Qichun Wei

EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases: Implications for targeted radiotherapy

BackgroundProteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.MethodsExpression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).ResultsEGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.ConclusionThe EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.

Serum fibrinogen level predicts the therapeutic response and prognosis in patients with locally advanced rectal cancer.

BACKGROUND/AIMS Preoperative chemoradiotherapy has become the current gold standard treatment for locally advanced rectal cancer. To date, no suitable prognostic markers could be used to identify rectal cancer patients who are most likely to experience a good outcome after preoperative chemoradiotherapy. The goal of this study was to evaluate whether serum fibrinogen level is suitable as a predictor of therapeutic response to preoperative chemoradiotherapy and prognosis for locally advanced rectal cancer. METHODOLOGY The study retrospectively analyzed the correlation between the pretherapeutic fibrinogen level and cancer response as well as prognosis in 53 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by surgery. Serum fibrinogen level more than 4.00g/L was defined as hyperfibrinogenemia. RESULTS Of the 53 patients, thirty-four (64.2%) had a fibrinogen level less than or equal to 4g/L (hypofibrinogenemia) and the other 19 cases above 4g/L (hyperfibrinogenemia). Ten of the studied 53 patients (18.9%) had a pathologic complete response after preoperative chemoradiotherapy. The percentage of patients who experienced a pathological complete response was lower among patients with hyperfibrinogenemia than those with hypofibrinogenemia (5.3% vs. 26.5%). Concerning the survival, 68.4% (13/19) patients with hyperfibrinogenemia died of disease, while only 29.4% (10/34) in hypofibrinogenemia group. The Kaplan-Meier survival curves of patients with hypofibrinogenemia versus hyperfibrinogenemia showed a highly significant separation (p<0.05). CONCLUSIONS For locally advanced rectal cancer patients, pre-therapeutic fibrinogen level might be a useful predictor of prognosis, and it might also be used as a biomarker to predict the therapeutic response.

MicroRNA-34a induces a senescence-like change via the down-regulation of SIRT1 and up-regulation of p53 protein in human esophageal squamous cancer cells with a wild-type p53 gene background

MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and a probable suppressor of diverse cancer cells; however, this miRNAs expression and anti-tumor mechanism in esophageal squamous cancer cells (ESCC) remains unclear. We explored these questions in three human ESCC lines, KYSE-450, KYSE-410, and ECa-109, with wild-type p53 and mutant p53 backgrounds. Through a specific stem-loop RT primer for miR-34a, we examined the relevant expression level of miR-34a in these three cell lines using real-time reverse transcription PCR (qRT-PCR). We found that the expression level of miR-34a induced by the DNA damage agent adrmycin (ADR) was both p53- and time-dependent. Following incubation with miR-34a, cellular growth inhibition was exhibited differently in the three cell lines harbored with different p53 backgrounds. Furthermore, the MTT assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to examine senescence-like phenotypes induced by miR-34a. Mechanistic investigation suggested that the down-regulation of Sirtuin1 (SIRT1) and up-regulation of p53/p21 contributed to the anti-tumor mechanism of miR-34a in wild-type p53 ECa-109 cells, while neither of the apoptosis-related proteins PARP and caspase-3 caused significant changes. In summary, our findings indicated that the intrinsic expression of miR-34a was relatively low and was expressed differently among different p53 backgrounds and ADR treatment times. The anti-tumor effect of miR-34a was primarily dependent on the regulation of SIRT1 and p53/p21 protein, not apoptosis-associated proteins.

Effect of patient-related delay in diagnosis on the extent of disease and prognosis in nasopharyngeal carcinoma.

Background The reasons causing the patient-related delay in diagnosis (PRDD) and the effects of PRDD on the extent of disease and prognosis in the nasopharyngeal carcinoma (NPC) remain uncertain. The aim of this study was to investigate the status of PRDD and evaluate the relationship between PRDD and prognostic factors of NPC. Methods The data of 216 patients with NPC, from 2002 to 2006, were analyzed retrospectively with respect to patient age, gender, smoking status, education experience, living area, and symptoms. PRDD was recorded as the time from initial symptoms to the first visit to a medical doctor. The extent of disease was determined by TNM staging according to the International Union Against Cancer classification in 1997. Results PRDD of the analyzed cases ranged from half a month to 24 months, with a mean delay in diagnosis of 5.6 months. Senior residents and low education population tended to have longer PRDD (p < 0.05). There was a significant correlation between PRDD and the degree of invasion, clinical stage of NPC (p < 0.05). Conclusion Senior residents and low education population tend to have longer PRDD. Delay in diagnosis correlates with the degree of invasion and stage of NPC.

Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy.

BackgroundThe knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of NSCLC was limited. In receptor-mediated targeted nuclide radiotherapy, tumor cells are killed with delivered radiation and therapeutic efficiency is mainly dependent on the receptor expression. Thus, the level and stability of receptor expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target. The goal of this study was to evaluate whether EGFR is suitable as target for clinical therapy.MethodsExpression of EGFR was investigated immunohistochemically in paired samples of lymph node metastases and corresponding NSCLC primary lesions (n = 51). EGFR expression was scored as 0, 1+, 2+ or 3+.ResultsPositive (1+, 2+ or 3+) EGFR immunostaining was evident in 36 of 47 (76.6%) analysed NSCLC primary tumors, and in 78.7% of the corresponding lymph node metastases. When EGFR expression is classified as positive or negative, discordance between the primary tumors and the corresponding metastases was observed in 5 cases (10.6%). EGFR overexpression (2+ or 3+) was found in 53.2% (25/47) of the NSCLC primary tumors and 59.6% of the corresponding metastases. Nine out of the 47 paired samples (19.2%) were discordant: Only three patients who had EGFR overexpression in the primary tumors showed EGFR downregulation (0 or 1+) in lymph node metastases, while six patients changed the other way around.ConclusionsThe EGFR expression in the primary tumor and the corresponding metastasis is discordant in about 10% of the patients. When overexpression is considered, the discordance is observed in about 20% of the cases. However, concerning EGFR overexpression in the primary tumors, similar expression in the metastases could be predicted with a reasonably high probability, which is encouraging for testing of EGFR targeted nuclide radiotherapy.

Expression status of fatty acid synthase (FAS) but not HER2 is correlated with the differentiation grade and prognosis of esophageal carcinoma.

BACKGROUND/AIMS Fatty acid synthase (FAS) and human epidermal growth factor receptor 2 (HER2) are overexpressed in a series of cancers. However, few studies have investigated the potential role of FAS and HER2 in esophageal carcinoma. The aim of this study was to evaluate the expression of FAS and HER2 and the possible link between FAS/HER2 expression and the pathological prognostic variables. METHODOLOGY The frequency of FAS and HER2 expression was determined immunohistochemically. The overall survival rate was analysed by the Kaplan-Meier method and the log-rank test using SPSS 17.0 software. RESULTS The majority of the cases were esophageal squamous cell carcinomas (n=142). FAS and HER2 overexpression in the studied cases are 73.2% and 14.1%, respectively. There was a significant difference in FAS expression regarding tumor differentiation and FAS overexpression showed its prognostic value for patients with different tumor differentiation. Meanwhile, HER2 overexpression did not significantly relate to the clinicopathological characteristics of the tumors, with the only exception of the surgical margins. CONCLUSIONS FAS and HER2 overexpression are common in esophageal carcinomas. FAS overexpression showed its prognostic value for esophageal carcinoma patients with different tumor differentiation, which lead us to consider FAS-inhibitors as potential candidates for target-based adjuvant therapies.

Interim analysis of a prospective randomized non-inferiority trial of cisplatin and fluorouracil induction chemotherapy with or without docetaxel in nasopharyngeal carcinoma

In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 278 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS benefit was observed for TPF compared to PF, though this difference was not statistically significant (84.5% vs. 77.9%, P = 0.380). Due to increased frequencies of grade 3 or 4 neutropenia and diarrhea, significantly more patients in the TPF group required treatment delays and dose modifications. Our findings suggest that PF induction chemotherapy has substantially better tolerance and compliance rates than TPF induction chemotherapy. However, the treatment efficacy of PF is not superior to TPF induction chemotherapy in patients with locoregionally-advanced NPC (ClinicalTrials.gov number, NCT01536223).

