Survival Rate Of Cancer Patients Research Articles

The 5-year relative survival rate among cancer patients in Henan province of China, 2015-2019

Objective: To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data. Methods: Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019. Results: During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion: The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

Expression and role of CNIH2 in prostate cancer.

Prostate cancer is one of the most common cancers in men and poses a significant threat to global male health. Traditional prostate cancer assessment methods have certain limitations, necessitating the identification of new prognostic factors and treatment targets. Our study revealed that low expression of the cornichon family AMPA receptor auxiliary protein 2 (CNIH2) gene was associated with a better progression-free survival rate in prostate cancer patients. The area under the receiver operating characteristic (ROC) curve (AUC) showed that the prognostic ability of the CNIH2 gene was high at 1, 3, and 5 years. The gene was an independent prognostic factor according to multivariate analysis. Functional verification experiments showed that knocking down the CNIH2 gene could inhibit the proliferation, migration and invasion of prostate cancer cells and could also inhibit tumor growth in nude mice. Our study is the first to reveal the important role of the CNIH2 gene in prostate cancer. This discovery provides a new research direction for individualized treatment and prognostic evaluation of prostate cancer.

FHOD3 Promotes the Progression of Lung Cancer by Regulating the Caspase-3-Mediated Signaling Pathway.

Lung cancer causes hundreds of thousands of deaths each year worldwide. FHOD3 was reported to accelerate the progression of brain cancer. However, its role in lung cancer is not clear. This study aimed to investigate the role of FHOD3 in lung cancer. The clinical significance of FHOD3 in lung cancer was analyzed based on the data from the TCGA database. The expression level of FHOD3 was detected by qPCR technology. Cell proliferation was detected by CCK-8 assay, and cell invasion was detected by transwell assay. The activity of caspase-3 was determined by the ELISA method, cell apoptosis was iden-tified by TUNEL assay, and protein expression was measured by western blotting technology. Based on the TCGA data, FHOD3 was overexpressed in tumor tissues compared to the normal tissues. Patients with higher FHOD3 expression exhibited a worse survival rate. The expression levels of FHOD3 in lung cancer cell lines were much higher than that in normal cells. When FHOD3 was knocked down, the ability of cell proliferation and invasion was sig-nificantly inhibited. Cell apoptosis rate was increased reversely. The activity of caspase-3 was increased significantly. In addition, the expression level of cleaved caspase-3 was increased. The expression levels of Bax, caspase-8, and ICAD were also increased significantly. However, the expression of antiapoptotic molecule Bcl-2 was decreased reversely. This suggests that the caspase-3-mediated apoptosis signaling pathway was activated by FHOD3 knockdown. FHOD3 was overexpressed and negatively associated with survival rate in lung cancer patients. FHOD3 regulates cell proliferation, invasion, and apoptosis through the caspase-3-mediated signaling pathway. This study indicates that FHOD3 is an important gene contributing to the progression of lung cancer and might be a new drug target for the therapy of lung cancer.

