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Human papillomavirus type 16 (HPV16) belongs to viruses of the high-risk type and is associated by overexpression of E6 and E7 oncoproteins, which determine the oncogenic properties of the virus, such as immortalization and malignant transformation of proliferating epithelial cells. The biogenesis of redox-sensitive proteins E6 and E7 at the early stages of viral infection leads to blocking of the cell antioxidant defense system and ubiquintin-dependent degradation of p53 and Rb tumor suppressors. Maintaining high rates of tumor cell proliferation contributes to an increase in the level of reactive oxygen species (ROS) and a shift in the redox balance towards oxidative processes. Reduced glutathione (GSH) provides antioxidant protection to tumor cells through S-glutathionylation of thiol groups of redox-sensitive proteins, which leads to the appearance of multidrug-resistant forms of cancer. In this regard, drugs restoring redox balance and increasing susceptibility to antitumor therapy are of particular importance. We have established that, Bacillus pumilus RNase (binase) modulates the redox-dependent regulatory mechanisms that ensure tumor cell resistance to apoptosis in HPV-16-positive SiHa cells of cervical squamous cell carcinoma,. Binase in nontoxic concentrations initiates a number of pre-apoptogenic changes, i.e., decreases ROS and reduced glutathione (GSH) levels, suppresses the expression of the E6 oncoprotein, activates the expression of the p53 tumor suppressor, and reduces the mitochondrial potential of tumor cells. Binase-induced disruption of the integrity of the mitochondrial membrane is a signal for activation of the mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

Introduction: Fluid cytology and the examination of malignant cells play an important role in the treatment of critical cases. The Department of Pathology (Cytopathology laboratory) receives samples for fluid cytology and examines malignant cells, reporting the White Blood Cell (WBC) count in the received fluid and the morphological findings of the cells examined on smears. Degeneration of cells in these body fluid samples, especially if the samples are not stored under proper conditions, is a common problem faced by many laboratories. Even overnight storage (12 hours) of these body fluids at temperatures of 4-8ºC (domestic refrigerators) may still cause some degree of degenerative changes. This becomes problematic in cytopathological reporting of body fluids, particularly when the samples are limited in amount or are from areas that cannot be re-aspirated {e.g., Cerebrospinal Fluid (CSF)}. While alcohol is a common fixative used for cell fixation in cytopathology, it is rarely used for fixing cells in fluid samples. Aim: To test the usage of absolute alcohol as a fixative in body fluid samples received in the cytopathology laboratory, which have been stored for 12 hours at two temperatures: room temperature and 4-8ºC. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at Subharti Medical College, Meerut, Uttar Pradesh, India. The study was conducted over the periods of two months, from February 2022 to March 2022. A total of 100 body fluid samples (including CSF, ascitic fluid, pleural fluids, etc.) sent for routine workup to the cytopathology laboratory were included in the study. Each body fluid sample (1 mL) was taken in two test tubes, and four drops of 100% (absolute) alcohol were added to both test tubes. The mixture of body fluid and absolute alcohol was then gently shaken, and one set of test tubes was kept at room temperature while the other set was kept at 4-8ºC. The data was tabulated in an MS Excel worksheet, and basic statistical analysis was performed. Results: The age range of cases whose samples were analysed was from one-week-old neonates to 65-year-old adults. The total number of fluid samples was 100, including 42 CSF samples, 23 ascitic fluid samples, 18 pleural fluid samples, and 17 Bronchoalveolar Lavage (BAL) fluid samples. Out of the 42 CSF samples, 15 showed preservation of morphology when the alcohol-body fluid mixture was kept at room temperature, while 22 cases showed preservation of the same mixture at 4-8ºC. Some samples showed no preservation (5 CSF), the reasons for which are discussed below. All the examined body fluids showed better preservation with alcohol at 4-8ºC. Conclusion: The addition of absolute alcohol as a fixative in fluids helps preserve the cytomorphological features of cells and provides better preservation for the diagnosis of fluid samples.

