New pharmacological strategies in the treatment of nonsmall cell lung cancer

According to the number of deaths lung cancer is the leading cancer type, and non-small cell lung carcinoma (NSCLC) is the most frequent subtype. Because of high NSCLC morbidity the aim of this paper is to discuss the appearance of new pharmacological possibilities in the lung cancer therapy. In the research field of new drugs there are two approaches that differ from the standard chemotherapy. According to one approach targeted therapy against specific molecules in the cancer cells is considered, like inhibitors of growth factors, or inhibitors of cell signalling (e.g. tyrosine kinase inhibitors, serine-threonine inhibitors), while on the other hand, drugs that could induce immune system in order to destroy lung cancer (like inhibitors of programmed death receptors, their ligands, or MAGE-A3 antagonists) are on the way to be discovered. Some of these drugs are approved by the U.S. Food and Drug Administration, while the others are in the first phases of clinical trials

Neurological signs and symptoms in patients with autoimmune thyroid disease

Neurological and/or psychiatric signs and symptoms can characterizise the clinical picture of encephalopathy associated with autoimmune thyroid diseases and high levels of serum antithyroid autoantibodies. To the best of our knowledge, the literature does not include data on neurological abnormalities in patients with autoimmune thyroid diseases without encephalopathy. Therefore, the aim of this study was to analyse the neurological signs and symptoms that are not associated with a previously identified disease in patients with autoimmune thyroid diseases. This study included 66 patients who were diagnosed with autoimmune thyroid disease. Before the neurological examination, a detailed history of neurological symptoms was obtained for each patient. No neurological symptoms had been present before the test in 47 of 66 patients (71%). Of the remaining 19 patients (29%), 13 of 66 (20%) patients had headache. Among patients with headache, the concentrations of thyroid peroxidise antibodies were slightly higher than in patients without headache, though the diff erence was not statistically significant (p=0.380, Mann-Whitney test). The patients who took part in this study complained of other neurological symptoms including vertigo (two patients, 3.0%), tingling of hands (two patients, 3.0%), transient weakness of one leg (one patient, 1.5%) and forgetfulness (one patient, 1.5%). Electroencephalography was performed only in patients with neurological symptoms and was normal in all of these patients. Hashimoto encephalopathy is probably not as rare as predicted, but, among our patients with autoimmune thyroid disease, we did not recognise any patients meeting the required diagnostic criteria for encephalopathy. Some of our patients had headache, which was not linked with any previously identified disease

Concentration of thyroglobulin and thyroglobulin-specific autoantibodies in patients with differentiated thyroid cancer after treatment with radioactive iodine 131

Background: Measurement of serum thyroglobulin (Tg) is primarily used as a tumor marker in the postoperative management of patients with differentiated thyroid cancer (DTC), while thyroglobulin autoantibodies (TgAbs) are elevated in some patients as well. The aim f this study was to evaluate the concentrations of Tg and TgAbs in DTC patients 3 and 6 months after radioiodine therapy and to analyze whether the development and course of TgAbs is related to the clinical status of DTC patients or Tg levels before and after radioiodine therapy. Methods: Pre-treatment measurements were made in conditions of stimulation of Tg secretion with endogenous thyroid-stimulating hormone (TSH) (TSH>25 mIU/L), while the measurements after the treatment were obtained in conditions of suppression of Tg secretion (TSH<0.15 mIU/L). Results: Concentrations of Tg were decreased in the sera of all patients with DTC 6 months after radioiodine treatment, as well as the mean concentration TgAbs. Thyroglobulin autoantibody concentrations in sera of patients without metastasis were higher than in those with DTC metastases. Individual values of TgAbs in patients without metastases after the radioiodine treatment were decreased, increased, or unchanged. Conclusion: The development and course of TgAbs in DTC patients cannot be predicted by Tg levels before and after radioiodine therapy

