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Article ; Online: Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment.

Samuels, Mark / Cilibrasi, Chiara / Papanastasopoulos, Panagiotis / Giamas, Georgios

2022 Volume 12, Issue 1

Abstract: Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour ... ...

Abstract	Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.
MeSH term(s)	Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Cell Communication ; Drug Resistance ; Extracellular Vesicles/metabolism ; Female ; Humans ; Neoplasms/metabolism ; Tumor Microenvironment
Language	English
Publishing date	2022-01-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12010132
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications.

Agnarelli, Alessandro / Vella, Viviana / Samuels, Mark / Papanastasopoulos, Panagiotis / Giamas, Georgios

Cancers

2022 Volume 14, Issue 18

Abstract: Gastric cancer has a median survival of 11 months, and this poor prognosis has not improved over the last 30 years. Recent pre-clinical data suggest that there is high tumour-related neoantigen expression in gastric cancer cells, suggesting that a ... ...

Abstract	Gastric cancer has a median survival of 11 months, and this poor prognosis has not improved over the last 30 years. Recent pre-clinical data suggest that there is high tumour-related neoantigen expression in gastric cancer cells, suggesting that a clinical strategy that enhances the host's immune system against cancer cells may be a successful approach to improve clinical outcomes. Additionally, there has been an increasing amount of translational evidence highlighting the relevance of PD-L1 expression in gastric cancer cells, indicating that PD-1/PD-L1 inhibitors may be useful. Several molecular subgroups of gastric cancer have been identified to respond with excellent outcomes to immunotherapy, including microsatellite instable tumours, tumours bearing a high tumour mutational burden, and tumours related to a chronic EBV infection. In gastric cancer, immunotherapy has produced durable responses in chemo-refractory patients; however, most recently there has been a lot of enthusiasm as several large-scale clinical trials highlight the improved survival noted from the incorporation of immunotherapy in the first line setting for advanced gastric cancer. Our review aims to discuss current pre-clinical and clinical data supporting the innovative role of immunotherapy in gastric cancer.
Language	English
Publishing date	2022-09-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14184378
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Article ; Online: Reconstituting Immune Surveillance in Breast Cancer: Molecular Pathophysiology and Current Immunotherapy Strategies.

Cilibrasi, Chiara / Papanastasopoulos, Panagiotis / Samuels, Mark / Giamas, Georgios

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: Over the past 50 years, breast cancer immunotherapy has emerged as an active field of research, generating novel, targeted treatments for the disease. Immunotherapies carry enormous potential to improve survival in breast cancer, particularly for the ... ...

Abstract	Over the past 50 years, breast cancer immunotherapy has emerged as an active field of research, generating novel, targeted treatments for the disease. Immunotherapies carry enormous potential to improve survival in breast cancer, particularly for the subtypes carrying the poorest prognoses. Here, we review the mechanisms by which cancer evades immune destruction as well as the history of breast cancer immunotherapies and recent developments, including clinical trials that have shaped the treatment of the disease with a focus on cell therapies, vaccines, checkpoint inhibitors, and oncolytic viruses.
MeSH term(s)	Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Female ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunologic Surveillance ; Immunotherapy/methods ; Immunotherapy, Adoptive/methods ; Oncolytic Virotherapy/methods
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-11-06
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/ijms222112015
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Article ; Online: Molecular basis of 5-fluorouracil-related toxicity: lessons from clinical practice.

Papanastasopoulos, Panagiotis / Stebbing, Justin

Anticancer research

2014 Volume 34, Issue 4, Page(s) 1531–1535

Abstract: We aim to present a comprehensive review of the molecular basis of 5-fluorouracil (5-FU) toxicity, of which dihydropyrimidine dehydrogenase (DYPD) deficiency is a well-known mechanism. The prevalence of partial DYPD deficiency is fairly common, ranging ... ...

