Structure-Based Discovery of High-Affinity Small Molecule Ligands and Development of Tool Probes to Study the Role of Chitinase-3-Like Protein 1.

Chitinase-3-like-1 (CHI3L1), also known as YKL-40, is a glycoprotein linked to inflammation, fibrosis, and cancer. This study explored CHI3L1's interactions with various oligosaccharides using microscale thermophoresis (MST) and AlphaScreen (AS). These investigations guided the development of high-throughput screening assays to assess interference of small molecules in binding between CHI3L1 and biotinylated small molecules or heparan sulfate-based probes.

Trends in Systemic Inflammatory Reaction (SIR) during Paclitaxel and Carboplatin Chemotherapy in Women Suffering from Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy treated with cytoreductive surgery followed by adjuvant taxane-platinum-based chemotherapy. It has been shown that the pretreatment systemic inflammatory reaction (SIR) in women with OC can be evaluated using the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII), depending on the stage of disease, and has prognostic value for overall survival. The aim of this study was to evaluate the changes in NLR, LMR, PLR and SII during chemotherapy.

The Direct and Indirect Costs of Breast Cancer in Poland: Estimates for 2017-2019.

Background: In Poland, breast cancer (BC) is the most frequently diagnosed cancer in women and the second most common cause of death after lung cancer. This disease has important economic implications for patients, public payers, and the whole Polish economy. This study aimed to estimate the total National Health Fund (NHF) expenditures on the diagnosis and treatment of patients with breast cancer.

Trends in Incidence and Mortality of Gynecological and Breast Cancers in Poland (1980-2018).

Background: This study aimed to analyze and determine the incidence and mortality trends in gynecological and breast cancers (BCs) in Poland. The gynecological cancers assessed were cervical cancer (CC), corpus uteri cancer (CUC), ovarian cancer (OC), vaginal cancer (VAC), and vulvar cancer (VUC).

Patients And Methods: Data concerning the incidence and mortality for the period of 1980-2018 were obtained from the Polish National Cancer Registry (PNCR).

Role of Systemic Inflammatory Reaction in Female Genital Organ Malignancies - State of the Art.

Systemic inflammatory reaction (SIR) is an unfavorable prognostic factor in many malignancies and has a role in all stages of the neoplastic process: initiation, promotion, and disease progression. Analysis of SIR can be performed by assessing indicators (eg, lymphocyte-to-neutrophil, platelet-to-lymphocyte, and monocyte-to-neutrophil ratios) and products of neutrophils and lymphocytes (ie, the systemic immune-inflammation index), or by examining the relationship between levels of C-reactive protein and albumin (based on the Glasgow Prognostic Score, modified Glasgow Prognostic Score, and C-reactive protein-to-albumin ratio). Risk stratification is essential in the clinical management of cancer; hence, the evaluation of these factors has potential applications in the clinical management of patients with cancer and in the development of new therapeutic targets.

Discovery of , a First-in-Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis.

Chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are the enzymatically active chitinases that have been implicated in the pathology of chronic lung diseases such as asthma and interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis. The clinical and preclinical data suggest that pharmacological inhibition of CHIT1 might represent a novel therapeutic approach in IPF. Structural modification of an advanced lead molecule led to the identification of compound (, a highly active CHIT1 inhibitor with both an excellent PK profile in multiple species and selectivity against a panel of other off-targets.

Benzoxazepine-Derived Selective, Orally Bioavailable Inhibitor of Human Acidic Mammalian Chitinase.

Human acidic mammalian chitinase (hAMCase) is one of two true chitinases in humans, the function of which remains elusive. In addition to the defense against highly antigenic chitin and chitin-containing pathogens in the gastric and intestinal contents, AMCase has been implicated in asthma, allergic inflammation, and ocular pathologies. Potent and selective small-molecule inhibitors of this enzyme have not been identified to date.

Development of Dual Chitinase Inhibitors as Potential New Treatment for Respiratory System Diseases.

Acidic mammalian chitinase (AMCase) and chitotriosidase-1 (CHIT1) are two enzymatically active proteins produced by mammals capable of cleaving the glycosidic bond in chitin. Based on the clinical findings and animal model studies, involvement of chitinases has been suggested in several respiratory system diseases including asthma, COPD, and idiopathic pulmonary fibrosis. Exploration of structure-activity relationships within the series of 1-(3-amino-1-1,2,4-triazol-5-yl)-piperidin-4-amines, which was earlier identified as a scaffold of potent AMCase inhibitors, led us to discover highly active dual (i.

Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion.

Objectives: Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone.

Material And Methods: The retrospective review of 6 consecutive SNMM (nasal cavity - 4 pts.

Discovery of selective, orally bioavailable inhibitor of mouse chitotriosidase.

This article describes our work towards the identification of a potent and selective inhibitor of mouse chitotriosidase (mCHIT1). A series of small molecule inhibitors of mCHIT1 and mAMCase have been developed from early lead compound 1. Examination of synthetized analogues led to discovery of several novel highly potent compounds.

Methods and results of local treatment of brain metastases in patients with breast cancer.

This article presents methods and results of surgical treatment and radiation therapy of brain metastases in breast cancer patients (brain metastases from breast cancer BMF-BC). Based on the literature data, it was shown that patients with single BMF-BC, aged less than 65 years, with Karnofsky score (KPS) of 70 or more and with cured or controlled extracranial disease are the best candidates to surgical treatment. Irrespective of the extracranial disease control status, there are indications for surgery in patients with symptomatic mass effect (tumour diameter larger than 3 cm) and patients with obstructive hydrocephalus from their BMF-BC.

Role of irradiation in combined treatment of head and neck paragangliomas at the Centre of Oncology in Krakow between 1970-2005.

Aim Of The Study: Aim of the study is to evaluate the results of postoperative radiotherapy of paragangliomas, prognostic factors and causes of treatment failure.

Material And Methods: Forty-four patients (39 females and 5 males) aged 20 to 74 years were treated for paraganglioma between 1970 and 2010 at the Centre of Oncology in Kraków. Patient survival probability was estimated with the Kaplan-Meier method.

Preliminary results of proton radiotherapy for choroidal melanoma - the Kraków experience.

Aim Of The Study: The objective of the study was to present the preliminary results of proton radiotherapy as a method for treating 15 patients with choroidal melanoma.

Material And Methods: The proton radiotherapy was administered using beams providing energy levels of 60 MeV, which ensures a clinical range of 28.4 mm.

[Proton beam radiotherapy of uveal melanoma--preliminary results].

Purpose: Presentation of the proton beam radiotherapy (PBR) as a method of treatment of the uveal melanoma patients in the Department of Ophthalmology and Ocular Oncology and Nuclear Physics Institute in Cracow, Poland and their preliminary results.

Material And Methods: Nine patients with only choroidal melanoma were treated using PBR between January and April 2011. There were 4 women (44%) and 5 men (56%), a mean age 56 years (38-72).

Postoperative irradiation of incompletely excised gemistocytic astrocytomas. Clinical outcome and prognostic factors.

Background And Purpose: Although gemistocytic astrocytomas are considered slow-growing tumors, they often behave aggressively and carry the least favorable prognosis among low-grade astrocytomas. The aim of this study is to evaluate the outcomes and prognostic factors of patients with incompletely excised gemistocytic astrocytomas irradiated postoperatively.

Patients And Methods: Records of 48 patients with incompletely excised gemistocytic astrocytoma, irradiated between 1976 and 1998 at the Department of Radiation Oncology, Maria Skłodowska-Curie Memorial Cancer Center, Cracow, Poland, were reviewed.