Search

Hodgkin Lymphoma (HL) typically presents similarly to an infectious etiology, thus awareness of its atypical presentations is essential. We present a case of an adult woman who was found to have HL after presenting with a dry, non-productive cough and showing cavitary lesions on chest computed tomography (CT). We also describe the clinical, laboratory, and radiological workup done leading to the diagnosis and management of HL in a critical care setting.

Simple Summary: An ultrasound-guided percutaneous lung biopsy performed by a pulmonologist is a safe, minimally invasive procedure for patients with suspected lung malignancies, providing an excellent diagnostic yield for a comprehensive molecular profiling and programmed death ligand 1 testing. Moreover, ultrasound-guided percutaneous lung biopsy may represent a successful approach for diagnosis of lung lymphoid lesions, with potential implication on reducing time-to-treatment time. Background: The recent advances in precision oncology for lung cancer treatment has focused attention on the importance of obtaining appropriate specimens for tissue diagnosis as well as comprehensive molecular profiling. CT scan-guided biopsies and bronchoscopy are currently the main procedures employed for tissue sampling. However, growing evidence suggests that ultrasound-guided biopsies may represent an effective as well as safe approach in this diagnostic area. This study explores the safety and the diagnostic yield for cancer molecular profiling in ultrasound-guided percutaneous lung lesion biopsies (US-PLLB). Methods: One hundred consecutive patients with suspected lung cancer, between January 2021 and May 2024, who had ultrasound-guided lung biopsies have been retrospectively analyzed. Molecular profiling was conducted with next-generation sequencing Genexus using Oncomine precision assay or polymerase chain reaction according to specimen quality. Qualitative immunohistochemical assay of programmed death ligand 1 (PD-L1) expression was evaluated by the Dako PD-L1 immunohistochemistry 22C3 pharmDx assay. The co-primary endpoints were the molecular diagnostic yield and the safety profile of US-guided lung biopsies. Results: From January 2021 to May 2024, 100 US-guided lung biopsies were carried out and 95 were considered for inclusion in the study. US-PLLB provided informative tissue for a histological evaluation in 93 of 95 patients with an overall diagnostic accuracy of 96.84% [Sensitivity: 92.63%; Specificity: 96.84%; PPV: 100%; NPV: 100%]. Sixty-Six patients were diagnosed with NSCLC (69.47%) and were considered for molecular diagnostic yield evaluation and PD-L1 testing. Four patients had malignant lymphoid lesions. US-PLLB was not adequate to achieve a final diagnosis in three patients (3.16%). Complete molecular profiling and PD-L1 evaluation were achieved in all patients with adenocarcinoma (molecular diagnostic yield: 100%). PD-L1 evaluation was achieved in 28 of 29 patients (96.55%) with either SCC or NOS lung cancer. The overall complication rate was 9.47% (n = 9). Six patients (6.31%) developed pneumothorax, while three patients (3.16%) suffered mild haemoptysis without desaturation. Conclusions: According to our findings, US-guided lung biopsy is a safe, minimally invasive procedure in patients with suspected lung malignancies, providing an excellent diagnostic yield for both comprehensive molecular profiling and PD-L1 testing. In addition, our results suggest that US-guided biopsy may also be an effective diagnostic approach in patients with suspected lung lymphoma. [ABSTRACT FROM AUTHOR]

Simple Summary: IRS4 (insulin receptor substrate4) belongs to a family of intracellular proteins that include IRS1 and IRS2 and whose physiological function is to transmit the effects of insulin and IGF1 inside the cell. IRS4 is the least studied of this family, and its expression has recently been shown to be increased in many types of cancer. IRS4 serves to connect different signaling pathways, such as MAP kinases and PI3K/AKT. In addition, it has been observed that it is capable of activating several oncogenes, such as BRK (breast tumor kinase) and feline sarcoma-related protein (FER). Increased IRS4 expression in cancer cells may be due to changes in the regulatory region of the gene or increased chromosomal aberrations. Our objective has been to carry out a review to assess the possibility that IRS4 behaves as a meeting point for different oncogene signaling pathways, which we have called the oncogene platform. The IRS (insulin receptor substrate) family of scaffold proteins includes insulin receptor substrate-4 (IRS4), which is expressed only in a few cell lines, including human kidney, brain, liver, and thymus and some cell lines. Its N-terminus carries a phosphotyrosine-binding (PTB) domain and a pleckstrin homology domain (PH), which distinguishes it as a member of this family. In this paper, we collected data about the molecular mechanisms that explain the relevance of IRS4 in the development of cancer and identify IRS4 differences that distinguish it from IRS1 and IRS2. Search engines and different databases, such as PubMed, UniProt, ENSEMBL and SCANSITE 4.0, were used. We used the name of the protein that it encodes "(IRS-4 or IRS4)", or the combination of these terms with the word "(cancer)" or "(human)", for searches. Terms related to specific tumor pathologies ("breast", "ovary", "colon", "lung", "lymphoma", etc.) were also used. Despite the lack of knowledge on IRS4, it has been reported that some cancers and benign tumors are characterized by high levels of IRS-4 expression. Specifically, the role of IRS-4 in different types of digestive tract neoplasms, gynecological tumors, lung cancers, melanomas, hematological tumors, and other less common types of cancers has been shown. IRS4 differs from IRS1 and IRS2 in that can activate several oncogenes that regulate the PI3K/Akt cascade, such as BRK and FER, which are characterized by tyrosine kinase-like activity without regulation via extracellular ligands. In addition, IRS4 can activate the CRKL oncogene, which is an adapter protein that regulates the MAP kinase cascade. Knowledge of the role played by IRS4 in cancers at the molecular level, specifically as a platform for oncogenes, may enable the identification and validation of new therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the incidence rate of second primary cancers (SPCs) and the cumulative incidence of metachronous [diagnosed > 2 months after a first primary cancer (FPC)] SPCs in patients with a breast FPC, and to compare the incidence of SPC [overall, synchronous (≤ 2 months of the FPC) and metachronous] with that expected in the general female population. Methods: A cohort of patients with a breast FPC from the North Region Cancer Registry of Portugal, diagnosed in 2000–2010 (n = 15,981), was followed to 31 December 2015 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs considering death as a competing event, and incidence rates and standardized incidence ratios of SPCs were estimated. Results: The diagnosis of an SPC occurred in 1229 (7.7%) of patients with a breast FPC. SPCs occurred mainly in the breast, followed by digestive organs, lung, thyroid, and female genital organs. Globally, patients with a breast FPC had a higher incidence for all types of cancer compared to the general female population, and in particular for cancers of the breast, stomach, colon, lung, lymphoma, uterus, and ovary. The 10-year cumulative incidence of metachronous SPCs following a breast FPC was 6.6% and the corresponding 10-year cumulative mortality was 26.2%. Conclusion: In Portugal, patients with a breast FPC have a higher incidence of cancer compared to the general female population, highlighting important aspects of care, surveillance, and counselling among this growing number of patients. [ABSTRACT FROM AUTHOR]

