Papers by Anna M . Czarnecka

Current treatment options in oncology, May 29, 2024
Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin, most commonly occurring in the... more Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin, most commonly occurring in the extremity but also in the retroperitoneum. The curative treatment for STS is radical surgery with wide margins, in some cases in combination with perioperative radiotherapy and chemotherapy. Nonradical resection (R2) of STS has been an emerging issue in recent decades, as optimal subsequent management remains debatable. Similarly, there is still no consensus on optimal surgical margins. Combining multiple treatment modalities in adjuvant therapy can achieve local and distant control in patients following surgery with positive margins. Patients who have undergone nonradical resection therefore require additional surgical interventions, and adjuvant radiotherapy resulting in a better prognosis but a higher number of complications. Following non-radical treatment, patients with limb and trunk wall sarcomas

Oncology in Clinical Practice, Feb 27, 2024
Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma (STS); it or... more Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma (STS); it originates from nervous tissue and typically develops in proximity to nerve trunks in the limbs and trunk. These tumors, constituting approximately 5% of soft tissue sarcomas, can either form spontaneously or arise from pre-existing neurofibromas. The majority (90%) of cases occur in individuals between the 2 nd and 5 th decades of life. The main risk factor for MPNST is von Recklinghausen disease (type 1 neurofibromatosis). The cornerstone of MPNST management involves radical surgical measures, specifically tumor excision within healthy tissue boundaries (wide local excision), which is complemented by adjuvant radiotherapy. In case of metastatic disease, palliative chemotherapy employing doxorubicin or a combination of doxorubicin and ifosfamide is utilized. Approximately 25-30% of patients experience clinical improvement after chemotherapy. Looking ahead, advancements in research on molecular biology may lead to the development of inhibitors demonstrating greater efficacy than traditional chemotherapy for MPNST patients. At present, ongoing clinical trials of the therapeutic management of MPNST encompass pembrolizumab, the combination of nivolumab with ipilimumab, pexydartinib (an inhibitor targeting KIT, CSF1R, and FLT3) in conjunction with sirolimus, sapanisertib (a TORC1/2 inhibitor), or LOXO-195 (an inhibitor of neurotrophic tyrosine kinase receptors NTRK type 1, 2, and 3).

Oncology in Clinical Practice, Apr 19, 2024
Malignant bone tumors (MBT) are a rare and heterogeneous group of tumors, arising mostly in child... more Malignant bone tumors (MBT) are a rare and heterogeneous group of tumors, arising mostly in children. Localized disease is usually treated with surgery, but prognosis worsens in advanced stages. Currently, with limited biomarkers in clinical use, prognosis depends on histological grading and clinical features. However, the use of biomarkers remains inadequate, limiting treatment efficacy and increasing the risk of recurrence and disease progression for patients. Potential biomarkers based on genomics, proteomics, and clinical characteristics are currently entering clinical use in multiple cancers. Biomarker research in MBT faces additional challenges resulting from the rarity of these entities. Emerging biomarker concepts require clinical validation to create robust frameworks for precision oncology. This review of new biomarkers is based on relevant literature from Pubmed, Scopus, and clinicatrials.gov databases retrieved in November 2023. At present, the definition of prognostic markers in malignant bone tumors remains challenging. More research is needed, particularly to tailor treatments based on advanced genetic profiling and analysis of individual tumor and patient characteristics. Many newly identified biomarkers have not been clinically validated.
Cancers, Nov 4, 2023
Soft tissue and bone sarcomas belong to a group of rare and malignant tumors. The treatment of th... more Soft tissue and bone sarcomas belong to a group of rare and malignant tumors. The treatment of these tumors is very complex and depends on their specific subtypes. Therefore, there is a great need to develop novel therapeutic options for patients with sarcomas. One such option may be to target tumor-associated macrophages (TAMs), which are involved in immunosuppression during tumor growth. High levels of TAMs are widely recognized as a poor prognostic factor in many tumors, including sarcomas, making them a promising target for future targeted therapies. In this review, we highlight the role of TAMs in the microenvironment of sarcomas, along with their clinical relevance, potential targetable markers on their surface, and the molecular pathways involved. We also discuss currently ongoing clinical trials with TAMs.

