Survival Rate Of Cancer Patients Research Articles

Chinese expert consensus on diagnosis and treatment of pulmonary nodules(2024)

Lung cancer is the leading cause of the incidence and mortality of malignant tumors in China. The 5-year survival rate released for China in 2018 was 19.7%. The 5-year survival rate for stage Ⅰ patients is 77%-92%. Early diagnosis and treatment of lung cancer are key to improving the 5-year overall survival rate and prognosis of lung cancer patients. Therefore, experts from the Academic Group of Lung Cancer in Chinese Thoracic Society and Chinese Alliance Against Lung Cancer Expert Group formulated the Chinese Expert Consensus on the Diagnosis and Treatment of Lung Nodules in 2015 to standardize the diagnosis and treatment of lung nodules. In 2018, this consensus was updated to formulate the Chinese Expert Consensus on Diagnosis and Treatment of Lung Nodules (2018 edition), and widely applied in multiple branch centers of Chinese Alliance Against Lung Cancer, proposing the Intelligent Treatment of Million Early Lung Cancer Project. Based on applied experience of the expert consensus in recent years, with reference to the latest evidence has been updated, Chinese Expert Consensus on Diagnosis and Treatment of Lung Nodules (2024 edition) was formulated. The updated content of this consensus mainly includes the following aspects: (1) Define the screening age of high-risk lung cancer populations in China based on the national conditions; (2) Propose definition of "difficult-to-determine pulmonary nodules" to avoid delaying the diagnosis and treatment; (3) Evaluate pulmonary nodules assisted by artificial intelligence (AI) imaging-assisted diagnostic system and propose human-machine MDT to avoid the limitations of AI; (4) Evaluate pulmonary nodules by routine and individualized evaluations for different populations, and make recommendations based on evidence-based management guidelines for different types and sizes of pulmonary nodules. In the updated consensus, 18 consensus points were recommended as a reference for clinical management of pulmonary nodules to improve the 5-year overall survival rate and the prognosis of lung cancer in China.

Ocular surface adverse reactions of antitumor-targeted drugs

With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.

Clinical changes in serum intercellular adhesion molecule 1 in cervical cancer patients receiving radiotherapy.

The levels of soluble intracellular adhesion molecule-1 (sICAM-1) increased in cervical cancer patients and those patients with recurrence. However, the pattern of change in sICAM-1 and its association with prognosis in cervical cancer patients after radiotherapy remain unknown. sICAM-1 level was detected using enzyme-linked immunosorbent assay in different patient groups. The predictive value of sICAM-1 for cervical cancer occurrence was evaluated using receiver operating characteristics analysis. The association of sICAM-1 with clinical pathology was analyzed using Fisher's exact test. Association of sICAM-1 with prognosis was evaluated by alteration of sICAM-1 level in cervical cancer patients with or without complete remission at pre-radiotherapy, post-radiotherapy, and post-follow-up. The survival rate of cervical cancer patients with low or high sICAM-1 was plotted using the Kaplan-Meier curve. sICAM-1 level significantly increased in cervical cancer patients and could predict the occurrence of cervical cancer. sICAM-1 was closely associated with tumor size, differentiation, and radiotherapy effect. Importantly, the level of sICAM-1 gradually decreased in patients with complete remission after radiotherapy, while it remained unchanged in those without complete remission. Furthermore, the cervical cancer patients with high expression of sICAM-1 had a shorter survival time. The level of sICAM-1 could predict the occurrence of cervical cancer and is closely related to the prognosis of cervical cancer patients after radiotherapy.

Mutations of the PIK3CA gene in patients with breast cancer in the Krasnoyarsk region

Aim. To identify population characteristics of the PIK3CA gene mutation among breast cancer patients in the Krasnoyarsk region.Materials and methods. The study included 140 patients with breast cancer with a certain mutation status of the PIK3CA gene, observed at the Krasnoyarsk Regional Clinical Oncology Center named after A.I. Kryzhanovsky. Determination of PIK3CA gene mutations (exons 2, 5, 8, 10 and 21) was carried out using commercial kits on equipment from Roche (Germany). Statistical processing of the obtained data was carried out using Microsoft Excel and Statistica 12 software products. The assessment of the factor of influence on the relapse-free and overall survival was carried out by constructing and comparing Kaplan–Meier curves. The result was considered statistically significant at a significance level of p <0.05.Results and conclusion. The overall frequency of occurrence of PIK3CA gene mutations is 38.6 %. The most common mutations are H1047X (55.4 %) in exon 21 and E545K (27.8 %) in exon 10. The median age of breast cancer patients with mutation status in the PIK3CA gene was 58.9 [49.0; 67.0] years, median time to relapse or progression was 62.2 [27.0; 84.0] months. There were no statistically significant differences in relapse-free survival between the presence and absence of mutations (p = 0.8). The effect of changes in PIK3CA on a decrease in overall survival rates (p = 0.047) in breast cancer patients was shown.

