Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients

AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.

Retroviral transduction of a mutant erbB-2 gene into human CD34^+ derived dendritic cells

Objective To successfully transduce a mutant erbB 2 gene into normal human CD34 + derived dendritic cells (DCs) and verify gene expression in these transduced dendritic cells Methods The packaging cell line PA317 was transfected with mutant erbB 2 gene DNA and the virus produced was used to infect packaging cell line PG13 The virus produced by PG13 was used to infect CD34 + derived dendritic cells by the spinoculation method using flasks coated with fibronectin material to facilitate retrovirus gene transter efficiency and the mutant erbB 2 gene expression was assessed by ABC staining and FACScan methods Results A mutant erbB 2 gene packaging cell line was produced and this mutant gene was transduced into human CD34 + derived DCs It was verified that the relatively large numbers of the transduced DCs expressed the mutant erbB 2 protein which was eradicated of the ability to transform mouse NIH3T3 fibroblast cells Conclusions Human DCs can be gene modified and these gene modified DCs may be useful in stimulating T lymphocytes for immunotherapy

Adjuvant therapy for gastric cancer:What have we learned since INT0116?

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapsefree and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

Integrated assessment of potential value of erbB-2 amplification or expression status as novel therapy target in Chinese children and adolescents with osteosarcoma

Background Targeted tumor therapies have been making rapid progress in recent years, and the erbB-2 oncogene is a suitable target. There was much discussion about the level of erbB-2 in osteosarcoma. The aim of this study was to investigate the erbB-2 amplification or expression status in osteosarcoma. Methods Fluorescence in situ hybridization （FISH） and DNA probes for erbB-2 and centromere 17 were used to examine the erbB-2 gene amplification status in 32 osteosarcoma samples, and expression of erbB-2 was analyzed by immunohistochemistry （IHC） and reverse transcription-polymerase chain reaction （RT-PCR）. Results None of the 32 osteosarcomas was observed by FISH to have the erbB-2 gene amplified, and no distinguishable membrane staining was seen in any case yet, nevertheless, erbB-2 overexpression was present in 6 tumor samples by RT-PCR. Conclusions The status of erbB-2 gene amplification and membrane overexpression is rare in osteosarcomas, and might suggest that the erbB-2 target agent should not be applied to osteosarcomas as single treatment.