Calcitriol promotes M2 polarization of tumor-associated macrophages in 4T1 mouse mammary gland cancer via the induction of proinflammatory cytokines.

Our research found that vitamin D3 (VD3) treatment increased lung metastasis in mice with 4T1 murine breast cancer (BC). This study aims to investigate the impact of VD3 on the activation of tumor-associated macrophages (TAMs) in BC. Mice bearing 4T1, E0771, 67NR BC cells, and healthy mice, were fed diets with varying VD3 contents (100-deficient, 1000-normal, and 5000 IU/kg-elevated). Some mice in the 1000 and 100 IU/kg groups received calcitriol. We studied bone metastasis and characterized TAMs and bone marrow-derived macrophages (BMDMs). 4T1 cells had higher bone metastasis potential in the 5000 IU/kg and calcitriol groups. In the same mice, an elevated tumor osteopontin level and M2 polarization of TAMs (MHCIIlow CD44high phenotype) were observed. Gene expression analysis confirmed M2 polarization of 4T1 (but not 67NR) TAMs and BMDMs, particularly in the 100 IU + cal group (increased Mrc1, Il23, and Il6). This polarization was likely due to COX-2/PGE2 induction in 4T1 calcitriol-treated cells, leading to increased proinflammatory cytokines like IL-6 and IL-23. Future studies will explore COX-2/PGE2 as a primary mediator of calcitriol-stimulated inflammation in the BC microenvironment, especially relevant for BC patients with VD3 deficiency and supplementation.

Incidence of different types of cancer in the follow-up period after primary diagnosis and treatment of melanoma. Single-centre 4-year follow-up on a population of 709 patients.

Introduction: Follow-up plays a key role in melanoma management, especially in the first years after diagnosis. During this period it is crucial to assess possible recurrence, progression of the disease or treatment complications. An important aspect is also the possibility of formation of new primary foci or other skin cancers. Aim: To assess the coincidence of skin lesions and cancers among the melanoma patients. Material and methods: Patients treated in the Comprehensive Cancer Centre between 2019 and 2022 were retrospectively analysed for occurrence of skin lesions diagnosed during the follow-up, and confirmed by biopsy. The lesions considered included skin cancers, dysplastic nevus and actinic keratosis. Results: In 100 (14%) out of 709 enrolled patients, 184 lesions were diagnosed. In 7 patients it was melanoma, in 49 BCC, and in 16 SCC. Dysplastic nevus and actinic keratosis were excised in 28 and 14 patients, respectively. More than one site of the skin lesion was observed in 39 patients, and more than one type of the lesion in 13 patients. Patients with lesions were on average 8.6 years older (p < 0.001), had less advanced tumours (p = 0.010), and primary melanoma was more often located on the head and neck (p = 0.056). Conclusions: Among melanoma patients, particular attention must be paid to, apart from early detection of melanoma recurrence and progression, the occurrence of new primary foci or independent skin cancers.

I Choose Health. It is OncoLogical!-Informative and Educational Campaign Dedicated to the High School Students in Poland.

Cancer is the second most common cause of death in Poland and the number of new cases is expected to increase by 28% over the next 10 years. Despite modifications and expenditure growth in the Polish health care system, oncological treatment outcomes are lower comparing to the other European Union countries. Early preventative interventions are effective in reducing the total number of cancers and improving early detection. OnkoLogika is an educational campaign launched in 2016 by the Comprehensive Cancer Centre, aimed at improving cancer awareness. One hundred and twenty students from 25 high schools of the Lower Silesia region in Poland participated in the OnkoLogika program, which consisted of four-segment workshops containing pre-/post-tests, theoretical and practical parts within the project. The mean number of correct answers from the both tests improved after educational intervention (p < 0.001). Students' knowledge increased, especially in relation to risk factors of breast cancer development (416.31% increase), HPV-related cancers (344.81% increase), risk factors and red flag signs of skin melanoma (120.31% and 99.05% increase respectively). Approx. 86% of participants were satisfied with the OnkoLogika with 14% of respondents being dissatisfied and 94% declared increased awareness about cancer prophylaxis. High schools students indicated insufficient time (250; 16.67%) and lack of details considering presented cancers (80; 5.33%) to be the major weaknesses of the program. Nevertheless, 94% of participants would recommend OnkoLogika to a friend. OnkoLogika promotes healthy lifestyle and helps acquire necessary knowledge about chosen cancers.

Modulation of Fibroblast Activity via Vitamin D3 Is Dependent on Tumor Type-Studies on Mouse Mammary Gland Cancer.