The influence of polymorphism of genes associated with breast cancer on the effectiveness of drug antitumor therapy

Background. Increasing the survival rate of breast cancer patients is a problem all over the world and directly depends on the early detection of a malignant tumor. Genome-wide associative studies (GWAS) as a minimally invasive method may be used in determining risk of breast cancer or detection at an early stage. The increase in the number of patients with disseminated breast cancer in the Republic of Kazakhstan makes it necessary to search for molecular genetic markers of breast cancer for their use in the diagnosis and treatment of patients with this pathology.Aim. To retrospectively estimate the correlation of the effectiveness of drug antitumor therapy for breast cancer with gene polymorphism.Materials and methods. The study included the results of genotyping biomaterial samples on high-density DNA chips (venous blood of 1,277 Kazakh patients (in the third generation) with a verified diagnosis of breast cancer with locally advanced and disseminated breast cancer who received anticancer therapy), clinical data of patients, data on the clinical efficacy and toxicity of drug therapy. GWAS data (genotypes) associated with identified responses to chemotherapy drugs were compared with similar data recorded in international databases.Results. The family history study showed 16.52 % of women in the questionnaires had a family history of various types of ESR, and 86.25 % of them had a burden of breast cancer in women of the first degree of kinship. The average age of patients with breast cancer was 48.79 ± 11.44 years. According to the TNM classification, cancer in situ was detected in 4.78 % of patients, stage I of the disease was recorded in 15.27 %, stage II in 63.43 %, stage III in 12.60 %, stage IV in 3.92 % of patients. The vast majority of the patients (96.9 %) had a nodular form of breast cancer. The distribution of the patients by tumor phenotype: luminal type A was found in 20.4 % of patients, luminal type B in 38.3 %, luminal type B with HER2 overexpression in 14.3 %, HER2 positive form in 11.9 % of cases, 12.4 % of patients had an aggressive form – triple negative breast cancer. 18 main genotypes were identified in the Kazakh population as a result of the analysis of associations of the effectiveness of neoadjuvant chemotherapy (its individual components, according to chemotherapy regimens) and individual gene polymorphisms.Conclusion. An associative relationship between different types of gene polymorphism and the characteristics of response to various chemotherapeutic drugs used in the treatment of breast cancer has been confirmed. The obtained results formed the basis for the development of recommendations for making changes to the clinical practice of the Republic of Kazakhstan in order to use them in identifying a genetic predisposition to breast cancer and the effectiveness of drugs used in treatment.

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

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

Advances in ovarian tumor stem cells and therapy.

Ovarian cancer is considered the most lethal among all gynecological malignancies due to its early metastatic dissemination, extensive spread, and malignant ascites. The current standard of care for advanced ovarian cancer involves a combination of cytoreductive surgery and chemotherapy utilizing platinum-based and taxane-based agents. Although initial treatment yields clinical remission in 70-80% of patients, the majority eventually develop treatment resistance and tumor recurrence. A growing body of evidence indicates the existence of cancer stem cells within diverse solid tumors, including ovarian cancer, which function as a subpopulation to propel tumor growth and disease advancement by means of drug resistance, recurrence, and metastasis. The presence of ovarian cancer stem cells is widely considered to be a significant contributor to the unfavorable clinical outcomes observed in patients with ovarian cancer, as they play a crucial role in mediating chemotherapy resistance, recurrence, and metastasis. Ovarian cancer stem cells possess the capacity to reassemble within the entirety of the tumor following conventional treatment, thereby instigating the recurrence of ovarian cancer and inducing resistance to treatment. Consequently, the creation of therapeutic approaches aimed at eliminating ovarian cancer stem cells holds great potential for the management of ovarian cancer. These cells are regarded as one of the most auspicious targets and mechanisms for the treatment of ovarian cancer. There is a pressing need for a comprehensive comprehension of the fundamental mechanisms of ovarian cancer's recurrence, metastasis, and drug resistance, alongside the development of effective strategies to overcome chemoresistance, metastasis, and recurrence. The implementation of cancer stem cell therapies may potentially augment the tumor cells' sensitivity to existing chemotherapy protocols, thereby mitigating the risks of tumor metastasis and recurrence, and ultimately improving the survival rates of ovarian cancer patients.

