- Department of Soft Tissue/Bone Sarcoma and Melanoma
Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw Poland
- Oncology, Cancer stem cells, Cancer, Cancer Cell Biology, Clinical Decision Making, Molecular Biology, and 17 moreMolecular Medicine, Molecular Genetics, Biochemistry, Cell Signaling, Cell Biology, Cellular Biology, Renal Cancer, Clinical oncology, Mitochondria, Drug Discovery, Angiogenesis, Drug Resistance, Targeted Therapy, Melanoma, Sarcoma, Soft Tissue Sarcoma, and Musculoskeletal Oncology, Benign Bone Tumors, Sarcoma Imaging(Molecular Medicine, Molecular Genetics, Biochemistry, Cell Signaling, Cell Biology, Cellular Biology, Renal Cancer, Clinical oncology, Mitochondria, Drug Discovery, Angiogenesis, Drug Resistance, Targeted Therapy, Melanoma, Sarcoma, Soft Tissue Sarcoma, and Musculoskeletal Oncology, Benign Bone Tumors, Sarcoma Imaging)edit
- Piotr Rutkowskiedit
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... 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.
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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... 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.
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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
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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... 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.
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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... 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.
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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... 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 ...
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Research Interests: Biochemistry, Epidemiology, Cellular Biology, Molecular Biology, Evidence Based Medicine, and 15 moreCancer, Literature and Medicine, Breast Cancer, Biology, Cell Biology, Cancer Cell Biology, Mitochondria, Cell Signaling, Apoptosis, Medicine, Mitochondrial DNA, Humans, Cell Proliferation, Biochemistry and cell biology, and Mitochondrion
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... 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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Background The risk of brain metastases (BM) in advanced melanoma (MM) is 40-50%. Historical median survival of MM patients (pts) with BMs was 4-5 months. Current systemic treatments with targeted therapy and immunotherapy prolong... more
Background The risk of brain metastases (BM) in advanced melanoma (MM) is 40-50%. Historical median survival of MM patients (pts) with BMs was 4-5 months. Current systemic treatments with targeted therapy and immunotherapy prolong survival up to > 2 years, while prognosis of BMs carrying pts is not fully defined and optimal treatment sequencing remain unknown. We aimed to analyze the contemporary treatment outcomes in this specific group of pts. Methods Clinical data, course of treatment and clinical outcomes of 376 subsequent stage IV melanoma patients with BMs treated in one reference institution in period 2000-2018 were analyzed retrospectively (39% of BMs pts diagnosed before 2014). Results Median age for BMS diagnosis was 61, 171 pts were BRAF+ and 118 - wild-type. Median time to BMs from melanoma diagnosis was 2.3 years (8% had BMs at diagnosis). In 1st line BRAF(-) pts were treated with anti-PD-1 in 36%, chemotherapy - 46%, while BRAF(+) pts – with BRAFi/MEKi - 68% and anti-PD-1 - 5%. For the whole group median overall survival (mOS) of BRAF(+) was 7 months, while mOS BRAF(-) - 4 m. mOS for patients treated initially with BRAFi/MEKi was 9 m, while for anti-PD1 - 15 m (but it may be related to less advanced cases preferred for immunotherapy). BMs treatment modality chosen primarily was neurosurgery in 78 (21%) pts, radiotherapy - 270 (72%) with increasing use of stereotactic radiosurgery in recent years, only systemic treatment was offered to 25 (7%) pts. OS was highly affected by the number of BMs, LDH and albumin level and GPA (Graded Prognostic Assessment) scale (all p
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Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that... more
Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. This review presents recent articles on the potential role of OSA in cancer development. Relevant research has focused on: molecular pathways mediating the influence of intermittent hypoxia on tumor physiology, animal and epidemiological human studies linking OSA and cancer. Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer-related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment.
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CAPPELLO F, CAMPANELLA C, RIBBENE A, BELLAFIORE M, CZARNECKA A, ANZALONE R., et al. (2005). Evalutaion of HSP60, Procaspase-3 and P53 expression after oxydative stress in NCI-H292 cells.. ... Evalutaion of HSP60, Procaspase-3 and P53... more
CAPPELLO F, CAMPANELLA C, RIBBENE A, BELLAFIORE M, CZARNECKA A, ANZALONE R., et al. (2005). Evalutaion of HSP60, Procaspase-3 and P53 expression after oxydative stress in NCI-H292 cells.. ... Evalutaion of HSP60, Procaspase-3 and P53 expression after ...
