Detection Of Tumor Cells Research Articles

Abstract 2679: Myeloid olfactory receptors in melanoma

Abstract Olfactory receptors are commonly found in the nasal cavity and function to detectodorants. However, very recent studies have determined that innate immune cells,including monocytes and macrophages, express olfactory receptors. OLFR2 (OR6A2 inhumans), was recently linked to atherosclerosis development through interaction with itsligand, octanal. Increased levels of octanal are considered as a risk factor foratherosclerosis. Conversely, octanal levels are associated with lower cancer incidence,suggesting that OLFR2 may play a protective role in cancer. Indeed, data from TheCancer Genome Atlas for liver and brain cancers show that OLFR2 expression isassociated with increased patient survival. Here, we utilized an orthotopic melanomamouse model using B16 cancer cells in C57/BL6 mice that had been transplanted witheither wild type or OLFR2 knockout bone marrow to directly test the role of OLFR2 onimmune cells in regulating tumor growth. We found that hematopoietic deletion of OLFR2exacerbated melanoma tumor growth in these mice; again, supporting the notion thatOLFR2 is anti-tumoral. The OLFR2+ cells present in the tumor were myeloid cells.Monocytes, non-classical monocytes specifically, function to detect cancer cells in tumorseeding sites, and recruit NK cells for tumor cell destruction. OLFR2-deficientmacrophages were found to migrate less to tumor cells in an in vitro assay, suggestingthat OLFR2 is involved in the sensing of newly seeding tumor cells, likely through sensingoctanal. Studies are ongoing to determine the exact functions of OLFR2+ monocytes andmacrophages in the tumor microenvironment. OLFR2 may be one of several olfactoryreceptors that is utilized by myeloid cells as a defense mechanism for detection of newlyseeding or metastatic tumor cells. As olfactory receptors are easily druggable targets,understanding their role in cancer prevention could lead to emerging newimmunotherapies for cancer. Citation Format: Elayne M. Benson, Klaus Ley, Marco Orecchioni, Catherine C. Hedrick. Myeloid olfactory receptors in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2679.

Abstract 3709: Single cell analysis from CSF of patients with suspected leptomeningeal metastasis

Abstract Introduction: Leptomeningeal metastases (LM) are diagnosed in up to 10% of metastatic cancer patients, the most frequent cancers being carcinomas of breast and lung or melanoma. Due to a dismal prognosis and an overall median survival of only four months new approaches for molecular analysis could help to identify individual treatment options. Material and Methods: In this study, we collected 28 cerebrospinal fluid (CSF) samples from patients with different primary tumors but suspected LM. CSF was divided in two parts for standard neuropathologic cytomorphology and detection of circulating tumor cells (CTCs) by using the CellSearch® CTC Kit, respectively. Subsequently, single Cytokeratin-positive CTCs were isolated for whole genome amplification by Ampli1TM and molecular analysis. Additionally, we were able to isolate cell-free DNA (cfDNA) from CSF in a subset of patients which we amplified by an adapted Ampli1TM library protocol. In a small subset of patients, we collected slices of formalin-fixed paraffin embedded (FFPE) primary tumors and systemic metastases for dissociation and isolation of pure subpopulations by DEPArrayTM technology. Isolated CTCs, cfDNA and subpopulations of tumor and stromal cells were analyzed for copy number variations (CNV) applying the Ampli1TM LowPass protocol on the Illumina MiSeqTM platform. Results: By comparing results from classical cytomorphology and CellSearch® workflow, we could find high concordance (24/28 samples) with a slightly higher tumor cell detection rate by CellSearch® (11 positive cases vs. 9 by cytomorphology). Importantly, we could confirm the malignant origin of isolated cells by CNV analysis in all patients positive in CellSearch® assay. Moreover, by comparing single cell data with cfDNA analysis of a subset of 20 samples, we could also detect a higher sensitivity for tumor detection in CTC-based analysis (8/20 cases positive) in comparison to cfDNA-based analysis (5/20 cases positive). In a comprehensive analysis of multiple samples of an individual patient, including CTCs and cfDNA from CSF at different time points, CTCs from blood and biopsies from multiple visceral metastasis, we could identify divergent genomic evolution between tumor cells from the central nervous syste Conclusion: In this proof-of-concept study we show that a liquid biopsy-based approach for single cell analysis from CSF holds potential for innovative diagnostic assays for patients with suspected LM. Combining CTC quantification with molecular single cell analysis could enable us to define predictive tests to select novel treatment options for patients with LM in the future. Citation Format: Caecilia Koestler, Giancarlo Feliciello, Florian Lueke, Kathrin Weidele, Saida Zoubaa, Peter Hau, Tobias Pukrop, Markus J. Riemenschneider, Christoph A. Klein, Bernhard Polzer. Single cell analysis from CSF of patients with suspected leptomeningeal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3709.

