CA125 Antigen Research Articles

Novel CA-125 antigen determination in serum by electrochemical methods with onion oil-containing organo-hydrogels

CA-125 antigen is a glycoprotein that can be found at distinct levels in blood samples according to the phases of ovarian cancer. Herein, we designed novel onion oil-organo-hydrogels (OOHGs) to detect CA-125 antigen at high sensitivity and selectively via electrochemical methods. OOHGs produced are characterized by swelling analysis and Fourier Transform Infrared Spectroscopy (FT-IR). Cyclic voltammetry (CV), Electro impedance spectroscopy (EIS), and Differential pulse voltammetry (DPV) techniques in the potentiostat triple electron system are used for performing the electrochemical measurements. Performances and electron transfer resistances of OOHGs and OOHG+CA-125s are researched via CV and EIS, and the sensitivity properties such as LOD and LOQ of the sensor are determined via DPV. OOHG-2 among OOHGs produced exhibited the highest performance with 0.8151 mA/cm2 (815.1 A/cm2) value at determining CA-125 in serum medium. Moreover, this electrode is found that exhibit a wide linear range like a 1-500 ng/mL concentration range. The limit of quantification (LOQ) and the lowest of detection (LOD) for the OOHG-2 electrode are calculated as 0.531 U/mL and 0.265 U/mL (S/N=3), respectively. Further, the CA-125 antigen of the OOHG-2 electrode in interference results is observed that can be detected with high selectivity. With these results, it can be noted that the OOHG-2 electrode holds great hope for detection ovarian cancer by electrochemical methods.

Coelenterate and Germinal-Müllerian Papilloma Cervix: A Mini-Review

Coelenterate and Germinal-Müllerian Papilloma Cervix: A Mini-Review

FLORA-5/GOG3035: Chemo-immunotherapy (paclitaxel-carboplatin-oregovomab [PCO] vs chemotherapy (paclitaxel-carboplatin-placebo [PCP]) as front-line treatment in patients with advanced epithelial ovarian cancer (EOC)—Phase III, double blind, placebo controlled, global, multinational study.

TPS5625 Background: Oregovomab, a murine IgGκ1 monoclonal antibody with high affinity binding to tumor associated antigen CA125, renders the target antigen CA125 more immunogenic or “neoantigen-like”. The proposed mechanism action is enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when oregovomab is combined with chemotherapy. In a randomized phase II study, oregovomab, in combination with paclitaxel and carboplatin, (PC) induced tumor immunity and demonstrated significant improvement in median PFS (41.8 months(m) PCO vs 12.2 m PC, HR 0.46, p = 0.0027) and median OS (N.E. PCO vs 43.2 m PCP, HR 0.35, p = 0.043) in patients with previously untreated EOC. Patients receiving adjuvant chemotherapy were included. Oregovomab combined with PC had a favorable toxicity profile. FLORA-5/GOG3035, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: In this phase 3, multicenter, double-blind, placebo-controlled trial, optimally debulked patients with FIGO III/IV EOC and serum CA125 ≥ 50 U/ml receiving adjuvant (Cohort 1) or patients receiving neoadjuvant chemotherapy post-interval cytoreductive surgery (Cohort 2) will be randomized to PC + oregovomab or placebo (PCO vs. PCP). Patients with germline BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with an additional dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients will be administered oregovomab/placebo after debulking surgery at cycles 4 and 6 with two additional doses at 6- and 18-weeks following cycle 6 in Cohort 2. No other front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim futility analysis will be performed. Secondary objectives include OS, frequency and severity of AEs, and QoL. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of correlative biomarkers. The study is actively enrolling in the US, Canada, Belgium, Italy, Spain, Czech Republic, Hungary, Poland Korea, Taiwan, Mexico Argentina, India and Chile. 518 of the planned 602 patients were enrolled at the time of submission. Clinical trial information: NCT04498117 .

Highly sensitive photoelectrochemical immunosensor for detecting cancer marker CA19-9 based on a new SnSe quantum dot.