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e21514 Background: Anti-programmed cell death-1 antibodies (anti-PD-1) have become a standard treatment option for melanoma patients. Currently, two anti-PD-1 antibodies are registered in the treatment of melanoma patients: nivolumab and... more
e21514 Background: Anti-programmed cell death-1 antibodies (anti-PD-1) have become a standard treatment option for melanoma patients. Currently, two anti-PD-1 antibodies are registered in the treatment of melanoma patients: nivolumab and pembrolizumab. Nivolumab is a human monoclonal antibody, while pembrolizumab is a humanized antibody. Unfortunately, there are very few clinical data comparing the efficacy and toxicity of nivolumab and pembrolizumab in routine practice. Methods: Consecutive patients treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) for unresectable or metastatic melanoma in comprehensive cancer centers between 03/2016 and 09/2020 were enrolled in the analysis. Baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level, and location of metastases) were evaluated to identify predictors of overall survival (OS). Data on response to treatment and the occurrence of irAEs were collected prospectively during anti-PD-1 treatment. OS were assessed using Kaplan–Meier and Cox models. The Chi-Square statistic was used for testing relationships between categorical variables. Median follow up for nivolumab and pembrolizumab group was 12.6 (range 0.2-52.1) and 10.7 (range 0.03-53.5) months, respectively. Results: Overall, 736 patients were included in the present analysis (443 nivolumab, 293 pembrolizumab). There were no statistically significant differences in baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level (normal vs elevated), brain metastasis and TNM stage) between the groups. Median OS for patients treated with nivolumab and pembrolizumab was 22 and was 17.3 months, respectively. There was no statistically significant difference in OS between the nivolumab and pembrolizumab groups (p = 0.12, HR = 1.2, Cl 95% 0.9-1.4). At multivariate analysis normal LDH levels, no brain metastases, and ECOG 0 or 1 were positive prognostic factors for OS both in nivolumab and pembrolizumab groups. In the nivolumab and pembrolizumab groups, 6% and 5% CR (complete response), 33% and 31% PR (partial response), 25% and 24% SD (stable disease), respectively, were observed. There was no statistical difference between the groups in the response to treatment (p = 0.65). There was no statistical difference between the groups in occurrence of the irAEs (p = 0.97) as well as in the type of irAEs. Conclusions: Our analysis in melanoma patients treated in routine practice with nivolumab or pembrolizumab confirmed no statistical differences in OS and treatment responses between these two anti-PD-1 antibodies. There were also no differences in toxicity between the two drugs. The choice of treatment should be based on the preferences of the patient and the physician.
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Pembrolizumab and nivolumab (anty-PD-1 antibody) are commonly used for the treatment of melanoma patients. However, their efficacy and safety have never been directly compared, leaving little guidance for clinicians to select the best... more
Pembrolizumab and nivolumab (anty-PD-1 antibody) are commonly used for the treatment of melanoma patients. However, their efficacy and safety have never been directly compared, leaving little guidance for clinicians to select the best therapy. The study included patients with inoperable or metastatic melanoma treated in first line with anti-PD-1 immunotherapy (nivolumab or pembrolizumab). In total 1037 patients were enrolled in the study, 455 (44%) patients were treated with pembrolizumab and 582 (56%) with nivolumab. The estimated median overall survival (OS) in the pembrolizumab and nivolumab groups was 17.4 and 20.0 months [P = 0.2323; hazard ratio (HR), 1.1; 95% confidence interval (CI), 0.94–1.28], respectively, whereas the median progression-free survival (PFS) was 5.6 and 7.5 months (P = 0.0941; HR, 1.13; 95% CI, 0.98–1.29), respectively. The estimated 2- and 3-year OS in the pembrolizumab and nivolumab groups were 42/34% and 47/37%, respectively, and the PFS was 25/21% and 29/23%, respectively. There were 391 (49%) immune-related adverse events (irAEs) of any grade during treatment, including 133 (42%) related to pembrolizumab treatment and 258 (53%) to nivolumab treatment. A total of 72 (9.6%) irAEs were in G3 or G4, including during pembrolizumab 29 (9%) and nivolumab 48 (11%). There were no differences in OS, PFS and overall response rates between nivolumab and pembrolizumab therapy in previously untreated patients with advanced/metastatic melanoma. There were no differences in the frequency of G1/G2 or G3/G4 irAEs. The choice of treatment should be based on the preferences of the patient and the clinician.
