Strategies For Management Of Cancer Research Articles

Organ preservation, for rectal cancer: general overview of the latest data from phase III randomized trials.

Organ preservation (OP) strategies are gaining interest in improving the quality of life in the management of rectal cancer, particularly for tumors located in the distal or middle rectum. The optimal OP protocol is still not standardized and relies on randomized trials. This review summarizes past and ongoing studies on OP protocols for adenocarcinoma of the distal and middle rectum. We searched for articles and abstracts on randomized clinical trials investigating OP approaches for rectal cancer, including data presented at the LUCARRE Congress held in Nice on November 25, 2023, covering ongoing and recently published trials on rectal preservation. Our review's findings are presented in four tables: the first evaluates key trials with overall survival (OS) as the primary endpoint; the second provides an overview of past Phase III trials; the third reviews Phase II/III trials that specifically focus on local excisions (LE); and finally, the fourth summarizes ongoing trials. Each table is accompanied by detailed comments elucidating the significance and implications of the presented data, alongside a review of current guidelines. We highlight the growing interest in OP strategies for rectal cancer management to enhance patients' quality of life. Despite the lack of international consensus on the optimal OP protocol, past and ongoing randomized trials provide valuable findings into the evolving management strategies of rectal cancer treatment. The presented data supports the role of randomized phase III trials to provide evidence for a change in clinical practice.

Exploring Risk Factors for Cervical Cancer that lead to Biopsy Examination in the United States: A Logistic Regression Analysis

Introduction: Cervical cancer remains a significant global health concern with a substantial impact on women's lives, particularly in less-developed countries where resources are already limited. The disease is primarily caused by high-risk subtypes of human papillomavirus (HPV) but is largely preventable. Objective: The primary objective of this study was to examine the factors that contribute to the development of cervical cancer and explore whether these factors are linked to the choice of cervical biopsy. Methods: The dataset from the UCI Repository was analyzed. Bivariate analysis was conducted to identify risk factors significantly associated with the occurrence of biopsy. Multiple logistic regression modeling was used to identify key predictors of biopsy likelihood. Results: Bivariate analysis showed several risk factors that were significantly associated with biopsy occurrence, including the duration of hormonal contraceptive use, a history of sexually transmitted diseases (STDs), specific STD types, cervical screening methods, and the number of STDs among patients. Further analysis using multiple logistic regression modeling identified two key predictors: prolonged ho rmonal contraceptive use (for 5 to 9 years) and the use of the Schiller cervical screening method. Conclusion: The findings of this study indicate the importance of targeted screening and prevention strategies in cervical cancer management, which could play a crucial role in reducing the disease burden.

Considerable decline in prostate cancer mortality in Nordic countries after 2000.

In the late 1990s, the Nordic countries, with Norway at the top, were among the countries with the highest prostate cancer mortality in the world. We present updated mortality rates from the Nordic countries and discuss possible interpretations of changes in trends. Age-standardized rates for prostate-specific mortality in 1985-2022, estimated lifetime risk of death (0-84 years) and annual changes in mortality were obtained from the NORDCAN database. Joinpoint regression was used to evaluate trend changes for the period 1985-2022. For comparison, rates from other European countries from 2022 were retrieved from the GLOBOCAN database. Between 1995-99 and 2018-22, mortality in men aged 40-84 years decreased from 38% in Denmark to 59% in Norway. By 2022 Norway had the second lowest mortality among the Nordic countries overall, and the lowest under 85 years. The life-time risk of dying from prostate cancer declined from 5.6-7.1% in 1995-99 to 3.1-4.2% in the last 5-year period. During the last years mortality has decreased most rapidly in Sweden (4.5% annually from 2016) and Norway (4.3% annually from 2014). The Nordic countries are no longer among the countries with the highest mortality in Europe. Mortality from prostate cancer has decreased significantly in the Nordic countries over the last decades. Possible explanatory factors are likely to include improvements in prostate cancer management strategies and treatment.