Abstract 5002: Next-generation mRNA-LNP vaccine prototype achieves tumor clearance in a GBM mouse model

Abstract Glioblastoma (GBM) is the most prevalent and aggressive primary brain tumor type with an abysmal prognosis, featuring an immunologically dampened tumor microenvironment and limited neoantigen production. Novel therapeutic strategies are urgently needed. A well-characterized GBM-associated mutation that can elicit an anti-tumor immune response is EGFRvIII mutation. The cancer-driver mutation is detected in approximately 30% of patients at the time of diagnosis and plays a pivotal role in the emergence of GBM. EGFRvIII is an in-frame epidermal growth factor receptor (EGFR) deletion generating a constitutively active oncogenic protein. Its highly immunogenic nature represents an ideal focal point for cutting-edge mRNA-LNP candidate therapeutics. To evaluate proprietary lipid nanoparticle (LNP) compositions for their capacity to induce anti-GBM immunity, we developed a murine transplantable GBM tumor model by neonatal electroporation. The somatically engineered glioblastomas harbor two targeted CRISPR knockouts and stably overexpress EGFRvIII to yield transplantable cell lines for orthotopic tumor initiation. One week after intracranial tumor cell implantation of 6-8 week-old female mice (day 0; n=10), half the animals were administered either buffer (control cohort) or our novel anti-EGFRvIII mRNA-LNP vaccine (experimental cohort). The regimen involved four intramuscular injections before monitoring tumor progression by MRI on day 30. The imaging revealed a high tumor burden in all control group animals, compared to no detectable tumor cells in vaccine-protected mice. All control group animals were humanely euthanized by day 38 due to symptoms associated with the growing brain tumor mass. The asymptomatic experimental animals received a fifth anti-EGFRvIII vaccination before MRI-based examinations on day 43 and day 78 confirmed that no tumor cells could be detected in vaccine-protected mice. The results highlight the potency and potential of our proprietary anti-EGFRvIII mRNA-LNP vaccine as a novel anticancer therapeutic. In addition, the established tumor model represents a valuable tool to test future mRNA-LNP designs. Outstanding cellular and molecular investigations will reveal vaccine-mediated mechanistic insights, allowing for the co-advancement of the tumor model and next-generation multi-target mRNA-LNP vaccine candidates. Citation Format: Robert Nechanitzky, Shannon Snelling Snelling, Kristofor Ellestad, Xueqing Lun, Kirstin Olsen, Yu Wu, Yury Karpov, Jun Liu, Matthew Gold, Haritha Menon, Rajesh Krishnan, Robert Georgantas, Pamela S. Ohashi, Douglas J. Mahoney, Jennifer A. Chan, Natalia Martin-Orozco. Next-generation mRNA-LNP vaccine prototype achieves tumor clearance in a GBM mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5002.

