Dual effect of vitamin D3 on breast cancer-associated fibroblasts.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Despite the well-known in vitro antitumoral effect of vitamin D3 (VD3), its impact on breast CAFs is almost unknown. In this study, we analyzed the ex vivo effects of calcitriol on CAFs isolated from breast cancer tissues. METHODS: CAFs were cultured with 1 and 10 nM calcitriol and their phenotype; gene expression, protein expression, and secretion were assessed. Calcitriol-treated CAFs-conditioned media (CM) were used to analyze the effect of CAFs on the migration and protein expression of MCF-7 and MDA-MB-231 cells. RESULTS: Tumor tissues from VD3-deficient patients exhibited lower levels of ß-catenin and TGFß1, along with higher levels of CYP24A1 compared to VD3-normal patients. In VD3-deficient patients, CAF infiltration was inversely associated with CYP24A1 levels and positively correlated with OPN levels. Calcitriol diminished CAFs' viability, but this effect was weaker in premenopausal and VD3-normal patients. Calcitriol reduced mRNA expression of CCL2, MMP9, TNC, and increased PDPN, SPP1, and TIMP1. It also decreased the secretion of CCL2, TNC, and the activity of MMP-2, while increasing cellular levels of TIMP1 in CAFs from all patient groups. In nonmetastatic and postmenopausal patients, PDPN surface expression increased, and CAFs CM from these groups decreased MCF-7 cell migration after ex vivo calcitriol treatment. In premenopausal and VD3-deficient patients, calcitriol reduced IDO1 expression in CAFs. Calcitriol-treated CAFs CM from these patients decreased OPN expression in MCF-7 and/or MDA-MB-231 cells. However, in premenopausal patients, calcitriol-treated CAFs CM also decreased E-cadherin expression in both cell lines. CONCLUSION: The effects of calcitriol on breast CAFs, both at the gene and protein levels, are complex, reflecting the immunosuppressive or procancer properties of CAFs. The anticancer polarization of CAFs following ex vivo calcitriol treatment may result from decreased CCL2, TNC (gene and protein), MMP9, and MMP-2, while the opposite effect may result from increased PDPN, TIMP1 (gene and protein), and SPP1. Despite these multifaceted effects of calcitriol on molecule expression, CAFs' CMs from nonmetastatic and postmenopausal patients treated ex vivo with calcitriol decreased the migration of MCF-7 cells.

Psychological and Physical Well-Being in Women Diagnosed with Breast Cancer: A Comprehensive Study of Anxiety, Depression, Sleep Quality, Physical Activity, and Sociodemographic Factors.

BACKGROUND The psychophysical state of breast cancer patients impacts several outcomes and parameters and can directly affect diagnosis, prehabilitation, and treatment. This questionnaire-based study aimed to compare anxiety levels, depression, physical activity, sleep quality, and sociodemographic features in women with breast cancer and healthy women at a breast cancer unit in Poland. MATERIAL AND METHODS The study enrolled 41 breast cancer patients with no proposed treatment or psychological disorder diagnosis and 50 healthy volunteers. After enrolment, the subjects completed the Spielberger State-Trait Anxiety Inventory (STAI), Beck's Depression Inventory (BDI), International Physical Activity Questionnaire (IPAQ), Pittsburgh Sleep Quality Index (PSQI), and a sociodemographic questionnaire. RESULTS In this study, anxiety levels measured by the STAI anxiety subscale (56.05 [9.18] vs 37.62 [8.35], P<0.001) and BDI-assessed depression levels were higher in the cancer group (12.34 [6.26] vs 6.68 [6.36], P<0.001). PSQI measured quality of sleep (QOS) (5.80 [3.44] vs 3.76 [3.35], p=0.003) and physical activity (PA) levels evaluated by IPAQ were lower for breast cancer patients (1684.62 [2401.19] vs 3473.44 [4756.78], P=0.042). CONCLUSIONS Anxiety, depression, poor quality of sleep, and insufficient PA were common in breast cancer patients. The occurrence of cancer was the main factor causing mental health deterioration in patients with breast cancer. Also, mental state and well-being differed in healthy women compared to breast cancer patients.

Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells.

