[Show abstract][Hide abstract] ABSTRACT: The assessment of gene expression profile in laryngeal cancer allows implementation of molecular biology methods in diagnostics,
as well as in prognosticating the course of disease, thus allowing taking most optimal decisions as regards the method of
treatment, scope of surgical procedure, or the necessity of adding complementary radiotherapy. The aim of the project was
to analyze the gene expression profile in laryngeal cancer using oligonucleotide microarrays, having in mind searching new
molecular markers for that carcinoma. The study comprised a group of 43 patients (38 males and 5 females) suffering from squamous
cell laryngeal carcinoma, diagnosed and surgically treated in the years 2005–2007 in the ENT Department of the Silesian Medical
University in Katowice, Poland. RNA was isolated from frozen tissue fragments, with the use of columns RNeasy Midi and Mini
Kit (Qiagen). For the examination of gene expression profile, oligonucleotide microarrays of high density were used, provided
by Affymetrix (U 133 2.0 PLUS) containing over 54,000 probes for over 47,000 transcripts. Four genes previously not examined
in that respect in laryngeal carcinoma, occurred to be good markers of the neoplasm. They are: metal-proteinase ADAM12, cyclin-dependent
kinase 2–CDK2, kinesin 14–KIF14, suppressor 1 of checkpoint–CHES1. The analysis of gene expression profile allows, in laryngeal
carcinoma, to point out to new genes, which in future may become molecular markers of the carcinoma.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 10/2009; 266(10):1501-1507. · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The assessment of gene expression profile in laryngeal cancer shall allow to implement molecular biology methods in diagnostics, as well as in prognosis of the course of disease. Thus, it may influence the choice of the most optimal decisions in regards to the method of treatment, extent of surgical procedure, or the necessity of adding post-operative radiotherapy. The aim of the project was to analyse the gene expression profile of laryngeal cancer using oligonucleotide microarrays, aiming to derive novel molecular markers for that carcinoma. The study comprised a group of 14 patients (12 males and 2 females) with squamous cell laryngeal carcinoma, diagnosed and surgically treated between 2005 - 2007 in the ENT Department of the Silesian Medical University in Katowice, Poland. RNA was isolated from frozen tissue fragments. To assess gene expression profile, high density oligonucleotide microarrays (Affymetrix U 133 Plus 2.0) were applied, with over 54 thousand probesets for over 47 thousand transcripts. Four genes, previously not assesed in diagnostic context in laryngeal carcinoma, seemed to be valuable markers of that neoplasm. These are: metalloproteinase ADAM12, cycline-dependent kinase 2 - CDK2, kinesine 14 - KIF14, suppressor 1 of checkpoint - CHES1.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 06/2009; 60 Suppl 1:57-63. · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We sought to assess whether extensive surgical treatment, postsurgical radioiodine therapy, or both decrease the risk of locoregional recurrence (LR) after curative primary treatment in children and adolescents diagnosed with differentiated thyroid cancer (DTC) at age <or=18 y.
To determine the incidence of and identify predictive factors for thyroid bed recurrence (TBR) or lymph node recurrence (NR), we performed a chart review and retrospective multivariate Cox regression analysis on 235 patients with DTC diagnosed at age <or=18 y and managed with curative intent at our tertiary referral center from 1973 to 2002; 40 of these patients had distant metastases at diagnosis. We also determined overall and recurrence-free survival and generated curves for these variables using Kaplan-Meier and Cox univariate analysis.
During a median follow-up of 82 mo (range, 5-402 mo), no DTC-related deaths occurred, 203 (86%) children remained recurrence-free, and 32 (14%) children had LR, including TBR in 9 (28% of LR), NR in 20 (63% of LR), and both in 3 (9% of LR). Among patients treated with radical intent and showing no distant metastases, the most recent thyroglobulin level was <1 ng/mL in all but 4% of cases. The median time from the first surgery to LR was 37 mo (range, 9-280 mo). In multivariate analysis, significant risk factors for TBR were less than total thyroidectomy and lack of postsurgical radioiodine treatment (respective risk increases of 9.5 [P = 0.04] and 11 times [P = 0.03]). For NR, classic papillary histology, incomplete primary lymph node management (i.e., lack of modified lymphadenectomy of affected lymph nodes or lack of confirmation of disease-free nodes by intraoperative staging), and absence of adjuvant radioiodine therapy were independent significant predictive factors that increased the recurrence risk by 1.9 (P = 0.02), 3.3 (P = 0.02), and 3.2 (P = 0.02) times, respectively. Age or sex did not correlate with LR risk.