Developing a Simple Conceptual Causal Model for Predicting Early Recurrence and Mortality after Curative Surgery for Colorectal Cancer Patients

Introduction: Colorectal cancer (CRC) represents the second leading cause of cancer-related mortality. This study focused on the development of a robust conceptual causal model designed to predict early recurrence and mortality following curative surgery in colorectal cancer patients. Methods: In this retrospective cohort study, we included 284 patients with colorectal cancer (CRC) who underwent surgery at the Imam Khomeini (RA) Clinic in Hamadan, Iran, between 2001 and 2017. Demographic characteristics, treatment modalities, and other relevant data were extracted from patient records. Predictors were analyzed using Generalized Structural Equation Modeling (GSEM) for survival analysis, employing an accelerated failure time (AFT) approach. Both unadjusted and adjusted time ratios (TRs) were calculated using STATA software. Results: The results of our developed causal model indicated that receiving chemotherapy was significantly associated with a shorter survival time ratio (TR = 0.415, 95% CI: 0.290-0.593), and recurrence time (TR = 0.363, 95% CI: 0.190-0.696). Conversely, patients who underwent multiple chemotherapy sessions exhibited a longer survival time (TR = 2.130, 95% CI: 1.790-2.534) and recurrence time (TR = 2.206, 95% CI: 1.609- 3.023). Age had a direct impact on the recurrence time (TR = 0.758, 95% CI: 0.602-0.955). Additionally, age had a significant direct effect on the receipt of chemotherapy, the cancer site, and the receipt of radiotherapy. Conclusion: In summary, our study's causal model reveals that chemotherapy shortens survival time but multiple sessions can extend both survival and recurrence times. Age significantly affects recurrence time and chemotherapy receipt. These findings highlight the importance of personalized treatment strategies in colorectal cancer management

Technical Considerations for Oncologic Colectomy

AbstractColectomy for malignant tumors or unresectable benign tumors requires preoperative planning based on cross-sectional imaging, consideration of neoadjuvant therapy, a decision on the extent of lymphadenectomy, and comprehensive knowledge of the relevant anatomy. Imaging review is critical for determining resectability and noting any aberrant anatomy. Based on the imaging, neoadjuvant therapy should be considered for bulky or locally advanced disease. The anatomical resection of the colon, mesentery, and lymph node basins is performed in accordance with the concept of complete mesocolic excision (CME), entailing the resection of the mesentery with visceral peritoneum intact, appropriate proximal and distal margins taken en bloc, and high ligation of the primary feeding vessels along which the lymph nodes are positioned. High ligation of the colic arteries is part of a standard lymphadenectomy and is intended to address possible micrometastatic nodal disease and proper staging for adjuvant therapy. Extended lymphadenectomy in the form of CME with central vascular ligation is indicated for patients with advanced T stage or clinical lymphadenopathy. Whether extended lymphadenectomy should be performed routinely is subject to debate. In this article, we review the indications and operative strategies for management of colon cancer in various locations in the colon, as well as key considerations for minimally invasive colectomy and advanced techniques such as CME with central vascular ligation.

Immunotherapy in Recurrent Ovarian Cancer.

It remains challenging to treat recurrent ovarian cancer effectively as traditional interventions like chemotherapy and surgery have limited long-term efficacy, highlighting an urgent need for innovative approaches. Immunotherapy offers potential advantages in modulating the immune response against tumor cells and has emerged as a promising strategy in ovarian cancer management. This review discusses various immunotherapy modalities, including active and passive immune strategies, for recurrent ovarian cancer. We systematically reviewed recent immunotherapy advances for recurrent ovarian cancer, including the efficacy and mechanisms of single and dual immune checkpoint inhibitors, checkpoint inhibitor combinations with chemotherapy or radiotherapy, anti-angiogenic agents, PARP inhibitors, antibody-drug conjugates (ADC), tumor vaccines, and adoptive cell therapies (ACT). Additionally, we assessed emerging research on biomarkers predictive of immunotherapy responsiveness in ovarian cancer. The findings indicate that immunotherapy, particularly combinations involving immune checkpoint inhibitors and other agents, demonstrates promising efficacy in recurrent ovarian cancer, with some therapies showing enhanced benefits in specific subtypes. The immune microenvironment in platinum-sensitive and -resistant cases exhibits distinct immunological profiles, influencing therapy outcomes. Several potential biomarkers have been identified, potentially aiding in patient stratification and treatment optimization. Immunotherapy significantly advances recurrent ovarian cancer treatment, with various combinations potentially improving outcomes. Further research on predictive biomarkers and immune microenvironment characteristics is crucial for personalizing immunotherapy approaches and enhancing their efficacy in managing recurrent ovarian cancer.