Mucosal melanoma (MM) is a very rare and aggressive type of cancer for which immunotherapy or targeted therapy such as BRAF/MEK inhibitors, used in cutaneous melanoma, usually fail. Due to our earlier experience showing the high effectiveness of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) inhibitors in reducing the activation of the MAPK and PI3K/AKT signalling pathways, we aim to test whether these drugs would also be effective for mucosal melanoma. Cells representing two commercially available mucosal melanoma cell lines (GAK and HMVII) and one cell line obtained from a patient's vaginal melanoma were treated with MET or EGFR inhibitors, or combinations of these agents. The dual-inhibitor treatment strategy resulted in a decrease of cell proliferation, migration and invasion. Moreover, combinations of inhibitors led to reduction of pEGFR/EGFR and pMET/MET ratio and downregulation of PI3K/AKT and MEK/ERK1/2-based signalling pathways. Our findings indicate a potential therapeutic strategy based on EGFR and MET inhibitors in mucosal melanoma, which should be further evaluated in vivo and in clinical experiments. They also suggest that targeting multiple receptor tyrosine kinases may block signalling crosstalk and possibly delay the appearance of resistance to kinase inhibitors in mucosal melanoma cells.

Numerical and physical modeling of breast cancer based on image fusion and artificial intelligence.

PURPOSE: The key problem raised in the paper is the change in the position of the breast tumor due to magnetic resonance imaging examinations in the abdominal position relative to the supine position during the surgical procedure. Changing the position of the patient leads to significant deformation of the breast, which leads to the inability to indicate the location of the neoplastic lesion correctly. METHODS: This study outlines a methodological process for treating cancer patients. Pre-qualification assessments are conducted for magnetic resonance imaging (MRI), and 3D scans are taken in three positions: supine with arms raised, supine surgical position (SS), and standing. MRI and standard ultrasonography (USG) imaging are performed, and breast and cancer tissue are segmented from the MRI images. Finite element analysis is used to simulate tissue behavior in different positions, and an artificial neural network is trained to predict tumor dislocation. Based on the model, a 3D-printed breast with a highlighted tumor is manufactured. This computer-aided analysis is used to create a detailed surgical plan, and lumpectomy surgery is performed in the SS. In addition, the geometry of the tumor is presented to the medical staff as a 3D-printed element. RESULTS: By utilizing a comprehensive range of techniques, including pre-qualification assessment, 3D scanning, MRI and USG imaging, segmentation of breast and cancer tissue, model analysis, image fusion, finite element analysis, artificial neural network training, and additive manufacturing, a detailed surgical plan can be created for performing lumpectomy surgery in the supine surgical position. CONCLUSION: The new approach developed for the pre-operative assessment and surgical planning of breast cancer patients has demonstrated significant potential for improving the accuracy and efficacy of surgical procedures. This procedure may also help the pathomorphological justification. Moreover, transparent 3D-printed breast models can benefit breast cancer operation assistance. The physical and computational models can help surgeons visualize the breast and the tumor more accurately and detailedly, allowing them to plan the surgery with greater precision and accuracy.

Melanoma cells induce dedifferentiation and metabolic changes in adipocytes present in the tumor niche.

BACKGROUND: One of the factors that affect the progression of melanoma is the tumor microenvironment, which consists of cellular elements, extracellular matrix, acidification, and a hypoxic state. Adipocytes are one of the types of cell present in the niche and are localized in the deepest layer of the skin. However, the relationship between fat cells and melanoma remains unclear. METHODS: We assessed the influence of melanoma cells on adipocytes using an indirect coculture system. We estimated the level of cancer-associated adipocyte (CAA) markers through quantitative PCR analysis. The fibroblastic phenotype of CAAs was confirmed by cell staining and western blotting analysis. The lipid content was estimated by lipid detection in CAAs using LipidSpot and by quantitative analysis using Oil Red O. The expression of proteins involved in lipid synthesis, delipidation, and metabolic processes were assessed through quantitative PCR or western blotting analysis. Lactate secretion was established using a Lactate-Glo™ assay. Proteins secreted by CAAs were identified in cytokine and angiogenesis arrays. The proliferation of melanoma cells cocultured with CAAs was assessed using an XTT proliferation assay. Statistical analysis was performed using a one-way ANOVA followed by Tukey's test in GraphPad Prism 7 software. RESULTS: Obtained CAAs were identified by decreased levels of leptin, adiponectin, resistin, and FABP4. Adipocytes cocultured with melanoma presented fibroblastic features, such as a similar proteolytic pattern to that of 3T3L1 fibroblasts and increased levels of vimentin and TGFßRIII. Melanoma cells led to a reduction of lipid content in CAAs, possibly by downregulation of lipid synthesis pathways (lower FADS, SC4MOL, FASN) or enhancement of lipolysis (higher level of phosphorylation of ERK and STAT3). Adipocytes cocultured with melanoma cells secreted higher IL6 and SerpinE1 levels and produced less CCL2, CXCL1, and angiogenic molecules. CAAs also showed metabolic changes comprising the increased secretion of lactate and enhanced production of glucose, lactate, and ion transporters. In addition, changes in adipocytes observed following melanoma coculture resulted in a higher proliferation rate of cancer cells. CONCLUSIONS: Melanoma cells led to decreased lipid content in adipocytes, which might be related to enhanced delipidation or reduction of lipid synthesis. Fibroblast-like CAAs showed metabolic changes that may be the reason for accelerated proliferation of melanoma cells.

