Neuroblastoma (NB) remains the critical challenge in pediatric oncology. It has the highest rate of spontaneous regression among all human cancers. Aurora kinase B (AURKB), a crucial regulator of malignant mitosis, is involved in chromosome segregation and cytokinesis. AZD1152-HQPA (Barasertib) is a small selective inhibitor of AURKB activity and currently bears clinical assessment for several malignancies. Studies suggested that microRNAs are involved in the pathobiology and chemoresistance of neuroblastoma. In the present study, we first investigated the restrictive potentials of AZD1152-HQPA on cell viability, colony formation, nucleus morphology, polyploidy, and cell-cycle distribution. We then studied the expressions level of 88 cancer-related miRNAs in untreated and AZD1152-HQPA-treated NB cell line (SK-N-MC) by real-time PCR using miRNA cancer-array system. After normalizing, the fold change of miRNAs was calculated in the AZD1152-HQPA-treated cell as compared to untreated. Our results demonstrate that the inhibition of AURKB by AZD1152-HQPA induced potent antitumor activity, suppressed cell survival, and triggered apoptosis and polyploidy in NB cells. AZD1152-HQPA, at a relevant concentration, modulated a substantial number of cancer-related miRNAs in NB cell. Interestingly, by screening the literature, among the 7 top AZD1152-HQPA-induced upregulated miRNAs (> 3-fold change; P < 0.01), all were potential tumor suppressors associated with cell apoptosis and cycle arrest, as well as inhibition of angiogenesis, invasion, and metastasis, while two downregulated miRNAs were known to have oncogenic function. Taken together, our study showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA.
Breast cancer is one of the most common cancers and is one of the biggest health threats in women around the world. Since the systematic review study in Iran has not been conducted so far, this study was designed to determine the role of family physicians or first-level care physicians in preventing breast cancer at various levels. In this systematic review, we found family physicians could play a significant role in all levels of breast cancer prevention, including roles in education, risk assessment and early detection of cancer, treatment and follow-up of patients with breast cancer and rehabilitation, and help improve quality of life. Survivors and those treated for breast cancer.
Variegate Porphyria (VP) is an inherited rare disorder that is caused by mutations in the protoporphyrinogen oxidase (PPOX) gene. This deficiency is associated with the accumulation of porphyrins and porphyrin precursors in the body, which, in turn, can potentially result in a variety of skin and neurological symptoms. Here, we reported a 7-year-old boy with homozygous VP and novel mutation on PPOX gene. He was admitted with three episodes of generalized tonic-clonic seizure in the last 6 months. He was presented with lesions, hyperpigmentation, fragility, and blistering of sun-exposed skin. The weakness of limbs and brachydactyly were observed. In the follow-up, he had aggressive behavior, learning disability and abdominal pain, particularly around the navel. Eventually, the whole exome sequencing (WES) result reported a novel homozygous pathogenic variant (c.1072G > A p.G358R) in PPOX gene which confirmed the VP. He had been advised to be away from the sun and use sunscreen regularly.
Introduction: In neonates, jaundice is the result of an imbalance between the production and conjugation of bilirubin. Overall, about 60% of full-term neonates experience jaundice in the first week of life. Metabolism of bilirubin and vitamin D occurs in two separate pathways, but because one stage of their production happens in liver, they may affect each other. Objectives: Diagnostic and therapeutic assays are based only on the opinion of obstetricians and gynecologists. The possible results of this study may help to explain preventive methods. In this study, we will evaluate the relationship between serum levels of vitamin D in the mother’s blood and the baby’s umbilical cord with the occurrence of neonatal jaundice. Patients and Methods: This prospective study (cohort) was performed on 110 mothers and their newborns in Firoozabadi hospital in Shahr-e Ray. The sampling method was non-probability convenience. Data including maternal age, nationality, gravidity, gestational age, maternal diseases such as chronic the liver and kidney disease, diabetes mellitus, hypertension and the use of anticonvulsant drugs were obtained from the maternity delivery records and mothers who did not meet the inclusion criteria were excluded at first. Maternal blood samples during labor and neonatal umbilical cord samples were used for assaying the serum levels of 25-hydroxy vitamin D, calcium (Ca) and phosphorus (P), alkaline phosphatase (ALP). All neonates visited for jaundice on days 7 and 14 after birth and tested for bilirubin levels if jaundice was observed. Results: There was no significant difference between neonates with normal and abnormal vitamin D levels in terms of jaundice on day 7 (P=0.571). Additionally, there was not a significant relationship between mothers with normal and abnormal vitamin D levels in terms of jaundice on day 7 in their neonates (P=0.587). However, a statistically significant relationship between normal vitamin D levels in mothers with jaundice in their neonates on day 14 (P=0.003) was detected. There was a significant relationship between normal maternal vitamin D with the incidence of neonatal jaundice on day 14 (relative risk = 0.32). In addition, evaluation of the relationship between normal and abnormal vitamin D levels in neonates with 14th day jaundice revealed no statistically significant relationship between the two groups of normal and abnormal (P=0.1). Mean serum ALP concentration in mothers of neonates who did not develop jaundice was significantly higher than mothers of neonates with severe jaundice (bilirubin >15 mg/ dL) (P=0.02). First minute Apgar score in neonates who had no jaundice or developed mild jaundice was significantly higher than neonates with severe jaundice (bilirubin >15 mg/dL) (P=0.026). Conclusion: Overall, in this study, no significant relationship was observed between neonatal 7th day jaundice with maternal and neonatal vitamin D levels. There was a significant relationship between maternal normal serum vitamin D levels with neonatal 14th day jaundice.
Introduction: Breast cancer is the most common type of cancer found in women and today represents a considerable challenge to public health. Drug resistance is the main challenges for good prognosis of breast cancer patients. Recent clinical trials suggest that targeting of epidermal growth factor receptor (EGFR) could have a beneficent effect on many patients with cancer. Amplification/overexpression of the EGFR gene as a signature genetic abnormality of breast cancer tumors can be a chemo resistant mechanism. Materials and Methods: In this study, we use Erlotinib as an EGFR inhibitor. We evaluate the effects of this drug on metabolic activity, viability, colony formation potential and migration of BC cell lines, MDA-MB-231, SK-BR-3 and BT-474. Results: Our results showed that Erlotinib reduced metabolic activity, cell proliferation, and colony forming fraction in treated BC cell lines. We also found that wound-healing rate was decreased after treatment. Conclusions: Present study uncovered a mechanism whereby EGFR inhibition overcomes the resistance of BC cells. The Erlotinib significantly interfere with survival and migration of treated BC cell lines. Taken together, targeted therapies are going to enhance the efficacy of anti-cancer treatment.
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