Fertility Preservation in Female Patients with Cancer Part II: Royan Institute Clinical Practice Guideline for Girls and Women with Cancer; A Review Study.

The fertility preservation (FP) is a paramount concern for oncology patients and should be regarded as an essential component of their overall cancer management strategy. The magnitude of this issue has been recognized in FP guidelines. The formulation and execution of harmonized guidelines and policies concerning the provision of FP services, inclusive of therapeutic strategies and standardization of procedures, are crucial to surmount disagreements regarding the delivery of these therapeutic services and avert delays in cancer treatment. The matter of FP and the methodology for managing the treatment and follow-up of cancer patients should be documented as a component of their management guideline, thereby providing patients with clear recommendations on fertility preservation. In this manuscript, we provide a succinct overview of existing international guidelines history and reference comprehensive networks of FP services for oncology patients. Furthermore, we present the Royan Institute's guideline specifically designed for preserving the fertility of female oncology patients.

Should all cervical cancer patients with positive lymph node receive definitive radiotherapy: a population-based comparative study.

The optimal initial management strategy for cervical cancer with lymph node metastases (LNM) remains a topic of ongoing debate. This study aimed to explore the correlation between surgery followed by postoperative radiotherapy (PORT) and definitive radiotherapy (RT), as well as their impact on the prognosis of patients with LNM. Patients with positive lymph nodes (PLNs) in 2009 FIGO stage I-III cervical cancer were selected from SEER database. Kaplan-Meier and log-rank analysis were utilized to assess survival outcomes. Cox and Interaction analyses were employed to compare the survival benefits. 2936 patients were included in this study. Multivariate analysis revealed the choice of primary treatment significantly impacted both cancer-specific survival (CSS) and overall survival (OS), serving as an independent prognostic factor for patients with LNM. After adjusting for imbalanced variables, surgery plus PORT exhibited significant improvements in CSS and OS in the stage I-II and PLNs ≤ 5 subgroups. However, no statistically significant difference was observed between the two treatment modalities in stage III and PLNs > 5 subgroups. Through interaction analysis, it was observed that stage I-II and PLNs ≤ 5 subgroups exhibited a significant survival benefit from surgery plus PORT. Surgery plus PORT could lead to improved outcomes for cervical cancer in patients with stage I-II or PLNs ≤ 5. However, this approach did not apply to patients with stage III or PLNs > 5. Therefore, a comprehensive assessment of LNM and local tumor spread should guide rationalized treatment modalities when managing patients presenting LNM.

Synthesis, Anti-proliferation, Apoptosis Induction in Breast Cancer Cells, and Aromatase Inhibition of Coumarin-Triazole Hybrids: In Vitro and In Silico Studies.

Breast cancer is one of the most common cancers found in women worldwide. Besides the availability of clinical drugs, drug resistance and considerable side effects are concerning issues driven the needs for the discovery of novel anticancer agents. Aromatase inhibition is one of the effective strategies for management of hormone-dependent breast cancer. Triazole, coumarin, and isatin are heterocyclic scaffolds holding great attention in the field of drug design. Molecular hybridization is a well-known strategy to achieve new molecules with improved potency and properties. Herein, a set of 27 triazole-based hybrids (i.e., coumarin-triazoles series 5-6 and isatin-triazoles series 7) were synthesized and investigated for their anti-proliferation, apoptosis induction, and aromatase inhibitory potentials. Anti-proliferative study against the hormone-dependent breast cancer (T47D) cell line indicated that coumarin-triazole 5h (R = NO2) and 6i (R = SO2NH2) were the two most potent antiproliferative agents. Particularly, compound 5h showed comparable potency and superior selectivity index than that of the reference drug, doxorubicin. Moreover, the coumarin-triazole 5h induced cellular apoptosis of the estrogen-dependent breast cancer (MCF-7) cells. Additionally, findings from the aromatase inhibitory assay suggested four compounds as potential aromatase inhibitors (i.e., 5i, 6f, 6g and 6i, IC50 = 1.4-2.4 μM). Two QSAR models with preferable predictive performances were constructed to reveal key properties influencing antiproliferative and aromatase inhibitory effects. Molecular docking was conducted to elucidate the possible binding modalities against the target aromatase enzyme. Key structural features essential for the binding were highlighted. Moreover, the drug-like properties of top-ranking compounds were assessed to ensure their possibilities for successful development.