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.

Severe complications of nivolumab monotherapy in an adolescent with malignant melanoma.

This study presents a case of a 17-year-old female patient who had previously undergone surgical resection of melanoma in the right periscapular area. She was administered adjuvant treatment with the PD-1 inhibitor nivolumab as monotherapy. The mechanism of action of this drug is based on increased stimulation of the immune system. The patient developed a series of complications including capillary leak syndrome and hypothyroidism after the fifth cycle of therapy, as a result of dysregulation of immunity. Nivolumab treatment had to be discontinued and glucocorticosteroids were administered as a salvage therapy. After several months, two relapses developed in the subcutaneous tissue - first in the left and then in the right iliac region, confirmed as distant metastases of malignant melanoma, treated with resections of the lesions and intensity-modulated radiation therapy. Follow-up imaging studies and clinical examinations showed no metastases or pathologically enlarged lymph nodes.

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.

Immune activation of the monocyte-derived dendritic cells using patients own circulating tumor cells.

BACKGROUND: Dendritic cell (DC) therapy counts to the promising strategies how to weaken and eradicate cancer disease. We aimed to develop a good manufacturing practice (GMP) protocol for monocyte-derived DC (Mo-DC) maturation using circulating tumor cells lysates with subsequent experimental T-cell priming in vitro. METHODS: DC differentiation was induced from a population of immunomagnetically enriched CD14 + monocytes out of the leukapheresis samples (n = 6). The separation was provided automatically, in a closed bag system, using CliniMACS Prodigy® separation protocols (Miltenyi Biotec). For differentiation and maturation of CD14 + cells, DendriMACs® growing medium with supplements (GM-CSF, IL-4, IL-6, IL-1B, TNFa, PGE) was used. Immature Mo-DCs were loaded with autologous circulating tumor cell (CTCs) lysates. Autologous CTCs were sorted out by size-based filtration (MetaCell®) of the leukapheresis CD14-negative fraction. A mixture of mature Mo-DCs and autologous non-target blood cells (NTBCs) was co-cultured and the activation effect of mature Mo-DCs on T-cell activation was monitored by means of multimarker gene expression profiling. RESULTS: New protocols for mMo-DC production using automatization and CTC lysates were introduced including a feasible in vitro assay for mMo-DC efficacy evaluation. Gene expression analysis revealed elevation for following genes in NTBC (T cells) subset primed by mMo-DCs: CD8A, CD4, MKI67, MIF, TNFA, CD86, and CD80 (p ≤ 0.01). CONCLUSION: Summarizing the presented data, we might conclude mMo-DCs were generated using CliniMACS Prodigy® machine and CTC lysates in a homogenous manner showing a potential to generate NTBC activation in co-cultures. Identification of the activation signals in T-cell population by simple multimarker-qPCRs could fasten the process of effective mMo-DC production.

Introduction of a pilot program to measure and improve the clinical care of melanoma patients in the Lower Silesian Voivodeship in Poland: a report of 20 months experience.