SURGICAL TREATMENT OF RECTAL CANCER WITH PRESERVATION OF THE LEFT COLIC ARTERY AND ICG NAVIGATION

Goal. To analyze the peculiarities of surgical diagnosis of lymphogenic metastasis in patients with colorectal cancer. Generalization of data from Ukrainian and foreign literature, results of randomized studies and meta-analyses. The study is based on the results of observation of 88 patients with colorectal cancer (CRC) of the prospective study group. To analyze the features of surgical diagnostics of lymphogenic metastasis in patients with colorectal cancer. Materials and methods. The results of surgical treatment of 88 patients with rectal cancer were analyzed and systematized. These patients underwent examination and treatment in 2023-2024 at the "Prykarpattian Clinical Oncology Center of the Ivano-Frankivsk Regional Council." The study included patients with stage II-III colorectal cancer (T2-3N0-2M0) without complicated courses. All patients received treatment based on NCCN recommendations. Surgical treatment was performed in standard volume with the removal of all regional lymph node groups and preservation of the left colic artery using real-time lymph node mapping with indocyanine green. All patients were divided into two study groups: Group I included 45 patients who underwent anterior or low anterior resection of the rectum with preservation of the left colic artery. This group was subdivided into two subgroups: Ia – 13 patients who underwent intraoperative indocyanine green injection for real-time lymph node visualization. Ib – 32 patients who did not receive this drug but underwent the same volume of surgery. Group II consisted of 43 patients who underwent anterior or low anterior resection of the rectum with high ligation of the inferior mesenteric artery. This group served as the control group. Results. The main mechanisms of lymphogenic metastasis in colorectal cancer patients in Ivano-Frankivsk were characterized. Literature data on the features of surgical diagnostics of colorectal cancer metastasis were summarized. A review of literature shows the social significance of these studies, as this pathology often leads to patient disability, requiring surgical interventions and further palliative treatment due to the widespread metastasis associated with this disease. The priority task for researchers remains the search for the most effective treatment methods for this pathology, based on randomized studies of colorectal cancer treatment and international protocols. According to the literature, surgical treatment of colorectal cancer remains insufficiently effective at the current stage of oncology. Modern methods offer low 5-year survival rates, emphasizing the need to study factors for individualized treatment. The overall 5-year survival rate for colorectal cancer patients from 2018-2022 was (45.8±2.3)%. The effectiveness of using real-time ICG navigation for lymph node mapping and preservation of the left colic artery in stage II-III (T2-4N1-2M0) rectal cancer patients has been proven. This technique allows for optimal lymphadenectomy, reducing the frequency of surgical complications by 14.7% (p<0.05). Conclusion. Ensuring radical resection of rectal cancer while maximizing blood supply preservation to the anastomosis is the main goal of colorectal surgeons. Over the past two decades, surgical techniques have significantly improved due to advancements in surgical equipment. It is anticipated that surgical technologies will further evolve towards enhancement and individualization in the future. Our procedure serves as an example of modern and personalized rectal cancer surgery.

Androgen Receptor Promotes Lung Cancer Metastasis by Modifying the miR23a-3p/EPHB2 Pathway.

This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients. Through various techniques, such as Argonaute immunoprecipitation, luciferase assays, and ChIP, this study confirmed the positive effects of androgen receptor (AR) on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models. The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level, which in turn required changes in miRNA-23a-3p. Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR. This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.

Development and validation of a prognostic model for colon cancer based on mitotic gene signatures and immune microenvironment analysis

BackgroundMitotic processes play a pivotal role in tumor progression and immune responses. However, the correlation between mitosis-related genes, clinical outcomes, and the tumor microenvironment (TME) in colon cancer remains unclear. This study aims to develop a prognostic and therapeutic significance model for colon cancer based on mitosis-related genes.MethodsRNA expression profiles and clinical data of 453 colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Mitosis-related genes were selected from the MsigDb database. The gene model was constructed using differential analysis, univariate and multivariate Cox regression, and Lasso regression analyses. The predictive model was validated using data from the GSE17536, GSE17537, and GSE39582 datasets. Predictive accuracy was evaluated via Receiver Operating Characteristic (ROC) curves, while nomograms were developed by integrating clinical and pathological features. Gene set enrichment analysis explored biological processes and pathways linked to the model. TME was assessed using ESTIMATE, and the proportion and function of immune cells were analyzed through CIBERSORT. Drug sensitivity analysis was conducted using the CTRP database.ResultsA predictive model based on 17 mitosis-related genes (KIFC1, CCNF, EME1, CDC25C, ORC1, CCNJL, ANKRD53, MEIS2, FZD3, TPD52L1, MAPK3, CDKN2A, EDN3, NPM2, PSRC1, INHBA, BIRC5) was created. The model exhibited robust predictive performance across both training and validation cohorts. Nomograms for predicting 3-, 5-, and 7-year survival rates in colon cancer (COAD) patients were generated. The model's correlation with immune cell infiltration and function was highlighted.ConclusionThe mitosis-related gene model serves as a valuable indicator for predicting survival outcomes in colon cancer patients.

Esophagojejunostomy using a circular stapler vs. a linear stapler for gastric cardia cancer patients: impact of upper margin length and tumor size on the survival rate.