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INTRODUCTION Malignant peripheral nerve sheath tumor (MPNST) accounts for about 5% of soft tissue sarcomas. It can occur as sporadic diseases or can be associated with type 1 neurofibromatosis. MPNST is usually associated with poor... more
INTRODUCTION Malignant peripheral nerve sheath tumor (MPNST) accounts for about 5% of soft tissue sarcomas. It can occur as sporadic diseases or can be associated with type 1 neurofibromatosis. MPNST is usually associated with poor prognosis, mostly due to their aggressive behavior, high metastatic potential, and resistance to chemotherapy. Our study aimed to determine treatment outcomes and associated prognostic factors in a large cohort of patients with MPNSTs treated at the reference sarcoma center. METHODS 239 consecutive patients (114 women and 125 men) diagnosed with MPNST between March 1998 and March 2018 who were treated with surgery with curative intent in the reference sarcoma center were included in the retrospective analysis. RESULTS The mean age at diagnosis was 51 years (range 15-86). 28 (11.7%) patients had neurofibromatosis type 1 associated tumors (NF1 positive). Median OS was 126.5 months and 5-year survival rate was 61.9% in the group treated with curative intent. Median DFS, LRFS and DMFS were 91.6, 126.5 and 126.5 months, respectively. We identified tumor size, high tumor grade and positive surgical margins as independent negative predictors of DFS, LRFS, DMFS and OS. CONCLUSIONS High-quality surgery remains a gold standard of MPNST treatment. High grade, size and quality of surgery are significant independent prognostic factors for overall survival. There is an unmet need for improvement, especially regarding the perioperative treatment and treatment of metastatic disease. Future studies on the biology of MPNST would lead to the development of novel treatment options and improvement of treatment outcomes.
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PEComa to rodzina rzadkich nowotworow pochodzenia mezenchymalnego, skladających sie z nablonkowatych komorek przynaczyniowych, wykazujących ekspresje markerow melanocytarnych i mioidalnych. Grupa ta obejmuje nowotwory lagodne, takie jak... more
PEComa to rodzina rzadkich nowotworow pochodzenia mezenchymalnego, skladających sie z nablonkowatych komorek przynaczyniowych, wykazujących ekspresje markerow melanocytarnych i mioidalnych. Grupa ta obejmuje nowotwory lagodne, takie jak naczyniakomieśniakowlokniak (AML) nerki, oraz niskozroznicowane guzy typu malignant PEComa o potencjalnie niekorzystnym przebiegu klinicznym, bedące glownym tematem niniejszego opracowania. PEComa rozpoznawane są najcześciej u kobiet w średnim wieku jako rozlegle guzy zlokalizowane w obrebie jamy brzusznej lub miednicy, objawiające sie bolem w rzucie guza i dolegliwościami związanymi z uciskiem na okoliczne narządy. Guzy typu PEComa nalezy odrozniac od nowotworow podścieliskowych przewodu pokarmowego (GIST), mieśniakomiesaka gladkokomorkowego, przerzutow czerniaka, typu chromofobowego raka nerkowokomorkowego, miesaka jasnokomorkowego i innych nowotworow z komponentą jasnokomorkową. Charakterystyczne dla tej grupy nowotworow są somatyczne mutacje inaktywujące w obrebie genow TSC1/TSC2 , skutkujące nadmierną aktywacją kompleksu mTORC1. W ostatnim czasie wyrozniono dodatkowo odrebną podgrupe nowotworow PEComa, charakteryzującą sie obecnością fuzji genu TFE3, ktora w efekcie takze wywoluje zwiekszoną aktywnośc ściezki sygnalizacyjnej mTOR. Do czynnikow negatywnych rokowniczo, wskazujących na zwiekszone ryzyko zlośliwego przebiegu PEComa zalicza sie najcześciej: rozmiar guza > 5 cm, nasiloną atypie cytologiczną i jądrową, naciekanie okolicznych tkanek oraz naczyn krwionośnych, obecnośc martwicy i wysoką aktywnośc mitotyczną. Podstawową metodą leczenia nowotworow z rodziny PEComa pozostaje radykalna resekcja, poniewaz guzy te charakteryzują sie wysoką opornością na radioterapie oraz chemioterapie. W odniesieniu do choroby zaawansowanej miejscowo bądź przerzutowej w literaturze dostepne są jedynie pojedyncze opracowania dotyczące uzyskania krotkotrwalych odpowiedzi na chemioterapie paliatywną zawierającą doksorubicyne, gemcytabine czy ifosfamid. Rośnie liczba doniesien, w postaci kilkudziesieciu opisow przypadkow oraz kilku retrospektywnych analiz, o potencjalnej skuteczności zastosowania w przypadkach nieresekcyjnych inhibitorow mTOR. Leki te powodują zmniejszenie rozmiarow guza pierwotnego i przerzutow oraz zmniejszenie dolegliwości, przy dających sie kontrolowac dzialaniach niepoządanych. Niestety, dostepne są takze opisy przypadkow calkowitej oporności na leczenie inhibitorami mTOR.