Aptamer-based electrochemical analysis platform for tumor cells and biomarkers detection

Early diagnosis and treatment of cancer can effectively improve patient survival rates and quality of life. One of the best options for early screening strategies is to track tumor cells and their markers. There is also an urgent need to develop accurate, susceptible, rapid, non-invasive, and low-cost detection methods. Among them, standard detection techniques for tumor cells include immunohistochemistry and histopathology, but they are expensive and require professional personnel. Both tumor cells and normal cells can secrete biomarkers, which can be obtained from biological samples (such as blood, urine, serum, etc.). Tumor biomarkers may be significantly elevated or changed in individuals with tumors. Common tumor biomarkers include proteins, nucleic acids, etc. In recent years, aptamer-based electrochemical analysis methods have been widely used in cancer diagnosis. Aptamers are obtained through in vitro screening technology and have high selectivity and affinity, which can improve the sensitivity of electrochemical analysis technology. This article reviews the achievements of aptamer-based electrochemical analysis methods in detecting tumor cells and tumor markers and the challenges and development prospects in cancer diagnosis.

Photoacoustic microscopy for real-time monitoring of near-infrared optical absorbers inside biological tissue.

We developed a high-speed optical-resolution photoacoustic microscopy (OR-PAM) system using a high-repetition-rate supercontinuum (SC) light source and a two-axes Galvano scanner. The OR-PAM system enabled real-time imaging of optical absorbers inside biological tissues with excellent excitation wavelength tunability. In the near-infrared (NIR) wavelength range, high-speed OR-PAM faces limitations due to the lack of wavelength-tunable light sources. Our study aimed to enable high-speed OR-PAM imaging of various optical absorbers, including NIR contrast agents, and validate the performance of high-speed OR-PAM in the detection of circulating tumor cells (CTCs). A high-repetition nanosecond pulsed SC light source was used for OR-PAM. The excitation wavelength was adjusted by bandpass filtering of broadband light pulses produced by an SC light source. Phantom and in vivo experiments were performed to detect tumor cells stained with an NIR contrast agent within flowing blood samples. The newly developed high-speed OR-PAM successfully detected stained cells both in the phantom and in vivo. The phantom experiment confirmed the correlation between the tumor cell detection rate and tumor cell concentration in the blood sample. The high-speed OR-PAM effectively detected stained tumor cells. Combining high-speed OR-PAM with molecular probes that stain tumor cells in vivo enables in vivo CTC detection.

PBA-Derived Heteroatom-Doped Mesoporous Graphitic Spheroids as Peroxidase Nanozyme for In Vitro Tumor Cells Detection.

Inspired by the two kinds of naturally occurring peroxidases (POD) with vanadium or heme (iron)-based active catalytic centers, we have developed a dual metal-based nanozyme with dual V and Fe-based active catalytic centers. Co-doping of graphene with heteroatoms has a synergistic effect on the catalytic properties of the nanomaterial as the distances of migration of the substrates drastically reduce. However, a few studies have reported the codoping of heterometallic elements in the graphene structure due to the complexity of the synthesis procedures. Herein, we report the synthesis of in situ doped bimetallic VNFe@C mesoporous graphitic spheroids nanozyme via pyrolysis without the assistance of any template assisted method. The Prussian-blue analog-based precursor material was synthesized by a facile one-step low-temperature synthesis procedure. The bimetallic spheroids showed an excellent affinity toward H2O2, with a Km value of 0.26 mM when compared to 0.436 for the natural POD, which is much better than the natural POD, which was utilized to detect tumor cells in vitro through the intracellular H2O2 produced by these cells under high oxidative stress. The VNFe@C mesoporous spheroids generate dual reactive oxygen species, including the •OH and •O2H- radicals, in the presence of H2O2, which are responsible for the POD-like activity of these nanozymes, while the bimetallic V/Fe doping plays a synergistic role in the enhancement of the activity of codoped graphitic spheroids.

Detection of effusion tumor cells under different storage and processing conditions.

