Cancer Research Articles

Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases.

The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR=1.61, 95% CI: 1.48-1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5years, ≥5years, ≥10years, ≥20years, and ≥30years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR=1.25, P <0.001), endometrial (SIR=1.40, P =0.019), cervical (SIR=2.56, P <0.001), and ovarian cancer (SIR=1.50, P =0.010). FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/.

Prediction of precancerous cervical cancer lesions among women living with HIV on antiretroviral therapy in Uganda: a comparison of supervised machine learning algorithms

BackgroundCervical cancer (CC) is among the most prevalent cancer types among women with the highest prevalence in low- and middle-income countries (LMICs). It is a curable disease if detected early. Machine learning (ML) techniques can aid in early detection and prediction thus reducing screening and treatment costs. This study focused on women living with HIV (WLHIV) in Uganda. Its aim was to identify the best predictors of CC and the supervised ML model that best predicts CC among WLHIV.MethodsSecondary data that included 3025 women from three health facilities in central Uganda was used. A multivariate binary logistic regression and recursive feature elimination with random forest (RFERF) were used to identify the best predictors. Five models; logistic regression (LR), random forest (RF), K-Nearest neighbor (KNN), support vector machine (SVM), and multi-layer perceptron (MLP) were applied to identify the out-performer. The confusion matrix and the area under the receiver operating characteristic curve (AUC/ROC) were used to evaluate the models.ResultsThe results revealed that duration on antiretroviral therapy (ART), WHO clinical stage, TPT status, Viral load status, and family planning were commonly selected by the two techniques and thus highly significant in CC prediction. The RF from the RFERF-selected features outperformed other models with the highest scores of 90% accuracy and 0.901 AUC.ConclusionEarly identification of CC and knowledge of the risk factors could help control the disease. The RF outperformed other models applied regardless of the selection technique used. Future research can be expanded to include ART-naïve women in predicting CC.

Quantitative exploration of barriers to access cancer services experienced by cancer patients in Lesotho

Background: Cancer mortality has been estimated to increase in sub-Saharan Africa to more than a million deaths in 2023. There is a need for an increase in cancer screening, diagnosis and treatment infrastructure to curb this rise in cancer mortality. Many people with cancer face significant barriers to accessing treatment.Aim: The study aimed to explore barriers to accessing cancer care services experienced by cancer patients in Lesotho.Setting: This study was conducted at the Senkatana oncology clinic in Maseru, Lesotho.Methods: The study adopted a quantitative cross-sectional design. Cancer patient interviews were conducted using a structured questionnaire.Results: A total of 115 patients responded to the questionnaire, and 79.1% were female. Over half of the participants (53.9%) found it difficult to access cancer services because they had to get services from multiple healthcare facilities in different areas. All of them had to join long queues. Distance from the healthcare facilities was also a challenge for a significant number (64.3%), and a substantial number (66.1%) had difficulties arranging transport to such facilities. Finally, financial issues, such as paying for transport, healthcare and diagnostic tests, were determined to be major constraints.Conclusion: The study concludes that most cancer patients face financial and practical barriers. This affects access to cancer services, particularly for patients not residing in Maseru.Contribution: The study shares information regarded as barriers to cancer services in a low- and middle-income country.

Development of a nomogram for predicting malnutrition in elderly hospitalized cancer patients: a cross-sectional study in China