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Introduction: In the general population, nasal obstruction is a common complaint. However, an objective evaluation of nasal obstruction is difficult. Nose examination, computed tomography (CT), acoustic rhinometry, and anterior... more
Introduction: In the general population, nasal obstruction is a common complaint. However, an objective evaluation of nasal obstruction is difficult. Nose examination, computed tomography (CT), acoustic rhinometry, and anterior rhinomanometry do not accurately reflect the discomfort reported by patients with nasal obstruction. In patients with nasal obstruction, this study evaluated nasal breathing with a unique device for continuous nasal-oral spirometry – a nasal-oral flow analyzer (NOFA); moreover, quality of life was compared between patients with normal nasal breathing on NOFA and of those with impaired nasal breathing on NOFA. Methods: Of 181 adult patients admitted to an ENT department due to nasal obstruction that were enrolled in the study, 97 (53.6%) completed all per-protocol assessments, including the SF-36 questionnaire and 3-hour, continuous nasal-oral spirometry with NOFA. Based on the presence of normal nasal breathing defined as ≥95% of nasal flow, the 97 patients were divided into those with normal nasal breathing (n=31) and impaired nasal breathing (n=66). Results: Patients with normal nasal breathing differed from those with impaired nasal breathing with respect to all SF-36 subscales (physical functioning, p=0.004; role-physical, p=0.009; bodily pain, p<0.001; general health, p=0.007; vitality, p=0.002; social functioning, p=0.008; mental health, p=0.009; physical component summary, p<0.001; mental component summary, p=0.02), except for the role-emotional subscale (p=0.1). Conclusions: Among patients with symptoms of nasal obstruction, compared to patients with normal nasal breathing, those with impaired nasal breathing had significantly lower quality of life in the physical and mental domains. Further research needs to determine whether NOFA can be used to diagnose nasal obstruction.
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Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis... more
Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three patients were aged 80-100, 218 patients were aged 65-79, and 208 patients were <65 years old. Baseline parameters were comparable. The median overall survival (OS) was 14.7, 18.7, 25.9, and the median progression-free survival (PFS) was 8.7, 7.7, and 6.2 months in the age groups of 80-100, 65-79, and <65 years, respectively. The median melanoma-specific survival (MSS) was 22.5, 27.8, and 31.6 months in the age groups of 80-100, 65-79, and <65 years, respectively. There was no statistically significant difference in OS (P = 0.2897), PFS (P = 0.7155), and MSS (P = 0.9235) between the group of 80-100 years old vs. 65-79 and vs. <65 years old patients. Overall response rate and disease control rate was similar in all groups (P = 0.06974 and P = 0.89435, respectively). Overall, the immune-related adverse event (irAE) rate was comparable in the three age groups (41, 34, and 37.5% in the groups of patients aged 80-100, 65-79, and <65 years, respectively). Also, the rates of G3 and G4 irAEs were comparable (4, 6, and 7% in the groups of patients, respectively). The efficacy and toxicity of anti-PD-1 therapy in octogenarians and nonagenarians with metastatic melanoma are similar as in patients aged <65 years and 65-79 years. The patients' age should not be considered as an exclusion criterion for anti-PD-1 treatment.
