Kurzfassung: The effect of PectaSol on Dox (Doxorubicin) cytotoxicity in terms of apoptosis and cell cycle changes in PCa (prostate cancer) cell lines (DU‐145 and LNCaP) has been investigated. Combination of PectaSol and Dox resulted in a viability of 29.4 and 32.6% ( P 〈 0.001) in DU‐145 and LNCaP cells. The IC 50 values decreased 1.5‐fold and 1.3‐fold in the DU‐145 and LNCaP cells respectively. In the DU‐145 cells, combination of PectaSol and Dox resulted in a reduction in p27 gene and protein expression ( P 〈 0.001). In LNCaP cells, this combination increased p53, p27 and Bcl‐2 expression. Treatment with both drugs in DU‐145 cells led to an increase in sub‐G 1 arrest (54.6% compared with 12.2% in Dox). In LNCaP cells, combination of the drugs led to an increased in G 2 /M arrest (61.7% compared with 53.6% in Dox). Based on these findings, progressive cytotoxicity effect of Dox and PectaSol together rapidly induce cell death in DU‐145 through apoptosis and in LNCaP cells through cell cycle arrest (G 2 /M arrest).

Kurzfassung: The limited availability of data on somatic gene evolution in breast cancer is challenging item to apply an appropriate clinical management for each individual. As human subtelomeric sequences are diverse‐prone and variable, they can be considered as hot spots for analysis of the health or disease status. We compared the hybridization signals of subtelomeric sequences in normal cells with those in auxiliary lymph nodes (ALNs) isolated from a single patient. Distinct signal intensities were found in all chromosomes: weak (5, 6, 9–12, and 16–19), medium (1, 5–9, 19, and X), and strong (2, 5, 9, 10, 16, and 18) intensities. Signal intensities in the patient's ALN and lymphocytes were higher than in normal tissues. The absence and presence of one or more hybridization signals and the presence of signals in the p and q arms were also variable. Whereas chromosomes 2, 3, 5, 7, 8, 10, 16, 18, 20, and X showed three hybridization spots, chromosomes 1, 4, 9, 12, 17, and 18–19 presented a reduced signal in the ALN and lymphocytes. In addition, signal intensity in the p arm was higher than in the q arm in most patients’ chromosomes. Therefore, we propose that subtelomeric hybridization be followed periodically in individuals with breast neoplasm to provide specific patterns. Such profiling could be considered as a prediction marker throughout the patients’ life. Together with the Ki67, cyclin D1, and cyclin E expression profiles, the subtelomeric hybridization profile could provide complementary information for cancer management.

