Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Epidermal growth factor-related peptides and their receptors in human malignancies

Background: The most accurate predictor of disease recurrence in patients treated for head and neck squamous cell carcinoma is, at present, the extent of regional lymph node metastasis. Since elevated levels of epidermal growth factor receptor (EGFR) and of its ligand, transforming growth factor-a (TGF-a), have been detected in primary tumors of patients with head and neck squamous cell carcinoma, we determined whether tumor levels of these proteins were of prognostic importance. Methods: Monoclonal antibodies specific for EGFR and TGF-a were used for immunohistochemical detection of each protein in tissue sections of primary tumors from 91 patients who were treated by surgical resection. Levels of immunoreactive EGFR and TGF-a were quantified by use of a computerized image analysis system and were normalized to appropriate standards. The logrank test and proportional hazards regression analysis were used to calculate the probability that EGFR and TGF-a levels were associated with disease-free survival (i.e., no recurrence of cancer) and cause-specific survival (i.e., patients do not die of their disease). All P values were two-sided. Results: When tumor levels of EGFR or TGF-a were analyzed as continuous variables, disease-free survival and cause-specific survival were reduced among patients with higher levels of EGFR (both P = .0001) or TGF-a (both P = .0001). In a multivariate analysis, tumor site, tumor level of EGFR, and tumor level of TGF-a were statistically significant predictors of disease-free survival; in a similar analysis, regional lymph node stage and tumor levels of EGFR and of TGF-a were significant predictors of cause-specific survival. Conclusion: Quantitation of EGFR and TGF-a protein levels in primary head and neck squamous cell carcinomas may be useful in identifying subgroups of patients at high risk of tumor recurrence and in guiding therapy. [J Natl Cancer Inst 1998; 90:824‐32]

http://thymic.org/uploads/biol_sub/genet4.pdf

Levels of TGF-α and EGFR Protein in Head and Neck Squamous Cell Carcinoma and Patient Survival

A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation.

https://science.sciencemag.org/content/sci/265/5175/1093.full.pdf

A specific inhibitor of the epidermal growth factor receptor tyrosine kinase

EGF-R positivity was shown to be present in 2500 (48%) of 5232 breast tumors in 40 different series of patients. The mean of the percentages of EGF-R positivity in the individual series reported by these 40 different groups of investigators is 45% (range 14-91%). Overall there are generally no clear differences between results obtained by radioligand binding assays, immunological methods, autoradiography, and measurement of EGF-R transcripts although the mean percentage of EGF-R-positive tumors determined by immunological methods tends to be somewhat lower. Nearly all studies indicate a negative relationship between EGF-R and steroid receptor status (28 of 31 studies for ER, 12/19 for PR) showing that EGF-R positivity is twice as high in ER or PR- negative tumors compared to ER or PR- positive tumors (approximately 50-60% vs. 30%). With regard to other prognostic factors the majority of investigators (10/18) also reported a significant (positive) correlation with tumor grade, but only a minority found a significant relationship between EGF-R status and patient age (2/9), menopausal status (1/7), histological type (3/7), tumor size (2/17), nodal status (5-9/20), ploidy (1/7), or proliferation indices (3/9). No relationship was observed with tumor insulin-like growth factor I receptor, PRL receptor (PRL-R), and LHRH receptor (LHRH-R) status, but an inverse relationship between EGF-R and somatostatin receptor may be present. However, it has to be stressed that the series in which the relationship between EGF-R status and other prognostic factors were investigated, contained relatively few patients (mostly less than 100). Therefore, when larger groups of patients are investigated, more significant relationships may be observed, especially with respect to nodal status, tumor ploidy, and proliferation indices. In fact, we calculated the presence of EGF-R positivity overall in 35% of 253 aneuploid tumors vs. in only 15% of 114 diploid tumors (P less than 0.0001). In addition most studies observed a trend, if no significant correlation, between higher EGF-R levels in tumors with the highest percentages of S-phase or Ki-67 expression. With regard to relapse-free and overall survival, five of nine different groups of investigators showed significant prognostic value of EGF-R after short-term (1- to 4-yr) follow-up, indicating that patients with EGF-R-positive tumors have a poor prognosis. However, three of five groups with a maximal follow-up of at least 6 yr found only a tendency for any relationship between EGF-R status and long-term outcome.

/pdf/the-clinical-significance-of-epidermal-growth-factor-2mq4nythpu.pdf

The Clinical Significance of Epidermal Growth Factor Receptor (EGF-R) in Human Breast Cancer: A Review on 5232 Patients

https://www.jstage.jst.go.jp/article/math1924/19/1/19_1_31/_pdf

Finite dimensional representations of the quantum group GLq(n; C) and the zonal spherical functions on Uq(n-1)_??_Uq(n)

Epidermal growth factor receptor expression as a prognostic indicator in breast cancer.

Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819900501%2965%3A9%3C1980%3A%3AAID-CNCR2820650917%3E3.0.CO%3B2-U

Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer

The expression of c- erb B-2 oncoprotein and epidermal growth factor receptor (EGFR) was examined by immunocytochemical and radioreceptor assays in 115 patients with primary breast cancer. In 48 of 115 patients (42%), the assays were found to be positive for the expression of c- erb B-2 oncoprotein, and, in 44 of 115 (35%) patients, the assays were positive for the expression of EGFR. There was no correlation between the expression of c- erb B-2 oncoprotein and EGFR. Clinical survey demonstrated that both c- erb B-2 oncoprotein expression and EGFR expression have independent prognostic values. Furthermore, when patients were divided into three groups on the basis of the expression of both c- erb B-2 oncoprotein and EGFR, those who were found to be positive for the expression of both c- erb B-2 oncoprotein and EGFR showed a worse prognosis than other groups. These results suggest that the combination of the expression of both c- erb B-2 oncoprotein and EGFR may be important in selecting patients who have a poor prognosis.

Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer patients.

Excitation temperature, rotational temperature, and electron density were obtained for a high-power (1-kW) microwave-induced nitrogen plasma (N2 MIP) at atmospheric pressure generated by an Okamoto cavity. With 1 kW input microwave power, an excitation temperature of 5500 K, a rotational temperature of 5000 K, and an electron density in the 1013 range were measured. Excitation and rotational temperatures were much closer than is the case with the commonly used argon inductively coupled plasma, suggesting that this N2 MIP is closer to local thermodynamic equilibrium (thermal).

Hirofumi Yamada

Papers

Finite dimensional representations of the quantum group GLq(n; C) and the zonal spherical functions on Uq(n-1)_??_Uq(n)

Epidermal growth factor receptor expression as a prognostic indicator in breast cancer.

Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer

Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer patients.

Excitation temperature in high-power nitrogen microwave-induced plasma at atmospheric pressure