ONCOPROTEINS AND TUMOR SUPPRESSOR PROTEINS IN CONGENITAL SACROCOCCYGEAL TERATOMAS

Congenital sacrococcygeal teratoma SCT is the most common germ cell tumor of infancy and childhood with a female preponderance. Most SCTs are diagnosed at birth, are benign, and consist of fully differentiated, mature tissues. Tumorigenesis of SCTs remains poorly understood. Almost nothing is known about possible oncogene activation or tumor suppressor inactivation in these rare tumors. We describe the presence of various oncoproteins and tumor suppressor proteins in eight cases of congenital SCT. The following oncogenes were examined: ras family c-H-, c-N-, and c-K-ras , early genes fos, jun , and tumor suppressor genes p53 and nm23-H-1 . There was no relationship between the intensity of expression of these oncoproteins and tumor suppressor genes and the following parameters: tumor size, age, and survival of the patients. We did not observe any difference, however, between the expression of the examined oncogenes and tumor suppressor genes nm23 and p53 in immature and mature teratomas. Our findings suggest that the ras family of oncogenes, fos and jun oncogenes, and nm23 and p53 tumor suppressor genes are present in congenital SCT, indicating a possible role in genesis and development of these tumors.     

Improvement to the Corrosion Resistance of Ti-Based Implants Using Hydrothermally Synthesized Nanostructured Anatase Coatings

The electrochemical behavior of polycrystalline TiO₂ anatase coatings prepared by a one-step hydrothermal synthesis on commercially pure (CP) Ti grade 2 and a Ti13Nb13Zr alloy for bone implants was investigated in Hank’s solution at 37.5 °C. The aim was to verify to what extent the in-situ-grown anatase improved the behavior of the substrate in comparison to the bare substrates. Tafel-plot extrapolations from the potentiodynamic curves revealed a substantial improvement in the corrosion potentials for the anatase coatings. Moreover, the coatings grown on titanium also exhibited lower corrosion-current densities, indicating a longer survival of the implant. The results were explained by considering the effects of crystal morphology, coating thickness and porosity. Evidence for the existing porosity was obtained from corrosion and nano-indentation tests. The overall results indicated that the hydrothermally prepared anatase coatings, with the appropriate morphology and surface properties, have attractive prospects for use in medical devices, since better corrosion protection of the implant can be expected.     

Solid lipid microparticles containing loratadine prepared using a Micromixer

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol® ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.     

[18F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer

Purpose

PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [¹⁸F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [¹⁸F]-JK-PSMA-7 under ADT.

Procedures

We examined the performance of [¹⁸F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL (second cohort). Finally, we compared detection rates between [¹⁸F]-JK-PSMA-7, [⁶⁸Ga]PSMA-11, and [¹⁸F]DCFPyL.

Results

In the first cohort, we detected [¹⁸F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10^?5) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10^?2). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10^?2) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [¹⁸F]-JK-PSMA-7 and [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295).

Conclusion

[¹⁸F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.

     

Recombinant human TSH increases uptake and effective half-life of radioiodine in thyroid hormone secreting metastases of follicular thyroid cancer

Follicular thyroid cancer with thyroid hormone secreting metastases is an extremely rare condition, with only a few cases reported world-wide. We here present the case of a 64-year-old female patient affected by follicular thyroid cancer with extensive thyroid hormone secreting metastases leading to TSH-suppression. We have also summarized the relevant diagnostic and therapeutic approaches and describe, for the first time, the effects of rhTSH-application in this rare tumor entity. In this patient, we found that rhTSH increased 131I-uptake into the thyroid hormone secreting metastases and prolonged the effective half-life of 131I. These effects of rhTSH should be considered when fixed activities of 131I are prescribed.     

Structural basis and prediction of substrate specificity in protein serine/threonine kinases

The large number of protein kinases makes it impractical to determine their specificities and substrates experimentally. Using the available crystal structures, molecular modeling, and sequence analyses of kinases and substrates, we developed a set of rules governing the binding of a heptapeptide substrate motif (surrounding the phosphorylation site) to the kinase and implemented these rules in a web-interfaced program for automated prediction of optimal substrate peptides, taking only the amino acid sequence of a protein kinase as input. We show the utility of the method by analyzing yeast cell cycle control and DNA damage checkpoint pathways. Our method is the only available predictive method generally applicable for identifying possible substrate proteins for protein serinethreonine kinases and helps in silico construction of signaling pathways. The accuracy of prediction is comparable to the accuracy of data from systematic large-scale experimental approaches.     

