Common Receptor Research Articles

Inhibitory DNA Aptamer Tools against SOCS3-gp130 Interactions.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a crucial role in transmembrane signal transduction, enabling cells to communicate with the extracellular environment, which requires precise regulation to prevent abnormal signaling outcomes. Within this complex pathway, suppressor of cytokine signaling 3 (SOCS3) acts as a pivotal negative regulator via binding to cytokine receptors. However, our understanding of the regulatory mechanisms governing SOCS3 interactions has been limited by the lack of suitable chemical probes. Aptamers, a notable category of chemical tools, have emerged as a viable avenue for the development of chemical inhibitors. In this study, we successfully identified specific inhibitory aptamers that bind to SOCS3 and effectively disrupt the interaction between SOCS3 and glycoprotein 130, a common cytokine receptor for interleukin-6 and leukemia inhibitory factor, which regulates the survival of normal human endometrial stromal cells. These aptamers not only provide a valuable chemical tool to advance our understanding of the regulatory dynamics of the JAK/STAT signaling pathway by SOCS3 but also hold great promise for the future development of therapeutic interventions.

Transcriptomic analysis of spleen-derived macrophages in response to lipopolysaccharide shows dependency on the MyD88-independent pathway in Chinese giant salamanders (Andrias davidianus)

BackgroundGram-negative bacteria are the main bacterial pathogens infecting Chinese giant salamanders (Andrias davidianus; CGS) in captivity and the wild, causing substantial economic losses in the CGS industry. However, the molecular mechanisms underlying pathogenesis following infection remain unclear.ResultsSpleen-derived macrophages from healthy CGS were isolated, cultured, and identified using density gradient centrifugation and immunofluorescence. A macrophage transcriptome database was established 0, 6, and 12 h post lipopolysaccharide stimulation using RNA-sequencing. In the final database 76,743 unigenes and 4,698 differentially expressed genes (DEGs) were functionally annotated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results showed that DEGs were concentrated in toll-like receptor–nuclear factor kappa B-related immune pathways. Ten DEGs were validated 12 h after lipopolysaccharide (LPS) stimulation. Although the common LPS recognition receptor toll-like receptor 4 was not activated and the key adaptor protein MyD88 showed no significant response, we observed significant up-regulation of the following adaptors: toll/interleukin-1 receptor domain-containing adaptor inducing interferon-β, tumour necrosis factor receptor-associated factor 6, and transforming growth factor-β activated kinase 1, which are located downstream of the non-classical MyD88 pathway.ConclusionsIn contrast to that in other species, macrophage activation in CGS could depend on the non-classical MyD88 pathway in response to bacterial infection. Our study provides insights into the molecular mechanisms regulating CGS antibacterial responses, with implications for disease prevention and understanding immune evolution in amphibians.

Integration of Consensus‐Based Pharmacophore Mapping and Molecular Docking in Sequential Virtual Screening: Toward the Discovery of Novel PI3Kγ Inhibitors

AbstractNumerous research studies have demonstrated the significant correlation of phosphatidylinositol‐3 kinase gamma (PI3Kγ) with the onset and progression of various human diseases, highlighting PI3Kγ as a promising therapeutic target. However, PI3Kγ demonstrates considerable similarity with other isoforms in the PI3K family, presenting significant challenges in the creation of PI3Kγ inhibitors. This study presents an ensemble‐based virtual screening approach to discover novel inhibitors targeting PI3Kγ. Eganelisib (IPI‐549) is the sole selective PI3Kγ inhibitor that has progressed to clinical trials, making it a significant model for the advancement of novel PI3Kγ inhibitors. Initially, common feature pharmacophore and receptor–ligand pharmacophore models were independently developed using IPI‐549 and its potent derivatives, in conjunction with the crystal complex of PI3Kγ/IPI‐549. Both qualitative pharmacophore models proved highly effective at distinguishing between active and inactive compounds. Then, four widely utilized docking programs were chosen for assessment, where the Glide_SP mode demonstrated superior predictive accuracy in sampling ligand conformations during binding, effectively distinguishing between PI3Kγ inhibitors and noninhibitors. Finally, a virtual screening protocol was conducted to screen the ChEMBL database, utilizing similarity search, consensus‐based pharmacophore mapping, and sequential molecular docking. This process resulted in the identification of multiple molecules exhibiting notable promise as potent PI3Kγ inhibitors.

