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Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare subtype of pancreatic cancer, accounting for less than 1% of all pancreatic tumors. Preoperative diagnosis is cumbersome as cross-sectional imaging is often not capable to distinguish between UC-OGC and other pancreatic tumors such as pancreatic adenocarcinoma, mucinous carcinoma or neuroendocrine tumors and specific tumor markers seem to be lacking. Endoscopic ultrasound r `m(EUS) with tissue acquisition via fine-needle aspiration (FNA) or biopsy (FNB) with microscopic HE staining and immunohistochemistry allows for an accurate diagnosis, thus influencing further treatment. We present herein the cases of two patients with osteoclast-like giant cells tumors of the pancreas diagnosed by EUS-guided fine needle biopsy and perform a literature review on the role of EUS-guided biopsy for diagnosis.

Background: The widespread use of prostate specific antigen (PSA) caused high rate of overdiagnosis. Overdiagnosis leads to unnecessary definitive treatments of prostate cancer (PCa) with detrimental side effects, such as erectile dysfunction and incontinence. The aim of this study was to evaluate the feasibility of an artificial neural network-based approach to develop a combinatorial model including prostate health index (PHI) and multiparametric magnetic resonance (mpMRI) to recognize clinically significant PCa at initial diagnosis. Methods: To this aim we prospectively enrolled 177 PCa patients who underwent radical prostatectomy and had received PHI tests and mpMRI before surgery. We used artificial neural network to develop models that can identify aggressive PCa efficiently. The model receives as an input PHI plus PI-RADS score. Results: The output of the model is an estimate of the presence of a low or high Gleason score. After training on a dataset of 135 samples and optimization of the variables, the model achieved values of sensitivity as high as 80% and 68% specificity. Conclusions: Our preliminary study suggests that combining mpMRI and PHI may help to better estimate the risk category of PCa at initial diagnosis, allowing a personalized treatment approach. The efficiency of the method can be improved even further by training the model on larger datasets.

High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease (NAFLD). As a result, this condition has recently become one of the leading causes of hepatocellular carcinoma (HCC). Furthermore, the incidence of NAFLD-associated HCC (NAFLD-HCC) is expected to increase in the near future. Advanced liver fibrosis is the most common risk factor for NAFLD-HCC. However, up to 50% of NAFLD-HCC cases develop without underlying liver cirrhosis. Epidemiological studies have revealed many other risk factors for this condition; including diabetes, other metabolic traits, obesity, old age, male sex, Hispanic ethnicity, mild alcohol intake, and elevated liver enzymes. Specific gene variants, such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3, transmembrane 6 superfamily member 2, and membrane-bound O-acyl-transferase domain-containing 7, are also associated with an increased risk of HCC in patients with NAFLD. This clinical and genetic information should be interpreted together for accurate risk prediction. Alpha-fetoprotein (AFP) is the only biomarker currently recommended for HCC screening. However, it is not sufficiently sensitive in addressing this diagnostic challenge. The GALAD score can be calculated based on sex, age, lectin-bound AFP, AFP, and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC. In addition, emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential. However, further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.

According to Global Cancer Statistics 2020, an estimated 19.3 million new cancer cases and almost 10 million cancer deaths occurred in 2020. Solid tumors represent approximately 90% of adult human cancers, hence they warrant significant attention from the research fraternity to improve upon the existing platforms of treatment and management of the malignancy. Only by a better understanding of the biology associated with cancer development and progression can we identify clinically relevant novel molecular targets that can not only improve upon the risk stratification of the patients, but also assist in overall disease management. PIWI-interacting RNA (piRNA) is a class of small non-coding RNA (26-31nt) that interacts with PIWI proteins to form the piRNA silencing complex (piRISC). PIWI is a subfamily of Argonaute, and piRNA must bind to PIWI to exert its regulatory role, although have been also described PIWI independent functions for piRNAs. Nearly 10 million unique piRNA sequences (2) have now been identified in humans alone that have been recognized to play a wide variety of roles including germline development, maintenance, and protection of the genome integrity by repressing the activity of transposons through post-transcriptional silencing or other epigenetic mechanisms. Emerging data suggests that piRNAs also have strong regulatory roles within the somatic tissues where they regulate gene expression by inducing histone modification and DNA methylation. Owing to their remarkable roles in maintaining cellular homeostasis, it is not surprising that the expression of piRNAs is reported to be frequently deregulated in several cancers. Current studies indicated that piRNAs are significantly abnormally expressed and are involved in the initiation, progression, and metastasis of different solid tumors, which may be the potential diagnostic tools, prognostic markers, and therapeutic targets for cancers. This special issue is a collection of original research and review articles on this topic.

Gastric cancer (GC) is recognized as one of the most common deadly malignancies worldwide and about 40–50% of patients present at diagnosis with an unresectable disease due to a locally advanced or already metastatic condition. Recently, therapeutic options for management of metastatic GC (mGC) have been approved allowing a potential improvement of patient cancer treatment response and also an establishment of a continuum of care for this aggressive disease. This report is the result of a literature review by an expert panel. The aim of this document is to provide evidence, wherever it is lacking, to provide expert opinion directed at strategic management of mGC, and in particular aspect at practical management where appropriate guidelines are not available. Treatment landscape with new therapeutic strategies for third line and beyond, role of imaging, prognostic factors, symptoms, and markers as well as the importance of multidisciplinary approach particularly the nutritional aspects are discussed.

Early cancer diagnosis requires ultrasensitive detection of tumor markers in blood. To this end, we develop a novel microcantilever immunosensor using nanobodies (Nbs) as receptors. As the smallest antibody (Ab) entity comprising an intact antigen-binding site, Nbs achieve dense receptor layers and short distances between antigen-binding regions and sensor surfaces, which significantly elevate the generation and transmission of surface stress. Owing to the inherent thiol group at the C-terminus, Nbs are covalently immobilized on microcantilever surfaces in directed orientation via one-step reaction, which further enhances the stress generation. For microcantilever-based nanomechanical sensor, these advantages dramatically increase the sensor sensitivity. Thus, Nb-functionalized microcantilevers can detect picomolar concentrations of tumor markers with three orders of magnitude higher sensitivity, when compared with conventional Ab-functionalized microcantilevers. This proof-of-concept study demonstrates an ultrasensitive, label-free, rapid, and low-cost method for tumor marker detection. Moreover, interestingly, we find Nb inactivation on sensor interfaces when using macromolecule blocking reagents. The adsorption-induced inactivation is presumably caused by the change of interfacial properties, due to binding site occlusion upon complex coimmobilization formations. Our findings are generalized to any coimmobilization methodology for Nbs and, thus, for the construction of high-performance immuno-surfaces. Electronic Supplementary Material Supplementary material (experimental section, HER2 detection using anti-HER2-mAb-functionalized microcantilevers) is available in the online version of this article at 10.1007/s12274-021-3588-4.

The new type of coronavirus could cause severe acute respiratory syndrome and injuries in other systems as well. Multiple organ damage can occur rapidly in patients infected with coronavirus disease 2019 (COVID‐19). Previous studies have shown that many laboratory biomarkers were not within the normal ranges in COVID‐19 patients. We aimed to summarize laboratory parameters and the tumor markers in COVID‐19 patients. This is a retrospective cohort study conducted on 53 women between the ages of 19–85 years infected with COVID‐19 at a training and research hospital between May 2020 and August 2020. Of the 53 women, 16 (30.2%) had leukopenia. The mean C‐reactive protein level was 18.42 ± 59.33 mg/L. The mean procalcitonin level was 0.1 ± 0.21 µg/L. The liver function tests were within normal limits. The mean creatinine level was 0.58 ± 0.37 mg/dl. Elevated levels of α‐fetoprotein (AFP) in 1 patient, elevated levels of carcinoembryonic antigen (CEA) in 2 patients, elevated levels of cancer antigen 125 (CA125) in 4 patients, elevated levels of CA19‐9 in 2 patients, and elevated levels of CA15‐3 in 2 patients were detected. One of 4 patients who were taken to the intensive care unit had elevated levels of AFP. In addition, 2 of 4 patients who were taken to the intensive care unit had elevated levels of CA125 and CA15‐3. Except for AFP, levels of all tumor markers of the patient who died were high. We found that COVID‐19 had no effect on tumor markers (CA125, CA19‐9, CA15‐3, AFP, and CEA).

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients.

Objective: To describe the presenting signs and symptoms, clinic-pathological findings of ovarian masses and to establish diagnostic value of clinical examination, ultrasonography and its correlation with histopathological diagnosis. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital, Rawalpindi Jun 2017 May 2018. Methodology: Women who underwent surgery for ovarian masses were included. Data was collected from hospital records including; age, presenting symptoms, duration of symptoms, changes in menstrual cycle, and the results of the physical examination. The preliminary diagnoses as well as the final diagnosis were noted. Results: A total of 83 patients with ovarian masses, who underwent surgery over the period of a year, were included. The most common symptom was abdominal pain in 56 (67.5%) followed by abdominal distention 9 (10.8%), dysmenorrhea 8(9.6%). When both clinical and sonological diagnosis were combined, the overall sensitivity, specificity, positive and negative predictive value for diagnosis and discriminating benign and malignant ovarian neoplasms were 87.5%, 96.7%, 70%, and 98.88%, respectively. Conclusion: In this study most, common symptom was abdominal pain both in benign and malignant ovarian masses. Whereas, abdominal distention was more common in malignant masses. Preoperative diagnostic approach should always include careful history taking, physical examination, imaging and evaluation of tumor markers. Early detection, thorough treatment and regular follow-up are the need of time to reduce the morbidity and mortality.

