Prevalence of Anxiety and Depression and Their Impact on the Quality of Life of Cancer Patients Treated with Palliative Antineoplasic Therapy - Results of the PALINT Trial.

BACKGROUND: Anxiety, depression, and psychological distress are common syndromes of advanced cancer; all have a negative impact on overall quality of life. However, these symptoms are not monitored explicitly and they are managed only by pharmacotherapy. Given the complex etiology of these symptoms, this biomedical approach is inadequate and inefficient. MATERIALS AND METHODS: Here, we present the results of a longitudinal assessment of distress, anxiety, and depression in a sample of 126 patients treated with palliative systemic therapy for advanced cancer in the PALINT trial. Symptoms and quality of life were assessed regularly using the Hospital Anxiety and Depression Scale (HADS) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), respectively. RESULTS: The baseline prevalence of significant distress, anxiety, and depression was 32,6; 35,9; and 56,5%, respectively. A decreasing trend in the prevalence of distress and anxiety occurred after 2 and months - distress (19.4 and 16.3%), anxiety (20.9 and 16.3%), and depression (46.3 and 46.9%). However, these changes did not reach statistical significance. The presence of anxiety and depression correlated negatively with overall quality of life. CONCLUSION: High rates of distress, anxiety, and depression are a strong argument for implementation of systematic screening for psychological distress, and for comprehensive psychosocial support for all patients with advanced cancer throughout the disease trajectory. The HADS questionnaire is a suitable tool for this type of screening. This work was supported by the grant of Ministry of Health AZV 15-33590A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 3. 12. 2018 Accepted: 24. 3. 2019.

Experimental strategies in gene therapy of cancer.

Gene therapy is a new and innovative approach to the treatment of malignant neoplasms, although it is still not capable of eradicating cancer in humans. Selection of the appropriate vector with maximal efficiency and minimal toxicity is crucial for gene therapy and numerous viral and non-viral (synthetic) methods for gene transfer have been developed. There are different gene therapy approaches for cancer treatment such as: 1) gene correction; 2) molecular chemotherapy; 3) proapoptotic gene therapy; 4) antiangiogenic gene therapy; 5) immune gene therapy; and 6) modulation of drug resistance/sensitivity. Cancer gene therapy represents one of the most rapidly developing areas in preclinical and clinical research. However, some problems need to be solved to make sure this strategy is safe, effective and long-lasting before it becomes routinely adopted in clinical practice.

Clustering of pedigrees using marker allele frequencies: impact on linkage analysis.

Ethnicity may form the basis for locus heterogeneity at certain susceptibility loci for complex diseases. Classification of pedigrees into ethnic groups is usually based upon self-report, but this may not be sensitive or specific. We investigated whether it is possible to cluster families from an admixed population using pedigree-specific marker allele frequencies. We used 323 autosomal microsatellite markers from 216 pedigrees who described themselves as either Caucasian or African American. First, we compared the stated ethnicity of pedigrees with clusters using pedigree-specific marker allele frequencies as input for a self-organizing map, a type of neural network. Using data from different chromosomes, nine pedigrees which were self-reported as African American were clustered with the Caucasian pedigrees. Removal of these nine pedigrees from the African American group did not markedly affect linkage results. We then proceeded to determine whether there was further heterogeneity between pedigrees using 1 x 3 nodes. Forty-four pedigrees were clustered in a group intermediate to the African American or Caucasian clusters. This group was composed of 36 and 8 pedigrees that described themselves as African American and Caucasian, respectively. Linkage analysis was performed in this group and results compared with the groups based upon self-reported ethnicity. Linkage to a region on chromosome 3 was observed in this intermediate group, which was more significant than any of the results obtained when pedigrees were grouped using self-reported ethnicity. Use of marker data may assist in clustering pedigrees with similar, ethnic backgrounds and may increase the power for genetic linkage studies.

Cytotoxicity of Co(III) Complexes of Arginine.