Common epidermal growth factor receptor mutations in north Indian patients with non-small cell lung carcinoma: evidence from real-time polymerase chain reaction.

Lung carcinoma was the ace cause of cancer deaths globally in 2022, with non-small cell lung carcinoma (NSCLC) accounting for 81% of the burden. Due to promising tyrosine kinase inhibitor (TKI) trials, NSCLC patients harboring epidermal growth factor receptor (EGFR) gene mutations are of interest. Our aim was to determine EGFR mutation prevalence in north India and its histologic and demographic correlations. We investigated the frequency of EGFR mutations in 40 patients with histologically confirmed NSCLC using real-time polymerase chain reaction. A 15% mutation frequency was observed in the study sample, involving 32 males and 8 females with a median age of 59 years. Squamous cell carcinoma (SCC) patients had only EXON20 (T790M, exon20 insertion) mutations, while adenocarcinoma patients had mutations in both EXON20 (T790M) and 21 (L858R) with mutation frequencies of 22% and 10%, respectively. 28% of the SCC patients were non-smokers, and 60% of these non-smokers had an EGFR mutation. South Indian and Asian studies have identified EXON19 (19-Del) and EXON21 (L858R) mutations as "common mutations" that account for nearly 80-90% of all mutations and respond well to TKIs. Interestingly, "common mutations" were found seldom in our study population, while the uncommon variants constitute 83% of all mutations, which we assume is due to diverse Indian genetics and ethnicity and co-existing signature mutations that involve the tyrosine kinase domain of EXON20. We suggest future genome-wide association studies to identify plausible genetic polymorphisms responsible for interethnic differences in EGFR mutation, which will contribute to better treatment and prevention of NSCLCs.

Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354.

Type 2 diabetes (T2D) and obesity are prevalent metabolic disorders affecting millions of individuals worldwide. A new effective therapeutic drug called tirzepatide for the treatment of obesity and T2D is a dual agonist of the GIP receptor and GLP-1 receptor. Tirzepatide is clinically more effective than GLP-1 receptor agonists but the reasons why are not well understood. Tirzepatide reportedly stimulates the GIP receptor more potently than the GLP-1 receptor. However, tirzepatide signaling has not been thoroughly investigated at the E354 (wildtype) or Q354 (E354Q) GIP receptor variants. The E354Q variant is associated increased risk of T2D and lower body mass index. To better understand GIP receptor signaling we characterized the activity of endogenous agonists and tirzepatide at both GIP receptor variants. Using Cos7 cells we examined wildtype and E354Q GIP receptor signaling, analyzing cAMP and IP1 accumulation as well as AKT, ERK1/2 and CREB phosphorylation. GIP(1-42) and GIP(1-30)NH2 displayed equipotent effects on these pathways excluding CREB phosphorylation where GIP(1-30)NH2 was more potent than GIP(1-42) at the E354Q GIP receptor. Tirzepatide favored cAMP signaling at both variants. These findings indicate that tirzepatide is a biased agonist towards Gαs signaling and suggests it equally activates the wildtype and E354Q GIP receptor variants. We also observed differences between the pharmacology of the GIP receptor variants with endogenous peptides, which may help to explain differences in phenotype. These findings contribute to a comprehensive understanding of GIP receptor signaling, and will aid development of therapies combating T2D and obesity.

Preformed mincle dimers stabilized by an interchain disulfide bond in the neck region.