Asandwich-type photoelectrochemical (PEC) immunosensor was constructed on a screen-printed electrode (SPE) using gold-coated tin selenide quantum dots (Au-SnSe QDs) to determinethe carbohydrate antigen 19 9 (CA19-9). Water-soluble Au-SnSe QDs were prepared by coating low-cost SnSe QDs, prepared by reacting tin(II) 2-ethyl hexanoate with selenium ions (HNaSe) without needing to add an external capping agent (SnSe QDs). SnSe-based QDs were characterized using high-resolution transmission electron microscopy (HR-TEM) and dynamic light scattering (DLS). DSP (dithio-bis (succinimidyl propionate)) as a linker was attached on Au@SnSe QDs and conjugated with CA19-9 monoclonal antibodies (Ab2-DSP-Au@SnSE QD). For capture probe assembling, an Au nano-layer was electrochemically deposited on a SPE by HAuCl4 reduction using 12 cycles of cyclic voltammetry (0 to - 1.4V) at the scan rate of 50mVs-1, then covered by self-assembly of DSP and covalent conjugation of CA19-9 Ab1. Our developed PEC immunosensor showed a significant photoelectrochemical response, recorded using chronoamperometry (0.3V), for the presence of CA19-9 antigen in serum samples under light irradiation, with adetection limit (LOD) of 0.0011 U mL-1 and adynamic range of 0.005-100 U mL-1. The recovery of CA19-9 determinationfrom serum samples was 101 to 113%.

Soluble PD‑L1 reflects cachexia status in patients with gastric cancer and is an independent prognostic marker for relapse‑free survival after radical surgery.

Soluble programmed death-ligand 1 (sPD-L1) levels can be used as a biomarker for gastric cancer (GC). However, comprehensive information regarding the sPD-L1 expression profiles and their association with cachexia in GC is lacking. Therefore, the present study evaluated the association between clinicopathological findings and sPD-L1 levels in patients with GC. Serum samples were collected from patients with GC during their first visit to Department of Esophageal-Gastro-Intestinal Surgery, Chiba University Hospital, Chiba, Japan (January 2012-December 2017; n=173), and sPD-L1 levels were measured using an enzyme-linked immunosorbent assay. Survival rates among 116 patients, excluding cases with preoperative chemotherapy or no radical procedures, were analyzed. sPD-L1 levels were associated with factors such as neutrophil-to-lymphocyte ratio, hemoglobin (Hb) and albumin (Alb) levels, total cholesterol and C-reactive protein (CRP) levels, and related to inflammation and nutrition in patients. Notably, the higher the number of applicable indicators related to cachexia (Hb <12 g/dl, Alb <3.2 g/dl, CRP >0.5 mg/dl and low body mass index) was, the higher the sPD-L1 value was. However, the pathological stage did not significantly differ between the groups. Clinicopathologically, there was no association with tumor depth, lymph node metastasis or vascular invasion; however, patients with the intestinal type had significantly higher sPD-L1 levels than patients with the diffuse type (P=0.032; Wilcoxon test). The overall survival did not significantly differ between the groups with low and high sPD-L1 levels; however, among patients who received radical treatment, the relapse-free survival was significantly worse in the high-sPD-L1-level group than in the low-sPD-L1-level group (P=0.025; log-rank test). Multivariate Cox regression analysis revealed that a high sPD-L1 concentration was a sign of poor prognosis, independent of pathological stage and cancer antigen CA19-9 (P=0.0029). Therefore, the present findings suggest that sPD-L1 can reflect cachexia status in patients with GC and may serve as a prognostic marker for relapse-free survival after radical GC surgery.