The incidence of gastric cancer is concomitantly rising with gastric cardia cancer worldwide. While the improvement of gastric cancer surgical techniques is glowing, this study assesses the impact of the upper margin length and tumor size on the survival rate for gastric cardia cancer patients who underwent total laparoscopic total gastrectomy(TLTG) or laparoscopic assisted total gastrectomy(LATG). A total of 63 patients with gastric cardia cancer who underwent laparoscopic total gastrectomy were retro-prospectively collected from January 2021 to May 2023. While assessing the impact of upper margin length and tumor size on the survival rate, esophagojejunostomy using a linear stapler has been compared to a circular stapler. The sixty-three patients met inclusion criteria; 32 (51%) underwent LATG and 31 (49%) underwent TLTG. Their mean age was 65 years (range, 45-77). The blood loss means in LATG and TLTG was 74.69 and 50.16 ml, respectively (p = 0.005), and surgery duration was higher in LATG than LATG with respective means of 247 min and 222.42 min. (p = 0.006). However, the tumor size means (p = 0.5), and upper margin length means (p = 0.052) were not significantly different in the LATG and TLTG groups, respectively. The number of resected and assessed lymph node was adequate in the LATG and TLTG groups. The current study still does not find an independent related risk from the upper margin length and tumor size to the survival rate according to the multiple regression analysis (p = 0.080). The upper margin length and tumor size do not have a relationship with the survival rate of the compared esophagojejunostomy (EJS) methods. The EJS using a linear stapler requires a shorter surgery duration and less blood loss than EJS using a circular stapler.

Leveraging programmed cell death signature to predict clinical outcome and immunotherapy benefits in postoperative bladder cancer

Bladder cancer is the fourth most common malignancy in men with poor prognosis. Programmed cell death (PCD) exerts crucial functions in many biological processes and immunotherapy responses of cancers. Cell death signature (CDS) is novel gene signature comprehensively considering the characteristics of 15 patterns of programmed cell death, which could affect the prognosis and immunotherapy benefits of cancer patients. Integrative machine learning procedure including 10 algorithms was conducted to construct a prognostic CDS using TCGA, GSE13507, GSE31684, GSE32984 and GSE48276 datasets. Immunophenoscore, intratumor heterogeneity (ITH), tumor immune dysfunction and exclusion (TIDE) score and five immunotherapy cohorts were used to evaluate the predictive value of CDS in immunotherapy response. The prognostic CDS constructed by StepCox[backward] + Ridge algorithms was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting overall survival of bladder cancer patients with the AUCs at 3-year, 5-year, and 7-year ROC of 0.740, 0.763 and 0.820 in TCGA cohort. Moreover, CDS score acted as an independent risk factor for overall survival rate of bladder cancer patients. Low CDS score had a higher abundance of immuno-activated cells, higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score, lower immune escape score, lower ITH score, lower cancer-related hallmarks score in bladder cancer. The CDS score was higher in non-responders in pan-cancer patients receiving immunotherapy. Our study constructed a novel prognostic CDS, which could serve as an indicator for predicting the prognosis in postoperative bladder cancer cases and immunotherapy benefits in pan-cancer. Low CDS score indicated a better prognosis and immunotherapy benefits.

Nanoscale Extracellular Vesicle-Enabled Liquid Biopsy: Advances and Challenges for Lung Cancer Detection.

Lung cancer is responsible for the death of over a million people worldwide every year. With its high mortality rate and exponentially growing number of new cases, lung cancer is a major threat to public health. The high mortality and poor survival rates of lung cancer patients can be attributed to its stealth progression and late diagnosis. For a long time, intrusive tissue biopsy has been considered the gold standard for lung cancer diagnosis and subtyping; however, the intrinsic limitations of tissue biopsy cannot be overlooked. In addition to being invasive and costly, it also suffers from limitations in sensitivity and specificity, is not suitable for repeated sampling, provides restricted information about the tumor and its molecular landscape, and is inaccessible in several cases. To cope with this, advancements in diagnostic technologies, such as liquid biopsy, have shown great prospects. Liquid biopsy is an innovative non-invasive approach in which cancer-related components called biomarkers are detected in body fluids, such as blood, urine, saliva and others. It offers a less invasive alternative with the potential for applications such as routine screening, predicting treatment outcomes, evaluating treatment effectiveness, detecting residual disease, or disease recurrence. A large number of research articles have indicated extracellular vesicles (EVs) as ideal biomarkers for liquid biopsy. EVs are a heterogeneous collection of membranous nanoparticles with diverse sizes, contents, and surface markers. EVs play a critical role in pathophysiological states and have gained prominence as diagnostic and prognostic biomarkers for multiple diseases, including lung cancer. In this review, we provide a detailed overview of the potential of EV-based liquid biopsy for lung cancer. Moreover, it highlights the strengths and weaknesses of various contemporary techniques for EV isolation and analysis in addition to the challenges that need to be addressed to ensure the widespread clinical application of EV-based liquid biopsies for lung cancer. In summary, EV-based liquid biopsies present interesting opportunities for the development of novel diagnostic and prognostic platforms for lung cancer, one of the most abundant cancers responsible for millions of cancer-related deaths worldwide.

