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A RAGE-Targeted Antibody-Drug Conjugate: Surface Plasmon Resonance as a Platform for Accelerating Effective ADC Design and Development
摘要： Antibodies, antibody-like molecules, and therapeutics incorporating antibodies as a targeting moiety, such as antibody-drug conjugates, offer significant potential for the development of highly efficacious drugs against a wide range of disorders. Despite some success, truly harnessing the superior targeting properties of these molecules requires a platform from which to effectively identify the best candidates for drug development. To streamline the development of antibody-drug conjugates targeting gynecological cancers within our laboratory, we incorporated surface plasmon resonance analysis (Biacore? T200) into our development toolkit. Antibodies, selected based on positive ELISA screens as suitable for development as antibody-drug conjugates, were evaluated using surface plasmon resonance to determine a wide range of characteristics including specificity, kinetics/affinity, the effect of linker binding, the impact of the drug to antibody ratio, and the effect of endosomal pH on antibody-antigen binding. Analysis revealed important kinetics data and information regarding the effect of conjugation and endosomal pH on our antibody candidates that correlated with cell toxicity and antibody internalization data. As well as explaining observations from cell-based assays regarding antibody-drug conjugate efficacies, these data also provide important information regarding intelligent antibody selection and antibody-drug conjugate design. This study demonstrates the application of surface plasmon resonance technology as a platform, where detailed information can be obtained, supporting the requirements for rapid and high-throughput screening that will enable enhanced antibody-drug conjugate development.
关键词： antibodies,antibody-drug conjugates,gynecological cancers,binding kinetics,surface plasmon resonance
更新于2025-11-21 11:08:12
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D30Angiogenesis evaluation in locally advanced colo-rectal and gastric cancers by probe-based Confocal Laser Endomicroscopy (pCLE)
摘要： Probe-based Confocal Laser Endomicroscopy ( pCLE) is an innovative endoscopic technique that allows taking high resolution images of the mucosa, facilitating the identification of cellular and subcellular microstructures permitting an evaluation of the microvasculature during endoscopic examination. Angiogenesis is a hallmark of cancer development inducing the formation of new vasculature to support its growth. The aim of our study was to evaluate tumor neoangiogenesis through pCLE imaging in locally advanced gastric and rectal cancer patients, before and after neoadjuvant radio-chemotherapy (RT/CT). Methods: 74 consecutive patients affected by Rectal Cancer (RC, 19F, 55 M mean age: 65 years) and 28 consecutive patients with Gastric Cancer (GC, 7F, 21 M mean age: 64 years) underwent endoscopy with pCLE-GastroFlex UHD probe (Mauna Kea Technologies) and i.v. fluorescein infusion in order to evaluate intratumoral vascularization and to evaluate the efficiency of blood flow. After RT/CT treatment, 33 RC (27M, 6F) and 7 GC (2F, 5M) patients were revaluated using pCLE; neoangiogenesis was evaluated according to Cannizzaro-Spessotto (CS) scale, assigning one point to each of the following features: tortuous vessels, large vessels, leakage and defective flux. Results: 22 out of 35 (62.8%) RC and 4 out of 9 (44,4%) GC patients showed an improvement of angiogenesis index, while in the remaining 13 RC (39.4%) and 5 GC (71.4%) there were no changes of the vascular architecture following the treatment. There was a significant difference ( p < 0.05) in neoangiogenesis CS scores between RC pre- (median CS score: 2.7) and post-RT/CT (median CS score: 1.6), while there’s no difference ( p > 0.05) between GC patients pre- (median CS score: 2.6) and post-therapy (median CS score: 2.0). Our data show a better reactivation of vessels’ morphology and functions in RC patients, with an improvement of angiogenesis index. In GC patients median angiogenesis index remained unmodified, without positive changes in vascular morphology, probably due to the presence of fibrosis. Conclusions: The results of our work demonstrate that pCLE technique is suitable to evaluate the alterations of the intratumoral microvasculature and reveal a functional improvement of vasculature in post-therapy RC patients. It may constitute a innovative approach in order to identify subjects that respond to the therapy, improving the outcome of the patients.
关键词： Cannizzaro-Spessotto (CS) scale,angiogenesis,probe-based Confocal Laser Endomicroscopy ( pCLE),neoadjuvant radio-chemotherapy (RT/CT),gastrointestinal (colorectal) cancers
更新于2025-09-23 15:19:57
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IGCS Intraoperative Technology Taskforce. Update on near infrared imaging technology: beyond white light and the naked eye, indocyanine green and near infrared technology in the treatment of gynecologic cancers
摘要： Surgery, by its very nature, relies on the ability of the surgeon to visualize and distinguish healthy and non-healthy tissue or structures. Without advanced technology, surgeons can visualize only that which can be seen with the naked eye or using white light imaging. Critical information on tissues, anatomical structures and physiological processes remain hidden and difficult to discern. Fluorescence imaging augments the basic surgical information. This form of imaging entails injecting a contrast or fluorescence agent (fluorophore) that is then illuminated by the appropriate wavelength of light required to excite the fluorophore. The excited fluorophore emits light of a slightly longer wavelength that is selectively imaged to produce a fluorescence image. The first fluorescent agent used in surgery was an intravenous injection of fluorescein, where it was used to enhance intracranial neoplasms. One particular imaging agent, indocyanine green, has been a significant driver of adoption of fluorescence imaging. Indocyanine green was first developed in 1955 by Kodak Research Laboratories and was approved by the Food and Drug Administration (FDA) in 1959 for retinal angiography. Since that time, this fluorophore has been used for a variety of surgical applications due to its unique properties: relative non-toxicity, depth of visualization through tissue, and remaining confined to intravascular and lymphatic spaces due to binding predominately to lipoproteins. The large depth of visualization results from the fluorescence properties of bound indocyanine green which is optimally excited with 805 nm light and emits over an approximate wavelength range from 810 nm to 875 nm. These near infrared wavelengths, invisible to the naked eye, pass through tissue particularly well due to the low adsorption of light by the various structures of tissue, such as hemoglobin and water. As a result, the tissue is relatively transparent to this light and images of structures as much as 5 mm below the tissue surface can be formed. By comparison, fluorescence imaging with fluorescein images only 2–3 mm below the tissue surface; thus subsurface structures cannot be imaged using visible fluorophores.