Circulating tumor cells (CTCs) shed into blood provide prognostic and/or predictive information. Previously, the authors established an assay to detect carcinoma cells from pleural fluid, termed effusion tumor cells (ETCs), by employing an immunofluorescence-based CTC-identification platform (RareCyte) on air-dried unstained ThinPrep (TP) slides. To facilitate clinical integration, they evaluated different slide processing and storage conditions, hypothesizing that alternative comparable conditions for ETC detection exist. The authors enumerated ETCs on RareCyte, using morphology and mean fluorescence intensity (MFI) cutoffs of >100 arbitrary units (a.u.) for epithelial cellular adhesion molecule (EpCAM) and <100 a.u. for CD45. They analyzed malignant pleural fluid from three patients under seven processing and/or staining conditions, three patients after short-term storage under three conditions, and seven samples following long-term storage at -80°C. MFI values of 4',6-diamidino-2-phenylindol, cytokeratin, CD45, and EpCAM were compared. ETCs were detected in all conditions. Among the different processing conditions tested, the ethanol-fixed, unstained TP was most similar to the previously established air-dried, unstained TP protocol. All smears and Pap-stained TPs had significantly different marker MFIs from the established condition. After short-term storage, the established condition showed comparable results, but ethanol-fixed and Pap-stained slides showed significant differences. ETCs were detectable after long-term storage at -80°C in comparable numbers to freshly prepared slides, but most marker MFIs were significantly different. It is possible to detect ETCs under different processing and storage conditions, lending promise to the application of this method in broader settings. Because of decreased immunofluorescence-signature distinctions between cells, morphology may need to play a larger role.

Detection of oral tumour cells using quantum optics with carbon/graphene dot models

Detection of oral tumour cells using quantum optics with carbon/graphene dot models

Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer

Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore’s independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.

Photoelectrochemical detection of circulation tumor cell based on metal-organic framework with incorporated copper peroxide nanodots as probe

Signal nanoprobe based on copper peroxide nanodots (CPNs) embedded within metal–organic frameworks (ZIF-8) was applied for developing photoelectrochemical (PEC) sensor for detection of circulation tumor cells (CTC). The nanoprobe can self-supply H2O2 by encapsulated CPNs under acidic condition. The produced H2O2 can help generate insoluble precipitation onto sensor surface in the presence of horseradish peroxidase (HRP), leading to suppressed PEC current intensity. MCF-7 was selected as model CTC, which was enriched and separated from samples by antibody modified magnetic beads (MB). Organic semiconductor BTA-C4Ph and PM6 were chosen to form n-p heterojunction on sensor surface with enhanced PEC current intensity. The PEC sensor was constructed based on “sandwich” protocol, which has a linear range from 5 cell/mL to 100 cell/mL and a limit of detection (LOD) of 3 cell/mL (S/N = 3) for MCF-7. What more, the sensor was successfully applied for detection of MCF-7 in whole blood samples.

Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo.

Tumorigenic assays are used during a clinical translation to detect the transformation potential of cell-based therapies. One of these in vivo assays is based on the separate injection of each cell type to be used in the clinical trial. However, the injection method requires many animals and several months to obtain useful results. In previous studies, we showed the potential of tissue-engineered skin substitutes (TESs) as a model for normal skin in which cancer cells can be included in vitro. Herein, we showed a new method to study tumorigenicity, using cancer spheroids that were embedded in TESs (cTES) and grafted onto athymic mice, and compared it with the commonly used cell injection assay. Tumors developed in both models, cancer cell injection and cTES grafting, but metastases were not detected at the time of sacrifice. Interestingly, the rate of tumor development was faster in cTESs than with the injection method. In conclusion, grafting TESs is a sensitive method to detect tumor cell growth with and could be developed as an alternative test for tumorigenicity.