BACKGROUND: In recent years, benchmarking and assessment methods to improve the quality of care have become increasingly important. Such approaches allow for a uniform assessment, comparisons between centers or over time, and the identification of weaknesses. In this study, the results of a 20-month pilot program to assess, monitor and improve the quality of care in melanoma patients primarily treated surgically are presented. METHODS: The pilot program started in May 2020 at the Lower Silesian Oncology, Pulmonology and Hematology Center (LSOPHC) in Wroclaw, Poland (Lower Silesian Voivodeship, southwestern province of Poland with a population of 2,9 million). The program involved the introduction of a synoptic histopathological protocol, medical coordinators, and a set of measures to assess oncological care. In total, 11 Skin Cancer Unit (SCU) measures were introduced to analyze clinical outcomes, diagnostic quality, and duration. Data from 352 patients covered by the program were analyzed. In addition, the completeness of diagnostics from external sites was compared to our own results. Furthermore, the timeliness of the initial diagnostic tests and in-depth diagnostics were assessed and compared to the timeliness before implementation of the pilot program. RESULTS: The introduced measures assessed the mortality related to oncological treatment, the rate of complications, advanced stages of melanoma, the completeness and duration of diagnostics, the involved nodes after lymphadenectomy, and melanoma screening. During the study period, the timeliness of the initial diagnostics was maintained at 87.8%, and the timeliness of the in-depth diagnostics at 89.5%. Compared to a similar period before the program, these values were 36.1% and 67.5%, respectively. CONCLUSION: The introduced measures seem to be effective and practical tools for benchmarking clinical and diagnostic aspects. They also allowed for a sensitive assessment of individual issues and indicated sensitive points. Furthermore, the actions undertaken in this pilot program allowed for a shortening of the duration of diagnostics.

The pilot project of the National Cancer Network in Poland: Assessment of the functioning of the National Cancer Network and results from quality indicators for lung cancer (2019-2021).

BACKGROUND: This analysis presents the outcomes of the operations of the National Cancer Network (NCN) pilot project in Lower Silesian Voivodeship, Poland, for lung cancer for the period of 2019-2021. The results concerning measures of the quality of medical processes were analysed. METHODS: Twenty-one measures used to gauge the quality of oncological care for lung cancer were assessed. Data collection and processing for the purpose of calculating the measures were carried out as part of the NCN pilot project based on the Regulation of the Ministry of Health enacted on 13 December 2018. The measures were calculated at the Voivodeship Coordination Center, and the data were derived from the centres included in the network in the area of the analysed voivodeship. RESULTS: A total of 3,638 patients diagnosed with lung cancer were enrolled in the NCN pilot program during the analysed period. For 3 measures, out of 21, target values were obtained. For 2 measures, the values differed significantly from the assumed target value. CONCLUSION: In our opinion, the NCN pilot study, as a test of the network's functioning, meets the assumed goal. The NCN assessment is based on, inter alia, analysis of the outcomes of oncological quality of care measures for lung cancer, and facilitates monitoring of the quality of medical services provided and the identification of areas for improvement. In addition, the pilot program, which will last until the end of 2022, will allow for further in-depth analysis regarding the network's limitations before implementing the system on a national scale in Poland. This will be the subject of further investigation.

Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts.

BACKGROUND: The tumor microenvironment consists of stromal cells, extracellular matrix, and physicochemical properties (e.g., oxygenation, acidification). An important element of the tumor niche are cancer-associated fibroblasts (CAFs). They may constitute up to 80% of the tumor mass and share some features with myofibroblasts involved in the process of wound healing. CAFs can facilitate cancer progression. However, their interaction with melanoma cells is still poorly understood. METHODS: We obtained CAFs using conditioned media derived from primary and metastatic melanoma cells, and via co-culture with melanoma cells on Transwell inserts. Using 2D and 3D wound healing assays and Transwell invasion method we evaluated CAFs' motile activities, while coverslips with FITC-labeled gelatin, gelatin zymography, and fluorescence-based activity assay were employed to determine the proteolytic activity of the examined cells. Western Blotting method was used for the identification of CAFs' markers as well as estimation of the mediators of MMPs' (matrix metalloproteinases) expression levels. Lastly, CAFs' secretome was evaluated with cytokine and angiogenesis proteomic arrays, and lactate chemiluminescence-based assay. RESULTS: Acquired FAP-α/IL6-positive CAFs exhibited elevated motility expressed as increased migration and invasion ratio, as well as higher proteolytic activity (area of digestion, MMP2, MMP14). Furthermore, fibroblasts activated by melanoma cells showed upregulation of the MMPs' expression mediators' levels (pERK, p-p38, CD44, RUNX), enhanced secretion of lactate, several cytokines (IL8, IL6, CXCL1, CCL2, ICAM1), and proteins related to angiogenesis (GM-CSF, DPPIV, VEGFA, PIGF). CONCLUSIONS: Observed changes in CAFs' biology were mainly driven by highly aggressive melanoma cells (A375, WM9, Hs294T) compared to the less aggressive WM1341D cells and could promote melanoma invasion, as well as impact inflammation, angiogenesis, and acidification of the tumor niche. Interestingly, different approaches to CAFs acquisition seem to complement each other showing interactions between studied cells. Video Abstract.