Introduction This study aimed to evaluate the role of tumor marker carbohydrate antigen (CA) 125 (CA125), CA19-9, carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Methods A retrospective analysis was performed. Fifty RA patients (24 patients with ILD and 26 patients without ILD), 10 healthy subjects and 14 patients with other connective tissue disease-associated interstitial lung disease were included. Serum levels of KL-6 and tumor markers CA19-9, CA125 and CEA were measured. Chest HRCT of patients with ILD was scored quantitatively according to the degree of fibrosis. Data on the C-reactive protein, erythrocyte sedimentation rate, rheumatoid factors and anti-cyclic peptide containing citrulline (anti-CCP) were also collected. Results Serum levels of KL-6, CA19-9, CA125 and CEA in the RA-ILD group were significantly higher than those in the RA-no-ILD group. The serum KL-6 level was positively correlated with the HRCT fibrosis score (r = 0.63, p = 0.002). The logistic regression analysis showed that CA19-9 and smoking were associated with RA-ILD [OR = 1.118, 95% CI = (1.038, 1.204), p = 0.003 for CA19-9, OR = 14.969, 95% CI = (1.750, 128.043), p = 0.013 for smoking]. Conclusions KL-6 level and tumor markers were elevated in RA-ILD, and strongly associated with the severity of ILD, supporting their value as pathogenically relevant biomarkers, which can contribute to noninvasive detection of this extra-articular disease complication., Plain Language Summary Interstitial lung disease (ILD) is a common pulmonary manifestation of RA associated with high morbidity and mortality. Our retrospective study was performed to investigate the clinical utility of tumor marker carbohydrate antigen (CA) 125 (CA125), CA19-9, carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) in the diagnosis and determining the severity of RA-ILD. Fifty RA patients (24 patients with ILD and 26 patients without ILD), 10 healthy subjects and 14 patients with other connective tissue disease-associated interstitial lung disease (CTD-ILD) were included. The results showed KL-6 level and tumor markers were elevated in RA-ILD, and strongly associated with the severity of ILD, which meant KL-6 and tumor markers might be useful pathogenically relevant biomarkers and could be predictors for the diagnosis and determination of severity of ILD in RA.

Background: The Prostate Health Index (PHI) and Proclarix (PCLX) have been proposed as blood-based tests for prostate cancer (PCa). In this study, we evaluated the feasibility of an artificial neural network (ANN)-based approach to develop a combinatorial model including PHI and PCLX biomarkers to recognize clinically significant PCa (csPCa) at initial diagnosis. Methods: To this aim, we prospectively enrolled 344 men from two different centres. All patients underwent radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/mL. We used an artificial neural network to develop models that can identify csPCa efficiently. As inputs, the model uses [-2]proPSA, freePSA, total PSA, cathepsin D, thrombospondin, and age. Results: The output of the model is an estimate of the presence of a low or high Gleason score PCa defined at RP. After training on a dataset of up to 220 samples and optimization of the variables, the model achieved values as high as 78% for sensitivity and 62% for specificity for all-cancer detection compared with those of PHI and PCLX alone. For csPCa detection, the model showed 66% (95% CI 66–68%) for sensitivity and 68% (95% CI 66–68%) for specificity. These values were significantly different compared with those of PHI (p < 0.0001 and 0.0001, respectively) and PCLX (p = 0.0003 and 0.0006, respectively) alone. Conclusions: Our preliminary study suggests that combining PHI and PCLX biomarkers may help to estimate, with higher accuracy, the presence of csPCa at initial diagnosis, allowing a personalized treatment approach. Further studies training the model on larger datasets are strongly encouraged to support the efficiency of this approach.

Objectives: The aim of this study was to compare prostate-specific antigen (PSA) kinetics – half-life time (HT), doubling time (DT), and elimination rate PSA (ePSA) in prostate cancer (PCa) monitoring. Implementation of ePSA in clinical practice could help simplify patient monitoring in the remission phase. Materials and Methods: A total of 49 PCa patients were examined by their PSA tests before prostatectomy and after 30 days, 91 days, and 24 months. Conventional PSA rate of change parameters (HT and DT) were compared to a new clinically understandable ePSA parameter. Results: We observed that implementation of inverse value (ePSA) rather than HT or DT has distinct advantages: (1) values are valid when PSA is unchanged (ePSA equals zero), (2) the concept of ePSA can be easily understood, as it is a growth fraction, (3) ePSA fluctuates within a narrow range and is thus easy to interpret, and (4) there are no mathematical flaws (no positive skewing). Conclusion: Exploring ePSA norm as ≤0% could help spot biochemical recurrence in a timely manner. Primary health care providers tend to use an irrelevant PSA threshold, that is, 4.0 ng/mL, in postoperative follow-up. The delayed referrals of patients in remission might be reduced if ePSA testing is adopted.

Objective of the study: improvement of diagnostic methods for pregnant women with tumor-like formations and ovarian tumors. Materials and methods. 60 pregnant women were examined and divided into 3 groups: group I – 28 pregnant women with ovarian tumors who underwent surgical treatment during pregnancy; group II – 21 women with ovarian tumors who underwent surgical treatment at various times after spontaneous delivery; group III (control) – 11 women with a normal course of pregnancy without ovarian tumors. Doppler ultrasound was performed on a mandatory basis at the screening time, and as well as needed. MRI was performed in 8 diagnostically difficult cases. In the II trimester of pregnancy at 12–24 weeks in 49 women with ovarian tumors tumor markers were determined: CA-125, HE-4, β2-microglobulin, transthyretin, transferrin and apolipoprotein A-I, and combined ROMA and RMI indices. Results. The analysis showed the characteristic echographic signs of most ovarian tumors in pregnant women. The overall accuracy of ultrasound in determining the ovarian tumor structure at the outpatient level was extremely low and amounted to 21.8%, in a specialized medical institution it was 79.2%. In the diagnosis of mature teratomas were found MRI sensitivity and specificity of 100%, less diagnostic value (sensitivity 91.7%, specificity 96.9%) was typical for endometrioid ovarian cysts. MRI efficiency in detecting malignant potential (borderline and malignant tumors) was quite high (sensitivity 80.0%, specificity 97.4%). The presence of any ovarian tumor, except for mature teratomas, was accompanied by a significant increase in CA-125 level. The strongest correlation was found for RMI index and CA-125 and HE-4 tumor markers. Conclusions. Doppler ultrasound and MRI are complementary highly informative methods for diagnosing ovarian tumors in pregnant women. Tumor markers used for the differential diagnosis of benign and malignant tumors outside pregnancy (CA-125, HE-4, apolipoprotein A-I, transferrin, transthyretin, β2-microglobulin) do not have a high enough diagnostic value in ovarian tumors in pregnant women, therefore their tests should be supportive.

Background Simple hepatic cysts are relatively common in adults, and mostly appear as asymptomatic incidental radiologic findings. Occasionally, a large cyst will cause symptoms. Elevations in the serum biomarkers protein induced by vitamin K absence (PIVKA)-II, cancer antigen (CA) 12-5, and CA19-9 are often associated with malignant tumors in the liver or bile ducts. This is the first report to describe a case of hepatic cyst with elevated levels of PIVKA-II and CA12-5. Case summary An 84-year-old Chinese woman was admitted with gradual abdominal distension. Her symptoms started 1 year ago, and she had poor appetite and a weight loss of 5 kg within the past 2 wk. She denied any symptoms associated with abdominal pain, fever and chills, nausea and vomiting, etc. The abdomen was enlarged, more in the right upper quadrant, without tenderness. Laboratory examination showed significantly increased serum levels of PIVKA-II, CA12-5, and CA19-9. A computed tomography scan revealed multiple round cysts in the liver with clear boundaries. The largest cyst was 20.1 cm × 12.2 cm × 19.6 cm in size, located in the right lobe of the liver with mild dilatation of the intrahepatic bile duct, but there was no contrast enhancement. Percutaneous drainage on the largest hepatic cyst and polycinnamol sclerosing agent injection into the cyst cavity were performed. After treatment, the patient's symptoms relieved and the elevated serum tumor makers reduced to the normal levels dramatically. Conclusion The present report identifies an unusual case of a giant hepatic cyst with marked elevation of serum tumor marker levels of PIVKA-II, CA12-5, and CA19-9. After treatment, these three serum markers dramatically decreased to normal levels. The mechanisms for the elevation of these tumor markers may be as follows: (1) A giant hepatic cyst compresses the liver, causing injury to the hepatocytes, which may lead to secretion of a large amount of PIVKA-II; and (2) Some tumor-associated antigens, such as carcinoembryonic antigen, CA19-9, CA12-5, and CA15-3, are expressed on inflammatory cells.