Journal of Applied Genetics, 2014
Complex I NADH-oxidoreductase-ubiquinone transports reducing equivalents from the reduced form of... more Complex I NADH-oxidoreductase-ubiquinone transports reducing equivalents from the reduced form of NADH to ubiquinone (coenzyme Q-CoQ). The purpose of this study was to analyze mutations in MT-ND1, MT-ND2, MT-ND3 and MT-ND6 genes and their effect on the biochemical properties, structure and functioning of proteins in patients with breast tumours. In research materials, in 50 patients, 28 total polymorphisms and five mutations were detected. Most detected polymorphisms (50 %, 14/28) were observed in MT-ND2 gene. Most of them were silent mutations. Five polymorphisms (m.G3916A, m.C4888T, m.A4918G, m.C5363T, m.C10283T) do not exist in the database. A total of five mutations in 13 patients (13/50) were detected, including two not described in the literature: m.C4987G and m.T10173C. It cannot be excluded that, through the mutations and polymorphism impact on the protein structure, they may cause mitochondrial dysfunction and contribute to the appearance of other changes in mtDNA. The results of our study indicate the presence of homological changes in the sequence of mtDNA in both breast cancer and in some mitochondrial diseases. Mutations in the examined genes in breast cancer may affect the cell and cause its dysfunction, as is the case in mitochondrial diseases.
The current treatment trends and survival patterns in melanoma patients with positive sentinel lymph node biopsy (SLNB): a multicenter nationwide study
Ejso, Feb 1, 2023

Research Square (Research Square), May 26, 2020
Background There is currently no consensus on optimal management of patients with primary or recu... more Background There is currently no consensus on optimal management of patients with primary or recurrent non-resectable/residual retroperitoneal sarcomas (RPS). The objective of this study was to document the outcomes of patients with primary or recurrent non-resectable/residual RPS treated in our center with de nitive radiotherapy (RT), and to perform systematic review on that topic. Methods A retrospective analysis of consecutive RPS patients treated in our center between 2000 and 2019 was performed. All consecutive patients who underwent de nitive conformal RT with image guidance for primary or recurrent non-resectable or macroscopically residual RPS were included. Additionally, the systematic review compliant with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed. Results 14 patients who met aforementioned criteria were found. Data on clinicopathological characteristics, RT and response to treatment were presented. RT allowed achieving prolonged local control of the disease i.e. no local progression of the disease for more than six months after RT in 12 patients. Achieved local control lasted more than 24 months in six cases, with none or minimal toxicity. 11 studies were included in the systematic review. Our results are in concordance to reports included in the review. Conclusions RT provided satisfactory local disease control with acceptable treatment tolerance in patients with primary or recurrent non-resectable/residual RPS. RT represents valuable treatment modality in this selected group of patients. Additional RT modalities i.e. particle therapy, MRI-guided RT or GRID/Lattice RT may be introduced to improve local control and minimize toxicity.

Nowotwory, Dec 13, 2022
Avelumab is a programmed death-ligand 1 (PD-L1) blocking human IgG1 lambda monoclonal antibody. I... more Avelumab is a programmed death-ligand 1 (PD-L1) blocking human IgG1 lambda monoclonal antibody. It was the first immunotherapy to be approved for the treatment of MCC. In March 2017, the FDA granted accelerated approval to avelumab for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC)-irrespective of prior therapy. In July 2017, the European Medicines Agency (EMA) recommended the approval of avelumab as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (mMCC). Approvals were based on the efficacy and safety demonstrated in JAVELIN Merkel 200 (NCT02155647), a multi-center, open-label, single-arm, phase II clinical trial [1]. Part A of the study consisted of patients treated in the second line with metastatic, chemotherapy-refractory MCC. Part B consisted of systemic treatment-naive patients who received avelumab as a first-line treatment for metastatic or distally recurrent MCC. In the first line the ORR is 39.7%. Durable responses lasting at least 6 months were observed and the majority of responses are observed early with the median time to response of 6.1 week. PFS rate at 6 and 12 months are 41% and 31%, respectively. Median OS is 20.3 months. The OS rate at 1 year is 60%.