Melanoma stimulates the proteolytic activity of HaCaT keratinocytes.

BACKGROUND: Keratinocytes constitute a major part of the melanoma microenvironment, considering their protective role towards melanocytes in physiological conditions. However, their interactions with tumor cells following melanomagenesis are still unclear. METHODS: We used two in vitro models (melanoma-conditioned media and indirect co-culture of keratinocytes with melanoma cells on Transwell inserts) to activate immortalized keratinocytes towards cancer-associated ones. Western Blotting and qPCR were used to evaluate keratinocyte markers and mediators of cell invasiveness on protein and mRNA expression level respectively. The levels and activity of proteases and cytokines were analysed using gelatin-FITC staining, gelatin zymography, chemiluminescent enzymatic test, as well as protein arrays. Finally, to further study the functional changes influenced by melanoma we assessed the rate of proliferation of keratinocytes and their invasive abilities by employing wound healing assay and the Transwell filter invasion method. RESULTS: HaCaT keratinocytes activated through incubation with melanoma-conditioned medium or indirect co-culture exhibit properties of less differentiated cells (downregulation of cytokeratin 10), which also prefer to form connections with cancer cells rather than adjacent keratinocytes (decreased level of E-cadherin). While they express only a small number of cytokines, the variety of secreted proteases is quite prominent especially considering that several of them were never reported as a part of secretome of activated keratinocytes' (e.g., matrix metalloproteinase 3 (MMP3), ADAM metallopeptidase with thrombospondin type 1 motif 1). Activated keratinocytes also seem to exhibit a high level of proteolytic activity mediated by MMP9 and MMP14, reduced expression of TIMPs (tissue inhibitor of metalloproteinases), upregulation of ERK activity and increased levels of MMP expression regulators-RUNX2 and galectin 3. Moreover, cancer-associated keratinocytes show slightly elevated migratory and invasive abilities, however only following co-culture with melanoma cells on Transwell inserts. CONCLUSIONS: Our study offers a more in-depth view of keratinocytes residing in the melanoma niche, drawing attention to their unique secretome and mediators of invasive abilities, factors which could be used by cancer cells to support their invasion of surrounding tissues. Video abstract.

Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer.

The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.

The effect of population-based screening on the incidence and detection on breast cancer in woman in Lower Silesia over the period 2005-2014.

INTRODUCTION: The National Cancer Control Programme 2006-2015 (NCCP) was implemented to improve the health situation of Polish women in 2006. Its effectiveness was evaluated by analysing trends of changes in incidence rates of pre-invasive (D05) and invasive (C50) breast cancers in three age cohorts: pre-screening cohort (<50), screening cohort (50-69) and post-screening cohort (>69). MATERIAL AND METHODS: Medical data of 13,089 women with C50 and 738 women with D05 diagnosed in 2005-2014 in the Lower Silesian Voivodeship (LS) were analysed. RESULT: In 2009-2014, incidence rates of C50 (p=0.0224) and D05 (p=0.0003) were found to be higher in the LS than those recorded for Poland. During this period, there were approx. 1,400 cases of C50 and 90-100 cases of D05 per year. After the NCCP had been implemented, there was a gradual increase in the proportion of the female population included in the mammography screening, from 32% in 2007 to 45% in 2014. The age group included in the screening programme experienced a significant increase in the proportion of pre-invasive cancers - from 3% in 2005 to 7-10% in 2010-2013. In that group, cancer was statistically more frequently detected in Tis- or T1- stages (p=0.0002). Beneficial effects of screening were also observed in post-screening women. There was no similar trend in patients aged <50. CONCLUSIONS: This analysis shows positive population effects of mammography screening. The least favourable changes in the detection of early stages of breast cancer were observed in female patients aged less than 50 years. This suggests that some modifications regarding both the age range and the screening interval in the Polish population should be considered.

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.

The report and analysis concerning the usefulness of basic telemedicine tools in the skin cancer diagnostic screening process during COVID-19 pandemics.