Visualization of tumor-associated neutrophils in malignant ascites of ovarian cancer with aptamer-decorated AIE probes

Neoadjuvant chemotherapy followed by interval debulking surgery is a recommended treatment for advanced-stage ovarian cancer (OC) patients to avoid bowel and spleen resection. Pre-operative chemotherapy requires ascites from OC patients for cytopathological examinations based on hematoxylin & eosin staining to detect tumor cells, whose low ratio make them difficult to be detected in ascites. Sensitive detection of tumor-related immunocytes (TRI) in ascites is not only indicative of underlying malignant ascites, but also could predict chemoresistance and poor overall survival of OC patients. The antibodies can only recognize immunocytes but cannot distinguish TRI. Herein, we identified an aptamer99 (Apt-99) using a fluorescence-activated cell sorting-based aptamer selection strategy, which could target tumor-related neutrophils (TRNs) with high binding affinity. In contrast, FAM-labeled Apt-99 couldn’t distinguish the neutrophils in the smears of other patients’ derived ascites or peritoneal lavages, such as metastatic ovarian cancer from colon carcinoma and myomas of the uterus. LC-MS/MS analysis, and the molecular docking experiments demonstrated that the target molecule of Apt-99 were S100A8&A9 heterodimers. Moreover, Apt-99-labeled aggregation-induced emission dots were facilely prepared and used for specifically visualizing the TRNs in the ascites smears. The findings indicated the diagnostic potential of Apt-99 and the possibility of further clinical trials.

Abstract C011: Detection of circulating tumor cells for the early detection of pancreatic cancer

Abstract Introduction The majority of pancreatic cancer patients are diagnosed with advanced, metastatic disease. Biomarkers to detect pancreatic cancer at earlier stages could drastically improve the poor survival rates. Circulating tumor cells (CTCs) are tumor cells that disseminate or are shed into the vascular system and have been detected in patients at pre-malignant stages. However, detecting these rare cells accurately and reliably remains a challenge. The AccuCyte-CyteFinder system uses density-based enrichment of blood nucleated cells followed by detection of CTCs using fluorescence staining, whole slide scanning and automated image analysis. This study aimed to examine whether CTCs could be used to identify patients with pancreatic lesions likely to malignant. Methods 50 patients undergoing an endoscopic ultrasound procedure for a pancreatic mass were recruited at the Royal Prince Alfred Hospital, Sydney, Australia or Chris O’Brien Lifehouse, Sydney, Australia. Peripheral blood was collected prior to the procedure and processed for CTCs on the AccuCyte-CyteFinder platform using a CK+ EpCAM+ CD45- staining panel. Results 28% (14/50) were found to have an intraductal papillary mucinous neoplasm (IPMN), 10% (5/50) pancreatic ductal adenocarcinoma (PDAC), 6% (3/50) pancreatic neuroendocrine tumor (PNET), 42% (21/50) non-neoplastic pancreatic cyst, and 14% (7/50) normal (no mass found). CTCs were highest in the PDAC group with an average of 5 cells/ml, followed by the IPMN (3 cells/ml), pancreatic cyst (2.5 cells/ml), and PNET (0 cells/ml). 86% (12/14) of IPMN patients had detectable CTCs. 2 IPMN patients with CTC counts of more than 5 cells/ml resulted in a resected sample having high-grade dysplasia while 3 IPMN patients with no/low CTC counts resulted in a resected sample having low-grade dysplasia. There was no correlation with the size of the pancreatic mass and CTC number. Conclusions CTCs could be detected in patients with pre-malignant pancreatic cancer and could determine malignancy. CTCs could potentially be used to detect pancreatic cancer early however, larger patient numbers and longer follow-up are required to validate these findings. Citation Format: Dannel Yeo, Vera Klemm, Payal Saxena, Althea Bastian, Heidi Strauss, Charbel Sandroussi, Sara Wahlroos, Peter Grimison, John E.J. Rasko. Detection of circulating tumor cells for the early detection of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C011.

Predicting axillary metastasis in breast cancer using lymphatic contrast-enhanced ultrasound-guided fine-needle aspiration of one lymph node.