Experimental & Molecular Medicine, 2003
Breast cancer is the leading cause of cancer death am ong wom en around the world and its inciden... more Breast cancer is the leading cause of cancer death am ong wom en around the world and its incidence is annually increasing. The vitam in D receptor (VDR) gene is a m em ber of the nuclear receptor superfam ily, w hich is expressed in breast tissue and know n to m odulate the rate of cell proliferation. Association betw een the VDR gene polym orphisms and cancer developm ent has been suggested by several studies. How ever, the relationship betw een VDR polym orphism s and breast cancer is controversial and has not been confirm ed by all studies. The purpose of this study w as to investigate the genotype frequencies and association of the VDR Bsm I and Taq I polym orphism s w ith breast cancer in Turkish patients. In this study, 78 patients w ith breast cancer and 27 healthy individuals w ere enrolled. The prevalence of the VDR Taq I and Bsm I alleles and the genotype frequencies in patients w ith breast cancer w as sim ilar to that in the norm al population. O ur data indicate that no significant differences exist between the patients and control subjects.

Expert Review of Anticancer Therapy, 2024
Introduction: Soft tissue sarcomas (STS) are a rare and diverse group of tumors. Curative options... more Introduction: Soft tissue sarcomas (STS) are a rare and diverse group of tumors. Curative options are limited to localized disease, with surgery being the mainstay. Advanced stages are associated with a poor prognosis. Currently, the prognosis of the patient is based on histological classification and clinical characteristics, with only a few biomarkers having entered clinical practice. Areas covered: This article covers extensive recent research that has established novel potential biomarkers based on genomics, proteomics, and clinical characteristics. Validating and incorporating these biomarkers into clinical practice can improve prognosis, prediction of recurrence, and treatment response. Relevant literature was collected from PubMed, Scopus, and clinicaltrials.gov databases (November 2023). Expert opinion: Currently, defining prognostic markers in soft tissue sarcomas remains challenging. More studies are required, especially to personalize treatment through advanced genetic profiling and analysis using individual tumor and patient characteristics.

Oncology in Clinical Practice, 2024
Aggressive angiomyxoma (AAM) is a rare benign soft tissue tumor that occurs predominantly in prem... more Aggressive angiomyxoma (AAM) is a rare benign soft tissue tumor that occurs predominantly in premenopausal women. Due to its nonspecific symptoms, AAM diagnosis may be challenging. The clinical diagnosis of AMM is challenging due to its rarity and nonspecific physical and radiological characteristics. Aggressive angiomyxoma can present manifestations similar to entities such as Bartolin cysts or angiomyofibroma. Histological examination shows a hypocellular and highly vascular tumor with a myxoid stroma containing cytologically bland stellate or spindle cells. The current gold standard of AAM treatment is surgical resection, with no difference in the recurrence rate observed for radical incisions. Aggressive angiomyxoma often stains positively for estrogen and progesterone receptors, leading to the exploration of gonadotropin-releasing hormone agonists as adjuvant or neoadjuvant therapy. The presence of chromosomal abnormalities, including translocation at the 12q13-15 locus involving the HMGA2 gene has been identified in AAM. Although AAM is benign and does not show potential for metastasis, its infiltrative nature in surrounding tissues and the high rate of postoperative recurrences warrant the use of the term 'aggressive. ' Surgical resection remains the current gold standard of treatment, but the possibility of therapy using gonadotropin-releasing hormone agonists has emerged. Ongoing and future studies of AAM can potentially reveal the role of hormones in tumor growth and genetic mutations responsible for its development.
Biomedicines, 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Intermittent sunitinib is an effective renal carcinoma treatment
Nature Reviews Urology, Mar 7, 2017
Intermittent sunitinib treatment is a feasible first-line approach in patients with renal cell ca... more Intermittent sunitinib treatment is a feasible first-line approach in patients with renal cell carcinoma (RCC), providing a median progression-free survival duration of 37.6 months. Cyclic re-introduction of sunitinib after a treatment break might increase the duration of a response owing to resistance to tyrosine kinase inhibitors being largely dependent on reversible changes in gene expression. Biomarkers are needed to enable selection of the best candidates for intermittent treatment.
Intermittent sunitinib is an effective renal carcinoma treatment
Nature Reviews Urology, 2017
Intermittent sunitinib treatment is a feasible first-line approach in patients with renal cell ca... more Intermittent sunitinib treatment is a feasible first-line approach in patients with renal cell carcinoma (RCC), providing a median progression-free survival duration of 37.6 months. Cyclic re-introduction of sunitinib after a treatment break might increase the duration of a response owing to resistance to tyrosine kinase inhibitors being largely dependent on reversible changes in gene expression. Biomarkers are needed to enable selection of the best candidates for intermittent treatment.
Multi-Chaperones-Interactors Network In Mitochondria (MtCIN): Its Role In Carcinogenesis and Methodology of Analysis
Journal of Cancer …, 2008

