51 research outputs found

    The Impact of Pamam Dendrimers on Her2-Positive Breast Cancer and the Early Stages of Embryogenesis

    No full text
    Poly (amidoamine) (PAMAM) dendrimers are widely used in drug delivery systems and gene transfection as drug carriers. They also exert several biological effects including modulating gene expression and interfering with transactivation of epidermal growth factor receptors, EGFR and HER2. HER2 is a major oncogene driving the proliferation of HER2-positive breast cancer cells and represents an important drug target in the treatment of breast cancer. However, it is not known whether PAMAMs can inhibit the activation of HER2 in breast carcinogenesis and whether this effect depends on the physicochemical properties of these polymers. In this study, we explored the anti-cancer effects of different generations and surface chemistries of PAMAMs on HER2-positive breast cancer cell lines. Additionally, the outcome of PAMAM dendrimers was examined in the early stages of embryogenesis. The anti-cancer effects of PAMAMs including cell viability, colony formation, and apoptosis were studied in HER2-positive breast cancer cells; SK-BR3 and ZR-75. Additionally, the effects of PAMAMs on angiogenesis and embryogenesis were investigated using a chicken embryo model. The underlying mechanisms of action were explored by RT-PCR and Western blotting analysis. PAMAMs exhibited significant anti-cancer effects that were more pronounced with cationic (-NH2) dendrimers, compared to neutral (-OH) or anionic (-COOH) and were greater in cationic G6 compared to cationic G4. Cationic G6 PAMAMs significantly decreased the viability of HER2-positive breast cancer cell lines down to 5.1% in SK-BR3 and to 5.7% in ZR-75 cells (p<0.001), in a dose and time-dependent fashion. Cationic polymers also resulted in cell cycle deregulation as well as inhibiting colony formation in soft agar compared to controls and to other PAMAMs studied (p<0.05). Cationic PAMAMs inhibited the phosphorylation of ErbB2, EGFR, and ERK1/2 and upregulated JNK1/2/3, similar to lapatinib, a clinically used inhibitor of HER2 receptor phosphorylation. Cationic PAMAMs also inhibited the angiogenesis of the chorioallantoic membrane (CAM) of the chicken embryo model. However, they exhibited substantial toxicity to the embryos at the early stages of their normal development. The exhibited anti-HER2 breast cancer effects of PAMAMs were generation and surface chemistry-dependent, and might be investigated further for the potential treatment of this cancer in the clini

    Suggesting new words to extract keywords from title and abstract

    No full text
    When talking about the fundamentals of writing research papers, we find that keywords are still present in most research papers, but that does not mean that they exist in all of them, we can find papers that do not contain keywords. Keywords are those words or phrases that accurately reflect the content of the research paper. Keywords are an exact abbreviation of what the research carries in its content. The right keywords may increase the chance of finding the article or research paper and chances of reaching more people who should reach them. The importance of keywords and the essence of the research and address is mainly to attract these highly specialized and highly influential writers in their fields and who specialize in reading what holds the appropriate characteristics but they do not read and cannot read everything. In this paper, we extract new keywords by suggesting a set of words, these words were suggested according to the many mentioned in the researches with multiple disciplines in the field of computer. In our system, we take a number of words (as many as specified in the program) that come before the proposed words and consider it as new keywords. This system proved to be effective in finding keywords that correspond to some extent with the keywords developed by the author in his research