Objective To establish a prediction model of malignancy for solitary pulmonary nodules (SPNs) on the basis of imaging, clinical characteristics and tumor marker levels. Methods Totally, 341 cases of SPNs were enrolled in this retrospective study, in which 70% were selected as the training group (n = 238) and the rest 30% as the verification group (n = 103). The imaging, clinical characteristics and tumor marker levels of patients with benign and malignant SPNs were compared. Influencing factors were identified using multivariate logistic regression analysis. The model was assessed by the area under the curve (AUC) of the receiver operating characteristic curve. Results Differences were evident between patients with benign and malignant SPNs in age, gender, smoking history, carcinoembryonic antigen (CEA), neuron-specific enolase, nodule location, edge smoothing, spiculation, lobulation, vascular convergence sign, air bronchogram, ground-glass opacity, vacuole sign and calcification (all P

An inclusion complexation, between polymerized β-cyclodextrin and cholesterol end-capping branched polyethylene glycol, was utilized for constructing a self-assembled hydrogel. The physicochemical properties, the in vitro release profiles of 5-Fluorouracil/methotrexate (anticancer drugs), and the surface morphology of the resulting hydrogel were studied. Moreover, in vivo studies were carried out on female rats bearing breast cancer. The results revealed that the prepared systems were white in color, rubbery, and homogenous. The in vitro release studies showed an efficient ability of the modified system for drug loading and release in a sustained release manner for 14 days. The surface morphology was spongy porous. Moreover, the tumors’ healing was indicated from the analysis of tumor volume, plasma tumor markers, and histopathological analysis, compared to the controlled rats. The pharmacokinetic parameters appeared significant differences (p < 0.05) in the Cmax and Tmax of the medicated hydrogel samples, as compared with sole or combined saline-injected samples. The whole AUC of each drug in the medicated hydrogel samples was five-fold more than the mixture administrated in PBS. In conclusion, the proposed work delivered a hydrogel system that has a convenient ability for localized sustained release of breast cancer management.

Even if today’s society is rapidly evolving there is still much that can be done. This applies in theoncological field. One of the main female health problems worldwide is represented by thegynecological cancers. Ovarian cancer is the main cause of mortality among women withgynecological cancers. Although its prevalence is lover compared to breast, uterine or cervicalcancer, the mortality and morbidity rates are significantly higher. The first step in the managementof ovarian cancer is represented by regular screening and rapid diagnosis. One of the most importanttolls is represented by serological markers dosage in order to estimate the type of tumor before thegynecological specific intervention. There is a real need to identify correctly the ovarian cancer asearly as possible in order to obtain the favorable prognosis that comes with the diagnosis in earlystage. Most of the ovarian cancers (above 90%) are represented by carcinomas which are frequentlydiagnosed in advanced stages. The roles of the biomarkers are to indicate the malignancy of anovarian tumor and to predict the relapse risk. The aim of this paper is to update the indicationsregarding the usage of serological markers in ovarian cancers and the importance of using them forour patients.

Background & Objective(s): Blackberry (BB) ranks highly among fruits with strong antioxidant activities. It contains appreciable levels of phenolic compounds, mainly gallic acid and anthocyanin that have been related to antioxidant activity in these fruits. Acrylamide (ACR) is a chemical with a very wide range of uses in industry. It has been detected in a widely consumed food item and accounts as one of the major health concern. The aim of this study was to compare the effect of BB juice as a natural source of antioxidant with either anthocyanin or gallic acid on the acrylamide harmful effect on kidneys in rats. Methods: A total of 50 adult male Albino rats equally allocated in five groups were used in this study. Rats in group 1 served as untreated control, group 2 rats were given ACR at dose of 50mg/kg BW, group 3 rats were given anthocyanin at a dose of 5 mg/kg BW + 50 mg/kg BW ACR, group 4 rats were given 3μg/kg gallic acid + 50 mg/kg ACR and group 5 rats were treated with 50 mg/kg BW ACR + 1.6 g/kg BW of BB juice. Rats were administered their respective doses on daily basis for eight weeks. Results: The results showed that there was a significant difference in body weight gain between experimental groups. It was noticed that ACR caused a significant decrease in some hematological parameters [red blood cell (RBC) count (2.2×106/L), hemoglobin level (9.0 g/dI) and platelet count (206×106/L)] and some antioxidants mean levels [glutathione (GSH) (6.1 μmol/ml), superoxide dismutase (SOD) (302.4 μmol/ml) and total antioxidant capacity (TAC) (1.3 μmol/ml)] compared to the control group. On the contrary, ACR caused a significant increase in white blood cell (WBC) count, kidney functions [uric acid (5.1 mg/dI), creatinine (1.5 mg/dI) and urea (76.4 mg/dI)], thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and tumor markers [Interleukin-6 (IL-6) (209.3 pg/ml), tumor necrosis factor- alpha (TFN-α) (120.5 pg/ml), and tumor suppressor gene (p53) (25.5 pg/ml)] than in the control group. On the other hand, we found that polyphenols caused a significant increase in RBC, hemoglobin, platelets and the best effect was observed with BB juice. The latter significantly increased the levels of GSH, SOD, and TAC, while polyphenols decrease WBC, uric acid, creatinine, urea, TBARS, NO, p53, TFN and IL6 levels compared to the ACR group. Histological examination for kidney tissue showed that ACR can damage the kidney structure but presence of polyphenols especially BB Juice may save kidney from damage. Conclusion: the result of this study suggested that BB Juice as a natural source of antioxidants is more protective than either anthocyanin or gallic acid alone against ACR toxicity on rat’s kidneys.

Chronic pruritus is a major and distressing symptom of many diseases of dermatological, neurological, psychogenic or systemic origin. This chronic itch could be a presenting sign of malignancy; therefore, paraneoplastic pruritus has also been associated with neuroendocrine tumors (NETs). This article focuses on a patient presenting with chronic pruritus for the past 12 months and who received numerous treatment schemes with very poor clinical improvement, that presented in the hospital for worsening of the chronic pruritus associated with skin rash and significant weight loss (approximately 6 kg over a 2-month period). The laboratory tests showed iron deficiency anemia, eosinophilia and negative tumor markers. In order to investigate the hypoanabolic and anemic syndromes, upper gastrointestinal endoscopy and colonoscopy, which showed no lesions or tumors, were employed. Skin biopsy was performed and antihistaminic and local steroid treatment was initiated. The patient's status worsened within a week and the patient was started on systemic steroid treatment with poor results. Computer tomography was performed to identify any tumor(s) located either in the pelvis or abdomen. A lesion was found in the terminal ileum, identified as a hypervascularized associating bulky lymphadenopathy. The patient was transferred to the surgical ward where right hemicolectomy with manual ileotransverse anastomosis L-L was performed. The histopathological result confirmed NET G2. The patient clinically improved, the skin lesions resolved and the itchiness disappeared. The general status improved significantly. NET G2 diagnosing was possible due to the atypic paraneoplastic sign: chronic pruritus. This case study highlights the association between itch and malignancy and presents an atypical way of NET presentation when all tumor markers remain negative.

Gene expression profiling; Lung neoplasms; Tumor biomarkers Perfil d'expressió gènica; Neoplàsies pulmonars; Biomarcadors tumorals Perfil de expresión génica; Neoplasias pulmonares; Biomarcadores tumorales Background Neoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC) has improved pathological responses and survival rates compared with chemotherapy alone, leading to Food and Drug Administration (FDA) approval of nivolumab plus chemotherapy for resectable stage IB-IIIA NSCLC (AJCC 7th edition) without ALK or EGFR alterations. Unfortunately, a considerable percentage of tumors do not completely respond to therapy, which has been associated with early disease progression. So far, it is impossible to predict these events due to lack of knowledge. In this study, we characterized the gene expression profile of tumor samples to identify new biomarkers and mechanisms behind tumor responses to neoadjuvant chemoimmunotherapy and disease recurrence after surgery. Methods Tumor bulk RNA sequencing was performed in 16 pretreatment and 36 post-treatment tissue samples from 41 patients with resectable stage IIIA NSCLC treated with neoadjuvant chemoimmunotherapy from NADIM trial. A panel targeting 395 genes related to immunological processes was used. Tumors were classified as complete pathological response (CPR) and non-CPR, based on the total absence of viable tumor cells in tumor bed and lymph nodes tested at surgery. Differential-expressed genes between groups and pathway enrichment analysis were assessed using DESeq2 and gene set enrichment analysis. CIBERSORTx was used to estimate the proportions of immune cell subtypes. Results CPR tumors had a stronger pre-established immune infiltrate at baseline than non-CPR, characterized by higher levels of IFNG, GZMB, NKG7, and M1 macrophages, all with a significant area under the receiver operating characteristic curve (ROC) >0.9 for CPR prediction. A greater effect of neoadjuvant therapy was also seen in CPR tumors with a reduction of tumor markers and IFNγ signaling after treatment. Additionally, the higher expression of several genes, including AKT1, BST2, OAS3, or CD8B; or higher dendritic cells and neutrophils proportions in post-treatment non-CPR samples, were associated with relapse after surgery. Also, high pretreatment PD-L1 and tumor mutational burden levels influenced the post-treatment immune landscape with the downregulation of proliferation markers and type I interferon signaling molecules in surgery samples. Conclusions Our results reinforce the differences between CPR and non-CPR responses, describing possible response and relapse immune mechanisms, opening the possibility of therapy personalization of immunotherapy-based regimens in the neoadjuvant setting of NSCLC. Work in the authors’ laboratories was supported by '‘Instituto de Salud Carlos III’' (ISCIII) PI19/01652 grant cofunded by European Regional Development Fund (ERDF), Bristol-Myers Squibb (BMS), Ministry of Science and Innovation RTC2017-6502-1 'INmunoSIGHT', RTC2019-007359-1 'BLI-O' and European Union’s Horizon 2020 research and innovation programme, CLARIFY 875160 grant, to MP. ThermoFisher provided reagents for RNA sequencing. AC-B received a Spanish Lung Cancer Group (SLCG) grant and is supported by a ISCIII-“Sara Borrell” contract CD19/00170. MCa is supported by PEJD-2019-PRE/BMD-17006 contract granted to AC-B.