Background: One of the most common causes of weight loss is malignant tumours (especially gastrointestinal, pancreatic, lung, lymphoma, renal and prostate cancers), which often cause weight loss through various mechanisms of this phenomenon [6]. A plethora of current reports state that unintentional weight loss (UWL) may be used as a marker prior to the development of malignant processes. Most studies suggest that the main endogenous sources of energy during weight loss progression in cancer are primarily triglycerides in adipose tissue and skeletal muscle protein [3]. Conclusions: We can report with certainty that weight loss is an important prognostic factor in cancer; the greater the degree of weight loss, the shorter the survival time. The prognostic effect of weight loss is greater in patients with a better prognosis. The aim of this literature review was to explain the pathogenetic chains involved in involuntary weight loss in malignant processes with the development of cancer cachexia, also reporting clinical signs and complications of these. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical features, imaging, pathology and management of patients with primary pulmonary lymphoma (PPL). Methodology: This is a case series study involving a retrospective analysis of 24 patients diagnosed with PPL between the years 2000-2019 at Instituto Nacional de Enfermedades Neoplásicas in Lima, Perú. Results: 73.9% of patients were male. Cough (78.3%) and weight loss (56.5%) were the most frequent clinical features. Dyspnoea and elevated values of DHL and B2 microglobulin were frequently altered in advanced stages. Diffuse large B cell lymphoma (DLBCL) represented 47.8% of the cases and the most common radiologic alterations were a mass (60%) and consolidation with air bronchogram (60%). The most utilised treatment was chemotherapy alone (60%). Three patients received only surgery. Median survival was 30 months. Five overall survival was 45%, and up to 60% in the case of mucosa-associated lymphoid tissue lymphoma. Conclusion: PPL is infrequent. Clinical features are unspecific and the principal finding is a mass, nodule or consolidation with air bronchogram. Definitive diagnosis needs biopsy and immunohistochemistry. There is no standard treatment, it depends on histology type and stage. [ABSTRACT FROM AUTHOR]

123 Background: Brain metastases (BM) portend high mortality rates. While whole brain radiation therapy (WBRT) is a commonly used treatment strategy for BM, stereotactic radiosurgery (SRS) has less neurocognitive toxicity with comparable survival. The objective of this study was to compare treatment practice patterns for SRS vs WBRT using a large national hospital database. Methods: The National Cancer Database (NCDB) was queried for patients ≥18 years treated with radiotherapy (RT) for a BM diagnosis between 2004-2020 and with known follow-up. Twelve cancers were included based on highest prevalence: breast, colorectal, kidney/bladder, liver, lung, lymphoma, melanoma, oral cavity, pancreas, prostate, and thyroid. Patients were grouped by first course RT modality (SRS vs WBRT) confirmed by fraction number (SRS: 1-5; WBRT: 5-15). Multivariable logistic regression assessed predictors of SRS as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). Analyses were adjusted for patient and cancer characteristics. Results: Of 112,232 patients with BM, 30,805 (27%) received SRS. Median age was 64 years. Most patients were White (84%), diagnosed in 2012-2020 (64%), with a higher income (56%), more education (55%), and Medicare/Medicaid (60%). The most common cancer treated with RT for BM was lung (85%). Patients were less likely to be treated with SRS if they were Korean (aOR=0.68; 95%CI=0.47-0.95), lower income (aOR=0.88; 95%CI=0.84-0.91), lower education (aOR=0.88; 95%CI=0.85-0.91), with Medicare/Medicaid (aOR=0.86; 95%CI=0.83-0.89) or no insurance (aOR=0.48; 95%CI=0.44-0.53), at a Midwest hospital (aOR=0.79; 95%CI=0.76-0.83; vs Northeast), and at a community (aOR=0.31; 95%CI=0.28-0.33; vs academic) or comprehensive community cancer program (aOR=0.56; 95%CI=0.54-0.58). Patients were more likely to be treated with SRS if they were Asian Indian or Pakistani (aOR=1.41; 95%CI =1.08-1.85), older (aOR=1.01; 95%CI=1.01-1.01), diagnosed in 2012-2020 (aOR=3.92; 95%CI=3.78-4.07; vs 2004-2011), lived farther from the hospital (aOR=1.00; 95%CI=1.00-1.00), and received chemotherapy (aOR=1.17; 95%CI=1.13-1.21). Conclusions: In one of the largest BM studies with over 110,000 US patients, disparities in SRS treatment patterns were identified. On adjusted analysis, SRS was less likely to be used for patients who were lower income, lower educational attainment, without private insurance, and treated at community centers. The data highlight populations with cancer and BM who may benefit from increased access to SRS. [ABSTRACT FROM AUTHOR]