In DTC patients <or=18 y of age, extensive initial therapy-consisting of total thyroidectomy combined with modified lymphadenectomy performed in case of lymph node metastases and followed by radioiodine therapy--is associated with a substantial decrease of DTC LR risk.
Journal of Nuclear Medicine 06/2007; 48(6):879-88. · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic knee synovitis with effusion, because of the special role of knee joint is an important therapeutic problem. This leads to searching for new treatment modalities. One of them is radiosynovectomy based on anti-proliferative and anti-inflammatory activity of ionizing radiation. It is made using 90Y mainly (high energy of beta [electrons] radiation [2.2 MeV], large average penetration in soft tissues [3.6 mm] and long physical half-life [2.7 days]).
Analyzed material is comprised of 30 patients (33 treatments) suffering from proliferative synovitis of knee joint treated by radiosynovectomy using intra-articular injection of 6 mCi 90Y. In 20 cases the reason of disease was non-specific reactive arthritis, in 5 rheumatoid arthritis, in 3 villonodular synovitis, in 3 psoriasis and in 2 ulcerative colitis. Symptoms duration varied from 3 to 144 months (mean 43). A knee circumference at the treatment day varied from 33.5 cm to 49 cm (mean 41). The operation was based on knee biopsy, evacuation of exudate and delivery of 6 mCi of colloid 90Y. Follow up ranged up to 14 months (mean 4.4). Patients were examined 2 weeks, 1, 3, 6 and 12 months after treatment. During examination a knee circumference was measured, a knee mobility, temperature and patella floating symptom were examined. Pain in treated region was assessed and amount of exudate was measured.
A knee circumference and exudate amount enlarged during following controls, and compared between the treatment day and the last control did not differ significantly (41 vs. 41.6 cm and 43 vs. 42.5 ml respectively) but number of biopsies decreased. A percentage of patients with impaired knee mobility also did not change (59% vs. 58%). Probably, it was caused by resignation from control examination when symptoms disappeared. A percentage of patients without pain relief decreased from 43.5% 2 weeks after treatment to 20% one year later and a patient percentage with complete pain relief increased from 8.5% to 60%. A patient percentage with increased knee temperature and with floating patella decreased significantly (54 vs. 25% and 83 vs. 48% respectively).
Obtained results do not allow to form univocal conclusions regarding effectiveness of 90Y radiosynovectomy. The decreasing biopsies number, decreasing percentage of patient with increased knee temperature and with floating patella; increased percentage of patients with analgetic effect and with total pain relief show a necessity of renewed evaluation of this treatment modality on the base of bigger patients number and longer and more precise observation.
[Show abstract][Hide abstract] ABSTRACT: We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.
[Show abstract][Hide abstract] ABSTRACT: The assessment of frequency and type of mutation and differences in prognosis between sporadic and hereditary type of medullary thyroid carcinoma (MTC), based on own DNA analysis, was performed.
The group of 190 persons with hereditary MTC or asymptomatic mutation carriers was analyzed. Patients with sporadic MTC without RET gene mutation were included into control group (708 persons). The recognition of MTC type was based on assessment of family history, physical examination and genetic analysis. The family history consisted of information about MTC, pheochromocytoma and other neoplasms and hyperparathyroidism in relatives.
