Implications For Treatment Research Articles

Melatonin-induced upregulation of telomerase activity interferes with macrophage mitochondrial metabolism and suppresses NLRP3 inflammasome activation in the treatment of Pneumonia

ObjectiveThis study aims to investigate the effects of melatonin-induced upregulation of telomerase activity on mitochondrial metabolism and NLRP3 inflammasome activation in macrophages, with the ultimate goal of elucidating potential therapeutic implications for pneumonia treatment. Materials and methodsMacrophages were treated with melatonin to assess its impact on telomerase activity. Mitochondrial function was evaluated through the measurement of reactive oxygen species (ROS) levels and cellular energy production. NLRP3 inflammasome activation was assessed by examining the production of inflammatory cytokines, such as interleukin-1β (IL-1β). The expression levels of key proteins involved in mitochondrial metabolism and NLRP3 inflammasome signaling were also analyzed. ResultsOur findings demonstrated that melatonin treatment significantly upregulated telomerase activity in macrophages. This was associated with a reduction in ROS levels and enhanced cellular energy production, indicating improved mitochondrial function. Moreover, melatonin treatment suppressed NLRP3 inflammasome activation, resulting in reduced secretion of IL-1β. The expression levels of proteins involved in mitochondrial metabolism and NLRP3 inflammasome signaling were modulated by melatonin. ConclusionThese results suggest that melatonin-induced upregulation of telomerase activity can interfere with mitochondrial metabolism and inhibit NLRP3 inflammasome activation in macrophages. This indicates a potential therapeutic role for melatonin in the treatment of pneumonia. Understanding the molecular mechanisms underlying these effects may lead to the development of novel therapeutic strategies targeting mitochondria and NLRP3 inflammasome activation for the management of pneumonia. Further investigations are warranted to fully uncover the therapeutic potential of melatonin and its implications for pneumonia treatment.

Enuresis and psychological concerns in a foster care population.

This study examined the relationships between psychological factors and enuresis in a population of children placed in foster care in New York State. Participants included 228 children (55% female, 45% male; 64% Black, 19% Hispanic/Latino, 7% White, 1% Asian, 3% multiracial) who were recently placed in care and had obtained an intake and psychological and/or psychiatric evaluation at the time of placement, which included foster parent or caregiver report about enuresis concerns at the time of assessment. This study conducted a review of those for whom enuresis concerns were identified and examined the prevalence of social-emotional concerns among this group when compared with the nonenuresis sample and the general population. The results showed that children in this foster care sample experience enuresis at a higher rate than children in the general population. Participants with enuresis tended to score lower on measures of adaptive and socialization skills and higher on measures of anxiety, depression, and posttraumatic stress. The findings have implications for treatment, which should include both behavioral and psychological interventions. Limitations, including self-reporting of enuresis and sample convenience, are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function.

The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and Olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

Alternative Lymphatic Drainage Pathways in the Trunk Following Oncologic Therapy.

Anatomic and functional descriptions of trunk and breast lymphedema following breast cancer treatment are emerging as indicators of lymphatic dysfunction. Indocyanine green-lymphangiography has been instrumental in characterizing this dysfunction in the extremity and can be applied to other regions. Previous work has established a validated Pittsburgh Trunk Lymphedema Staging System to characterize such affected areas. This study aims to identify risk and protective factors for the development of truncal and upper extremity lymphedema using alternative lymphatic drainage, providing implications for medical and surgical treatment. Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between 12/2014 and 3/2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated for axillary and inguinal lymphatic flow. A linear-weighted Cohen's kappa statistic was calculated comparing alternative drainage evaluation. Binomial regression was used to compute relative risks (RRs). Significance was assessed at alpha = 0.05. Eighty-six sides (46 patients) were included. Twelve sides underwent no treatment and were considered controls. Eighty-eight percent of the noncontrols had alternative lymphatic flow to the ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen's kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of developing truncal lymphedema [RR 0.78, confidence interval (CI) 0.63-0.97, P = 0.04; RR 0.32, CI 0.13-0.79, P = 0.01, respectively]. Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, P = 0.02; RR 1.92, CI 1.09-3.39, P = 0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection were associated with increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, P = 0.01; RR 2.83, CI 1.23-6.52, P = 0.01, respectively). Building upon previous work, this study shows risk and protective factors for the development of truncal and upper extremity lymphedema. Most prevalent alternative channels drain to the ipsilateral axilla and groin. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of truncal lymphedema. Patients with radiation, axillary dissection, and contralateral axillary drainage were associated with increased risk of upper extremity lymphedema. These findings have important clinical implications for postoperative manual lymphatic drainage and for determining eligibility for lymphovenous bypass surgery.