Background: Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking. Methods: We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions. Results: A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL. Conclusion: This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making. PLAIN LANGUAGE SUMMARY: Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL), a rare extranodal non-Hodgkin's lymphoma (EN-NHL), has a very poor prognosis as an aggressive lymphoma. We screened individuals from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with PP-DLBCL between 2010 and 2019. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, we built a new predictive model to aid in clinical decision making. [ABSTRACT FROM AUTHOR]

The machine learning process in high-dimensional datasets is far more complicated than in low-dimensional datasets. In high-dimensional datasets, Feature Selection (FS) is necessary to decrease the complexity of learning. However, FS in high-dimensional datasets is a complex process that requires the combination of several search techniques. The Chimp Optimization Algorithm, known as ChOA, is a new meta-heuristic method inspired by the chimps' individual intellect and sexual incentive in cooperative hunting. It is basically employed in solving complex continuous optimization problems, while its binary version is frequently utilized in solving difficult binary optimization problems. Both versions of ChOA are subject to premature convergence and are incapable of effectively solving high-dimensional optimization problems. This paper proposes the Binary Improved ChOA Algorithm (BICHOA) for solving the bi-objective, high-dimensional FS problems (i.e., high-dimensional FS problems that aim to maximize the classifier's accuracy and minimize the number of selected features from a dataset). BICHOA improves the performance of ChOA using four new exploration and exploitation techniques. First, it employs the opposition-based learning approach to initially create a population of diverse binary feasible solutions. Second, it incorporates the Lévy mutation function in the main probabilistic update function of ChOA to boost its searching and exploring capabilities. Third, it uses an iterative exploration technique based on an exploratory local search method called the β -hill climbing algorithm. Finally, it employs a new binary time-varying transfer function to calculate binary feasible solutions from the continuous feasible solutions generated by the update equations of the ChOA and β -hill climbing algorithms. BICHOA's performance was assessed and compared against six machine learning classifiers, five integer programming methods, and nine efficient popular optimization algorithms using 25 real-world high-dimensional datasets from various domains. According to the overall experimental findings, BICHOA scored the highest accuracy, best objective value, and fewest selected features for each of the 25 real-world high-dimensional datasets. Besides, the reliability of the experimental findings was established using Friedman and Wilcoxon statistical tests. [ABSTRACT FROM AUTHOR]

The pyruvate dehydrogenase kinase-3 (PDK3) plays an important role in the regulation of a variety of cancers, including lung, by inhibiting the pyruvate dehydrogenase complex (PDC), shifting energy production towards glycolysis necessary for cancer metabolism. In this study, we aimed to identify potential PDK3 inhibitors using a computer-based drug design approach. Virtual screening of the FDA-approved library of 3839 compounds was carried out, from which Bagrosin and Dehydrocholic acid appeared best due to their strong binding affinity, specific interactions, and potential biological characteristics, and thus were selected for further investigations. Both compounds show strong interactions with functionally important residues of the PDK3 with a binding affinity of − 10.6 and − 10.5 kcal/mol for Bagrosin and Dehydrocholic acid, respectively. MD simulation studies for 100 ns suggest the formation of stable complexes, which is evident from RMSD, RMSF, Rg, and SASA parameters. The PCA and FEL analysis suggested admirable global energy minima for the bagrosin-PDK3 and dehydrocholic acid-PDK3 complexes. Finally, we identified FDA-approved drugs, Bagrosin and Dehydrocholic acid, that offer valuable resources and potential therapeutic molecules for targeting lung cancer. Further clinical investigations are required to validate the clinical utility of selected molecules. [ABSTRACT FROM AUTHOR]

Transmembrane potassium ion channels are crucial for ion transport, metabolism, and signaling, and serve as promising targets for anti-cancer therapies. However, their hydrophobic transmembrane nature requires detergents, posing a major bottleneck for experimental handling. In this paper, we present a structural bioinformatics study of six experimentally determined and twelve modeled potassium channel structures, in which hydrophobic amino acids (L, I/V, and F) were systematically replaced with neutral hydrophilic ones (Q, T, and Y), making the proteins more water-soluble. QTY (computationally predicted) and native (experimental and repredicted) variants show remarkable structural similarity (RMSD: ~0.50 Å – ~2.14 Å) despite significant sequence differences. QTY variants, both rigid and refined with MD simulations, maintain comparable to native variants stability, solvent-accessible surface area (SASA), and ionic, aromatic, and van der Waals interactions but differ in the grand average of hydropathy (GRAVY), solubility, and hydrophobic contacts. Overall, our study presents a computational approach for designing hydrophilic potassium ion channels while maintaining the native global structure that could potentially simplify their practical use by eliminating the need for detergents. [ABSTRACT FROM AUTHOR]