The sugar-binding receptor mincle stimulates macrophages when it encounters surface glycans on pathogens, such as trehalose dimycolate glycolipid in the outer membrane of mycobacteria. Binding of oligosaccharide ligands to the extracellular C-type carbohydrate-recognition domain (CRD) in mincle initiates intracellular signaling through the common Fc receptor γ (FcRγ) adapter molecule associated with mincle. One potential mechanism for initiation of signaling involves clustering of receptors, so it is important to understand the oligomeric state of mincle. Affinity purification of mincle from transfected mammalian cells has been used to show that mincle exists as a pre-formed, disulfide-linked dimer. Deletion of cysteine residues and chemical crosslinking further demonstrate that the dimers of mincle are stabilized by a disulfide bond between cysteine residues in the neck sequence that links the CRD to the membrane. In contrast, cysteine residues in the transmembrane region of mincle are not required for dimer formation or association with FcRγ. A protocol has been developed for efficient production of a disulfide-linked extracellular domain fragment of mincle in a bacterial expression system by appending synthetic dimerization domains to guide dimer formation in the absence of the membrane anchor.

The modulation of social and non-social behavior by arginine vasotocin in the common waxbill, Estrilda astrild

The influence of the neuropeptide arginine vasotocin (AVT) has been demonstrated across various species, on an ample range of behaviors, yet the results appear to be highly species-specific. In this study, we aimed to test how AVT influences both social and non-social behaviors in the common waxbill Estrilda astrild, a highly social estrildid finch. Through a within-subject design study, we experimentally manipulated AVT pathways through muscular injections of both an agonist and an antagonist of AVT at different dosages, and performed competition over food tests to assess behavioral changes. Our observations reveal a decrease in birds' movements with both low and high dosages of AVT. Additionally, the higher AVT dosage led to a significant decrease in birds' feeding, aggressive behavior, and allopreening. Conversely, the lower AVT dosage increased the duration of allopreening, which is a proxy for affiliation. The use of Manning Compound, a V1a antagonist, did not produce any changes in behavior, however, the absence of affinity studies for this compound in birds makes it difficult to interpret these results. It is plausible that in common waxbills, AVT V1b or V1a receptors may be involved in regulating movement, feeding, aggressive behavior, and allopreening, rather than V2 AVT receptors.

Molecular Mechanism of pH-Induced Protrusion Configuration Switching in Piscine Betanodavirus Implies a Novel Antiviral Strategy.

Many viruses contain surface spikes or protrusions that are essential for virus entry. These surface structures can thereby be targeted by antiviral drugs to treat viral infections. Nervous necrosis virus (NNV), a simple nonenveloped virus in the genus of betanodavirus, infects fish and damages aquaculture worldwide. NNV has 60 conspicuous surface protrusions, each comprising three protrusion domains (P-domain) of its capsid protein. NNV uses protrusions to bind to common receptors of sialic acids on the host cell surface to initiate its entry via the endocytic pathway. However, structural alterations of NNV in response to acidic conditions encountered during this pathway remain unknown, while detailed interactions of protrusions with receptors are unclear. Here, we used cryo-EM to discover that Grouper NNV protrusions undergo low-pH-induced compaction and resting. NMR and molecular dynamics (MD) simulations were employed to probe the atomic details. A solution structure of the P-domain at pH 7.0 revealed a long flexible loop (amino acids 311-330) and a pocket outlined by this loop. Molecular docking analysis showed that the N-terminal moiety of sialic acid inserted into this pocket to interact with conserved residues inside. MD simulations demonstrated that part of this loop converted to a β-strand under acidic conditions, allowing for P-domain trimerization and compaction. Additionally, a low-pH-favored conformation is attained for the linker connecting the P-domain to the NNV shell, conferring resting protrusions. Our findings uncover novel pH-dependent conformational switching mechanisms underlying NNV protrusion dynamics potentially utilized for facilitating NNV entry, providing new structural insights into complex NNV-host interactions with the identification of putative druggable hotspots on the protrusion.

