Search

Skin Cancer is caused due to the mutational differences in epidermis hormones and patch appearances. Many studies are focused on the design and development of effective approaches in diagnosis and categorization of skin cancer. The decisions are made on independent training dataset under limited editions and scenarios. In this research, the kaggle based datasets are optimized and categorized into a labeled data array towards indexing using Federated learning (FL). The technique is developed on grey wolf optimization algorithm to assure the dataset attribute dependencies are extracted and dimensional mapping is processed. The threshold value validation of the dimensional mapping datasets is effectively optimized and trained under the neural networking framework further expanded via federated learning standards. The technique has demonstrated 95.82% accuracy under GWO technique and 94.9% on inter-combination of Trained Neural Networking (TNN) framework and Recessive Learning (RL) in accuracy. [ABSTRACT FROM AUTHOR]

Observational studies showed that metabolic phenotypes were associated with the risk of developing breast cancer (BC). However, those results are inconsistent regarding the magnitude of the association, particularly by subtypes of breast cancer. Furthermore, the mechanisms of the association remain unclear. We performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of metabolic risk factors on breast cancer in the European population. Assessed individually using MR, body mass index (BMI) (odds ratio [OR] 0.94, 95% Confidence interval [CI] 0.90–0.98, P = 0.007), high-density lipoprotein cholesterol (HDL-C) (OR 1.10, 95% CI 1.07–1.13, P = 6.10 × 10–11) and triglycerides (TG) (OR 0.92, 95% CI 0.90–0.96, P = 1.58 × 10–6) were causally related to breast cancer risk. In multivariable MR, only HDL-C (OR 1.08; 95% CI 1.02–1.14; P = 0.02) retained a robust effect, suggesting that the genetic association between BMI, HDL-C and TG with breast cancer risk in univariable analysis was explained via HDL-C. These findings suggest a possible causal role of HDL-C in breast cancer etiology. [ABSTRACT FROM AUTHOR]

Mortality from non cancer causes in patients with gallbladder cancer (GBC) still unclear. This study evaluated the causes and risk factors of non cancer death during different follow-up periods after GBC diagnosis. Non cancer causes of death for GBC patients diagnosed between 2000 and 2017 in Surveillance, Epidemiology and End Results database were analyzed and standardized mortality rates (SMR) for each non cancer death were calculated. Predictors for non cancer death were identified through multivariate competing risk analysis. A total 11,927 GBC patients were identified for further analysis, 9393 died during follow up. The largest proportion of non cancer deaths occurred > 3 years after diagnosis (39.4%). Most common non cancer cause were cardiovascular disease (43.3%), followed by other cause of death (34.4%) and infectious diseases (8.6%). Compared with US general population, GBC patients has higher risk of death from disease of heart (SMR, 1.58; 95%CI, 1.41–1.75), septicemia (SMR,3.21; 95%CI, 2.27–4.40), diabetes mellitus (SMR,1.97; 95%CI, 1.43–2.63), alone with other causes. Non cancer causes accounted for a significant proportion of deaths during the follow-up period after GBC diagnosis. The risk of non cancer death is higher in GBC patients than in the general population. Our study provides comprehensive assessment of death from non cancer cause in GBC patients, which has important implications for health management in GBC patients. [ABSTRACT FROM AUTHOR]

Obesity is a modifiable risk factor in cancer development, especially for gastrointestinal cancer. While the etiology of colorectal cancer is well characterized by the adenoma-carcinoma sequence, it remains unclear how obesity influences colorectal cancer development. Dietary components of a high fat diet along with obesity have been shown to modulate the cancer risk by perturbing the homeostasis of intestinal stem cells, yet how adiposity impacts the development of genomic instability has not been studied. Mutational signatures are a powerful way to understand how a complex biological response impacts genomic stability. We utilized a mouse model of diet-induced obesity to study the mutational landscape of intestinal crypt cells after a 48-week exposure to an experimental high fat diet in vivo. By clonally enriching single crypt derived cells in organoid culture and obtaining whole genome sequences, we analyzed and compared the mutational landscape of intestinal epithelial cells from normal diet and high fat diet mice. Single nucleotide substitution signatures and indel signatures present in our cohort are found equally active in both diet groups and reflect biological processes of normal aging, cellular replication, and oxidative stress induced during organoid culturing. Thus, we demonstrate that in the absence of activating mutations or chemical exposure, high fat diet alone is not sufficient to increase genomic instability. [ABSTRACT FROM AUTHOR]

