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  1. Article: Cutaneous Sebaceous Carcinoma Presenting as a Large Fungating Breast Tumour in Synchronicity With Primary Carcinomata of the Breasts.

    Makaranka, Stanislau / Frixou, Mikaela / Mustafa, Ahmed / Husain, Ehab

    Cureus

    2022  Volume 14, Issue 9, Page(s) e28896

    Abstract: Sebaceous carcinomas are rare malignant tumours which arise from sebaceous glands. They are subclassified into ocular and extraocular subtypes and most commonly occur in the head and neck region. Tumours below the neck occur infrequently, and most ... ...

    Abstract Sebaceous carcinomas are rare malignant tumours which arise from sebaceous glands. They are subclassified into ocular and extraocular subtypes and most commonly occur in the head and neck region. Tumours below the neck occur infrequently, and most commonly resemble benign skin lesions such as pyogenic granulomata and molluscum contagiosum, or malignant skin tumours like basal and squamous cell carcinomas (SCCs). We report a case of an 86-year-old lady presenting with a fungating breast tumour which began as a "mole" and exhibited insidious growth over five years to reach a maximum size of 10 cm. An excision biopsy was performed by the breast surgery team and histopathological analysis revealed a sebaceous carcinoma arising from the skin adnexa. On subsequent follow up, the patient was found to have a 19 mm mass in the left breast and a 20 mm mass in the right breast, which was P5 and P3 on clinical palpation, respectively. Core biopsies of left and right breast lesions showed invasive lobular carcinoma and invasive ductal carcinoma with lobular features respectively; the patient was started on primary letrozole treatment. The patient also went on to have a 2 cm wide local excision of the sebaceous carcinoma scar which was excised down to the pectoralis fascia. This is a unique presentation of a sebaceous gland carcinoma presenting as a fungating breast tumour. These tumours have a high metastatic potential and local recurrence rate, and can co-exist with primary carcinoma of the breast.
    Language English
    Publishing date 2022-09-07
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2747273-5
    ISSN 2168-8184
    ISSN 2168-8184
    DOI 10.7759/cureus.28896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The gut microbiome and melanoma: A review.

    Makaranka, Stanislau / Scutt, Freya / Frixou, Mikaela / Wensley, Katherine E / Sharma, Ravi / Greenhowe, Jennifer

    Experimental dermatology

    2022  Volume 31, Issue 9, Page(s) 1292–1301

    Abstract: Disturbances in the microbial ecosystem have been implemented in chronic inflammation, immune evasion and carcinogenesis, with certain microbes associated with the development of specific cancers. In recent times, the gut microbiome has been recognised ... ...

    Abstract Disturbances in the microbial ecosystem have been implemented in chronic inflammation, immune evasion and carcinogenesis, with certain microbes associated with the development of specific cancers. In recent times, the gut microbiome has been recognised as a potential novel player in the pathogenesis and treatment of malignant melanoma. It has been shown that the composition of gut microbiota in early-stage melanoma changes from in situ to invasive and then to metastatic disease. The gut bacterial and fungal profile has also been found to be significantly different in melanoma patients compared to controls. Multiple studies of immune checkpoint inhibitor (ICI) therapies have shown that the commensal microbiota may have an impact on anti-tumor immunity and therefore ICI response in cancer patients. When it comes to chemotherapy and radiotherapy treatments, studies demonstrate that gut microbiota are invaluable in the repair of radiation and chemotherapy-induced damage and therapeutic manipulation of gut microbiota can be an effective strategy to deal with side effects. Studies demonstrate the oncogenic and tumor-suppressive properties of the gut microbiome, which may play a role in the pathogenesis of melanoma. Despite this, investigations into specific interactions are still in its infancy, but starting to gain momentum as more significant and clinically relevant effects are emerging.
    MeSH term(s) Carcinogenesis ; Gastrointestinal Microbiome ; Humans ; Immunotherapy ; Melanoma/therapy ; Microbiota ; Neoplasms ; Skin Neoplasms/therapy
    Language English
    Publishing date 2022-07-11
    Publishing country Denmark
    Document type Journal Article ; Review
    ZDB-ID 1130936-2
    ISSN 1600-0625 ; 0906-6705
    ISSN (online) 1600-0625
    ISSN 0906-6705
    DOI 10.1111/exd.14639
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Type 1 Diabetes in STAT Protein Family Mutations: Regulating the Th17/Treg Equilibrium and Beyond.

    Fabbri, Marco / Frixou, Mikaela / Degano, Massimo / Fousteri, Georgia

    Diabetes

    2019  Volume 68, Issue 2, Page(s) 258–265

    Abstract: Improvements in the immunological, molecular, and genetic technologies such as next-generation sequencing have led to an exponential increase in the number of monogenic immune dysregulatory syndromes diagnosed, where type 1 diabetes (T1D) forms part of ... ...

