Cancer Research Articles

HER2/neu 655 polymorphism, trastuzumab-induced cardiotoxicity, and survival in HER2-positive breast cancer patients.

HER2 overexpression in breast cancer correlates with poor outcomes. The incorporation of Trastuzumab into the treatment regimen has notably improved patient prognoses. However, cardiotoxicity emerges in approximately 20% of patients treated with the drug. This study aims to investigate the association between the HER2 655 A > G polymorphism, Trastuzumab-induced cardiotoxicity, and patient survival. The study involved 88 patients treated with Trastuzumab. Cardiotoxicity, defined as a reduction in left ventricular ejection fraction (LVEF) from baseline or the emergence of clinical signs of congestive heart failure, was identified during treatment follow-up. Genotyping of HER2 655 A > G employed TaqMan SNP technology. Genotype frequencies of HER2/neu 655 (53 AA, 32 AG, and 3 GG) were consistent with Hardy-Weinberg equilibrium. No significant differences were observed in mean baseline LVEF between patients who developed cardiotoxicity and those who did not. Within these groups, neither AA nor AG genotypes showed an association with changes in mean baseline or reduced LVEF levels. Logistic regression analysis, adjusted for hormonal status and anthracycline treatment, revealed that AG genotype carriers face a significantly higher risk of cardiotoxicity compared to AA carriers (OR = 4.42; p = 0.037). No association was found between the HER2/neu 655 A > G polymorphism and disease-free or overall survival, regardless of whether the data was adjusted for stage or not. HER2 655 A > G polymorphism is significantly linked to an increased risk of Trastuzumab-induced cardiotoxicity but does not correlate with variations in disease-free survival or overall survival rates.

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis.

Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction. In this systematic review and meta-analysis, we aimed to evaluate candidate biomarkers and their association with cancer-associated VTE. We searched Medline, EMBASE and Cochrane Central for studies that evaluated biomarkers in adult cancer patients from inception to September 2022. We included studies reporting on VTE after a cancer diagnosis with biomarker measurements performed at a defined timepoint. Median/Mean differences (for continuous measures) and Odds Ratios (for dichotomous measures) with 95% confidence intervals were estimated and pooled using random-effects models. We included 114 studies in the systematic review. Of these, 50 studies were included in the meta-analysis. We identified two biomarkers at cancer diagnosis (factor VIII and time to peak thrombin), three biomarkers pre-chemotherapy (d-dimer, fibrinogen and mean platelet volume) and, one biomarker preoperatively (platelet count) that had significant median or mean differences. Additionally, we found that hemoglobin <100g/L and white blood count >11 x 109/L were significantly associated with future VTE risk only when measured at cancer diagnosis. Pre-chemotherapy neutrophil lymphocyte ratio >3 and preoperative platelet count ≥400 x 109/L were also found to be associated with future VTE risk. In conclusion, this study identified nine candidate blood biomarkers that may help in optimizing VTE prediction in cancer patients that should be further explored in future studies.

The effect of a pre- and post-operative exercise program versus standard care on physical activity and sedentary behavior of patients with esophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (the PERIOP-OG Trial): a randomized controlled trial†.

Neoadjuvant cancer treatment (NCT) reduces both physical fitness and physical activity (PA) levels, which can increase the risk of adverse outcomes in cancer patients. This study aims to determine the effect of exercise prehabilitation on PA and sedentary behavior (SB) in patients undergoing NCT and surgery for esophagogastric malignancies. This study is a randomized pragmatic controlled multi-center trial conducted across three Irish hospitals. Participants were aged ≥18 years scheduled for esophagectomy or gastrectomy and were planned for NCT and surgery. Participants were randomized to an exercise prehabilitation group (EX) that commenced following cancer diagnosis, continued to the point of surgery, and resumed following recovery from surgery for 6weeks or to usual care (UC) who received routine treatment. The primary outcome measures were PA and SB. Between March 2019 and December 2020, 71 participants were recruited: EX (n = 36) or UC (n = 35). No significant differences were found between the EX group and UC group on levels of PA or SBs across all measured timepoints. Significant decreases in moderate-vigorous physical activity levels (MVPAs) were found between baseline and post-surgery (P = 0.028), pre-surgery and post-surgery (P = 0.001) and pre-surgery and 6-week follow-up (P = 0.022) for all participants. Step count also significantly decreased between pre-surgery and post-surgery (P < 0.001). Baseline aerobic fitness was positively associated to PA levels and negatively associated with SB. Esophagogastric cancer patients have lower than recommended levels of PA at the time of diagnosis and this decreased further following completion of NCT. An optional home- or group-based exercise intervention was not effective in improving PA levels or behaviors across the cancer treatment journey.