To address the limitations of traditional optimization methods in achieving high accuracy in high-dimensional problems, this paper introduces the snow leopard optimization (SLO) algorithm. SLO is a novel meta-heuristic approach inspired by the territorial behaviors of snow leopards. By emulating strategies such as territory delineation, neighborhood relocation, and dispute mechanisms, SLO achieves a balance between exploration and exploitation, to navigate vast and complex search spaces. The algorithm's performance was evaluated using the CEC2017 benchmark and high-dimensional genetic data feature selection tasks, demonstrating SLO's competitive advantage in solving high-dimensional optimization problems. In the CEC2017 experiments, SLO ranked first in the Friedman test, outperforming several well-known algorithms, including ETBBPSO, ARBBPSO, HCOA, AVOA, WOA, SSA, and HHO. The effective application of SLO in high-dimensional genetic data feature selection further highlights its adaptability and practical utility, marking significant progress in the field of high-dimensional optimization and feature selection. [ABSTRACT FROM AUTHOR]

High-dimensional Feature Selection Problems (HFSPs) have grown in popularity but remain challenging. When faced with such complex situations, the majority of currently employed Feature Selection (FS) methods for these problems drastically underperform in terms of effectiveness. To address HFSPs, a new Binary variant of the Ali Baba and the Forty Thieves (BAFT) algorithm known as binary adaptive elite opposition-based AFT (BAEOAFT), incorporating historical information and dimensional mutation is presented. The entire population is dynamically separated into two subpopulations in order to maintain population variety, and information and knowledge about individuals are extracted to offer adaptive and dynamic strategies in both subpopulations. Based on the individuals' history knowledge, Adaptive Tracking Distance (ATD) and Adaptive Perceptive Possibility (APP) schemes are presented for the exploration and exploitation subpopulations. A dynamic dimension mutation technique is used in the exploration subpopulation to enhance BAEOAFT's capacity in solving HFSPs. Meanwhile, the exploratory subpopulation uses Dlite Dynamic opposite Learning (EDL) to promote individual variety. Even if the exploitation group prematurely converges, the exploration subpopulation's variety can still be preserved. The proposed BAEOAFT-based FS technique was assessed by utilizing the k-nearest neighbor classifier on 20 HFSPs obtained from the UCI repository. The developed BAEOAFT achieved classification accuracy rates greater than those of its competitors and the conventional BAFT in more than 90% of the applied datasets. Additionally, BAEOAFT outperformed its rivals in terms of reduction rates while selecting the fewest number of features. [ABSTRACT FROM AUTHOR]

Introduction: Several risk scores have been proposed to predict venous thromboembolism (VTE) in hospitalized patients. However, their predictive performances in lung cancer patients receiving immune checkpoint inhibitors (ICIs) is unclear. We aimed to validate and compare their performances of the Caprini, Padua and Khorana risk scores in lung cancer patients receiving ICIs. Methods: This was a retrospective cohort study of patients with lung cancer treated with ICIs at West China Hospital between January 2018 and March 2022. The primary outcome was VTE during 12 months of follow-up from the first day of treatment with ICIs. The predictive performances of risk scores was determined using receiver operating characteristic (ROC) curve analysis. Results: Among the 1115 eligible patients with lung cancer who received ICIs, 105 patients (9.4%) experienced VTE during the 12-month follow-up period. There was a statistically significant difference in the cumulative incidence of VTE between the different risk levels as determined by Caprini and Padua scores (all P < 0.001). However, no significant difference was observed for the Khorana score (P = 0.488). The Caprini and Padua scores demonstrated good discriminative performances (AUC 0.743, 95% CI 0.688-0.799 for Caprini score; AUC 0.745, 95% CI 0.687‐0.803 for Padua score), which were significantly better than that of the Khorana score (AUC 0.553, 95% CI, 0.493‐0.613) (P < 0.05). Conclusion: In our study, the Caprini and Padua risk scores had better discriminative ability than the Khorana score to identify lung cancer patients treated with ICIs who were at high risk of VTE. [ABSTRACT FROM AUTHOR]

Background: Electronic Patient-Reported Outcome Measures (ePROMs) have emerged as valuable tools in cancer care, facilitating the comprehensive assessment of patients' physical, psychological, and social well-being. This study synthesizes literature on the utilization of ePROMs in oncology, highlighting the diverse array of measurement instruments and questionnaires employed in cancer patient assessments. By comprehensively analyzing existing research, this study provides insights into the landscape of ePROMs, informs future research directions, and aims to optimize patient-centred oncology care through the strategic integration of ePROMs into clinical practice. Methods: A systematic review was conducted by searching peer-reviewed articles published in academic journals without time limitations up to 2024. The search was performed across multiple electronic databases, including PubMed, Scopus, and Web of Science, using predefined search terms related to cancer, measurement instruments, and patient assessment. The selected articles underwent a rigorous quality assessment using the Mixed Methods Appraisal Tool (MMAT). Results: The review of 85 studies revealed a diverse range of measurement instruments and questionnaires utilized in cancer patient assessments. Prominent instruments such as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PROCTCAE) were frequently referenced across multiple studies. Additionally, other instruments identified included generic health-related quality of life measures and disease-specific assessments tailored to particular cancer types. The findings indicated the importance of utilizing a variety of measurement tools to comprehensively assess the multifaceted needs and experiences of cancer patients. Conclusion: Our systematic review provides a comprehensive examination of the varied tools and ePROMs employed in cancer care, accentuating the perpetual requirement for development and validation. Prominent instruments like the EORTC QLQ-C30 and PRO-CTCAE are underscored, emphasizing the necessity for a thorough assessment to meet the multifaceted needs of patients. Looking ahead, scholarly endeavours should prioritize the enhancement of existing tools and the creation of novel measures to adeptly address the evolving demands of cancer patients across heterogeneous settings and populations. [ABSTRACT FROM AUTHOR]