Abstract	We aim to present a comprehensive review of the molecular basis of 5-fluorouracil (5-FU) toxicity, of which dihydropyrimidine dehydrogenase (DYPD) deficiency is a well-known mechanism. The prevalence of partial DYPD deficiency is fairly common, ranging between 3-5% in the general population, whereas it can be as high as 12% in African-American females. More than 50 genetic polymorphisms have been described as being associated with decreased enzymatic activity, whereas the c.1905+1G>A point mutation is the most commonly found (52% of cases), with a prevalence of heterozygosity in the general population ranging between 1-2%. Several methods have been utilized to identify reduced DYPD activity; functional tests are expensive and only available in specialized centers. Genotyping alone is not reliable enough, as some of the polymorphisms may not result in significantly reduced DYPD activity. The rate of cardiotoxicity associated with 5-FU or capecitabine does not seem to be related to DYPD deficiency, and has been estimated to range between 1.2-8%. Several pathophysiological mechanisms seem to contribute to 5-FU cardiotoxicity, including coronary spasm, increased endothelial thrombogenicity and myocardial inflammation. Tegafur/uracil and raltitrexed may be alternative options for patients with partial DYPD deficiency and previous manifested 5-FU cardiotoxicity, respectively. Pharmacogenetics is expected to further identify and clarify the mechanisms associated with 5-FU-related toxicity, thus aiding the oncology societies to formulate specific guidance on pre-treatment testing.
MeSH term(s)	Antimetabolites, Antineoplastic/adverse effects ; Antimetabolites, Antineoplastic/therapeutic use ; Dihydropyrimidine Dehydrogenase Deficiency ; Dihydrouracil Dehydrogenase (NADP)/genetics ; Drug-Related Side Effects and Adverse Reactions/genetics ; Drug-Related Side Effects and Adverse Reactions/metabolism ; Fluorouracil/adverse effects ; Fluorouracil/therapeutic use ; Humans ; Pharmacogenetics ; Polymorphism, Genetic
Chemical Substances	Antimetabolites, Antineoplastic ; Dihydrouracil Dehydrogenase (NADP) (EC 1.3.1.2) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2014-04-01
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article ; Online: The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor.

Agnarelli, Alessandro / Lauer Betrán, Andrea / Papakyriakou, Athanasios / Vella, Viviana / Samuels, Mark / Papanastasopoulos, Panagiotis / Giamas, Christina / Mancini, Erika J / Stebbing, Justin / Spencer, John / Cilibrasi, Chiara / Ditsiou, Angeliki / Giamas, Georgios

International journal of molecular sciences

2023 Volume 24, Issue 1

Abstract: Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical ... ...

Abstract	Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel. We also report the binding affinity between LMTK3 and C36 as demonstrated via microscale thermophoresis (MST). In addition, C36 exhibits a mixed-type inhibition against LMTK3, consistent with the inhibitor overlapping with both the adenosine 5'-triphosphate (ATP)- and substrate-binding sites. Treatment of different breast cancer cell lines with C36 led to decreased proliferation and increased apoptosis, further reinforcing the prospective value of LMTK3 inhibitors for cancer therapy.
MeSH term(s)	Cell Line, Tumor ; Prospective Studies ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Humans
Chemical Substances	Protein Kinase Inhibitors ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; LMTK3 protein, human (EC 2.7.11.1)
Language	English
Publishing date	2023-01-03
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/ijms24010865
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Article ; Online: Nuts and cancer: where are we now?

Papanastasopoulos, Panagiotis / Stebbing, Justin

The Lancet. Oncology

2013 Volume 14, Issue 12, Page(s) 1161–1162

MeSH term(s)	Animals ; Diet/adverse effects ; Humans ; Neoplasms/epidemiology ; Neoplasms/prevention & control ; Nuts ; Risk Factors ; Risk Reduction Behavior
Language	English
Publishing date	2013-10-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(13)70516-3
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Follicular Lymphoma in a Patient with Previously Treated Early Breast Cancer; the Role of PET Imaging and Repeat Tissue Diagnosis.