Diagnostic and serological study of Breast Cancer in women in Maysan Province, Iraq

The current study was designed to examine the association between breast cancer grading and levels of CA15-3 was studied in addition to the correlation between ABO blood groups and breast cancer. The study involved (140) breast cancer women, and (140) blood samples were collected from healthy women who served as control. The total patients were divided according to their ages into three groups (30-39), (40-49) and (≥50), and ABO blood groups. Moreover, the grades of breast cancer were divided into three groups, and their correlation with serum CA15-3 levels was studied. The current study shows a significant correlation between breast cancer grading and levels of serum CA15-3 antigen. The study also showed that breast cancer is elevated with age. The results demonstrated a great association between the ABO blood groups and breast cancer. Blood group type (A) recorded the highest frequency and percentage (42.14%) of patients with breast cancer. The non-A-blood type (O, B and AB) percentage was as follows (32.14%, 19.29% and 6.43%, respectively). Thus, monitoring breast cancer occurrences in women with blood group A early could be an and excellent strategy to control and facilitate the event of breast cancer. Keywords: Breast cancer, CA15-3, blood groups, breast cancer grading.

Application of Various Optical and Electrochemical Nanobiosensors for Detecting Cancer Antigen 125 (CA-125): A Review.

Nowadays, diagnosing early-stage cancers can be vital for saving patients and dramatically decreases mortality rates. Therefore, specificity and sensitivity in the detection of cancer antigens should be elaborately ensured. Some early-stage cancers can be diagnosed via detecting the cancer antigen CA-125, such as ovarian cancer, and required treatments can be applied more efficiently. Thus, detection of CA-125 by employing various optical or electrochemical biosensors is a preliminary and crucial step to treating cancers. In this review, a diverse range of optical and electrochemical means of detecting CA-125 are reviewed. Furthermore, an applicable comparison of their performance and sensitivity is provided, several commercial detection kits are investigated, and their applications are compared and discussed to determine whether they are applicable and accurate enough.

New Quantum-Dot-Based Fluorescent Immunosensor for Cancer Biomarker Detection

Cancer antigen 15-3 (CA 15-3) is a biomarker for breast cancer used to monitor response to treatments and disease recurrence. The present work demonstrates the preparation and application of a fluorescent biosensor for ultrasensitive detection of the cancer antigen CA 15-3 protein tumor marker using mercaptopropionic-acid-functionalized cadmium telluride (CdTe@MPA) quantum dots (QDs) conjugated with CA 15-3 antibodies. First, the QDs were synthesized by the hydrothermal route, resulting in spherical nanoparticles up to 3.50 nm in diameter. Subsequently, the QD conjugates were characterized by Fourier transform infrared spectroscopy (FTIR), UV absorption, and fluorescence. The interaction between the conjugates and the protein was studied by fluorescence spectroscopy in buffer and in 10-fold diluted commercial human serum. Calibration in spiked serum samples gave a detection limit of 0.027 U/mL, 1000-fold lower than the clinical limit for CA 15-3 (25 U/mL to 30 U/mL), indicating that this is an ultrasensitive technique. In addition, a rapid response was obtained within 10 min. The biosensor was selective in the presence of the interfering serum proteins BSA, CEA, and CA-125, with a maximum interference of 2% for BSA. The percent recovery was close to 100% with maximum relative standard deviation (RSD%) values of 1.56. Overall, the developed CA 15-3 biosensor provides a simple and sensitive method for ultrasensitive monitoring of breast cancer, as well as the ability to detect other molecules of interest in human serum matrices.

Moving Towards Dawn: KRas Signaling and Treatment in Pancreatic Ductal Adenocarcinoma.

