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Article: Menopausal Status Contributes to Overall Survival in Endometrial Cancer Patients.

Barczyński, Bartłomiej / Frąszczak, Karolina / Wnorowski, Artur / Kotarski, Jan

2023 Volume 15, Issue 2

Abstract: Endometrial cancer is the most common female genital tract malignancy in developed countries that occurs predominantly in postmenopausal women. The primary objective of our research was to investigate whether menopause status together with selected ... ...

Abstract	Endometrial cancer is the most common female genital tract malignancy in developed countries that occurs predominantly in postmenopausal women. The primary objective of our research was to investigate whether menopause status together with selected conventional prognostic indicators may contribute to overall (all-cause) survival in endometrial cancer patients. For this purpose, we applied the Cox proportional hazards regression model. Patients in advanced FIGO stage showed a relatively poor survival rate. The time since last menstruation and postoperative FSH concentration were identified as unfavorable prognostic factors in our model. Additionally, age at diagnosis, BMI value, adjuvant treatment (brachytherapy), and parity showed no impact on survival. To our knowledge, this is the first study to report a prognostic model for endometrial cancer including exact time from last menstruation as one of the prognostic variables. Due to the fact that there are no stratifying systems to reliably predict survival in patients with endometrial cancer, there is a strong need to revise and update existing models using complementary prognostic indicators. Collection of precise data on various risk factors may contribute to increased accuracy of artificial intelligence algorithms in order to personalize cancer care in the near future.
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15020451
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Article ; Online: Clinical Relevance of Mortalin in Ovarian Cancer Patients.

Rajtak, Alicja / Czerwonka, Arkadiusz / Pitter, Michael / Kotarski, Jan / Okła, Karolina

Cells

2023 Volume 12, Issue 5

Abstract: ... ...

Abstract	Background
MeSH term(s)	Humans ; Female ; Ecosystem ; Ascites ; Clinical Relevance ; Proteomics ; Ovarian Neoplasms
Chemical Substances	mortalin
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12050701
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Article ; Online: Perspectives of metformin use in endometrial cancer and other gynaecological malignancies.

Barczyński, Bartłomiej / Frąszczak, Karolina / Kotarski, Jan

Journal of drug targeting

2021 Volume 30, Issue 4, Page(s) 359–367

Abstract: Insulin resistance and hyperinsulinemia play a key role in type 1 endometrial cancer pathogenesis. Most of these cancers develop on a background of overweight or type 2 diabetes mellitus (T2DM). One of the medications widely used in the treatment of T2DM ...

Abstract	Insulin resistance and hyperinsulinemia play a key role in type 1 endometrial cancer pathogenesis. Most of these cancers develop on a background of overweight or type 2 diabetes mellitus (T2DM). One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways. Many epidemiological studies on diabetic patients show potential preventative role of metformin in endometrial cancer patients, but data regarding its therapeutic role is still limited. So far, most of attention has been paid to the concept of metformin use in fertility sparing treatment of early-stage cancer. Another investigated alternative is its application in patients with primary advanced or recurrent disease. In this review we present the latest data on clinical use of metformin in endometrial cancer patients and potential underlying mechanisms of its activity. Finally, we present some most important clinical information regarding metformin efficacy in other gynaecological malignancies, mainly breast and ovarian cancer.
MeSH term(s)	Diabetes Mellitus, Type 2/drug therapy ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/metabolism ; Female ; Genital Neoplasms, Female/drug therapy ; Humans ; Hypoglycemic Agents/therapeutic use ; Metformin/therapeutic use
Chemical Substances	Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2021-11-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1187110-6
ISSN	1029-2330 ; 1061-186X
ISSN (online)	1029-2330
ISSN	1061-186X
DOI	10.1080/1061186X.2021.2005072
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Article ; Online: Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors.

Pawłowska, Anna / Rekowska, Anna / Kuryło, Weronika / Pańczyszyn, Anna / Kotarski, Jan / Wertel, Iwona

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest ...

Abstract	The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10-15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.
MeSH term(s)	Humans ; Female ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Inhibitors/metabolism ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Lymphocytes, Tumor-Infiltrating ; Immunotherapy ; Carcinoma, Ovarian Epithelial/drug therapy ; Tumor Microenvironment
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2023-06-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310859
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Article ; Online: Vaginal and Cervical Microbiota Composition in Patients with Endometrial Cancer.

Barczyński, Bartłomiej / Frąszczak, Karolina / Grywalska, Ewelina / Kotarski, Jan / Korona-Głowniak, Izabela

International journal of molecular sciences

2023 Volume 24, Issue 9

Abstract: According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to ... ...