The Role of AKR1B10 in Lung Cancer Malignancy Induced by Sublethal Doses of Chemotherapeutic Drugs.

Chemotherapy remains a cornerstone in lung cancer treatment, yet emerging evidence suggests that sublethal low doses may inadvertently enhance the malignancy. This study investigates the paradoxical effects of sublethal low-dose chemotherapy on non-small-cell lung cancer (NSCLC) cells, emphasizing the role of Aldo-keto reductase family 1 member B10 (AKR1B10). We found that sublethal doses of chemotherapy unexpectedly increased cancer cell migration approximately 2-fold and invasion approximately threefold, potentially promoting metastasis. Our analysis revealed a significant upregulation of AKR1B10 in response to taxol and doxorubicin treatment, correlating with poor survival rates in lung cancer patients. Furthermore, silencing AKR1B10 resulted in a 1-2-fold reduction in cell proliferation and a 2-3-fold reduction in colony formation and migration while increasing chemotherapy sensitivity. In contrast, the overexpression of AKR1B10 stimulated growth rate by approximately 2-fold via ERK pathway activation, underscoring its potential as a target for therapeutic intervention. The reversal of these effects upon the application of an ERK-specific inhibitor further validates the significance of the ERK pathway in AKR1B10-mediated chemoresistance. In conclusion, our findings significantly contribute to the understanding of chemotherapy-induced adaptations in lung cancer cells. The elevated AKR1B10 expression following sublethal chemotherapy presents a novel molecular mechanism contributing to the development of chemoresistance. It highlights the need for strategic approaches in chemotherapy administration to circumvent the inadvertent enhancement of cancer aggressiveness. This study positions AKR1B10 as a potential therapeutic target, offering a new avenue to improve lung cancer treatment outcomes by mitigating the adverse effects of sublethal chemotherapy.

The Impact of Specific High-Pathogenic Tp53 Mutations on Survival in Head and Neck Cancers

Head and neck cancers (HNC) constitute about 30-40 % of all cancers in India. tp53 tumor suppressor gene is the most common gene mutated in HNC but has not been demonstrated to have any diagnostic or prognostic significance. therefore, we hypothesize that the survival rate and prognosis of head and neck cancer patients are linked with certain specific high-pathogenic tp53 hot spot mutations. To evaluate the hypothesis, we conducted a retrospective study on a cohort of 100 HNC patients between April 2013 and April 2018. targeted deep sequencing was performed to identify specific somatic mutations. Kaplan–Meier analysis and log-rank tests were performed. Tp53 mutations were identified in 47 of the 100 cases, with dual mutations in 4 patients. Functional characteristics displayed loss of function in 54.9% and gain of function in 27.5 % of cases. the majority of cases displayed missense aberration (74.5%), followed by nonsense mutations (11.76%). Of these pathogenic mutations, 33.3% fell into 6 hot spot residues while mini hot spot residues constituted 20.5% of the mutations. There was no statistically significant difference in the median survival rate between patients with and without the out tp53 mutation. however, the median survival rate was linked with poor prognosis in patients with specific pathogenic hot spot mutations in 247, 248, 245, and 175 residues (p value= 0.028). The majority of hot spot mutations (66%) showed a gain of function which may have been contributory to the pathogenicity of the disease. Results provide evidence that the existence of high-pathogenicity hot spot residues appears to be the only mutation that warrants further research to identify the therapeutic and prognostic significance of the tp53 gene in the treatment of HNC. further systemic studies are recommended to validate this hypothesis.

Cancer-associated fibroblasts (CAFs) gene signatures predict outcomes in breast and prostate tumor patients

BackgroundOver the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed.MethodsRNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm.ResultsData obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts.ConclusionWe identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study.