Abstract A046: Disparities in cancer burden and survival rates in persistent poverty communities in Los Angeles County

Abstract Objective: Persistent poverty census tracts (PPT) are those with socioeconomic challenges where prolonged economic disadvantages may significantly influence health outcomes. This study examined the cancer burden and survival patterns in PPTs compared to non-PPTs in Los Angeles County (LAC) considering disparities by race/ethnicity and stage at diagnosis. Methods: A comprehensive analysis of 2012-2021 Cancer Registry data examined age-adjusted incidence rates (AAIRs) and survival rates for lung, colorectal, liver, stomach, breast, and prostate cancers, which are the Norris Comprehensive Cancer Center priority cancers. Cancer-specific data were further stratified by racial/ethnic group and stage at diagnosis, and compared across residents in PPTs, non-PPTs, and LAC overall. Survival rates were calculated using the Kaplan-Meier method and differences between groups were assessed by log-rank tests. Results: PPTs in LAC were characterized by a higher proportion of racial/ethnic minorities, lower education levels, and higher unemployment compared to non-PPTs. In all racial/ethnic groups combined, AAIRs for lung, breast, and prostate cancers were lower in PPTs than non-PPTs, whereas AAIRS for liver and stomach cancers were higher in PPTs, with no differences for colorectal cancer. Disparities emerged when considering race and ethnicity, with higher lung cancer AAIRs among Non-Hispanic White (NHW) and Black/African American (B/AA) PPT residents compared to non-PPT, while AAIRs for lung and colorectal cancers were lower among Hispanic/Latino (H/L) PPT residents compared to non-PPTs. Breast and prostate cancer AAIRs remained lower in PPTs than in non-PPTS regardless of racial/ethnic group. Patients in PPTs exhibit significantly lower five-year survival rates across all studied cancers, except stomach, compared to non-PPTs. B/AA patients showed the lowest five-year survival rates for lung and colorectal cancer, with patients in PPTs experiencing significantly lower rates than patients in non-PPTs regardless of disease stage (p < 0.01 for early- or late-stage). Liver cancer survival rates were notably low, especially for H/L and Asian/Pacific Islander patients in PPTs, with five-year survival for late-stage cancer at 4.9% (95%CI: 2.8-8.5) and 5.4% (95%CI: 2.1-14.0), respectively. Patients in PPTs with late-stage breast or prostate cancer exhibited significantly lower 5-year survival (compared to non-PPTs) across all race/ethnicities, with B/AA patients experiencing the lowest survival rates for breast cancer and NHW patients experiencing the lowest survival rates for prostate cancer. Conclusions: Cancer outcomes for patients in PPTs were significantly poorer compared to those in non-PPT communities. The notably lower AAIRs in PPTs versus non-PPTs for more screen-able cancers, such as breast, prostate, and early-stage colorectal cancer, suggest a need for greater efforts to provide access to routine screening in areas affected by persistent poverty, though other causes cannot be ruled out. Citation Format: Miriam L Gorbatov, Joel S. Mendez, Myles Cockburn, Laura K. Thompson, Lihua Liu, Jennifer Tsui, Kali Zhou, V. Wendy Setiawan, Chanita Hughes-Halbert, Mariana C. Stern. Disparities in cancer burden and survival rates in persistent poverty communities in Los Angeles County [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A046.

Plectalibertellenone A suppresses colorectal cancer cell motility and glucose metabolism by targeting TGF-β/Smad and Wnt pathways.