    PAMAM Dendrimers as Anti-HER2 Positive Breast Cancer Treatment

    No full text
    Background: Poly (amidoamine) dendrimers (PAMAMs) are widely used in drug delivery systems and gene transfection as drug carriers. They also exert several biological effects like modulating gene expression, particularly EGFR (ErbB1) signaling pathway, which raises the question of whether these polymers can also inhibit the phosphorylation of HER2 (ErbB2) in breast cancer. However, this area haven't been investigated before. Methods: In this study, we evaluated the anticancer effects of different generations and surface chemistries of PAMAMs on HER2 positive breast cancer cells (SkBr3 and ZR-75 cell lines). Cell viability and morphological changes were evaluated upon treatment with PAMAMs. Also, their effect on colony formation in soft agar was assessed. Additionally, western blot was performed to understand the underlying mechanisms of action. Results: PAMAMs anticancer effects were found to follow a specific trend, as they were more significant in cationic polymers and in higher generations. Cationic PAMAMs reduced cell viability of HER2 positive breast cancer cells up to 5.1% in SkBr3 and to 28% in ZR-75 (p<0.001), in a dose and time-dependent manner. Cationic polymers also resulted in changing the morphology in the examined cell lines, as well as inhibiting colony formation in soft agar compared to controls (p<0.001). The mechanism of action was found to be mediated by inhibiting the phosphorylation of erbB2 and JNK1/2/3. Conclusion: These anticancer effects of PAMAM dendrimers make them promising molecules, which can add benefit to current anti-HER2 treatments and be employed successfully in different biomedical application

    Metformin and HER2-positive breast cancer: Mechanisms and therapeutic implications

    No full text
    Due to the strong association between diabetes and cancer incidents, several anti-diabetic drugs, including metformin, have been examined for their anticancer activity. Metformin is a biguanide antihyperglycemic agent used as a first-line drug for type II diabetes mellitus. It exhibits anticancer activity by impacting different molecular pathways, such as AMP-inducible protein kinase (AMPK)-dependent and AMPK-independent pathways. Additionally, Metformin indirectly inhibits IGF-1R signaling, which is highly activated in breast malignancy. On the other hand, breast cancer is one of the major causes of cancer-related morbidity and mortality worldwide, where the human epidermal growth factor receptor-positive (HER2-positive) subtype is one of the most aggressive ones with a high rate of lymph node metastasis. In this review, we summarize the association between diabetes and human cancer, listing recent evidence of metformin's anticancer activity. A special focus is dedicated to HER2-positive breast cancer with regards to the interaction between HER2 and IGF-1R. Then, we discuss combination therapy strategies of metformin and other anti-diabetic drugs in HER2-positive breast cancer

    Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.

    No full text
    Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2 breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2 breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2 breast cancer management, we also review mathematical models pertaining to the dynamics of HER2 breast cancer and immune checkpoint inhibitors

    Caries, oral hygiene status and dates consumption among Saudi female university students

    No full text
    Authors: Al Essa, Noura A., Al Mutairi, Manal A., Al Ohali, Hadeel M. From Intern, King Saud University College of Dentistry Authors: El Hejazi, Ahmed, Associate Professor, RDS Department, Operative Dentistry Division, King Saud University College of Dentistry, Riyadh. Author: Chohan, Arham, Lecturer, PDS Department, Pediatric Dentistry Division, King Saud University College of Dentistry, RiyadhThe objectives of the present study were to determine the caries experience, oral hygiene status and consumption of dates among Saudi female University students. A total of 406 female University students were examined for dental caries and oral hygiene. The information about oral hygiene practices and consumption of dates was obtained through a selfadministered questionnaire. The mean DMFT was 10.01 (SD 4.71) with a decay (D) component of 5.87 (SD 4.28), missing (M) component of 0.83 (SD 1.44) and filled component of 3.31 (SD 3.92). There was significant (p< .05) difference observed between the mean DMFT scores of the students from various age groups. Only one-fourth (25.6%) of the students had good oral hygiene. A positive correlation (p< .0001) was exhibited between the mean DMFT scores and oral hygiene. Almost all (98.0%) students used brush to clean their teeth. A majority of the students were cleaning their teeth twice (47.0%) or thrice (22.4%) daily and only about one in ten (12.3%) students’ used miswak to clean their teeth. More than three-fourth (81.0%) students were eating dates and about one-fourth (24.4%) of the students were eating 5-10 dates per day. No significant (p> .05) correlation was observed between caries and dates consumption. It was concluded that the caries prevalence and severity was very high. Only small percentage of the students had good oral hygiene and eight in every ten students was eating dates daily
    corecore