Early gastric cancer (EGC) is a common malignant tumor of the digestive system, and its lymph node metastasis and survival prognosis have been concerning. By retrospectively analyzing the clinical data of EGC patients, we can better understand the status of lymph node metastasis and its impact on survival and prognosis. To evaluate the prognosis of EGC patients and the factors that affect lymph node metastasis. The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study. There were 561 males and 450 females. The mean age was 58 ± 11 years. The patient underwent radical gastrectomy. The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens. The outcomes were as follows: (1) Lymph node metastasis in EGC patients; (2) Analysis of influencing factors of lymph node metastasis in EGC; and (3) Analysis of prognostic factors in patients with EGC. Normally distributed measurement data are expressed as mean ± SD, and a t test was used for comparisons between groups. The data are expressed as absolute numbers or percentages, and the chi-square test was used for comparisons between groups. Rank data were compared using a nonparametric rank sum test. A log-rank test and a logistic regression model were used for univariate analysis. A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis. The Kaplan-Meier method was used to calculate the survival rate and construct survival curves. A log-rank test was used for survival analysis. Analysis of influencing factors of lymph node metastasis in EGC. The results of the multifactor analysis showed that tumor length and diameter, tumor site, tumor invasion depth, vascular thrombus, and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC (odds ratios = 1.80, 1.49, 2.65, 5.76, and 0.60; 95%CI: 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, and 0.48-0.76, respectively; P < 0.05). Analysis of prognostic factors in patients with EGC. All 1011 patients with EGC were followed up for 43 (0-13) months. The 3-year overall survival rate was 97.32%. Multivariate analysis revealed that age > 60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC (hazard ratio = 9.50, 2.20; 95%CI: 3.31-27.29, 1.00-4.87; P < 0.05). Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged > 60 years and ≤ 60 years were 99.37% and 94.66%, respectively, and the difference was statistically significant (P < 0.05). The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42% and 97.92%, respectively, and the difference was statistically significant (P < 0.05). The lymph node metastasis rate of EGC patients was 23.64%. Tumor length, tumor site, tumor infiltration depth, vascular cancer thrombin, and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients. Age > 60 years and lymph node metastasis are independent risk factors for EGC prognosis.

Five-year survival rate of cancer patients in Ethiopia – systematic review and meta-analysis, 2022

Background: Cancer and other non-communicable diseases (NCDs) were once thought to be diseases of high-income countries. However, new studies suggest that they are now a major public health burden in low- and middle-income countries as well. The rate of survival after diagnosis significantly varied across types of cancer and the treatment options they received. Therefore, we conducted this study to determine the survival status of cancer patients in Ethiopia. Methods: PubMed, Web of Science, Google Scholar, and Scopus databases from inception to 10 April 2022 were searched to identify relevant studies. A funnel plot and Egger’s regression test were used to determine publication bias. The I 2 statistic was used to check heterogeneity between the studies. DerSimonian and Laird random effects model was applied to estimate pooled effect size and 95% confidence interval across studies. Sensitivity analysis was deployed to determine the effect of a single study on the overall estimation, and the analysis was done using STATA Version 14 software. Results: A total of 19 studies with 12 847 study participants were included to estimate the pooled survival rate of cancer patients. The estimated pooled survival rate of cancer patients in Ethiopia was 57.15 (95% CI: 56.34–57.97). Regarding the subgroup analysis, based on cancer type, the highest pooled survival rate was recorded among prostate cancer patients at 80.47 (95% CI: 73.60–87.34), followed by cervical cancer patients at 60.89 (95% CI: 37.78–84.00) while the smallest was among colorectal cancer patients at 40.04 (95% CI: 9.11–70.9) and based on study design the highest pooled survival rate was among prospective cohort study at 63.91 (95% CI: 30.86–96.96). Based on publication year, the highest pooled survival rate was recorded in 2020 with 69.61 (95% CI: 48.51–90.70), followed by in 2018 at 63.13 (95% CI: 50.01–76.25). Conclusion: The survival rate of cancer patients is low in Ethiopia. This demonstrates that the survival of cancer patients is a major problem in Ethiopia. Therefore, situation-based interventions and preventive strategies should be developed to enhance the survival rate of cancer patients.