    Abstract Improvements in the immunological, molecular, and genetic technologies such as next-generation sequencing have led to an exponential increase in the number of monogenic immune dysregulatory syndromes diagnosed, where type 1 diabetes (T1D) forms part of the autoimmune manifestations. Here, we reviewed the mutations in the signal transducer and activator of transcription (STAT) protein family, namely gain-of-function (GOF) mutations in
    MeSH term(s) Animals ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/metabolism ; Humans ; Mutation/genetics ; STAT1 Transcription Factor/genetics ; STAT3 Transcription Factor/genetics ; T-Lymphocytes, Regulatory/metabolism ; Th17 Cells/metabolism
    Chemical Substances STAT1 Transcription Factor ; STAT3 Transcription Factor
    Language English
    Publishing date 2019-01-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db18-0627
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The use of growth hormone therapy in adults with Prader-Willi syndrome: A systematic review.

    Frixou, Mikaela / Vlek, Diane / Lucas-Herald, Angela K / Keir, Lindsay / Kyriakou, Andreas / Shaikh, M Guftar

    Clinical endocrinology

    2020  Volume 94, Issue 4, Page(s) 645–655

    Abstract: Objective: Despite clear benefits in the management of children with Prader-Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to conduct a systematic review to evaluate the effects of GH on body ... ...

    Abstract Objective: Despite clear benefits in the management of children with Prader-Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to conduct a systematic review to evaluate the effects of GH on body composition, bone health and cardiovascular health in adults with PWS.
    Design: A systematic computerized literature search of the PubMed database was conducted by two independent reviewers. Inclusion criteria were individuals over the age of 16 years with a genetic diagnosis of PWS who had received GH therapy, together with assessment of body composition, bone health or cardiovascular health.
    Results: Twenty full-text papers met the inclusion criteria, encompassing 364 unique patients. No differences in body mass index (BMI) were noted, although 2 studies reported increased BMI after GH cessation. Data demonstrated statistically significant increases in lean body mass and reductions in percentage fat mass. Studies reported inconsistent effects of GH on cholesterol and echocardiography parameters. No studies reported differences in bone mineral density, although one reported improved bone geometry. Minor adverse events including pretibial oedema, headache and transient impaired glucose tolerance were reported in 7 studies.
    Conclusions: These data suggest that GH is safe and well tolerated in adults with PWS, with evidence of improvement in body composition. Further longitudinal studies are still required to investigate the effects of GH on bone and cardiovascular health. Where GH is used in adults with PWS, this should be managed by a specialist multidisciplinary team with regular monitoring initiated.
    MeSH term(s) Adolescent ; Adult ; Body Composition ; Bone Density ; Child ; Growth Hormone ; Human Growth Hormone/therapeutic use ; Humans ; Prader-Willi Syndrome/drug therapy
    Chemical Substances Human Growth Hormone (12629-01-5) ; Growth Hormone (9002-72-6)
    Language English
    Publishing date 2020-12-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
    ZDB-ID 121745-8
    ISSN 1365-2265 ; 0300-0664
    ISSN (online) 1365-2265
    ISSN 0300-0664
    DOI 10.1111/cen.14372
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The relationship between members of the canonical NF-kB pathway, tumour microenvironment and cancer specific survival in colorectal cancer patients.

    Quinn, Jean A / Bennett, Lindsay / Patel, Meera / Frixou, Mikaela / Park, James H / Roseweir, Antonia / Horgan, Paul G / McMillan, Donald C / Edwards, Joanne

    Histology and histopathology

    2019  Volume 35, Issue 6, Page(s) 569–578

    Abstract: Background: The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway colorectal in cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway ... ...

    Abstract Background: The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway colorectal in cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway members in a tissue microarray of 242 patients. The relationship between expression, the tumour microenvironment and cancer-specific survival were examined.
    Results: All the investigated members of the pathway were expressed in CRC tissue. In addition, cytoplasmic pTAK1 was associated with the tumour microenvironment (P=0.045) and cancer-specific survival (CSS) (P=0.032). When cytoplasmic pTAK1 was stratified by BRAF status, cytoplasmic pTAK1 expression association with CSS was strengthened (P=0.014). Cytoplasmic IKKβ was significantly associated with the inflammatory cell infiltrate (P=0.015) as graded by Klintrup Makinen grade, systemic inflammation as assessed by neutrophil-lymphocyte ratio (P=0.03) and CSS (P=0.046). On multivariate analysis cytoplasmic IKKβ was independently associated with CSS (HR 1.75,95%CI 1.05-2.91, P=0.033).
    Conclusion: Cytoplasmic pTAK1 was significantly associated with CSS and this was enhanced in patients with tumours that expressed wild type BRAF. High expression of cytoplasmic IKKβ was significantly associated with decreased CSS and with markers of the tumour microenvironment. These results support the hypothesis that NF-κB pathway members are poor prognostic markers in patients with CRC, but this requires to be validated in a large independent cohort.
    MeSH term(s) Adult ; Aged ; Biomarkers, Tumor/metabolism ; Cohort Studies ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Female ; Humans ; Immunohistochemistry/methods ; Inflammation ; MAP Kinase Kinase Kinases/metabolism ; Male ; Middle Aged ; NF-kappa B/metabolism ; Prognosis ; Tumor Microenvironment
    Chemical Substances Biomarkers, Tumor ; NF-kappa B ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP kinase kinase kinase 7 (EC 2.7.11.25)
    Language English
    Publishing date 2019-10-08
    Publishing country Spain
    Document type Journal Article
    ZDB-ID 83911-5
    ISSN 1699-5848 ; 0213-3911
    ISSN (online) 1699-5848
    ISSN 0213-3911
    DOI 10.14670/HH-18-168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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