The mutations located in codon 634 of exon 11 were the most often (43% of all mutations and 49% of mutations in syndrome MEN 2A/FMTC). The age of diagnosis was ranged between 7 and 71 years (mean age: 39 +/- 15.2 years, median age: 41 years). In hereditary MTC the mean age of diagnosis was 27 +/- 13.9 years and was significantly lower than in sporadic one, where it was 45.7 +/- 14.3 years. The relationship between diagnosis, age and subtypes of hereditary MTC was assessed--no significant differences in examined subgroups were observed. The mean age of diagnosis in MEN 2A/FMTC and MEN 2A syndrome was 28-29 years, in MEN 2B - 21 years. The overall survival in sporadic MTC after 5 years was 97%, in hereditary MTC - 79%. Analysis performed after excluding suprarenal causes of death revealed no statistically significant differences in overall survival between both subtypes of MTC.
1. Hereditary MTC is still diagnosed too late, besides of DNA analysis. 2. In hereditary and sporadic MTC the prognosis is comparable.
Endokrynologia Polska 01/2006; 57(4):407-14. · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In our study we present chosen elements of microarray analysis of gene expression profile in papillary thyroid cancer. The study group included 16 papillary thyroid cancer tissues and 16 corresponding normal tissues. Samples were analyzed on high density oligonucleotide microarrays (GeneChip HG-U133A) which contain 22.000 genes. 110 genes, which had significant changed expression, were selected by MAS 5.0 program. 3 genes were chosen to the deeper analysis: dipeptidylpeptidase 4 (DPP4), fibronectin 1 (FN1), tissue inhibitor of metalloproteinase 1 (TIMP1). DPP4-RNA were absent in normal tissue while in cancer tissue it was detected in large amount. FN1 and TIMP1 expression were detected in normal tissue but markedly increased in papillary thyroid cancer. Among these 3 genes DPP4 seems to be the best molecular marker for papillary thyroid cancer.
Endokrynologia Polska 01/2005; 56(5):752-7. · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study was undertaken to verify whether the RET gene polymorphisms are associated with MTC in patients negative for germline mutations. Two hundred five patients with apparent sporadic MTC were subjected to genetic analysis of RET exons 10, 11, 13, 14, 16 and 22 RET germline mutation carriers were identified with 10.7% frequency. The frequency among 26 patients not older than 30 was 27%. In patients excluded for known mutations we analyzed two polymorphic sites: RET codon 769 and 836. As control group, 90 healthy subjects were investigated. In young patients the observed allelic frequencies were 32% for variant L769/CTG and 5% for variant S836/AGT. Although these values were higher than in older MTC patients (22 and 3%, respectively), as well as in the control group (27 and 2%) the difference was insignificant. We conclude that in Polish patients polymorphisms at RET codons 769 and 836 are not associated with medullary thyroid carcinoma.
Cancer Detection and Prevention 02/2004; 28(4):231-6. · 2.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We sought to evaluate the efficacy, biochemical effects, safety and outcome of recombinant human thyroid-stimulating hormone (rhTSH) as an adjunct to radioiodine treatment of advanced differentiated thyroid carcinoma (DTC). We also sought to determine whether rhTSH is useful as an adjunct to radioiodine treatment following isotretinoin re-differentiation therapy of DTC metastases that have lost function. Therefore, in 54 consecutive patients who had retained bulky metastatic and/or locoregional lesions of DTC despite the exhaustion of other therapeutic options, we gave one to four courses of two consecutive daily intramuscular injections of rhTSH, 0.9 mg, followed by a therapeutic activity of (131)I per os on day 3. Fifty patients had received prior radioiodine treatment aided by l-thyroxine (T(4)) withdrawal. We included in the study 23 patients who had received a trial of isotretinoin therapy for re-differentiation of confirmed de-differentiated metastases. In a blinded, within-patient comparison of post-therapy whole-body scans after the first rhTSH-aided and latest withdrawal-aided treatments in patients with functional metastases at baseline, 18 of 27 (67%) scan pairs were concordant, four (15%) were discordant in favour of the rhTSH-aided scan and five (19%) were discordant in favour of the withdrawal-aided scan. In total, 37 (74%) of 50 paired scans were concordant, eight (16%) favoured rhTSH and five (10%) favoured withdrawal. All differences appeared to be attributable to clinical causes, not to any difference between endogenous and exogenous TSH stimulation. Reflecting the biochemical activity of rhTSH and the release of thyroglobulin (Tg) due to tumour destruction, median