Oxidative stress (OS) and inflammation are known to play an important role in chronic diseases, including cancer, and specifically colorectal cancer (CRC). The main objective of this study was to explore the diagnostic potential of OS markers in patients with CRC, which may translate into an early diagnosis of the disease. To do this, we compared results with those in a group of healthy controls and assessed whether there were significant differences. In addition, we explored possible correlations with the presence of tumors and tumor stage, with anemia and with inflammatory markers used in clinical practice. The study included 80 patients with CRC and 60 healthy controls. The following OS markers were analyzed: catalase (CAT), reduced glutathione (GSH) and oxidized glutathione (GSSG) in serum; and 8-oxo-7,8-dihydro-2 '-deoxyguanosine (8-oxodG) and F2-isoprotanes in urine (F2-IsoPs). Tumor markers (CEA and CA 19.9), anemia markers (hemoglobin, hematocrit and medium corpuscular volume) and inflammatory markers (leukocytes, neutrophils, N/L index, platelets, fibrinogen, C-reactive protein, CRP and IL-6) were also determined. Comparison of means between patients and controls revealed highly significant differences for all OS markers, with an increase in the prooxidant markers GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and a decrease in the antioxidant markers CAT and GSH. Tumor and inflammatory markers (except CRP) correlated positively with GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and negatively with CAT and GSH. In view of the results obtained, OS markers may constitute a useful tool for the early diagnosis of CRC patients.

The immune system plays a critical role in the prevention and eradication of cancerous lesions. Indeed, cancer immunology is a rapidly growing area of study that has already generated several FDA-approved treatments and cellular therapies to address mechanisms by which various cancers evade immune clearance. Recent studies look to expand the clinical use of these current therapies and to identify novel targets for future treatments in order to meet the unmet medical needs of the cancer patient population. Recently, multiple correlative studies have identified Carabin (Tbc1d10c) as a potential biomarker for cancer prognosis, including head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma. Two mechanistic studies have shown that Carabin acts as a negative feedback inhibitor of canonical TCR and BCR signaling during lymphocyte activation. One group demonstrated that Carabin inhibits CD4+ T-cell activation by binding to and inhibiting the actions of Ras and calcineurin, leading to decreased NFAT and AP-1 transcriptional activity. The second group corroborated the impact of Carabin signaling on the Ras/MAPK pathway in B cells and implicated a role for Carabin in autoimmune diseases in both mice and humans. Collectively, these studies suggest Carabin���s potential role in chronic inflammation and as a pro-tumorigenic target in human cancers. The data presented in Chapters 2-3 demonstrate an immunosuppressive role for Carabin in tumorigenesis. Using three murine tumor models, we identified a novel cancer phenotype in immune competent germline Carabin-ablated (Carabin-/-) mice: these mice showed a twofold decrease in tumor growth and an increase in tumor-free survival compared to wild-type (Carabin+/+) mice. Further assessment identified Carabin expression localized to cells of the immune lineage within the tumor microenvironment (TME), and tumor immunophenotyping showed a twofold increase in the percent of Carabin-/- total and activated CD8+ T cells infiltrating the tumors. Carabin-/- CD8+ T cells displayed an increase in TCR activation and tumor cell killing with no impact on proliferation or migration, indicating that the identified tumor outcome phenotype is due to a suppressive action on the CD8+ TCR activation pathway. Adoptive transfer of tumor antigen-restricted CD8+ T cells into immune-deficient Rag2-/- mice led to reduction of tumor growth in mice receiving Carabin-/- CD8+ T cells. Thus, the data in Chapters 2-3 demonstrate that Carabin deficiency confers tumor resistance via increased CD8+ T-cell anti-tumor activity. This anti-tumor activity is due to an increase in basal NF-��B activity specifically within CD8+ T cells. NF-��B perturbation is the result of a twofold increase in MEKK3 (Map3k3) protein and its downstream phosphorylation of the IKK complex to activate canonical NF-��B. MEKK3 knockdown by siRNA rescued the Carabin-/- in vitro molecular and cellular phenotype without impacting Carabin+/+ CD8+ T cells, and therefore supports the assertion that Carabin signaling is mediated by downstream MEKK3 activity. The NF-��B pathway is critical for T-cell activation and effector function. NF-��B perturbation was selective to CD8+ T cells and not found in CD4+ T cells. Thus, Carabin may be a novel target to mediate NF-��B signaling specifically in CD8+ T cells to improve their effector function within the TME without simultaneously impacting NF-��B in neoplastic or immunosuppressive cells. This is the first study to identify a causative link between Carabin and solid tumor malignancies, to demonstrate a unique mechanism for Carabin in the CD8+ T-cell response to tumorigenesis, and to suggest Carabin as a novel CD8+ T-cell-specific NF-��B inhibitor.

Background and Objectives: Regulatory T cells (Tregs) are usually enriched in ovarian cancer (OC), and their immunosuppressive function plays a key role in tumorigenesis and progression. We mainly explored the phenotypical characterization of Treg-related markers on αβ and γδ T cell subsets in patients with OC. Materials and Methods: Thirty-six untreated patients with OC at the Women’s Hospital of Nanjing Medical University from September 2019 to August 2021 were enrolled. Phenotypical characterization of Tregs-related markers were detected by flow cytometry (FCM). Enzyme-linked immunosorbent assay was used to detect the levels of carbohydrate antigen (CA125) and transforming growth factor β (TGF-β). The level of human epididymis protein 4 (HE4) was detected by electrochemiluminescence immunoassay. Results: Circulating CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subpopulations from OC patients have elevated Foxp3, CD25, CD122, Vδ1, and reduced CD28 expression compared to benign ovarian tumor (BOT) patients and healthy controls (HC). The upregulation of Foxp3 and Vδ1 and the downregulation of CD28 were highly specific for maintaining the immunosuppression function of CD4+ Tregs, CD3+γδ T cells, and CD8+ Tregs in OC patients. These Treg subpopulations were able to discriminate OC from BOT and HC. The levels of CA125, HE4, and TGF-β were increased in OC patients. A significant positive correlation between Treg subpopulations and CA125, HE4, and TGF-β was revealed. Conclusions: Proportions of CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subsets were significantly increased in OC patients and were positively correlated with FIGO stage/metastasis status, CA125, HE4, and TGF-β. These indicators have the potential to be used as immunosurveillance biomarkers for OC.

Background Cervical cancer shows great differences in depth of invasion, metastasis, and other biological behaviors. The location of the lesion is special, so it is usually difficult to determine the clinical stage. This study aimed to explore the clinical value of magnetic resonance imaging (MRI) and tumor serum markers for the preoperative diagnosis of cervical cancer lymph node metastasis and para-uterine invasion. Methods A total of 200 patients with cervical cancer admitted to our hospital from January 2019 to January 2020 were collected as the research subjects. Comparing the diagnosis results of preoperative MRI scan, serum tumor markers, and postoperative pathological examination using single factor comparison, we determined the MRI scan results, the comprehensive matching rate between serum tumor markers (squamous cell carcinoma antigen (SCCA), carbohydrate antigen 125 (CA125)) and postoperative pathological results, and the differences of sensitivity, specificity, and accuracy in the prediction of lymph node metastasis and para-uterine infiltration of cervical cancer. Results The levels of SCCA and CA125 in patients with para-uterine invasion and lymph node metastasis were higher than those of patients without invasion and metastasis. Among them, the level of SCCA was significantly different (PP>0.05), so MRI combined with serum SCCA was selected for combined diagnosis in the later period. The sensitivity, specificity, and accuracy of MRI diagnosis of cervical cancer and para-uterine infiltrating lymph node metastasis and metastasis were 55.2, 91.6, and 89.5% and 55.2, 91.6, and 89.5%, respectively. These data in MRI combined with serum SCCA were 76.3, 95.3, and 94.3% and 63.2, 96.0, and 95.1%, respectively. The accuracy of tumor markers combined with MRI in the diagnosis of cervical cancer lymph node metastasis and para-uterine invasion was higher than that of MRI. Conclusions MRI combined with serum SCCA can more accurately identify cervical cancer lymph node metastasis and para-uterine invasion compared with MRI alone. Tumor marker combined with MRI diagnosis is an important auxiliary method for cervical cancer treatment and can provide comprehensive and reliable clinical evidence for evaluation before cervical cancer surgery.