Fine-needle aspiration (FNA) is a microinvasive method to diagnose lymph nodes. This study aims to determine the capability of lymphatic contrast-enhanced ultrasound (LCEUS)-guided FNA in predicting the axillary metastasis with the target of one lymph node (LN) in patients with breast cancer. LCEUS was prospectively performed in 105 patients with breast cancer. The most suspicious LN was targeted based on the characters of LCEUS. FNA was performed in the LN, followed by localization using a guide wire. The detection of lymph cells and/or tumour cells was recognized as a puncture success. Cytologic diagnosis was compared with histologic diagnosis of wire-marked LN for diagnosing accuracy and compared with histologic diagnosis of axillary LNs for predicting accuracy. LCEUS-guided FNA was performed in all 105 female patients who underwent axillary dissection. The puncture success rates were 74.3%, 91.4%, and 97.1% for three sequential groups (P = .010). In diagnosing LN metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 89.7%, 100%, and 95.7%, respectively. In predicting axillary metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 81.4%, 100%, and 91.3%, respectively. The microinvasive LCEUS-guided FNA of one lymph node can be an accurate method and may help predict axillary metastasis in patients with breast cancer. This study presented that LCEUS combined with FNA would be practical in clinic. The characters of LCEUS could indicate the suspicious LNs and promote the accuracy in predicting axillary metastasis.

Multiparameter flow cytometric detection and analysis of rare cells in in vivo models of cancer metastasis.

Rapid and reliable circulating tumor cell (CTC) and disseminated tumor cell (DTC) detection are critical for rigorous evaluation of in vivo metastasis models. Clinical data show that each step of the metastatic cascade presents increasing barriers to success, limiting the number of successful metastatic cells to fewer than 1 in 1,500,000,000. As such, it is critical for scientists to employ approaches that allow for the evaluation of metastatic competency at each step of the cascade. Here, we present a flow cytometry-based method that enables swift and simultaneous comparison of both CTCs and DTCs from single animals, enabling evaluation of multiple metastatic steps within a single model system. We present the necessary gating strategy and optimized sample preparation conditions necessary to capture CTCs and DTCs using this approach. We also provide proof-of-concept experiments emphasizing the appropriate limits of detection of these conditions. Most importantly, we successfully recover CTCs and DTCs from murine blood and bone marrow. In Supplemental materials, we expand the applicability of our method to lung tissue and exemplify a potential multi-plexing strategy to further characterize recovered CTCs and DTCs. This approach to multiparameter flow cytometric detection and analysis of rare cells in in vivo models of metastasis is reproducible, high throughput, broadly applicable, and highly adaptable to a wide range of scientific inquiries. Most notably, it simplifies the recovery and analysis of CTCs and DTCs from the same animal, allowing for a rapid first look at the comparative metastatic competency of various model systems throughout multiple steps of the metastatic cascade.

Advances in circulating tumor cells for early detection, prognosis and metastasis reduction in lung cancer.

Globally, lung cancer stands as the leading type of cancer in terms of incidence and is the major source of mortality attributed to cancer. We have outlined the molecular biomarkers for lung cancer that are available clinically. Circulating tumor cells (CTCs) spread from the original location, circulate in the bloodstream, extravasate, and metastasize, forming secondary tumors by invading and establishing a favorable environment. CTC analysis is considered a common liquid biopsy method for lung cancer. We have enumerated both in vivo and ex vivo techniques for CTC separation and enrichment, examined the advantages and limitations of these methods, and also discussed the detection of CTCs in other bodily fluids. We have evaluated the value of CTCs, as well as CTCs in conjunction with other biomarkers, for their utility in the early detection and prognostic assessment of patients with lung cancer. CTCs engage with diverse cells of the metastatic process, interfering with the interaction between CTCs and various cells in metastasis, potentially halting metastasis and enhancing patient prognosis.

In Situ Immunofluorescence Imaging of Vital Human Pancreatic Tissue Using Fiber-Optic Microscopy.

