| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Green, Henrik, et al.
(författare)
-
mdr-1 single nucleotide polymorphisms in ovarian cancer tissue – G2677T/A correlates with response to paclitaxel chemotherapy
- 2006
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 12:3 pt 1, s. 854-859
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: P-glycoprotein, encoded by the mdr-1 gene, confers multidrug resistance to a variety of antineoplastic agents, e.g., paclitaxel. Recently, different polymorphisms in the mdr-1 gene have been identified and their consequences for the function of P-glycoprotein, as well as for the treatment response to P-glycoprotein substrates, are being clarified. We analyzed the allelic frequencies at polymorphic sites G2677T/A and C3435T in ovarian cancer patients with good or poor response to treatment with paclitaxel in combination with carboplatin in order to evaluate their predictive values. Experimental Design: Fifty-three patients were included in the study; 28 of them had been relapse-free for at least 1 year and 25 had progressive disease or relapsed within 12 months. A reference material consisting of 200 individuals was also analyzed. The genotypes of each single nucleotide polymorphism (SNP) were determined using Pyrosequencing. Results: The G2677T/A SNP was found to significantly correlate with treatment outcome. The probability of responding to paclitaxel treatment was higher in homozygously mutated patients (T/T or T/A; Fisher's exact test; P < 0.05). The frequency of the T or A alleles was also higher in the group of patients who had a good response (P < 0.05). There was also a dose-dependent influence of the number of mutated alleles on the response to paclitaxel treatment (Χ2 test for linear-by-linear association; P = 0.03). However, the C3435T SNP was not found to correlate to treatment outcome. Conclusions: The mdr-1 polymorphism G2677T/A in exon 21 correlates with the paclitaxel response in ovarian cancer and may be important for the function of P-glycoprotein and resistance to paclitaxel and provide useful information for individualized therapy.
|
|
| 15. |
|
|
| 16. |
- Horvath, György, 1942, et al.
(författare)
-
Cancer odor in the blood of ovarian cancer patients: a retrospective study of detection by dogs during treatment, 3 and 6 months afterward.
- 2013
-
Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- In recent decades it has been noted that trained dogs can detect specific odor molecules emitted by cancer cells. We have shown that the same odor can also be detected in the patient's blood with high sensitivity and specificity by trained dogs. In the present study, we examined how the ability of dogs to detect this smell was affected by treatment to reduce tumor burden, including surgery and five courses of chemotherapy.
|
|
| 17. |
- Horvath, György, et al.
(författare)
-
Different volatile signals emitted by human ovarian carcinoma and healthy tissue
- 2010
-
Ingår i: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 6:6, s. 1043-1049
-
Tidskriftsartikel (refereegranskat)abstract
- Many cancers are detected at a late stage resulting in high mortality rates. Thus, it is essential to develop inexpensive and simple methods for early diagnosis. Detection of different malignancies using canine scent, as well as other technical methods, has been reported in peer-reviewed journals, indicating that this may represent a new diagnostic tool for malignancies. Aim: This study aims to test the detection of different volatile organic compound signals emitted by ovarian carcinoma and normal tissues. Materials & methods: A previously tested electronic nose is used in the pilot study to analyze human grade 3 seropapillary ovarian carcinoma samples. The recorded signals were compared with healthy human Fallopian tube specimens. A variety of algorithms were tested and confusion matrices compared. In parallel, an external validation study was performed using the same type and grade of human ovarian carcinomas with healthy myometrium (first part) and postmenopausal ovarium (second part) specimens as controls. Both sample types were obtained from individuals who did not participate in the pilot study. Results: Method sensitivity was 100% (15 of 15) in the pilot study. The first part of the validation study demonstrated that 84.8% of cancer tissues (sensitivity: 84.8%) and 88.6% of the control samples (specificity: 88.6%) were correctly classified. In the second part the JRip algorithm correctly classified 75% of cancer tissues (sensitivity: 75%) and 80% of the control ovarian tissues (specificity: 80%). Collating results gives a sensitivity of 84.4%, whereas overall specificity was 86.8%. Conclusion: Although based on a limited number of samples, our results strongly suggest that specific volatile organic compound signals emitted by ovarian carcinomas may be used for early diagnosis of the disease.
|
|
| 18. |
- Horvath, György, 1942, et al.
(författare)
-
Different volatile signals emitted by human ovarian carcinoma and healthy tissue.
- 2010
-
Ingår i: Future oncology (London, England). - : Future Medicine Ltd. - 1744-8301 .- 1479-6694. ; 6:6, s. 1043-9
-
Tidskriftsartikel (refereegranskat)abstract
- Many cancers are detected at a late stage resulting in high mortality rates. Thus, it is essential to develop inexpensive and simple methods for early diagnosis. Detection of different malignancies using canine scent, as well as other technical methods, has been reported in peer-reviewed journals, indicating that this may represent a new diagnostic tool for malignancies.
|
|
| 19. |
|
|
| 20. |
- Horvath, György, 1942, et al.
(författare)
-
Function of the exon 7 deletion variant estrogen receptor alpha protein in an estradiol-resistant, tamoxifen-sensitive human endometrial adenocarcinoma grown in nude mice.
- 2002
-
Ingår i: Gynecologic oncology. - : Elsevier BV. - 0090-8258. ; 84:2, s. 271-9
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In addition to hormone and DNA binding, interactions, including competition with other proteins, appear to be a critical component of transcriptional regulation by the estrogen receptor alpha (ER(alpha)). In vitro studies suggest that exon deletion (Delta exon) variant forms of ER(alpha) may also play an important role in determining the progression from hormone dependence to hormone independence in receptor positive tumors. METHODS: We investigated the presence of ERalpha mRNA and protein variants and their possible role in a moderately differentiated human endometrial adenocarcinoma grown in nude mice. In addition to wild-type (wt), RT-PCR assay of the tumor revealed the presence of two mRNA variants, a low concentration of Delta5 and a high concentration of Delta7 ER(alpha). We detected wt, Delta7, and Delta5,7 mRNA by sequencing the transcripts after stable transfection of three HeLa cells with either splice variant. The linked in vitro translation/transcription assay of the transfected cells and the Western blot analysis of the original tumor generated both wt (66 kDa) and Delta7 (52 kDa), Delta5,7 (46 kDa) ER(alpha) proteins. RESULTS: Tumor growth was characterized as estradiol and progesterone resistant but tamoxifen sensitive, i.e., neither estradiol nor progesterone treatment altered the growth rate, whereas tamoxifen treatment significantly increased the tumor volume doubling time. Estradiol treatment decreased the wt and increased the Delta7 variant ER(alpha) protein expression significantly in a dose-dependent manner. Tamoxifen treatment, however, increased the expression of both proteins whereas progesterone had no effect. Estradiol treatment did not influence expression of the Delta5,7 variant protein, which increased significantly in the tamoxifen-treated tumors. Gel mobility shift assays revealed that both wt and Delta7 ER(alpha) proteins bind to the consensus DNA sequence, whereas the Delta5,7 variant protein did not. CONCLUSIONS: We conclude that estradiol, tamoxifen, and progesterone regulate wt and variant ER(alpha) mRNA and protein expression separately and differently and that this hormonal regulation probably occurs, via different mechanisms, at the transcriptional or posttranscriptional level. The Delta7 variant ER(alpha) may play a crucial role in the determination of hormone sensitivity and thus in the outcome of hormone treatment of human endometrial adenocarcinomas.
|
|