Anti-cancer Therapies in Adults and Their Effects on Cardiovascular System: A Review

The cardio-oncology as a field has been expanded by the rapid development of innovative cancer therapies. While these treatments had significantly improved the overall survival rates for cancer patients, they also carried the risk of cardiovascular and metabolic toxicities. A comprehensive and accurate diagnosis of cancer was paramount to initiate appropriate and effective treatment strategies. It was essential to recognize that each type of cancer presents unique characteristics and complexities, necessitating personalized treatment approaches tailored to individual patients. These treatment regimens often encompassed a combination of modalities such as surgery, radiotherapy, systemic therapy, including chemotherapy, antineoplastic hormonal agents, targeted therapies, and supportive care interventions. By implementing a tailored treatment plan based on the specific nature of the cancer, healthcare professionals might optimize therapeutic outcomes while minimizing adverse effects, ultimately improving the overall prognosis and quality of life for cancer patients. The concise review aims to underscore the effects of cancer and its treatments on cardiovascular health, drawing insights from prior research. By synthesizing findings from existing studies, we aim to elucidate the intricate relationship between cancer therapies and cardiovascular outcomes. Consequently, there is a pressing need for an updated summary to inform contemporary clinical practice, ensuring that healthcare professionals are equipped with the latest knowledge to provide optimal care for cancer patients while safeguarding their cardiovascular well-being.

Survival Analysis of Lung Cancer Patients at Dr. Saiful Anwar Hospital

Background: Comprising 14% of all cancer, lung cancer is the main cause of cancer-related mortality worldwide. Previous studies showed various findings regarding the survival rate of lung cancer, and factors significantly correlated with survival rate in lung cancer patients. Aim: This research aims to identify the profile and survival rate of lung cancer patients receiving chemotherapy in Saiful Anwar General Hospital from 2018 to 2020. Methods: This cohort retrospective study used medical records of patients diagnosed with lung cancer who underwent chemotherapy from 2018 to 2020. Data analysis was done using the Mantel Cox log rank test. Survival data shown as progression free survival (PFS) and overall survival (OS) were shown using Kaplan-Meier curves. Results: Subjects were largely male (73,2%). Adenocarcinoma is the most often type of lung cancer found (59,8%) with wild type EGFR mutation being the most prevalent (20,6%). Carboplatin – Paclitaxel is the most widely used chemotherapy regimen (54,6%). Survival analysis showed a significant correlation between age, OS, and PFS (p &lt; 0,05) Conclusion: Various factors such as gender, cancer cell type, EGFR mutation, and chemotherapy regimen were not found to be related to survival rate in lung cancer patients. A significant correlation between age and survival rate showed potential in utilizing age as a predictor of survival rate in lung cancer patients.

Assessment of peripheral dose as a function of distance and depth from cobalt-60 beam in water phantom using TLD-100

BackgroundInnovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100).MethodsThe PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm.ResultsThe results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor.ConclusionIt is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.

Molecular Mechanism of WWOX Inhibiting the Development of Esophageal Cancer by Inhibiting Hippo Signaling Pathway.

With the emergence of combined surgical treatments, complemented by radiotherapy and chemotherapy, survival rates for esophageal cancer patients have improved, but the overall 5-year survival rate remains low. Therefore, there is an urgent need for further research into the pathogenesis of esophageal cancer and the development of effective prevention, diagnosis, and treatment methods. We initially utilized the GeneCards and DisGeNET databases to identify the esophageal cancer-associated gene WWOX (WW domain containing oxidoreductase). Subsequently, we employed RT-qPCR (Reverse transcription-quantitative PCR) and WB (western blot) to investigate the differential expression of WWOX in HEEC (human esophageal endotheliocytes) and various ESCC (esophageal squamous cell carcinoma) cell lines. We further evaluated alterations in cell proliferation, migration and apoptosis via CCK8 (cell counting kit-8) and clonal formation, Transwell assays and flow cytometry. Additionally, we investigated changes in protein expressions related to the Hippo signaling pathway (YAP/TEAD) through RT-qPCR and WB. Lastly, to further elucidate the regulatory mechanism of WWOX in ESCC, we performed exogenous YAP rescue experiments in ESCC cells with WWOX overexpression to investigate the alterations in apoptosis and proliferation. Results indicated that the expression of WWOX in ESCC was significantly downregulated. Subsequently, upon overexpression of WWOX, ESCC cell proliferation and migration decreased, while apoptosis increased. Additionally, the expression of YAP and TEAD were reduced. However, the sustained overexpression of YAP attenuated the inhibitory effects of WWOX on ESCC cell malignancy. In conclusion, WWOX exerts inhibitory effects on the proliferation and migration of ESCC and promotes apoptosis by suppressing the Hippo signaling pathway. These findings highlight the potential of WWOX as a novel target for the diagnosis and treatment of esophageal cancer.

