The generally accepted mechanism of metformin’s effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin’s beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects. The aim of this review is to describe the potential anti-cancer and anti-aging properties of metformin and discuss the possible underlying mechanisms.
B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.
Purpose: The ICRU 89 recommends reporting a set of vaginal dose points for cervical cancer treatments in order to quantify the goodness of implant. This vaginal dose reporting method for combined external beam radiotherapy and brachytherapy has been adopted by the EMBRACE II study protocol. Large variations in dose between patients and centers have been reported. The aim of this study was to determine possible discrepancies with consensus observers from the same institution. Therefore, the inter-and intra-observer variability were analyzed. Material and methods: For five patients, five experienced observers reported dose at the proposed vaginal points twice. The effect of inter-and intra-observer variations on total dose was analyzed by estimating biologically equivalent dose EQD 2 (α/β = 3 Gy). Coefficient of variation (CV) was used to provide a measure of data dispersion as a proportion to the mean. Results: The maximum inter-observer deviation among all patients and all points ranged from 0.5 Gy to 24.1 Gy in EQD 2. The higher inter-observer discrepancies were found at points at 3 o'clock and at 6 o'clock, with respect to ovoids. In case of the maximum intra-observer deviation, it ranged from 0.5 Gy to 14.2 Gy, with higher deviation points at 12 o'clock and 9 o'clock, with respect to ovoids. Conclusions: There is a need to ensure consistency in vaginal points reporting. The impact of the dosimetric inter-and intra-observer variability should also be considered when dealing with dose tolerances and limits due to the potential dose gradient.
Conclusion SMILE adenocarcinoma is a rare entity of cervical tumour, recently described in the literature. Its treatment should not differ from other forms of invasive cervical carcinoma. However, knowledge of this entity and its capacity for invasion and distant metastasis is important to ensure proper management of patients.
Due to the excellent prognosis, some authors affirm that it is possible to perform a conservative surgery in young women who have not fulfilled their reproductive desire, without having repercussions in terms of overall survival.The objective of the study was to know the treatment and the overall survival of the Borderline Ovarian Tumors in young women. Methodology A retrospective cohort study was conducted. The study period was from January 2012 to January 2020. A total of 131 women with Borderline Ovarian Tumors were included in the study. Information was collected about: demographic data, diagnosis, type of surgery performed, disease-free survival, and overall survival. Two cohorts were established: conservative treatment (n = 37) vs radical treatment (n = 94). Result(s)* 131 women with a diagnosis of Borderline Ovarian Tumors were diagnosed, representing 16.7% of all the malignant ovarian tumors within this period (n = 784). 91.5% were diagnosed in Stage I according to the FIGO classification and the most histological line frequent was the mucinous (49.2%). The risk of global relapse was 6.2% and overall survival was 95.4%.Regarding the group of patients who underwent conservative surgery, the risk of relapse was 13.5% (n = 5) compared to 3.2% (n = 3) in the group radical treatment, (p = 0.042).The Overall survival was 100% in women with conservative surgery compared to radical surgery, 94.6%, (p = 0.130). Conclusion* Borderline Ovarian Tumors present excellent prognosis, obtaining great positive results in overall survival regarding the performance of conservative surgery in young women with unfulfilled reproductive desire.
The radioprotective effect ex vivo, in vitro and in vivo of vitamins was reviewed using PubMed and Embase and conducted according to the PRISMA statement. A total of 38 articles were included in this review, which includes the radioprotective effect of vitamins from ex vivo, in vitro and in vivo studies. Vitamins A, C, D and E were used alone, in combination or with other nutritional and non-nutritional compounds. The use of vitamins in natural form or supplementation can be useful to reduce the radiation effect in the body, organs and/or cells. Only four (A, C, D and E) out of thirteen vitamins have been detected with radioprotective properties being mainly vitamin E followed by vitamin C, A and D.
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