The mediating effect of self-efficacy on family functioning and psychological resilience in prostate cancer patients

AimsProstate cancer patients face impaired body image and psychological distress during the diagnosis and treatment of the disease, which leads to changes in mood, cognition and behavior. Psychological resilience has been shown to buffer shocks and stresses from the disease. Therefore, this study investigates the relationship between family functioning and psychological resilience in prostate cancer patients and the mediating role of self-efficacy between family functioning and psychological resilience to provide a relevant theoretical basis for improving patients' psychological status by providing relevant theoretical basis.MethodUsing a cross-sectional design, participants were 215 patients with prostate cancer admitted to and treated in a tertiary hospital in Jiangsu province, China. Questionnaires were administered using the general information questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), the Family Adaptation, Partnership, Growth, Affection, and Resolution Index (APGAR), and the General Self-efficacy Scale (GSES). Data were analyzed using descriptive and correlational analyses and the bootstrap mediation test was used to test the effect relationship between the variables.ResultsFamily functioning, self-efficacy and psychological resilience were significantly and positively correlated (r = 0.526, P &amp;lt; 0.01; r = 0.378, P &amp;lt; 0.01; r = 0.358, P &amp;lt; 0.01). The mediating effect of psychological resilience between family functioning and psychological resilience was significant, accounting for 42.56%.ConclusionFamily function and self-efficacy have been shown to increase the level of psychological resilience in prostate cancer patients. Attention should be paid to the mental health problems of prostate cancer patients, early screening and intervention, and the use of patients' family resources to improve their confidence in recovering from the disease, thus increasing their psychological resilience and improving their mental health.

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab.

Encorafenib-cetuximab has been approved for pretreated BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results. This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval. Individual patient data and pathology reports were collected. Overall survival (OS) was compared to BEACON and subgroup analyses were conducted for patients who would have been eligible and ineligible for BEACON. 166 patients were included with a median follow-up time of 14.5 months. Median OS was 6.7 months (95% CI:6.0-8.3) and differed from BEACON (9.3 months; 95% CI:8.0-11.3, p-value 0.002). Thirty-six percent of real-world patients would have been ineligible for the BEACON trial. Trial ineligible subgroups with symptomatic brain metastases and WHO performance status ≥2 had the poorest median OS of 5.0 months (95% CI:4.0-NR) and 3.9 months (95% CI:2.4-NR). This real-world cohort of mCRC patients treated with encorafenib-cetuximab showed a clinically relevant efficacy-effectiveness gap for OS. The chance of survival benefit from encorafenib-cetuximab in patients with brain metastases and/or WHO performance status ≥2 is negligible as neither efficacy nor effectiveness has been demonstrated.

Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy

Objective This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. Methods A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. Results A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (P = 0.001) and PFS (P < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. Conclusion This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

The Patient Activation Measure-13 (PAM-13) in an oncology patient population: psychometric properties and dimensionality evaluation