"Pancreatic ductal adenocarcinoma (PDAC)" is robust, nearly clueless, and all-around deadly among all tumors. Below 10 %, the general 5-year endurance period has remained adamantly unaltered in the last 30 years, regardless of enormous clinical and therapeutic endeavors. The yearly number of deaths is more than the number of recently analyzed cases. Not a classic one, but "Carbohydrate Antigen CA19- 9" remains the prevailing tool for diagnosis. MicroRNAs and non-invasive techniques are now incorporated for the effective prognosis of PDAC than just CA19-9. Mutated "Rat sarcoma virus Ras" conformation "V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRas" is 95 % accountable for PDAC, and its active (GTP-bound) formation activates signaling cascade comprising "Rapidly accelerated fibrosarcoma Raf"/"Mitogen-activated protein kinase MEK"/ "Extracellular signal-regulated kinase ERK" with "Phosphoinositide 3-kinase PI3K"/ "protein kinase B Akt"/ "mammalian target of rapamycin mTOR" pathways. KRas has acquired the label of 'undruggable' since the crosstalk in the nexus of pathways compensates for Raf and PI3K signaling cascade blocking. It is arduous to totally regulate KRascoordinated PDAC with traditional medicaments like "gemcitabine GEM" plus nabpaclitaxel/ FOLFIRINOX. For long-haul accomplishments aiming at KRas, future endeavors should be directed to combinatorial methodologies to adequately block KRas pathways at different standpoints. Currently they are contributing to healing PDAC. In this review article, we outline the function of KRas in carcinogenesis in PDAC, its signaling cascade, former techniques utilized in hindering Kras, current and future possibilities for targeting Kras.

68Ga-Prostate-Specific Membrane Antigen PET/CT in Ovarian Tumors: Potential to Differentiate Benign and Malignant Tumors Before Surgery: A Preliminary Report.

Ovarian cancer is usually diagnosed in an advanced stage of disease due to the absence of specific symptoms and a lack of sensitive diagnostic methods. Prostate-specific membrane antigen (PSMA) is expressed on prostate cancer cells but can be found in other tumors such as ovarian cancer.The aim of this pilot study was to evaluate the feasibility of using 68Ga-PSMA-11 PET/CT in detection of ovarian neoplasm before surgical treatment. Eight women with mean age of 56.0 ± 16.2 years were included in the study. All patients underwent transvaginal ultrasound followed by CT scan of the chest and abdomen as qualification for surgery. Within a 1-week interval, PET/CT was performed on a Siemens Biograph scanner, 60 minutes after injection of 2 MBq/kg 68Ga-PSMA-11. In 3 cases (37.5%), the 68Ga-PSMA-11 PET/CT was positive, whereas histological examination confirmed 2 serous ovarian cancer cases and 1 ovarian borderline tumor. The SUVmax in the serous ovarian cancer was 8.7 and 4.1, and in the borderline ovarian tumor, it was 13.8. No correlation was found between antigen CA-125 level and 68Ga-PSMA expression. Range of tumor SUVmax was not correlated with stage of disease. The remaining 62.5% (5/8) were negative in 68Ga-PSMA-11 PET/CT, and histopathology confirmed benign pelvic tumor. The initial experience supports the potential to use 68Ga-PSMA-11 in ovarian cancer to differentiate malignant and benign tumors before surgery.This study was approved by the Ethical Committee of the Medical University of Warsaw (KB/2/A/2018).

Redox features of hexaammineruthenium(III) on MXene modified interface: Three options for affinity biosensing

In this article we describe construction of a bioreceptive interface for detection of a breast cancer biomarker carbohydrate antigen CA15-3. The conductive interface was patterned by a 2D nanomaterial MXene, to which a mixed layer containing sulfobetaine and carboxybetaine was electrochemically grafted through a diazonium moiety. Such a modified interface was then applied for covalent immobilisation of anti-CA15-3 antibody as a bioreceptive probe for detection of a breast cancer biomarker. Two different strategies were applied for final construction of an immunosensor i.e. an interface finally blocked by bovine serum albumin or an immunosensor without such modification. Finally, electrochemical reading was accomplished using a soluble redox probe Ru(NH3)63+ ion for detection of CA15-3 in a clinically relevant range up to 50 U mL−1. The results indicate that immunosensor based on non-blocked interface can be applied for biosensing using two modes of action: 1. differential pulse voltammetry (a plot of a peak current vs. analyte concentration) and 2. an electrochemical impedance spectroscopy (a plot of a charge transfer resistance vs. analyte concentration). The electrode blocked by bovine serum albumin (BSA) can be used by additional 3. mode of action: through detection of changes in the potential (a plot Epvs. c). Additionally, we reveal and explain that Ru(NH3)63+ is redox probe, which can be applied as interfacial molecular nanoscale ruler to distinguish negatively charged protein molecules present in the close proximity (≤ 6 nm) of the electrode (in our case adsorbed BSA molecules) from the negatively charged protein molecules at a larger distance (>12 nm) from the electrode (i.e. CA15-3 analyte).