ObjectivesThe Patient-Generated Subjective Global Assessment (PG-SGA) serves as a specialized nutritional assessment instrument designed for cancer patients. Despite its specificity, the complexity and time requirements of this tool, along with the necessity for administration by trained professionals, limit its practicality in clinical settings. Our objective is to identify a straightforward, efficient, and dependable nutritional assessment tool to promote broader adoption in clinical practice.MethodsThis study encompassed a total of 450 patients diagnosed with cancer. Of these, 315 individuals constituted the training set, and the remaining 135 were allocated to the external validation set. The model variables were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) regression method. Binary logistic regression outcomes facilitated the development of a nomogram, offering a visual depiction of the predicted probabilities. The predictive accuracy of the nomogram model was evaluated by calculating the area under the Receiver Operating Characteristic (ROC) curve.ResultsThe LASSO method detected four variables that were included in the final prediction model: age, serum albumin levels (ALB), body mass index (BMI), and activities of daily living (ADL). The area under the curve (AUC) for this prediction model was 0.905. Both the internal and external calibration curves for malnutrition showed that the predictive nomogram model was highly accurate.ConclusionThe study has developed a prediction model that demonstrates remarkable accuracy in forecasting malnutrition. Furthermore, it presents a streamlined nutritional assessment tool aimed at swiftly identifying cancer patients at nutritional risk, thereby facilitating oncologists in delivering targeted nutritional support to these individuals.

CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias

Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many healthcare settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the diagnosis of fusion-driven leukemias. We validated these assays using diagnostic APL and CML patient samples from academic centers and dried blood spots from low-resource environments, demonstrating 100% sensitivity and specificity. We identified assay optimizations to enable the use of these tests outside of tertiary cancer centers and clinical laboratories, enhancing the potential impact of this technology. Rapid point-of-care diagnostics can improve outcomes in cancer patients by expanding access to therapies for highly treatable diseases that would otherwise lead to serious adverse outcomes due to delayed or missed diagnoses.

Relationships between nine neuropsychiatric disorders and cervical cancer: insights from genetics, causality and shared gene expression patterns

BackgroundNeuropsychiatric disorders and cervical cancer exert substantial influences on women’s health. Furthermore, neuropsychiatric disorders frequently manifest as common symptoms in cancer patients, potentially increasing the risk of malignant neoplasms. This study aimed to identify neuropsychiatric disorders that are genetically and causally related to cervical cancer and to investigate the molecular mechanisms underlying these associations.MethodsGWAS data related to nine neuropsychiatric disorders, namely, schizophrenia, bipolar disorder, autism spectrum disorder, Parkinson’s disease, anxiety, Alzheimer’s disease, mood disorders, depression, and alcohol dependence, were obtained to calculate heritability (h2) and genetic correlation (rg) with cervical cancer using linkage disequilibrium score regression (LDSC). Mendelian randomization (MR) analysis of the two cohorts was employed to assess the causal effects. Shared gene expression pattern analysis was subsequently conducted to investigate the molecular mechanism underlying these significant associations.ResultsAnxiety, mood disorders, depression, and alcohol dependence were genetically correlated with cervical cancer (all adjusted P < 0.05). Only depression was causally related to cervical cancer in both the discovery (ORIVW: 1.41, PIVW = 0.02) and replication cohorts (ORIVW: 1.80, PIVW = 0.03) in the MR analysis. Gene expression pattern analysis revealed that 270 genes related to depression and cervical cancer, including tumour necrosis factor (TNF), were significantly upregulated in cervical cancer patients, while vascular endothelial growth factor A (VEGFA), transcription factor AP-1 (JUN), and insulin-like growth factor I (IGF-I) were associated with prognosis in cervical cancer patients (all P < 0.05). These overlapping genes implicated the involvement of multiple biological mechanisms, such as neuron death, the PI3K-Akt signalling pathway, and human papillomavirus infection.ConclusionsGenetic, causal and molecular evidence indicates that depression increases the risk of cervical cancer. The TNF, VEGFA, JUN, and IGF-1 genes and the neuron death, PI3K-Akt, and human papillomavirus infection signalling pathways may possibly explain this association.