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Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST 1.1 defined progression. The clinical concept of treating selected patients (pts) beyond disease progression (PD) is supported by so-called... more
Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST 1.1 defined progression. The clinical concept of treating selected patients (pts) beyond disease progression (PD) is supported by so-called pseudoprogression phenomenon. The aim of this study was to evaluate real-life practice and outcomes related to treatment beyond (RECIST) progression (TBP) in advanced melanoma patients. Of 584 subsequent melanoma pts analyzed 77 (13.2%) received TBP. In this cohort, the median time to first PD (TTFP) was 5.29 months (m), while time to second PD (TTSP)—8.02 m. On TBP 23.4% pts achieved an objective response (OR), and next 42.9%—stabilization of the disease (SD). 1st PD was reported most often as the development of a new lesion or increase (> 20%) of the diameter of three or more targets. In about 50% second PD was observed as an increase in the diameter of different targets that in 1st PD. Multimodal treatment resulted in 9.82 m TTSP, while ITH alone—4.93 m (p = 0.128). An oligoprogressive pattern of first PD was associated with longer TTSP (HR 0.55, 95% CI: 0.32–0.94). Median OS after first PD was 28.75 months and correlated with OR during TBP (HR 0.18, 95% CI: 0.004–0.76). Selected clinically fit melanoma patients, despite evidence of first radiographic progression, may benefit from continued treatment with PD-1 checkpoint inhibitors, but the findings should be validated in larger prospective trials. Multidisciplinary treatment should be offered to advanced melanoma patients, including radiosurgery or stereotactic radiotherapy of single loci progressing during immunotherapy.
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(Wpływ sunitinibu i axitinibu na komórki raka jasnokomórkowego nerki)
(Ocena ekspresji genu TRBeta1 w komórkach raka jasnokomórkowego nerki (ccRCC) i komórkach zdrowej nerki oraz ocena wpływu T3 i braku stymulacji TRBeta1 na proliferację tych komórek.)
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Endometrial carcinoma is the most frequently diagnosed cancer among gynecological malignancies in highly developed countries. Since 20 years research has been conducted to define the molecular pathology of this disease and much is already... more
Endometrial carcinoma is the most frequently diagnosed cancer among gynecological malignancies in highly developed countries. Since 20 years research has been conducted to define the molecular pathology of this disease and much is already known, but adequate prognostic, diagnostic and monitoring markers are still missing. Recently a new perspective has been opened by mitochondrial research. The role of abnormalities of those organelles and mutations of the mitochondrial genome has been defined in some types of cancer and is still under investigation. MtDNA mutations are also found in endometrial adenocarcinoma, although their impact on cell physiology has not been described so far. Some processes involving mitochondria are widely known and described by numerous papers. This includes electron transport and apoptosis, but other await further research. In a wide spectrum of projects a forward genetics approach has been used, as cancer tissue samples were collected from subjects with defined diagnosis and metabolic abnormalities and mtDNA mutations were checked. Thanks to this approach characteristic patterns of mitochondrial disruptions have been assigned to specific types of cancer. This review focuses on molecular characteristics of endometrial adenocarcinoma with special focus on mitochondrial abnormalities. Research on cancer molecular pathology in endometrial adenocarcinoma may lead to the development of specific screening and/or diagnostic markers.
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For many years mitochondria have been implicated in the process of carcinogenesis. At the begining of 20th century Otto Warburg has started research focused on failure of oxidative metabolism in cancer cells. In his work he described... more
For many years mitochondria have been implicated in the process of carcinogenesis. At the begining of 20th century Otto Warburg has started research focused on failure of oxidative metabolism in cancer cells. In his work he described „disruption of respiration” as typical for cancer cells. Warburg’s discovery resulted in establishment of many projects focused on the role of mitochondria in cell transformation. Since that time multiple research groups have reported mitochondria DNA mutations in majority of cancer types. Recently re-analyses of raw data has been published and have shown multiple methodical errors in previous reports. This paper presents critical analysis and summary of mitochondria polymorphisms and somatic mutations research in oncology.
Literature analysis that includes latest methodological guidelines established for mtDNA analysis and evidence based medicine reports proves that cancer patients harbour specific pattern of inherited mtDNA polymorphisms and low numer of somatic mutations. It seems that mitochondrial genotype (including haplotype) may be classified as cancer predisposing factor.
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cancer, molecular marker, mitochondria, mtDNA mutation, mtDNA polymorphism, Evidence Based Medicine
Literature analysis that includes latest methodological guidelines established for mtDNA analysis and evidence based medicine reports proves that cancer patients harbour specific pattern of inherited mtDNA polymorphisms and low numer of somatic mutations. It seems that mitochondrial genotype (including haplotype) may be classified as cancer predisposing factor.