Exploring the Role of 2D-Graphdiyne as a Charge Carrier Layer in Field-Effect Transistors for Non-Covalent Biological Immobilization against Human Diseases.

Graphdiyne's (GDY's) outstanding features have made it a novel 2D nanomaterial and a great candidate for electronic gadgets and optoelectronic devices, and it has opened new opportunities for the development of highly sensitive electronic and optical detection methods as well. Here, we testified a non-covalent grafting strategy in which GDY serves as a charge carrier layer and a bioaffinity substrate to immobilize biological receptors on GDY-based field-effect transistor (FET) devices. Firm non-covalent anchoring of biological molecules via pyrene groups and electrostatic interactions in addition to preserved electrical properties of GDY endows it with features of an ultrasensitive and stable detection mechanism. With emerging new forms and extending the subtypes of the already existing fatal diseases, genetic and biological knowledge demands more details. In this regard, we constructed simple yet efficient platforms using GDY-based FET devices in order to detect different kinds of biological molecules that threaten human health. The resulted data showed that the proposed non-covalent bioaffinity assays in GDY-based FET devices could be considered reliable strategies for novel label-free biosensing platforms, which still reach a high on/off ratio of over 104. The limits of detection of the FET devices to detect DNA strands, the CA19-9 antigen, microRNA-155, the CA15-3 antigen, and the COVID-19 antigen were 0.2 aM, 0.04 pU mL-1, 0.11 aM, 0.043 pU mL-1, and 0.003 fg mL-1, respectively, in the linear ranges of 1 aM to 1 pM, 1 pU mL-1 to 0.1 μU mL-1, 1 aM to 1 pM, 1 pU mL-1 to 10 μU mL-1, and 1 fg mL-1 to 10 ng mL-1, respectively. Finally, the extraordinary performance of these label-free FET biosensors with low detection limits, high sensitivity and selectivity, capable of being miniaturized, and implantability for in vivo analysis makes them a great candidate in disease diagnostics and point-of-care testing.

Validation of a genotype-based algorithm that identifies individuals with low, intermediate, and high serum CA19-9 levels in cancer-free individuals and in patients with colorectal cancer

BackgroundSerum levels of Carbohydrate antigen CA19-9 are determined by the genotype of fucosyltransferases 2 and 3. To validate, possibly modify, and improve a grouping algorithm based on these genotypes.MethodsCA19-9 levels genotypes and of fucosyltransferase 2 and 3 were analyzed in cancer-free and colorectal cancer patients. Patients were assigned to groups with low (group A), intermediate (B), or high (C) CA19-9 biosynthetic activity based on a previously developed grouping algorithm based on genotype of fucosyltransferases 2 and 3.ResultsThree hundred thirty-eight patients were included (n=177 cancer-free). Of cancer-free patients 7.9%, 75.7%, and 16.4% were assigned to groups A, B, and C, respectively. In colorectal cancer patients it 7.5%, 77.0%, and 15.5%, respectively. There were significant differences between median CA19-9 levels in the three groups (P<0.001) in both cohorts. The T59G single-nucleotid polymorphism in fucosyltransferase 3 had a significant influence on CA19-9 levels in cancer-free group B patients, which led to establishment of subgroups B1 and B2. However, no difference in CA19-9 levels between these subgroups was found in colorectal cancer patients. A receiver-operating characteristic showed similar areas under the curve for original group B as well as for subgroups B1 and B2.ConclusionsThe grouping algorithm based on genotype of fucosyltransferases 2 and 3, which defines groups with distinct CA19-9 serum levels, was validated in cancer-free patients and in colorectal cancer patients. No clinically relevant improvement to the grouping algorithm was identified.

Electrochemical Immunoassay for Tumor Marker CA19-9 Detection Based on Self-Assembled Monolayer.