Decoding the immune landscape: a comprehensive analysis of immune-associated biomarkers in cervical carcinoma and their implications for immunotherapy strategies.

Cervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women's health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged as a promising avenue for treating cervical cancer. For patients with persistent or recurrent metastatic cervical cancer, If the sequence of dead receptor ligand-1 (PD-L1) is positive, ICI show significant clinical efficacy. PD-L1 expression serves as a valuable biomarker for assessing ICI therapeutic efficacy. However, the complex tumor immune microenvironment (TIME), encompassing immune cell composition and tumor-infiltrating lymphocyte (TIL) status, also exerts a profound influence on tumor immunity and prognosis. Given the remarkable strides made by ICI treatments in improving the survival rates of cervical cancer patients, it becomes essential to identify a comprehensive biomarker that integrates various TIME aspects to enhance the effectiveness of ICI treatment. Therefore, the quest for biomarkers linked to multiple facets of TIME in cervical cancer is a vital pursuit. In this study, we have developed an Immune-Associated Gene Prognostic Index (IRGPI) with remarkable prognostic value specifically for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The Cancer Genome Atlas CESC dataset (n = 305) was meticulously analyzed to pinpoint key immune-related genes via weighted gene co-expression network analysis and differential gene expression assays. Subsequently, we employed Cox regression analysis to construct the IRGPI. Furthermore, the composition of immune cells and TIL status were examined using CIBERSORT and TIDE. Tumor expression of Epigen, LCN10, and P73 were determined with immunohistochemistry. The resulting IRGPI, composed of EPGN, LCN10, and TP73 genes, displayed a strong negative correlation with patient survival. The discovery was validated with a patient cohort from our hospital. The IRGPI not only predicts the composition of immune cell subtypes such as Macrophages M1, NK cells, Mast cells, Plasma cells, Neutrophils, Dendritic cells, T cells CD8, and T cells CD4 within CESC, but also indicates TIL exclusion, dysfunction, and PD-1 and PD-L1 expression. Therefore, the IRGPI emerges as a promising biomarker not only for prognostic assessment but also for characterizing multiple immune features in CESC. Additionally, our results underscored the significant associations between the IRGPI and immune cell composition, TIL exclusion, and dysfunction, along with PD-1 and PD-L1 expression in the TIME. Consequently, the IRGPI stands out as a biomarker intimately connected to both the survival and TIME status of CESC patients, offering potential insights into immunotherapy strategies for CESC.

A New Approach for Assessment of Neutrophil Extracellular Traps Through Immunofluorescence Staining in Whole Blood Smears.

Neutrophils, constituting 50%-70% of circulating leukocytes, play crucial roles in host defense and exhibit anti-tumorigenic properties. An elevated peripheral blood neutrophil-to-lymphocyte ratio is associated with decreased survival rates in cancer patients. In response to exposure to various antigens, neutrophils release neutrophil granular proteins, which combine to form web-like structures known as neutrophil extracellular traps (NETs). Previously, the relative percentage of NETs was found to be increased in resected tumor tissue samples from patients with gastrointestinal malignancies. The presence of NETs in peripheral blood is indicative of underlying pathological conditions. Hence, employing a non-invasive method to detect NETs in peripheral blood, along with other diagnostic tests, shows potential as a valuable tool not just for identifying different inflammatory disorders but also for assessing disease severity and determining patient suitability for surgical resection. While reliable methods exist for identifying NETs in tissue, accurately quantifying them in whole blood remains challenging. Many previous methods are time-consuming and rely on a limited set of markers that are inadequate for fully characterizing NETs. Therefore, we established a unique sensitive smear immunofluorescence assay based on blood smears to identify NETs in only as little as 2 μL of whole blood. To identify the NET complexes that have enhanced specificities, this combines the use of various antibodies against neutrophil-specific CD15, NET-specific myeloperoxidase (MPO), citrullinated histone H3 (Cit H3), and nuclear DNA. This protocol offers an easy, affordable, rapid, and non-invasive method for identifying NETs; thus, it can be utilized as a diagnostic marker and targeted through various therapeutic approaches for treating human malignancies. Key features • Characterization of neutrophil extracellular traps in whole blood smears through immunofluorescence staining. • Affordable and quantitative approach to neutrophil extracellular trap detection.