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cancer, molecular marker, mitochondria, mtDNA mutation, mtDNA polymorphism, Evidence Based Medicine
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Abstract: Supernumerary, old or damaged cells of multicellular organisms are eliminated by apoptosis programmed cell death. Apoptosis is accompanied by series of characteristic morphological and biochemi-cal events. The cell activates a... more
Abstract: Supernumerary, old or damaged cells of multicellular organisms are eliminated by apoptosis programmed cell death. Apoptosis is accompanied by series of characteristic morphological and biochemi-cal events. The cell activates a cascade of cysteine proteases, caspases, that digest target proteins. Nucleases are also activated, which together leads to irreversible cell damage within few hours. Mitochon-
dria are the cell compartment that integrates signals from different apoptotic pathways activated by
ischemia, heat shock or growth hormones depletion. Mitochondria play the primary role in coordination
and amplification of cell autodegradation signals. They regulate apoptosis by sequestration of pro- and antiapoptotic proteins. Perturbation of activation or execution of apoptosis is characteristic feature of cancer cells.
dria are the cell compartment that integrates signals from different apoptotic pathways activated by
ischemia, heat shock or growth hormones depletion. Mitochondria play the primary role in coordination
and amplification of cell autodegradation signals. They regulate apoptosis by sequestration of pro- and antiapoptotic proteins. Perturbation of activation or execution of apoptosis is characteristic feature of cancer cells.
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Recently published papers report a large number of mitochondrial DNA mutations in many different cancer types, but their significance for electron transport chain proteins remains unknown. This review covers structural mutations of... more
Recently published papers report a large number of mitochondrial DNA mutations in many different cancer types, but their significance for electron transport chain proteins remains unknown. This review covers structural mutations of mitochondrial genes, choosing prostate cancer, esophageal cancer and epithelioma as research models. As all mitochondrial genes encode subunits of the electron transport chain, the review focuses on the consequences of structural mutations on cell metabolism
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The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumor's size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission Tomography... more
The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumor's size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission Tomography (PET) supports this process with additional information about the tumor's metabolism. Numerous publications show that PET-CT has a great influence on the evaluation of the size of the tumor, presence of lymph node metastases, choice of treatment and the prognosis of the recurrence. Cancer cells represent a specific metabolic state. These cells intake large quantities of glucose and utilize it in the process of glycolysis. The oxidative phosphorylation is not efficient in the transformed cells and defects in mitochondrial functions are at the heart of malignant cell transformation. Disruption of the oxidative phosphorylation chain has been described in the neoplasms. As a consequence, in cancer the glycolysis is active even in the normoxic environment. This metabolic shift in cell transformation has been described in early XX century and so called Warburg's hypothesis profoundly influenced the present perception of cancer metabolism, positioning what is termed aerobic glycolysis in the mainstream of clinical oncology. Today we know that neoplastic cells differ at the proteomic level. A subset of different proteins such as hexokinase II or HIF are upregulated. These abnormalities might be used as the neoplastic markers.
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Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA... more
Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should
not be excluded from this analysis. mtDNA have been reported in many cancers of head and neck region. Mitochondrial D-loop has been proven to be mutation hot - spot with majority of mutations in the positions 303 to 315 of poly-C tract. Data show that 37% of patients with prema-lignant lesions and 62% with carcinoma in situ are positive for mtDNA mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6 were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured in similar number of cases. Neoplastic cells undifferentiation and disease progression is accompanied by multiplication of mtDNA number and increased mtDNA
content. mtDNA content corellates with the stage of the disease. mtDNA mutations faciliate cell proliferation and inhibit apoptosis by increasing the production of ractive oxygen species (ROS).
Cells harbouring mutated mtDNA have increased proliferation rate, as increased ROS concentration may act as an endogenous growth factor.
not be excluded from this analysis. mtDNA have been reported in many cancers of head and neck region. Mitochondrial D-loop has been proven to be mutation hot - spot with majority of mutations in the positions 303 to 315 of poly-C tract. Data show that 37% of patients with prema-lignant lesions and 62% with carcinoma in situ are positive for mtDNA mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6 were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured in similar number of cases. Neoplastic cells undifferentiation and disease progression is accompanied by multiplication of mtDNA number and increased mtDNA
content. mtDNA content corellates with the stage of the disease. mtDNA mutations faciliate cell proliferation and inhibit apoptosis by increasing the production of ractive oxygen species (ROS).
Cells harbouring mutated mtDNA have increased proliferation rate, as increased ROS concentration may act as an endogenous growth factor.