Constructing lncRNA-miRNA-mRNA networks specific to individual cancer patients and finding prognostic biomarkers

BackgroundThe competitive endogenous RNA (ceRNA) hypothesis suggests that microRNAs (miRNAs) mediate a regulatory relation between long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) which share similar miRNA response elements (MREs) to bind to the same miRNA. Since the ceRNA hypothesis was proposed, several studies have been conducted to construct a network of lncRNAs, miRNAs and mRNAs in cancer. However, most cancer-related ceRNA networks are intended for representing a general relation of RNAs in cancer rather than for a patient-specific relation. Due to the heterogeneous nature of cancer, lncRNA-miRNA-mRNA interactions can vary in different patients.ResultsWe have developed a new method for constructing a ceRNA network of lncRNAs, miRNAs and mRNAs, which is specific to an individual cancer patient and for finding prognostic biomarkers consisting of lncRNA-miRNA-mRNA triplets. We tested our method on extensive data sets of three types of cancer (breast cancer, liver cancer, and lung cancer) and obtained potential prognostic lncRNA-miRNA-mRNA triplets for each type of cancer.ConclusionsAnalysis of expression patterns of the RNAs involved in the triplets and survival rates of cancer patients revealed several interesting findings. First, even for the same cancer type, prognostic lncRNA-miRNA-mRNA triplets can be different depending on whether lncRNA and mRNA show opposite or similar expression patterns. Second, prognostic lncRNA-miRNA-mRNA triplets are often more predictive of survival rates than RNA pairs or individual RNAs. Our approach will be useful for constructing patient-specific lncRNA-miRNA-mRNA networks and for finding prognostic biomarkers from the networks.

Radiomic analysis reveals diverse prognostic and molecular insights into the response of breast cancer to neoadjuvant chemotherapy: a multicohort study

BackgroundBreast cancer patients exhibit various response patterns to neoadjuvant chemotherapy (NAC). However, it is uncertain whether diverse tumor response patterns to NAC in breast cancer patients can predict survival outcomes. We aimed to develop and validate radiomic signatures indicative of tumor shrinkage and therapeutic response for improved survival analysis.MethodsThis retrospective, multicohort study included three datasets. The development dataset, consisting of preoperative and early NAC DCE-MRI data from 255 patients, was used to create an imaging signature-based multitask model for predicting tumor shrinkage patterns and pathological complete response (pCR). Patients were categorized as pCR, nonpCR with concentric shrinkage (CS), or nonpCR with non-CS, with prediction performance measured by the area under the curve (AUC). The prognostic validation dataset (n = 174) was used to assess the prognostic value of the imaging signatures for overall survival (OS) and recurrence-free survival (RFS) using a multivariate Cox model. The gene expression data (genomic validation dataset, n = 112) were analyzed to determine the biological basis of the response patterns.ResultsThe multitask learning model, utilizing 17 radiomic signatures, achieved AUCs of 0.886 for predicting tumor shrinkage and 0.760 for predicting pCR. Patients who achieved pCR had the best survival outcomes, while nonpCR patients with a CS pattern had better survival than non-CS patients did, with significant differences in OS and RFS (p = 0.00012 and p = 0.00063, respectively). Gene expression analysis highlighted the involvement of the IL-17 and estrogen signaling pathways in response variability.ConclusionsRadiomic signatures effectively predict NAC response patterns in breast cancer patients and are associated with specific survival outcomes. The CS pattern in nonpCR patients indicates better survival.

Hemostatic radiotherapy: a narrative review of the literature.