Abstract In recent years, the development of antitumor drugs has been dedicated to natural products. Amygdalin is a natural herbal cyanoglycoside that has anticarcinogenic effect on many types of cancers once hydrogen cyanide (HCN) is released. The main objective of the present study is to synthesize and investigate the potential of carboxymethyl chitosan nanoparticles (CMC NPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer and normal cell lines. In this study, carboxymethyl chitosan nanoparticles encapsulated with amygdalin (CMC-Am NPs) were prepared and characterized through their particle size, surface charge, chemical structure and dielectric properties. Also, the invitro drug release of amygdalin from CMC NPs was studied. Additionally, the cytotoxcity of the amygdalin and CMC-loaded amygdalin NPs were evaluated through MTT assay. The results showed that the prepared CMC-loaded amygdalin NPs exhibited a small particle size of 129 nm, high zeta potential value of − 43 mV and confirmed the amygdalin stability and compatibility with CMC NPs. Furthermore, the CMC NPs demonstrated sustained release of amygdalin during 24 h. Moreover, compared to free amygdalin, amygdalin-loaded CMC NPs have significant anti-cancerous effect on human colon HCT-116 and breast MCF-7 cancer cell lines while being safe on normal cells BJ1. In conclusion, CMC NPs can be employed as an efficient drug delivery vehicle for controlled and sustained amygdalin release with enhanced cytotoxicity on malignant cells without harming normal cells.

In recent years, the development of antitumor drugs has been dedicated to natural products. Amygdalin is a natural herbal cyanoglycoside that has anticarcinogenic effect on many types of cancers once hydrogen cyanide (HCN) is released. The main objective of the present study is to synthesize and investigate the potential of carboxymethyl chitosan nanoparticles (CMC NPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer and normal cell lines. In this study, carboxymethyl chitosan nanoparticles encapsulated with amygdalin (CMC-Am NPs) were prepared and characterized through their particle size, surface charge, chemical structure and dielectric properties. Also, the invitro drug release of amygdalin from CMC NPs was studied. Additionally, the cytotoxcity of the amygdalin and CMC-loaded amygdalin NPs were evaluated through MTT assay. The results showed that the prepared CMC-loaded amygdalin NPs exhibited a small particle size of 129 nm, high zeta potential value of − 43 mV and confirmed the amygdalin stability and compatibility with CMC NPs. Furthermore, the CMC NPs demonstrated sustained release of amygdalin during 24 h. Moreover, compared to free amygdalin, amygdalin-loaded CMC NPs have significant anti-cancerous effect on human colon HCT-116 and breast MCF-7 cancer cell lines while being safe on normal cells BJ1. In conclusion, CMC NPs can be employed as an efficient drug delivery vehicle for controlled and sustained amygdalin release with enhanced cytotoxicity on malignant cells without harming normal cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Prediction of volume expected to be attained by a tumor of fourth grade malignancy becomes difficult when problem is subject to changes in time or when there exists heterogeneity among oncogenes for different subjects. The attempt here was to develop a time independent model which will only depend on some other radiomic properties of the tumor, also accommodating for the heterogeneity feature. Our model gives highly accurate results when we subject the initial volume of the tumor and eventually discover that the probability of no tumor cells remaining undetected is sufficiently high. Our model results are for glioblastoma tumor, but it can be applied on any other tumor volume prediction problem, and especially can be reliably adopted for tumors of high malignancy level. Predicting the eventual volume of tumor cells, that might proliferate from a given tumor, can help in cancer early detection and medical procedure planning to prevent their migration to other organs. In this work, a new statistical framework is proposed using Bayesian techniques for detecting the eventual volume of cells expected to proliferate from a glioblastoma (GBM) tumor. Specifically, the tumor region was first extracted using a parallel image segmentation algorithm. Once the tumor region was determined, we were interested in the number of cells that could proliferate from this tumor until its survival time. For this, we constructed the posterior distribution of the tumor cell numbers based on the proposed likelihood function and a certain prior volume. Furthermore, we extended the detection model and conducted a Bayesian regression analysis by incorporating radiomic features to discover those non-tumor cells that remained undetected. The main focus of the study was to develop a time-independent prediction model that could reliably predict the ultimate volume a malignant tumor of the fourth-grade severity could attain and which could also determine if the incorporation of the radiomic properties of the tumor enhanced the chances of no malignant cells remaining undetected. [ABSTRACT FROM AUTHOR]

