scholarly journals IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1140
Author(s):  
Toshio Fujisawa ◽  
Bharat H. Joshi ◽  
Sho Takahashi ◽  
Yusuke Takasaki ◽  
Akinori Suzuki ◽  
...  

IL-13Rα2 is a high-affinity binding protein for its ligand IL-13 and a cancer-testis antigen as it is expressed in the testis. IL-13Rα2 is highly expressed in various cancers, including pancreatic cancer, and consists of three domains: extracellular, transmembrane, and cytoplasmic. The extracellular domain binds to the ligand to form a biologically active complex, which initiates signaling through AP-1 and other pathways. IL-13Rα2 is also expressed in diseased cells such as fibroblasts that are involved in various inflammatory diseases, including cancer. We have reported that IL-13Rα2 is a prognostic biomarker for malignant glioma, adrenocortical cancer, and pancreatic cancer. In pancreatic cancer, a small sample of tissue could be examined for the expression of IL-13Rα2 by using the endoscopic ultrasound-fine needle aspiration technique (EUS-FNA). In addition, a peptide-based targeted approach using Pep-1L peptide could be used to study the biodistribution and whole-body cancer imaging for the screening of pancreatic cancer in suspected subjects.

2015 ◽  
Vol 112 (52) ◽  
pp. 15850-15855 ◽  
Author(s):  
Jacob L. Houghton ◽  
Brian M. Zeglis ◽  
Dalya Abdel-Atti ◽  
Robert Aggeler ◽  
Ritsuko Sawada ◽  
...  

Molecular imaging agents for preoperative positron emission tomography (PET) and near-infrared fluorescent (NIRF)-guided delineation of surgical margins could greatly enhance the diagnosis, staging, and resection of pancreatic cancer. PET and NIRF optical imaging offer complementary clinical applications, enabling the noninvasive whole-body imaging to localize disease and identification of tumor margins during surgery, respectively. We report the development of PET, NIRF, and dual-modal (PET/NIRF) imaging agents, using 5B1, a fully human monoclonal antibody that targets CA19.9, a well-established pancreatic cancer biomarker. Desferrioxamine (DFO) and/or a NIRF dye (FL) were conjugated to the heavy-chain glycans of 5B1, using a robust and reproducible site-specific (ss) labeling methodology to generate three constructs (ssDFO-5B1, ssFL-5B1, and ssdual-5B1) in which the immunoreactivity was not affected by the conjugation of either label. Each construct was evaluated in a s.c. xenograft model, using CA19.9-positive (BxPC3) and -negative (MIAPaCa-2) human pancreatic cancer cell lines. Each construct showed exceptional uptake and contrast in antigen-positive tumors with negligible nonspecific uptake in antigen-negative tumors. Additionally, the dual-modal construct was evaluated in an orthotopic murine pancreatic cancer model, using the human pancreatic cancer cell line, Suit-2. The ssdual-5B1 demonstrated a remarkable capacity to delineate metastases and to map the sentinel lymph nodes via tandem PET-computed tomography (PET/CT) and NIRF imaging. Fluorescence microscopy, histopathology, and autoradiography were performed on representative sections of excised tumors to visualize the distribution of the constructs within the tumors. These imaging tools have tremendous potential for further preclinical research and for clinical translation.


2018 ◽  
Vol 22 (2) ◽  
pp. 297-300
Author(s):  
V.V. Nevmerzhitsky ◽  
V.Yu. Ivannik ◽  
V.V. Kazmirchuk ◽  
T.N. Moiseenko ◽  
T.A. Volkov ◽  
...  

