Two main problems examining the mechanism of cancer progression in the tissues using the computational models are lack of enough knowledge on the effective factors for such events in vivo environments and lack of specific parameters in the available computational models to simulate such complicated reactions.
In this study, it was tried to simulate the progression of cancerous lesions in the bone tissues by an independent parameter from the anatomical and physiological characteristics of the tissues, so to degrade the orthotropic mechanical properties of the bone tissues, a virtual temperature was determined to be used by a well-known framework for simulation of damages in the composite materials. First, the reliability of the FE model to simulate hyperelastic response in the intervertebral discs (IVDs) and progressive failure in the bony components were verified by simulation of some In-Vitro tests, available in the literature. Then, the progression of the osteolytic damage was simulated in a clinical case with multiple myeloma in the lumbar vertebrae.
The FE model could simulate stress-shielding and diffusion of lesion in the posterior elements of the damaged vertebra which led to spinal stenosis. The load carrying shares associated with the anterior half and the posterior half of the examined vertebral body and the posterior elements were estimated equal to 41 %, 47 % and 12 %, respectively for the intact condition, that changed to 14 %, 16 % and 70 %, when lesion occupied one third of the vertebral body.
Correlation of the FE results with the deformation shapes, observed in the MRIs for the clinical case study, indicated appropriateness of the procedure, proposed for simulation of the progressive osteolytic damage in the vertebral segments. The future studies may follow simulation of tumor growth for various metastatic tissues using the method, established here.

OBJECTIVE: The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett\'s esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).
METHODS: The morphologic features of nondysplastic crypts in baseline biopsy specimens from 212 BE patients (2956 biopsy specimens) were graded histologically using a 4-point scale (crypt atypia levels, 0-3). DNA content abnormalities were detected using flow cytometry.
RESULTS: In patients who had dysplasia in their baseline biopsy specimens, dysplasia was associated significantly with increasing grades of crypt atypia in the background nondysplastic Barrett\'s esophagus (P < .001). In a subset of patients without dysplasia at baseline (N = 149), a higher grade of crypt atypia was associated with longer Barrett\'s esophagus segment length (5.5 vs 3.3 cm; P = .0095), and a higher percentage of cells with 4N DNA content (3.67 ± 1.27 vs 2.93 ± 1.22; P = .018). Crypt atypia was associated with the development of any neoplasia (low-grade dysplasia and HGD/EAC). Although no significant association was noted between the grade of crypt atypia and increased 4N, aneuploidy, or progression to HGD/EAC, only patients with grade 2 or 3 crypt atypia showed increased 4N, aneuploidy, or progression to HGD/EAC.
CONCLUSIONS: Patients with Barrett\'s esophagus likely develop dysplasia via a progressive increase in the level of crypt atypia before the onset of dysplasia, and these changes may reflect some alteration of DNA content.

Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome\'s q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.

Prostate cancer (PCa) is the second most prevalent malignancy and the fifth cause of cancer-related deaths in men. A crucial challenge is identifying the population at risk of rapid progression from hormone-sensitive prostate cancer (HSPC) to lethal castration-resistant prostate cancer (CRPC). We collected 78 HSPC biopsies and measured their proteomes using pressure cycling technology and a pulsed data-independent acquisition pipeline. We quantified 7355 proteins using these HSPC biopsies. A total of 251 proteins showed differential expression between patients with a long- or short-term progression to CRPC. Using a random forest model, we identified seven proteins that significantly discriminated long- from short-term progression patients, which were used to classify PCa patients with an area under the curve of 0.873. Next, one clinical feature (Gleason sum) and two proteins (BGN and MAPK11) were found to be significantly associated with rapid disease progression. A nomogram model using these three features was generated for stratifying patients into groups with significant progression differences (p-value = 1.3×10-4). To conclude, we identified proteins associated with a fast progression to CRPC and an unfavorable prognosis. Based on these proteins, our machine learning and nomogram models stratified HSPC into high- and low-risk groups and predicted their prognoses. These models may aid clinicians in predicting the progression of patients, guiding individualized clinical management and decisions.

MicroRNAs are non-coding RNAs fundamental to metazoan development and disease. Although the aberrant regulation of microRNAs during mammalian tumorigenesis is well established, investigations into the contributions of individual microRNAs are wrought with conflicting observations. The underlying cause of these inconsistencies is often attributed to context-specific functions of microRNAs. We propose that consideration of both context-specific factors, as well as underappreciated fundamental concepts of microRNA biology, will permit a more harmonious interpretation of ostensibly diverging data. We discuss the theory that the biological function of microRNAs is to confer robustness to specific cell states. Through this lens, we then consider the role of miR-211-5p in melanoma progression. Using literature review and meta-analyses, we demonstrate how a deep understating of domain-specific contexts is critical for moving toward a concordant understanding of miR-211-5p and other microRNAs in cancer biology.

[This corrects the article DOI: 10.3389/fonc.2022.862116.].