Aim To evaluate the prognostic value of tumor markers in a European cohort of patients with resectable gastric cancer. Methods We performed a post hoc analysis of the CRITICS trial, in which 788 patients received perioperative therapy. Association between survival and pretreatment CEA, CA 19-9, alkaline phosphatase, neutrophils, hemoglobin and lactate dehydrogenase were explored in uni- and multivariable Cox regression analyses. Likelihoods to receive potentially curative surgery were investigated for patients without elevated tumor markers versus one of the tumor markers elevated versus both tumor markers elevated. The association between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 patients with available ctDNA data. Results In multivariable analysis, in which we corrected for allocated treatment and other baseline characteristics, elevated pretreatment CEA (HR 1.43; 95% CI 1.11-1.85, p < 0.001) and CA 19-9 (HR 1.79; 95% CI 1.42-2.25, p < 0.001) were associated with worse OS. Likelihoods to receive potentially curative surgery were 86%, 77% and 60% for patients without elevated tumor marker versus either elevated CEA or CA 19-9 versus both elevated, respectively (p < 0.001). Although both preoperative presence of ctDNA and tumor markers were prognostic for survival, no association was found between these two parameters. Conclusion CEA and CA 19-9 were independent prognostic factors for survival in a large cohort of European patients with resectable gastric cancer. No relationship was found between tumor markers and ctDNA. These factors could potentially guide treatment choices and should be included in future trials to determine their definitive position.

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.

Currently, there are no reliable biomarkers for the diagnosis of pancreatic cancer (PaC). Glycoproteomic approaches that analyze the glycan determinants on specific glycoproteins have proven useful to develop more specific cancer biomarkers than the corresponding protein levels. In PaC, mesothelin (MSLN) is a neo-expressed glycoprotein. MSLN glycosylation has not been described and could be altered in PaC. In this work, we aimed to characterize MSLN glycans from PaC cells and serum samples to assess their potential usefulness as PaC biomarkers. First, we analyzed MSLN glycans from PaC cell lines and then we developed an enzyme-linked lectin assay to measure core fucosylated-MSLN (Cf-MSLN) glycoforms. MSLN glycans from PaC cells were analyzed by glycan sequencing and through Western blotting with lectins. All of the cell lines secreted MSLN, with its three N-glycosylation sites occupied by complex-type N-glycans, which were mainly α2,3-sialylated, core fucosylated and highly branched. The Cf-MSLN glycoforms were quantified on PaC serum samples, and compared with MSLN protein levels. The Cf-MSLN was significantly decreased in PaC patients compared to control sera, while no differences were detected by using MSLN protein levels. In conclusion, Cf-MSLN glycoforms were differently expressed in PaC, which opens the way to further investigate their usefulness as PaC biomarkers This research was funded by the Spanish Ministry of Science and Innovation (grant numbers BIO 2015-66356-R and PID2020-115686RB-I00) and by the University of Girona (grant numbers MPCUdG2016/028, PONT 2019/20 and PONT 2020/04). R.S. acknowledges funding from the Science Foundation Ireland Starting Investigator Research grant (SFI SIRG) under grant number (13/SIRG/2164)

Background Lung cancer is one of the most common malignancies, and there is a trend of increasing incidence in young patients. The preoperative diagnosis of pulmonary nodules is mainly based on the combination of imaging and tumor markers. There is no relevant report on the diagnostic value of tumor markers in young pulmonary nodules. Our study was designed to explore the value of five tumor markers in young patients with pulmonary nodules. Methods We reviewed the medical records of 390 young patients (age ≤45 years) with pulmonary nodules treated at two separate centers from January 1, 2015, to January 1, 2021. Malignant pulmonary nodules were confirmed in 318 patients, and the other 72 patients were diagnosed with benign pulmonary nodules. The gold standard for diagnosis of pulmonary nodules was surgical biopsy. The conventional serum biomarkers included cytokeratin 19 (CYFRA21‐1), pro‐gastrin‐releasing‐peptide (ProGRP), carcinoembryonic antigen (CEA), neuron‐specific enolase (NSE), and squamous cell carcinoma‐associated antigen (SCCA). The diagnostic values of five tumor markers were analyzed by receiver operating characteristic (ROC) curves. Results There were no significant differences in the expression of five tumor markers between the groups (p > 0.05). Single tumor marker (CYFRA21‐1, ProGRP, CEA, NSE, and SCCA) showed a limited value in the diagnosis of malignant pulmonary nodules, with the AUC of 0.506, 0.503 0.532, 0.548, and 0.562, respectively. The AUC of the combined examination was only 0.502~0.596, which did not improve the diagnostic value. Conclusions Five conventional tumor markers had a limited diagnostic value in young patients with pulmonary nodules., Preoperative diagnosis of pulmonary nodules is mainly based on the combination of imaging and tumor markers. Our study found the expression of the five tumor markers (CYFRA21‐1, ProGRP, CEA, NSE, and SCCA) did not differ significantly in young patients with pulmonary nodules. The AUC of tumor markers did not exceed 0.600, whether it was a single tumor marker or a combination of tumor markers.

Obesity is a medical condition characterized by an excessive accumulation of body fat with consequent metabolic syndrome. In obesity, modulation of metabolic pathways plays critical roles in the pathogenesis of many diseases. Our study linked obesity, metabolic stress and tumor by evaluating the levels of tumor markers and cortisol (a stress-induced hormone) in obese individuals. Thirty-three obese (18 males, 15 females, body mass index=34 ± 3.8 Kg/M2) and 37 apparently non-obese (19 males, 18 females, body mass index=22 ± 1.4 Kg/M2) individuals (controls) volunteered to participate in this study. All participants were not on drugs (i.e. alcohol, cigarette or steroids) and were healthy adults without apparent medical problems. Every participant had his/her body weight and height taken, and the body mass index (BMI) calculated before inclusion in the study. Obesity was defined by using the body mass index (BMI; Kg/M2), where a BMI higher than 25 Kg/M2 was used as an index of overweight, while a BMI higher than 30 Kg/M2 was used as a cut-off point to indicate obesity. Plasma levels of carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and cortisol were determined in these subjects using enzyme linked immunosorbent assay methods. In the obese subjects, plasma levels of CA125 and cortisol increased significantly (p0.05) changes compared with controls. Metabolic changes could account for the increased rate of synthesis of cortisol and CA125 in obesity.

BACKGROUND The incidence of pancreatic neuroendocrine tumors (PNETs) is now increasing rapidly. The tumor grade of PNETs significantly affects the treatment strategy and prognosis. However, there is still no effective way to non-invasively classify PNET grades. Machine learning (ML) algorithms have shown potential in improving the prediction accuracy using comprehensive data. AIM To provide a ML approach to predict PNET tumor grade using clinical data. METHODS The clinical data of histologically confirmed PNET cases between 2012 and 2018 were collected. A method of minimum P for the Chi-square test was used to divide the continuous variables into binary variables. The continuous variables were transformed into binary variables according to the cutoff value, while the P value was minimum. Four classical supervised ML models, including logistic regression, support vector machine (SVM), linear discriminant analysis (LDA) and multi-layer perceptron (MLP) were trained by clinical data, and the models were labeled with the pathological tumor grade of each PNET patient. The performance of each model, including the weight of the different parameters, were evaluated. RESULTS In total, 91 PNET cases were included in this study, in which 32 were G1, 48 were G2 and 11 were G3. The results showed that there were significant differences among the clinical parameters of patients with different grades. Patients with higher grades tended to have higher values of total bilirubin, alpha fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4. Among the models we used, LDA performed best in predicting the PNET tumor grade. Meanwhile, MLP had the highest recall rate for G3 cases. All of the models stabilized when the sample size was over 70 percent of the total, except for SVM. Different parameters varied in affecting the outcomes of the models. Overall, alanine transaminase, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4 affected the outcome greater than other parameters. CONCLUSION ML could be a simple and effective method in non-invasively predicting PNET grades by using the routine data obtained from the results of biochemical and tumor markers.