BackgroundAccurate assessment and enhancement of health-related skills among oncology patients are pivotal for optimizing cancer care. The Patient Activation Measure (PAM-13), a questionnaire designed to reflect an individual’s knowledge, skills, and confidence in self-healthcare management, has been validated across diverse countries and settings. Concerns have been raised regarding the cross-situational applicability, as patients with specific diseases and cultural backgrounds interpret questionnaire items differently. This study aimed to examine the structural validity and psychometric properties of the PAM-13 in an oncological patient cohort.MethodsBaseline data from a longitudinal non-randomized controlled study involving cancer out-patients (n = 1,125) from Comprehensive Cancer Centres in Southern Germany were analysed. The German version of the PAM-13 was employed. With classical test and item response theory methods data quality, reliability, convergent and structural validity, as well as psychometric properties were assessed. Exploratory (EFA) and confirmatory factor analyses (CFA) were employed to investigate the postulated unidimensionality of the underlying construct. With a partial credit model (PCM) we examined item fit, targeting, local independence and differential item functioning.ResultsParticipants were predominantly female (73.0%) with a breast cancer diagnosis (41.3%). While items were generally well-accepted, ceiling effects were observed and a high mean PAM-13 score (69.7, SD = 14.2) was noted, potentially compromising responsiveness to interventions. Reliability was adequate (Cronbach’s α = 0.81), person and item separation reliability were good to excellent (0.81 and 0.99, respectively). Explorations of the unidimensionality of the construct (EFA, CFA, PCM) yielded inconclusive results, hinting towards a two-factor solution. Item difficulty rankings deviated from the original. No differential item functioning was identified, and local independence was confirmed.ConclusionsWhile the PAM-13 serves as a valuable instrument for comprehending and promoting health-related skills in cancer patients, the identification of ceiling effects, disordered item-difficulty rankings, and inconclusive findings regarding unidimensionality contribute to the expanding body of evidence, emphasizing the dependency of PAM-13’s validity and reliability on distinctive characteristics within the population under investigation. Future research should prioritize refining or adding PAM-13 items to better capture the specific health-related challenges within diverse populations, paving the way for more effective patient engagement strategies in oncology.Trial registration numberDRKS00021779

ANALYSIS OF REGULATORY AND LEGAL SUPPORT FOR THE PREVENTION OF DIABETES MELLITUS IN CHILDREN

Diabetes mellitus has become one of the most prevalent chronic diseases in childhood today. International forecasts suggest that the incidence of diabetes will continue to rise in the coming decades, leading to a lifelong burden for millions of children worldwide. Therefore, prediction, prevention, and optimal treatment of diabetes, as well as early prevention of serious long-term complications, remain essential. Providing highly qualified medical care to diabetic patients is a crucial step in preventing the development of complications. The purpose of this article is to review existing research on diabetes prevention strategies for children, considering the different levels of medical care support available. Materials and Methods. This study investigates the organization of preventive care for children with diabetes in Ukraine. Researchers employed three key methods: bibliosemantic analysis, content analysis focused on analyzing Ukraine relevant regulations and legal frameworks, and the method of systemic approach and analysis to gain a comprehensive understanding of how preventive care is currently organized for children with diabetes in Ukraine. Results. In Ukraine, preventive measures and the provision of medical care to pediatric patients with diabetes in the past years and today are regulated by a number of documents and orders of the Ministry of Health. As part of the Comprehensive Program “Diabetes Mellitus” (1999) and in accordance with the Order of the Ministry of Health of Ukraine “On Improving the Organization of Providing Endocrinological Care to the Population of Ukraine” (2006), the State Register of Patients with Diabetes Mellitus (SYNADIAB) was created. The next step was the approval of the State Target Program “Diabetes Mellitus”. Subsequently, the Project of the national program “Health 2020: Ukrainian Dimension” became an effective tool, which outlined the main principles of the program implementation in the “Endocrinology” section for 2013-2020. It defined measures at all stages of diabetes prevention, such as primary prevention, which consists of maintaining and strengthening the general state of health and preventing or delaying the development of diabetes; secondary prevention should improve early detection of diabetes mellitus; tertiary prevention, which ensures the effectiveness and safety of treatment of children with diabetes to prevent the development of long-term complications. Today, the guidelines for the management of children with diabetes mellitus have been continued in such documents as “Diabetes Mellitus in Children”, Evidence-Based Clinical Guidelines (2023) and Standards of Care (2023). Conclusion. Diabetes mellitus is a chronic disease that ranks third in prevalence after cardiovascular and cancerous diseases and second in the structure of endocrine diseases after thyroid gland pathology. Today, the prevalence of diabetes mellitus among children is constantly increasing and, therefore, solving the issues associated with this disease is one of the priority tasks for the national health care system. This is because diabetes mellitus is associated with a high risk of complications leading to loss of work capacity, disability, and mortality across various population groups. Organizing high-quality medical care and establishing an effective prevention system based on the latest medical technologies is crucial. Diabetes demands attention. Understanding the risks and prevention of the disease can significantly increase the chances of protection and a long, healthy life through timely treatment.