serum Tg concentration rose approximately fourfold between baseline and day 6 of the rhTSH-aided treatment course. rhTSH was well tolerated, with mostly minor, transient toxicity, except for neck oedema in three patients with neck infiltrates and pathological spine fracture in one patient with a large vertebral metastasis. At 6 months, complete response occurred in one (2%), partial response in 12 (26%) and disease stabilisation in 19 (40%) of 47 evaluable patients. The rate of complete + partial response was 41% and that of disease stabilisation, 30%, in the 27 evaluable patients with functional metastases at baseline; the corresponding rates were 10% and 55% in the 20 evaluable patients with non-functional metastases at baseline. Although within-patient comparison of early outcome after both modalities is limited by a significantly greater median number of courses and a greater median cumulative activity of radioiodine given under withdrawal, response to rhTSH-aided and withdrawal-aided treatment was similar in 23 (52%) of 44 evaluable patients, superior with rhTSH in 12 (27%) and superior with withdrawal in seven (16%). In two patients, a superior response was obtained after isotretinoin pretreatment and rhTSH and attributed to re-differentiation therapy. In conclusion, our study provides preliminary evidence that rhTSH safely and effectively aids radioiodine treatment of advanced DTC, and does so to an at least equivalent degree as does T(4) withdrawal.
European journal of nuclear medicine and molecular imaging 09/2003; 30(8):1077-86. · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this paper we present the preliminary results of a prospective trial of the efficacy of simultaneous radiotherapy and anti-EGFR (125)I radioimmunotherapy of malignant gliomas with 2 years' total survival as the end-point, raising the question whether anti-EGFR (125)I radioimmunotherapy influences the disease-free survival in these patients.
Patients with anaplastic astrocytoma or primary glioblastoma were previously treated by a macroscopically radical neurosurgical approach and randomized either to radiotherapy + radioimmunotherapy arm or treated by radiotherapy alone. Seven patients were included in the group with radioimmunotherapy, among them five with GBM and two with AA, and five patients in the control arm. Patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques. Anti-EGFR (125)I monoclonal antibody 425 radioimmunotherapy (50 mCi/course) was started during 4th week of radiotherapy and was repeated three times in one week intervals.
Time of follow-up ranges between 2 and 10 months in the anti-EGFR (125)I radioimmunotherapy arm and 4 and 9 months in the control arm. Recurrence was diagnosed in all patients in the EGFR (125)I group with a lethal outcome in two of them and in 4 patients in the control group. Median time to recurrence was 2 and 5 months respectively.
Taking into account early recurrences observed, we propose to continue the studies on the efficacy of adjuvant anti-EGFR (125)I radioimmunotherapy in a selected group of patients in whom the greatest benefit may be expected on the basis of molecular studies, among them EGFR expression investigation.
Nuclear medicine review. Central & Eastern Europe: journal of Bulgarian, Czech, Macedonian, Polish, Romanian, Russian, Slovak, Yugoslav societies of nuclear medicine and Ukrainian Society of Radiology 02/2002; 5(1):29-33.
[Show abstract][Hide abstract] ABSTRACT: The study was undertaken to evaluate the frequency of inherited medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease. A stepwise algorithm was used depending on clinical indices and the age of patient at MTC diagnosis.
One hundred sixteen patients with MTC verified by postoperative pathologic examination were subjected to genetic analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain reaction, restriction endonuclease digestion, and DNA sequencing.
Among 116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10 and 11). The frequency of inherited disease among patients younger than 45 years at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11. Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1% additional diagnoses, giving a risk of 16.3% in this age group. One previously unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and 4.5% in polymorphic variants L769L and S836S, respectively, were observed. The frequency for L769L was higher than in older patients (P <.05).
The frequency of inherited disease among apparent sporadic medullary thyroid carcinoma patients is close to 10% in the Polish population of MTC patients. The extended analysis of all known RET proto-oncogene mutation sites is obligatory in patients younger than 45 years at diagnosis, but we also see the need to analyze the impact of rarer mutations in older patients.