Colorectal cancer (CRC) is the second most common cause of cancer-related death and represents a serious worldwide health problem. CRC metastasis decreases the survival rate of cancer patients, underscoring the need to identify novel anticancer agents and therapeutic targets. Here, we introduce Plectalibertellenone A (B) as a promising agent for the inhibition of CRC cell motility and glucose metabolism and explore its mechanism of action in CRC cells. Plectalibertellenone A suppressed TGF-β gene expression and the activation of the TGF-β/Smad signaling pathway, leading to reverse epithelial to mesenchymal transition (EMT) by modulating the expressions of EMT markers and transcriptional factors such as E-cadherin, N-cadherin, vimentin, Slug, Snail, Twist, and ZEB1/2. Furthermore, disruption of Wnt signaling inhibited CRC motility and glucose metabolism including glycolysis and oxidative phosphorylation, primarily affecting glycolytic enzymes, GLUT1, HK2, PKM2, LDHA, and HIF-1α under hypoxic condition. Therefore, Plectalibertellenone A is a potential drug candidate that can be developed into a promising anticancer treatment to prevent CRC metastasis and inhibit glucose metabolism.

Lung Cancer Detection Using Convolutional Neural Networks

Lung cancer is among the most prevalent and deadly cancers worldwide. Accurate diagnosis and early detection are critical for improving lung cancer patient outcomes and survival rates. Thanks to developments in medical imaging technology, computer-aided diagnosis (CAD) systems have shown a great deal of promise in helping radiologists identify and diagnose lung cancer from medical images. Here, we present the use of convolutional neural networks (CNNs) to create an early detection system (CAD) for lung cancer. The suggested approach uses lung computed tomography (CT) scans as input and use a CNN architecture to extract high-level features from the pictures. We use transfer learning to enhance a CNN model trained on a large dataset of CT images. The CNN model has been taught to determine if a specific CT image contains lung cancer or not. We evaluate the performance of the proposed CAD system on a dataset of CT scans of the lungs from different institutions. The trial's results show that our CNN-based CAD system can reliably and precisely identify lung cancer from CT scans. We also show the comparative performance of our proposed system against the state-of-the-art machine learning methods for lung cancer prediction. In conclusion, the suggested CNN-based deep learning-based CAD system has produced encouraging results for lung cancer detection from CT scans. The approach might help radiologists identify and classify lung cancer early on, leading to better patient outcomes and survival rates. The viability and usefulness of the suggested approach in clinical practice require more study

Physical Activity and Its Effects on Cancer Prevention, Survival Rates, and Recovery

Introduction and Objective: Physical activity is any movement using skeletal muscles. It can be classified into four main categories: occupational, household, transport and recreational. These activities can also vary in intensity. This article aims to describe how physical activity affects cancer prevention, survival rates and recovery. Review and Methods: Review and summary of studies and meta-analysis of studies available in open-source format on Google Scholar and PubMed. State of Knowledge: Extensive research shows that regular physical activity reduces the risk of several cancers, particularly breast, colon, and endometrial cancers. Epidemiological studies consistently find that more active individuals have a lower incidence of certain cancers. Physical activity is also a useful adjunct to treatment, alleviating its negative effects. The protective effect of physical activity is believed to be dose-dependent, with greater benefits from higher frequencies, durations, and intensities. Recent studies suggest that physical activity may also improve survival rates in cancer patients, particularly for prostate, colorectal, and breast cancers. Conclusions: The current data strongly supports the inclusion of regular physical activity as a key component of cancer prevention strategies. It may also be beneficial for cancer patients to enhance their chances of survival. Public health guidelines stress the importance of exercise to lower cancer risk and improve overall health.

Cytoarchitecture of Breast Cancer Cells under Diabetic Conditions: Role of Regulatory Kinases-Rho Kinase and Focal Adhesion Kinase.