Vitamin D3 and its analogs are known to modulate the activity of fibroblasts under various disease conditions. However, their impact on cancer-associated fibroblasts (CAFs) is yet to be fully investigated. The aim of this study was to characterize CAFs and normal fibroblasts (NFs) from the lung of mice bearing 4T1, 67NR, and E0771 cancers and healthy mice fed vitamin-D3-normal (1000 IU), -deficient (100 IU), and -supplemented (5000 IU) diets. The groups receiving control (1000 IU) and deficient diets (100 IU) were gavaged with calcitriol (+cal). In the 4T1-bearing mice from the 100 IU+cal group, increased NFs activation (increased α-smooth muscle actin, podoplanin, and tenascin C (TNC)) with a decreased blood flow in the tumor was observed, whereas the opposite effect was observed in the 5000 IU and 100 IU groups. CAFs from the 5000 IU group of E0771-bearing mice were activated with increased expression of podoplanin, platelet-derived growth factor receptor ß, and TNC. In the 100 IU+cal group of E0771-bearing mice, a decreased blood flow was recorded with decreased expression of fibroblast growth factor 23 (FGF23) and C-C motif chemokine ligand 2 (CCL2) in tumors and increased expression of TNC on CAFs. In the 67NR model, the impact of vitamin D3 on blood flow or CAFs and lung NFs was not observed despite changes in plasma and/or tumor tissue concentrations of osteopontin (OPN), CCL2, transforming growth factor-ß, vascular endothelial growth factor, and FGF23. In healthy mice, divergent effects of vitamin D3 supplementation/deficiency were observed, which lead to the creation of various body microenvironments depending on the mouse strain. Tumors developing in such microenvironments themselves modified the microenvironments by producing, for example, higher concentrations of OPN and stromal-cell-derived factor 1 (4T1), which influences the response to vitamin D3 supplementation/deficiency and calcitriol administration.

An analysis of clinical effectiveness of electrochemotherapy in the treatment of advanced metastatic malignant melanoma performed in the eastern part of Central Europe: a single-centre experience.

Introduction: Patients with cutaneous malignant melanoma (MM), in case of non-resectability of the lesions, have only a limited pool of the available treatment options. In recent years especially electrochemotherapy (ECT) has become an increasingly important therapy in locoregionally advanced MM. Aim: In this study an analysis of the ECT treatment of locoregionally advanced malignant melanoma was presented. Material and methods: Six ECT cycles in 5 patients were performed in the Wroclaw Comprehensive Cancer Centre. Treatment response, long-term observation, technical data downloaded from electroporator and photographs taken before and after the ECT were assessed in the analysis. Results: In total, 200 nodules in 5 patients were treated with ECT in palliative intent. After 5 out of 6 ECT cycles, the particular clinical response has been observed. Four patients with primary unresectable lesions underwent 11 surgeries of the cutaneous metastases. In long-term follow-up in 2 patients, of whom one died 19 months after the ECT, the disease progressed and in another two, no recurrence was observed. Conclusions: ECT is an encouraging therapy for patients in whom the recurrent cutaneous melanoma cannot be treated with other methods, however, access to this method in eastern part of Central Europe is limited. The presented study seems to confirm the usefulness of this palliative approach in a specific group of patients suffering from cutaneous MM.

Virtual Therapy Complementary Prehabilitation of Women Diagnosed with Breast Cancer-A Pilot Study.

Breast cancer is becoming an important issue due to its various consequences and epidemiology. Studies are showing that it extremely impacts the mental health as well as the physical activity of the patients. In addition to the most common symptom, which is fatigue, patients also have problems with the quality of sleep. Therefore, this study aimed to evaluate the effectiveness of virtual reality (VR) therapy in improving the mental state and quality of sleep, as well as increasing the physical activity (PA) of patients diagnosed with breast cancer. The study was conducted in a hospital's Breast Unit and included patients at the time of diagnosis of malignant breast cancer. A total of 16 subjects randomly divided into experimental (n = 9), and control (n = 7) groups were measured with the Beck Depression Scale, Mental Adjustment to Cancer Scale, International Physical Activity Questionnaire, and Pittsburgh Sleep Quality Index at two timepoints. The experimental intervention consisted of a 2-week (8 sessions) Virtual Therapeutic Garden (VRTierOne) procedure performed daily for about 15 min. Significant differences were identified between groups in the interactions between the main factors seen in the destructive style of the Mini-Mac scale: F(1.14) = 4.82, p = 0.04, and between multiple experiments: F(1.14)= 5.54, p = 0.03 showing a significant reduction in the destructive style of coping with the disease in the study group after therapy (32.44 vs. 28.33, p = 0.003). The level of main effects [study] for the constructive style is F(1.14) = 3.93, p = 0.06 with a significant increase in constructive style in the study group (43.33 vs. 45.33, p = 0.044). Significant differences in levels of depression between multiple experiments: F(1.14) = 5.04, p = 0.04, show a significant reduction in the severity of depressive symptoms was found in the experimental group after therapy (13.33 vs. 8.11, p = 0.02). However, the analysis did not show significant differences between group analyses (p = 0.25). It seems that VR reduces the severity of depressive symptoms and reduces the destructive style and can be an effective option in improving the mental state of patients diagnosed with breast cancer.