Dual-phase nanoscissors disrupt vasculature-breast cancer stem cell crosstalk for breast cancer treatment

Clinical treatment effects of breast cancer are heavily frustrated by the malignant crosstalk between tumor vasculature and breast cancer stem cells (BCSCs). This study introduces a two-phase therapeutic strategy targeting the interplay between tumor vasculature and BCSCs to overcome this challenge. Here, we designed an FLG/ZnPc nanoscissor, which combines mild photodynamic therapy (PDT) to generate reactive oxygen species (ROS) with vascular normalization therapy (VNT) to break the crosstalk between tumor vessels and BCSCs. In the first phase, our approach breaks the vascular niche that supports BCSCs by restoring tumor vascular function and promoting ROS-induced BCSCs differentiation into less malignant forms, enhancing treatment sensitivity. The second phase employs high-impact photothermal therapy (PTT) to ablate tumor masses. This integrated “mild PDT-PTT” approach aims to reduce tumor growth and metastasis, offering a comprehensive strategy for effective breast cancer management.

Do Salivary Cullin7 Gene Expression and Protein Levels Provide Advantages over Plasma Levels in Diagnosing Breast Cancer?

In addition to the tumor suppressor role of Cullin 7 (Cul7), one of the proteins belonging to the Cullin (Cul) family, studies have also suggested that Cul7 may act as an oncogene under certain conditions. The role of the Cul7 molecule in breast cancer is still unclear, and understanding its function could have significant implications for identifying novel therapeutic targets or improving diagnostic strategies in breast cancer management. In this study, the levels of the Cul7 molecule in plasma and noninvasive material saliva were investigated, and its possibility as a marker for breast cancer was discussed. Protein levels of blood and saliva samples taken from breast cancer patients and a healthy control group were measured by the ELISA (Enzyme-Linked Immunosorbent Assay) method. Gene expression levels between the two groups were analyzed by the qPCR (quantitative Polymerase Chain Reaction) method. In our study, Cul7 mRNA and protein expression levels were examined in 60 breast cancer patients and 20 healthy female controls, and a statistically insignificant difference was found between the patient and control groups in both plasma and saliva samples (p > 0.05). No correlation was found between the clinical characteristics of the patients and plasma and saliva Cul7 gene expression and protein levels (p > 0.05). Considering the possibility of Cul7 being a biomarker at the protein and mRNA levels, plasma is thought to be a better study material for Cul7. Our findings suggest that in the context of a study on salivary material, the expression of Cul7 at the mRNA level may have better potential utility as a biomarker.

Impact of American Thyroid Association's Revised Cancer Management Guidelines on Thyroid Cancer Incidence Trends: A Retrospective Cohort Study, 2000-2020.

Background: The past four decades have seen a steady increase in thyroid cancer in the United States (US). This study investigated the impact of the American Thyroid Association (ATA)'s revised cancer management guidelines on thyroid cancer incidence trends and how the trends varied by socioeconomic, histologic, geographic, and racial and ethnic characteristics from 2000 to 2020. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) database to identify thyroid cancer cases diagnosed among US patients between 2000 and 2020. We employed joinpoint regression software to fit, assess, and compare thyroid cancer incidence trends over time stratified by socioeconomic status (SES), histologic type, geographic location, and race/ethnicity. Results: Between 2000 and 2009, there was an average annual increase of 5.8% in thyroid cancer incidence (average annual percent change (AAPC): 5.8, p < 0.05). Subsequently, there was a modest rise (AAPC: 1.1, p < 0.05) from 2010 to 2015, followed by a significant annual decrease of 4.8% from 2016 to 2020 (AAPC: -4.8, p < 0.05). The joinpoint regression models identified prominent inflection points around 2009 and 2015, aligning with the years of the ATA's cancer management revisions. These intricate dynamics in thyroid cancer incidence trends from 2000 to 2020 were shaped by SES and histologic, geographic, and racial/ethnic factors. Conclusions: Thyroid cancer incidence trends over the past two decades can be partially explained by the changes in thyroid cancer screening and management recommendations. These findings underscore the importance of cancer management strategies and highlight the need for targeted interventions to address disparities in thyroid cancer incidence across minority demographic groups.

