Non-Weakly Supercyclic Weighted Composition Operators

We give sufficient conditions under which a weighted composition operator on a Hilbert space of analytic functions is not weakly supercyclic. Also, we give some necessary and sufficient conditions for hypercyclicity and supercyclicity of weighted composition operators on the space of analytic functions on the open unit disc

Comparison of Sensitivity and Specificity of Papanicolaou Test, Visual Inspection of Cervix with Acetic Acid (VIA) and Colposcopy in Cervical Cancer Screening in Patients with Secondary Immunodeficiency

Purpose: Cervical cancer is one of the most common problems in public health, especially in developing countries, which is identifiable by screening programs. This study aimed to compare the sensitivity and specificity of Papanicolaou test, visual inspection of cervix with acetic acid and colposcopy in immunodeficient patients. Methods: This examination on the test study was conducted on 135 immunodeficient patients who were referred to Afzalipour Hospital, Kerman, for cervical cancer screening from 2017 to 2018. In the first visit of all the patients, 3 separate tests of Papanicolaou test, VIA and colposcopy were simultaneously performed, and the results were recorded. To analyze the data, descriptive and analytical methods and SPSS software version 20 were used. Results: Most of the cases were between 20 and 40 years old. The most frequency of immunodeficiency was noted among patients with AIDS (19.3). According to the results of the colposcopy, VIA, Papanicolaou test and biopsy, 77, 77.8, 73.3 and 77 of the results were normal, respectively. Most patients were ASCUS in Papanicolaou test, and twenty-one of them were cervical intraepithelial neoplasia 1 (15.6). Sensitivity, specificity, positive and negative predictive values of colposcopy were more than those of VIA and Papanicolaou test (74.1, 92.3, 74.1 and 92.3, respectively). Conclusion: The results of the study showed that colposcopy is an appropriate method for cervical cancer screening in immunodeficient patients. Accordingly, at times when it is not possible to screen with other methods such as Papanicolaou test, this method may be used in preliminary evaluation. © 2021, Association of Gynecologic Oncologists of India

Improved anticancer efficiency of Mitoxantrone by Curcumin loaded PLGA nanoparticles targeted with AS1411 aptamer

Objective(s): Mitoxantrone (MTX) is one of the most commonly used chemotherapeutic agents for treatment of different cancers. However, prolonged treatment with MTX results in unwanted side effects and drug resistant cancer cells. Combination therapies and exploiting of targeted nanoparticles have the potential of improving the efficiency of drug treatment as well as reducing the side effects. Curcumin (CUR) is a biological molecules with anticancer property. In this study, we investigated whether targeted PLGA (Poly Lactic-co-Glycolic Acid)-CUR nanoparticles (NPs) can reinforce the effect of MTX on breast cancer cells. Materials and Methods: PLGA NPs containing CUR targeted with AS1411 aptamer were prepared by single emulsion evaporation method. Physicochemical properties of NPs were investigated. The cytotoxicity of non-targeted and targeted NPs along with MTX was evaluated on MCF7, 4T1 and L929 cell lines. Results: The results showed that PLGA-CUR NPs were synthetized with an average encapsulation efficiency of 66 with a mean size of 18

Evaluation of primary cutaneous malignant melanoma according to Breslow and Clarke pathological indices

Background: Malignant melanoma is one of the fatal cutaneous neoplasms which are curable by early diagnosis. This neoplasm is diagnosed by the biopsy of the suspected lesion. It is essential to classify the tumor based on its histology, thickness, phase of growth, level of invasion, mitotic rate, presence of regression, inflammatory infiltration and ulceration. These descriptions yield some knowledge about the progression of disease and suggest an estimate of the status of the screening system for early diagnosis. Methods: This is a cross-sectional retrospective descriptive study. Pathological slides with diagnosis of malignant melanoma from 1377 to 1379 that present in the pathology department were assessed according to mentioned pathological indices and the 10-year survival calculated in this regard. Results: We assessed 47 cases with mean age of 57.38 (SD=5.85) and the gender distribution was 51.1% male and 42.2% female. More than 42% of cases were in Clarke level I, 2.1% Clarke level II, 6.4% Clarke level III, 40.4% Clarke level IV and 8.5% Clarke level V. Fifty three percent of patients were breslow thickness equal to or less than 0.75 millimeter(mm) , 8.5% between 0.76 to 1.69 mm , 27.7% between 1.7 to 3.6 mm and 10.6% greater than 3.61 mm. Mean breslow thickness show no significant difference between males and females but there is a significant relation between thickness and age of the patients. Mean 10-year survivals of patients were 75% and were greater in females than males. We found a linear relation between patient age and breslow thickness that is calculated by the following equation: Log Breslow thickness (mm) = - 0.625 + 0.016×age (year) Conclusion: Complete recording of clinical and pathological data of patients with malignant melanoma make a proper stream to reach a surveillance system

Targeted delivery of galbanic acid to colon cancer cells by PLGA nanoparticles incorporated into human mesenchymal stem cells

