Development of the Inhibitors that Target the PD-1/PD-L1 Interaction-A Brief Look at Progress on Small Molecules, Peptides and Macrocycles.

Cancer immunotherapy based on antibodies targeting the immune checkpoint PD-1/PD-L1 pathway has seen unprecedented clinical responses and constitutes the new paradigm in cancer therapy. The antibody-based immunotherapies have several limitations such as high production cost of the antibodies or their long half-life. Small-molecule inhibitors of the PD-1/PD-L1 interaction have been highly anticipated as a promising alternative or complementary therapeutic to the monoclonal antibodies (mAbs). Currently, the field of developing anti-PD-1/PD-L1 small-molecule inhibitors is intensively explored. In this paper, we review anti-PD-1/PD-L1 small-molecule and peptide-based inhibitors and discuss recent structural and preclinical/clinical aspects of their development. Discovery of the therapeutics based on small-molecule inhibitors of the PD-1/PD-L1 interaction represents a promising but challenging perspective in cancer treatment.

Causes of delays in breast cancer diagnosis in Poland.

Breast cancer is the most common malignant tumor in women. The results of breast cancer treatment to a large extent depend on the time of the primary diagnosis of the disease. AIM: The aim of this study was to determine the most common causes of the delay and the delay time in the diagnosis of breast cancer in Polish women. MATERIALS AND METHODS: The study was performed using a diagnostic survey and analysis of medical documentation from the Subcarpathian Regional Oncology Center, Poland. A total of 231 patients with diagnosed breast cancer were recruited to the study. RESULTS: Delays in diagnosing of breast cancer were found in 83.1% of all the patients. The average time from the first symptom observation by a woman to the first medical consultation was on average 61.7 days. The most common cause of the delay in medical consultation in the examined group was a fear of diagnosing cancer (31.2%). CONCLUSIONS: The examined women require permanent health education in the field of breast cancer and the importance of early diagnosis of the disease for the effectiveness of treatment and prognosis.

The Slowly Enlarging Ventriculus Terminalis.

BACKGROUND: A cerebral spinal fluid (CSF) cavity within the conus medullaris has been described by the term ventriculus terminalis (VT) or the fifth ventricle. The finding of a VT on MRI imaging of the lumbar spine is often incidental but may be found in patients with low back pain or neuromuscular deficits. These lesions, when identified, are thought to regress or remain stable in terms of size, although some have been described to enlarge in the presence of post-traumatic meningeal hemorrhages or deformities of the vertebral canal. CASE REPORT: We describe a case of a slowly growing VT in a patient with progressing lower limb weakness without any history or imaging findings of trauma or spinal canal abnormalities. CONCLUSIONS: We present an intriguing case of a slowly growing VT in a woman with progressive neurological symptoms. Surgical fenestration provided complete symptomatic relief and follow-up imaging two years after surgery demonstrated no evidence of recurrence. This, to our knowledge, is the first described case of a slowly enlarging VT independent of any other imaging findings.

The Influence of the Surgical Treatment Method on the Quality of Life of Women With Breast Cancer.

Objective: Breast cancer is the most common malignant neoplasm among women in Poland. The primary treatment for breast cancer is surgery. The choice of surgical treatment method can significantly affect the quality of life of women with breast cancer. Materials and Methods: Women treated surgically because of breast cancer were included. The quality of life was assessed by survey using the quality of live questionnaire (QLQ)-C30 and QLQ-BR23 (European Organization for the Research and Treatment of Cancer) questionnaires, taking into account the following factors: The method of surgery performed and comparing breast conserving therapy (BCT) with mastectomy, and breast reconstruction or the lack of it. Results: The study included 243 subjects. Women had a reduced overall quality of life (53.88 points out of 100), in particular emotional (59.77) and sexual (17.49) functioning, and a poor body image assessment (61.57). Patients after BCT functioned better in physical (p = 0.001) and sexual (p = 0.007) terms, and also experienced lower pain intensity (p = 0.003) and shoulder discomfort (p = 0.024). The quality of life was significantly higher (p = 0.003) in the opinion of women who underwent breast reconstructive surgery. Conclusion: The quality of life of women depends on the surgical treatment method used when treating breast cancer. For this reason, the choice of method, whenever possible, should promote breast protection or its postoperative reconstruction.