Papanastasopoulos, Panagiotis / Merchant, Shairoz / Kenny, Laura

The breast journal

2015 Volume 21, Issue 6, Page(s) 691–692

MeSH term(s)	Breast Neoplasms/therapy ; Carcinoma, Ductal, Breast/therapy ; Ear ; Female ; Humans ; Lymph Nodes/diagnostic imaging ; Lymph Nodes/pathology ; Lymphoma, Follicular/diagnostic imaging ; Lymphoma, Follicular/pathology ; Mediastinum ; Middle Aged ; Neoplasms, Second Primary/pathology ; Positron-Emission Tomography ; Retroperitoneal Space
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	1289960-4
ISSN	1524-4741 ; 1075-122X
ISSN (online)	1524-4741
ISSN	1075-122X
DOI	10.1111/tbj.12511
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Zs.A 4483: Show issues

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Article ; Online: HIV-related Kaposi's Sarcoma with Musculoskeletal Involvement in the Modern Antiretroviral Era.

Papanastasopoulos, Panagiotis / Annan, Bertrand / Dalla Pria, Alessia / Bower, Mark

Anticancer research

2016 Volume 36, Issue 7, Page(s) 3465–3469

Abstract: Aim: To describe the patterns of disease and clinical outcomes of MSK-KS in people living with HIV in the era of (combination anti-retroviral therapy cART).: Patients and methods: We reviewed our prospectively collected dataset of patients with HIV ... ...

Abstract	Aim: To describe the patterns of disease and clinical outcomes of MSK-KS in people living with HIV in the era of (combination anti-retroviral therapy cART). Patients and methods: We reviewed our prospectively collected dataset of patients with HIV with biopsy-proven KS; 17 out of 1,489 seropositive patients were identified with subsequent evidence of MSK involvement by KS. We collected data with regards to clinicopathological parameters and radiological patterns of disease. Results: Fourteen patients (82.4%) had AIDS Clinical Trials Group T1 stage disease at presentation including four (23.5%) with non-nodal visceral disease. At the time of MSK-KS diagnosis, more than 80% of 14 patients had excellent HIV control. The median interval between initial KS to MSK-KS diagnosis was 3.3 years. Five-year overall survival rate from initial KS diagnosis was 76%, and 60% from MSK-KS diagnosis. The majority of patients were asymptomatic and MSK-KS involvement was demonstrated during imaging prompted by progression of their mucocutaneous KS. The majority of lesions were lytic with cortical involvement on cross-sectional imaging, whereas a soft-tissue component was commonly associated with long-bone involvement. Conclusion: MSK-KS continues to be a rare entity in the modern era of cART, however patients appear to experience significantly improved survival.
MeSH term(s)	Adult ; Anti-HIV Agents/therapeutic use ; Bone Neoplasms/mortality ; Bone Neoplasms/secondary ; Bone Neoplasms/therapy ; Bone Neoplasms/virology ; Female ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Male ; Middle Aged ; Muscle Neoplasms/mortality ; Muscle Neoplasms/secondary ; Muscle Neoplasms/therapy ; Muscle Neoplasms/virology ; Sarcoma, Kaposi/mortality ; Sarcoma, Kaposi/secondary ; Sarcoma, Kaposi/therapy ; Sarcoma, Kaposi/virology ; Survival Analysis ; Treatment Outcome ; Young Adult
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2016-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Zs.A 1642: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: A Unique Case of Extraovarian Sex-Cord Stromal Fibrosarcoma, With Subsequent Relapse of Differentiated Sex-Cord Tumor.

Wang, Jayson / Papanastasopoulos, Panagiotis / Savage, Philip / Smith, James Richard / Fisher, Cyril / El-Bahrawy, Mona A

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

2015 Volume 34, Issue 4, Page(s) 363–368

Abstract: Primary fibrosarcoma arising from ovarian sex-cord stroma is a very rare neoplasm, with only a few reports in the literature. These tumors have been reported to express inhibin which allows their distinction from fibrosarcomas of soft tissue. Here, we ... ...