Blood cells in thyroid cancer patients: A possible influence of apoptosis

© 2016 Olgica B. Vrndic. The side effects of radioactive iodine (131-I) treatment of differentiated thyroid cancer (DTC) patients include reduction of peripheral blood cell counts. The aim of this study was to analyze some potential changes in blood cell counts of DTC patients after 131-I therapy, especially CD3-positive, CD19-positive, and CD56-positive peripheral blood lymphocytes (PBL), as well as the possible role of apoptosis in selected lymphocyte populations. The study group included 24 thyroid cancer patients and 24 control subjects. Peripheral blood samples from patients and controls were analyzed using 5-color flow cytometry. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. There was a statistically significant decrease of all blood cells after the 131-I therapy. The CD19+ B lymphocyte population was the most affected (5.82 ± 3.21% before therapy vs. 3.93 ± 2.60% after therapy, p = 0.008). This decrease was correlated with the degree of apoptosis of peripheral blood lymphocytes (Spearman's r = 0.563, p = 0.013). We concluded that 131-I therapy of DTC patients led to a decrease of all peripheral blood cells, especially CD19+ B lymphocytes. This directly correlated with apoptosis of PBLs, indicating that radiation damage to B cells leads to subsequent elimination by apoptosis

Radioiodine therapy accelerates apoptosis in peripheral blood lymphocytes of patients with differentiated thyroid cancer

Both apoptosis and micronuclei formation reflect cytogenetic damage in cells and could contribute to cell homeostasis. The aim of this study was to evaluate apoptosis in peripheral blood lymphocytes (PBLs) of patients with differentiated thyroid cancer (DTC) before and after 131-iodine (131-I)-therapy and its correlation with micronuclei (MN) frequency. The study population included 18 DTC patients and 18 healthy donors. Apoptotic cells were detected using the Annexin V-FITC/7-AAD kit and MN frequency by cytokinesis-block MN assay. The difference between early apoptosis in PBLs of DTC patients before therapy and controls (9.88 ± 4.99% vs. 6.64 ± 2.07%, p = 0.003) was significant, as well as between early apoptosis in PBLs of DTC patients before and after 131-I-therapy (9.88 ± 4.99% vs. 13.53 ± 6.57%, p = 0.008). The MN frequency and early apoptosis in PBLs of DTC patients was positively correlated before (r = 0.540, p = 0.021) and after 131-I-therapy (r = 0.585, p = 0.014). Thyroid cancer patients had a significantly increased early apoptosis in PBLs, which further increased after 131-I-therapy in association with MN frequency

Correlation between micronuclei frequency in peripheral blood lymphocytes and retention of 131-I in thyroid cancer patients

Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50 ± 6.90 vs. 27.10 ± 19.50 MN) and significantly decreased the CBPI (1.52 ± 0.20 vs. 1.38 ± 0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined. © 2013 Tohoku University Medical Press

Apoptosis and genome instability in children with autoimmune diseases

© 2018 The Author(s). As apoptosis and genome instability in children with autoimmune diseases (AIDs) are insufficiently investigated, we aimed to analyse them in peripheral blood lymphocytes (PBLs) of children and adolescents with Hashimoto's thyroiditis (HT), Graves' disease (GD) and type 1 diabetes mellitus (T1DM), including possible factors that could affect their occurrence. The study population included 24 patients and 19 healthy controls. Apoptotic cells were detected using an Annexin V-FITC/7-AAD kit. Genome instability was measured as micronuclei (MNs) frequency using the cytokinesis-block MN assay. In addition, comet assay was performed for determination of genome instability as genome damage index (GDI) in new subpopulation of patients with T1DM. The percentage of apoptotic PBLs in patients with AID was significantly lower than in control subjects. There was a positive correlation between thyroid-stimulating homone (TSH) concentration and the proportion of cells in late stage apoptosis in patients with autoimmune thyroid diseases (AITDs). The MN frequency in patients was significantly higher than in controls. Individuals with HT or T1DM had a significantly higher MN frequency than those with GD. Similarly, the value of GDI in patients with T1DM was significantly higher than in controls. The level of apoptosis was positively correlated with MN frequency as well as with GDI in patients with AID. In conclusion, children with AITD (HT and GD) and T1DM have a significantly lower level of apoptosis in PBLs and significantly higher MN frequency as GDI than healthy subjects. Apoptosis and the level of genome instability in these patients with AID are positively correlated