51 research outputs found
The Impact of Pamam Dendrimers on Her2-Positive Breast Cancer and the Early Stages of Embryogenesis
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
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PAMAM Dendrimers as Anti-HER2 Positive Breast Cancer Treatment
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
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
Structural and photoluminescence properties of Ni doped CdS nanoparticles synthesis by sol gel method
Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.
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
Microstructural and optical properties of CdS nanoparticles synthesized by sol gel method
Microstructural and optical properties of sol gel synthesized CdS nano particles using CTAB as a surfactant
Caries, oral hygiene status and dates consumption among Saudi female university students
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
Optical properties of cerium oxide (CeO2) nanoparticles synthesized by hydroxide mediated method
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