Sociotropy and video game playing: Massively multiplayer online role-playing games versus other games

IntroductionInternet Gaming Disorder (IGD) is associated with several psychiatric disorders. Previous research on IGD has predominantly focused on Massively Multiplayer Online Role-playing Games (MMORPGs), considered to be pro-social games as they foster interpersonal relationships necessary for in-game progress. Sociotropy is a personality trait characterized by a cognitive approach to dealing with interpersonal relationships. Individuals with high sociotropy have a strong desire for approval from others. Beck's cognitive theory of depression posits that high sociotropy can lead to depressive symptoms when faced with interpersonal stress. We used the I-PACE model to account for the consequences of distal factors such as sociotropy on the development and maintenance of IGD. The aim of this study was therefore to compare MMORPG players with players of other game genres in terms of sociotropy, social anxiety and depression. We hypothesized that sociotropy could serve as a predictor of IGD, particularly among MMORPG players. MethodsA total of 233 French videogame players recruited from specialized internet gaming forums participated in the study via questionnaires. Different scales were used to assess depression and social anxiety symptoms, IGD intensity, and sociotropy and autonomy. Results & discussionMMORPG players reported higher psychological distress than players of other game genres. For all players, sociotropy, rather than autonomy, was found to be a predictor of social anxiety symptoms and IGD intensity. Sociotropy and depression explained IGD intensity only for MMORPG players and not for players of other game genres. The social dimension appears to be more prominent among MMORPG players and could be one of the main personality traits predicting this specific internet gaming disorder. The treatment implications for internet gaming disorder are discussed.

Exploring the Intersection of Narcolepsy and Attention Deficit Hyperactivity Disorder: Similarities, Differences, and Clinical Implications

Narcolepsy and attention deficit hyperactivity disorder (ADHD) are distinct neurobiological conditions characterized by overlapping symptoms, including excessive daytime sleepiness and cognitive dysfunction. Despite their differences in etiology and pathophysiology, recent studies have highlighted a potential association between the two disorders, with a significant prevalence of ADHD symptoms observed in narcolepsy patients. This narrative review explores the similarities and differences between narcolepsy and ADHD, focusing on their shared symptomatology, neurobiological mechanisms, challenges in diagnosis, and treatment implications. While both disorders exhibit disruptions in dopaminergic and noradrenergic neurotransmitter systems, differential diagnosis remains challenging due to overlapping clinical presentations. Polysomnography findings, such as appearance of sleep onset rapid eye movements in narcolepsy patients, provide important distinctions that enable accurate diagnosis. Treatment strategies often involve stimulant medications for symptom management; however, nonpharmacological interventions, such as cognitive behavioral therapy, have been shown to have the potential to improve patient outcomes. Clinicians must consider the possibility of coexisting narcolepsy in ADHD patients and vice versa to ensure appropriate treatment selection and optimal patient care. Further research is needed to refine diagnostic criteria, elucidate the complex interplay between the two disorders, and develop personalized therapeutic approaches. A multidisciplinary approach involving sleep specialists, neurologists, psychiatrists, and psychologists is essential to address the diverse biopsychosocial needs of patients with concurrent narcolepsy and ADHD.

