Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. “Follicular” refers to origin of cells and in the same time to growth pattern - building follicles. Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. Increasing number of immunohistochemical markers is in the continual process of evaluation. Tissue microarrays incorporating, total 201 cases, out of which 122 malignant and 79 benign follicular lesions, including neoplastic and non-neoplastic, were constructed and immunostained with antibodies to CD56, CK19, Galectin-3, HBME-1. Tissue cores were exclusively being acquired from tumour/lesion on interface with normal thyroid tissue. A systematic review of literature was done for period from the year 2001 to present time. All analysed markers may make a difference between benign lesions/tumours from differentiated thyroid carcinomas (p = <0.01, for all markers). Expression of all markers is significantly higher in papillary carcinoma than in follicular adenoma (p < 0.01). Statistically significant difference in expression of Galectin-3 and CD56 between follicular carcinoma and follicular adenoma was registered (p = 0.043; p = 0.028, respectively). The only marker which expression showed statistically significant difference between adenoma and carcinoma of Hurthle cells was Galectin 3 (p = 0.041). CK19 and HBME-1 were significantly expressed more in papillary carcinoma as compared to follicular carcinoma. Galectin 3 is most sensitive marker for malignancy, while loss of expression of CD56 is very specific for malignancy. Expected co-expression for combination of markers in diagnosis of follicular lesions decreases sensitivity and increases specificity for malignancy.
The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin include drug resistance and significant side effects. Due to their better stability, as well as the possibility to introduce biologically active ligands in their axial positions constructing multifunctional prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations. Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV) conjugates demonstrated higher or comparable activity with respect to cisplatin against different human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1), and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice, 1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the mitotic rate.
Three triphenyltin( iv ) compounds with carboxylato N -functionalized 2-quinolones are reported. The compounds showed remarkable anticancer activity in lower micromolar concentrations. The most active compound exhibited a better in vivo profile than cisplatin.
Adrenocortical carcinoma (ACC) is aggressive, but rare tumours that have not been sufficiently studied. The aim of our study was to present the demographic and clinical characteristics of patients with ACC, to determine the overall survival rates, analyse the effect of prognostic factors on survival, as well as to identify favorable and unfavourable predictors of survival. The study included 72 patients (42 women and 30 men) with ACC. We analysed the prognostic value of the demographic and clinical characteristics of the patients, tumour characteristics, therapy administered and survival rates. Kaplan-Meier survival curves and the log-rank test were used to estimate the overall and specific survival probabilities and the Cox regression model was used to identify independent prognostic factors for survival. The patients had mean age of 50 years. The 1-, 5-, and 10-year probabilities of survival in patients with ACC were 52.5 %, 41.1 %, and 16.4 %, respectively. The median survival time was 36 months. The results of multivariate Cox regression analysis showed that the presence of lymphatic metastases (HR = 7.37, 95 % CI = 2.31-23.48, p = 0.001) and therapy with mitotane (HR = 0.11, 95 % CI = 0.04-0.27, p = 0.001) were independent prognostic factors for survival. The presence of lymphatic metastasis is an unfavourable prognostic factor, while postoperative therapy with mitotane is a favorable prognostic factor for survival in patients with ACC.