Disease relevance of IRX2

• Frequent amplifications and abundant expression of TRIO, NKD2, and IRX2 in soft tissue sarcomas [1].
• Of these, TRIO, coding for a guanidine nucleotide exchange factor, was consistently overexpressed in all cases, while IRX2 and NKD2, both involved in the regulation of developmental processes via the WNT pathway, showed a characteristic expression only in MPNSTs [1].
• Histologic findings in patients with head and neck squamous cell carcinoma receiving perilymphatic natural cytokine mixture (IRX-2) prior to surgery [2].
• A natural cytokine mixture (IRX-2) and interference with immune suppression induce immune mobilization and regression of head and neck cancer [3].
• The adverse effects of the IRX-2 protocol were negligible except for an allergic skin rash (n = 1) and parotiditis (n = 1) [4].

High impact information on IRX2

• A strong Fgf8 signal activates the Ras-ERK signaling pathway, which in turn activates Irx2 in a rostrodorsal part of the hindbrain, and forces this tissue to differentiate into cerebellum [5].
• Detailed nonparametric multidimensional scaling analysis further showed that the expression of TRIO, IRX2, and NKD2 strongly correlated with the gene copy number [1].
• A novel primate specific gene, CEI, is located in the homeobox gene IRXA2 promoter in Homo sapiens [6].
• An open reading frame coding for an unknown protein is identified in the promoter of IRXA2 on chromosome 5p [6].
• This new gene is composed of four exons and it is orientated in a head-to-head manner to IRXA2 [6].

Chemical compound and disease context of IRX2

• OBJECTIVES: To test the efficacy of a natural cytokine mixture (IRX-2), cyclophosphamide, indomethacin, and zinc to induce immune regression of squamous cell carcinoma (SCC) of the head and neck (H&N) prior to conventional therapy and to characterize the responses [4].

Biological context of IRX2

• Data suggest IRX-2 functions in epithelial cell differentiation and demonstrate regulated expression during ductal and lobular proliferation as well as lactation [7].
• OBJECTIVE: To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in histology [8].
• The treatment with IRX-2 was not associated with significant side effects and 24 of patients showed improvement in eating, breathing or phonation or reduced pain and bleeding [9].
• The reversal of sinus histiocytosis, by IRX-2 treatment, in association with nodal expansion suggests that tumor antigen processing via dendritic cells is defective in cancer-bearing patients and that it is corrected by the treatment [8].

Anatomical context of IRX2

• In contrast to the popular notion that thymic involution cannot be reversed in the adult, studies from the author's laboratory indicate that in aged hydrocortisone stressed mice, a natural Type 1-cytokine mixture (IRX-2) hastens the reversal of thymic involution and promotes T-cell responses to cytokines and mitogens [10].
• CONCLUSIONS: The IRX-2 immunotherapy induced lymphocyte mobilization and infiltration in H&N SCC associated with clinical and histological tumor responses indicative of immune regression in all 15 patients [4].
• A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma [11].
• The T cell and/or B cell areas of LN of IRX-2-treated patients showed a high correlation with T and/or B cell infiltration into these tumors (p<0.001) [8].

Associations of IRX2 with chemical compounds

• The patients were treated with 20 days of perilymphatic injections of IRX-2 (administered subcutaneously at the base of the skull) in combination with contrasuppression consisting of a low-dose infusion of cyclophosphamide (300 mg/m2), and daily oral indomethacin and zinc (StressTabs) in a 21-day cycle before surgery and/or radiotherapy [4].

Other interactions of IRX2

• Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast [7].
• The combination of a natural cytokine mixture (IRX-2) with thymosin alpha1 had a very large effect and increased the absolute number of peripheral T lymphocytes as measured in the spleen [10].
• The expression profile of the gene analysed in 9 different human tissues reveals that it is expressed in a coordinated fashion with IRXA2, which has led to the name CEI (Coordinated Expression to IRXA2) [6].

Analytical, diagnostic and therapeutic context of IRX2

• The lymph nodes of IRX-2-treated H and N SCC patients showed increased size (over both control groups), increased T cell area and density and decreased follicles and sinus histiocytosis [8].

References