A CA19-9 electrochemical immunosensor was constructed using a hybrid self-assembled membrane modified with a gold electrode and applied to detect real samples. Hybrid self-assembled membranes were selected for electrode modification and used to detect antigens. First, the pretreated working electrodes were placed in a 3-mercaptopropionic acid (MPA)/β-mercaptoethanol (ME) mixture for 24 h for self-assembly. The electrodes were then placed in an EDC/NHS mixture for 1 h. Layer modification was performed by stepwise dropwise addition of CA19-9 antibody, BSA, and antigen. Differential pulse voltammetry was used to characterize this immunosensor preparation process. The assembled electrochemical immunosensor enables linear detection in the concentration range of 0.05–500 U/mL of CA19-9, and the detection limit was calculated as 0.01 U/mL. The results of the specificity measurement test showed that the signal change of the interfering substance was much lower than the response value of the detected antigen, indicating that the sensor has good specificity and strong anti-interference ability. The repeatability test results showed that the relative standard deviations were less than 5%, showing good accuracy and precision. The CA19-9 electrochemical immunosensor was used for the actual sample detection, and the experimental results of the standard serum addition method showed that the RSD values of the test concentrations were all less than 10%. The recoveries were 102.4–115.0%, indicating that the assay has high precision, good accuracy, and high potential application value.

Secondary Gerstmann syndrome, a case report

IntroductionGerstmann syndrome is a rare neurological disorder that consist primarily of 4 neuropsychological signs that include acalculia (impairment in performing calcultaions), digital agnosia (dificulty discriminating their own fingers), agraphia (impairment or dificulty to write by hand); and left-right disorientation (impairment of distinguishing left from right.ObjectivesPresentation of a case report of a patient with Gertsmann syndrome secondary to breast cancer metastasis.MethodsWe analyze the case of a 79 years-old female with a history of breast cancer in remission, with a severe depressive episode of 8 months of evolution, dysphoria, apathy, decrease in the ability to carry out basic activities of daily life, acute personality changes and sleep disruption. 15 days previous to the first examination the patient suffers gait disturbances, falling from her own height, memory impairment, suicide ideation and nomination aphasia.ResultsAt the examination we encounter digital agnosia, acalculia, agraphia, right-left disorientation, right hemiparesis. MRI are taken founding 3 tumor lesions in the left and right frontal lobe, 2 solid lesions with a necrotic appearance in the right parietal lobe, one of them in the angular gyrus of the parietal cortex. CT scan found a solid tumor-like lesion in the left pulmonary apex. CA-125 antigen 429.5 U/mL. She was sent to continue her treatment with oncology, receiving radiotherapy.ConclusionsThe psychiatric abnormalities secondary to Gerstmann syndrome make the relatives of this patient seek psychiatric care, requiring multidisciplinary work to reach an accurate diagnosis. Gerstmann syndrome is a rare neurological condition that can mimic lots of other clinical pictures.DisclosureNo significant relationships.

FLORA-5/GOG3035: Frontline chemo-immunotherapy (paclitaxel-carboplatin-oregovomab [PCO] versus chemotherapy (paclitaxel-carboplatin-placebo [PCP]) in patients with advanced epithelial ovarian cancer (EOC)—Phase III, double-blind, placebo-controlled, global, multinational study.