In locally advanced cancer, bleeding is a common clinical presentation and radiotherapy (RT) provides a noninvasive, well-tolerated, cost-effective treatment. However, the choice for fractionation dose and schedule seem to merely depend on physician's preference rather than specific guidelines. We reviewed the available literature on palliative hemostatic RT for response rate (RR) and bleeding duration in relation with the given dose. The PubMed database was used to search for articles, which were assessed by predetermined inclusion and exclusion criteria. A total of 54 articles, published over the last 20 years until December 2023 were analyzed for dose and/or fractionation regimen and their relation to the RR. A variety of fractionation schedules are used for palliative symptom control, including hemostasis. Research focusing on hemostatic irradiation specifically and prospective studies are rare. Moreover, to our knowledge, there are no specific (prospective) studies ongoing. Both external beam radiotherapy (EBRT) and brachytherapy lead to bleeding control and daily or weekly hypofractionated irradiation is safe and effective for both high and low biological equivalent dose (BED) regimens. If feasible, based on patient condition, some studies favor higher BED regimens to obtain more durable tumor/ higher bleeding response. Higher radiation dose for thoracic irradiation may be indicative for simultaneous presentation of obstruction and/or dysphagia. Brachytherapy may be used solely or in combination with EBRT or in the setting of re-irradiation. Short-course regimens are preferred in patients in with low performance index scores. For future studies, multivariate analysis, including BED, can be important to assess efficacy of different fractionation schedules for a variety of tumor etiologies. Hemostatic RT, both by EBRT and brachytherapy, appears to be a safe and effective palliative treatment that clinically and statistically significantly reduces bleeding in cancer patients. The available literature is limited regarding prospective and uniform evaluation of hemostatic RT, including fractionation schedules. BED seems to be indicative for a better RR for specific indications. Current evidence suggests that treatment decisions should be tailored according to the patients' condition, tumor etiology and other clinical symptoms. More (prospective) research focusing on hemostasis is necessary to develop clear guidelines.

Exploring the integration of dentistry within a multidisciplinary palliative care team: does bedside dental care improve quality of life and symptom burden in inpatient palliative care patients?

Despite the significant impact of oral problems on the quality of life of palliative care patients, comprehensive studies are lacking. This study is the first of its kind to address this gap by including both a dental examination and an intervention and assessing quality of life using the EORTC QLQ OH 15 questionnaire. The objective of this study is to explore the impact of incorporating dentists into inpatient palliative care, with a focus on enhancing quality of life and alleviating symptom burden. In this monocentric study, data were gathered from a palliative care unit over an 8-month period. At the beginning of the multidisciplinary treatment, T0, patients underwent both a dental examination and interviews utilizing established questionnaires, the EORTC QLQ-C30 (core, general) and OH 15 (oral health). A week later, at T1, patients underwent a follow-up examination and interview. The QLQ-C30 and OH15 are widely recognized instruments developed by the European Organisation for Research and Treatment of Cancer (EORTC) for evaluating health related quality of life in cancer patients. A total of n = 103 patients (48.5% women) were enrolled in the study. The median duration since their last dental visit was 1year, and the dental condition at T0 was desolate. At T1, statistically and clinically significant changes in oral quality of life and symptom burden were observed. Noteworthy changes were noted in the OH-QoL score (median 63 vs. 92, p < 0.001), sticky saliva (median 33 vs. 0, p < 0.001), sensitivity to food and drink (median 33 vs. 0, p < 0.001), sore mouth (median 33 vs. 0, p > 0.001), and poorly fitting dentures (median 33 vs. 0 p < 0.001). Additionally, improvements were observed in xerostomia candidiasis and mucositis. The study highlights the powerful contribution of integrating a dentist in inpatient palliative care. With very little dental effort and simple ward and bedside treatments, significant improvements in the oral symptom burden of critically ill palliative patients can be achieved. This contributes to improved care status, relief of distressing symptoms, and ultimately improved quality of life. The results strongly support the consideration of dental support as an integral part of palliative care units.

Low rates of complications and β-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

Covalent Organic Frameworks as Potential Drug Carriers and Chemotherapeutic Agents for Ovarian Cancers.

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.