Czerniak jest nowotworem zlośliwym rozwijającym sie z melanocytow, ktore są komorkami barwnikowym... more Czerniak jest nowotworem zlośliwym rozwijającym sie z melanocytow, ktore są komorkami barwnikowymi wystepującymi glownie w skorze i stanowią swoistą ochrone skory przed promieniowaniem ultrafioletowym (UV). Melanocyty wystepują rowniez poza skorą — miedzy innymi w galce ocznej, w blonie śluzowej przewodu pokarmowego od jamy ustnej do odbytu, jamy nosowej i zatok obocznych nosa oraz w drogach moczowo-plciowych. Znane są liczne przypadki, w ktorych czerniak rozwija sie w wymienionych lokalizacjach. Glownym czynnikiem odpowiadającym za rozwoj czerniaka skory jest promieniowanie UV. W przypadkach czerniakow blon śluzowych czynniki etiologiczne nadal nie zostaly poznane. Czerniak blon śluzowych rozwija sie najcześciej skrycie — w miejscach ukrytych i niedostepnych standardowemu badaniu — a zatem mija dluzszy czas, zanim zostaje postawione prawidlowe rozpoznanie (zwykle dzieje sie to w chwili stadium uogolnienia, gdy nie ma mozliwości zastosowania skutecznego leczenia miejscowego). To, w ...

Oncology Reports, 2009
Mitochondria have been implicated in cell transformation since Otto Warburg considered 'respirati... more Mitochondria have been implicated in cell transformation since Otto Warburg considered 'respiration damage' to be a pivotal feature of cancer cells. Numerous somatic mitochondrial DNA (mtDNA) mutations have been found in various types of neoplasms, including breast cancer. Establishing the mtDNA mutation pattern in breast cancer cells may enhance the specificity of cancer diagnostics, detection and prediction of cancer growth rate and/or patients' outcomes; and therefore be used as a new molecular cancer bio-marker. The aim of this review is to summarize data on mtDNA mutation involvement in breast cancer and estimate effects of resulting amino acid changes on mitochondrial protein function. In this article published mtDNA mutation analyses are critically evaluated and interpreted in the functional context. Contents 1. Introduction 2. Structural mitochondrial DNA (mtDNA) mutations in breast cancer 3. Conclusions
Frontiers in Bioscience, 2010
Mitochondrial genome polymorphisms influence developmentof vulvar cancer more
Methodology for Mitochondrial DNA Research In Oncology: Goals and Pitfalls
ARS Medica …, 2008
Anna Czarnecka's Papers: Methodology For Mitochondrial DNA Research In Oncology: Goals And P... more Anna Czarnecka's Papers: Methodology For Mitochondrial DNA Research In Oncology: Goals And Pitfalls , Breast cancer as a mitochondrial disorder , Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in.
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Papers by Anna M . Czarnecka