TPS5619 Background: Oregovomab, a murine IgGκ1 monoclonal antibody, has high affinity binding to tumor associated antigen CA125, thus, rendering the target antigen CA125 more immunogenic or “neoantigen-like” through altered and enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when oregovomab is combined with chemotherapy. In a randomized phase II study, oregovomab in combination with paclitaxel and carboplatin (PC) induced tumor immunity and demonstrated significant improvement in median PFS (41.8 months(m) PCO vs 12.2 m PC, HR 0.46, p=0.0027) and median OS (N.E. PCO vs 43.2 m PC, HR O.35, p=0.043) in patients with previously untreated EOC. Oregovomab combined with PC had a favorable toxicity profile. FLORA-5/GOG3035, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: The study is a phase 3, multicenter, double-blind, placebo-controlled trial. Optimally debulked patients with FIGO III/IV EOC and serum CA125 ≥ 50 U/ml receiving adjuvant (Cohort 1) or patients receiving neoadjuvant chemotherapy post-interval cytoreductive surgery (Cohort 2) will be randomized to PC + oregovomab or placebo (PCO vs. PCP). Patients with germline BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with an additional dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients will be administered oregovomab/placebo after debulking surgery at cycles 4 and 6 with two additional doses at 6- and 18-weeks following cycle 6 in Cohort 2. No other front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim futility analysis will be performed. Secondary objectives include OS, frequency and severity of AEs, and QoL. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of correlative biomarkers. The study is actively enrolling in the US, Canada, Belgium, Italy, Spain, Czech Republic, Hungary, Poland, Korea, Taiwan, Mexico, Argentina, and Chile. 179 patients were enrolled at time of submission. Clinical trial information: NCT04498117.

Network Meta-analysis of peroral Chinese patent medicines for activating blood and resolving stasis in treatment of endometriosis

Network Meta-analysis was performed to systematically compare the efficacy of different Chinese patent medicines for activating blood and resolving stasis in the treatment of endometriosis and to provide evidence-based references for clinical medication regimens. The relevant randomized controlled trials(RCTs) involving Chinese patent medicines combined with conventional treatment(experimental group) vs conventional treatment(control group) were retrieved from Chinese and English literature databases. The bias risk assessment tool recommended in Cochrane handbook 5.3 was used to evaluate the quality of the included studies. The result data of each outcome index was extracted for network Meta-analysis in Stata 15.0. A total of 44 RCTs were included in this study, involving 4 345 patients and 9 Chinese patent medicines. The network Meta-analysis revealed the following trends.(1)In terms of reducing the visual analogue scale(VAS) scores, Dan'e Fukang Plaster+conventional treatment&gt;Xuefu Zhuyu Capsules+conventional treatment&gt;Gongliuxiao Capsules+conventional treatment.(2)In terms of reducing cancer antigen CA125, Xiaojin Capsules+conventional treatment&gt;Shaofu Zhuyu Granules+conventional treatment&gt;Dan'e Fukang Plaster+conventional treatment.(3)In terms of reducing estradiol(E_2), Gongliuxiao Capsules+conventional treatment&gt;Xiaojin Capsules+conventional treatment&gt;Sanjie Zhentong Capsules+conventional treatment.(4) In terms of reducing recurrence rate, Guizhi Fuling Capsules+conventional treatment&gt;Xuefu Zhuyu Capsules+conventional treatment&gt;Dan'e Fukang Plaster+conventional treatment. The peroral Chinese patent medicines for activating blood and resolving stasis combined with conventional treatment have better efficacy in the treatment of endometriosis than conventional treatment. However, considering the low quality of the included literature, large-scale high-quality clinical trials are needed in the future research.

The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets.

Simple SummaryOvarian cancer is the most lethal gynaecological malignancy, of which serous carcinoma is the most common subtype. The lack of symptoms and sensitive diagnostic tests for the early stages of its development may explain why diagnosis often occurs late, when the neoplasm has already spread outside the pelvis. Currently, the standard treatment for high-grade serous ovarian carcinomas (HSOCs) involves cytoreductive surgery followed by platinum-based systematic chemotherapy, which does not reduce either recurrence or mortality. Despite intense efforts to develop novel therapies using new chemotherapeutic agents, such as anti-angiogenesis agents and poly (ADP-ribose)-polymerase inhibitors, to improve patient outcomes, the five-year survival for this malignancy remains low. Therefore, it is important to identify new targetable molecules for the early diagnosis, monitoring, and treatment of this malignancy. The aim of this review is to discuss the role of mesothelin in serous ovarian carcinomas, focusing on diagnostic, prognostic, and therapeutic perspectives.Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.