Introduction: A rapid spread of the emerging COVID-19 pandemic limited the availability of professional medical advice. As a result, a significant increase in the number of undiagnosed and chronically ill patients without medical care was noticed. In reaction to the urgent need, the telemedical consultation, instead of the classical form, may be introduced as a vulnerable tool in preclinical evaluation of patients with potentially malignant skin lesions. Aim: In this study the results of the implementation of telemedical consultation programme with the intention to early detect the skin cancers in patients who, due to the COVID-19 pandemic, could not undergo the standard consultation was presented. Material and methods: The programme of remote dermatological consultation, which was introduced on 1 June 2020, covered all patients who had no possibility or will to visit the standard healthcare units. In case of suspicion of life-threatening skin lesions patients were invited for additional diagnostics or surgery. Obtained data, including demography, age, surgery description and pathomorphological examination were descriptively analysed. Results: In total, 80 consecutive patients were enrolled during the screening programme. In total, 31 lesions in 25 patients were excised. In this group there were 10 serious diagnoses including 5 cases of basal cell carcinoma, melanoma in situ and dysplastic nevi. Moreover, another 10 patients were referred to other specialists or specific recommendations were advised. Conclusions: An alternative track using teledermatology for patients with skin diseases was successfully introduced under the specific conditions of epidemiologic danger. Despite its disadvantages teledermatology enabled the diagnosis and treatment in a significant number of serious cases.

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.

Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy.

Malignant melanoma is a highly metastatic type of cancer, which arises frequently from transformed pigment cells and melanocytes as a result of long-term UV radiation exposure. In recent years, the incidence of newly diagnosed melanoma patients reached 5% of all cancer cases. Despite the development of novel targeted therapies directed against melanoma-specific markers, patients' response to treatment is often weak or short-term due to a rapid acquisition of drug resistance. Among the factors affecting therapy effectiveness, elements of the tumor microenvironment play a major role. Melanoma niche encompasses adjacent cells, such as keratinocytes, cancer-associated fibroblasts (CAFs), adipocytes, and immune cells, as well as components of the extracellular matrix and tumor-specific physicochemical properties. In this review, we summarize the current knowledge concerning the influence of cancer-associated cells (keratinocytes, CAFs, adipocytes) on the process of melanomagenesis, tumor progression, invasiveness, and the emergence of drug resistance in melanoma. We also address how melanoma can alter the differentiation and activation status of cells present in the tumor microenvironment. Understanding these complex interactions between malignant and cancer-associated cells could improve the development of effective antitumor therapeutic strategies.

Superparamagnetic iron oxide: a novel tracer for sentinel lymph node detection in vulvar cancer.

OBJECTIVES: Superparamagnetic techniques for sentinel lymph node (SLNs) biopsy in breast cancer is well recognized but remains novel in the literature in relation to early stage vulvar cancer. The aim of this study was to compare and validate SLN detection using a superparamagnetic iron oxide tracer and a magnetometer probe compared with the standard procedure with a radioisotope (99Tc-technetium 99) and a gamma probe, in patients with vulvar cancer. METHODS: Patients were included in the study with squamous vulvar tumors less than 4 cm in diameter and without suspicious groin lymph nodes on preoperative magnetic resonance imaging. Patients must have previously qualified for SLN biopsy with a radiotracer as the standard of care. The primary endpoint was the proportion of successful SLN detection with superparamagnetic iron oxide tracer versus 99Tc. The secondary endpoints were average number of SLNs retrieved per patient, proportion of SLNs detected (nodal detection rate), and proportion of pathologically positive results (malignancy rate) per patient and per node comparing both SLN detection methods. RESULTS: A total of 20 patients were included in the study. SLNs were found in all patients with both methods, resulting in similar average distributions (3.1/3.2 SLN per patient). The SLN detection rate per patient was 100% with both techniques. Nodal detection sensitivity was 98.5% for the superparamagnetic technique and 93.8% for the radiotracer. Percentage of metastatic lymph nodes detected was 100% with both tracers. The rate of lymph node positivity was 21.5% (14 lymph nodes with metastases) and for patients 45% (9 patients with nodal metastases). Additionally, SLN tainted brown due to superparamagnetic iron oxide nanoparticles in 19 of 20 patients. CONCLUSIONS: The use of superparamagnetic iron oxide tracer in patients with vulvar cancer seems reliable and not inferior to the standard approach with radiotracer.