Cell-Specific Contribution of IL-4 Receptor α Signaling Shapes the Overall Manifestation of Allergic Airway Disease.

IL-4 and IL-13 play a critical role in allergic asthma pathogenesis via their common receptor IL-4Rα. However, the cell-specific role of IL-4Rα in mixed allergen (MA)-induced allergic asthma has remained unclear. Therefore, we aimed to identify the cell-specific contribution of IL-4Rα signaling in the manifestation of various pathological outcomes in mice with allergic airway disease. We compared MA-induced pathological outcomes between hematopoietic progenitor cell (HPC)- or non-HPC-specific IL-4Rα-deficient chimera, myeloid cell-specific IL-4Rα-deficient (LysMcre+/+IL-4Rαfl/fl), and airway epithelial cell-specific IL-4Rα-deficient (CCSP-Cre+/IL-4Rαfl/fl) mice. Chimeric mice with systemic IL-4Rα sufficiency displayed hallmark features of allergic asthma, including eosinophilic and lymphocytic infiltration, type 2 (T-helper type 2) cytokine/chemokine production, IgE production, and lung pathology. These features were markedly reduced in chimeric mice with systemic IL-4Rα deficiency. Non-HPC-specific IL-4Rα-deficient mice displayed typical inflammatory features of allergic asthma but with markedly reduced mucous cell metaplasia (MCM). Deletion of IL-4Rα signaling on airway epithelial cells, a subpopulation within the non-HPC lineage, resulted in almost complete absence of MCM. In contrast, all features of allergic asthma except for MCM and mucin production were mitigated in HPC-specific IL-4Rα-deficient chimeric mice. Deleting IL-4Rα signaling in myeloid cells, a subpopulation within the HPC lineage, significantly alleviated MA-induced allergic airway inflammatory responses, but, similar to the HPC-specific IL-4Rα-deficient chimeric mice, these mice showed significant MCM and mucin production. Our findings demonstrate that the differential allergen responsiveness seen in mice with HPC-specific and non-HPC-specific IL-4Rα deficiency is predominantly driven by the absence of IL-4Rα in myeloid cells and airway epithelial cells, respectively. Our findings also highlight distinct and mutually exclusive roles of IL-4Rα signaling in mediating pathological outcomes within the myeloid and airway epithelial cell compartments.

Study Reveals a New Approach to Treating Tripple Negative Breast Cancer

riple-negative breast cancer (TNBC) makes up about 15% of all breast cancer cases worldwide. It's particularly hard to treat because it lacks the three common receptors that most therapies target. As a result, most TNBC patients undergo high doses of non-targeted chemotherapy, which often leads to severe side effects such as hair loss, nausea, and pain. The spread of TNBC cells to other organs, such as the brain or lungs, is the main cause of death in patients.

Divergent sensory pathways of sneezing and coughing

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

Chemokine Receptor CCR2 Is Protective toward Outer Hair Cells in Chronic Suppurative Otitis Media.

Chronic suppurative otitis media (CSOM) is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. Previously, we discovered that outer hair cell (OHC) loss occurred in the basal turn of the cochlea and that macrophages are the major immune cells associated with OHC loss in CSOM. Macrophage-associated cytokines are upregulated. Specifically, CCL-2, an important member of the MCP family, is elevated over time following middle ear infection. CCR2 is a common receptor of the MCP family and the unique receptor of CCL2. CCR2 knockout mice (CCR2-/-) have been used extensively in studies of monocyte activation in neurodegenerative diseases. In the present study, we investigated the effect of CCR2 deletion on the cochlear immune response and OHC survival in CSOM. The OHC survival rate was 84 ± 12.5% in the basal turn of CCR2+/+ CSOM cochleae, compared with was 63 ± 19.9% in the basal turn of CCR2-/- CSOM cochleae (p ≤ 0.05). Macrophage numbers were significantly reduced in CCR2-/- CSOM cochleae compared with CCR2+/+ CSOM cochleae (p ≤ 0.001). In addition, CCL7 was upregulated, whereas IL-33 was downregulated, in CCR2-/- CSOM cochleae. Finally, the permeability of the blood-labyrinth barrier in the stria vascularis remained unchanged in CCR2-/- CSOM compared with CCR2+/+ CSOM. Taken together, the data suggest that CCR2 plays a protective role through cochlear macrophages in the CSOM cochlea.