Purpose: In light of the known benefits of physical activity (PA) for cancer survivors, this exploratory study sought to investigate the uptake of PA among this population in the United States. Methods: Using the National Health Interview Survey data from 2009 to 2018, lung, breast, colorectal, prostate, ovarian, and lymphoma cancer survivors were identified, and their PA adherence measured per the standards of the American College of Sports Medicine. Logistic regression and the Fairlie decomposition were used, respectively, to identify correlates of PA and to explain the difference in PA adherence between races. Results: Uptake of PA was significantly different between Whites and minorities. Blacks had lower odds than Whites (adjusted odds ratio: 0.77; 95% confidence interval, 0.66–0.93), whereas Mixed Race had twice the odds of Whites (adjusted odds ratio: 1.94; 95% confidence interval, 0.27–0.98) of adhering to PA recommendations. Decomposition identified education, family income-to-poverty ratio, body mass index, number of chronic conditions, alcohol use, and general health as key factors accounting for the PA disparity between cancer survivors of White and Black or Multiple/Mixed racial group. Conclusion: These findings could help inform behavioral PA interventions to improve their design and targeting to different racial groups of cancer survivors. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a devastating disease initiated and maintained by a rare subset of cells called leukemia stem cells (LSCs). LSCs are responsible for driving disease relapse, making the development of new therapeutic strategies to target LSCs urgently needed. The use of mass spectrometry–based metabolomics profiling has enabled the discovery of unique and targetable metabolic properties in LSCs. However, we do not have a comprehensive understanding of metabolite differences between LSCs and their normal counterparts, hematopoietic stem and progenitor cells (HSPCs). In this study, we used an unbiased mass spectrometry–based metabolomics analysis to define differences in metabolites between primary human LSCs and HSPCs, which revealed that LSCs have a distinct metabolome. Spermidine was the most enriched metabolite in LSCs compared with HSPCs. Pharmacological reduction of spermidine concentrations decreased LSC function but spared normal HSPCs. Polyamine depletion also decreased leukemic burden in patient-derived xenografts. Mechanistically, spermidine depletion induced LSC myeloid differentiation by decreasing eIF5A-dependent protein synthesis, resulting in reduced expression of a select subset of proteins. KAT7, a histone acetyltransferase, was one of the top candidates identified to be down-regulated by spermidine depletion. Overexpression of KAT7 partially rescued polyamine depletion–induced decreased colony-forming ability, demonstrating that loss of KAT7 is an essential part of the mechanism by which spermidine depletion targets AML clonogenic potential. Together, we identified and mechanistically dissected a metabolic vulnerability of LSCs that has the potential to be rapidly translated into clinical trials to improve outcomes for patients with AML. Editor's summary: A major concern for patients with acute myeloid leukemia is relapse after treatment. Leukemic stem cells (LSCs), which reside in the bone marrow and maintain the pool of leukemic cells, are the main culprits behind relapse and thus need to be targeted to prevent relapse from occurring. To identify targetable vulnerabilities of LSCs, Rondeau et al. performed metabolomics profiling of LSCs compared with healthy hematopoietic stem and progenitor cells (HSPCs). They identified the polyamine spermidine as a metabolite specifically enriched in LSCs and then showed that reducing spermidine or total polyamine concentrations could impair LSC function by down-regulating expression of a histone acetyltransferase, KAT7. Polyamine depletion reduced leukemia burden in patient-derived mouse models, suggesting that this could be a therapeutic approach to prevent relapse for patients with AML. —Courtney Malo [ABSTRACT FROM AUTHOR]

Introduction: Imaging in renal cell carcinoma (RCC) is a constantly evolving landscape. The incidence of RCC has been rising over the years with the improvement in image quality and sensitivity in imaging modalities resulting in "incidentalomas" being detected. We aim to explore the latest advances in imaging for RCC. Methods: A literature search was conducted using Medline and Google Scholar, up to May 2024. For each subsection of the manuscript, a separate search was performed using a combination of the following key terms "renal cell carcinoma", "renal mass", "ultrasound", "computed tomography", "magnetic resonance imaging", "18F-Fluorodeoxyglucose PET/CT", "prostate-specific membrane antigen PET/CT", "technetium-99m sestamibi SPECT/CT", "carbonic anhydrase IX", "girentuximab", and "radiomics". Studies that were not in English were excluded. The reference lists of selected manuscripts were checked manually for eligible articles. Results: The main imaging modalities for RCC currently are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Contrast-enhanced US (CEUS) has emerged as an alternative to CT or MRI for the characterisation of renal masses. Furthermore, there has been significant research in molecular imaging in recent years, including FDG PET, PSMA PET/CT, 99mTc-Sestamibi, and anti-carbonic anhydrase IX monoclonal antibodies/peptides. Radiomics and the use of AI in radiology is a growing area of interest. Conclusions: There will be significant change in the field of imaging in RCC as molecular imaging becomes increasingly popular, which reflects a shift in management to a more conservative approach, especially for small renal masses (SRMs). There is the hope that the improvement in imaging will result in less unnecessary invasive surgeries or biopsies being performed for benign or indolent renal lesions. [ABSTRACT FROM AUTHOR]

