Glioblastoma is remarkably periodic primary brain tumor, characterizing an eminently heterogeneous pattern of neoplasms that are utmost destructive and threatening cancers.
An enhanced and upgraded knowledge of the various molecular pathways that cause malignant changes in glioblastoma has resulted in advancement of numerous biomarkers and the interpretation of various agents that pointedly target tumor cells and microenvironment. In this review, literature or information on various targeted therapy for glioblastoma is discussed. English language articles were scrutinized in plentiful directory or databases like PubMed, ScienceDirect, Web of Sciences, Google Scholar, and Scopus. The important keywords used for searching databases are “Glioblastoma,” “Targeted therapy in glioblastoma,” “Therapeutic drugs in glioblastoma,” and “Molecular targets in glioblastoma.”
Matrix metalloproteinase-9 (MMP-9) is one of the widely studied enzymes of the extracellular matrix which can degrade various matrix biomolecules. The gene coding for this enzyme has been found to be associated with various multifactorial diseases, including cancer. More specifically, the expression of MMP-9 and polymorphisms of its gene have been found to be correlated with the formation and the invasiveness of different types of cancer. Hence, the latter gene can potentially be used both as a clinical genetic marker and a possible target in anticancer therapy. The present minireview explores the role of the MMP-9 gene in the process of tumor formation, growth, and metastasis and presents an overview of the polymorphisms of the gene associated with cancer as well as its regulation mechanisms, to provide an insight into the potential clinical applications. Nevertheless, further clinical trials and research are still required to reach more valuable conclusions for the clinical implications of the recent findings.
Breast cancer is a multifactor, multistage, and heterogeneous disease. Systemic treatment of breast cancer has changed significantly over the last decade. With a better knowledge of the pathogenesis, researchers and scientists have discovered numerous signaling pathways and synonymous therapeutic targets in breast cancer. Because of the molecular nature of breast cancer, which makes it difficult to understand, previous attempts to treat or prevent it have failed. However, recent decades have provided effective therapeutic targets for treatment. In this review, literature or information on various targeted therapy for breast cancer is discussed. English language articles were explored in numerous directory or databases like PubMed, Web of Sciences, Google Scholar, ScienceDirect, and Scopus. The important keywords used for searching databases are “Breast cancer,” “Targeted therapy in breast cancer,” “Therapeutic drugs in breast cancer,” and “Molecular targets in breast cancer.”
Early detection of urothelial cancer offers the potential for effective and successful treatment. Despite previous efforts, currently, there is not a well-validated, recommended screening program in any country. This integrative, literature-based review provides details on how recent molecular advances may further advance early tumor detection. The minimally invasive liquid biopsy is capable of identifying tumor material in human fluid samples from asymptomatic individuals. Circulating tumor biomarkers (cfDNA, exosomes, etc.) are very promising and are attracting the interest of numerous studies for the diagnosis of early-stage cancer. However, this approach definitely needs to be refined before clinical implementation. Nevertheless, despite the variety of current obstacles that require further research, the prospect of identifying urothelial carcinoma by a single urine or blood test seems truly intriguing.
Acute myeloid leukemia (AML) is an immensely heterogeneous disease characterized by the clonal growth of promyelocytes or myeloblasts in bone marrow as well as in peripheral blood or tissue.
Enhancement in the knowledge of the molecular biology of cancer and recognition of intermittent mutations in AML contribute to favorable circumstances to establish targeted therapies and enhance the clinical outcome. There is high interest in the development of therapies that target definitive abnormalities in AML while eradicating leukemia-initiating cells. In recent years, there has been a better knowledge of the molecular abnormalities that lead to the progression of AML, and the application of new methods in molecular biology techniques has increased that facilitating the advancement of investigational drugs.
In this review, literature or information on various gene mutations for AML is discussed. English language articles were scrutinized in plentiful directories or databases like PubMed, Science Direct, Web of Sciences, Google Scholar, and Scopus. The important keywords used for searching databases is “Acute myeloid leukemia”, “Gene mutation in Acute myeloid leukemia”, “Genetic alteration in Acute myeloid leukemia,” and “Genetic abnormalities in Acute myeloid leukemia.”
Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The KIF14 and MDM4/PI3KC2β and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments. Aneuploidy was assessed by enumerating the copy numbers of chromosomes 8 and 12. Replication timing and aneuploidy were detected cytogenetically using multicolors fluorescence in situ hybridization assay applied in 135 EFT. Patients with trisomy 8 presented an association with an asynchronous replication pattern (SD) of MDM4/PI3KC2β genes (p = 0.013). Trisomy 12 was associated with a synchronous pattern (DD) of KIF14 probe signals (p = 0.04). The DD synchronous replication pattern of KIF14 showed a correlation with age (p < 0.0001), and the SS synchronous replication pattern of the same locus showed a correlation with lung metastatic (p = 0.012). The subgroup of patients presenting with multiplet signals of MDM4/PI3KC2β showed an association with treatment response (p = 0.045) and age (p = 0.033). Replication pattern of KIF14 may, significantly, be associated with chromosomal instability as MDM4/PI3KC2β may be a considerably new marker of poor treatment response in EFT patients.
Idiopathic toe walking (ITW) describes a condition affecting approximately 4.5% of children. Toe walking is an accompanying symptom for many hereditary disorders. This retrospective study uses next-generation sequencing-panel-diagnosis to investigate the feasibility of genetic testing to research the possible genetic causes of ITW and for differential diagnosis.
Data were taken from our inhouse database, the minimum age for participants was 3 years. Underlying neurological or orthopaedic conditions were tested for and ruled out prior to diagnosing ITW. Patients, who experienced complications before, during or immediately after birth, children with autism, and patients toe walking less than 50% of the time were excluded.
Eighty-nine patients were included in the study, in which 66 (74.2%) patients were boys and 23 (25.8%) girls. Mean age at testing was 7.7 years (range: 3-17 years). Fifteen of the 89 patients included in the study (16.9%) had a genetic variant identified as likely pathogenic or pathogenic by the genetics laboratory. Additionally, we found 129 variants of uncertain significance. About 65.2% of patients showed a pes cavus foot deformity, 27% of patients reportedly had at least one relative who also displayed the gait anomaly, and 37.1% had problems with their speech development.
Despite the limitations of the sample size and the scope of our genetic testing targets, our results indicate that research into the genetic causes of ITW could better our understanding of the causes of ITW in otherwise healthy children, to help develop novel methods to detect serious conditions early. ITW could be an early onset symptom for further hereditary conditions.
Background and Aim Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can—via molecular mimicry and the consequent cross-reactivity—also hit human proteins involved in infantile diseases.
Methods Human proteins that—if altered—associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena.
Results Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible.
Conclusion Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela.
Objective In this study, we aimed to evaluate the efficacy and safety of combination therapy, consisting of intravenous immunoglobulin (IVIg) and corticosteroids, in comparison to respective monotherapies in the treatment of relapsed immune thrombocytopenia (ITP) in adults.
Methods A retrospective analysis of clinical data was conducted on 205 adult patients with relapsed ITP who received first-line combination therapy or monotherapy in multiple centers across China from January 2010 to December 2022. The study evaluated the patients' clinical characteristics, efficacy, and safety.
Results We found that the proportion of patients with platelet counts in complete response was significantly higher in the combination group (71.83%) compared with the IVIg group (43.48%) and the corticosteroids group (23.08%). The mean PLTmax in the combination group (178 × 109/L) was significantly higher than that in the IVIg group (109 × 109/L) and the corticosteroids group (76 × 109/L). Additionally, the average time for platelet counts to reach 30 × 109/L, 50 × 109/L, and 100 × 109/L in the combination group was significantly shorter than in the monotherapy groups. The proportion curves for reaching these platelet counts during treatment were also significantly different from those in the monotherapy groups. However, there were no significant differences in the effective rate, clinical characteristics, and adverse events among the three groups.
Conclusion We concluded that combining IVIg and corticosteroids was a more effective and faster treatment for relapsed ITP in adults than using either therapy alone. The findings of this study provided clinical evidence and reference for the use of first-line combination therapy in the treatment of relapsed ITP in adults.
This study aimed to define the copy numbers of SMN1 and SMN2 genes and the diagnosis rate and carrier frequency of spinal muscular atrophy (SMA) in the Thrace region of Turkey. In this study, the frequency of deletions in exons 7 and 8 in the SMN1 gene and SMN2 copy numbers were investigated. A total of 133 cases with the preliminary diagnosis of SMA and 113 cases with the suspicion of being an SMA carrier from independent families were analyzed by multiplex ligation-dependent probe amplification method for SMN1 and SMN2 gene copy numbers.