Recurrence patterns in patients with high-grade glioma following temozolomide-based chemoradiotherapy

There is currently no consensus regarding the optimal radiation volume for high-grade glioma (HGG). The brain volume irradiated is associated with the extent of radiation neurotoxicity. When reducing the treatment volume, the risk of geographic tumor miss should be considered. In such cases, the recurrence patterns and, particularly, the rate of marginal tumor recurrence, are important indices for determining the optimal radiation volume. In the present study, a smaller-target delineation protocol with limited margins was adopted. The postoperative enhancing tumor and resection cavity were defined as gross tumor volume (GTV); 1 and 2 cm were added to the GTV to create clinical target volume (CTV1 and CTV2), which received 60 and 54 Gy, respectively. At a median follow-up of 14 months, 54 HGG patients developed tumor recurrence. The median overall and progression-free survival were 14 and 10.5 months, respectively. A total of 34 patients developed central recurrence, 8 presented with in-field recurrence, 2 developed marginal recurrence, 2 had distant recurrence and 11 patients developed cerebrospinal fluid dissemination, 2 of whom developed central recurrence, with 1 patient simultaneously developing marginal recurrence. Local recurrence (central and in-field) was found to be the main recurrence pattern. As the rate of marginal recurrence was low (<5%), it appears that the smaller irradiated volume in the present study was appropriate. However, clinical trials investigating limited irradiation volume are required to validate our findings.

Long-Term Relief of Cerebral Radiation Necrosis Treated with Low-Dose Bevacizumab - a Report of 2 Cases

Background: Radiation necrosis is 1 of the most significant complications of brain tumor irradiation. The standard treatment for patients with radiation necrosis consists of corticosteroids to reduce the amount of cerebral edema and, if required, cyst drainage. Case Reports: 2 patients with symptomatic radiation necrosis initially unresponsive to steroid treatment were treated with repeated low-dose bevacizumab at 5 mg/kg body weight. Rapid and lasting symptom relief, as well as neuroradiological improvement was seen in both cases. A dramatic rapid magnetic resonance imaging response with decrease in contrast enhancement was found shortly after administering the first dose of bevacizumab. The improvement of perifocal edema was relatively slower than of the reduction of enhancement. Only a slight reduction in size of the involved area could be expected after the first dose of bevacizumab. Further shrinkage was seen after the second and third doses. The individuals reported have been doing well for more than 45 and 22 months, respectively, after the initiation of bevacizumab treatment. Conclusion: Our data add to the literature supporting of the use of bevacizumab as an effective therapeutic agent for radiation necrosis, particularly in cases unresponsive to steroid treatment.

Dynamic MRI follow-up of radiation encephalopathy in the temporal lobe following nasopharyngeal carcinoma radiotherapy

The natural course of radiation encephalopathy following nasopharyngeal carcinoma (NPC) radiotherapy remains poorly understood. The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and evolution of radiation encephalopathy. A series of 162 follow-up MRI examinations from 68 NPC patients with radiation encephalopathy in the temporal lobes were analyzed retrospectively. Each component of radiation encephalopathy was defined as follows: i) contrast enhanced lesions were enhanced lesions on contrast enhanced T1-weighted images (T1WI); ii) white matter lesions were lesions of homogeneous hyperintensity on T2-weighted images (T2WI) and hypointensity on T1WI; iii) cysts were round or oval well-defined lesions of hyperintensity on T2WI; iv) hemosiderin deposition were nodular or annular hypointense lesions with lower hypointense than normal white matter on both T1WI and T2WI; v) gray matter lesions were defined as disruption or erosion of hyperintensity in the cortex on T2WI. Contrast enhanced lesions, white matter lesions, gray matter lesions, cysts and hemosiderin deposition were detected in 105 (100.0%), 98 (93.3%), 94 (89.5%), 2 (1.7%) and 2 (1.7%) cases of the 105 initial diagnosed temporal lobe lesions. Contrast enhanced lesions were the most commonly observed, followed by white matter lesions, gray matter lesions, temporal lobe atrophy, cysts and hemosiderin deposition. In addition, 12 new lesions were identified during the follow-up, 4 of which presented as solid enhanced nodular lesions. Importantly, in 11 of the 117 (9.4%) affected temporal lobes, solid enhanced nodular lesions were observed to be the only initial abnormalities to occur. For those enhanced nodular lesions measuring <0.8 cm, no necrosis could be detected. On the contrary, all the contrast enhanced lesions measuring >2.0 cm exhibited a necrotic core. To the best of our knowledge, the present study revealed for the first time solid enhanced nodular lesions as the earliest MRI abnormalities of radiation encephalopathy following NPC radiotherapy.