In search of suitable tool to target the endoplasmic reticulum of human tumor cells, a non-cytotoxic aza-BODIPY derivative was designed and accessed in a simple synthesis in a few steps from commercially available starting materials. This aza-BODIPY was conjugated to 3-O-acetyl-triterpene carboxylic acids (glycyrrhetinic, ursolic, oleanolic, and betulinic acid) using a piperazinyl spacer. The resulting conjugates exhibited no cytotoxicity but were able to selectively target the ER.

To analyze the heterogeneity between different cell types in pediatric Wilms tumor (WT) tissue, and identify the differentially expressed genes (DEGs) of malignant tumor cells, thereby establishing a prognostic model. The single-cell sequencing data of pediatric WT tissues were downloaded from the public database. Data filtration and normalization, principal component analysis, and T-distributed stochastic neighbor embedding cluster analysis were performed using the Seurat package of R language. Cells were divided into different clusters, malignant tumor cells were extracted, and DEGs were obtained. Then, the pseudo-time trajectory analysis was performed. Prognostic biomarkers were determined by univariate and multivariate COX regression analyses and LASSO regression analysis. Kaplan–Meier survival analysis and receiver operator characteristic curve analysis were performed. Combined with the prognostic biomarkers and clinical characteristics, a nomogram was generated to predict WT prognosis. The prognostic power was validated in the external datasets. Cells in the WT tissue were divided into 10 clusters. Three prognostic biomarkers that affected the survival time of patients were screened from 215 DEGs in malignant tumor cells, and a nomogram was constructed using the three genes and clinical characteristics. The area under the curve (AUC) values of 3- and 5-year disease-free survival were 0.756 and 0.734, respectively. In the external validation dataset, the AUC value of this nomogram model was 0.826. Based on the single-cell RNA-seq, we recognized cell clusters in the WT tissue of children, identified prognostic biomarkers in malignant tumor cells, and established a comprehensive prognostic model. Our findings might provide new ideas and methods for the diagnosis and treatment of WT. [ABSTRACT FROM AUTHOR]

For centuries, herbal drugs have been used in various civilizations across the globe. India has its own ancient awareness on herbal drugs that people used without knowing their medicinal value or why they consume them. The changing lifestyle that individuals nowadays are leading and the increasing amount of synthetic chemicals and pollutants that they are being exposed to, many diseases and disorders are becoming more prevalent in modern societies. Cancer is one of these illnesses that causes morbidity and mortality among humankind, contributing to 9.6 million deaths annually. Even drug-resistant types of cancer have begun to increase, requiring a search for innovative and effective remedies. Herbal drugs may provide that potential cure. Plants like Boerhavia diffusa (Punarnava), Curcuma longa (Turmeric), Tinospora cordifolia, Simarouba glauca and many others are known to possess anti-cancerous properties. Molecular isolation and chemical modification of active compounds may be the key to finding the cure everyone is looking for. This paper examines herbal drugs that are being studied extensively, due to their anticancer properties. [ABSTRACT FROM AUTHOR]

