Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups

Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated. Methods: SATB2 expression was analysed in 1039 CRCs and correlated with clinicopathological and morphological factors, CDX2 expression as well as survival parameters within the overall cohort and in clinicopathological subgroups. Results: SATB2 loss was a strong prognosticator in univariate analyses of the overall cohort (p < 0.001 for all survival comparisons) and in numerous subcohorts including high-risk scenarios (UICC stage III/high tumour budding). SATB2 retained its prognostic relevance in multivariate analyses of these high-risk scenarios (e.g., UICC stage III: DSS: p = 0.007, HR: 1.95), but not in the overall cohort (DSS: p = 0.1, HR: 1.25). SATB2 loss was more frequent than CDX2 loss (22.2% vs. 10.2%, p < 0.001) and of higher prognostic relevance with only moderate overlap between SATB2/CDX2 expression groups. Conclusions: SATB2 loss is able to identify especially aggressive CRCs in high-risk subgroups. While SATB2 is the prognostically superior immunohistochemical parameter compared to CDX2 in univariate analyses, it appears to be the less sensitive marker for colorectal differentiation as it is lost more frequently.

Monitoring Group Activity of Hamsters and Mice as a Novel Tool to Evaluate COVID-19 Progression, Convalescence, and rVSV-ΔG-Spike Vaccination Efficacy

The COVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models included the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of human COVID-19. A group activity of animals in their home cage continuously monitored by the HCMS100 (Home cage Monitoring System 100) was used as a sensitive marker of disease, successfully detecting morbidity symptoms of SARS-CoV-2 infection in hamsters and in K18-hACE2 mice. COVID-19 convalescent hamsters rechallenged with SARS-CoV-2 exhibited minor reduction in group activity compared to naive hamsters. To evaluate the rVSV-ΔG-spike vaccination efficacy against SARS-CoV-2, we used the HCMS100 to monitor the group activity of hamsters in their home cage. A single-dose rVSV-ΔG-spike vaccination of the immunized group showed a faster recovery than the nonimmunized infected hamsters, substantiating the efficacy of rVSV-ΔG-spike vaccine. HCMS100 offers nonintrusive, hands-free monitoring of a number of home cages of hamsters or mice modeling COVID-19.

Assessing mPTC Progression during Active Surveillance: Volume or Diameter Increase?

Active surveillance (AS) is considered an alternative to immediate surgery in micropapillary thyroid carcinoma (mPTC). However, the definition of clinical mPTC progression during AS is controversial. We evaluated changes in tumor size using both tumor diameters and volume in 109 patients with mPTC followed in an AS protocol for a mean period of 31 ± 18 months. At the time of data lock, 19/109 (17.4%) mPTC reached and maintained a volume increase of ≥50%. However, only 3/19 (15.7%) showed progression, according to the diameter increase. The remaining 16 showed a slight diameter growth without reaching the original protocol progression criteria. The mean mPTC growth rate in stable cases was 0.37 mm3/month, while it was significantly greater in the mPTC, which achieved a volume change ≥50% with respect to the other. The two mPTC that developed a significant diameter increase had a growth rate of 41 and 18 mm3/month. Instead, the growth rates of the three mPTC that developed lymph node metastases were 0, 2.5 and 16 mm3/month. The ≥50% volume increase appears to be a too sensitive marker of disease progression, with a downstream higher surgery rate. The assessment of growth rate could distinguish mPTC with high and low growth rates, which would allow us to tailor the algorithm of the evaluations to a more appropriate timing.

Synovial Fluid Mitochondrial DNA Concentration Reflects the Degree of Cartilage Damage After Naturally Occurring Articular Injury

Posttraumatic osteoarthritis (PTOA) is a debilitating sequela to joint injury with no current therapeutics that can slow its progression. Early intervention, prior to the development of degenerative joint changes, has the potential for greater therapeutic success but requires early detection of joint injury. In other tissue types, trauma is associated with the extracellular release of mitochondrial DNA (mtDNA), which serves as a mitochondria-specific Damage Associated Molecular Pattern (mDAMP) to perpetuate inflammation. We demonstrated that chondrocytes release mtDNA following cellular stress and that mtDNA is increased in equine synovial fluid following experimental and naturally occurring mechanical injury to the joint surface. Moreover, we found a strong correlation between the degree of cartilage damage and mtDNA concentration. Finally, impact-induced mtDNA release was mitigated by mitoprotective treatment. These data suggest synovial fluid mtDNA may represent a sensitive marker of early articular injury, prior to the onset of changes on standard diagnostic imaging modalities.