Background: Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms. Methods and findings: Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use. Conclusions: In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites. Meena Rafiq and co-workers explore the predictive value of abnormal blood tests for detecting cancer in patients presenting to primary care with non-specific abdominal symptoms. Author summary: Why was this study done?: Half of all patients with as-yet-undetected cancer will first present with nonspecific symptoms that can be challenging to diagnose. Many of these patients are investigated in primary care with commonly used blood tests that could help to identify which patients are most likely to have underlying cancer (to prioritise them for referral) and which patients can be safely monitored in primary care. This study aimed to assess the predictive value of abnormal blood tests for detecting cancer in patients presenting to primary care with 2 nonspecific abdominal symptoms. What did the researchers do and find?: Using linked UK primary care data (CPRD), we conducted a cohort study of 477,870 patients aged ≥30 years presenting with new abdominal pain or bloating and calculated the predictive value of 19 abnormal blood test results for detecting cancer by age and sex. Males and females aged ≥60 presenting with either symptom had a risk of underlying cancer exceeding the 3% threshold used by the UK National Institute for Health and Care Excellence for recommending urgent cancer referral. In patients aged 30 to 59 with abdominal pain or bloating, several blood abnormalities updated a patient's cancer risk to above the 3% threshold and they should be considered for urgent cancer referral. What do these findings mean?: Commonly used primary care blood test results can improve the detection of underlying cancer in patients consulting with nonspecific abdominal symptoms. These findings can inform updates to clinical guidelines to allow detection of additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites. Limitations include the results applying to patients who had been recorded as having abdominal pain and bloating by their clinician and who had been selected by the clinician for blood testing (and therefore have a higher cancer risk that all patients with abdominal pain and bloating). [ABSTRACT FROM AUTHOR]

Background: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. Methods: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. Results: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. Conclusions: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL. [ABSTRACT FROM AUTHOR]

Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of cancers in specific developmental stages. Distinct DNA methylation profiles were identified in our data on early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters to distinguish between differentially methylated states. We infer from this data set, the epigenetic context, and the related literature that a CpG-rich, 2800 bp region, a prominent CpG island, surrounding the transcription start of the hTERT gene is the crucial epigenetic zone for the development of a potent biomarker. In order to accurately describe this region, we have named it "Acheron" (Ἀχέρων). In Greek mythology, this is the river of woe and misery and the path to the underworld. Exploitation of the DNA methylation profiles focused on this region, e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up a wide range of new possibilities for diagnosis, determination of prognosis, follow-up, and detection of residual disease. It may also have broad implications for the choice of chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Cancer survivors are developing more subsequent tumors. We sought to characterize patients with multiple (=2) primary cancers (MPC) to assess associations and genetic mechanisms. Methods: Patients were prospectively consented (01/2013-02/2019) to tumor-normal sequencing via a custom targeted panel (MSK-IMPACT). A subset consented to return of results of =76 cancer predisposition genes. International Agency for Research on Cancer (IARC) 2004 rules for defining MPC were applied. Tumor pairs were created to assess relationships between cancers. Age-adjusted, sex-specific, standardized incidence ratios (SIR) for first to second cancer event combinations were calculated using SEER rates, adjusting for confounders and time of ascertainment. Associations were made with germline and somatic variants. Results: Of 24,241 patients, 4,340 had MPC (18%); 20% were synchronous. Most (80%) had two primaries; however, 4% had =4 cancers. SIR analysis found lymphoma-lung, lymphoma-uterine, breast-brain, and melanoma-lung pairs in women and prostate-mesothelioma, prostate-sarcoma, melanoma-stomach, and prostate-brain pairs in men in excess of expected after accounting for synchronous tumors, known inherited cancer syndromes, and environmental exposures. Of 1,580 (36%) patients who received germline results, 324 (21%) had 361 pathogenic/likely pathogenic variants (PV), 159 (44%) in high penetrance genes. Of tumor samples analyzed, 55% exhibited loss of heterozygosity at the germline variant. In those with negative germline findings, melanoma, prostate, and breast cancers were common. Conclusions: We identified tumor pairs without known predisposing mutations that merit confirmation and will require novel strategies to elucidate genetic mechanisms of shared susceptibilities. Impact: If verified, patients with MPC with novel phenotypes may benefit from targeted cancer surveillance. [ABSTRACT FROM AUTHOR]

The article introduces an innovative approach to global optimization and feature selection (FS) using the RIME algorithm, inspired by RIME-ice formation. The RIME algorithm employs a soft-RIME search strategy and a hard-RIME puncture mechanism, along with an improved positive greedy selection mechanism, to resist getting trapped in local optima and enhance its overall search capabilities. The article also introduces Binary modified RIME (mRIME), a binary adaptation of the RIME algorithm to address the unique challenges posed by FS problems, which typically involve binary search spaces. Four different types of transfer functions (TFs) were selected for FS issues, and their efficacy was investigated for global optimization using CEC2011 and CEC2017 and FS tasks related to disease diagnosis. The results of the proposed mRIME were tested on ten reliable optimization algorithms. The advanced RIME architecture demonstrated superior performance in global optimization and FS tasks, providing an effective solution to complex optimization problems in various domains. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence. [ABSTRACT FROM AUTHOR]