Insight into Insulin-like Growth Factor-1 Receptor (IGF-1R) gene mutations: Implications for growth disorders and treatment: A review of the literature and case report

Background: Insulin-like Growth Factor -1 Receptor (IGF-1R) and its ligand, IGF-1, are crucial for human tissue growth and development. Mutations in IGF-1R and, to a lesser extent, IGF-1 genes lead to diverse growth disorders, characterized by intrauterine growth retardation and postnatal growth challenges. Case report: We present a case of a 6-year-old girl with speech and mild cognitive delays, exhibiting normal motor skills, no neurological issues, and standard vital signs. Her growth parameters indicated significant retardation, with a height standard deviation score (Ht-SDS) of -2 and an IGF-1 level of +1.8 SDS, normal thyroid function and delayed bone age. Genetic analysis identified a 3335 mbp interstitial loss in 15q26.1, encompassing the IGF-1R gene, critical for growth and development. Literature review: Analysis of 34 papers provided insight into the genetic complexities of IGF-1R and IGF-1 mutations. Studies ranged from familial cases to cohort studies, uncovering mutations including missense mutations, deletions, and copy number variations (CNVs), each associated with unique growth disorder phenotypes. Advances in diagnostic techniques like multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing (WES) have been pivotal in identifying these mutations, facilitating more targeted management approaches. Conclusions: This case and review of literature underscore the importance of an integrated genetic, endocrine, and developmental approach in managing growth hormone deficiency (GHD) and IGF-1 resistance. The variability in growth disorders and response to therapy highlights the need for personalized treatment plans, informed by genetic insights, to optimize outcomes for patients with these complex conditions.

Exosomal miR-1470 is a diagnostic biomarker and promotes cell proliferation and metastasis in colorectal cancer.

In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC. We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR-1470 in healthy volunteers and CRC patients were analyzed using qRT-PCR. To evaluate the diagnostic potential of the selected miR-1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR-1470 in CRC cell lines, we detected the miR-1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR-1470 in SW480, HCT-116 cells. Exosomal miR-1470 exhibited significant up-regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876-0.7920) for exosomal miR-1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR-1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR-1470 in CRC cell lines. CCK8 proliferation assay showed that miR-1470 promoted the proliferation ability of SW480 and HCT-116 cells. Transwell assay showed that miR-1470 promoted the migration and invasion ability of SW480 and HCT-116 cells. This suggested that non-invasive diagnosis of CRC is possible by detecting the level of miR-1470 in exosomes, which has important implications for early detection and treatment of this disease.

Prismatic adaptation coupled with cognitive training as novel treatment for developmental dyslexia: a randomized controlled trial

Despite intense and costly treatments, developmental dyslexia (DD) often persists into adulthood. Several brain skills unrelated to speech sound processing (i.e., phonology), including the spatial distribution of visual attention, are abnormal in DD and may represent possible treatment targets. This study explores the efficacy in DD of rightward prismatic adaptation (rPA), a visuomotor adaptation technique that enables visuo-attentive recalibration through shifts in the visual field induced by prismatic goggles. A digital intervention of rPA plus cognitive training was delivered weekly over 10 weeks to adolescents with DD (aged 13–17) assigned either to treatment (N = 35) or waitlist (N = 35) group. Efficacy was evaluated by repeated measures MANOVA assessing changes in working memory index (WMI), processing speed index (PSI), text reading speed, and words/pseudowords reading accuracy. rPA treatment was significantly more effective than waitlist (p ≤ 0.001; ηp2 = 0.815). WMI, PSI, and reading speed increased in the intervention group only (p ≤ 0.001, ηp2 = 0.67; p ≤ 0.001, ηp2 = 0.58; p ≤ 0.001, ηp2 = 0.29, respectively). Although modest change was detected for words and pseudowords accuracy in the waitlist group only (words: p ≤ 0.001, d = 0.17, pseudowords: p = 0.028; d = 0.27), between-group differences were non-significant. rPA-coupled cognitive training enhances cognitive and reading abilities in adolescents with DD. This innovative approach could have implications for early remedial treatment.

MTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.