Patient satisfaction with oncological care during the virus pandemic - SARS-CoV-2 taking into account social and demographic factors.

INTRODUCTION AND OBJECTIVE: The aim of the study was to examine the perception of medical services by oncological patients during the pandemic, identifying the key factors influencing it. The assessment of patient satisfaction with the treatment and care provided by doctors and other hospital staff provides important information on the quality of health services. MATERIAL AND METHODS: The study involved 394 patients diagnosed with cancer treated as inpatients in five oncology departments. The diagnostic survey method was used with a proprietary questionnaire and the standardized EORTC IN-PATSAT32 questionnaire. Calculations were carried out using Statistica 10.0 with p≤0.05 s considered statistically significant. RESULTS: Overall patient satisfaction with cancer care was 80.77/100. Higher values were shown for the competences of nurses than for doctors, especially for their interpersonal skills (79.34 - nurses vs. 74.13 - doctors) and availability (80.11 - nurses vs. 75.6 - doctors). It was also shown that the level of satisfaction with cancer care increased with age; women rated cancer care lower than men (p = 0.031), particularly its aspect related to the competences of doctors. A lower degree of satisfaction was observed among rural residents (p=0.042). Other demographic data, such as marital status and education, determined satisfaction with cancer care on the selected scale although it did not affect the overall level of satisfaction. CONCLUSIONS: The analysed socio-demographic factors, primarily age, gender and place of residence, determined some of the scales concerning patient satisfaction with cancer care during the COVID-19 pandemic. The results of this and other studies of a similar profile should be used in the formation of health policy, particularly in implementing programmes to improve the quality of cancer care in Poland.

Patient Satisfaction with Oncological Care during the SARS-CoV-2 Virus Pandemic.

Recently, the outbreak of the SARS-CoV-2 virus and the COVID-19 pandemic significantly affected the health situation of the entire society and necessitated reorganization of health care including oncology. The objective of this study was to examine the perception of medical services by cancer patients during the pandemic and to identify the key elements influencing the level of satisfaction with oncological care. Of note, 394 patients diagnosed with cancer treated in inpatient oncology wards participated in the study (Poland). The diagnostic survey method was used. A survey questionnaire developed by the authors was used and validated the EORTC IN-PATSAT32 questionnaire. The calculations were made in Statistica 10.0 (Statsoft; 2011, Dell Inc., Round Rock, TX, USA). The average general level of satisfaction with oncological care in the study group was 80.77 out of a total score of 100, representing the highest level of satisfaction. Levels of satisfaction varied according to time since diagnosis (longer time-greater satisfaction) and were lower where treatment was delayed or perceived as disorganised. Nearly half of the respondents felt the threat of the SARS-CoV-2 infection, despite the fact that most of them believed that the hospital was well prepared to diagnose and treat cancer patients during the COVID-19 pandemic. Convincing patients about the proper preparation of health care for diagnostics and therapy is an important element influencing patient satisfaction with oncological care.

Quality of Life of Women with Breast Cancer and Socio-Demographic Factors.

BACKGROUND: Breast cancer treatment is an aggressive therapy that affects the deterioration of women's quality of life (QOL) in many areas. Knowledge about factors that influence the assessment of the QOL is of particular importance. The aim of the study was to analyse areas of the quality of life of women with breast cancer, taking into account social and demographic factors. METHODS: The research was carried included 324 women with breast cancer. The research was carried out using a diagnostic survey, the author's questionnaire and a standardized questionnaire for measuring the QOL of women treated for breast cancer, ie the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC) QLQ-C30 and QLQ-QLQ module BR23. Statistical analysis uses Statistica 10.0 software. The results were considered statistically significant when the calculated probability met the inequality of p.

Impact of Time to Initiation of Treatment on the Quality of Life of Women with Breast Cancer.