Objectives: To assess cumulative effective dose (CED) over a 4-year period in patients undergoing multimodality recurrent imaging at a major hospital in the USA. Methods: CED from CT, fluoroscopically guided intervention (FGI), and nuclear medicine was analyzed in consecutive exams in a tertiary care center in 2018–2021. Patients with CED ≥ 100 mSv were classified by age and body habitus (underweight, healthy weight, overweight, obese), as per body mass index percentiles < 5th, 5th to < 85th, 85th to < 95th, and ≥ 95th (age 2–19 years), and its ranges < 18.5, 18.5–24.9, 25–29.9, and ≥ 30 (≥ 20 years), respectively. Results: Among a total of 205,425 patients, 5.7% received CED ≥ 100 mSv (mean 184 mSv, maximum 1165 mSv) and their ages were mostly 50–64 years (34.1%), followed by 65–74 years (29.8%), ≥ 75 years (19.5%), 20–49 years (16.3%), and ≤ 19 years (0.29%). Body habitus in decreasing occurrence was obese (38.6%), overweight (31.9%), healthy weight (27.5%), and underweight (2.1%). Classification by dose indicated 172 patients (≥ 500 mSv) and 3 (≥ 1000 mSv). In comparison, 5.3% of 189,030 CT patients, 1.6% of 18,963 FGI patients, and 0.19% of 41,401 nuclear-medicine patients received CED ≥ 100 mSv from a single modality. Conclusions: The study of total dose from CT, FGI, and nuclear medicine of patients with CED ≥ 100 mSv indicates major (89%) contribution of CT to CED with 70% of cohort being obese and overweight, and 64% of cohort aged 50–74 years. Clinical relevance statement: Multimodality recurrent exams are common and there is a lack of information on patient cumulative radiation exposure. This study attempts to address this lacuna and has the potential to motivate actions to improve the justification process for enhancing patient safety. Key Points: • In total, 5.7% of patients undergoing multimodality recurrent imaging (CT, fluoroscopically guided intervention, nuclear medicine) incurred a dose of ≥ 100 mSv. • Mean dose was 184 mSv, with 15 to 18 times contribution from CT than that from fluoroscopically guided intervention or nuclear medicine. • In total, 70% of those who received ≥ 100mSv were either overweight or obese. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated thrombosis (CAT) is a severe cause of mortality and morbidity in cancer patients, while active cancer is present in 20% of all patients with venous thromboembolism (VTE). CAT presents several peculiarities that distinguish this entity from other clinical settings associated with VTE. Management of thromboembolic events in CAT is extremely challenging because of the multifactorial pathophysiology of this clinical setting. The objective of this review is to enlighten the complicated pathophysiology of CAT, discuss the available biomarkers for early identification of high-risk patients, and summarize the current guidelines regarding the treatment and management of thrombotic events in cancer patients. Dysregulated hemostasis in cancer patients is associated with various clinical conditions, from thromboembolic complications to disseminated intravascular coagulation. Despite the well-established association between cancer and thromboembolic complications, the mechanisms involved are not completely elucidated. There are several predisposing factors in cancer for increased thrombus generation, such as immobilization and chemotherapy. The term cancer-associated thrombosis (CAT) has been introduced to describe the close bidirectional relationship between cancer and thromboembolic events. Conventional coagulation tests (PT/aPTT) are more accurate in detecting a hypocoagulable rather than a hypercoagulable state; thus, their contribution to CAT management is limited. Traditionally, D-dimer levels have been the most common laboratory study for the evaluation of thrombotic risk. However, D-dimer levels only display a snapshot of the coagulation cascade, and they cannot provide a dynamic evaluation of evolving clot formation. Non-conventional assays, such as viscoelastic methods and microparticle formation are promising tools for the identification of patients at risk for developing CAT. Recent guidelines from the American Society of Clinical Oncology counsel against the estimation of thrombotic risk through a single test and recommend the use of scoring systems that take into account several risk factors. The present review outlines the current insights into the pathophysiological mechanisms of CAT and provides a comprehensive review of the latest advances in the laboratory assessment of CAT and the recent guidelines for the management of patients at risk for developing thromboembolic complications. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection. Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening. Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma. Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC. [ABSTRACT FROM AUTHOR]

Feature selection is an important technique used in bioinformatics modeling to reduce the dimensionality of high-dimensional data. However, filter-based approaches that have shown better performance often depend on specific measurement methods, which can limit their effectiveness. To address this problem, this paper proposes a novel cascade feature selection approach, named the cascade entropy-fisher score (CEFS), that combines entropy score (ES)-based and Fisher score (FS)-based feature selection. CEFS involves a two-step process where in the first step, the entropy of each gene in the dataset is calculated to measure the uncertainty associated with its expression levels across different samples. In the second step, the Fisher score is computed to measure the extent to which the gene's expression levels differ between classes of samples. CEFS has been shown to outperform other methods in identifying disease-specific genes in gene expression datasets, making it a promising tool for disease diagnosis and prognosis. The proposed method was evaluated on biomedical datasets, and its effectiveness was measured in terms of accuracy, sensitivity, specificity, and area under the curve (AUC). The results showed that CEFS has comparable performance to state-of-the-art feature selection methods in the literature. Additionally, the selected features were fed to an ensemble of three classifiers, including support vector machine (SVM), k-nearest neighbor (k-NN), and decision tree (DT), to evaluate performance in the classification stage. The ensemble approach is based on majority voting, which aggregates the outputs of the individual classifiers to determine the final label. The results demonstrate the potential of CEFS in machine learning applications, particularly in the context of disease diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis presented to hospital with worsening subacute shortness of breath. CT pulmonary angiogram demonstrated ground glass changes involving all lung lobes with an apicobasal gradient. These changes, combined with longterm steroid exposure for granulomatous hepatitis without pneumocystis prophylaxis, raised concern for pneumocystis jirovecii pneumonia (PJP). A subsequent bronchoscopic lavage specimen was positive on PCR for PJP and the patient was started on appropriate therapy. Clinical and radiological changes initially improved but after completion of therapy, symptoms and radiological abnormalities returned. Retreatment with secondline treatment resulted again in initial improvement followed by relapse with acute deterioration. Further investigations for an alternate diagnosis were made, with a surgical lung biopsy performed finally revealing immunosuppression-related Epstein-Barr virus positive large B cell lymphoma with lymphomatoid granulomatosis of grade 3 pattern. [ABSTRACT FROM AUTHOR]

