Strong Long-Term Survival with Targeted Therapy in Inoperable/Metastatic Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) belong to a group of cancers called soft-tissue sarcomas. Soft-tissue sarcomas develop in the tissues that support and connect the body, including muscles, nerves, tendons and joints. In this paper we report a case of 67-years old man with unresectable GIST and associated liver metastasis who experienced a very good response to Imatinib mesylate (Glivec®) therapy in first line for over 10 years. Even after progression and discovery of liver metastasis, increasing the Glivec® dose proved to be an efficient strategy with no added toxicity and an overall satisfactory quality of life.

The effect of temozolomide in combination with doxorubicin in glioblastoma cells in vitro.

BACKGROUND: Prior to 2000, the DNA alkylating agents nitrosoureas were used as standard treatment of glioblastoma. Current treatments for glioblastoma patients consist of surgery followed by radiation in combination with temozolomide. Despite therapeutic advances, the prognosis for glioblastoma patients remains grim, with a five-year overall survival below 15%. In this study, our team analyzed the interaction between temozolomide and doxorubicin in a glioblastoma cell line, in vitro. MATERIALS AND METHOD: The cell line, established from a patient who underwent surgery at the "Bagdasar Arseni Emergency Hospital", was exposed to 10 µM and 100 µM of temozolomide and 10 nM and 100 nM of doxorubicin, respectively, over a period of 7, 10 and 14 days, in monotherapy and in combination. RESULTS: The results showed that both temozolomide (66.5% cytotoxicity for the 10 µM dose at 14 days) de and doxorubicin (66.8% cytotoxicity for the 10 nM dose after 14 days) were very effective in killing cancer cells in monotherapy, but failed to produce a synergistic effect when used in combination. CONCLUSION: While the results may be discouraging, they present an interesting prospect into how certain drug interactions can impact treatment response.

ß-arrestin 1 transfection induced cell death in high grade glioma in vitro.

The best known functions of ß-arrestins (ß-arr) are to regulate G protein-coupled receptors (GPCR) signaling through receptor desensitization and internalization. Many reports also suggest that ß-arrs play important role in immune regulation and inflammatory responses, under physiological and pathological conditions. Recent studies have shown that ß-arr 1 silencing halts proliferation and increases temozolomide (TMZ) response in glioblastoma (GBM) cells. The focus of this paper is to analyze the role of ß-arr 1 overexpression in the 18 high grade glioma (HGG) cell line in terms of viability and their response to TMZ treatment. For this reason, the cell line was transfected with ß-arr 1 and the effect was analyzed after 24 h, 48 h and 72 h in terms of proliferation and treatment response. We observed that ß-arr 1 overexpression induced a time and dose dependant inhibition in the HGG cells. Unexpectedly, ß-arr transfection resulted in a very mild increase in TMZ toxicity after 24 h, becoming non-statistically significant at 72 h. In conclusion, we showed that ß-arr 1 overexpression inhibits cell proliferation in the 18 cell line but only has a very modest effect on treatment response with the alkylating agent TMZ.

Current and emerging EGFR therapies for glioblastoma.

Glioblastomas (GBMs) are the most lethal and hard to treat malignancies in clinical practice. The standard of care for treating GBM involving surgery and adjuvant radiotherapy and concomitant temozolomide (TMZ) has remained virtually unchanged in the past decade. Molecular targeted therapies against cancer-specific structures have reported mediocre results in the treatment of GBM, due to multiple factors such as the presence of the blood brain barrier or a vast array of molecular alterations which greatly hinder the action of the most therapeutic agents. One such therapy is directed against the epidermal growth factor (EGF) and its' receptor (EGFR) using either monoclonal antibodies or tyrosine kinase inhibitors. Even though anti-EGF/EGFR treatment produced encouraging results in other forms of cancer it failed to present any clinical benefit for patients with GBM. Lately, immunotherapies that focus on using the host's own immune system against cancer cells have gained popularity, with approaches like peptide vaccination being successfully used in clinical trials for different types of malignancies. These immune-based therapies could hold the key to improving both the prognosis and quality of life for patients suffering for cancers previously considered incurable, such as GBM.

The Influence of EGFR Inactivation on the Radiation Response in High Grade Glioma.

Lack of effectiveness of radiation therapy may arise from different factors such as radiation induced receptor tyrosine kinase activation and cell repopulation; cell capability to repair radiation induced DNA damage; high grade glioma (HGG) tumous heterogeneity, etc. In this study, we analyzed the potential of targeting epidermal growth factor receptor (EGFR) in inducing radiosensitivity in two human HGG cell lines (11 and 15) that displayed similar growth patterns and expressed the receptor protein at the cell surface. We found that 15 HGG cells that express more EGFR at the cell surface were more sensitive to AG556 (an EGFR inhibitor), compared to 11 HGG cells. Although in line 15 the effect of the inhibitor was greater than in line 11, it should be noted that the efficacy of this small-molecule EGFR inhibitor as monotherapy in both cell lines has been modest, at best. Our data showed a slight difference in the response to radiation of the HGG cell lines, three days after the treatment, with line 15 responding better than line 11. However, both cell lines responded to ionizing radiation in the same way, seven days after irradiation. EGFR inhibition induced radiosensitivity in 11 HGG cells, while, in 15 HGG cells, the effect of AG556 treatment on radiation response was almost nonexistent.