Influence of a novel platinum compound--cis-dichloro (dimethylsulphoxide) (1-beta-D-rybofuranosyl-1,2,4-triazolo-3-arboxyamide) platinum (II)--"Pt-rib-1"--on cell cycle and apoptosis in ClS91 and B16 mouse melanoma in vitro

Cisplatin has a significant role in the treatment of selected human tumors including advanced melanoma, but new platinum compounds are still in focus of search for better properties. Modern drug design is often based on studies detecting the abilities of tested drug to induce apoptosis and disturb cell cycle. Aim of the study was to establish the influence of a platinum complex Pt-rib-1 on cell cycle and apoptosis occurrence in mouse melanoma B16 and ClS91 cells. Pt-rib-1 is a ribavirin derivative. previously characterized and described as cytotoxic to B16 and ClS91 mouse melanoma cells in vitro. The new platinum complex (Pt-rib-1); cis- dichloro (dimethylsulphoxide) (1- beta- D-ribofuranosyl- 1,2,4-triazolo -3- carboxyamide) platinum (II) was supplied. Cisdiaminodichloroplatinum (II), (cisplatin) was used in control groups. To detect apoptotic and necrotic cells, Annexin V- conjugated with fluorescein isothiocyanate (Annexin V-FITC, Immunotech) and propidium iodide (IP, Immunotech) were used. Apoptosis detection were done using fluorescence microscopy and flow cytometry. The total DNA content within the cell indicated phase of the cell cycle. DNA content was measured using flow cytometry. Values given represent the mean from three determinations. Results were presented as mean +/- standard deviation (SD). Statistical analysis was done using t-Student test. There were 70.4% of apoptotic cells in the ClS91 culture after 24 h incubation with Pt-rib-1 at a concentration of 2.04 x 10(-3) M (4 x IC50). In B16 group, 83.2 per cent of apoptotic cells was found after 24h incubation with Pt-rib-1 at high concentration (2.30 x 10(-3) M). A 24-h experiment shows a threshold at a concentration higher than 3 x IC50 responsible for apoptosis induction in B16 and ClS91 cells. After 48 h incubation with Pt-rib-1 the per cent of apoptotic cells increased gradually with rising concentrations of Pt-rib-1 up to a final concentration of 2.04 x 10(-3) M and 0.92 x 10(-3) M in ClS91 and B16 groups, respectively. Cell accumulation was observed in S phase after 48 h incubation with Pt-rib-1. The per cent of cells in S phase increased from 31 to 51.1% and 38.8 to 50.0% in ClS91 and B16 culture, respectively. There were no B16 and ClS91 cells in G2/M phase after incubation with higher concentrations of Pt-rib-1 (from 0.2 to 2.0 x 10(-5) M/dm3). Pt-rib-1 partially exhibits action of cisplatin. which has no specific influence on cell cycle and ribavirin. probably responsible for DNA synthesis delay.     

Effect of intense training on plasma leptin in male and female swimmers

PURPOSE: The purpose of this study was to determine whether fasting plasma leptin concentration was altered with an increase in training volume in competitive male and female athletes. METHODS: Intercollegiate male (N = 9) and female (N = 12) swimmers were examined during the preseason and at two times during the mid-season (mid-season 1 and mid-season 2) when training volume was relatively high (33,000 m.wk(-1)). Body composition (hydrostatic weighing), energy intake and expenditure, and fasting plasma leptin concentration were measured. RESULTS: In the women, there was a significant (P < 0.05) decline in fat mass (2 kg) with the increase in training volume, which was not accompanied by a reduction in fasting leptin (12.8 +/- 1.5 vs 11.0 +/- 1.2 vs 11.0 +/- 1.5 ng.mL(-1) for preseason, mid-season 1, and mid-season 2, respectively). In the men, there were no significant changes in body composition, body mass, or fasting leptin (4.4 +/- 0.8 vs 4.3 +/- 0.8 vs 4.6 +/- 0.8 ng.mL(-1), respectively). CONCLUSION: These findings suggest 1) plasma leptin is not sensitive to an increase in training volume and 2) leptin may not be indicative of changes in fat mass with an increase in training volume in female athletes. These data suggest that leptin may not be useful in monitoring relative training stress in athletes.     

Large complex odontoma of the left maxillary sinus

Odontomas as a group are the most common odontogenic neoplasms. They are mixed lesions containing fully formatted dental tissues, both epithelial and mesenchymal, and are usually found during a routine radiographic examination or as a factor in noneruption. Odontomas can be divided into two types: the complex and the compound odontoma. Both types are composed of enamel, dentin, cementum and pulp tissues, but in complex odontomas the tissues are arranged in a haphazard fashion with no discernible dental structures, whereas in compound odontomas the dental tissues exist in a more regular pattern so that the lesion consists of tooth-like structures. We report a case of a 23-year-old man with a large complex odontoma involving the left maxilla and maxillary sinus with clinical, radiographic and histological findings. Because of the size of the mass and its clinical course, benign neoplasms were considered in the differential diagnosis. Surgery was the treatment of choice, and recurrence of the lesion is not expected.