Background: Adenomyosis (AM) is a common benign uterine disease that threatens the normal life of patients. Cells associated with microenvironmental immune ecology are crucial in AM, although they are not as well understood at the cellular level. Methods: Single-cell sequencing (scRNA-seq) data were used to construct an AM global single-cell map, to further identify relevant cell clusters and infer chromosomal copy number variation (CNV) in AM samples. The biological functions of cell clusters were explored and cellular evolutionary processes were inferred by enrichment analysis and pseudotime analysis. In addition, a gene regulatory network (GRN) analysis was constructed to explore the regulatory role of transcription factors in AM progression. Results: We obtained the expression profiles of 42260 cells and identified 10 cell clusters. By comparing the differences in cell components between AM patients and controls, we found that significant abundance of endometrial cells (EC), epithelial cells (Ep), endothelial cells (En), and smooth muscle cells (SMC) in AM patients. Cell clusters with high CNV levels possessing tumour-like features existed in the ectopic endometrium samples. Moreover, the Ep clusters were significantly involved in leukocyte transendothelial cell migration and apoptosis, suggesting an association with cell apoptosis and migration. En clusters were mainly involved in pathways in cancer and apoptosis, indicating that En has certainmalignant features. Conclusion: This study identified cell clusters with immune-related features, investigated the changes in the immune ecology of the microenvironment of these cells during AM, and provided a new strategy for the treatment of AM. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics. [ABSTRACT FROM AUTHOR]

Cellular analysis of body fluids (BF) has clinical relevance in several medical conditions. The objective of this study is twofold: (1) evaluate the analytical performance of the BF mode of Mindray BC-6800 Plus compared to manual counts under microscopy and (2) analyse if the high-fluorescent cell counts provided by the analyser (HF-BF) are useful to detect malignancy. A total of 285 BF was analysed: 250 corresponding to patients without neoplasia and 35 to patients with malignant diseases. Manual differential counts were performed in BF with ≥250 cells/μL. Percentages and absolute counts were obtained on the BC-6800Plus for total nucleated cells (TC-BF), mononuclear, polymorphonuclear and HF-BF. Statistical analysis was performed using Mann-Whitney U-test, Spearman's correlation, Passing-Bablok regression, Bland-Altman graph and ROC curve. To compare manual and automatic total cell counts, samples were divided in three groups: <250, 250–1,000 and >1,000 cells/μL. Correlation was good in all cases (r=0.72, 0.73 and 0.92, respectively) without significant differences between both methods (p=0.65, 0.39 and 0.30, respectively). The concordance between methods showed values of 90%. Considering malignant samples, median HF-BF values showed significant higher values (102 cells/μL) with respect to non-malignant (4 cells/μL) (p<0.001). The cut-off value of 8.5 HF-BF/μL was able to discriminate samples containing malignant cells showing sensitivity and specificity values of 89 and 71%, respectively. Considering both, HF-BF and TC-BF values, sensitivity and specificity values were 100 and 53%, respectively. This study reveals that the Mindray BC-6800Plus offers an accurate and acceptable performance, showing results consistent with the manual method. It is recommended to consider both HF-BF and TC-BF values for the screening of the microscopic evaluation to ensure the detection of all malignant samples. [ABSTRACT FROM AUTHOR]

The review provides information on the mechanisms of the antitumor action of natural and synthetic compounds of the tropolone series, obtained over the past 30 years in studies on cell cultures and, to a lesser extent, in in vivo experiments. Interest in this group of substances is due to the urgent need of clinical oncology for drugs that effectively damage malignant cells and, at the same time, are safe for healthy tissues. The processes that realize the effects of colchicine, hinokithiol (ß-tuyaplicin) and some of their derivatives (derivatives of bistropolone, α-substituted tropolones, etc.) have been studied most fully. Herewith, more numerous mechanisms of realization of the antitumor effect of hinokithiol and its derivatives were revealed in comparison with colchicine. In addition to the disruption in the formation of the cell division spindle, shown for colchicine and colchamine, such phenomena as caspase-dependent apoptosis and some other types of apoptosis, autophagy, limitation of mitochondrial metabolism, DNA damage and demethylation, and accelerated aging of malignant cells etc. have been described. The promising properties of 2‑quinolyl 1,3‑tropolone derivatives have been shown, and the relationship of their antitumor effect with the induction of apoptosis and changes in the activity of the ERK signaling pathway in some types of malignant cells have been revealed. The results indicate a multiplicity of possible ways of the influence of tropolones on the state of malignant cells, the conditions for the implementation of ones need to be clarified, especially with a lack of information about in vivo processes.The review includes information from the literature presented in the Scopus, WoS, Pubmed databases. 35 % of articles have been published in the last 5 years.