Analysis of lung cancer measures of the National Cancer Network pilot study in Poland for potential improvement in the quality of advanced-stage lung cancer therapy.

BACKGROUND: This study aimed to present the performance of the National Cancer Network's (NCN) pilot program in the Lower Silesian Voivodeship (southwestern province of Poland with a population of 2,9 million in 2019), to analyse measures describing lung cancer patients and to determine whether those measures can be used to improve the treatment outcomes of stage III and IV patients with lung cancer in Poland. METHODS: Three measures of the NCN pilot programme were analysed: "Percentage of patients with genetic and molecular testing for predictive factors", "Assessment of the completeness of a pathological examination", and "Percentage of stage III and IV cancer patients". As many as 2,218 patients with ICD-10-CM Diagnosis Code C34 were included in the NCN pilot program from 1 to 2019 to 31 December 2020, in the Lower Silesian Voivodeship. The scores of each measure were calculated quarterly by the Regional Coordinating Centre, Wroclaw Comprehensive Cancer Center, Wroclaw, Poland. RESULTS: Genetic and molecular testing among stage III and IV patients was performed in only 40% and 60% of patients, respectively. The incompleteness of histopathological examinations did not exceed 0.5%. Stage III and stage IV patients accounted for 37% and 35% of the analysed patients, respectively. CONCLUSIONS: The NCN pilot program measures presented in this study appear to be highly sensitive, simple, and transparent tools to monitor the quality of lung cancer diagnosis and assess clinical staging in patients within a specific region. An increase in the proportion of stage III and IV patients who will undergo genetic and molecular testing in the era of modern drug therapies should result in improved treatment outcomes in this patient group. In the present analysis, the values of the main analysed measure, which evaluates the number of genetic and molecular tests for predictive factors for lung cancer, were subject to significant fluctuations during the pilot project. Both upwards and downwards trends were observed. Further analysis in the future is warranted to eliminate the unfavourable factors influencing the obtained values of the measure.

Association between histological type of tumour growth and patient survival in t2-t3 lymph node-negative rectal cancer treated with sphincter-preserving total mesorectal excision.

For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by log-rank test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P < 0.01). In multivariate analysis these parameters significantly and independently influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.

[The effectiveness of population-based breast cancer screening programme]. / Skutecznosc populacyjnego programu wczesnego wykrywania raka piersi.

UNLABELLED: Well-organised mammography screening programme can significantly reduce the breast cancer mortality However, changes in mortality rates take a long time thus some early indicators are usually used to monitor the effectiveness of the programme. If these operational objectives are accomplished then the programme can replicate the mortality reduction achieved in randomised trials. THE AIM OF THIS STUDY: To evaluate the quality of breast cancer screening programme in the region of Lower Silesia during the first year of its operating. MATERIAL AND METHODS: Centrally organised breast cancer screening has been introduced since the beginning of the year 2007. This population-based programme is designed for women aged 50-69. Females undergoing treatment or being followed-up due to breast cancer are not invited. Screen-film two-view mammography without clinical examination is used as a screening test which is to be performed every two years. The second level diagnostic tools are breast clinical examination and additional imaging (mammography and ultrasound). Following further assessment women are referred to the examination at the routine round length of the programme, at the less interval (short-term recall) or biopsy procedures. Quality assessment was done via early indicators according to the European guidelines. RESULTS: The attendance rate was 41% (79,143 women screened within 192,613 eligible population for one year). Technical repeat rate, further assessment rate, and short-term recall rate were: 0.26%, 6.85%, and 0.91%, respectively. Pathologically confirmed breast cancer was revealed in 364 women giving the detection rate 4.59 for 1000. Cancer detection rate to expected incidence ratio was 3.35. CONCLUSIONS: Mammography service performed during the first year of breast cancer screening programme in the region of Lower Silesia conforms to quality assessment parameters recommended by the European guidelines at the acceptable level. The main problem at the start of this programme is too low coverage. Invitation process must be strongly intensified to improve long-term effectiveness and to significantly reduce breast cancer mortality.