A hallmark of cancer is a tumor cell's ability to evade immune destruction. Somatic mutations in tumor cells that prevent immune destruction have been extensively studied. However, somatic mutations in tumor infiltrating immune (TII) cells, to our knowledge, have not been previously studied. Understandably so since normal hematopoiesis prevents the accumulation of somatic mutations in immune cells. However, clonal hematopoiesis does result in the accumulation of somatic mutations in immune cells. These mutations cannot "drive" tumor growth, however, they may "facilitate" it by inhibiting an effective anti-tumor immune response. To identify potential immunosuppressive clonal hematopoietic (CH) mutations in TII cells, we analyzed exome and RNA sequencing data from matched tumor and normal blood samples, and single-cell RNA sequencing data, from breast cancer patients. We selected mutations that were somatic, present in TII cells, clonally expanded, potentially pathogenic, expressed in TII cells, unlikely to be a passenger mutation, and in immune response associated genes. We identified eight potential immunosuppressive CH mutations in TII cells. This work is a first step towards determining if immunosuppressive CH mutations in TII cells can affect the progression of solid tumors. Subsequent experimental confirmation could represent a new paradigm in the etiology of cancer. [ABSTRACT FROM AUTHOR]

In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient's biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient's blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients' biological samples—gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis. [ABSTRACT FROM AUTHOR]

Head and neck cancer etiology and architecture is quite diverse and complex, impeding the prediction whether a patient could respond to a particular cancer immunotherapy or combination treatment. A concomitantly arising caveat is obviously the translation from pre-clinical, cell based in vitro systems as well as syngeneic murine tumor models towards the heterogeneous architecture of the human tumor ecosystems. To bridge this gap, we have established and employed a patient-derived HNSCC (head and neck squamous cell carcinoma) slice culturing system to assess immunomodulatory effects as well as permissivity and oncolytic virus (OV) action. The heterogeneous contexture of the human tumor ecosystem including tumor cells, cancer-associated fibroblasts and immune cells was preserved in our HNSCC slice culturing approach. Importantly, the immune cell compartment remained to be functional and cytotoxic T-cells could be activated by immunostimulatory antibodies. In addition, we uncovered that a high proportion of the patient-derived HNSCC slice cultures were susceptible to the OV VSV-GP. More specifically, VSV-GP infects a broad spectrum of tumor-associated lineages including epithelial and stromal cells and can induce apoptosis. In sum, this human tumor ex vivo platform might complement pre-clinical studies to eventually propel cancer immune-related drug discovery and ease the translation to the clinics. [ABSTRACT FROM AUTHOR]

The purpose of this clinical study was to investigate the efficacy and safety of airway stent implantation and transarterial infusion chemotherapy in the sequential treatment of severe airway stenosis caused by esophageal cancer. Data of patients with advanced esophageal cancer complicated by severe airway stenosis treated with airway stent implantation and transarterial infusion chemotherapy were retrospectively analyzed. Furthermore, dyspnea, clinical efficacy, adverse reactions, and survival of patients were evaluated. 71 patients were included in this study. There were 28 patients with grade III dyspnea and 43 patients with grade IV dyspnea before airway stent implantation, and 34 patients with grade I dyspnea, 35 patients with grade II dyspnea and 2 patients with grade III dyspnea after airway stent implantation. After airway stent implantation and 1–3 courses of transarterial infusion chemotherapy, 11, 41 and 19 patients had complete response, partial response and stable response respectively. Total disease control rate (DCR) and objective response rate (ORR) were 100.0% and 73.2%, respectively. During the follow-up, 32 patients died of organ failure, 24 patients died of tumor-related respiratory failure, and 10 patients died of gastrointestinal bleeding. The median survival time of all patients was 8 months, and the 1-year survival rate was 40.8%. Airway stent implantation combined with arterial infusion chemotherapy is safe and effective for sequential treatment of esophageal cancer with severe airway stenosis. [ABSTRACT FROM AUTHOR]