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients’ survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.

Prognostic stratification of patients with pT4bN0M0 colorectal cancer following multivisceral resection: a multi-institutional case series analysis.

Colorectal cancer (CRC) patients with stage pT4b are a complex group as they show differences in tumor-infiltrated organs. Patients with the same stage often exhibit differences in prognosis after multivisceral resection (MVR). Thus far, some important prognostic factors have not been thoroughly investigated. Here, we identified the prognostic factors influencing CRC patients at pT4bN0M0 stage to better stratify the prognostic differences among patients. A retrospective analysis was conducted on patients diagnosed to have locally advanced CRC and who underwent MVR at three medical institutions from January 2010 to December 2021. The prognostic factors affecting the survival of CRC patients at pT4bN0M0 stage were identified by multivariate Cox proportional hazard models. We then classified the prognosis into different grades on the basis of these independent prognostic factors. We enrolled 690 patients with locally advanced CRC who underwent MVR; of these, 172 patients with pT4bN0M0 were finally included. Patients with digestive system (OS: hazard ratio [HR]=0.441; 95% confidence interval [CI]=0.217-0.900; P=0.024; DFS: HR=0.416; 95% CI=0.218-0.796; P=0.008) or genitourinary system invasion (OS: HR=0.405; 95% CI=0.193-0.851; P=0.017; DFS: HR=0.505; 95% CI=0.267-0.954; P=0.035) exhibited significantly better overall survival (OS) and disease-free survival (DFS) as compared to those with gynecological system invasion, while the OS and DFS were similar between the diggestive system and genitourinary system invasion groups (OS: HR=0.941; 95% CI=0.434-2.042; P=0.878; DFS: HR=1.211; 95% CI=0.611-2.403; P=0.583). Multivariate analysis showed that age (OS: HR=2.121; 95% CI=1.157-3.886; P=0.015; DFS: HR=1.869; 95% CI=1.116-3.131; P=0.017) and type of organs invaded by CRC (OS: HR=3.107; 95% CI=1.121-8.609; P=0.029; DFS: HR=2.827; 95% CI=1.142-6.997; P=0.025) were the independent prognostic factors that influenced the overall survival (OS) and disease-free survival (DFS) of CRC patients with pT4bN0M0 disease. The OS and DFS of patients showing invasion of the gynecological system group were significantly worse (P=0.004 and P=0.003, respectively) than those of patients with invasion of non-gynecological system group. On the basis of the above-mentioned two independent prognostic factors, patients were assigned to high-, medium-, and low-risk groups. Subgroup analysis showed that the OS and DFS of the medium- and high-risk groups were significantly worse (P=0.001 and P=0.001, respectively) than those of the low-risk group. Patients with pT4bN0M0 CRC show significant differences in their prognosis. The type of organs invaded by CRC is a valuable indicator for prognostic stratification of CRC patients with pT4bN0M0.

Pilot robotic mastectomy in Singapore (PRoMiSing I) study: first safety and feasibility prospective cohort trial in South East Asia.

Robotic mastectomy has been performed worldwide since 2015. The advantages of the robotic approach in nipple-sparing mastectomy have been proven with better visualization and preservation of blood supply to the nipple-areolar complex (NAC), with a lower incidence of necrosis. It also allows smaller incisions for both mastectomy and immediate breast reconstruction. To date, no centers in Singapore and Southeast Asia offer robotic mastectomy. We believe that robotic mastectomy is a feasible and safe technique that can be utilized by our population. This study aimed to ascertain the surgical outcomes and perform a learning curve analysis in patients undergoing robotic mastectomy in a multi-ethnic South East Asian population. A single arm prospective pilot study of eligible patients aged 21-70 years old with early breast cancer or high-risk patients indicated for risk reducing mastectomy who were eligible and consented for robotic mastectomy were enrolled in this trial from 22nd December 2022 to 15th December 2023. A total of 29 consecutive robotic mastectomies were performed. The mean total operative time was 95±10.2 minutes. The average blood loss was 5.7±1.9ml and the average length of stay was 1.05 days. The mean mastectomy specimen weight was 251 g, and there was no conversion to conventional mastectomy in any case. Furthermore, there were no 30-days morbidity or complications in terms of wound infection requiring intervention, flap and nipple-areolar complex (NAC) necrosis, and postoperative hematoma/bleeding requiring intervention. This study contributes to the current evidence that robotic mastectomy is a safe and feasible option, and could prove to be a great alternative to conventional mastectomy. Further prospective trials examining the long-term oncological outcomes of robotic mastectomy will be performed to establish the oncologic safety of this technique in breast cancer treatment.