Journal of Clinical Oncology 04/2001; 19(5):1374-80. · 18.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intraoperative probes become increasingly important in the surgical management of cancer. Attempts with gamma probe guided surgery to improve the completeness of surgical excision of radioiodine avid tissues in thyroid cancer have been performed through several decades. The first Polish results by Pomorski et al. have shown that gamma probe guided surgery after preoperative dose of 131I have allowed locating and increasing the completeness of thyroid excision. These results have been substantiated by other authors. However, in the evaluation of intraoperative gamma probe localization of 131I avid tissues one should remember of the limitations of the method. The article begins with a discussion of the statistical limitations of the radiation detection and of the key performance parameters that characterize detectors. Later on we continue with the description of specific aspects concerning gamma probe guided surgery in thyroid cancer.
[Show abstract][Hide abstract] ABSTRACT: The diagnostics with the use of recombinant human TSH for the follow-up of differentiated thyroid carcinoma (DTC) has been already approved. In more than 400 diagnostic scans, rhTSH proved to be effective in promoting 131I uptake in thyroid remnants and DTC metastases in patients receiving suppressive doses of thyroxine. However, information about its application in radioiodine treatment of DTC are scarce, especially with respect to patients with metastatic disease. In this review we have described our own results obtained during rhTSH aided radioiodine treatment of 42 patients with advanced DTC with reference to current literature data about diagnostic and therapeutic application of rhTSH.
[Show abstract][Hide abstract] ABSTRACT: Retinoids, a large group of compounds structurally related to vitamin A, are able to induce redifferentiation of thyroid cancer cells. The aim of the study is to present our early results of retinoids redifferentiation therapy of thyroid cancer patients. In 15 patients with advanced thyroid cancer, whose cancer foci did not concentrate radioiodine, 13-cis retinoic acid (Roaccutan) was given for 6 weeks before radioiodine treatment. Radioiodine therapy was performed under exogenous TSH stimulation (Thyrogen). Three patients were treated twice. The planned retinoid dose was delivered to 11 patients. In the other four patients the reduction of retinoids dose was necessary due to severe side effects. In post-therapeutic scintigraphy radioiodine uptake was visible in two out of seven patients (29%) with lung metastases, in 5 out of 9 (56%) with locoregional disease and in two with bone metastases. On the whole, in 50% of patients reinduction of radioiodine uptake was visible, however, in most patients only a very discrete one. Thyroglobulin concentration before and after retinoids therapy did not differ significantly. CONCLUSIONS: In a subgroup of patients 13-cis retinoic acid can induce radioiodine uptake, however, prospective studies in larger groups of patients are necessary to prove its clinical application.
[Show abstract][Hide abstract] ABSTRACT: Preliminary results of treatment of inherited medullary thyroid carcinoma, diagnosed primarily with genetic analysis of mutation of protooncogene RET are presented. Among 16 carriers of mutation identical with mutation diagnosed earlier in proband, there were 4 patients with clinically obvious medullary thyroid carcinoma and 12 asymptomatic carriers. In all patients, in whom calcitonin level was increased preoperatively, its normalization was obtained. The paper summarizes these aspects of cooperation between geneticians and physicians in which diagnostic results influence clinical decisions (indication and time of thyroid and lymph nodes surgery and it's spectrum, range of diagnostic procedures towards pheochromocytoma and parathyroid hyperplasia in relation to the found mutation).
[Show abstract][Hide abstract] ABSTRACT: The study was undertaken to evaluate the frequency of RET polymorphisms at codons 769 and 836 in young medullary thyroid carcinoma (MTC) patients in whom the presence of a known germline mutation has been excluded. 40 patients aged 10-29 were subjected to genetic analysis of RET exons 10, 11, 13, 14 and 16 and compared to 140 older patients. The hereditary component occurred to be very high in young MTC patients: 57% carry the germline mutation, other 28% exhibit at least one rare polymorphic variant of RET. The observed allelic frequencies were 38% for polymorphic variant L769CTG and 6% for variant S836AGT. The results were significantly higher than those obtained in the group of older patients: 20% and 1% for L769CTG and S836AGT, respectively. Our results speak in favour that the polymorphism in RET codon 769 and 836 may also be a factor predisposing to the development of MTC in young age.