Tumor microenvironment consists of malignant and non-malignant cells. The interaction of these dynamic and different cells is responsible for tumor progression at different levels. The non-malignant cells in TME contain cells such as tumor-associated macrophages (TAMs), cancer associated fibroblasts, pericytes, adipocytes, T cells, B cells, myeloid-derived suppressor cells (MDSCs), tumor-associated neutrophils (TANs), dendritic cells (DCs) and Vascular endothelial cells. TAMs are abundant in most human and murine cancers and their presence are associated with poor prognosis. The major event in tumor microenvironment is macrophage polarization into tumor-suppressive M1 or tumor-promoting M2 types. Although much evidence suggests that TAMS are primarily M2-like macrophages, the mechanism responsible for polarization into M1 and M2 macrophages remain unclear. TAM contributes cancer cell motility, invasion, metastases and angiogenesis. The relationship between TAM and tumor cells lead to used them as a diagnostic marker, therapeutic target and prognosis of cancer. This review presents the origin, polarization, role of TAMs in inflammation, metastasis, immune evasion and angiogenesis as well as they can be used as therapeutic target in variety of cancer cells. It is obvious that additional substantial and preclinical research is needed to support the effectiveness and applicability of this new and promising strategy for cancer treatment.

Aim: The aim of this study is to know the pattern of urine cytology (UC) requests seen in Uyo and how relevant they were to the management of the patients. Materials and Methods: This retrospective study was carried out in the Department of Pathology, University of Uyo Teaching Hospital. The extracted data from the cytology registers were analyzed using the Statistical Package for the Social Sciences version 17. Results: A total of 46 patients did UC during the period. The patients were aged between 21 years and 90 years, with a mean age of 56.89 ± 14.65. Thirty (67.4%) were male. The age group of 60–69 years accounted for most cases (37.8%). Suspicion of bladder cancer was the most common indication as it was seen in 28.9% (n = 13) of cases. Thirty-eight cases (84.4%) were referred from urology clinic, 2 each (4.4%) from general outpatient clinic, general surgery clinic, and from gynecology clinic. In 44.4% (n = 20) of cases, the cytological diagnosis was inflammatory smear, while the UC was normal in 24.4% (n = 11) cases. Malignant cells were seen in 11.1% of (n = 5) cases. Of the 13 cases that the indication was suspected bladder cancer, only four were positive for malignant cells and one was suspicious on UC. No malignant cell or suspicious cell was seen in any of the UC specimens from patients that had prostate cancer, lower urinary tract outlet obstruction with hematuria due to prostatic enlargement. Conclusion: UC should not be requested for in prostatic diseases since the reports are always negative or at most inflammatory. The department should start using The Paris System of UC reporting to assist the managing physician/surgeon to take the best decision.

Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as "on-target, off-tumor toxicity", limit CAR-T application. Here, we identify the target antigen expression patterns of CAR therapies in 18 tissues and organs (peripheral blood mononuclear cells, bone marrow, lymph nodes, spleen, heart, ascending aortic tissue, trachea, lung, skin, kidney, bladder, esophagus, stomach, small intestine, rectum, liver, common bile duct, and pancreas) from healthy human samples. The atlas determines target antigens expressed on some normal cell types, which facilitates elucidating the cause of "on-target, off-tumor toxicity" in special tissues and organs by targeting some antigens, but not others. Moreover, we describe the target antigen expression patterns of B-lineage-derived malignant cells, acute myeloid leukemia (AML), and solid tumors. Overall, the present study indicates the pathogenesis of "on-target, off-tumor toxicity" during CAR therapies and provides guidance on taking preventive measures during CAR treatment. [ABSTRACT FROM AUTHOR]

Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as “on-target, off-tumor toxicity”, limit CAR-T application. Here, we identify the target antigen expression patterns of CAR therapies in 18 tissues and organs (peripheral blood mononuclear cells, bone marrow, lymph nodes, spleen, heart, ascending aortic tissue, trachea, lung, skin, kidney, bladder, esophagus, stomach, small intestine, rectum, liver, common bile duct, and pancreas) from healthy human samples. The atlas determines target antigens expressed on some normal cell types, which facilitates elucidating the cause of “on-target, off-tumor toxicity” in special tissues and organs by targeting some antigens, but not others. Moreover, we describe the target antigen expression patterns of B-lineage-derived malignant cells, acute myeloid leukemia (AML), and solid tumors. Overall, the present study indicates the pathogenesis of “on-target, off-tumor toxicity” during CAR therapies and provides guidance on taking preventive measures during CAR treatment.

Abstract Background Apoptosis plays an important role in the development and homeostasis of multicellular organisms and its deregulation may result in many serious diseases, including cancer. Now it is clear that some oncogenic mutations disrupt apoptosis, leading to tumour initiation, progression or metastasis. Here, expression of apoptotic genes in context of drug resistance was investigated. Methods We examined total of 102 samples from leukemic patients (n = 60) and patients with solid tumours (n = 42). We used RT-PCR to determine the levels of mRNA expression and the in vitro chemoresistance of leukemic cells was evaluated using the MTT assay. Results We found statistically significant increase in mRNA expression of all investigated proteins (p53, BAX, Bcl-2 and Bcl-XL) between the leukemia samples and leukocytes from healthy volunteers. We did not find any significant difference in mRNA levels among the solid tumour samples. Notably, we showed a significant positive correlation in both leukemic and solid tumour patient groups between p53 and BAX mRNA. We found that the highest values for the Bcl-2/BAX ratio were in solid tumours in comparison to leukemic cells or normal leukocytes. Moreover, we assessed the impact of p53 and BAX mRNA levels on the sensitivity of the leukemic cells to selected cytostatics. Conclusions Elevated levels of p53 and BAX mRNA may indicate cellular response to possible changes in genomic DNA integrity associated with malignant transformation. We suggest that the BAX gene is regulated by the p53 protein but the initiation of apoptosis through the transcription activation of BAX is blocked by the high levels of Bcl-2. Given that the apoptosis resistance mechanisms are different among oncological patients as well as stages of identical malignancy cases, personalized and specific combination therapy is proposed to be more effective in clinical application.

Abstract Background Epithelial ovarian cancer is the second most lethal gynecological cancer worldwide. Ascites can be found in all clinical stages, however in advanced disease stages IIIC and IV it is more frequent and could be massive, associated with worse prognosis. Due to the above, it was our interest to understanding how the ascites of ovarian cancer patients induces the mechanisms by which the cells present in it acquire a more aggressive phenotype and to know new proteins associated to this process. Methods A proteomic analysis of SKOV-3 cells treated with five different EOC ascites was performed by two-dimensional electrophoresis coupled to MALDI-TOF. The level of expression of the proteins of interest was validated by RT-PCR because several of these proteins have only been reported at the messenger level. Results Among the proteins identified that increased their expression in ascites-treated SKOV-3 cells, were Ran GTPase, ZNF268, and Synaptotagmin like-3. On the other hand, proteins that were negatively regulated by ascites were HLA-I, HSPB1, ARF1, Synaptotagmin 1, and hnRNPH1, among others. Furthermore, an interactome for every one of these proteins was done in order to identify biological processes, molecular actions, and cellular components in which they may participate. Conclusions Identified proteins participate in cellular processes highly relevant to the aggressive phenotype such as nuclear transport, regulation of gene expression, vesicular trafficking, evasion of the immune response, invasion, metastasis, and in resistance to chemotherapy. These proteins may represent a source of information which has the potential to be evaluated for the design of therapies directed against these malignant cells that reside on ovarian cancer ascites.