Identification and uptake of cervical cancer screening during active surveillance in HIV-positive women attending a primary health care facility in Tshwane District, South Africa

Cervical cancer constitutes 20 - 25% of cancers in women in Sub-Saharan Africa. It is a preventable disease, subject to adequate screening, management and follow up. Nevertheless, more than half a million women worldwide develop invasive cervical cancer annually, with middle-and low-income countries achieving only 19% of successful screening coverage compared with high-income countries (63%). The age-standardised incidence rate for cervical cancer in South Africa is 24.71 per 100 000 women.

Towards proactive palliative care in oncology: developing an explainable EHR-based machine learning model for mortality risk prediction

BackgroundEx-ante identification of the last year in life facilitates a proactive palliative approach. Machine learning models trained on electronic health records (EHR) demonstrate promising performance in cancer prognostication. However, gaps in literature include incomplete reporting of model performance, inadequate alignment of model formulation with implementation use-case, and insufficient explainability hindering trust and adoption in clinical settings. Hence, we aim to develop an explainable machine learning EHR-based model that prompts palliative care processes by predicting for 365-day mortality risk among patients with advanced cancer within an outpatient setting.MethodsOur cohort consisted of 5,926 adults diagnosed with Stage 3 or 4 solid organ cancer between July 1, 2017, and June 30, 2020 and receiving ambulatory cancer care within a tertiary center. The classification problem was modelled using Extreme Gradient Boosting (XGBoost) and aligned to our envisioned use-case: “Given a prediction point that corresponds to an outpatient cancer encounter, predict for mortality within 365-days from prediction point, using EHR data up to 365-days prior.” The model was trained with 75% of the dataset (n = 39,416 outpatient encounters) and validated on a 25% hold-out dataset (n = 13,122 outpatient encounters). To explain model outputs, we used Shapley Additive Explanations (SHAP) values. Clinical characteristics, laboratory tests and treatment data were used to train the model. Performance was evaluated using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC), while model calibration was assessed using the Brier score.ResultsIn total, 17,149 of the 52,538 prediction points (32.6%) had a mortality event within the 365-day prediction window. The model demonstrated an AUROC of 0.861 (95% CI 0.856–0.867) and AUPRC of 0.771. The Brier score was 0.147, indicating slight overestimations of mortality risk. Explanatory diagrams utilizing SHAP values allowed visualization of feature impacts on predictions at both the global and individual levels.ConclusionOur machine learning model demonstrated good discrimination and precision-recall in predicting 365-day mortality risk among individuals with advanced cancer. It has the potential to provide personalized mortality predictions and facilitate earlier integration of palliative care.

S309-CAR-NK cells bind the Omicron variants in vitro and reduce SARS-CoV-2 viral loads in humanized ACE2-NSG mice.

Chimeric antigen receptor (CAR)-NK cells can be "off-the-shelf" products that treat various diseases, including cancer, infections, and autoimmune diseases. In this study, we engineered natural killer (NK) cells to express S309 single-chain fragment variable (scFv), to target the Spike protein of SARS-CoV-2, hereinafter S309-CAR-NK cells. Our study shows that S309-CAR-NK cells are effective against different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants. The S309-CAR-NK cells can (i) directly bind to SARS-CoV-2 pseudotyped virus (PV), (ii) competitively bind to SARS-CoV-2 PV with 293T cells expressing the human angiotensin-converting enzyme 2 (hACE2) receptor (293T-hACE2 cells), (iii) specifically target and lyse A549 cells expressing the spike protein, and (iv) significantly reduce the viral loads of SARS-CoV-2 wild-type (strain USA/WA1/2020) in the lungs of NOD/SCID gamma (NSG) mice expressing hACE2 (hACE2-NSG mice). Altogether, the current study demonstrates the potential use of S309-CAR-NK immunotherapy as an alternative treatment for COVID-19 patients.