Objective: The aim of this study was to investigate the efficacy of mesenchyme stem cells (MSCs) derived from human adipose tissue (hMSCs) as carriers for delivery of galbanic acid (GBA), a potential anticancer agent, loaded into poly (lactic-co-glycolic acid) (PLGA) nanoparticles (nano-engineered hMSCs) against tumor cells. Materials and Methods: GBA-loaded PLGA nanoparticles (PLGA/GBA) were prepared by single emulsion method and their physicochemical properties were evaluated. Then, PLGA/GBA nanoparticles were incorporated into hMSCs (hMSC/PLGA-GBA) and their migration ability and cytotoxicity against colon cancer cells were investigated. Results: The loading efficiency of PLGA/GBA nanoparticles with average size of 214±30.5 nm into hMSCs, was about 85 and 92 at GBA concentration of 20 and 40 μM, respectively. Nano-engineered hMSCs showed significant higher migration to cancer cells (C26) compared to normal cells (NIH/3T3). Furthermore, nano-engineered hMSCs could effectively induce cell death in C26 cells in comparison with non-engineered hMSCs. Conclusion: hMSCs could be implemented for efficient loading of PLGA/GBA nanoparticles to produce a targeted cellular carrier against cancer cells. Thus, according to minimal toxicity on normal cells, it deserves to be considered as a valuable platform for drug delivery in cancer therapy. © 2022 Mashhad University of Medical Sciences. All rights reserved

Impact of elevated anti-apoptotic MCL-1 and BCL-2 on the development and treatment of MLL-AF9 AML in mice

Many acute myeloid leukaemias (AMLs) express high levels of BCL-2 and MCL-1, especially after therapy. To test the impact of these anti-apoptotic proteins on AML development and treatment, we used haemopoietic reconstitution to generate MLL-AF9 AMLs expressing BCL-2 or Mcl-1 transgenes. AMLs with elevated BCL-2 or MCL-1 had a higher proportion of mature myeloid cells but, like conventional MLL-AF9 AMLs, were readily transplantable. Short-term cell lines established from multiple primary AMLs of each genotype were tested in vitro for susceptibility to chemotherapeutics currently used for treating AML (daunorubicin, etoposide, cytarabine); the proteasome inhibitor bortezomib; CDK7/9 inhibitors; and BH3 mimetics, which bind and inhibit pro-survival proteins. The BH3 mimetics tested, alone and in combination with the other drugs, were: ABT-737 which, like its clinical counterpart navitoclax, targets BCL-2, BCL-XL and BCL-W; BCL-2-specific ABT-199 (venetoclax); BCL-XL-specific A-1331852; and S63845, a new MCL-1-specific BH3 mimetic. As single agents, daunorubicin and bortezomib had the greatest efficacy. Elevated MCL-1 or BCL-2 reduced sensitivity to daunorubicin but, surprisingly, not to bortezomib. MCL-1 markedly enhanced resistance to ABT-737 and ABT-199 but not S63845, and BCL-2 increased resistance to S63845 but not to ABT-737 or ABT-199. Notable synergies were achieved by combining BH3 mimetics with daunorubicin: S63845 increased the sensitivity of both MCL-1 and BCL-2 overexpressing MLL-AF9 AMLs, and ABT-737 aided in killing those overexpressing BCL-2. Synergy between daunorubicin and ABT-199 was also apparent in vivo, although not curative. Impressive synergistic responses were achieved for human MLL-fusion AML cell lines treated with daunorubicin plus either ABT-737, ABT-199 or S63845, and with ABT-199 plus S63845, with or without daunorubicin. Our data suggest that AML patients may benefit from combining conventional cytotoxic drugs with BH3 mimetics targeting BCL-2 or MCL-1 or, if tolerated, both these agents

The relationship between vitamin D receptor (VDR) rs2228570 and rs7975232 genetic variants and the risk of recurrent pregnancy loss

Objective: Recurrent pregnancy loss is one of the most common medical events that occur in the first and second trimesters. Hence, this study aimed to evaluate the relationship between vitamin D receptor (VDR) polymorphisms (rs2228570 and rs7975232) and the risk of recurrent pregnancy loss. The effect of rs2228570 polymorphism on protein stability was also predicted via in silico investigation. Methods: This cross-sectional study was conducted on 52 women with recurrent pregnancy loss and 52 control women without pregnancy loss. We used the polymerase chain reaction technique to amplify the polymorphism regions on the chromosome. The PCR products were cut by FokI and ApaI restriction enzymes and the obtained data were analyzed. Results: Our results showed the case group consisted of 32.7 wild type, 65.4 heterozygote, and 1.9 homozygote genotypes for polymorphism rs7975232.The controls included 48.1 wild type, 42.3 heterozygote, and 9.6 homozygote genotypes. There was a significant difference between polymorphism rs7975232 and recurrent pregnancy loss (P = 0.034). These genotypes for rs2228570 polymorphism were53.8 wild type, 38.5 heterozygote, and 7.7 homozygote. However, the control group included 80.8 wild type, 15.4 heterozygote, and 3.8 homozygote. There was a significant difference between polymorphism rs2228570 and recurrent pregnancy loss (P = 0.014). Conclusion: We found a significant difference between VDR rs2228570 and rs7975232 genetic variants with recurrent pregnancy loss. Protein stability was also decreased following single nucleotide polymorphism in VDR rs2228570. © 202