INTRODUCTION: Breast cancer is the most common malignancy in women. Due to the large number of women living with breast cancer and the increasing incidence of this cancer, it is very important to understand the factors determining the quality of life (QOL) of patients. THE AIM OF THE STUDY: The aim of the study was to determine the impact of time to initiation of treatment on the quality of life of women with breast cancer. MATERIALS AND METHODS: The study involved 324 women with breast cancer, treated at the Podkarpackie Oncology Centre in Brzozów, Poland. The study was conducted using a diagnostic survey, using a standardised questionnaire to measure the quality of life of women treated for breast cancer, i.e., the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 and the QLQ-BR23 module, as well as a proprietary survey questionnaire. Statistical analysis was performed using the Statistica 10.0 software (StatSoft Inc., 2011). A p value of <0.05 was considered statistically significant. RESULTS: The examined women had a reduced overall quality of life and health (M = 53.88). The quality of life was higher in women who consulted a doctor the earliest after noticing initial symptoms of the disease, i.e., up to one week (M = 57.58), compared to patients who delayed the decision (over four weeks; M = 47.8) (p = 0.002). The quality of life was also considered higher by women who received treatment within two weeks of diagnosis (M = 56.79) and was lower for patients who waited for treatment for more than two months (M = 43.68). Statistically significant relationships were demonstrated for functional scales and disease intensity. CONCLUSIONS: Women diagnosed with breast cancer had a considerably lower overall quality of life. A relatively higher quality of life was experienced by patients who consulted a doctor the earliest after discovering symptoms of the disease and those whose waiting time for treatment was shorter. In a systematic manner, the individual stages of diagnosis should be maximally reduced and breast cancer treatment initiated without delay.

Di-bromo-Based Small-Molecule Inhibitors of the PD-1/PD-L1 Immune Checkpoint.

Immune checkpoint blockade is one of the most promising strategies of cancer immunotherapy. However, unlike classical targeted therapies, it is currently solely based on expensive monoclonal antibodies, which often inflict immune-related adverse events. Herein, we propose a novel small-molecule inhibitor targeted at the most clinically relevant immune checkpoint, PD-1/PD-L1. The compound is capable of disrupting the PD-1/PD-L1 complex by antagonizing PD-L1 and, therefore, restores activation of T cells similarly to the antibodies, while being cheap in production and possibly nonimmunogenic. The final compound is significantly smaller than others reported in the literature while being nontoxic to cells even at high concentrations. The scaffold was designed using a structure-activity relationship screening cascade based on a new antagonist-induced dissociation NMR assay, called the weak-AIDA-NMR. Weak-AIDA-NMR finds true inhibitors, as opposed to only binders to the target protein, in early steps of lead compound development, and this process makes it less time and cost consuming.

Acceptance of illness by women with breast cancer.

INTRODUCTION: Despite great progress in the diagnostics and treatment, breast cancer still remains the most frequently diagnosed malignant cancer in women. The outcomes of cancer treatment depend, to a considerable extent, on the degree of acceptance of the illness. The objective of the study was determination of the level of acceptance of the disease among the examined women with breast cancer. MATERIAL AND METHODS: The study covered a group of 231 women who received treatment for breast cancer in the Rev. Bronislaw Markiewicz Subcarpathian Oncology Centre in Brzozow, south-eastern Poland, and conducted by the method of a diagnostic survey, using an author constructed questionnaire and the standard Acceptance of Illness Scale, adapted by Z. Juczynski. Statistical analyses were performed using the software IBM SPSS v. 21.0.0.1. The p values p≤0.05 were considered statistically significant. RESULTS: The mean level of acceptance of the illness in the examined group of women was 26.53 (SD = 7.71; Me = 26). The largest number of respondents (50.6%) obtained scores within the range of 20-29, according to the AIS Scale. From among the adopted variables, the level of acceptance of the illness significantly varied according to age and occupational activity. However, no such differences were confirmed according to the place of residence, marital status, education level, or the type of occupation performed. CONCLUSIONS: In the examined group of women, a mediocre level of acceptance of cancer was observed. The respondents' age and occupational situation exerted a significant effect on the level of acceptance of the illness. The results of the study should be considered as satisfactory because the number of women with a high level of acceptance of breast cancer was more than twice as high as those ones with a low acceptance of the disease.

Surgical method of treatment and level of satisfaction with life among women diagnosed with breast cancer, according to time elapsed since performance of surgery.