Objects This study aims to explore the Cancer antigen 724 (CA724) reference values spatial distribution characteristics in healthy Chinese adults. The study can provide regional reference for medical diagnosis. Study Design The relationship between CA724 and 25 geographical environmental factors was analyzed firstly. Artificial neural network simulation training was used to construct the prediction model. The national forecast distribution map of the CA724 reference values was obtained by the geostatistical mapping method. Analyzing and exploring the influence mechanism of geographical environment factors on CA724 reference values. Methods Collecting 34470 cases from more than 106 cities healthy adults CA724 reference values via several paper databases in 10 recent years. Correlation analysis, RBF artificial neural networks and trend surface analysis were applied to explore if there was any tendency of spatial variation. The Kriging interpolation of geostatistical analysis was developed to reveal the spatial distribution characteristics of the CA724 reference values. Results The distribution of CA724 reference values of Chinese healthy adults shows a downward trend from south to north. CA724 reference values have negative correlations with latitude, annual sunshine duration and topsoil cation exchange capacity in clay. CA724 have positive correlations with annual mean air temperature, annual mean relative humidity, and annual precipitation amount. High temperature and high humidity environment will reduce gastrointestinal function and breeze various mold bacteria. Lack of sunshine can easily lead to vitamin C deficiency in the body. These will increase the incidence of gastrointestinal diseases and gastric cancer, then increase the CA724 value. Conclusion CA724 reference values show spatial autocorrelation and regional variation. There are some geographical environment factors effected Chinese healthy adults CA724 reference values. Geographic factors such as sunshine, temperature, and humidity have effects on CA724 reference values can provide new ideas and directions of prevention and clinical diagnosis in the future.

Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitor (TIMP-2) may play an important role in the pathogenesis of cancer disease. We investigated the plasma levels and diagnostic power (ROC curve analysis) of M-CSF, MMP-2, TIMP-2 and tumor markers CA 125 and SCC-Ag in cervical cancer (CC) patients as compared to control group. The study included 89 patients with cervical cancer. The control group consisted of 50 healthy, untreated women. The plasma levels of M-CSF, MMP-2 and TIMP-2 were determined using ELISA, CA 125 and SCC-Ag - by CMIA method. The median levels of M-CSF, TIMP-2, SCC-Ag and CA 125 in the entire group of CC were significantly different than compared to the healthy women group. MMP-2 showed the highest value of sensitivity from all examined parameters (in stage I of CC - 93.10%, II - 82.76%, III and IV - 96.88%, total group - 92.05%). The highest specificity was obtained by M-CSF (86%). The area under the ROC curve (AUC) of M-CSF (0.8051) was the largest of all the tested parameters (even higher than commonly used tumor markers) in the group of cervical cancer. The combination of M-CSF, MMP-2 or TIMP-2 with SCC antigen resulted in an increase AUCs in all cases (0.8760;0.7880;0.8081;respectively). The findings of this study suggest the usefulness of all examined parameters in the diagnostics of CC patients. Out of the tested substances, M-CSF also appears to be the best candidate for cancer diagnostics in all stages of the disease, based on ROC analysis.

Background: Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. Objective: The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. Method: Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens. Results: Median age was 64-years old and 58% were female patients. The median follow-up was 42 months. The progression free survival (PFS) at this time was 63% and overall survival (OS), 66%. In the patients with tumors expressing Myc proto-oncogene protein (MYC) and B-cell lymphoma 2 (BCL2), assessed by immunohistochemistry (IHC), known as dual protein expressers, median post-progression survival was 31 (15–45) months. An increased proliferative index were associated with a high rate of progression (hazard ratio 2.31 [95% confidence interval [1.05–5.12]; p = 0.04). The cell of origin (COO), identified by IHC, was not able to predict PFS (p = 0.76). The MYD88 L265P mutation was present in 10.8% (9/83) of patients and did not show a prognostic correlation. Conclusion: In conclusion, the MYD88 mutation, although an important tool for diagnosis and a possible target drug, presented at a low frequency and was not a prognostic marker in this population. Keywords: Diffuse large B-cell lymphomas, MYD88, DLBCL, Tumor markers

Background: Sorafenib is the currently recommended therapy in patients with advanced hepatocellular carcinoma (HCC). Among the several biomarkers available for the evaluation of the therapeutic response and prognosis, there is perfusion magnetic resonance imaging (p-MRI) that, through measurement of the vascular permeability unit (ktrans), may retrieve useful information regarding the microvascular properties of focal liver lesions. The aim of this study was to evaluate the impact of sorafenib therapy in patients with advanced HCC using the p-MRI technique. Materials and Methods: In this retrospective study, 27 patients with the diagnosis of advanced HCC were included for palliative therapy using sorafenib. MRI of the liver was performed before the beginning of the oral therapy (T0), after 3 (T3), and after 6 months (T6). Dynamic acquisitions of the tumor (n = 50, during the first 2 min after contrast injection) were obtained in the coronal plane and were used to compute the parametric perfusion maps, acquiring the ktrans value using the extended Tofts pharmacokinetic model. Results: The value of ktrans obtained at T0 was significantly different from the value of ktrans obtained at T6 (p = 0.028). There were no significant differences between T0 and T3 (p = 0.115) or a correlation between ktrans at T0 and the size of the lesion (p = 0.376). The ktrans value at T0 in patients with progressionfree survival (PFS) > 6 months was not significantly different from the ktrans value in patients with PFS ≤6 months (p = 0.113). The ktrans value at T0 was not significantly different between patients who were previously submitted to chemoembolization and those who were not submitted (p = 0.587). Conclusion: In this pilot study, the ktrans value may serve as a biomarker of tumor response to antiangiogenic therapy, but only 6 months after its initiation. Clinical outcomes such as PFS were not predicted before the initiation of treatment. Introdução: O sorafenib é a terapêutica atualmente recomendada em doentes com carcinoma hepatocelular avançado. Entre os vários biomarcadores disponíveis para a avaliação da resposta terapêutica e do prognóstico, existe a perfusão por Ressonância Magnética na qual, através da unidade de permeabilidade vascular (ktrans), se obtém informação relativa às propriedades microvasculares das lesões tumorais. O objetivo deste estudo foi avaliar o impacto da terapêutica com sorafenib em doentes com carcinoma hepatocelular avançado, através da técnica de perfusão por Ressonância Magnética (p-RM). Materiais e Métodos: Neste estudo observacional retrospetivo, foram incluídos 27 doentes, com diagnóstico de carcinoma hepatocelular avançado com indicação para terapêutica paliativa com sorafenib. Foi realizado estudo de Ressonância Magnética hepática antes do início da terapêutica com sorafenib (T0), aos 3 (T3) e aos 6 meses (T6) após o seu início. As imagens adquiridas no plano coronal (n = 50, durante os primeiros 2 minutos após a injeção de contraste paramagnético) foram utilizadas para fusão dos mapas paramétricos de perfusão, obtendo-se o valor de ktrans, usando o modelo farmacocinético de Tofts. Resultados: O valor de ktrans obtido em T0 foi significativamente diferente do valor de ktrans obtido em T6 (p = 0.028). Não existiram diferenças significativas entre T0 e T3 (p = 0.115) ou correlação entre o valor de ktrans em T0 e a dimensão da lesão (p = 0.376). Associadamente, o valor de ktrans em T0 nos doentes com sobrevivência livre de progressão superior a 6 meses não foi significativamente diferente do valor de ktrans nos doentes com sobrevivência livre de progressão inferior ou igual a 6 meses (p = 0.113). O valor de ktrans em doentes com ou sem tratamento prévio por quimioembolização não mostrou diferença estatisticamente significativa (p = 0.587). Conclusão: Neste estudo inicial, o valor de ktrans pode servir como biomarcador da perfusão tumoral na resposta à terapêutica anti-angiogénica, 6 meses após o seu início. O seu valor antes do inicio do tratamento não permitiu predizer o desfecho clinico em termos de sobrevivência livre de doença nos pacientes submetidos ou não a prévia quimioembolização.

Based on surface-enhanced Raman scattering (SERS) technology, Au@Ag@4MBA@5′-NH2-ssDNA probes and a Ag/TiO2@3′-NH2-ssDNA substrate were prepared and constructed into a sandwich structure to develop a high sensitivity bioassay of miRNA-21. The Au@Ag@4MBA@5′-NH2-ssDNA probes were prepared by immobilizing 5′-NH2-ssDNA onto the surfaces of 4MBA-labelled Au@Ag core–shell nanoparticles, and the Ag/TiO2@3′-NH2-ssDNA substrate was prepared by immobilizing 3′-NH2-ssDNA on the surface of Ag/TiO2 nanowires SERS-active substrates. The experimental results showed that the SERS-based sandwich bioassay of miRNA-21 presented a low limit of detection of 0.75 fM and a broad dynamic range from 1.0 fM to 1.0 nM. Also, the test data for the SERS-based sandwich bioassay were not only consistent with that of the real-time fluorescence quantitative polynucleotide chain reaction (RT-qPCR) method but also displayed higher detection sensitivity. It was shown that the SERS-based sandwich bioassay of miRNA-21 has importance for use in potential applications involving diagnosing clinical cancer patients.