The application of mean number of DNA breakpoints in sperm cryopreservation

Growing concerns over declining male semen quality and rising infertility have shifted attention to male fertility. Sperm cryopreservation emerges as a crucial tool in preserving male fertility, especially for patients who need proactive preservation, such as cancer patients before undergoing radiation or chemotherapy. Although cryopreservation does not directly address infertility, effective preservation can support future fertility. However, the process may compromise sperm DNA integrity. Despite their impairment, damaged sperm often retain vitality and may still have the potential to fertilize an egg. Nonetheless, if damaged sperm fertilize an egg, excessive DNA damage could impede embryo implantation and development, despite the egg's repair capabilities. Consequently, precise detection of sperm DNA damage is crucial and urgent. To better address the issue of sperm DNA damage detection, we have introduced a novel fluorescence biosensor technology known as the TDT/SD Probe. This technology utilizes terminal deoxynucleotidyl transferase (TdT) and strand displacement probes to accurately detect the number of sperm DNA breakage points during the cryopreservation process. Experimental results reveal that the number of sperm DNA breakpoints significantly increases after both sperm vitrification (8.17 × 105) and conventional slow freezing (10.80 × 105), compared to the DNA breakpoints of fresh semen samples (5.19 × 105). However, sperm vitrification has the least impact on sperm breakage points. This research provides innovative means for further optimizing sperm preservation techniques by offering a novel DNA damage detection method, enabling more precise assessment of sperm DNA damage during the freezing process.

Computed tomography-measured body composition can predict long-term outcomes for stage I-III colorectal cancer patients

BackgroundThere remains a pressing need to identify biomarkers capable of reliably predicting prognostic outcomes for colorectal cancer (CRC) patients. As several body composition parameters have recently been reported to exhibit varying levels of prognostic significance in particular cancers, the present study was devised to assess the ability of body composition to predict long-term outcomes for CRC patients with different stages of disease.MethodsIn total, this retrospective analysis enrolled 327 stage I-III CRC patients whose medical records were accessed for baseline demographic and clinical data. Primary outcomes for these patients included disease-free and overall survival (DFS and OS). The prognostic performance of different musculature, visceral, and subcutaneous fat measurements from preoperative computed tomography (CT) scans was assessed.ResultsOver the course of follow-up, 93 of the enrolled patients experienced recurrent disease and 39 died. Through multivariate Cox regression analyses, the visceral/subcutaneous fat area (V/S) ratio was found to be independently associated with patient DFS (HR=1.93, 95% CI: 1.24–3.01, P=0.004), and the skeletal muscle index (SMI) as an independent predictor for OS (HR=0.43, 95% CI: 0.21–0.89, P=0.023). Through subgroup analyses, higher V/S ratios were found to be correlated with reduced DFS among patients with stage T3/4 (P=0.011), lymph node metastasis-positive (P=0.002), and TNM stage III (P=0.002) disease, whereas a higher SMI was associated with better OS in all T stages (P=0.034, P=0.015), lymph node metastasis-positive cases (P=0.020), and in patients with TNM stage III disease (P=0.020).ConclusionBoth the V/S ratio and SMI offer potential utility as clinical biomarkers associated with long-term CRC patient prognosis. A higher V/S ratio and a lower SMI are closely related to poorer outcomes in patients with more advanced disease.

Exploring the effects of post operative hyperoxic intermittent stimuli on reticulocyte levels in cancer patients: a randomized controlled study.

Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries. This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann-Whitney tests, and linear and logistic regression. The final analysis included 33 patients (median age 62 [IQR 58-66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3-57.8) versus - 5.3% (IQR - 19.2-57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines' values. This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings. The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

Nodal Surgery for Patients ≥ 70 Undergoing Mastectomy for DCIS? Choose Wisely.