Kurzfassung: Successful cancer evolution (CE) relies on the sequential molecular and functional events including 1) telomere; 2) sub-telomere; 3) epigenetic; 4-6) hit-episodes; 7) an innovative cell cycle machinery, as the multi-phase, and 8) chromosomal abnormalities. In this regard, eight available, fundamental/evolutionary and strategic key information (Evolutionary- ID) presented. Telomere length (TL), has the fundamental role in cancer development, with serious challenges in the clinical managements. Breast cancer and brain tumor are an unresolved problem in Science and Medicine. Besides, an early and translatable diagnostic- prognostic-predictive platform, by considering the targets-ID, is required. Diverse TL in two cases affected with astrocytoma with grade IV, revealed to be 12500 and 15000 bp in tumor, and 10000 and 9000 bp at genomic level. Interestingly, TL is declined in the lymph node, i.e., occurrence of evolution. Sub-telomeres (STs) through the cellular journey, are the neighboring destination at genomic and somatic level. The evolutionary pattern of STs has not been, routinely, decoded to the personalized clinical managements. The ST-sequences, are diversely predisposed to variety of environmental factors and play influential role in healthy individuals and the patients. An early detection is available by analysis of the ST- hybridized signals in the biopsy of auxiliary lymph nodes (ALN), and/or by circulating tumor cells (CTCs) into the blood stream. Diverse pattern of signal frequency and intensity in individual chromosomes at both somatic (ALN) and genomic (lymphocytes) levels were remarkable. The most common involved targets included chromosomes 5 and 9, 16 and 19; with diverse intensity at p and q chromosomal arms respectively. These findings have the predisposing, and an initial influence through the patients’ course of disease. ST- signals, by providing the STs-ID, offer periodical and predictive, indices in cancer screening and therapy. Furthermore, the complementary, cell cycle protein expression (PE) including Ki67, cyclin D1, and cyclin E, accelerates an early clinical management through the period of disease based on the CTCs. Epigenetics is the next molecular destination by focusing on the genomic/somatic index, as an evolutionary Epigenetics-ID with its impact on the cancer management. The target panel is Ataxia Telangiectasia mutated gene (ATM) as the molecular marker and an initiator of different cancers. ATM has remarkable roles, including: 1) in DNA double strand break (DSB), 2) to initiate different types of neoplastic disorders, including cancer, and 3), polymorphism, D1853N as a peridisposing marker by initiating the hit process. The influential characteristics include: family history of neoplastic disorders through the pedigree, the key role of ATM promoter methylation, cooperation of ATM/Rb protein expression, D1853N- marker, telomere length (TL) and the clinico-pathological characteristics in different types of brain tumors, and the environmental factors. Interestingly, TL has an independent influence on the progressive cancer evolution. An early detection by CTCs based on the D1853N/Sub-TL/Cell cycle checkpoints based on the PE assay and molecular test facilitate an early detection and therapy, based on the personalized approach. By highlighting the preventive insight in Medicine, a brief record on the “Methylation in Chorionic villus samples (CVS)” with aim of an early detective strategy is provided. All nine CVS samples were methylated for the MCPH1 gene. An early detection is possible either through CV sampling or by the circulating CV cells in the maternal blood. Evolutionary Hit includes: presence of D1853N polymorphism of ATM, as the hit-initiator through an evolutionary and progressive molecular based sequential alterations led to discovery of three-hit hypothesis in a patient affected with astrocytoma. More hits include five, and eight- hit hypotheses in primary breast cancer patients. Such platforms are considered as the individualized model in cancer. The pedigrees and details at the molecular follow-up studies and functional alteration at protein level are available in the provided sections. Novel strategy of Cell cycle phases in breast cancer is the major intersection for cancer therapy. The novel cell cycle hypothesis (CCH) highlights the mosaic based of dual and/or multi-phases, as minor clones at single cell level in the breast cancer (BC) -patients, escorted by the normal cell population. Such mosaicism provided an archetypal, unique diagnostic and therapeutic model, by applying different mosaic patterns (MPs) as well as “G1/S, S/G2 and G1/S/G2, and accompanied by normal phases, as a sole including G1, S, and G2 at the single cells level. Diagnosis is based on the mode of signal copy numbers (SCN) and the related PE. Interestingly MPs were also unmasked in patients with chronic myelogeneous leukemia and other solid tumors. Finally, the predisposing/predictive/prognostic/preventive square provides an innovate CDKs inhibitor-based therapy in BC and other cancers. Personalized base cancer therapy is the confusing procedure and requires the pedigree-based data, personalized, evolutionary based information including molecular and functional at both genomic and somatic, at single cell level. The target territories comprise cell cycle phases, proteins, Telomere length, telomerase, sub-telomere, and Epigenetics. The aim is directing the cell cycle fundamental forces back to normal, by performing: 1) Applying personalized, single cell-based approach, at molecular, functional level, pedigree analysis, and balancing the micro-/macro-environmental factors, including nutrition. 2) Satisfactory high single cell enumeration based on the FISH and protein expression assays; 3) Decoding the required dosage and combined therapeutic regimens accordingly, 4) Unmasking the cell cycle combined (mosaic) phases including different Cyclins; and 5) Bilateral cooperation between Pharmacology, Medicine, and Cancer Genetics/cell biology. Let’s combine the evolutionary based strategy by translating the personalized data at molecular/ Functional/ Informative, and pedigree-based level to the personalized therapy.

Kurzfassung: Postmenopausal women are at greater risk of depression. Depression may negatively affect the quality of life of women. An emotional freedom technique (EFT) is an evidence-based therapy combining cognitive and exposure components with acupressure. This study aimed to evaluate the effect of EFT on depression in postmenopausal women. Methods This was a randomized controlled trial in which 88 women with mild to moderate depression recruited from a menopausal clinic in Ahvaz, Iran, and randomly assigned into two groups of EFT (n=44) and control for sham therapy (n=44). Women in the EFT group received two sessions of training and asked to continue EFT for 8 weeks, one time per day. The Beck Depression Inventory (BDI2) completed by women before and after the intervention. The control group received training on sham acupressure points similar to the intervention group. Data collected using a demographic and BDI2. Women requested to complete the BDI2 before and after the intervention. The independent t-test, chi-square, and ANCOVA were used to analyze data. Results The mean depression score in the intervention group reduced from 20.93 ± 4.6 to 10.96 ± 4.38 in comparison to the control group that reduced from 19.18 ± 2.79 to 17.01 ± 6.05 after intervention (p=0.001). After the 8 week intervention, the frequency of moderate depression decreased from 56.8 to 9.35% in the intervention and from 50 to 29.5% in the control group. In total, 63.4 and 34.15% in the intervention and control groups were free of depression respectively after the intervention (p 〈 0.001). Conclusions The results of this study showed that using EFT for 8 weeks could significantly reduce the mean score of depression in postmenopausal women. Using this method in public health centers for postmenopausal women is recommended.