An O-acetyl sialic acid specific lectin was purified from the hemolymph of the marine crab Atergatis integerrimus by affinity chromatography using BSM (Bovine Submaxillary Mucin) coupled to cyanogen bromide activated Sepharose 4B and biospecific adsorption using formalinized buffalo erythrocytes. The purified AiL (Atergatis integerrimus lectin) showed an 1218 fold increase in specific activity when compared to the crude hemolymph agglutinin. The lectin, on non - denaturing PAGE showed a single band of 216 kDa and when subjected to SDS - PAGE, the lectin resolved into three subunits of molecular weight 70, 72 and 74 kDa. Physico chemical characterization revealed the lectin as pH and temperature sensitive, calcium dependent and sensitive to calcium chelators. Based on the calcium dependency of the lectin, AiL could be classified as a C-type lectin. The purified lectin agglutinated buffalo erythrocytes with greater avidity and was inhibited by the glycoproteins BSM, thyroglobulin, fetuin, PSM, and sugars raffinose, trehalose, l - fucose, α - Lactose, melibiose and GluNAc suggesting the affinity of the lectin to sialic acid. Reduction in HA with asialo buffalo erythrocytes and HAI titer with desialylated BSM, confirms the sialic acid specificity of the lectin. The reduction in HAI following de - O - acetylation confirms the specificity of the lectin for O - acetyl sialic acid. FTIR analysis confirms the purified lectin as a glycoprotein with spectral bands corresponding to amide bands and saccharides. Thus this study paves way to assess the therapeutic application of this lectin that could be targeted to modified sialic acid moieties that are expressed on the malignant cells and pathogenic microbes and also deduce the crystal structure of the lectin. • The marine crab, Atergatis integerrimus is the potent source of lectin. • A novel O-acetyl sialic acid specific lectin was isolated from this crab. • The molecular weight of the purified lectin was 216 kDa with three sub units. • The purified lectin agglutinated various erythrocytes with greater avidity. • It has wide application in determining sialic acid moieties on the malignant cells. [ABSTRACT FROM AUTHOR]

Tumor microenvironment consists of malignant and non-malignant cells. The interaction of these dynamic and different cells is responsible for tumor progression at different levels. The non-malignant cells in TME contain cells such as tumor-associated macrophages (TAMs), cancer associated fibroblasts, pericytes, adipocytes, T cells, B cells, myeloid-derived suppressor cells (MDSCs), tumor-associated neutrophils (TANs), dendritic cells (DCs) and Vascular endothelial cells. TAMs are abundant in most human and murine cancers and their presence are associated with poor prognosis. The major event in tumor microenvironment is macrophage polarization into tumor-suppressive M1 or tumor-promoting M2 types. Although much evidence suggests that TAMS are primarily M2-like macrophages, the mechanism responsible for polarization into M1 and M2 macrophages remain unclear. TAM contributes cancer cell motility, invasion, metastases and angiogenesis. The relationship between TAM and tumor cells lead to used them as a diagnostic marker, therapeutic target and prognosis of cancer. This review presents the origin, polarization, role of TAMs in inflammation, metastasis, immune evasion and angiogenesis as well as they can be used as therapeutic target in variety of cancer cells. It is obvious that additional substantial and preclinical research is needed to support the effectiveness and applicability of this new and promising strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

In the current study, we have experimentally and computationally presented vibrational decihertz (dHz), centihertz (cHz), millihertz (mHz), microhertz (μHz), nanohertz (nHz), picohertz (pHz), femtohertz (fHz), attohertz (aHz), zeptohertz (zHz) and yoctohertz (yHz) imaging and spectroscopy comparative study on malignant and benign human cancer cells and tissues under synchrotron radiation.