The THE RELATIONSHIP OF TUMOUR BUDDING AND TUMOUR INFILTRATING LYMPHOCYTES IN DIAGNOSTIC BREAST CORE BIOPSIES WITH PATHOLOGICAL RESPONSE IN RESECTION SPECIMENS

Background: Breast cancer, ranks as the second-leading global cancer-related cause of death. This article highlights prognostic significance of tumour budding and tumour infiltrating lymphocytes, emphasizing their roles in guiding treatments. Recent discoveries support their pivotal contribution in enhancing risk assessments and refining management strategies in breast cancer. Methods: A retrospective study of 80 in house at Shaukat Khanum Memorial Cancer Hospital diagnosed with invasive ductal carcinoma in the year 2014. Patients were categorized into two groups based on receptor status: Group 1 (ER/PR positive, Her2 negative, or ER/PR/Her2 positive) and Group 2 (Triple negative and ER/PR negative, Her2 positive). Each group had 40 cases. Pathologists evaluated tumour budding, tumour infiltrating lymphocytes, Nottingham Grading, and receptor status on core biopsies. Study aimed to determine the relationship of TB and TILs assessed on core biopsies on corresponding resection specimen in terms of pathological tumour stage and overall survival after therapy. Results: In Group I, TILs &gt;50% correlated with lower pathological tumour stage, while &lt;50% correlated with higher post- treatment tumour stage. In Group II, most had &lt;50% TILs, but some responded well. Low TB-Status in Group I linked to higher rates of ypT0, while in Group II, high TB-Status corresponded with high PT stage, i.e., yPT1 suggesting prognostic value for TILs and TB in breast cancer response and staging. Conclusions: Study suggests that higher TILs percentages correlate with improved treatment response and survival in contrast to lower TILs. Similarly, lower TB-status is associated with complete treatment response (y PT0) and higher TB- status is directly related to poor treatment response and higher tumour stage.

Upregulation of HPV16E1 and E7 expression and FOXO3a mRNA downregulation in high-grade cervical neoplasia.

Cervical cancer remains a significant global health concern, ranking as the fourth most prevalent cancer among women worldwide. Human papillomaviruses (HPV) transcribe many genes that might be responsible for cervical cancer development. This study aims to investigate the correlation between the expression of HPV16 early genes and the mRNA expression of human FOXO3a, a tumor suppressor gene, in association with various stages of cervical precancerous lesions. Eighty-five positive HPV16 DNA cervical swab samples were recruited and categorized based on cytology stages, i.e., negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL). RT-qPCR was performed to amplify HPV16E1, E4, E6, E6*I, E7, and human FOXO3a mRNA expression in all samples. The relative expression of those genes was calculated using GAPDH as a control. Detection of FOXO3a mRNA expression in the cervical cancer cell line by RT-qPCR and meta-analysis of FOXO3a expression using the RNA-Seq dataset by GEPIA2 were analyzed to support the conclusions. Among the cervical samples, HPV16E1 and E7 were significantly increased expression correlating to disease severity. HPV16E4 mRNA expression was 100% detected in all LSIL samples, with a significant increase observed from normal to LSIL stages. Conversely, FOXO3a mRNA expression decreased with disease severity, and the lowest expression was observed in HSIL/squamous cell carcinoma (SCC) samples. In addition, similar results of FOXO3a downregulation were also found in the cervical cancer cell line and RNA-Seq dataset of cervical cancer samples. HPV16 early mRNA levels, including E1 and E7, increase during cancer progression, and downregulation of FOXO3a mRNA is a characteristic of cervical cancer cells and HSIL/SCC. Additionally, HPV16E4 mRNA expression was consistently detected in all LSIL samples, suggesting the presence of active viral replication. These findings might lead to further investigation into the interplay between HPV gene expression and host cell factors for targeted therapeutic strategies in cervical cancer management.

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma.

