Biomedical subjects

Ulla Puistola

Publications and source records attributed to Ulla Puistola.

9 recordsLinked to original sources

PubMed2006

A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

Adult↗

PubMed2006

Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line.

p14(ARF) tumor suppressor protein regulates p53 by interfering with mdm2-p53 interaction. p14(ARF) is activated in response to oncogenic stimuli but little is known of the responses of endogenous p14(ARF) to different types of cellular stress or DNA damage. Azidothymidine (AZT) is being tested in several clinical trials as an enhancer of anticancer chemotherapy. However, the knowledge of the relationship between AZT and cellular pathways, e.g. p53 pathway, is very limited. In this study, we show that AZT, cisplatin (CDDP) and docetaxel (DTX) all induce unique molecular responses in OVCAR-3 ovarian carcinoma cells carrying a mutated p53, while in A2780, ovarian carcinoma and MCF-7 breast carcinoma cells with wild type p53, all of these drugs cause similar p53 responses. We found that endogenous p14(ARF) protein in OVCAR-3 cells is down-regulated by DTX but induced by AZT and a short CDDP pulse treatment. In HT-29 colon carcinoma cells with a mutated p53, all treatments down-regulated p14(ARF) protein. Both CDDP and AZT increased the expression of p14ARF mRNA in OVCAR-3 cells. Differences in cell death induced by these drugs did not explain the differences in protein and mRNA expressions. No increase in the level of either c-Myc or H-ras oncoproteins was seen in OVCAR-3 cells after AZT or CDDP-treatment. These results suggest that p14(ARF) can respond to DNA damage without oncogene activation in cell lines without functional p53.

Antineoplastic Agents↗

PubMed2006

Surgical treatment of ovarian cancer in different hospital categories--a prospective nation-wide study in Finland.

This prospective nation-wide study was performed to evaluate the effect of hospital category and subspeciality training on surgical treatment of ovarian cancer. Data were obtained from a questionnaire filled in by the operating unit, and from the surgical and histopathology reports. The survey included 307 patients. Half of them were operated in the university hospitals where gynaecologic oncologists performed 72% of the operations. This was the case in only 4% and 19% in the central and district hospitals, respectively. In university hospitals, pelvic lymphadenectomy was performed in 88%, and para-aortic lymphadenectomy in 73%, of the patients with stage I disease. The corresponding figures ranged from 11% to 21% in central and district hospitals. For stage III patients operated by gynaecologic oncologists, the estimated odds ratio for no macroscopic tumour was 3.0 times higher (95% CI 1.2-7.5) than for those operated by general gynaecologists. These results favour centralisation of surgical treatment of ovarian cancer.

Adolescent↗

PubMed2006

[Not Available].

Explore the source record for details and available documents.

Journal Article↗

PubMed2004

Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been linked to aggressive behavior in several malignancies. Gelatinases (MMP-2 and MMP-9) in particular are prognostic factors in many adeno- and epithelial cancers. However, no conclusive data exist concerning the role of gelatinases in endometrial cancer. METHODS: Eighty-eight patients with endometrial cancer, treated between 1988 and 1993 in Umeå University Hospital, were included. MMP-2 and MMP-9 proteins were analyzed immunohistochemically from paraffin-embedded tissues by using specific monoclonal antibodies. The staining results were compared to the clinical data. RESULTS: Fifty-two percent of the cases were positive for MMP-9 and 72% for MMP-2. The overexpression of the proteins of either MMP-2 or MMP-9 was associated with poor survival. The predictive value of MMP-2 expression was most distinct in stage I cancers. An association was found between the positivity of MMP-2 and MMP-9. Only 3% of the cases were highly positive for both gelatinases and 18% of the cases were negative for both MMPs. Both gelatinases correlated to the histological grade. MMP-9 also correlated to the clinical stage of the disease, whereas MMP-2 did not. There was no apparent association with either depth of invasion, menopausal status, or the age of the patient. CONCLUSION: MMP-2 and MMP-9 could serve as markers for the clinical behavior of endometrial cancer. They may further be linked to a tendency to cancer relapse. Thus, these gelatinases may turn out to be potentially useful in decision making about the need for an adjuvant treatment.

Endometrial Neoplasms↗

PubMed2004

Genome-wide scanning for linkage in Finnish breast cancer families.