Abstract	According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy due to benign disease, atypical hyperplasia, and endometrial cancer; The study included 96 patients, who undergone surgical treatment due to benign uterine disease, precancerous endometrial lesion, and endometrial cancer. Quantitative and qualitative real-time PCR analysis of DNA isolated from vaginal fornix and endocervical canal samples was performed to detect the 19 most commonly identified microorganisms, including different
MeSH term(s)	Humans ; Female ; Cervix Uteri/microbiology ; Vagina/microbiology ; Endometrial Neoplasms/genetics ; Uterine Diseases ; Microbiota/genetics ; RNA, Ribosomal, 16S/genetics
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2023-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24098266
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Article ; Online: Chaos and cancers. Theories concerning carcinogenesis.

Kwasniewski, Wojciech / Stupak, Aleksandra / Kotarski, Jan / Gozdzicak-Jozefiak, Anna

Ginekologia polska

2021 Volume 92, Issue 4, Page(s) 318–321

Abstract: One of the most intriguing problems in biomedical sciences is the theory explaining cancer formation. It is known that cancer is the result of many molecular processes, the presence of oncogenic factors and the loss of apoptosis of affected cells. We ... ...

Abstract	One of the most intriguing problems in biomedical sciences is the theory explaining cancer formation. It is known that cancer is the result of many molecular processes, the presence of oncogenic factors and the loss of apoptosis of affected cells. We currently have hypotheses based on carcinogenesis because of a single cell gene mutation, i.e. somatic mutation theory (SMT), or disorders in tissue architecture and intercellular communication called (TOFT) Tissue Organization Field Theory. An attempt to combine these separate and compatible cause and effect pathways into one unified theory of cancer transformation is the theory of chaotic adaptation. The new interpretative model is the systemic-evolution theory of cancer (SETOC) which postulates disintegration between the symbiosis of "energy" and "information" in normal cells. There are also epidemiological studies confirming that some types of cancer arise from viral infection. So, let us ask the question, can one hypothesis explain all the features of cancer?
MeSH term(s)	Adaptation, Physiological ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic ; Humans ; Mutation ; Neoplasms
Language	English
Publishing date	2021-03-23
Publishing country	Poland
Document type	Journal Article
ZDB-ID	130894-4
ISSN	2543-6767 ; 0017-0011
ISSN (online)	2543-6767
ISSN	0017-0011
DOI	10.5603/GP.a2021.0003
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Article ; Online: Integration of local and systemic immunity in ovarian cancer: Implications for immunotherapy.

Rajtak, Alicja / Ostrowska-Leśko, Marta / Żak, Klaudia / Tarkowski, Rafał / Kotarski, Jan / Okła, Karolina

Frontiers in immunology

2022 Volume 13, Page(s) 1018256

Abstract: Cancer is a disease that induces many local and systemic changes in immunity. The difficult nature of ovarian cancer stems from the lack of characteristic symptoms that contributes to a delayed diagnosis and treatment. Despite the enormous progress in ... ...

Abstract	Cancer is a disease that induces many local and systemic changes in immunity. The difficult nature of ovarian cancer stems from the lack of characteristic symptoms that contributes to a delayed diagnosis and treatment. Despite the enormous progress in immunotherapy, its efficacy remains limited. The heterogeneity of tumors, lack of diagnostic biomarkers, and complex immune landscape are the main challenges in the treatment of ovarian cancer. Integrative approaches that combine the tumor microenvironment - local immunity - together with periphery - systemic immunity - are urgently needed to improve the understanding of the disease and the efficacy of treatment. In fact, multiparametric analyses are poised to improve our understanding of ovarian tumor immunology. We outline an integrative approach including local and systemic immunity in ovarian cancer. Understanding the nature of both localized and systemic immune responses will be crucial to boosting the efficacy of immunotherapies in ovarian cancer patients.
MeSH term(s)	Humans ; Female ; Immunotherapy ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/therapy ; Immunologic Factors ; Tumor Microenvironment
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2022-11-10
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1018256
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Article: Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions.

Żak, Klaudia / Zaremba, Bartłomiej / Rajtak, Alicja / Kotarski, Jan / Amant, Frédéric / Bobiński, Marcin

Cancers

2022 Volume 14, Issue 8

Abstract: The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods ... ...