The Reactive Carbonyl Derivatives of Proteins, Methylglyoxal, and Malondialdehyde in Blood of Women with Breast Cancer

BACKGROUND: Every year 1.5 million women in the world are diagnosed with breast cancer (BC). In 2018, more than 260,000 new cases of cancer and more than 40,000 deaths due to this disease were detected. At the same time, in Kazakhstan, an intensive indicator of the incidences of BC in 2018 amounted to 25.3% per population of 100 thousand people (2017–24.5%) with a growth rate of 3.1%, which in absolute numbers are 4,648 new cases per year. In terms of mortality, BC ranks third after lung and stomach cancer (6.8%). AIM: This necessitates a detailed study of the molecular mechanisms that underlie the development and progression of BC. One of the mechanisms of carcinogenesis is oxidative stress (OS). An increase in malondialdehyde (MDA) levels was detected in the early stages of cancer. It was suggested that MDA, due to its high cytotoxicity, acts as a promoter of the tumor and cocarcinogen agent. METHODS: Therefore, violation of the parameters of OS in BC is in no doubt. However, according to the literature data analysis, these results are ambiguous and contradictory. There are no studies on a comprehensive assessment of the oxidative destruction of lipids, proteins, and nucleic acids in BC. CONCLUSION: The nature and direction of changes in various components of OS in patients with BC have not been adequately studied, which is necessary for a correct assessment of the involvement of OS in the mechanism of the pathological process and determination of a sensitive marker of the risk of BC or its progression.

DOES CARDIAC TROPONIN€“I IS RECOGNIZED AS AN EARLY POSTOPERATIVE MARKER FOR MYOCARDIAL DAMAGE IN CHILDREN?

Introduction:Cardiac troponin-I being a sensitive marker of myocardial damage needs to be analyzed in children undergoing cardiopulmonary by-pass surgery, as perioperative myocardial damage may be a significant factor of postoperative cardiac performance. The present study aims to test the prognostic value of Cardiac troponin-I concerning the early postoperative course after pediatric cardiac surgery. Methods:Cardiac troponin – I levels were measured and correlated with intra and postoperative parameters of thirty-three children undergoing open-heart surgery. The cutoff point for the definition of a high and a low-risk group of Cardiac troponin-I values was set at 25 ng/ml. Results:Overall, cTnI peak value was higher than 25 ng/ml in 21 patients among these,4 died, and two of them were reported with the value of >100 ng/ml. 38.7% of the patients were complicated by different types of arrhythmias. Junctional ectopic tachycardia was the most common type of arrhythmia,while heart block complication was found only in one case, which was temporarily treated by pacing for less than 24 hours. The results showed significant correlation of troponin I values with dobutamine dose mg/kg (p-value=0.043), dobutamine duration (p-value=0.020), creatinine (p-value= 0.002), and internalcare unit stay (p-value= 0.003). Conclusion: The present study confirms that troponin I is specific and sensitive marker of myocardial injury after pediatric cardiac surgery.

Expression of S100, HMB45 and Melan A in Oral Mucosal Melanoma

Background: Malignant melanomas of the oral cavity are rare tumours. The diagnosis of mucosal melanoma can be difficult especially when it presents itself in its amelanotic form. Methodology: An electronic search was carried out on Pubmed and Medline database to find studies addressing this question published between Jan 2001 and April 2020. Multiple studies are done to determine the staining and positivity of the above mentioned three markers were found. A total of 4 studies were finally selected for this review which tried to determine the efficiency of these three markers in the diagnosis of oral mucosal melanomas. Results: The patient’s data that stained positive S100, HMB45 and Melan A from 4 studies were selected. Conclusion: S100 continues to remain the most sensitive marker for melanoma with its promising ability in diagnosing the desmoplastic variant. The lack of specificity is still a drawback of S100.