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Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD79b, CD45, CD23, CD22 and CD81 serve as reliable prognostic indicators in CLL as well as the human leukocyte antigen (HLA) with its well-documented associations with various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Although it is one of the most prevalent neoplasms, there is a need for biomarkers that can improve survival. This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing was performed for HLA typing. The results indicate that several CD markers are statistically associated with different HLA alleles, specifically CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01. In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL.

Background: Gastrointestinal adenocarcinomas are a worldwide and some of the most important causes of death related to cancers. MLH1, PMS2, and K-Ras are some of the main molecules responsible for the control of cellular proliferation. They are widely used as biomarkers for the evaluation of the features of tumoral processes and the clinicopathological characteristics. They depend on the type of cells implied in the tumoral process, and it can be observed in the concentrations of them in different biological fluids. Maspin, also known as peptidase inhibitor 5 or serpin B5 is a tumor suppressor which inhibits invasion and angiogenesis and also regulates apoptosis, but it can also present oncogenic activity depending on tumor location and histology and on the subcellular maspin localization. Its correlations with gastric and colorectal carcinomas have been emphasized in a series of articles, and in this work, a method is used to quantify the concentrations of maspin in three biological fluids, allowing correlations with pathological features. Methods: Patients with their clinical and pathological features were selected from the database of the project GRAPHSENSGASTROINTES and used accordingly with the Ethics committee approval nr. 32647/2018 awarded by the County Emergency Hospital from Targu-Mures. Three kinds of samples have been analyzed (saliva, whole blood, and urine) using a stochastic method using stochastic microsensors. Results: The results obtained using stochastic sensors were correlated with the location of cancer, and there have been elaborated a series of criteria to differentiate gastric cancers from colorectal ones. Conclusions: There can be differentiation between the two types of cancers by using the concentrations of MLH1, PMS2, and K-Ras in saliva and urine samples or the levels of maspin in whole blood and urine or in whole blood, urine, and saliva. The data analysis led to a series of criteria for evaluation of the cancer location. Using only MLH1 and PMS2 concentrations in one of the two kinds of samples was only indicative and did not cover most cases. The use of the criteria only for MLH1 and PMS2 increased the probability of finding out the location, but the best results require the concentrations of K-Ras in the two kinds of samples as additional criteria.

Abstract Two stochastic microdisks were designed and validated for the DNA mismatch repair assessment in gastric and colon cancers, through determining simultaneously the concentrations of MLH1, MSH2, MSH6, PMS2, and of KRAS in whole blood, urine, saliva, and tumoral tissues. The active surface of the stochastic microdisks was composed of a thin layer of graphene paste decorated with nitrogen, boron, and sulfur and modified with inutec (SP) and with frutafit (FT), respectively. High sensitivities were recorded when the SP was used as modifier. All limits of determination were of fg mL−1 magnitude order. The paired student‐t‐test done at 99.00 % confidence level revealed that there are no significative differences between the results obtained using the two stochastic microdisks. Validation of the screening tests of whole blood, urine, saliva, and tumoral tissues was also done using the recovery tests when % recovery was higher than 87.00 %, with %RSD values lower than 1.00 %.

(1) Background: The human MutS homolog, hMSH2, is known to be involved in DNA mismatch repair and is responsible for maintaining the stability of the genome. When DNA damage occurs, MSH2 promotes cell apoptosis via the regulation of ATR/Chk2/p53 signal transduction, and MSH2 deficiency is also related to accelerated telomere shortening in humans. MSH2 missense mutations are involved in a defective DNA reparation process, and it can be implied in carcinogenesis, as it is already involved in well-known cancer-related syndromes such as Lynch syndrome. Human MSH6, which stands for mutS homolog 6, is a member of the MMR family that is responsible for the repair of post-replicative mismatched DNA bases. It is also one of the proteins with gene mutations that are associated with a high risk of developing Lynch syndrome, leading to a large series of tumors. (2) Methods: Patients and their clinical and pathological features were selected from the database of the project GRAPHSENSGASTROINTES and used accordingly, with ethics committee approval no. 32647/2018 awarded by the County Emergency Hospital from Targu-Mures. Analyses were conducted on whole blood, saliva, urine, and tumoral tissue samples using a stochastic method with stochastic microsensors. (3) Results: The results obtained using stochastic sensors were correlated with a series of macroscopic and microscopic pathological features for each sample type. Criteria or relationships were established for tumor location, vascular and perineural invasions, lymph node metastases, the presence of tumor deposits, and the presence of a mucus compound in the tumor mass. (4) Conclusions: The correlation between the concentrations of MSH2 in the four types of samples and the pathological features allowed for the fast characterization of a tumor, which can help surgeons and oncologists choose personalized treatments. Also, the colorectal tumor location was correlated with the concentration of MSH2 in whole blood, urine, and saliva. MSH6, which stands for mutS homolog 6, is not only useful in immunohistochemistry but in pathology practice as well. In this paper, the relationships between MSH6 levels in four biological fluids—whole blood, saliva, urine, and tissues—and tumor locations among the colorectal area, gross features, presence of a mucinous compound, molecular subtype, stroma features, and vascular invasions are presented.