Routine sentinel lymphadenectomy (SLNB) for early-stage HR+/HER2- breast cancer in women ≥70 is discouraged by Choosing Wisely, but whether SLNB can be routinely omitted in women ≥70 with DCIS undergoing mastectomy is unclear. This study aims to evaluate rates of axillary surgery and nodal positivity (pN+) in this population to determine the impact of axillary surgery on treatment decisions. Females ≥70 with DCIS undergoing mastectomy were identified from the National Cancer Database (2012-2020). The rate of upstaging to invasive cancer (≥pT1) or pN+ was assessed. Subset analyses were conducted for ER+ patients. Adjuvant therapies were evaluated among ≥pT1 patients after stratifying by nodal status. Of 9,030 patients, 1,896 (21%) upstaged to ≥pT1. Axillary surgery was performed in 86% of patients, predominantly sentinel lymphadenectomy (SLNB, 65%). Post hoc application of Choosing Wisely criteria demonstrated that 93% of the entire cohort and 97% of ER+ DCIS patients could have avoided axillary surgery. Nodal positivity was 0.3% among those who didn't upstage, and 12% among those upstaging to ≥pT1, with <2% having pN2-3 disease, irrespective of receptor subtype. Node-positive patients had higher adjuvant therapy usage, but there was no recommendation for adjuvant chemotherapy or radiation for 71% and 66% of pN+ patients, respectively. Axillary surgery can be omitted for most patients ≥70 undergoing mastectomy for ER+ DCIS, aligning with recommendations for invasive cancer, and omission can be considered in those with ER- disease. Future guidelines incorporating preoperative imaging, as in the SOUND trial, may aid in identifying patients benefiting from axillary surgery.

Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer

BackgroundPancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer.MethodsIn the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T.ResultsWe found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48–72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal.ConclusionsIn this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia.

When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. We aimed to identify independent risk factors for IE in patients with VGS BSI. This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Living Bacteriophage Engineering for Functional Material Synthesis, Bioanalytical Sensing and Disease Theranostics

Facing the increasingly global crisis of antibiotic resistance, it is urgent to develop new antibacterial agents and methods. Simultaneously, as research progresses, the occurrence, development, and treatment of diseases, especially some malignant cancers, are found to be closely associated with the bacterial microenvironment, prompting us to reconsider the efficiency of existing antibacterial strategies for disease treatments. Bacteriophages have been employed as antibacterial agents for an extended period owing to their high biocompatibility and particular targetability toward the host bacterial strains. Nonetheless, they are almost neglected due to their slow and limited efficacy in antibacterial practice, especially in acute and severe infectious cases. In recent years, fantastic advancements in various biochemical technologies, such as bacteriophage display technology, genetic engineering, and chemical molecular engineering, have enabled scientists to conduct a broader range of modifications and transformations on the existing bacteriophages with inherited unique characteristics of themselves. As a result, a series of novel bacteriophage platforms are designed and fabricated with significantly enhanced properties and multiplied functionalities. These offer new avenues for combating infections caused by drug-resistant bacteria and treatment of malignancies that are associated with bacterial infections, holding great significance and potential in the innovative theranostic applications.

The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis.

Cancer initiates as a consequence of genomic mutations and its subsequent progression relies in part on increased production of ribosomes to maintain high levels of protein synthesis for unchecked cell growth. Recently, cytidine deaminases have been uncovered as sources of mutagenesis in cancer. In an attempt to form a connection between these 2 cancer driving processes, we interrogated the cytidine deaminase family of proteins for potential roles in human ribosome biogenesis. We identified and validated APOBEC3A and APOBEC4 as novel ribosome biogenesis factors through our laboratory's established screening platform for the discovery of regulators of nucleolar function in MCF10A cells. Through siRNA depletion experiments, we highlight APOBEC3A's requirement in making ribosomes and specific role within the processing and maturation steps that form the large subunit 5.8S and 28S ribosomal (r)RNAs. We demonstrate that a subset of APOBEC3A resides within the nucleolus and associates with critical ribosome biogenesis factors. Mechanistic insight was revealed by transient overexpression of both wild-type and a catalytically dead mutated APOBEC3A, which both increase cell growth and protein synthesis. Through an innovative nuclear RNA sequencing methodology, we identify only modest predicted APOBEC3A C-to-U target sites on the pre-rRNA and pre-mRNAs. Our work reveals a potential direct role for APOBEC3A in ribosome biogenesis likely independent of its editing function. More broadly, we found an additional function of APOBEC3A in cancer pathology through its function in ribosome biogenesis, expanding its relevance as a target for cancer therapeutics.