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P < 0.05) epithelium thickness in the cancer groups as compared to the vehicle and control groups at both the PM and M. Overall, this study discovered that NTCU is capable of developing PM and M lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research. [ABSTRACT FROM AUTHOR]

Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case–control study (2008–2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal (OR≥9 hours: 1.59; 95%CI 1.30–1.94) and gastric cancer (OR≥9 hours: 1.95; 1.37–2.76); short sleep was associated with increased odds of gastric cancer (OR≤5 hours: 1.32; 0.93–1.88). Frequent and long daytime naps increased the odds of colorectal (OR6–7 naps/week, ≥30 min: 1.32; 1.14–1.54) and gastric cancer (OR6–7 naps/week, ≥30 min: 1.56; 1.21–2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) represents the most commonly diagnosed human cancer among persons of European ancestry with etiology mainly attributed to sun-exposure. In this study we investigated mutations in coding and flanking regions of PTCH1 and TP53 and noncoding alterations in the TERT and DPH3 promoters in 191 BCC tumors. In addition, we measured CpG methylation within the TERT hypermethylated oncological region (THOR) and transcription levels of the reverse transcriptase subunit. We observed mutations in PTCH1 in 58.6% and TP53 in 31.4% of the tumors. Noncoding mutations in TERT and DPH3 promoters were detected in 59.2% and 38.2% of the tumors, respectively. We observed a statistically significant co-occurrence of mutations at the four investigated loci. While PTCH1 mutations tended to associate with decreased patient age at diagnosis; TP53 mutations were associated with light skin color and increased number of nevi; TERT and DPH3 promoter with history of cutaneous neoplasms in BCC patients. Increased reverse transcriptase subunit expression was observed in tumors with TERT promoter mutations and not with THOR methylation. Our study signifies, in addition to the protein altering mutations in the PTCH1 and TP53 genes, the importance of noncoding mutations in BCC, particularly functional alterations in the TERT promoter. [ABSTRACT FROM AUTHOR]

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) emerges as a promising tool to identify the ions (small molecules) indicative of disease states from the surface of patient tissues. In TOF-SIMS analysis, an enhanced ionization of surface molecules is critical to increase the number of detected ions. Several methods have been developed to enhance ionization capability. However, how these methods improve identification of disease-related ions has not been systematically explored. Here, we present a multi-dimensional SIMS (MD-SIMS) that combines conventional TOF-SIMS and metal-assisted SIMS (MetA-SIMS). Using this approach, we analyzed cancer and adjacent normal tissues first by TOF-SIMS and subsequently by MetA-SIMS. In total, TOF- and MetA-SIMS detected 632 and 959 ions, respectively. Among them, 426 were commonly detected by both methods, while 206 and 533 were detected uniquely by TOF- and MetA-SIMS, respectively. Of the 426 commonly detected ions, 250 increased in their intensities by MetA-SIMS, whereas 176 decreased. The integrated analysis of the ions detected by the two methods resulted in an increased number of discriminatory ions leading to an enhanced separation between cancer and normal tissues. Therefore, the results show that MD-SIMS can be a useful approach to provide a comprehensive list of discriminatory ions indicative of disease states. [ABSTRACT FROM AUTHOR]