An Overview of Familial Hypocalciuric Hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is one of the rare reasons for hypercalcemia. FHH is an autosomal dominant disease that is inheritable. The most common calcium sensitive receptors (CaSR) develop because of the inactivation of. In addition, they also develop due to the function loss of AP2S1 and GNA11. The FHH sickness is characterized by hypercalcemia, hypocalciuria, the regular or increased level of the parathyroid hormone, and normal renal function. The symptoms of hypercalcemia are usually not observed. It is often diagnosed by calculating the calcium/creatine clearance ratio of a 24-hour urine sample, and then genetically looking at it. FHH is usually a benign disorder, and when symptomatic and rarely complications develop, calcimimetics are used or parathyroidectomy can be performed. In conclusion, FHH is a benign and genetically transmitted, moderate cause of hypercalcemia. It is rare and usually asymptomatic.

Distinct, common and synergistic effects of insulin and IGF-1 receptors on healthy murine ageing

ObjectiveReduced IGF-1 signalling is an evolutionarily conserved mediator of longevity, yet the magnitude of this effect is substantially larger in organisms retaining a common insulin and IGF-1 receptor. Whether this reflects the failure to simultaneously reduce IGF-1 and insulin signalling in mammalian model systems remains unexplored, as is the associated impact on markers of healthy ageing. We set out to address these uncertainties. MethodsWe compared the duration of healthy life (healthspan) in male mice with haploinsufficiency of the insulin receptor (IRKO), IGF-1 receptor (IGF-1RKO), or both (DKO), versus wildtype (WT) littermates. Cognitive performance was defined using nesting studies at 3- and 24-months of age. Brain transcriptome was characterised at 3- and 18-months of age using RNA-seq. ResultsHealthspan was longer in DKO versus WT, with IRKO and IGF-1RKO being intermediate. At 2 years of age, DKO also exhibited preserved nesting behaviour in contrast with all other genotypes. Differential insulin sensitivity or weight gain during ageing did not explain the preserved healthspan of DKO, since these were comparable to IRKO littermates. Brain transcriptomics at 18 months of age revealed lower expression of canonical ageing-associated genes in DKO versus WT, although many of these findings were replicated in IRKO versus WT or IGF-1RKO vs WT. ConclusionsReduced insulin and IGF-1 receptor expression have both common and synergistic effects upon elements of healthy mammalian ageing, suggesting future ageing studies should consider targeting both insulin and IGF-1 signalling.

Safety assessment of neurokinin-1 receptor antagonist: real-world adverse event analysis from the FAERS database.

Aprepitant, fosaprepitant, and netupitant are three common neurokinin-1 receptor antagonists (NK-1RAs) used to prevent chemotherapy-induced nausea and vomiting, following highly or moderately emetogenic chemotherapy. Understanding their different adverse event (AE) profiles may help clinicians make appropriate treatment decisions. All data collected from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2023 underwent disproportionality analysis to detect, evaluate, and compare AE signals of the three NK-1RAs. A total of 3,904, 1,123, and 243 AE reports related to aprepitant, fosaprepitant, and netupitant, respectively, were extracted from the FAERS database. Of these, more than 50% of respondents were female, and most of them were aged 45-65years. General disorders and administration-site conditions, and gastrointestinal disorders were the most frequent signals in the system organ class of the three NK-1RA drugs. In addition, aprepitant was strongly associated with joint deposit (ROR = 26.27) and fosaprepitant was closely related to seizure-like phenomena (ROR = 26.90); two preferred terms (PTs) were not mentioned in the manual. Statistically, netupitant was likely to induce death (N = 63, ROR = 8.78, 95% CI: 6.75-11.42). Additionally, neutropenic colitis, colitis, and stomatitis were unique to netupitant. Furthermore, the AE profiles of the three NK-1RA drugs were different by gender. The AE profiles for aprepitant, fosaprepitant, and netupitant were different. In addition to paying attention to common AEs, clinicians need to pay attention to new emerging AEs, such as joint deposit, seizure-like phenomena, neutropenic colitis, colitis, and stomatitis, regarding the three NK-1RA drugs. Furthermore, the AE compositions of the three NK-1RA drugs were different in different genders, and clinicians should take these factors into account when selecting NK-1RAs for CINV treatment.