Esta es la versión pre-print del artículo, el cual se encuentra disponible en la siguiente URL: https://onlinelibrary.wiley.com/doi/full/10.1111/jop.12791 More than 90% of malignant tumors of the head and neck are oral squamous cell carcinomas (OSCC). Early OSCC detection using salivary biomarkers could prevent malignant transformations and enhance patient survival. A systematic search in MEDLINE and the Central Register of Controlled Trials and meta-analysis were undertaken to identify the screening potential of 6 salivary biomarkers for early OSCC detection: IL-8, IL1-β, DUSP-1 and S100P mRNAs, miR125a and miR200a microRNAs. The sensitivities of IL-8 (0.41; 95%CI 0.19-0.99), IL1-β (0.26; 95%CI 0.19- 0.99), DUSP-1 (0.61; 95%CI 0.01-0.98), and S100P (0.67; 95%CI 0.32- 0.99) were calculated. Specificities of the biomarkers analyzed were found to be IL-8 (0.69; 95%CI 0.66-0.99), IL1-β (0.47; 95%CI 0.46 - 0.90), DUSP-1 (0.75; 95%CI 0.33-1) and S100P (0.73; 95%CI 0.18-0.99). Early detection of OSCC was best achieved by screening for salivary mRNA DUSP-1 and S100P. Further investigation is required into miRNAs as novel biomarkers

Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, NTRK) and on those alterations with approvals in multiple malignancies (BRAF, ERBB2, RET, BRCA, PD-L1), we also describe several biomarkers or indications that are likely to lead to an approved drug in the near future (e.g., KRAS G12C, PD-L1 amplification, HER2 overexpression in colon cancer, HER2 mutations in lung cancer). Finally, we detail the current landscape of additional actionable alterations (EGFR, ALK, ROS1, MET) in lung cancer, a biomarker-rich malignancy that has greatly benefitted from the precision oncology revolution.

Background Hepatic inflammatory pseudotumor (IPT) is a rare, benign, tumor-like lesion. Because there are no characteristic laboratory markers or radiological features, hepatic IPT is often misdiagnosed as a malignant neoplasm such as hepatocellular carcinoma (HCC). Case presentation A 68-year-old man with liver dysfunction due to chronic hepatitis C virus infection and alcoholic liver disease presented with hepatic tumors in segments III and VIII. The levels of serum alpha-fetoprotein (AFP) and its Lens culinaris agglutinin-reactive fraction, AFP lectin 3 (AFP-L3), were elevated to 822.8 ng/ml and 75.2%, respectively. The tumor showed contrast enhancement on contrast-enhanced computed tomography and various accumulation on positron emission tomography. Based on these biological and imaging features, HCC was suspected, and we performed laparoscopic partial hepatectomy for these two tumors. Pathological diagnosis revealed that both tumors were hepatic IPTs with no malignant characteristics. After hepatectomy, the serum AFP and AFP-L3 levels decreased to the normal range. Conclusion We report a very rare case of hepatic IPT with elevated serum AFP and AFP-L3, mimicking HCC. Clinicians should include this rare neoplasm in the differential diagnoses of hepatic tumors even when the serum markers for HCC are elevated.

Tumor cells not only show a vigorous metabolic state, but also reflect the disease progression and prognosis from their metabolites. To judge the progress and prognosis of ovarian cancer is generally based on the formation of ascites, or whether there is ascites recurrence during chemotherapy after ovarian cancer surgery. To explore the relationship between the production of ascites and ovarian cancer tissue, metabolomics was used to screen differential metabolites in this study. The significant markers leading to ascites formation and chemoresistance were screened by analyzing their correlation with the formation of ascites in ovarian cancer and the clinical indicators of patients, and then provided a theoretical basis. The results revealed that nine differential metabolites were screened out from 37 ovarian cancer tissues and their ascites, among which seven differential metabolites were screened from 22 self-paired samples. Sebacic acid and 20-COOH-leukotriene E4 were negatively correlated with the high expression of serum CA125. Carnosine was positively correlated with the high expression of serum uric acid. Hexadecanoic acid was negatively correlated with the high expression of serum γ-GGT and HBDH. 20a,22b-Dihydroxycholesterol was positively correlated with serum alkaline phosphatase and γ-GGT. In the chemotherapy-sensitive and chemotherapy-resistant ovarian cancer tissues, the differential metabolite dihydrothymine was significantly reduced in the chemotherapy-resistant group. In the ascites supernatant of the drug-resistant group, the differential metabolites, 1,25-dihydroxyvitamins D3-26, 23-lactonel and hexadecanoic acid were also significantly reduced. The results indicated that the nine differential metabolites could reflect the prognosis and the extent of liver and kidney damage in patients with ovarian cancer. Three differential metabolites with low expression in the drug-resistant group were proposed as new markers of chemotherapy efficacy in ovarian cancer patients with ascites.

The purpose of this study was to analyze the published cases regarding large ovarian masses in adolescents, in order to find useful clinical implications for the diagnosis and management of the condition. The methodology employed a systematic review of reported cases of large/giant ovarian tumor in adolescence. The main objective was to assess the imagery findings, histology of the tumor, and the type of surgery performed. Our study included 58 patients with the tumor diameters ranged between 11 and 42 cm, with a median value of 22.75 cm and a mean diameter of 24.66 ± 8.50 cm. The lesions were benign in 47 cases (81%), borderline in 2 cases (3.4%), and malign in 9 cases (15.6%). We found no statistically significant difference (p > 0.05) between the size of the tumors and the ovarian markers levels. At the same time, a statistically significant difference was identified (p=

Yunqi Bao,1 Wei Zhang,1 Dandan Shi,2 Weili Bai,1 Dongdong He,1 Dan Wang1 1Department of Rheumatology, Xi’an Fifth Hospital, Xian, 710000, Shaanxi, People’s Republic of China; 2Department of Radiology, Xi’an Fifth Hospital, Xian, 710000, Shaanxi, People’s Republic of ChinaCorrespondence: Dan WangDepartment of Rheumatology, Xi’an Fifth Hospital, 112 Xiguanzheng Street, Lianhu District, Xian, 710000, Shaanxi, People’s Republic of ChinaEmail wdtougao2021@163.comObjective: The main aims of this study were to explore the relationships between serum tumor markers and connective tissue disease-related interstitial lung disease (CTD-ILD) and to evaluate the clinical value of tumor markers for investigating interstitial lung disease (ILD) in patients with connective tissue disease (CTD).Methods: The study included 235 patients with CTD (90 CTD without ILDs, 145 CTD-ILD). Clinical information and the levels of inflammatory and tumor markers, including carbohydrate antigen (CA) 19– 9, CA125, carcinoembryonic antigen (CEA), CA153, and cytokeratin 19 fragments (CYFRA21-1), were obtained in all the patients.Results: A significant difference between CTD with or without ILD and higher levels of tumor markers was observed in the CTD-ILD group, including CA19-9 (p< 0.001), CEA (p< 0.001), CA153 (p< 0.001), and CYFRA21-1 (p< 0.001). There was no significant difference in serum tumor marker levels in the various types of CTD (rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, inflammatory myositis, systemic sclerosis, and mixed connective tissue disease). The levels of CA153 [odds ratio (OR)=1.159] and CYFRA21-1 (OR=2.269) were clearly related to the risk of CTD-ILD. The diagnostic value of CA153 [area under receiver operating characteristic curve (AUC)=0.736] and CYFRA21-1 (AUC=0.718) was confirmed for ILDs in CTD patients, at cut-off values of 9.45 U/mL and 2.13 ng/mL, respectively.Conclusion: There is a positive correlation between serum tumor marker levels and CTD-ILD. Higher levels of CA153 and CYFRA21-1 suggest an increased risk of developing ILD and may therefore be useful as biomarkers for detecting CTD-ILD in the clinical setting.Keywords: connective tissue disease, tumor markers, interstitial lung disease

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2227-9059/9/5/463 Este artículo pertenece al número especial "MicroRNAs, tRNA fragments, and circular RNAs: pivotal regulators of gene expression and their roles in human diseases". Osteosarcoma (OS) is a rare form of cancer with high death rate but is one of the most frequent forms of bone cancer in children and adolescents. MiRNAs are small endogenous RNAs that regulate gene expression post-transcriptionally. The discovery of miRNAs could allow us to obtain an earlier diagnosis, predict prognosis and chemoresistance, and lead to the discovery of new treatments in different types of tumors, including OS. Despite the fact that there is currently only one clinical trial being carried out on a single miRNA for solid tumors, it is very probable that the number of clinical trials including miRNAs as prognostic and diagnostic biomarkers, as well as potential therapeutic targets, will increase in the near future. This review summarizes the different miRNAs related to OS and their possible therapeutic application.