Diabetes greatly reduces the survival rates in breast cancer patients due to chemoresistance and metastasis. Reorganization of the cytoskeleton is crucial to cell migration and metastasis. Regulatory cytoskeletal protein kinases such as the Rho kinase (ROCK) and focal adhesion kinase (FAK) play a key role in cell mobility and have been shown to be affected in cancer. It is hypothesized that diabetes/high-glucose conditions alter the cytoskeletal structure and, thus, the elasticity of breast cancer cells through the ROCK and FAK pathway, which can cause rapid metastasis of cancer. The aim of the study was to investigate the role of potential mediators that affect the morphology of cancer cells in diabetes, thus leading to aggressive cancer. Breast cancer cells (MDA-MB-231 and MCF-7) were treated with 5 mM glucose (low glucose) or 25 mM glucose (high glucose) in the presence of Rho kinase inhibitor (Y-27632, 10 mM) or FAK inhibitor (10 mM). Cell morphology and elasticity were monitored using atomic force microscopy (AFM), and actin staining was performed by fluorescence microscopy. For comparative study, normal mammary breast epithelial cells (MCF-10A) were used. It was observed that high-glucose treatments modified the cytoskeleton of the cells, as observed through AFM and fluorescence microscopy, and significantly reduced the elasticity of the cells. Blocking the ROCK or FAK pathway diminished the high-glucose effects. These changes were more evident in the breast cancer cells as compared to the normal cells. This study improves the knowledge on the cytoarchitecture properties of diabetic breast cancer cells and provides potential pathways that can be targeted to prevent such effects.

Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer.

USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2.

Post-translational modifications of proteins play a pivotal role in both the initiation and progression of ovarian cancer. Despite the recognition of USP33 as a significant factor in various cancers, its specific function and underlying mechanisms in ovarian cancer remain elusive. Proteomics and ubiquitinomics approaches were coupled to screen novel substrate proteins directly regulated by USP33. Our findings unveil that USP33 was observed to eliminate K27- and K48-linked ubiquitin chains from CBX2 at the K277 position. Notably, acetylation of CBX2 at K199, catalyzed by lysine acetyltransferase GCN5, was found to enhance its interaction with USP33, subsequently promoting further deubiquitination and stabilization. Functionally, our experiments demonstrate that USP33 significantly enhances ovarian cancer proliferation and metastasis in a CBX2-dependent manner. Furthermore, analysis revealed a direct positive correlation between the expression levels of USP33 and CBX2 proteins in human specimens, with elevated levels being associated with reduced survival rates in ovarian cancer patients. These findings elucidate the mechanism by which USP33 augments ovarian cancer progression through the stabilization of CBX2, underscoring the USP33-CBX2 axis as a promising therapeutic target in ovarian cancer management.

CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition.

EGFR-TKIs have been used as frontline treatment in patients with advanced non-small cell lung cancer (NSCLC) suffering from the EGFR mutation. Gefitinib, the first-generation EGFR-TKI, has greatly improved survival rates in lung cancer patients, whereas acquired gefitinib resistance is still a critical issue that needs to be overcome. In our research, high expression levels of CIB2 were found in gefitinib-resistant lung cancer cells. CIB2 knockout rendered gefitinib-resistant cells more sensitive to gefitinib, and overexpression of CIB2 in parental cells was sufficient to induce more resistance to gefitinib. Inhibition of CIB2 in gefitinib-resistant lung cancer cells significantly induced cell apoptosis. To clarify the major molecular mechanism by which CIB2 increases gefitinib resistance, we demonstrated that raised CIB2 in lung cancer cells promoted epithelial-to-mesenchymal transition (EMT) through upregulation of ZEB1. Moreover, FOSL1 transcriptionally regulated CIB2 expression. Finally, CIB2 rendered tumors resistant to gefitinib treatment in vivo. Our results explored a new mechanism: upregulated CIB2 promoted EMT through ZEB1 to regulate gefitinib resistance, which could be a candidate therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.