Comprehensive comparative analysis of the periodontal pathogen Porphyromonas gingivalis: exploring the pan-genome, the reconstruction of the gene regulatory network and genome-scale metabolic network.

Porphyromonas gingivalis is a nonmotile, obligate anaerobic, Gram-negative bacterium known for its association with periodontal disease and its involvement in systemic diseases such as atherosclerosis, cardiovascular disease, colon cancer and Alzheimer's disease. This bacterium produces several virulence factors, including capsules, fimbriae, lipopolysaccharides, proteolytic enzymes and hemagglutinins. A comparative genomic analysis revealed the open pangenome of P. gingivalis and identified complete type IV secretion systems (T4SS) in strain KCOM2805 and almost complete type VI secretion systems (T6SS) in strains KCOM2798 and ATCC49417, which is a new discovery as previous studies did not find the proteins involved in secretion systems IV and VI. Conservation of some virulence factors between different strains was observed, regardless of their genetic diversity and origin. In addition, we performed for the first time a reconstruction analysis of the gene regulatory network (GRN), identifying transcription factors and proteins involved in the regulatory mechanisms of bacterial pathogenesis. In particular, QseB regulates the expression of hemagglutinin and arginine deaminase, while Rex may suppress the release of gingipain through interactions with PorV and the formatum/nitrate transporter. Our study highlights the central role of conserved virulence factors and regulatory pathways, particularly QseB and Rex, in P. gingivalis and provides insights into potential therapeutic targets.

The Use of Chatbots in Head and Neck Mucosal Malignancy Treatment Recommendations.

As cancer patients increasingly use chatbots, it is crucial to recognize ChatGPT's potential in enhancing health literacy while ensuring validation to prevent misinformation. This study aims to assess ChatGPT-3.5's capability to provide appropriate staging and treatment recommendations for head and neck mucosal malignancies for vulnerable populations. Forty distinct clinical vignettes were introduced into ChatGPT to inquire about staging and treatment recommendations for head and neck mucosal malignancies. Prompts were created based on head and neck cancer (HNC) disease descriptions (cancer location, tumor size, lymph node involvement, and symptoms). Staging and treatment recommendations according to the 2021 National Comprehensive Cancer Network (NCCN) guidelines were scored by three fellowship-trained HNC surgeons from two separate tertiary care institutions. HNC surgeons assessed the accuracy of staging and treatment recommendations, such as the completeness of surgery and the appropriateness of treatment modality. Whereas ChatGPT's responses were 95% accurate at recommending the correct first-line treatment based on the 2021 NCCN guidelines, 55% of the responses contained inaccurate staging. Neck dissection was incorrectly omitted from treatment recommendations in 50% of the cases. Moreover, 40% of ChatGPT's treatment recommendations were deemed unnecessary. This study emphasizes ChatGPT's potential in HNC patient education, aligning with NCCN guidelines for mucosal malignancies, but highlights the importance of ongoing refinement and scrutiny due to observed inaccuracies in tumor, nodal, metastasis staging, incomplete surgery options, and inappropriate treatment recommendations. Otolaryngologists can use this information to caution patients, families, and trainees regarding the use of ChatGPT for HNC education without expert guidance.

A novel perineal exposure method in laparoscopic abdominal perineal resection of rectal cancer: a case series study