Epilepsy remains a major health concern as anti-seizure medications frequently fail, and there is currently no treatment to stop or prevent epileptogenesis, the process underlying the onset and progression of epilepsy. The identification of the pathological processes underlying epileptogenesis is instrumental to the development of drugs that may prevent the generation of seizures or control pharmaco-resistant seizures, which affect about 30% of patients. mTOR signalling and neuroinflammation have been recognized as critical pathways that areactivated in brain cells in epilepsy. They represent a potential node of biological convergence in structural epilepsies with either a genetic or anacquired aetiology. Interventional studies in animal models and clinical studies give strong support to the involvement of each pathway in epilepsy. In this Review, we focus on available knowledge about the pathophysiological features of mTOR signalling and the neuroinflammatory brain response, and their interactions, in epilepsy. We discuss mitigation strategies for each pathway that display therapeutic effects in experimental and clinical epilepsy. A deeper understanding of these interconnected molecular cascades could enhance our strategies for managing epilepsy. This could pave the way for new treatments to fill the gaps in the development of preventative or disease-modifying drugs, thus overcoming the limitations of current symptomatic medications.

Incidental pathogenic germline alterations detected through liquid biopsy in patients with solid tumors: prevalence, clinical utility and implications.

Liquid biopsy, a minimally invasive approach for detecting tumor biomarkers in blood, has emerged as a leading-edge technique in cancer precision medicine. New evidence has shown that liquid biopsies can incidentally detect pathogenic germline variants (PGVs) associated with cancer predisposition, including in patients with a cancer for which genetic testing is not recommended. The ability to detect these incidental PGV in cancer patients through liquid biopsy raises important questions regarding the management of this information and its clinical implications. This incidental identification of PGVs raises concerns about cancer predisposition and the potential impact on patient management, not only in terms of providing access to treatment based on the tumor molecular profiling, but also the management of revealing genetic predisposition in patients and families. Understanding how to interpret this information is essential to ensure proper decision-making and to optimize cancer treatment and prevention strategies. In this review we provide a comprehensive summary of current evidence of incidental PGVs in cancer predisposition genes identified by liquid biopsy in patients with cancer. We critically review the methodological considerations of liquid biopsy as a tool for germline diagnosis, clinical utility and potential implications for cancer prevention, treatment, and research.

High antibiotic resistance rates in Helicobacter pylori strains in Turkey over 20 years: implications for gastric disease treatment.

Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

The Application of Long-Read Sequencing to Cancer.

Cancer is a multifaceted disease arising from numerous genomic aberrations that have been identified as a result of advancements in sequencing technologies. While next-generation sequencing (NGS), which uses short reads, has transformed cancer research and diagnostics, it is limited by read length. Third-generation sequencing (TGS), led by the Pacific Biosciences and Oxford Nanopore Technologies platforms, employs long-read sequences, which have marked a paradigm shift in cancer research. Cancer genomes often harbour complex events, and TGS, with its ability to span large genomic regions, has facilitated their characterisation, providing a better understanding of how complex rearrangements affect cancer initiation and progression. TGS has also characterised the entire transcriptome of various cancers, revealing cancer-associated isoforms that could serve as biomarkers or therapeutic targets. Furthermore, TGS has advanced cancer research by improving genome assemblies, detecting complex variants, and providing a more complete picture of transcriptomes and epigenomes. This review focuses on TGS and its growing role in cancer research. We investigate its advantages and limitations, providing a rigorous scientific analysis of its use in detecting previously hidden aberrations missed by NGS. This promising technology holds immense potential for both research and clinical applications, with far-reaching implications for cancer diagnosis and treatment.

EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: multi-site feasibility study

Background and study aims: The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods: In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results: In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and head of pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions: PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

Yield and Utility of Routine Epilepsy Panel Genetic Testing Among Young Patients With Seizures.