Are 19del and L858R really different disease entities?

Clinicians have recognized the similarities and differences between the two subtypes of common epidermal growth factor receptor (EGFR) mutations, but actual treatment strategies have not yet changed. The L858R mutation can be understood by considering the pharmacological conformational plasticity of the receptor protein and the presence of other co-occurring mutations, whether subtypes of EGFR or non-EGFR mutations and differences in downstream signaling pathways. As long as we know that molecular differences lead to biological differences, it is a challenge for all of us that our treatment strategies must change.

Immunotherapy in Breast Cancer.

Breast cancer is a disease encompassing a spectrum of molecular subtypes and clinical presentations, each with distinct prognostic implications and treatment responses. Breast cancer has traditionally been considered an immunologically "cold" tumor, unresponsive to immunotherapy. However, clinical trials in recent years have found immunotherapy to be an efficacious therapeutic option for select patients. Breast cancer is categorized into different subtypes ranging from the most common positive hormone receptor (HR+), human epidermal growth factor receptor 2 (HER2)-negative type, to less frequent HER2- positive breast cancer and triple-negative breast cancer (TNBC), highlighting the necessity for tailored treatment strategies aimed at maximizing patient outcomes. Despite notable progress in early detection and new therapeutic modalities, breast cancer remains the second leading cause of cancer death in the USA. Moreover, in recent decades, breast cancer incidence rates have been increasing, especially in women younger than the age of 50. This has prompted the exploration of new therapeutic approaches to address this trend, offering new therapeutic prospects for breast cancer patients. Immunotherapy is a class of therapeutic agents that has revolutionized the treatment landscape of many cancers, namely melanoma, lung cancer, and gastroesophageal cancers, amongst others. Though belatedly, immunotherapy has entered the treatment armamentarium of breast cancer, with the approval of pembrolizumab in combination with chemotherapy in triple-negative breast cancer (TNBC) in the neoadjuvant and advanced settings, thereby paving the path for further research and integration of immune checkpoint inhibitors in other subtypes of breast cancer. Trials exploring various combination therapies to harness the power of immunotherapy in symbiosis with various chemotherapeutic agents are ongoing in hopes of improving response rates and prolonging survival for breast cancer patients. Biomarkers and precise patient selection for the utilization of immunotherapy remain cardinal and are currently under investigation, with some biomarkers showing promise, such as Program Death Lignat-1 (PDL-1) Combined Positive Score, Tumor Mutation Burden (TMB), and Tumor Infiltrating Lymphocytes (TILs). This review will present the current landscape of immunotherapy, particularly checkpoint inhibitors, in different types of breast cancer.