BackgroundAbdominal perineal resection (APR) of rectal cancer, also known as Mile’s procedure, is a classic procedure for the treatment of rectal cancer. Through the improvement of surgical skills and neoadjuvant therapy, the sphincter-preserving rate in rectal cancer patients has improved, even in patients with ultralow rectal cancer who underwent APR in the past. However, APR cannot be completely replaced by low anterior resection (LAR) in reality. APR still has its indications, when the tumor affects the external sphincter, etc. Good perineal exposure in APR is difficult and can seriously affect surgical safety and the long-term prognosis.MethodsWe reviewed the records of 16 consecutive patients with rectal cancer who underwent APR at Anqing Municipal Hospital from January 2022 to April 2023, including 11 males and 5 females, with an average age of 64.8 ± 10.3 years. The perineal operation was completed with the Lone-Star® retractor-assisted (LSRA) exposure method. After incising the skin and subcutaneous tissue, a Lone-Star® retractor was placed, and the incision was retracted in surrounding directions with 8 small retractors, which facilitated the freeing of deep tissues. We dynamically adjusted the retractor according to the plane to fully expose the surgical field.ResultsAll 16 patients underwent laparoscopic-assisted APR successfully. Thirteen procedures were performed independently by a single person, and the others were completed by two persons due to intraoperative arterial hemostasis. All specimens were free of perforation and had a negative circumferential resection margin (CRM). Postoperative complications occurred in 4 patients, including urinary retention in 1 patient, pulmonary infection in 1 patient, intestinal adhesion in 1 patient and peristomal dermatitis in 1 patient, and were graded as ClavienDindo grade 3 or lower and cured. No distant metastasis or local recurrence was found for any of the patients in the postoperative follow-up.ConclusionsThe application of the LSRA exposure method might be helpful for perineal exposure during APR for rectal cancer, which could improve intraoperative safety and surgical efficiency, achieve one-person operation, and increase the comfort of operators.

HIF2A mediates lineage transition to aggressive phenotype of cancer-associated fibroblasts in lung cancer brain metastasis

ABSTRACT Brain metastasis is the most devasting form of lung cancer. Recent studies highlight significant differences in the tumor microenvironment (TME) between lung cancer brain metastasis (LCBM) and primary lung cancer, which contribute significantly to tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are the major component of pro-tumor TME with high plasticity. However, the lineage composition and function of CAFs in LCBM remain elusive. By reanalyzing single-cell RNA sequencing (scRNA-seq) data (GSE131907) from lung cancer patients with different stages of metastasis comprising primary lesions and brain metastasis, we found that CAFs undergo distinctive lineage transition during LCBM under a hypoxic situation, which is directly driven by hypoxia-induced HIF-2α activation. Transited CAFs enhance angiogenesis through VEGF pathways, trigger metabolic reprogramming, and promote the growth of tumor cells. Bulk RNA sequencing data was utilized as validation cohorts. Multiplex immunohistochemistry (mIHC) assay was performed on four paired samples of brain metastasis and their primary lung cancer counterparts to validate the findings. Our study revealed a novel mechanism of lung cancer brain metastasis featuring HIF-2α-induced lineage transition and functional alteration of CAFs, which offers potential therapeutic targets.

Letter to the editor for the article"From early risk to 1-year mortality: a comprehensive assessment of postoperative venous thromboembolism in upper gastrointestinal cancer patients - a nationwide cohort study".

Letter to the editor for the article"From early risk to 1-year mortality: a comprehensive assessment of postoperative venous thromboembolism in upper gastrointestinal cancer patients - a nationwide cohort study".

Reference-free inferring of transcriptomic events in cancer cells on single-cell data

BackgroundCancerous cells’ identity is determined via a mixture of multiple factors such as genomic variations, epigenetics, and the regulatory variations that are involved in transcription. The differences in transcriptome expression as well as abnormal structures in peptides determine phenotypical differences. Thus, bulk RNA-seq and more recent single-cell RNA-seq data (scRNA-seq) are important to identify pathogenic differences. In this case, we rely on k-mer decomposition of sequences to identify pathogenic variations in detail which does not need a reference, so it outperforms more traditional Next-Generation Sequencing (NGS) analysis techniques depending on the alignment of the sequences to a reference.ResultsVia our alignment-free analysis, over esophageal and glioblastoma cancer patients, high-frequency variations over multiple different locations (repeats, intergenic regions, exons, introns) as well as multiple different forms (fusion, polyadenylation, splicing, etc.) could be discovered. Additionally, we have analyzed the importance of less-focused events systematically in a classic transcriptome analysis pipeline where these events are considered as indicators for tumor prognosis, tumor prediction, tumor neoantigen inference, as well as their connection with respect to the immune microenvironment.ConclusionsOur results suggest that esophageal cancer (ESCA) and glioblastoma processes can be explained via pathogenic microbial RNA, repeated sequences, novel splicing variants, and long intergenic non-coding RNAs (lincRNAs). We expect our application of reference-free process and analysis to be helpful in tumor and normal samples differential scRNA-seq analysis, which in turn offers a more comprehensive scheme for major cancer-associated events.