Objective: We examined the yield of routine epilepsy panel genetic testing in pediatric patients. Methods: We retrospectively reviewed epilepsy genetic panel results routinely performed in the hospital or clinic on patients <8 years old from July 2021 to July 2023. We evaluated demographics, family history, seizure type, severity, and frequency, development, tone and movement abnormalities, dysmorphism, and electroencephalography (EEG) or magnetic resonance imaging (MRI) results as predictors of results. Results: 65 patients were included with mean age 4.5 years. Sixty percent of patients were male; 11 patients had pathogenic variants (16.9%), 7 were carriers for autosomal recessive conditions (10.8%), 36 had variants of uncertain significance (55.4%), and 11 tested negative (16.9%). Pathogenic variants and variants of uncertain significance were unassociated with demographics, clinical features, imaging, or family history. Conclusion: Variants identified have potential implications for treatment (SCN1), comorbidity screening (TSC1), reproduction (ATAD1, PSAT1, and CLN8), and prognostication (FOXG1). Patients not routinely screened for a genetic cause of epilepsy by our standard practices had clinically relevant results.

Late-forming supernumerary teeth: A case series.

The aim of this case series was to illustrate the development of late-forming supernumerary teeth (LFST) and highlight the implications for orthodontic treatment. There are limited studies relating to the aetiology, prevalence and treatment of LFST and the cases presented here demonstrate the management of LFST within a tertiary care centre. Five cases are presented, which show various presentations and chronological ages in the development of LFST. This case series emphasises the significance of maintaining a low threshold for suspecting LFST in patients where supernumerary teeth have previously been identified. It also highlights the importance of regular clinical and radiographic reviews. Timely identification can help prevent complications and optimise treatment outcomes.

Abstract 2894: Targeting NOS2 and the tumor microenvironment in endometrioid ovarian cancer: Implications for treatment and survival

Abstract Purpose of the study: The final aim of the study is to disrupt the deleterious effect of the tumor microenvironment by targeting inducible Nitric Oxide Synthase 2 (NOS2). NOS2 has a role in cancer cell proliferation and immune cells inactivation. It is upregulated by cytokines released from the tumor proinflammatory environment and the adipose tissue. By targeting and reverting NOS2 functions, we want to develop a therapeutic modality that inhibits endometrioid ovarian cancer (EOC) progression and reactivates the immune response in the ovarian cancer tumor microenvironment (OC-TME). Experimental procedures: We analyzed ovarian cancer patients’ cohorts using TNMPlot, Kaplan-Meier Plotter and The Human Protein Atlas. We simulated the tumor proinflammatory microenvironment by administering Interferon-gamma (IFN-ϒ, 25 ng/mL), Interleukin 1 Beta (IL1-β, 10 ng/mL), Tumor Necrosis Factor-alpha (TNF-α, 10 ng/mL) on A2780 EOC human cell line. We also administered conditioned media (CM) from breast fat adipose tissue to assess the influence of lipid components on cytokines release. After upregulating NOS2, we tested the efficacy of Cisplatin in combination with L-NMMA, a NOS2 inhibitor, on A2780 cells through proliferation assays using RealTime-Glo™ MT Cell Viability Assay (Promega®). In addition, to assess the immune landscape in ovarian cancer, we developed a syngeneic model administering ID8 cells (murine OC cell line) through intraperitoneal injection (IP) in C57BL/6 mice. Results: The findings indicated higher NOS2 RNA expression levels in tumors than in normal samples according to TNMPlot (p = 6.84e-01). KMPlotter analysis revealed that patients with high NOS2 expression treated with Cisplatin had a significantly shorter survival rate (10.64 months) compared to those with lower NOS2 expression (25 months, p = 0.0088). Patients untreated with Cisplatin and exhibiting high NOS2 expression also showed lower survival rates (11 months) than those with lower NOS2 expression (34 months, p = 0.056). Furthermore, cytokine treatments increased NOS2 protein levels in A2780 cells after 48 hours, and CM similarly elevated NOS2 protein levels. Subsequent administration of Cisplatin and Cisplatin + L-NMMA to cytokine-treated A2780 cells notably reduced cell proliferation by 85% and 89%, respectively. Conclusion: Taken together, our results showed the importance of a proinflammatory environment and adipose tissue in NOS2 upregulation. These findings show a potential correlation between endometriosis, obesity, and endometrioid ovarian cancer. With the development of an in vivo and in vitro model, we can gain a better understanding of the role of NOS2 in immune inactivation as well as in cell proliferation in EOC. Citation Format: Gianmarco Melone, Mailin Li, Ivonne Uzair, Maria Chervo, Karina Ortega, Wei Qian, Jianying Zhou, Liliana Guzman, Sean Hynes, Sharon Glynn, Christoforos Thomas, Polina Matre, Lewis Francis, Jenny Chang. Targeting NOS2 and the tumor microenvironment in endometrioid ovarian cancer: Implications for treatment and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2894.