The cytotoxicity of four Co(III) complexes of arginine on nontumour MDBK cells and on two cell lines derived from transplantable tumors, LSCC-SF(Mc29) and LSR-SF (SR), was evaluated comparative!y. Based on the cytotoxic concentration required to inhibit cell surveillance by 50% cc(nabla') it was found that: (i) the cytotoxicity of complexes tested increases when the concentration decreased; (ii) the cell surveillance depends on both complex and cell specificities. The complex specificity was illustrated by the order 1 > 4 > 2 >/= 3 . The cell specific response was demonstrated by the fact that LSCC-SG (Mc29) cells were up to 60 times more sensitive to 1 while LSR-SF (SR) cells were up to 1000 times more sensitive to 2 as compared to MDBK cells. Furthermore, with the prolongation of action on nontumour cells the cytotoxicity of 4 decreased up to 300 times while for both tumour cells it was independent on the duration of action.

Fluorescent and electron-microscopy immunoassays employing polyclonal and monoclonal antibodies for detection of goose parvovirus infection.

Polyclonal antibodies (PAbs) raised in geese and eight mice hybridomas secreting monoclonal antibodies (MAbs) against the goose parvovirus (GPV) were prepared. They were used for development of immunofluorescence (IF) and immunoelectron-microscopic (IEM) techniques to demonstrate the GPV infection in infected organs and biological fluids. The GPV antigens were established by immunofluorescence within the nuclei and the cytoplasm of many infected cells of the chorioallantoic membrane of goose and Peckin duck embryos, liver and heart of mortally diseased goslings. By means of IEM it was possible to detect the GPV in native organ homogenate supernatants and allantoic fluids. All techniques used in the study could be successfully applied for rapid diagnosis of the GPV infection. The test systems on the basis of MAbs should, however, be preferred. By means of immunoblotting (IB) using PAbs and MAbs four viral proteins (VP) with MW 88, 77, 65 and 60 kDa were demonstrated. Contrary to the others the VP with MW 65 kDa was the most antigenically reactive though invisible in the SDS-PAGE and Coomassie-blue dye-stained preparations.

Investigations on the aminoacid content of tumor associated antigens of rat sarcoma cells induced by virus.

In our previous work (Alexandrov et al., 1996) was reported that the rat sarcoma cells induced by SR-RSV express two tumor associated antigens (TAA). The one TAA has a molecular weight of 52 kD and is detected by the help of a monoclonal antibody 2C2 only on the outer side of the plasma membrane of the sarcoma cells. The other antigen, with molecular weight of 28 kD, is expressed on the outher and inner side of the membrane. The antigens were isolated as a pure fraction by polyacrylamide electrophoresis and prepared for aminoacid analysis after that. The consisting 16 bound aminoacids were in different amounts. Both antigens are rich in glycine and poor in aromatic and sulphur-containing aminoacids. The presence of glucosamine and galactosamine in the antigens proves their glycoprotein nature. The received data show that the both TAA-s differ not only in molecular weights, place of expression and functional activity, but also in the amount of the bound aminoacids which constitute their proteins.

A second putative mRNA binding site on the Escherichia coli ribosome.

Translation in bacteria is initiated by a base-pairing interaction between the extreme 3'-end of the small-subunit rRNA and a purine-rich domain (Shine-Dalgarno (SD) sequence) preceding the initiation codon at the 5'-end of most bacterial mRNAs. Here, we describe the identification of a second functional and alternative site on the Escherichia coli ribosome which is capable of interacting with mRNA devoid of SD sequences and initiate the translation. This site is localized between nt 1340 and 1360 of the 16S rRNA in E. coli and is complementary to the untranslated region at the 5'-end of tobacco mosaic virus RNA (omega sequence).

Domains in human interferon alpha-1 gene containing tandems of arginine codons AGG play the role of translational initiators in E. coli.