The fight against staphylococcal infection, increasing the effectiveness of methods of prevention and treatment of diseases of staphylococcal etiology is of interest to scientists and practitioners, both in Ukraine and around the world. The urgency of this problem is growing rapidly, as there is a tendency to increase the resistance of not only staphylococci, but also other gram-positive bacteria. The spread of methicillin-resistant staphylococci restricts the choice of antibiotics for the treatment of diseases of staphylococcal etiology. Staphylococcus aureus is the most common and dangerous type, which is one of the main factors of purulent-inflammatory lesions of the skin and mucous membranes. As a result of mutations, pathogenic staphylococci acquired resistance to antibacterial drugs. The main disadvantage of modern antibiotics is their non-selectivity. As a result of mutations, pathogenic staphylococci acquired resistance to antibacterial drugs. The main disadvantage of modern antibiotics is their non-selectivity. One of the unique and promising medicinal plants, which contains a rich complex of biologically active substances (BAS), is common hops (Humulus lupulus L.). The complex of BAS (flavonoids, hormones, vitamins, bitter, phenolic compounds, essential oils) causes anti-inflammatory, bactericidal, hyposensitizing and analgesic action of hops. The purpose of this work is to determine the antistaphylococcal activity of the carbon dioxide extract of hops and to justify the development on its basis of new antimicrobial agents for the prevention and treatment of infectious and purulent-inflammatory diseases. The following methods were used: microbiological (method of diffusion into agar (well method)) and mathematical and statistical. The high antimicrobial activity of the carbon dioxide extract of hops has been established for museum test strains of the genus Staphylococcus. The results of the studies testify to the prospects of further study of the bactericidal properties of the extract of hops carbon dioxide with the aim of creating effective antimicrobial agents on its basis for the prevention and treatment of infectious and purulent-inflammatory diseases of staphylococcal etiology.


2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  

2020 ◽  
Vol 14 (2) ◽  
pp. 436-442
Author(s):  
Jun Heo

Although infected pancreatic necrosis can develop as a result of rare conditions involving trauma, surgery, and systemic infection with an uncommon pathogen, it usually occurs as a complication of pancreatitis. Early phase of acute pancreatitis can be either edematous interstitial pancreatitis or necrotizing pancreatitis. The late complications of pancreatitis can be divided into pancreatic pseudocyst due to edematous interstitial pancreatitis or walled-off necrosis due to necrotizing pancreatitis. During any time course of pancreatitis, bacteremia can provoke infection inside or outside the pancreas. The patients with infected pancreatic necrosis may have fever, chills, and abdominal pain as inflammatory symptoms. These specific clinical presentations can differentiate infected pancreatic necrosis from other pancreatic diseases. Herein, I report an atypical case of infected pancreatic necrosis in which abdominal pain, elevation of white blood cell, and fever were not found at the time of admission. Rather, a 10-kg weight loss (from 81 to 71 kg) over 2 months nearly led to a misdiagnosis of pancreatic cancer. The patient was finally diagnosed based on endoscopic ultrasound-guided fine-needle aspiration. This case highlights that awareness of the natural course of pancreatitis and infected pancreatic necrosis is important. In addition, endoscopic ultrasound-guided fine-needle aspiration should be recommended for the diagnosis and treatment of indeterminate pancreatic lesions in selected patients.


Antibodies ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 20
Author(s):  
Iftekhar Mahmood

Antibody-drug conjugates (ADCs) are biopharmaceutical products where a monoclonal antibody is linked to a biologically active drug (a small molecule) forming a conjugate. Since the approval of first ADC (Gemtuzumab ozogamicin (trade name: Mylotarg)) for the treatment of CD33-positive acute myelogenous leukemia, several ADCs have been developed for the treatment of cancer. The goal of an ADC as a cancer agent is to release the cytotoxic drug to kill the tumor cells without harming the normal or healthy cells. With time, it is being realized that ADCS can also be used to manage or cure other diseases such as inflammatory diseases, atherosclerosis, and bacteremia and some research in this direction is ongoing. The focus of this review is on the clinical pharmacology aspects of ADC development. From the selection of an appropriate antibody to the finished product, the entire process of the development of an ADC is a difficult and challenging task. Clinical pharmacology is one of the most important tools of drug development since this tool helps in finding the optimum dose of a product, thus preserving the safety and efficacy of the product in a patient population. Unlike other small or large molecules where only one moiety and/or metabolite(s) is generally measured for the pharmacokinetic profiling, there are several moieties that need to be measured for characterizing the PK profiles of an ADC. Therefore, knowledge and understanding of clinical pharmacology of ADCs is vital for the selection of a safe and efficacious dose in a patient population.


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