Surgical resection is the only curative option for pancreatic carcinoma, but disease-free and overall survival times after surgery are limited due to early tumor recurrence, most often originating from local microscopic tumor residues (R1 resection). The intraoperative identification of microscopic tumor residues within the resection margin in situ could improve surgical performance. The aim of this study was to evaluate the effectiveness of fiber-optic microscopy for detecting microscopic residues in vital pancreatic cancer tissues. Experimental Design. Fresh whole-mount human pancreatic tissues, histological tissue slides, cell culture, and chorioallantoic membrane xenografts were analyzed. Specimens were stained with selected fluorophore-conjugated antibodies and studied using conventional wide-field and self-designed multicolor fiber-optic fluorescence microscopy instruments. Whole-mount vital human tissues and xenografts were stained and imaged using an in situ immunofluorescence protocol. Fiber-optic microscopy enabled the detection of epitope-based fluorescence in vital whole-mount tissue using fluorophore-conjugated antibodies and enabled visualization of microvascular, epithelial, and malignant tumor cells. Among the selected antigen-antibody pairs, antibody clones WM59, AY13, and 9C4 were the most promising for fiber-optic imaging in human tissue samples and for endothelial, tumor and epithelial cell detection. Fresh dissected whole-mount tissue can be stained using direct exposure to selected antibody clones. Several antibody clones were identified that provided excellent immunofluorescence imaging of labeled structures, such as endothelial, epithelial, or EGFR-expressing cells. The combination of in situ immunofluorescence staining and fiber-optic microscopy visualizes structures in vital tissues and could be proposed as an useful tool for the in situ identification of residual tumor mass in patients with a high operative risk for incomplete resection.

Electrochemical detection of tumor cells based on proximity labelling-assisted multiple signal amplification

Electrochemical detection of tumor cells based on proximity labelling-assisted multiple signal amplification

Development of therapeutic monoclonal antibodies against DKK1 peptide-HLA-A2 complex to treat human cancers

BackgroundTargeted immunotherapy with monoclonal antibodies (mAbs) is an effective and safe method for the treatment of malignancies. Development of mAbs with improved cytotoxicity, targeting new and known tumor-associated antigens, therefore...

A Low-Cost Microstrip Patch Antenna Based Metamaterials for Non-Invasive Breast Tumor Detection

Microstrip patch antennas have been used extensively in broadband telecommunication applications. Despite their countless promises, their narrow bandwidth and the loss at high-frequency bands have limited their usage in medical applications. The purpose of this work is to design a patch antenna sensor that is a low-cost microstrip sensor which is suitable for biomedical application to detect a breast cancer tumor. The proposed antenna sensor is comprised of three layers namely ground, substrate and microstrip patch sensor that can be easily fabricated by using standard printed circuit board technique. The comparison study between two resonance frequency at 1.8 GHz and 2.9 GHz has been performed and investigated by especially accurate simulation with the presence and absence of tumor cell. Results obtained using computer simulation technology CST Studio Suite 3D EM simulation and analysis software indicates that the design can detect tumor by using phase shift detection and depth of the return loss. The result shows that the antenna return loss is getting lower in -39 dB at 1.8 GHz and -12 dB at 2.9 GHz and the phase shift detected with the presence of the tumor cell. Specific absorption rate has been also calculated (0.746 and 0.934 W/kg) and found to be in acceptable range and not exceed the standard value of &lt;1.6 W/kg, which mean that the patch sensor is compatible for human and biomedical application. The breast phantom models without/with a tumor have been numerically simulated by using the antenna operating as a transceiver for the detection of cancer tumor cells. Two parameters have been observed, the frequency phase shift and the deep amount of reflection return loss. In summary, this study concludes that a lower frequency band will result in higher penetration depth but a lower resolution. Meanwhile, higher frequency band will provide a better resolution, but the penetration depth will be lesser as seen in the comparison study between 1.8 GHz and 2.9 GHz. The proposed work could provide a pathway on the design of electromagnetic sensors for biomedical applications.