Diagnostic value of combined detection of CA72-4, CA19-9, and carcinoembryonic antigen comparing to CA72-4 alone in gastric cancer: a systematic review and meta-analysis

BackgroundGastric cancer (GC) is one of the most common malignant tumors in humans. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4 are all serum tumor markers for diagnosis of gastric cancer. However, the results of studies reporting the diagnosis of the combined three varied. In this study, the combined diagnostic performance of these 3 serum tumor markers was systematically evaluated.MethodsPubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang data were searched for literature on serum tumor markers CEA, CA19-9, and CA72-4 in the diagnosis of gastric cancer. The inclusion criteria were designed according to the Participants, Intervention, Control, Outcomes, Study (PICOS) principles. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scoring scale was used to assess the quality of the literature. After extracting the data, Stata 16.0 software was used for meta-analysis.ResultsA total of 10 articles were finally included, and a total of 6,574 patients participated in diagnosis, 3,077 for confirmed GC and 3,497 for non-GC respectively. Meta-analysis results showed that the diagnostic sensitivity of the combined diagnosis of the 3 tumor markers was 0.67 [95% confidence interval (CI): 0.54, 0.77], the specificity was 0.89 (95% CI: 0.82, 0.93), the positive likelihood ratio was 5.9 (95% CI: 3.5, 9.8), the negative likelihood ratio was 0.38 (95% CI: 0.27, 0.53), and the diagnostic odds ratio (DOR) was 16 (95% CI: 8, 32). The diagnostic sensitivity of CA72-4 diagnosis alone was 0.58 (95% CI: 0.40, 0.73), specificity was 0.86 (95% CI: 0.80, 0.90), the positive likelihood ratio was 4.0 (95% CI: 3.1, 5.1), the negative likelihood ratio was 0.49 (95% CI: 0.34, 0.71), and the DOR was 8 (95% CI: 5, 14). The area under the ROC curve (AUC) values of the combined three diagnosis and CA72-4 diagnosis alone were 0.87 (95% CI: 0.83, 0.89) and 0.84 (95% CI: 0.81, 0.87), respectively, the difference was statistically significant (Z=4.86, P<0.05).DiscussionThe combined use of the 3 tumor markers has higher sensitivity and specificity than single marker diagnosis in the diagnosis of gastric cancer.

A Novel Electrochemical Immunosensor Based on COF-LZU1 as Precursor to Form Heteroatom-Doped Carbon Nanosphere for CA19-9 Detection.

Porous carbon sphere materials have a large variety of applications in several fields due to the large surface area, adaptable porosity, and good conductivity they possess. Obtaining a steady carbon sphere using the green synthesis method remains a significant challenge. In this experiment, covalent organic frameworks (COFs) were used as a precursor and Fe3O4NPs were integrated into the precursor in order to synthesize a porous carbon sphere material using the one-step pyrolysis method. COFs have an ordered porous structure, perpetual porosity, large surface area, and low density and display good environmental tolerance. These properties make them an excellent precursor for synthesizing porous carbon sphere, which maintains good morphology at high temperatures, and it is not involved in the removal of dangerous reagent and small size restrictions during the synthesis process. In addition to the formation of a porous carbon sphere, transition metal carbon material that contains N element can be an active catalyst. The composites exhibit better activity when Fe is doped into carbon materials containing N element than that of other doped transition metals including Mn and Co. In this situation, the integration of Fe3O4NPs and N element in the COF precursor exposed the active sites of the composites and the two substances synergistically improved the electrocatalytic properties, and the composites were named Fe3O4@NPCS. The constructed Fe3O4@NPCS/GCE immunosensor was applied as a means of detecting CA19-9 antigen and presented a wide linear range from 0.00001 to 10 U/mL with a low detection limit of 2.429 μU/mL (S/N = 3). In addition, the prepared immunosensor was utilized for detecting CA19-9 antigen in the real human serum, and the recovery rates were in the range from 95.24% to 106.38%. Therefore, a porous carbon sphere prepared by COFs as a precursor can be applied for the detection of CA19-9 antigen in real samples, which could be an excellent strategy for CA19-9 antigen detection and could potentially promote the development of COF materials in various electrochemical fields.