Bone metastases represent about 70% of breast cancer metastases and are associated with worse prognosis as the tumor cells acquire more aggressive features. The selection and investigation of patients with a high risk of developing bone metastasis would have a significant impact on patients’ management and survival. The patients were selected from the database of Carol Davila Clinical Nephrology Hospital of Bucharest. Their tumor specimens were pathologically processed, and a representative area was selected. This area was scanned using an Olympus VS200 slide scanner and further analyzed using QuPath software v0.4.4. A representative group of approximately 60–100 tumor cells was selected from each section, for which the following parameters were analyzed: nuclear area, nuclear perimeter, long axis and cell surface. Starting from these measurements, the following were calculated: the mean nuclear area and mean nuclear volume, the nucleus to cytoplasm ratio, the length of the two axes, the long axis to short axis ratio, the acyclicity and anellipticity grade and the mean internuclear distance. The tumor cells belonging to patients known to have bone metastasis seemed to have a lower nuclear area (2, p = 0.0035), smaller long axis (p = 0.0015), smaller values for the small axis (p = 0.0008), smaller mean nuclear volume (3, p = 0.0146) and lower mean internuclear distance (p = 0.0007) but a higher nucleus to cytoplasm ratio (>1.1, p = 0.0418), higher axis ratio (>1.2, p = 0.088), higher acyclicity grade (>1.145, p = 0.0857) and higher anellipticity grade (>1.14, p = 0.1362). These parameters can be used for the evaluation of risk category of developing bone metastases. These results can be useful for the evaluation of bone metastatic potential of breast cancer and for the selection of high-risk patients whose molecular profiles would require further investigations and evaluation.

(1) Background: Human SERPINB5, commonly known as maspin, has diverse functions as a tumor suppressor. Maspin has a novel role in cell cycle control, and common variants were discovered to be associated with gastric cancer (GC). Maspin was proven to also affect the EMT and angiogenesis of gastric cancer cells via the ITGB1/FAK pathway. Information about the maspin concentrations correlated with different pathological features of the patients may facilitate the fast diagnosis and personalized treatment of patients. The novelty of this study is given by the correlations established for the maspin levels in different biological features and clinicopathological features. These correlations can be extremely useful for surgeons and oncologists. (2) Patients and methods: Patients with clinical and pathological features, given the small number of samples available for this study, were selected from the database of the project GRAPHSENSGASTROINTES, and used in accordance with the Ethics Committee approval nr. 32,647/2018 awarded by the County Emergency Hospital from Targu-Mures. Stochastic microsensors were used as new screening tools for the determination of the concentration of maspin in four types of samples: tumoral tissues, blood, saliva and urine. (3) Results: The results obtained using the stochastic sensors were correlated with those tabulated in the clinical and pathological database. A series of assumptions regarding the values and practice important features for surgeons and pathologists were made. (4) Conclusions: This study provided a few assumptions regarding the correlations between the values of maspin levels in the analyzed samples and the clinical and pathological features. These results may be useful as preoperative investigations in order to help surgeons localize, approximate and choose the best treatment. These correlations may facilitate minim invasive and fast diagnosis of gastric cancer based on reliable detection of maspin concentration in biological samples (tumoral tissues, blood, saliva and urine).

Maspin is an important biomarker which was proven to be correlated to many pathological features that can help the oncologists, the surgeons and also the pathologists for choosing the personalized treatment of the patients. Maspin expression correlates with the budding of colorectal adenocarcinomas that is usually used mostly in immunohistochemistry. In this preliminary study, a small number of patients with clinical and pathological features were selected. Four kinds of samples (tumoral tissues, blood, saliva and urine) were analyzed using a stochastic method using stochastic microsensors. Whole blood maspin concentration values were related to budding, molecular subtype and location. Tissular maspin concentrations were related to location, maxi-mum diameter and pN value from TNM staging system. Salivary maspin concentrations were related to budding, mucinous compound and macroscopic features. Urinary maspin concentrations were related to pT value from TNM staging system, budding and molecular subtype. The correlations made in this paper may be used for fast diagnostic of colorectal adenocarcinomas, after which, it will be tested on a significant number of patients confirmed with colon cancer, in different stages of evolution.

Two-needle 3D stochastic microsensors based on boron- and nitrogen-decorated gra-phenes, modified with N-(2-mercapto-1H-benzo[d]imidazole-5-yl), were designed and used for the molecular recognition and quantification of CA 72-4, CA 19-9, CEA and CA 125 biomarkers in biological samples such as whole blood, urine, saliva and tumoral tissue. The NBGr-2 sensor yielded lower limits of determination. For CEA, the LOD was 4.10 × 10−15 s−1 g−1 mL, while for CA72-4, the LOD was 4.00 × 10−11 s−1 U−1 mL. When the NBGr-1 sensor was employed, the best results were obtained for CA12-5 and CA19-9, with values of LODs of 8.37 × 10−14 s−1 U−1 mL and 2.09 × 10−13 s−1 U−1 mL, respectively. High sensitivities were obtained when both sensors were employed. Broad linear concentration ranges favored their determination from very low to higher concentrations in biological samples, ranging from 8.37 × 10−14 to 8.37 × 103 s−1 U−1 mL for CA12-5 when using the NBGr-1 sensor, and from 4.10 × 10−15 to 2.00 × 10−7 s−1 g−1 mL for CEA when using the NBGr-2 sensor. Student’s t-test showed that there was no significant difference between the results obtained utilizing the two microsensors for the screening tests, at a 99% confidence level, with the results obtained being lower than the tabulated values.