Background Accurate prediction of malignancy risk for pulmonary lesions with pleural effusion improves early diagnosis of lung cancer. This study aimed to develop and validate a model to predict lung cancer. Methods Clinical data of 536 patients with pulmonary diseases were collected. The risk factors were identified by regression analysis. Three prediction models were developed. The predictive performances of the models were measured by the area under the curves (AUCs) and calibrated with 1000 bootstrap samples to minimize the over‐fitting bias. The net benefits of the models were evaluated by decision curve analysis. Finally, a separate cohort of 134 patients was used to validate the models externally. Results Seven independent risk factors were identified from 18 clinical variables, which included the pleural fluid carcinoembryonic antigen (CEA), serum cytokeratin‐19 fragment (CYFRA 21‐1), the ratio of CEA in the pleural fluid to serum, extrathoracic cancer history (>5 years), tumor size, vessel convergence, and lobulation. The AUCs of the three models were 0.976, 0.927, and 0.944 in the training set and 0.930, 0.845, and 0.944 in the external set, respectively. The accuracies of the three models were 89.6%, 81.4%, and 88.8%. Model 1 showed the best iteration fit (R 2 = 0.84, 0.68, and 0.73) and a higher net benefit on decision curve analysis when compared to the other two models. Conclusion The advantageous model could assess the risk of lung cancer in patients with pleural effusion and act as a useful tool for early identification of lung cancer., Accurate prediction of malignant risk of pulmonary lesions with pleural effusion can improve the early diagnosis of lung cancer. We developed and validated a lung cancer prediction model, with variables including CEA, CYFRA21‐1, the ratio of CEA in the pleural fluid to serum, extrathoracic cancer history (>5 years), and radiological signs. The prediction performance of validation set (AUC = 0.930, 95% CI: 0.884–0.975) of this model is great, and the net benefit of decision curve analysis is also superior. We also developed two other models, one based on tumor markers and one based on imaging signs, and found that the combination of the two was indeed superior to the single in the diagnosis of cancer. Besides, all the parameters of the models are objective, readily available, and need no extra tests. Our advantage model can assess the risk of lung cancer in patients with pleural effusion and provide a useful tool for early clinical identification of lung cancer.

Objective: To evaluate the effect of sintilimab combined with chemotherapy on tumor markers and immune function in advanced non-small cell lung cancer. Methods: The study was conducted at Xi’an Medical University, China. The 120 patients with advanced NSCLC who were treated in our hospital from January 2016 to January 2020 were randomly divided into two groups, with 60 cases in each group. Patients in the control group received conventional GP chemotherapy, while those in the experimental group received intravenous injection of sindilimab on the basis of conventional GP chemotherapy. The changes of serum tumor markers CYFRA211, CEA, CA125 and T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/CD8+ in the two groups prior to and after treatment were compared and analyzed. At the same time, the clinical efficacy at six months was compared between the two groups. Results: The serum tumor markers CYFRA211, CEA and CA125 in the two groups after treatment were lower than those before treatment, and the difference was statistically significant (P=0.00). Specifically, the above-mentioned markers in the experimental group decreased more significantly than those in the control group, and the difference was statistically significant (CYFRA211, CA125, p=0.00; CEA, p=0.01; the levels of CD3+ and CD4+ in the experimental group were higher than those in the control group after treatment, with statistical significance (CD3+, p=0.00; CD4+, p=0.01)). No significant change can be seen in CD8+ (p=0.14), and the level of CD4+/CD8+ in the experimental group was higher than that in the control group, with a significant difference (p=0.02). The complete remission rate (CR) was 22% in the experimental group and 8% in the control group (P=0.04), which was statistically significant. The progress rate (PD) of the experimental group was significantly lower than that of the control group, with statistical significance (p=0.02). The overall response rate (RR) of the experimental group was more advantageous than that of the control group, with a statistically significant difference (p=0.01). Conclusion: Compared with chemotherapy alone, significant therapeutic effects can be obtained in the treatment of advanced non-small cell lung cancer with sintilimab combined with chemotherapy. With this combination regimen, the level of serum tumor markers can be significantly reduced, the cellular immune function of patients can be improved, with the overall response rate of treatment increased, and the risk of progressive disease of patients reduced. doi: https://doi.org/10.12669/pjms.37.4.3820 How to cite this:Liang X, Wei Z. Effect of Sintilimab combined with Chemotherapy on Tumor Markers and Immune Function of advanced non-small cell lung cancer. Pak J Med Sci. 2021;37(4):1063-1068. doi: https://doi.org/10.12669/pjms.37.4.3820 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC.

Vanillylmandelic acid (VMA), homovanillic acid (HVA), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are classical tumor markers and are used as standard clinical evaluations for patients with neuroblastoma (NB). Minimal residual disease (MRD) can be monitored by quantifying several sets of NB-associated mRNAs in the bone marrow (BM) and peripheral blood (PB) of patients with NB. Although MRD in BM and PB has been revealed to be a strong prognostic factor that is independent of standard clinical evaluations, its interrelation with tumor markers remains uncharacterized. The present study determined the levels of tumor markers (VMA, HVA, NSE and LDH) and MRD (BM-MRD and PB-MRD) in 133 pairs of concurrently collected BM, PB and urine samples from 19 patients with high-risk NB. The patients were evaluated during the entire course of treatment, which included 10 diagnoses, 32 treatments, 36 post-treatment, 9 relapses and 46 post-relapse sample pairs. The level of BM-MRD and PB-MRD was determined by quantifying 7 NB-mRNAs (collapsin response mediator protein 1, dopamine beta-hydroxylase, dopa decarboxylase, growth-associated protein 43, ISL LIM homeobox 1, pairedlike homeobox 2b and tyrosine hydroxylase) using droplet digital PCR. In overall sample pairs, tumor markers (VMA, HVA, NSE and LDH) demonstrated weak but significant correlations (P

BACKGROUND In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are relevant as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. AIM To examine the impact of the tumor marker alpha-fetoprotein (AFP) or PIVKA-II in detecting very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona stage 0) in the large number of very small HCC. The difference in the behavior of these tumor markers in HCC development was also examined. METHODS A total of 933 patients with single-nodule HCC were examined. They were subdivided into 394 patients with HCC nodules ≤ 2 cm in maximum diameter and 539 patients whose nodules were > 2 cm. The rates of patients whose AFP and PIVKA-II showed normal values were examined. RESULTS The positive ratio of the marker PIVKA-II was significantly different (P < 0.0001) between patients with nodules ≤ 2 cm in diameter and those with nodules > 2 cm, but there was no significant difference in AFP (P = 0.4254). In the patients whose tumor was ≤ 2 cm, 50.5% showed normal levels in AFP and 68.8% showed normal levels in PIVKA-II. In 36.4% of those patients, both AFP and PIVKA-II showed normal levels. The PIVKA-II-positive ratio was markedly increased with an increase in the tumor size. In contrast, the positivity in AFP was increased gradually and slowly. CONCLUSION In the surveillance of very small HCC nodules (≤ 2 cm in diameter, Barcelona clinical stage 0) the tumor markers AFP and PIVKA-II are not so useful.

One of the hallmarks of cancer cells is increased energy requirements associated with the higher rate of cellular proliferative activity. Metabolic changes in rapidly dividing cancer cells are closely associated with increased uptake of glucose and abnormal activity of lactate dehydrogenase (LDH), which regulates the processing of glucose to lactic acid. As serum LDH levels were found to be commonly increased in cancer patients and correlated with poor clinical outcome and resistance to therapy, the determination of LDH has become a standard supportive tool in diagnosing cancers or monitoring the effects of cancer treatment.The aim of this review is to summarize the current knowledge about methods and the practical utility for measuring both the total LDH and LDH isoenzymatic activities in the diagnosis, prognosis and prediction of cancer diseases.

BackgroundPleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we aimed to find indicators for the auxiliary diagnosis of lung cancer-associated MPE by analyzing and then validating the optimal threshold levels of these biomarkers in pleural fluid (PF) and serum, as well as the PF/serum ratio.Patients and methodThe study has two sets of patients, i.e. the training set and the test set. In the training set, 348 patients with PE, between January 1, 2016 and December 31, 2017, were divided into BPE and MPE based on the cytological diagnosis. Subsequently, the optimal cut-off levels of tumor biomarkers were analyzed. In the test set, the diagnostic compliance rate was verified with 271 patients with PE from January 1, 2018 to July 31, 2019 to evaluate the auxiliary diagnostic value of the aforementioned indicators.ResultIn the training set, PF CEA at the cut-off value of 5.23 ng/ml was the most effective indicator for MPE compared with other tumor biomarkers (allp ConclusionPF CEA at the cut-off level of 5.23 ng/ml was the most effective indicator for identifying lung cancer-associated MPE among the five common tumor biomarkers.

Invasive lobular carcinoma is often challenging to diagnose due to the lack of physical examination findings and macrocalcifications on mammography. The cells of invasive lobular carcinoma form a distinct single file pattern that can be identified on histology slides. Often, when patients present, there is metastasis to the bones, lymph nodes, and gastrointestinal tract. Tumor markers are a valuable tool in identification, especially the loss of E-cadherin protein. However, if E-cadherin protein is not available, epidermal membrane antigen, which inhibits E-cadherin, can prove to be a significant diagnostic tool. Epidermal membrane antigen was the key tumor marker in our patient case. Other tumor markers and histology stains can drive treatment plans and help predict prognosis.