Abstract Background At present, infrared (IR) imaging is used both as a non-invasive and a non-ionizing technology. Using an IR camera, it is possible to measure body surface temperature in order to detect tumors and malignant cells. Tumors have a high amount of vasculature and an enhanced metabolism rate, which may result in an increase in body surface temperature by several degrees above its normal level. Methods Using thermograms, it is possible to assess various tumor parameters, such as depth, intensity, and radius. Also, by solving for Penne's bioheat equation, it is possible to develop the analytical method to solve for inverse heat conduction problem (IHCP). Results In the present study, these parameters were optimized using artificial neural networks in order to localize the heat source in the medium (i.e. female breast) more accurately. Conclusion Eventually, a new formula was derived from Penne’s bioheat equation to estimate the depth and radius of the embedded heat source. Moreover, by analyzing the data, errors of the parameters could be estimated.

Uncontrolled immune response to a pathogen or any protein can lead to tissue damage and autoimmune diseases, that represent aberrant immune responses of the individual to its own cells and/or proteins. The immune checkpoint system is the regulatory mechanism that controls immune responses. Tumor cells escape the immune surveillance mechanism, avoiding immune detection and elimination by activating these checkpoints and suppressing the anti-tumor response, thus allowing formation of tumors. Antigenic modulation facilitates masking and contributes to the escape of tumor cells. In addition, there are growing cell promoters, like transforming growth factor β (TGF-β), contributing to escape mechanisms. Targeting the immunological escape of malignant cells is the basis of immune oncology. Checkpoint inhibitors, cytokines and their antibodies may enhance the immune system’s response to tumors. Currently, immunomodulatory agents have been designed, evaluated in clinical trials and have been approved by both European and United States Drug Agencies. The present review is a reflection of the increasingly important role of the checkpoint inhibitors. Our aim is to review the side effects with the emphasis on hepatic adverse reactions of these novel biological drug interventions.

Landomycin A (LA) is a new antitumor antibiotic of angucycline group, possessing high antitumor activity against cancer cells of different origin, which induces early apoptosis in target cells. It was shown that under LA action the level of reactive oxygen species (ROS) in human T-leukemia cells had increased 5.6 times in comparison to control already at the 1st hour after the addition of studied antibiotic to the culture medium. At the 6th hour after incubation of cells with LA the nucleosomal DNA cleavage, chromatin condensation and nucleus fragmentation were observed, indicating apoptotic cell death. Catalase (scavenger of hydrogen peroxide), mannitol (scavenger of hydroxyl radicals) and superoxide dismutase (scavenger of superoxide radicals) reduced the level of ROS production under LA, suggesting the generation of H2O2, OH• and O2– radicals, respectively. It was revealed that catalase and mannitol effectively inhibited LA-mediated tumor cell death, increasing 2.5 times the percentage of alive cells in comparison to LA. However, superoxide dismutase had no significant inhibitory effect on cytotoxic activity of LA, indicating the minor role of superoxide anions in the implementation of antitumor activity of this antibiotic. Combination of catalase, mannitol and superoxide dismutase with LA increased 4-fold the percentage of alive cells in comparison to the action of LA. Dynamics of ROS formation confirms that the increase of ROS is a very rapid process, but at the same time it is not a direct consequence of apoptosis triggering, mediated by mitochondria

Abstract. The paper represents a synopsis of current publications concerning existence of free extracellular DNA. Such DNAs are not associated with cells of the organism, being revealed in nearly all body fluids. Recent data show that the cell-free DNA is determined in normal, healthy organism as well. Increased level of free DNA plasma and serum are detectable in many diseases, including autoimmune disorders, malignant neoplasias, myocardial infarction, etc. In many cases, free DNA may be suggested as predictive markers for various distinct diseases, as well as worsening of their clinical course. Physiological role of free DNA is not yet clear, like as its importance in development of certain diseases. It was shown that free DNA may exert stimulatory or suppressive effects upon functions of immunocompetent cells. Free extracellular DNA may also perform an inducing role for autoimmune conditions. In addition, one may assume that free DNA may be a carrier of genetic information in the body between tumor and normal cells in the body, like as between normal cells in various organs and tissues.