Breast cancer remains a significant cause of mortality globally, necessitating effective treatment strategies. Neoadjuvant chemotherapy (NAC) is widely employed to minimize tumor burden and prevent local spread, with treatment efficacy varying based on molecular subtypes. Despite advancements, resistance to conventional therapies persists, prompting the exploration of alternative approaches, including immune cell therapy. Tumor-infiltrating lymphocytes (TILs) have emerged as immunological biomarkers in breast cancer, exhibiting associations with molecular subtypes and treatment response. This retrospective study assessed the clinico-pathological relationship between stromal TILs and AR expression across molecular subtypes of invasive breast carcinoma in an Indian cohort. Thirty-seven patients receiving NAC followed by modified radical mastectomy were analyzed for TILs and molecular subtyping. Immunohistochemistry was used to determine hormone receptor status and AR expression. A higher AR positivity was observed in hormone receptor-positive/Her2neu-negative and hormone receptor-positive/Her2neu-positive tumors compared to triple-negative breast cancers (TNBCs). Significant associations were observed between AR expression and tumor grade, but not with age or Her2neu status. Although no significant correlation was found between AR and complete response to NAC, a weak negative correlation between AR and TILs was noted. Notably, TNBCs with negative AR and Ki67 index exhibited poorer responses to NAC, emphasizing the need for adjuvant therapy. These findings underscore the complex interplay between AR, TILs, and treatment response in breast cancer, highlighting the potential of personalized therapeutic approaches. Further research is warranted to elucidate the prognostic significance of AR and its implications for tailored treatment strategies in breast cancer management.

Updates on Breast Reconstruction: Surgical Techniques, Challenges, and Future Directions.

The increasing global incidence of breast cancer underscores the significance of breast reconstruction in enhancing patients' quality of life. Breast reconstruction primarily falls into two categories: implant-based techniques and autologous tissue transfers. In this study, we present a comprehensive review of various aspects of implant-based reconstruction, including different types of implants, surgical techniques, and their respective advantages and disadvantages. For autologous breast reconstruction, we classified flaps and optimal harvest sites and provided detailed insights into the characteristics, benefits, and potential complications associated with each flap type. In addition, this review explores the emerging role of fat grafting, which has received increasing attention in recent years. Despite advancements, there remains substantial scope for further improvements in breast reconstruction, emphasizing not only aesthetic outcomes, but also a reduction in complications and postoperative recovery. By offering a comprehensive overview of the historical evolution, current landscape, and future prospects of breast reconstruction, this review aims to provide readers with a comprehensive understanding of breast cancer management strategies.

Nanoparticle-Assisted Cancer Imaging and Targeted Drug Delivery for Early-Stage Tumor Detection and Combined Diagnosis-Therapy Systems for Improved Cancer Management

Nanoparticle-assisted imaging and targeted drug delivery represent a transformative approach in cancer diagnostics and therapeutics, particularly for early-stage tumor detection and integrated diagnosis- therapy systems. This review explores recent advancements in nanoparticle technology for magnetic resonance imaging (MRI), computed tomography (CT), optical imaging, and ultrasound, emphasizing the efficacy of nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs), gold and bismuth nanoparticles, and quantum dots as contrast agents. Nanoparticles offer unique advantages, including enhanced permeability and retention (EPR) effects, ligand-receptor targeting, and microenvironment-responsive drug release, which improve localization and accumulation in tumor tissues. Additionally, dual-function theranostic systems utilizing nanoparticles enable simultaneous diagnostic imaging and therapy, allowing real-time monitoring of therapeutic efficacy and minimizing off-target effects. The integration of nanoparticles for both diagnostic and therapeutic purposes holds significant promise for precision oncology, providing a more personalized, minimally invasive, and effective cancer management strategy. This review also discusses current limitations, including issues of biocompatibility, toxicity, and regulatory challenges, while proposing future directions to overcome these barriers. By presenting a comprehensive analysis of nanoparticle platforms in oncology, this paper aims to underscore their potential in revolutionizing cancer diagnosis and therapy, ultimately contributing to improved patient outcomes and advancing the field of nanomedicine.

Serum urea concentration and risk of 16 site-specific cancers, overall cancer, and cancer mortality in individuals with metabolic syndrome: a cohort study

BackgroundThe relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS.MethodsWe analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini–Hochberg correction was used to account for multiple comparisons.ResultsOver the median follow-up period of 11.86 years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91–0.99), 0.68 (0.50–0.92), and 0.76 (0.64–0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02–1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45–0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74–0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77 years for cancer mortality outcome, 5034 cancer deaths were detected. An “L-shaped” nonlinear dose–response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77–0.91).ConclusionsSerum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies.