关键词： gynecologic cancers,fluorescence imaging,indocyanine green,near infrared imaging,surgical technology
更新于2025-09-23 15:19:57
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Insight into the efficiency of oxygen introduced photodynamic therapy (PDT) and deep PDT against cancers with various assembled nanocarriers
摘要： Photodynamic therapy (PDT) has been used in the treatment of cancers and other benign diseases for several years in clinic. However, the hypoxia of tumors and the penetration limitation of excitation light to tissues can dramatically reduce the efficacy of PDT to cancers. To overcome these drawbacks, various assembled nanocarriers such as nanoparticles, nanocapsules, nanocrystals, and so on were introduced. The assembled nanocarriers have the ability of loading photosensitizers, delivering O2 into tumors, generating O2 in situ in tumors, as well as turning near-infrared (NIR) light, X-rays, and chemical energy into ultraviolet or visible light. Therefore, it is easy for the nanocarriers to improve the hypoxia microenvironment or increase the treatment depth of cancers, which will improve the efficiency of PDT to some degree. In recent years, a number of investigations were focused on these subjects. We will summarize the advances of nanocarriers in PDT, especially in O2 introduction PDT and deep PDT. The perspectives, challenges, and potential in translation of PDT will also be discussed.
关键词： Oxygen introduction,Photodynamic therapy (PDT),Cancers,Nanocarriers,Deep PDT
更新于2025-09-19 17:13:59
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Multiple Squamous Neoplasms Arising in a Red Tattoo After Laser Tattoo Removal
摘要： Tattoos are common around the world, although not without risk. Tattooing may result in several complications, including infections, foreign-body and sarcoidal granulomatous reactions, delayed-type hypersensitivity reactions, keloid formation, pseudolymphomas, pseudoepitheliomatous hyperplasia, as well as koebnerization and pathergy of associated pre-existing skin diseases. Tattoos may even potentiate cutaneous neoplasms including benign growths, such as seborrheic keratoses, and malignant neoplasms, such as nonmelanoma skin cancers (NMSCs) and malignant melanoma. Although the mechanism underlying neoplasia due to tattoos is poorly understood, it has been suggested that trauma from the procedure itself, the carcinogenic potential of the dyes, or chronic inflammation could play a role. In this study, we present a case of multiple NMSCs developing within the red pigmented area of a tattoo after repeated laser tattoo removal treatments.
关键词： squamous neoplasms,nonmelanoma skin cancers,red tattoo,laser tattoo removal,tattoo
更新于2025-09-12 10:27:22
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Genitourinary syndrome of menopause (GSM) and laser VEL: a review
摘要： The purposeof this publication is to summarize the results of the vaginal erbium:yttrium-aluminum-garnet (Er:YAG) Smooth? laser (VEL) on the vaginal atrophy component of the genitourinary syndrome of menopause (GSM). GSM has two categories of clinical signs related to estrogen deficiency: symptoms of vulvovaginal atrophy (VVA) and urinary symptoms. This symptomatology is chronic, progressive over the years and affects a majority of women concerned by natural menopause but not exclusively: we must also consider the growing number of survivors of gynecological or non-gynecological cancers (breast, cervix, uterus, vagina, anus, etc.). At a time when hormonal treatment of menopause is contested as is the installation of under urethra prosthesis, the innovation provided by the VEL technology has the merit of offering the women concerned an effective therapeutic alternative with the security of a patent. The VEL technology has an original and unique process: acting only by thermal effect and not by ablation on tissue, VEL is a safe solution in terms of side effects and potential complications. Studies have been increasing since 2012 and all demonstrate a significant improvement in the GSM signs and symptoms, as well as an improved sexual life after VEL treatment. Double-blind, placebo-controlled, randomized studies are expected in order to ultimately confirm the safety and effectiveness of VEL.
关键词： dyspareunia,genitourinary syndrome of menopause,gynecological cancers,collagen,vaginal atrophy,menopause,laser erbium Smooth?
更新于2025-09-12 10:27:22
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Liquid Crystals: A Novel Approach for Cancer Detection and Treatment
摘要： Liquid crystals are defined as the fourth state of matter forming between solid and liquid states. Earlier the applications of liquid crystals were confined to electronic instruments, but recent research findings suggest multiple applications of liquid crystals in biology and medicine. Here, the purpose of this review article is to discuss the potential biological impacts of liquid crystals in the diagnosis and prognosis of cancer along with the risk assessment. In this review, we also discussed the recent advances of liquid crystals in cancer biomarker detection and treatment in multiple cell line models. Cases reviewed here will demonstrate that cancer diagnostics based on the multidisciplinary technology and intriguingly utilization of liquid crystals may become an alternative to regular cancer detection methodologies. Additionally, we discussed the formidable challenges and problems in applying liquid crystal technologies. Solving these problems will require great effort and the way forward is through the multidisciplinary collaboration of physicists, biologists, chemists, material-scientists, clinicians, and engineers. The triumphant outcome of these liquid crystals and their applications in cancer research would be convenient testing for the detection of cancer and may result in treating the cancer patients non-invasively.
关键词： biosensor,biomarker,antitumor drug,liquid crystals,cancers
更新于2025-09-10 09:29:36