Abstract 4630: Clinical and epidemiological profile of neuroendocrine differentiation- A hospital-based retrospective study

Abstract Background: Neuroendocrine differentiation (NED) in carcinomas is poorly studied globally, despite its distinct clinical features, disease progression, pathology, treatment outcomes, and poor prognosis. Therefore, it is imperative to conduct further analysis utilizing extensive clinical samples to unveil the clinical and epidemiological profile of NED. Methods: A retrospective study was conducted to analyze the histopathological samples of patients diagnosed with malignant tumor using immunohistochemical techniques for NED markers, such as ChrA, Syno and CD56. The morbidity and prognosis of NED patient would be analyzed subsequently. Eligible patients must have pathologically confirmed gastric cancer, colorectal cancer, lung cancer, esophageal cancer and prostate cancer with no prior neoadjuvant chemotherapy or radiotherapy received before surgery. Patients aged 18-75 years with normal organ functions were enrolled. Results: Between January 2017 and June 2018, over 450 cases were enrolled. Preliminary analysis focused on 36 esophageal cancer (EC) and 44 prostatic cancer (PC) samples. NED markers were expressed in 4 (11.1%) of 36 EC patients, including 4 cases positive for Syno, 1 case positive for ChrA, and 2 cases positive for CD56. Meanwhile, NED markers were expressed in 15 (34.1%) of 44 PC patients, including 10 cases positive for Syno, 15 cases positive for ChrA, and 2 cases positive for CD56. Conclusion: Neuroendocrine differentiation is obviously observed in EC and PC. The encouraging prevalence rate of NED may have clinical implications for individualized treatment. Further research is needed to explore this area in more detail. Citation Format: Yaru Wen, Susheng Shi. Clinical and epidemiological profile of neuroendocrine differentiation- A hospital-based retrospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4630.

Nanocarbon Dimensionality and Oxidation Degree Influence the Sorption of Atenolol: Implications for Water Treatment

Nanocarbon Dimensionality and Oxidation Degree Influence the Sorption of Atenolol: Implications for Water Treatment

Abstract 1144: Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery

Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by concomitant and adjuvant temozolomide chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the brain parenchyma, where they give rise to the recurrent tumor. Based on gene expression, the tumor core can be subtyped into mesenchymal, proneural and classical areas, each being associated with differences in genetic alterations and cellular composition. In contrast, the tumor periphery where migrating tumor cells infiltrate brain parenchyma is less characterized in patients. Using spatial transcriptomics (n = 11), we show that specific malignant states colocalize in tumor core areas with necrosis and microvascular proliferation. Malignant cells within proneural or mesenchymal subtyped cores displayed, as expected, many differences in genetic expression, although such differences disappeared in the tumor periphery. Malignant cells residing in the tumor periphery had increased expression of genes related to neurodevelopmental pathways and synaptic connectivity. Our findings show similarities in cellular states across tumor subtypes with implications for post-operative treatment and provide an updated view of the spatial landscape of glioblastomas. Citation Format: Dylan Harwood, Vilde Pedersen, Nicolai S. Bager, Ane Y. Schmidt, Tobias O. Stannius, Ausrine Areskeviciute, Knud Josefsen, Dorte S. Nørøxe, David Scheie, Hannah E. Rostalski, Ulrik Lassen, Frederik O. Bagger, Joachim Weischenfeldt, Dieter H. Heiland, Kristoffer Vitting-Seerup, Signe R. Michaelsen, Bjarne W. Kristensen. Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1144.