Serum Stabilin1 as a Prognostic Marker in Adults Acute Leukemia Patients

Abstract Background STAB-1 (common lymphatic endothelial and vascular endothelial receptor) was found to be expressed on tumor lymphatic vessels in different malignancies and it is a bad prognostic marker. This study will assess the role of serum stabilin1 (STAB1) as a prognostic marker in adult patients with newly diagnosed acute leukemia and correlate it with the other well established prognostic markers. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Aim of the Work To measure STAB1 expression in patients with AML and patients with ALL and assess its role as a prognostic factor with correlating it with other prognostic factors. Patients and Methods A case control study in Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department for one year on total 75 subjects divided into: 25 patients with newly diagnosed acute myeloid leukemia (AML), 25 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and 25 age and sex matched healthy control subjects. The study population was recruited from Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department. Results There was no significant difference between cases of acute leukemia pts and control group as there was no statistically significant difference between control and patients group regarding sex, age, spleen size, liver size, LDH, CRP, uric acid and ESR of the studied subjects. Our study shows that as regard CBC; there was significant difference between the studied groups as regard leucocytic count, BUT Platelets, and hemoglobin was insignificant, which was also described in the study. Our study showed that there was high statistically significant difference between the acute leukemia patients and the healthy control group as regard sabilin1. Our study shows that the mean serum level of stabilin1 in the patients who didn’t respond to chemotherapy was higher than that of the patients that responded to chemotherapy. Conclusion There was high statistically significant difference between the studied groups as stabilin1. There was significant correlation between stabilin2 and chemotherapy response. Stabilin1 expression levels also identified a new subgroup at a higher risk for relapse and with a poor prognosis in acute leukemia patients. Stabilin 1 can be used as a prognostic factor in patients with acute leukemia.

A heterogeneous tumor immune microenvironment of uncommon epidermal growth factor receptor mutant non-small cell lung cancer.

Common epidermal growth factor receptor (EGFR) mutations are usually not considered for immunotherapy in non-small cell lung cancer (NSCLC) due to poor efficacy. However, whether uncommon EGFR mutations are suitable for immunotherapy has not been thoroughly studied. Thus, we explored the tumor immune microenvironment (TME) features in uncommon EGFR mutant NSCLC. In this study, a total of 41 patients with EGFR mutations were included, the majority (85.4%) of whom were stage I. Among them, 22 patients harbored common mutations, while 19 patients presented with uncommon mutations. Compared with common mutations, uncommon mutations exhibited more infiltrating T cells and fewer M2 macrophages, upregulated expression of antigen processing and a presentation pathway. Unsupervised clustering based on the mIF profile identified two classes with heterogeneous TME in uncommon mutations. Class 1 featured the absence of PD-1+ cytotoxic T cell infiltration, and class 2 displayed a hotter TME because of the downregulated expression of hypoxia (p < 0.001), oxidative phosphorylation (p = 0.009), and transforming growth factor beta signaling (p = 0.01) pathways as well as increased expression of CTLA4 (p = 0.001) and PDCD1 (p = 0.004). The association of CTLA4 and PDCD1 with TME profiles was validated in a TCGA lung adenocarcinoma cohort with uncommon EGFR mutations. Our study reveals the distinct and heterogeneous TME features in uncommon EGFR mutant NSCLC.

Investigation of age and smoking in NSCLC patients with uncommon EGFR mutations.

In addition to the two common epidermal growth factor receptor (EGFR) mutations, there are many uncommon mutations. Due to the high number of uncommon types, as well as the rarity of patients, there is lack of information regarding patient demographics, especially age distribution and smoking status. Against this background, we conducted an analysis to clarify the background of patients with uncommon EGFR mutations, especially considering their age distribution and smoking status. We retrospectively reviewed the medical records of non-small cell lung cancer (NSCLC) patients diagnosed in a multicenter clinical practice from 2002 to 2023. Patients included all cases of non-advanced and advanced NSCLC with uncommon EGFR mutations. Information on 158 patients with uncommon EGFR mutation was collected. Median age was 72 years, with the age distribution showing that most patients were in their 70s. There was a significant difference between the proportion of patients aged up to 59 years and the proportion aged 75 years or older. In 88 patients with a smoking habit history, a significant correlation was found between smoking index and age. Among non-smokers, there was a peak between ages 70 and 74, which was older than the peak among smokers. Even in elderly patients and NSCLC patients with a history of smoking, although it is unclear whether EGFR mutation is common or uncommon, EGFR gene testing should be performed considering the possibility of these patients being EGFR-positive.