Abstract	The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to create different scales analyzing available parameters and to combine them with imaging methods with the aim of ULMs and ULM preoperative differentiation ULMs and ULM. Moreover, it has been observed that the technology, meaning machine learning models and artificial intelligence (AI), is entering the world of medicine, including gynecology. Therefore, we can predict the diagnosis not only through symptoms, laboratory tests or imaging methods, but also, we can base it on AI. What is the best option to differentiate ULM and ULMS preoperatively? In our review, we focus on the possible methods to diagnose uterine lesions effectively, including clinical signs and symptoms, laboratory tests, imaging methods, molecular aspects, available scales, and AI. In addition, considering costs and availability, we list the most promising methods to be implemented and investigated on a larger scale.
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14081966
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Article: The State of Health and the Quality of Life in Women Suffering from Endometriosis.

Ruszała, Monika / Dłuski, Dominik Franciszek / Winkler, Izabela / Kotarski, Jan / Rechberger, Tomasz / Gogacz, Marek

Journal of clinical medicine

2022 Volume 11, Issue 7

Abstract: Quality of life is related to good health, family relations, feeling of self-esteem, and ability to cope with difficult situations. Endometriosis is a chronic condition which affects different areas of life. The lack of satisfaction in everyday life is ... ...

Abstract	Quality of life is related to good health, family relations, feeling of self-esteem, and ability to cope with difficult situations. Endometriosis is a chronic condition which affects different areas of life. The lack of satisfaction in everyday life is mainly due to constant pain. The process of adjusting to a life with illness is associated with negative emotions. The aim of the article is to review the current state of knowledge concerning the impact of social and medical factors on a population of women affected by endometriosis. Women with endometriosis have an impaired quality of life compared to the general female population. Psychological consequences of endometriosis include: depression, anxiety, powerlessness, guilt, self-directed violence, and deterioration of interpersonal relations. It may contribute to lower productivity at work and less satisfying intimate life. A multi-disciplinary, evidence-based care is needed. The disease can take away the ability to be physically active, obtain an education, work continuously, and interact with friends. Social support and cognitive-behavioral therapy are extremely important for healing.
Language	English
Publishing date	2022-04-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11072059
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Article ; Online: Immunohistochemical Expression of LHRH Receptor in Different Compartments of Female Genital Tract in Patients With Endometrial Cancer.

Barczyński, Bartłomiej / Frąszczak, Karolina / Wertel, Iwona / Zakrzewska, Ewelina / Zdunek, Małgorzata / Szumiło, Justyna / Kotarski, Jan

Applied immunohistochemistry & molecular morphology : AIMM

2022 Volume 30, Issue 7, Page(s) 509–516

Abstract: Luteinizing hormone-releasing hormone receptor (LHRHR) expression has been reported in various cancers, including endometrial neoplasms. Thus, LHRHR provides a potential point for therapeutic approach using LHRH analogs as carrier molecules for ... ...

Abstract	Luteinizing hormone-releasing hormone receptor (LHRHR) expression has been reported in various cancers, including endometrial neoplasms. Thus, LHRHR provides a potential point for therapeutic approach using LHRH analogs as carrier molecules for chemotherapeutic agents in this cancer population. However, clinical data did not prove any potential benefits for patients. We decided to assess LHRHR expression in patients with endometrial cancer to explain possible lack of efficacy in previous clinical reports. LHRHR expression was assessed immunohistochemically in different anatomic and histogenetic compartments of female genital tract of patients with endometrial cancer. The study sample consisted of paraffin tissue blocks obtained from patients who has undergone primary surgery owing to endometrial cancer. Strong LHRHR expression was found in endometrial cancer, fallopian tube, and concurrent atypical hyperplasia. Interestingly, LHRHR expression showed significant differences depending on the respective compartment of the ovary analyzed. Level of LHRHR expression in patients with primary advanced and unresectable disease, particularly in certain ovarian compartments may be substantially lower, which may influence the use of new targeted therapy regimens. The studies on secondary Müllerian system compartment and its hormonal receptor status may be crucial to understand mechanisms of lack of efficacy of LHRH hybrid molecules anti-cancer treatment.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Endometrial Neoplasms/metabolism ; Female ; Genitalia, Female/metabolism ; Gonadotropin-Releasing Hormone/metabolism ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Receptors, LHRH/metabolism ; Receptors, LHRH/therapeutic use
Chemical Substances	Antineoplastic Agents ; Receptors, LHRH ; Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2022-07-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1473273-7
ISSN	1533-4058 ; 1062-3345 ; 1541-2016
ISSN (online)	1533-4058
ISSN	1062-3345 ; 1541-2016
DOI	10.1097/PAI.0000000000001046
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