SMN1 homozygous deletions were detected in 34 patients (25.5%) of 133 cases with the suspicion of SMA. Cases diagnosed with SMA type I was 41.17% (14/34), 29.4% (10/34) with type II, 26.4% (9/34) with type III, and 2.94% (1/34) with type IV. The SMA carrier rate was 46.01% in 113 cases. In 34 SMA cases, SMN2 copy numbers were: two copies - 28 cases (82.3%), three copies - 6 cases (17.6%). SMN2 homozygous deletions were detected in 15% (17/113) of carrier analysis cases. The consanguinity rate of the parents was 23.5% in SMA diagnosed cases. In this study, we had a 25.5% of SMA diagnosis rate and 46% SMA carrier frequency. The current study also showed the relatively low consanguinity rate of the Thrace region, with 23.5% according to the east of Turkey.
The molecular diagnostics industry has historically relied on sanitized clinical trials and commoditized data sources to inform its biomarker discovery and validation process—an under-substantiated approach that was ultra-expensive, resource-consuming and did not reflect how representative a new biomarker would be in broader patient populations. In an effort to gain more accurate insight into the patient experience and bring innovative biomarkers to market more efficiently and accurately, the industry is now expanding into extended real-world data. To access the needed breadth and depth of patient-centric data, diagnostic companies must collaborate with a healthcare data analytics partner that has three key assets: (i) a broad and deep megadata with metadata, (ii) a data-rich provider network, and (iii) an outcomes-improvement engine to support the next generation of molecular diagnostics (Dx) and therapeutics (Rx) development.
Congenital disorder of glycosylation (CDG) is an autosomal recessively inherited disorder. Hypotonia, stroke-like episodes, and peripheral neuropathy are also associated with the condition that typically develops during infancy. The patient, a 12-year-old girl born to healthy consanguineous parents, was diagnosed with cerebral palsy as a child. The affected patient has hypotonia, inadequate speech, strabismus, and developmental delay with mild mental retardation, which are key symptoms of CDG. Whole-exome sequencing (WES) identified the known missense pathogenic variant PMM2 c.710 C > T, p.T237M in the patient coding for the phosphomannomutase 2 (PMM2) confirming molecular testing of CDG. The patient's parents carried heterozygous PMM2 c.710 C > T variants. This study highlights the importance of WES in patients with a developmental disability or other neurological conditions, which is also useful in screening risk factors in couples with infertility or miscarriage issues.
Background Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age. The primary objective of the study was to assess the association of IL-1RA gene polymorphism in children aged 2 to 59 months with CAP and the secondary objective was to assess the association of gene polymorphism with mortality among hospitalized CAP cases.
Study Design This case-control study was conducted in a tertiary teaching institute in Northern India. Hospitalized children aged 2 to 59 months with World Health Organization-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital. Genotyping was done using polymerase chain reaction to analyze the variable number of tandem repeats of IL-1RA gene polymorphism.
Result From October 2019 to October 2021, 330 cases (123, 37.27% female), and 330 controls (151, 45.75% female) were recruited. Genotype A2/A2 of the IL-1RA gene was found to be associated with the increased risk for CAP children with adjusted odds ratio (AOR) of 12.24 (95% confidence interval [CI] 5.21-28.7, p < 0.001). A2 and A4 alleles were also found to be at risk for CAP. A1/A2 genotype was found to be protective for CAP with an AOR of 0.29 (95% CI 0.19-19.0.45). The genotype A2/A2 and A2 allele of IL-1RA gene was associated with child mortality with CAP cases.
Conclusion In IL1RA gene, A2/A2 genotype and A2 allele were associated with increased risk of CAP and A1/A2 were found to be protective for CAP. The genotype A2/A2 and A2 was associated with CAP mortality.
This study analyzed KISS1 and its receptor KISSR for peptide sharing with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was found that SARS-CoV-2 shares numerous minimal immune pentapeptide determinants with KISSR only. The peptide sharing has a high immunologic potential since almost all the common peptides are present in 101 SARS-CoV-2-derived immunoreactive epitopes. Data are in favor of configuring molecular mimicry as an epigenetic factor that can alter KISSR thus causing the hypogonadotropic hypogonadism syndrome with which altered KISSR associates.