INTRODUCTION: In women diagnosed with breast cancer one of the methods most commonly applied in therapy is surgical treatment, which consists in a breast conserving surgery or total removal of the breast. The applied type of surgical treatment may exert an effect on the satisfaction with life of the women. OBJECTIVE: The aim of the study was evaluation of the satisfaction with life among women surgically treated for breast cancer, according to the type of surgery on the breast, and the time elapsed since its performance. MATERIAL AND METHODS: The study included 121 patients of the Sub-Carpathian Oncology Centre in Brzozów, south-east Poland, who had undergone surgical treatment due to breast cancer. The women expressed their informed consent to participate in the study. The method of a diagnostic survey was applied. RESULTS: The women obtained a mediocre result in satisfaction with life - 5.64 sten scores. Patients who had undergone mastectomy had a considerably lower level of satisfaction with life, compared to those after breast-conserving surgery (4.73 sten scores vs. 6.30 sten scores). Evaluations of the satisfaction with life in the examined group significantly differed according to the time elapsed since performance of surgery. CONCLUSIONS: There is a need for undertaking actions directed to women who have undergone surgical treatment for breast cancer within the period from 2-5 years, aimed at improving the satisfaction with life in this group of patients. In addition, special support should be provided for women who have undergone mastectomy, especially during the period of more than 1 and up to 2 years.

Satisfaction with life among women with breast cancer - selected demographic and social factors.

OBJECTIVE: The aim of the study was evaluation of satisfaction with life among women ill with breast cancer, with consideration of selected demographic and social factors. MATERIAL AND METHODS: In the study participated 121 patients from the Sub-Carpathian Oncology Centre in Brzozów, Poland, who had undergone surgical treatment due to breast cancer. The method of a diagnostic survey was used. The research instruments were an author-constructed questionnaire and the Satisfaction with Life Scale. RESULTS: Women who received surgical treatment due to breast cancer evaluated their satisfaction with life on a mediocre level. Younger patients had a lower satisfaction with life than those who were older. Women living in urban areas evaluated their satisfaction with life in more positive terms than rural women. In turn, education level, marital status and material standard had no effect on the level of satisfaction with life among the women in the study. CONCLUSIONS: According to the SWLS, women with the diagnosis of breast cancer obtained a mean result of 5.64 sten scores Younger women evaluated their satisfaction with life in more positive terms than those who were older. Women who lived in urban areas obtained a considerably higher result according to the SWLS, compared to rural inhabitants. Marital status, education level, material standard and occupational activity of the women were insignificant in the respondents' evaluation of satisfaction with life.

Analysis of the Content of Chromium in Certain Parts of the Human Knee Joint.

Chromium is an essential microelement in the human body. It exerts an effect on bones by modulating their biochemical parameters: alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). With considerable accumulation of chromium in the skeleton, the activity of alkaline phosphatase was found to decrease, which affected bone formation rate. The study objective was to analyze chromium content in the knee tissues. Tissues for analysis were obtained during endoprosthesoplasty of the knee joint and included tibia, femur, and meniscus tissues. Samples were collected from 50 patients, including 36 women and 14 men. The analysis was performed using the inductively coupled plasma atomic emission spectroscopy (ICP-AES) method, by means of a Varian 710-ES apparatus. The results revealed no significant differences in the content of chromium in the knee joint tissues between women and men. The highest level of chromium was found in the femoral bone of the knee joint, then in the meniscus, and was lowest in the tibia, although the differences were statistically insignificant. Chromium content increased with age.

The Content of Structural and Trace Elements in the Knee Joint Tissues.

Many elements are responsible for the balance in bone tissue, including those which constitute a substantial proportion of bone mass, i.e., calcium, phosphorus and magnesium, as well as minor elements such as strontium. In addition, toxic elements acquired via occupational and environmental exposure, e.g., Pb, are included in the basic bone tissue composition. The study objective was to determine the content of strontium, lead, calcium, phosphorus, sodium and magnesium in chosen components of the knee joint, i.e., tibia, femur and meniscus. The levels of Sr, Pb, Ca, P, Na and Mg were the highest in the tibia in both men and women, whereas the lowest in the meniscus. It should be noted that the levels of these elements were by far higher in the tibia and femur as compared to the meniscus. In the components of the knee joint, the level of strontium showed the greatest variation. Significant statistical differences were found between men and women only in the content of lead.