The combination of paclitaxel and ramucirumab is the second-line therapy of choice in the treatment of advanced gastric cancer. To date, no biomarkers are available in gastric cancer to predict the outcome of antiangiogenic therapy. The present prospective study included 35 patients undergoing second-line therapy with ramucirumab and paclitaxel. Serum samples were systematically collected from the beginning of therapy and at each cycle until disease progression. Multiplex analysis of a panel of angiogenic factors identified markers for which the changes at defined time intervals were significantly different in patients with progression-free survival ≤3 (Rapid Progression Group) compared to those with progression-free survival >3 (Control Disease Group). Comparative analysis revealed significantly different results in the two groups of patients for VEGFC and Angiopoietin-2, both involved in angiogenesis and lymphangiogenesis. VEGFC increased in the progressive-disease group, while it decreased in the control-disease group. This decrease persisted beyond the third cycle, and it was statistically significant compared to the basal level in patients with longer progression-free survival. Angiopoietin-2 decreased significantly after 2 months of therapy. At progression time, there was a significant increase in VEGFC and Angiopoietin-2, suggesting the activation pathways counteracting the blockade of VEGFR2 by ramucirumab. Overall results showed that a greater change in VEGFC and Angiopoietin-2 levels measured at the beginning of the third cycle of therapy corresponded to a lower risk of progression and thus to longer progression-free survival.

BACKGROUND: Pigment epithelium derived factor (PEDF) is a secreted protein that strongly suppresses angiogenesis and directly inhibits cancer cells proliferation. The differential expression of PEDF has been observed in multiple types of human tumors. However, it is unclear as to how PEDF expression is associated with cancer progression and if PEDF could serve as a prognostic marker for cancer patients.
METHODS: We performed a comprehensive search for the studies on PEDF expression in 14 top-ranked types of solid tumor cancer with the highest incidence. A systemic approach was used to screen for qualified studies and to extract data. Meta-analysis was performed to investigate if PEDF expression is associated with the TNM staging, tumor size, lymph node invasion, distal metastasis and pathological grade of tumor in a pan-cancer manner. A Kaplan-Meier curve was plotted with the digitally-reconstituted patient survival data to study the effect of PEDF expression on the prognosis of cancer patients.
RESULTS: A total of nine studies were selected, reviewed and analyzed. Meta-analysis suggested that decreased PEDF protein expression was associated with higher TNM staging (OR = 2.13, 95% CI: 1.61-2.81), larger tumor size (OR = 1.42, 95% CI: 1.1-1.84), larger possibility of lymph node invasion (OR = 1.68, 95% CI: 1.26-2.22) and higher pathological grade (OR = 1.6, 95% CI: 1.2-2.13). No correlation was found between PEDF expression and tumor distal metastasis, gender or age. In addition, low PEDF protein level in tumor tissue is correlated with shorter overall survival (P < 0.05).
CONCLUSIONS: Low PEDF protein expression in cancer is significantly associated with more advanced cancer progression and significantly poorer survival. The differential clinical outcome among patients with various PEDF expression suggests its prognostic value.

BACKGROUND: Current NHS guidelines recommend that treatment of colorectal patients referred through the two-week wait referral system should occur within sixty two days from the date of referral. The COVID-19 pandemic which started in March 2020 has however led to significant delays in the delivery of health services, including colorectal cancer treatments. This study investigates the effects of delayed colorectal cancer treatments during the COVID pandemic on disease progression.
METHODS: A retrospective chart review of 107 patients with histologically confirmed diagnosis of colorectal cancer was conducted. The occurrence of cancer upstaging after initial diagnosis was assessed and compared between patients with treatment delays and patients who received treatments within the period recommended by NHS guidelines. A logistic regression was performed to evaluate the association between treatment delays beyond 62 days and cancer upstaging.
RESULTS: The median age of the cohort was 71.2 years and 64.5% of the patients were over 65 years. Treatment delays were observed in 53.3% of reviewed patients. Patients with treatment delays received cancer treatments 95.8 (31.0) days on average after referral, compared to 46.3 (11.5) days in patients who experienced no treatment delays (p-value<0.0001). 38.6% of patients with treatment delays experienced cancer upstaging by the time of treatment, compared to 20% in the non-delay group (p-value = 0.036). Patients who received treatment after sixty two days from date of referral were 3.27 times more likely to experience colorectal cancer upstaging compared to those who received timely treatments.
CONCLUSIONS: Although an effective response to the Covid-19 pandemic requires the reallocation of healthcare resources, there is a need to ensure that treatments and health outcomes of patients with chronic diseases such as colorectal cancer continue to be prioritized and delivered in timely fashion.

Although studies have investigated cadmium and prostate cancer (PC) incidence and mortality, the role of cadmium in PC progression might be more clinically relevant. In this observational study, we assessed the association between air cadmium exposure and PC aggressiveness, with PC stage defined as metastatic or localized and Gleason grade defined as high (Gleason score ≥ 8) or low (Gleason score ≤ 6) among PC patients from the 2010-2014 US Surveillance, Epidemiology, and End Results database. The 2005 and 2011 National Air Toxics Assessment provided county-level air cadmium concentrations. Results were presented as odds ratios (OR) with 95% confidence intervals (CI) and were calculated using random intercept mixed effects logistic regression, comparing the 80th to 20th percentile of exposure. We adjusted for age, sociodemographic status, smoking prevalence, and overall air quality at the county level, and stratified by race, age, and degree of urbanization. The cohort consisted of 230,540 cases from 493 counties. Strong associations were observed in nonmetropolitan, urban areas: (OR 1.26, CI 1.14-1.39) for metastatic vs. localized and (OR 1.41, CI 1.27-1.57) for high- vs. low-grade PC where 40 million Americans reside. This study may be hypothesis-generating to inform future studies and public health measures.