Only a proportion of breast cancer families has germline mutations in the BRCA1 or BRCA2 genes, suggesting the presence of additional susceptibility genes. Finding such genes by linkage analysis has turned out to be difficult due to the genetic heterogeneity of the disease, phenocopies and incomplete penetrance of the mutations. Isolated populations may be helpful in reducing the level of genetic heterogeneity and in providing useful starting points for further genetic analyses. Here, we report results from a genome-wide linkage analysis of 14 high-risk breast cancer families from Finland. These families tested negative for BRCA1 and BRCA2 germline mutations and showed no linkage to the 13q21 region, recently proposed as an additional susceptibility locus. Suggestive linkage was seen at marker D2S364 (2q32) with a parametric two-point LOD score of 1.61 (theta=0), and an LOD score of 2.49 in nonparametric analyses. Additional genotyping of a 40 cM chromosomal region surrounding the region of interest yielded a maximum parametric two-point LOD score of 1.80 (theta=0) at D2S2262 and a nonparametric LOD score of 3.11 at an adjacent novel marker 11291M1 in BAC RP11-67G7. A nonparametric multipoint LOD score of 3.20 was seen at 11291M1 under the assumption of dominant inheritance. While not providing proof of linkage considering the small number of families and large number of laboratory and statistical analyses performed, these results warrant further studies of the 2q32 chromosomal region as a candidate breast cancer susceptibility locus. Both linkage and association studies are likely to be useful, particularly in other isolated populations.

Base Sequence↗

PubMed2003

Activin B in patients with granulosa cell tumors: serum levels in comparison to inhibin.

BACKGROUND: Activins and inhibins are polypeptide hormones/growth factors of primarily gonadal origin. In the ovary, activins and inhibins are primarily synthesized by granulosa cells. Serum inhibin measurements have been used for the follow-up of patients with granulosa-cell tumors (GCT) after surgery. METHODS: We have employed a recently developed assay to study whether activin B (A) measurements can be used as a marker of progression of GCTs. Additionally, these measurements have been compared with simultaneously run inhibin measurements using a commercial assay. Serum samples of three patients suffering from GCTs (all stage Ia) were collected at primary surgery and at controls thereafter. RESULTS: In patient AM, serum inhibin levels have remained elevated while A levels are low; there has been no evidence of a residual tumor. In patient AR, there has been no clinical evidence of a residual tumor, and both serum A and inhibin levels have remained low. In patient PP, a residual tumor was found 6 years after primary surgery; at the time A levels were elevated, while inhibin levels remained low. CONCLUSION: We introduce A as a promising new marker for postoperative follow-up of patients suffering from GCTs.

Activins↗

PubMed2002

Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum.

The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly (arm A) or every 3 weeks (arm B). and to assess the safety of intravenous steroids versus standard peroral premedication. Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were randomized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks. The median delivered dose intensity was 77.6 mg/m2/week in the weekly arm, and 72.7 mg/m2/week in the every 3 weeks arm. WHO grade 3-4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity, response rate, time to progression or survival between arms was observed. Weekly paclitaxel at a dose of 67 mg/m2/week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks. Intravenous steroids are a safe alternative to oral steroids.

Administration, Oral↗

PubMedDate not supplied

The value of sequential serum measurements of gelatinases and tissue inhibitors during chemotherapy in ovarian cancer.

BACKGROUND: Gelatinases and tissue inhibitors of metalloproteinases (TIMPs) are involved in tumour invasion and metastasis. High pre-operative TIMP-1 serum values have been previously found to correlate to aggressive features in ovarian cancer patients. This study has examined the clinical value of sequential serum measurements of gelatinases and TIMPs during ovarian cancer treatment. PATIENTS AND METHODS: Serum gelatinase and TIMP values were measured in 48 patients receiving cytotoxic chemotherapy for ovarian cancer. The serum values were analysed by enzyme-linked immunosorbent assay (ELISA) in the third and sixth chemotherapy cycles, and compared to the treatment response. RESULTS: Increased MMP-9 (matrix metalloproteinase-9), TIMP-2 and MMP-2 mean serum values were observed in optimally operated patients with a complete response to treatment, compared to those with a partial response. No significant differences were found in the change of circulating TIMP-1 values in the different chemotherapy response groups. CONCLUSION: Measuring the serum values of gelatinases or TIMP-2 sequentially during chemotherapy might be beneficial for response evaluation in optimally operated patients, whereas the serum TIMP-1 values might not contribute to an evaluation of the treatment response.

Adult↗