II CRC at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with MMP-9 antibody. Forty-eight percent of all CRC samples were positive for MMP-9. There was no significant correlation between MMP-9 expression and age, depth of invasion, and lymph node status. However, MMP-9 expression was significantly related to histological grade (p = 0.03) and location of the tumor (p = 0.01), therefore, being lower in high-grade tumors and most intense in carcinomas of the descending colon and rectum. Tumors with high MMP-9 expression showed a higher recurrence rate than tumors with low expression (p = 0.02). MMP-9 negative tumors had a more favorable disease-free survival (DFS) than those expressing MMP-9 (p = 0.03). The same was true with disease-specific survival (DSS; p = 0.02) as well, high expression of MMP-9 being associated with shorter survival rates. In multivariate (Cox) survival analysis, MMP-9 expression proved to be an independent predictor of DFS, but not DSS, which was predicted by age and sex only. Quantification of MMP-9 expression seems to provide valuable prognostic information in stage II CRC, particularly, in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.Journal of Gastrointestinal Cancer 11/2009; 40(3-4):91-7. -
Article: Mouse Subrenal Capsule Assay Chemosensitivity and DNA Flow Cytometry Parameters of Human Melanoma Metastases
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ABSTRACT: Chemosensitivity was analyzed by mouse subrenal capsule assay (SRCA) in 103 human melanoma metastases 79 of which were also analyzed by DNA flow cytometry. The most effective combination was dacarbazine, vincristine, and carmustine (DOB), followed by cisplatin plus etoposide (Plat-VP16). By the original criteria of the assay, 35% of tumors were sensitive to DOB treatment while 15% responded to Plat-VP16. Chemosensitivity of DNA diploid and aneuploid tumors showed no significant difference; 35% of the aneuploid tumors were sensitive to DOB and 19% to Plat-VP16, whereas 41% and 13% respectively of the diploid tumors were sensitive. An association between DNA index and chemosensitivity was observed. Growth of the implant was observed in 44% of tumors with a DNA index above 1.5 receiving DOB treatment, whereas only 12% of tumors with an aneuploid DNA index ≤1.5 grew. No significant difference was observed in the SPF of chemotherapy sensitive and insensitive tumors, though a tendency to lower SPF was observed in sensitive tumors.07/2009; 33(4):431-437.
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Institutions
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2009–2013
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University of Turku
- Department of Oncology and Radiotherapy
Turku, Western Finland, Finland
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2012
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University of Benghazi
Benghazi, Sha`biyat Banghazi, Libya
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2002–2012
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Turku University Hospital
Turku, Western Finland, Finland
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1998–2009
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Helsinki University Central Hospital
- Department of Oncology
Helsinki, Province of Southern Finland, Finland
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