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  1. Article ; Online: The State of Immunotherapy in Hepatobiliary Cancers.

    Ilyas, Farhan Z / Beane, Joal D / Pawlik, Timothy M

    Cells

    2021  Volume 10, Issue 8

    Abstract: Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is ... ...

    Abstract Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.
    MeSH term(s) Antibodies, Bispecific/therapeutic use ; Biliary Tract Neoplasms/therapy ; Cancer Vaccines/therapeutic use ; Carcinoma, Hepatocellular/therapy ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Immunotherapy, Adoptive ; Liver Neoplasms/therapy ; Oncolytic Viruses ; Tumor Microenvironment/immunology
    Chemical Substances Antibodies, Bispecific ; Cancer Vaccines ; Immune Checkpoint Inhibitors
    Language English
    Publishing date 2021-08-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10082096
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comparing Multivisceral Resection with Tumor-only Resection of Liposarcoma Using the Win Ratio.

    Gorji, Leva / Nikahd, Melica / Onuma, Amblessed / Tsilimigras, Diamantis / Madison Hyer, J / Ruff, Samantha / Ilyas, Farhan Z / Contreras, Carlo / Grignol, Valerie P / Kim, Alex / Pollock, Raphael / Pawlik, Timothy M / Beane, Joal D

    Annals of surgical oncology

    2024  Volume 31, Issue 5, Page(s) 3389–3396

    Abstract: Background: Multivisceral resection of retroperitoneal liposarcoma (LPS) is associated with increased morbidity and may not confer a survival benefit compared with tumor-only (TO) resection. We compared both approaches using a novel statistical method ... ...

    Abstract Background: Multivisceral resection of retroperitoneal liposarcoma (LPS) is associated with increased morbidity and may not confer a survival benefit compared with tumor-only (TO) resection. We compared both approaches using a novel statistical method called the "win ratio" (WR).
    Methods: Patients who underwent resection of LPS from 2004 to 2015 were identified from the National Cancer Database. Multivisceral resection was defined as removal of the primary site in addition to other organs. The WR was calculated based on a hierarchy of postoperative outcomes: 30-day and 90-day mortality, long-term survival, and severe complication.
    Results: Among 958 patients (multivisceral 634, TO 324) who underwent resection, the median age was 63 years (interquartile range [IQR] 54-71) with a median follow-up of 51 months (IQR 30-86). There was no difference in the WR among patients who underwent TO versus multivisceral resection in the matched cohort (WR 0.82, 95% confidence interval [CI] 0.61-1.10). In patients aged 72-90 years, those who underwent multivisceral resection had 36% lower odds of winning compared with patients undergoing TO resection (WR 0.64, 95% CI 0.40-0.98). A subgroup analysis of patients classified as not having adjacent tumor involvement at the time of surgery revealed that those patients who underwent multivisceral resection had 33% lower odds of winning compared to TO resection (WR 0.67, 95% CI 0.45-0.99).
    Conclusions: Based on win-ratio assessments of a hierarchical composite endpoint, multivisceral resection in patients without adjacent tumor involvement may not confer improved outcomes. This method supports the rationale for less invasive resection of LPS in select patients, especially older patients.
    MeSH term(s) Humans ; Child, Preschool ; Lipopolysaccharides ; Liposarcoma/surgery ; Retroperitoneal Neoplasms/surgery ; Colorectal Neoplasms/pathology ; Retrospective Studies
    Chemical Substances Lipopolysaccharides
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1200469-8
    ISSN 1534-4681 ; 1068-9265
    ISSN (online) 1534-4681
    ISSN 1068-9265
    DOI 10.1245/s10434-024-14985-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4042: 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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  3. Article ; Online: ASO Visual Abstract: Comparing Multivisceral Resection with Tumor-Only Resection of Liposarcoma Using the Win Ratio.