OTO-IVM is a method of fertility preservation for patients with ovarian tumors

Introduction. An increasing number of patients of reproductive age get cancer and are highly interested in preserving fertility. Survival rates for cancer patients are improving. Methods of reproductive technologies are being improved to preserve the ability to bear children. Rehabilitation aimed to ensure a satisfactory quality of life takes on a new meaning, and with the development of new technologies, the level of possible assistance also changes. Today, rehabilitation measures for cancer patients of reproductive age should undoubtedly include all possible ways to preserve and restore fertility. Aim: preservation of fertility in patients with ovarian tumors. Material and Methods. After ovariectomy, the ovaries were transported to the embryology laboratory, where oocyte-cumulus complexes were extracted and subsequently matured using the OTO-IVM (ovarian tissue oocyte in vitro maturation) method. The resulting mature oocytes (Metaphase II) were cryopreserved by vitrification or, if a partner was available, fertilized by ICSI (intracytoplasmic sperm injection), the embryos were cultured to the blastocyst stage and also cryopreserved by vitrification. Cryopreserved oocytes and embryos can be used by patients after cancer treatment in assisted reproductive technology programs. Results. A total of 218 OCCs were recovered, 29.8 % were degraded oocytes (n=65). The proportion of OCC suitable for ripening was 153 (70.2 %). After 36 or 48 hours, 65 oocytes matured in 13 patients, which amounted to 42.5 % of oocytes without signs of degradation. In 11 patients the OCC was removed from the tumor-affected ovary. 149 oocytes were obtained, of which 50 (33.6 %) were oocytes with signs of degradation. The remaining 99 (66.4 %) of OCCs had satisfactory quality; after maturation, the Metaphase II stage reached in 49 (49.5 %) of oocytes. As a result, biological material was cryopreserved in 13 of 15 patients: 5 embryos and 60 oocytes.

Impact of a multimodal effort re-education programme on functionality, physical performance, and functional capacity in cancer patients with dyspnoea: a randomised experimental study

BackgroundIn recent years, there has been a significant increase in the survival rates of cancer patients. However, this has also led to an increase in side effects, such as dyspnoea, which can negatively impact of patients. We propose a programme for re-educating effort. The main objective is to test the effectiveness of this programme in improving respiratory symptoms and functionality in cancer patients.MethodologyExperimental, prospective, longitudinal, randomised study with a parallel fixed-assignment scheme (CG-IG). The patients were selected from the Medical Oncology Service of the University Hospital Complex of Salamanca (CAUSA), Spain. Two parallel intervention programmes were designed for the two study groups (Conventional Clinical Practice-Effort Re-education Programme). Primary variables: dyspnoea (MRC), functionality (Barthel); secondary variables: physical performance (SPPB) and functional capacity (ECOG) and the socio-demographic variables (age, sex, anatomopathological diagnosis, and number of treatment lines).ResultsThe study sample consisted of 182 patients, with 12 excluded, resulting in a final sample size of n = 170. Sex distribution (CG: 52.9% male and 47.1% female; IG: 49.4% male and 50.6% female). The primary oncological diagnosis was lung cancer, and the most frequent tumour stages were III and IV. Statistically significant differences were found between the IG and CG scores (p < 0.001, d = 0.887, 95% CI) and between the IG and CG scores (p = 0.004, d = 0.358, 95% CI), indicating that the IG performed better.ConclusionThe results of this study support the beneficial effects of an exercise re-education programme, carried out by an interdisciplinary team in improving the autonomy of oncology patients with dyspnoea.Trial registrationThe clinical trial was registered in ClinicalTrials.gov (NCT04186754). (03 September 2019).

Long-term effects of the chronic administration of doxorubicin on aged skeletal muscle: An exploratory study in mice

The widely used chemotherapeutic drug doxorubicin (DOX) has been associated with adverse effects on the skeletal muscle, which can persist for years after the end of the treatment. These adverse effects may be exacerbated in older patients, whose skeletal muscle might already be impaired by aging. Nonetheless, the mediators responsible for DOX-induced myotoxicity are still largely unidentified, particularly the ones involved in the long-term effects that negatively affect the quality of life of the patients. Therefore, this study aimed to investigate the long-term effects of the chronic administration of DOX on the soleus muscle of aged mice. For that and to mimic the clinical regimen, a dose of 1.5 mg kg−1 of DOX was administered two times per week for three consecutive weeks in a cumulative dose of 9 mg kg−1 to 19-month-old male mice, which were sacrificed two months after the last administration. Body wasting and the atrophy of the soleus muscle, as measured by a decrease in the cross-sectional area of the soleus muscle fibers, were identified as long-term effects of DOX administration. The atrophy observed was correlated with increased reactive oxygen species production and caspase-3 activity. An impaired skeletal muscle regeneration was also suggested due to the correlation between satellite cells activation and the soleus muscle fibers atrophy. Systemic inflammation, skeletal muscle energy metabolism and neuromuscular junction-related markers do not appear to be involved in the long-term DOX-induced skeletal muscle atrophy. The data provided by this study shed light on the mediators involved in the overlooked long-term DOX-induced myotoxicity, paving the way to the improvement of the quality of life and survival rates of older cancer patients.