The AGG and AGA are the least used arginine codons in E. coli but they are the most preferable ones in eukaryotes. The low expression of some eucaryotic genes (such as human alpha-1 interferon gene) which contain clusters of AGG codons is explained either by the limited pool of the tRNA(AGG) (Varenne and Lazdunski, 1986) or by the competition of these clusters with the Shine-Dalgarno (SD) sequence (Ivanov et al., 1992). The aim of the present study is to demonstrate the in vivo capacity of AGG tandems to bind to bacterial ribosomes. The two tandems of AGG codons (Arg12 Arg13 and Arg163 Arg164) of hIF alpha 1 with their surrounding nucleotides were cloned in a bacterial expression plasmid containing a strong promoter and a reporter gene (chloramphenicol acetyltransferase, CAT) devoid of a ribosome binding site. The results obtained showed that both AGG tandems initiated translation of the CAT mRNA with an efficiency equal to that of the consensus SD sequence and several fold higher than the native SD sequence of the CAT gene.

Expression of human alpha 1 interferon genes in vectors containing tandemly located promoters recognized by two different RNA polymerases (Escherichia coli and T7).

An expression vector containing two tandemly located promoters (T7 and P1) and two transcription terminators recognized by two different RNA polymerases (T7 RNA polymerase and Escherichia coli RNA polymerase) was constructed. Human alpha 1 interferon gene variants were cloned in this vector and their expression was studied in E. coli strains containing [E. coli BL2I (DE3)] or devoid (E. coli BL21) of the gene for the T7 RNA polymerase. We report that simultaneous activity of the two promoters reduces the level of gene expression when compared with the levels of expression corresponding to either P1 or T7 promoter alone.

Efficiency of the 5'-terminal sequence (omega) of tobacco mosaic virus RNA for the initiation of eukaryotic gene translation in Escherichia coli.

Recent studies have demonstrated that the 5' leader (omega sequence) of tobacco mosaic virus RNA has a certain enhancing capacity for translation of mRNA in both prokaryotes and eukaryotes. In order to estimate the efficiency of omega to initiate translation of mRNA in Escherichia coli, in comparison to the Shine-Dalgarno (S/D) sequence, we have inserted eight different eukaryotic genes into two types of E. coli expression vectors containing one constitutive promoter (P1) but different translation-initiation sites (S/D or omega delta 3 sequence, respectively). The efficiency of transcription and translation in vivo was evaluated for these vectors by measuring the yield of protein and both the level and stability of mRNA. We report that substitution of omega delta 3 for S/D decreases the yield of expressed protein 4-1900-fold and the content of gene-specific mRNA is decreased by about sevenfold. However, in comparison with the S/D sequence, the level of protein expressed under the translational control of omega delta 3 is less sensitive to changes in the 5' coding region. We also report that the omega sequence contains a region of 10-12 nucleotides complementary to the small ribosomal subunit RNA (rRNA) of E. coli, Eikenella corrodens and Xenopus laevis, and to the rRNA of the (small ribosomal) subunit of Oryza sativa.

Effect of tandemly repeated AGG triplets on the translation of CAT-mRNA in E. coli.

It has been shown that tandems of rare arginine codons AGG have a strong inhibitory effect on translation of mRNA in E. coli [5]. This has been explained by the rate-limiting interaction of these codons with the less abundant tRNA(AGG) [6]. In this study tandemly repeated AGG triplets were introduced into the chloramphenicol acetyltransferase (CAT) gene either upstream of the initiation ATG codon or downstream of it (both in frame and out of frame) and the expression of the modified genes was investigated. We report that the addition of AGG clusters resulted in a substantial inhibitory effect on CAT gene expression independently of their localization in mRNA. This inhibitory effect is explained by a competition of the tandem AGGAGG with the natural Shine-Dalgarno (SD) sequence (consensus AAGGAGGU) for the 3'-end of the 16S small ribosomal RNA (rRNA).