Abstract	Primary fibrosarcoma arising from ovarian sex-cord stroma is a very rare neoplasm, with only a few reports in the literature. These tumors have been reported to express inhibin which allows their distinction from fibrosarcomas of soft tissue. Here, we report a case of a fibrosarcoma arising in the broad ligament. Despite being totally separate from the ovary, the tumor was diagnosed as sex-cord stromal type on the basis of inhibin expression. Furthermore, this patient suffered a recurrence of her tumor in the pelvis, which showed both the fibrosarcomatous, as well as other sex-cord elements, confirming the sex-cord stromal differentiation of the sarcoma. To our knowledge, this is the first case of a sex-cord stromal fibrosarcoma arising from an extraovarian site. Furthermore, this is also the first case of a recurrent fibrosarcoma, which showed redifferentiation of the tumor into other sex-cord components.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Cell Differentiation ; Female ; Fibrosarcoma/metabolism ; Fibrosarcoma/pathology ; Humans ; Immunohistochemistry ; Inhibins/metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Pelvic Neoplasms/metabolism ; Pelvic Neoplasms/pathology ; Pelvic Neoplasms/secondary ; Sex Cord-Gonadal Stromal Tumors/metabolism ; Sex Cord-Gonadal Stromal Tumors/pathology
Chemical Substances	Biomarkers, Tumor ; Inhibins (57285-09-3)
Language	English
Publishing date	2015-07
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604859-6
ISSN	1538-7151 ; 0277-1691
ISSN (online)	1538-7151
ISSN	0277-1691
DOI	10.1097/PGP.0000000000000151
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Zs.A 1814: Show issues

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Article ; Online: Clinical characteristics and outcomes for patients with an initial emergency presentation of malignancy: a 15 month audit of patient level data.

Savage, Philip / Sharkey, Rachel / Kua, Teresa / Papanastasopoulos, Panagiotis / McDonald-Burrows, Zoe / Hassan, Shazalia / Probst, Fay / Sanders, Ali / Millington, Hugh

Cancer epidemiology

2015 Volume 39, Issue 1, Page(s) 86–90

Abstract: Aim: To investigate the demographics, diagnoses and outcomes for new adult cancer patients with an initial presentation via the A&E or acute oncology teams.: Background: Patients with initial emergency presentation of malignancy have been documented ... ...

Abstract	Aim: To investigate the demographics, diagnoses and outcomes for new adult cancer patients with an initial presentation via the A&E or acute oncology teams. Background: Patients with initial emergency presentation of malignancy have been documented to have poorer treatment outcomes and shorter survival. Patient level data on this subject is relatively limited with regard to the demographics, diagnoses and the clinical factors that may underlie late presentations. Methods: A 15 month audit of the patients presenting with a new diagnosis of malignancy was performed in 2011-2012. Data on demographics, diagnosis and outcome were assembled and analysed. The clinical data on emergency presentations were compared to reference information on the incidence and median age at presentation for each malignancy within the standard population. Results: During the study a total of 178 new cancer patients presented via the A and E service. The most frequent diagnoses were lung cancer with 21% of cases and CNS and colorectal cancer each with 9% of cases. There was a higher incidence of emergency new presentations of lung cancer, CNS tumours, ovarian, pancreatic and testicular cancer than in the standard population, whilst breast cancer, bladder cancer and prostate cancer patients were under-represented. The median age at diagnosis was 74 and for a number of malignancies including CNS tumours, breast cancer, colorectal cancer and head and neck cancer the emergency cases presented at significantly greater ages than in the standard population. Overall 27% of patients were unfit or unsuitable for a diagnostic biopsy, this group had only a 3 month median survival compared to 14 months for those suitable for biopsy and treatment. Conclusion: Despite a wide range of initiatives, the emergency and late diagnosis of patients with metastatic cancer remains a significant challenge with many patients too advanced and unwell at presentation for active treatment. These patients tend to be older and have malignancies that present with either non-specific symptoms or symptoms requiring acute assessment. Improving the pathways for these patients will be challenging and require additional planning on improving awareness and access for these potentially hard to reach patients.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biopsy ; Emergencies ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/pathology ; Prospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2015-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2508729-0
ISSN	1877-783X ; 1877-7821
ISSN (online)	1877-783X
ISSN	1877-7821
DOI	10.1016/j.canep.2014.11.001
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