Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit
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Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit
Importance: The use of a prognostic gene expression profiling (GEP) test in skin melanoma (CM) rose despite a lack of support as a standard of care.
Objective: To develop guidelines for the Group’s national Prevention of Melanoma Work (MPWG) on the integration testing of GEP in the management of patients with CM, including (1) a review of published data using a test GEP, (2) the definition of criteria for acceptable performance, (3) the current recommendations for the use of GEP testing in clinical practice, and (4) consideration for future studies.
review of the evidence: The members MPWG melanoma and other international specialists participated in two online surveys and then hold a summit. Published data and meeting abstracts 2015-2019 are reviewed.
Findings: The members MPWG optimistic about the future use of GEP prognostic testing to improve risk stratification and improve clinical decision making but recognize that the utility is currently limited by the performance of the test in patients with stage disease study published I. GEP test results have not been evaluated in the context of all clinicopathologic factors relevant or as a predictor of metastatic nodal region to replace the sentinel lymph node biopsy (SLNB).
Performance tests PMP has generally been reported for small groups of patients who represent a stage specific tumor or in the aggregate, so that the performance of a particular stage can not be ascertained, and without the survival compare the results with data from the Joint Committee of the American Cancer 8 edition of melanoma system staging database international ones. There are significant challenges for the conduct of clinical trials combining GEP testing with SLNB and adjuvant therapy. The members MPWG supports perform retrospective study evaluated several GEP test on the sample archive platform fully explained before the start of prospective studies recommend avoiding the use of expensive and GEP routine testing to direct patient management through prospective studies support their clinical utility.
Conclusion and relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, the intensity of follow-up or surveillance imaging and postoperative adjuvant therapy. The MPWG recommend further studies to assess the validity and clinical application of existing and emerging GEP test. Decisions about testing GEP and management of patients based on the results of this should only be done in the context of the discussion of the limitations of testing with the patient or in a multidisciplinary group.
Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit
In vitro and ex vivo gene expression profiling revealed differential kinetic response of Hsp and UPR genes associated with resistance to protease inhibitors in multiple myeloma
Extensive inter-individual variation in response to chemotherapy (sensitive vs. resistant tumor) is a serious cause of concern in the treatment of multiple myeloma (MM). In this study, we used a human myeloma cell lines (HMCLs), and patient-derived CD138 + cells to compare the gene expression patterns of kinetic changes among congenital proteasome inhibitor (PI) HMCLs PI-resistant and -sensitive following the test dose with the second-generation PI Ixazomib ,
We found 1553 genes that change significantly post treatment in PI-sensitive HMCLs compared with only seven in HMCLs PI-resistant (p <0.05). Unique genes arranged in PI-resistant line that Rictor (activated), HNF4A, miR-16-5p (activated), MYCN (inhibits) and MYC (inhibit).
Description: Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.
Description: Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.
Description: Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.
Description: Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IRGC . This antibody is tested and proven to work in the following applications:
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IRGC . This antibody is tested and proven to work in the following applications:
Description: IRGC Antibody: Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.
Description: IRGC Antibody: Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of GTPase proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. IRG genes have been found in a number of mammals and lower species including mice, rats, zebrafish and humans. Most of the mouse genes contain interferon-stimulated response elements which mediate transcriptional activation by IFNs. In humans, only two IRG genes have been found: human IRGC encodes a full-length IRG protein that, like the mouse homologue, is constitutively expressed in testis, while human IRGM encodes a considerably truncated protein that is constitutively expressed in cultured cells including some macrophage cell lines. As the two human genes IRGC and IRGM are not subject to IFN control, it has been suggested that the host resistance mechanism supported by IRG proteins in the mouse is lacking in humans.
Description: A polyclonal antibody against IRGC. Recognizes IRGC from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB
Ingenuity pathway analysis (IPA) using a kinetic response gene on identifying proteasome ubiquitination pathway (PUP), and nuclear factor erythroid 2-related factor 2 (NRF2) -mediated oxidative stress response as canonical pathway up in Ix-sensitive cell lines and cell patient- derived, while EIF2 signal and mTOR signaling pathways that are unique to PI resistance.