Background: Although there is evidence that ribonucleotide reductase subunit M2 (RRM2) is associated with numerous cancers, pan-cancer analysis has seldom been conducted. This study aimed to explore the potential carcinogenesis of RRM2 in pan-cancer using datasets from The Cancer Genome Atlas (TCGA). Methods: Data from the UCSC Xena database were analyzed to investigate the differential expression of RRM2 across multiple cancer types. Clinical data such as age, race, sex, tumor stage, and status were acquired to analyze the influence of RRM2 on the clinical characteristics of the patients. The role of RRM2 in the onset and progression of multiple cancers has been examined in terms of genetic changes at the molecular level, including tumor mutational burden (TMB), microsatellite instability (MSI), biological pathway changes, and the immune microenvironment. Results: RRM2 was highly expressed in most cancers, and there was an obvious correlation between RRM2 expression and patient prognosis. RRM2 expression is associated with the infiltration of diverse immune and endothelial cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI). Moreover, the cell cycle is involved in the functional mechanisms of RRM2. Conclusions: Our pan-cancer study provides a comprehensive understanding of the carcinogenesis of RRM2 in various tumors. [ABSTRACT FROM AUTHOR]

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events. [ABSTRACT FROM AUTHOR]

Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a very rare presentation of MALT lymphoma. The presence of a completely negative autoimmune and inflammatory background makes it a real challenge and very rare presentation (probably the second reported case in the literature). We report a case of primary pulmonary MALT lymphoma with negative autoimmune background, demonstrating as multifocal bulky variceal masses causing significant clinical symptoms. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription-3 (STAT3) is the most studied member from seven latent cytoplasmatic transcription factors (STATs 1-4, 5a, 5b and 6) that are closely associated with the occurrence of many types of cancer (breast, leukemia, lung, lymphoma, ovarian and prostate). STAT3 contains four functional domains, from which the Src homology 2 domain (SH2 domain) is the major target for inhibition of these proteins. Inhibition results in STAT3 tyrosine 705 (Y705) phosphorylation, dimerization, nuclear transport, DNA binding and transcription induction. The benzo[b]thiophene 1,1-dioxide (BTP) as a pharmacophore is part of many STAT3 inhibitors, such as Stattic, HJC0123, HJC0149 and HJC0416 (1,2,3). Stattic (6-nitro derivate of BTP) is a small molecule which selectively inhibited STAT3 SH2 domain function in vitro (3). HJC0123, HJC0149 and HJC0416 are carboxamides made from 6-amino derivate of BTP and substituted aromatic carboxylic acids (1,2). In this study we have in silico designed, synthesized and purificated 8 new Stattic-carboxamides. Their physical chemical properties were predicted in silico and then experimentally evaluated. Their biological activity was tested on murine and human cancer cell lines. Results were evaluated and compared to Stattic as a reference compound. [ABSTRACT FROM AUTHOR]

Non-coding ribonucleic acids (ncRNAs) have been recently shown to contribute to tumorigenesis by mediating changes in metabolism. ncRNAs act as key molecules in metabolic pathways regulation. The dysregulation of ncRNAs during cancer progression contributes to altered metabolic phenotypes leading to reprogrammed metabolism. Since ncRNAs affect different tumor processes by regulating mitochondrial dynamics and metabolism, in the future ncRNAs can be exploited in disease detection, diagnosis, treatment, and resistance. The purpose of this review is to highlight the role of ncRNAs in mitochondrial metabolic reprogramming and to relate their therapeutic potential in the management of genitourinary cancer. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is a devastating condition for women under 40 years old. Chemotherapy, especially the use of cisplatin, has been demonstrated to promote the apoptosis of granulosa cells in primary and secondary follicles, leading to POF. Our previous studies demonstrated that fat mass- and obesity-associated (FTO) plays an essential role in protecting granulosa cells from cisplatin-induced cytotoxicity. Various studies have suggested that the Hippo/YAP signalling pathway plays a significant role in regulating cell apoptosis and proliferation. Additionally, YAP1 is the main downstream target of the Hippo signalling pathway and is negatively regulated by the Hippo signalling pathway. However, whether the Hippo/YAP signalling pathway is involved in the protective effect of FTO on granulosa cells has not been determined. In this study, we found that after cisplatin treatment, the apoptosis of granulosa cells increased in a concentration-dependent manner, accompanied by the downregulation of FTO and YAP1. Furthermore, overexpression of FTO decreased cisplatin-induced granulosa cell apoptosis, inhibited the Hippo/YAP kinase cascade-induced phosphorylation of YAP1, and promoted the entry of YAP1 into the nucleus. The downstream targets of YAP1 (CTGF, CYR61, and ANKRD1) were also increased. Si-RNA-mediated downregulation of FTO promoted cisplatin-induced granulosa cell apoptosis, activated the Hippo/YAP kinase cascade, and inhibited the YAP1 entry into the nucleus. These effects were completely reversed by the small molecule inhibitor of YAP1-verteporfin (VP). Taken together, these data suggested that FTO-YAP1 plays a positive role in regulating the proliferation of injured granulosa cells induced by cisplatin. [ABSTRACT FROM AUTHOR]