    Gorji, Leva / Nikahd, Melica / Onuma, Amblessed / Tsilimigras, Diamantis / Hyer, J Madison / Ruff, Samantha / Ilyas, Farhan Z / Contreras, Carlo / Grignol, Valerie P / Kim, Alex / Pollock, Raphael / Pawlik, Timothy M / Beane, Joal D

    Annals of surgical oncology

    2024  Volume 31, Issue 6, Page(s) 4152–4153

    MeSH term(s) Humans ; Liposarcoma/surgery ; Liposarcoma/pathology ; Prognosis ; Survival Rate
    Language English
    Publishing date 2024-03-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1200469-8
    ISSN 1534-4681 ; 1068-9265
    ISSN (online) 1534-4681
    ISSN 1068-9265
    DOI 10.1245/s10434-024-15108-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4042: 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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  4. Article ; Online: The Role of AKT in Soft Tissue Sarcoma: Review and Insights.

    Wang, Yu / Ilyas, Farhan Z / Kheradmandi, Mahsa / Tsilimigras, Diamantis I / Grignol, Valerie P / Contreras, Carlo / Tsichlis, Philip N / Pollock, Raphael E / Beane, Joal D

    Molecular cancer research : MCR

    2022  Volume 20, Issue 10, Page(s) 1471–1480

    Abstract: Soft tissue sarcomas (STS) are a biologically diverse group of mesenchymal tumors that predominantly exhibit a poor prognosis. Surgical resection is considered the mainstay of treatment and provides the only chance for long-term survival. However, some ... ...

    Abstract Soft tissue sarcomas (STS) are a biologically diverse group of mesenchymal tumors that predominantly exhibit a poor prognosis. Surgical resection is considered the mainstay of treatment and provides the only chance for long-term survival. However, some patients present with locally advanced, unresectable disease, and for those who are able to undergo resection, tumor recurrence occurs in over half of patients. In addition, the efficacy of conventional systemic therapies remains dismal. The serine/threonine kinase AKT pathway is one of the most frequently aberrantly activated signaling pathways that has been verified in many types of human cancer. Dysregulation of the AKT cascade is known to result in tumorigenesis and aggressive clinical behavior for many tumor types, including STS. EGFRs, with its downstream effectors, PI3K and protein kinase B (AKT)/mTOR, have been investigated for decades as promising targets for the treatment of STS, but significant challenges remain and the prognosis of patients with advanced STS has not improved in over two decades. In this review, we will first describe the AKT pathway and its role in STS tumor biology and then discuss the current challenges in targeting the AKT pathway to treat patients with advanced sarcoma.
    MeSH term(s) Humans ; Neoplasm Recurrence, Local ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism ; Sarcoma/genetics ; Sarcoma/metabolism ; Serine ; Soft Tissue Neoplasms/drug therapy ; Soft Tissue Neoplasms/genetics ; Soft Tissue Neoplasms/metabolism ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances Serine (452VLY9402) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-07-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-21-0844
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5744: 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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  5. Article ; Online: Targeted knockdown of Kv1.3 channels in T lymphocytes corrects the disease manifestations associated with systemic lupus erythematosus.

    Khodoun, Marat / Chimote, Ameet A / Ilyas, Farhan Z / Duncan, Heather J / Moncrieffe, Halima / Kant, K Shashi / Conforti, Laura

    Science advances

    2020  Volume 6, Issue 47

    Abstract: Lupus nephritis (LN) is an autoimmune disease with substantial morbidity/mortality and limited efficacy of available therapies. Memory T (Tm) lymphocytes infiltrate LN kidneys, contributing to organ damage. Analysis of LN, diabetic nephropathy, and ... ...

    Abstract Lupus nephritis (LN) is an autoimmune disease with substantial morbidity/mortality and limited efficacy of available therapies. Memory T (Tm) lymphocytes infiltrate LN kidneys, contributing to organ damage. Analysis of LN, diabetic nephropathy, and healthy donor kidney biopsies revealed high infiltration of active CD8
    MeSH term(s) Animals ; CD40 Ligand ; Gene Knockdown Techniques ; Humans ; Interferon-gamma ; Kidney/pathology ; Kv1.3 Potassium Channel/genetics ; Leukocytes, Mononuclear/pathology ; Lupus Erythematosus, Systemic ; Lupus Nephritis/etiology ; Lupus Nephritis/pathology ; Mice ; Nanoparticles ; T-Lymphocytes
    Chemical Substances Kv1.3 Potassium Channel ; CD40 Ligand (147205-72-9) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2020-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abd1471
    Database MEDical Literature Analysis and Retrieval System OnLINE

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