Relationship between infiltration of tissue-resident memory T cells (TRM) in head and neck squamous cell carcinoma (HNSCC) tissue and localization and age.

6089 Background: Elevated levels of tumor-infiltrating lymphocytes (TILs) have been correlated with improved survival rates in cancer patients. Among TIL subgroups, tissue-resident memory T cells (TRM, CD8+CD103+) are recognized as pivotal contributors to the anti-cancer immune response. In this study, we aimed to evaluate TRM presence in Head and Neck Squamous Cell Carcinoma (HNSCC) tissue utilizing a developed tissue microarray (TMA) and a multiplex immunohistochemistry (MxIHC) approach. Methods: HNSCC cases from Southampton Hospital spanning the years 2000 to 2016 were reviewed, resulting in the identification of approximately 300 cases with sufficient primary tumor material. A TMA was constructed by triplicate coring of marked tumor areas on all slides. Subsequently, MxIHC, incorporating markers such as CD8 and CD103, was performed using a stain-scan-strip methodology. Digital image analysis software was employed to analyze scanned slides, and a quality check (QC) was conducted. Results: Following QC, 193 primary tumors remained (hypopharynx and larynx: n = 28, lip and oral cavity: n = 51, oropharynx: n = 114). Significantly higher counts of CD8 T cells and TRM were observed in the combined group of oropharynx, lip and oral cavity compared to the combined group of larynx and hypopharynx. This significance persisted even after excluding HPV negative oropharynx cases. HNSCC of the lip and oral cavity itself had statistically more TRM than larynx and hypopharynx. No differences were found in the subgroups between tonsil and tongue base. Stratifying the analysis by age revealed a statistically significant increase in TRM infiltration in HNSCC among young patients (≤50 years) compared to the 51-60 years and 61-70 years age groups, a pattern not observed for CD8 alone. Conclusions: This study underscores the importance of HNSCC heterogeneity and highlights the impact of age on immune infiltration, emphasizing the unique contribution of TRM in the anti-cancer immune response.

The utility of multiple clinical variables in predicting survival outcome for patients with rectal cancer: An integrated regression and retrospective cohort analysis.

e15610 Background: Prior studies have investigated clinical factors impacting the survival rates of rectal cancer patients. However, a robust and precise model for discerning these risks, which can be identified by integrated regressions analysis has yet to be established. The aim of this study is to develop and evaluate the diagnostic value of the constructed prediction model based on selected clinical variables. Methods: Patients diagnosed with stage II-III rectal cancer (April 2015-June 2021) were retrospectively enrolled as the primary cohort. Individual variables were extracted and then subjected to a K-adaptive partitioning algorithm for cut-off point determination and grouping. The Cox and least absolute shrinkage and selection operator regression (LASSO) regression were applied for independent predictors selection over significant overall survival (OS), and a nomogram was subsequently constructed. The performance of the constructed model was evaluated using the receiver operating characteristics (ROC) curves, calibration curves, and decision curve analysis (DCA), and stepwise compared with data cohorts derived from TCGA and SEER databases. Results: The Cox-LASSO analysis results considered the four independent variables as significant predictors, yielding the risk score equation: 1.086(for CEA level≥7.5 ng/ml) -1.7756(if gender is male) +1.829*(pT stages) +0.582*(pN stages). Notably, the distal resection margin (DRM) was excluded from the final model following the analysis (p = 0.060, 95%CI: -0.04-2.17). The constructed model (C-index:0.790, 95%CI: 0.673-0.743, AUC:0.873) outperformed the conventional TNM staging models (C-index:0.539, 95%CI:0.121-0.957, AUC:0.735). It stratified patients into low- or high-risk groups with significant OS differences (93% vs. 37%, p≤0.0001, respectively). The calibration curves for OS probability showed strong homogeneities between predictions and actual observations. DCA revealed positive net benefits at evaluated first, third, and fifth years. Moreover, the external validations confirmed the accurate prediction following the constructed model, with AUC of 0.745 and 0.705 for the TCGA and SEER datasets, respectively. Conclusions: This study resulted in a novel and effective prediction model for rectal cancer patients based on conventional clinical characteristics. It demonstrated solid performance and can serve as a convenient tool for OS prediction, aiding in rectal cancer patients' risk scoring and clinical decision-making.