Abstract B008: Exploring the Dual Roles of RNAs as Oncogenic Drivers and Therapeutic Targets in Cancer: A Cross-Sectional Study

Abstract RNAs have emerged as pivotal molecules in the complex landscape of cancer biology, acting as both drivers of oncogenesis and therapeutic targets. This cross-sectional experimental design research explores the dual roles of RNAs, particularly focusing on the interplay between non-coding RNAs (ncRNAs), messenger RNAs (mRNAs), and their regulatory networks in various cancer types. The study systematically analyzes RNA expression profiles across a broad spectrum of cancer samples, employing high-throughput sequencing technologies combined with bioinformatics tools to identify key RNA species that contribute to tumorigenesis. The experimental design includes the collection of tumor and adjacent normal tissues from patients diagnosed with breast, lung, and colorectal cancers. RNA extraction and sequencing are performed to generate comprehensive expression profiles. Differential expression analysis is conducted to pinpoint RNAs that are significantly dysregulated in cancerous tissues compared to their normal counterparts. Subsequently, functional assays, including RNA interference (RNAi) and CRISPR/Cas9-mediated gene editing, are utilized to validate the oncogenic or tumor-suppressive roles of these RNAs in cancer cell lines. To further elucidate the mechanistic pathways, the study integrates data from RNA-binding protein immunoprecipitation (RIP) and crosslinking immunoprecipitation (CLIP) assays, providing insights into the RNA-protein interactions that influence cancer progression. Additionally, the research evaluates the therapeutic potential of targeting these RNAs, using small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) in preclinical cancer models. Preliminary findings highlight the significance of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) in modulating key signaling pathways involved in cell proliferation, apoptosis, and metastasis. This study underscores the importance of RNA-based diagnostics and therapeutics, paving the way for innovative treatment strategies in cancer management. Citation Format: Fathelrahman M Gameel. Exploring the Dual Roles of RNAs as Oncogenic Drivers and Therapeutic Targets in Cancer: A Cross-Sectional Study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B008.

Analysis of immune status and prognostic model incorporating lactic acid metabolism-associated genes

BackgroundCancer development is intricately linked with metabolic dysregulation, including lactic acid metabolism, which plays a pivotal role in tumor progression and immune evasion. However, its specific implications in gastric adenocarcinoma (STAD) remain unclear. This study introduces a novel methodology to evaluate lactic acid metabolism comprehensively in STAD, aiming to elucidate its prognostic significance and impact on immunotherapy efficacy. Targeted therapies directed at key lactic acid metabolism genes (LMGs) identified within the tumor microenvironment (TME) hold promise for personalized treatment strategies.MethodsLactic acid metabolism patterns were assessed in 415 STAD patients using a panel of 21 LMGs. Cox regression and Lasso regression analyses were employed to develop a predictive risk model based on differentially expressed genes (DEGs). Validation of the model was conducted using independent cohorts from the GEO and TCGA databases, as well as additional datasets focused on immunotherapy responses. Further investigations into TME dynamics of lactic acid metabolism included functional assays targeting SLC16A3, a pivotal gene identified through our analyses.ResultsPatients were stratified into distinct risk groups based on their lactic acid metabolism profiles. Low-risk patients exhibited attenuated lactic acid metabolism, correlating with favorable clinical outcomes characterized by prolonged survival and enhanced responsiveness to immunotherapy. Notably, tumor cells within the TME demonstrated heightened levels of active lactic acid metabolism, particularly impacting tumor-infiltrating lymphocytes such as CD8 + T cells and regulatory T cells. Mechanistically, SLC16A3 emerged as a critical regulator promoting STAD cell proliferation, invasion, and migration while modulating the metabolic landscape.ConclusionThis study underscores the prognostic value of a lactic acid metabolism-based model in STAD, providing insights into its potential as a predictive biomarker for patient stratification and therapeutic targeting. The findings highlight SLC16A3 as a promising candidate for therapeutic intervention aimed at modulating lactic acid metabolism in the TME, thereby advancing personalized treatment strategies in gastric cancer management.