DNA repair has been suggested to be a major cause of spontaneous drug resistance in patients with lung adenocarcinomas (LADC). Among the DNA repair-related proteins, excision repair ...cross-complementation group 1 (ERCC1) has been shown to be essential for repairing cisplatin-induced interstrand cross-linkage. However, the role of other DNA repair-related proteins in drug resistance has not been clearly elucidated. In this study, we used suppression subtractive hybridization and microarray analysis to identify the DNA repair-related genes associated with cisplatin resistance. We focused on the association of XPC protein expression, which plays a pivotal role in the earliest response to global genomic repair, with the survival of LADC patients. Using suppression subtractive hybridization and a microarray analysis to identify drug resistance-associated DNA repair-related genes, we found that the mRNA levels of ERCC1, MSH-3, MSH-6 and XPC were significantly increased in LADC patients. Since the results of ERCC1 mRNA expression corresponded well with those in previous reports, in this study we focused on the clinical correlation between XPC expression and patient survival. The level of XPC protein was determined by immunohistochemical and immunoblotting analyses. We detected the XPC protein in 46 (43%) of 107 pathological LADC samples. XPC protein expression correlated with tumor stage, cigarette smoking and poor survival. In the in vitro experiments with LADC cell lines, increased XPC expression was associated with elevated drug resistance, and silencing of XPC expression reduced cisplatin resistance. Our results suggest that XPC expression predicts drug resistance in LADC.
DNA repair is one of the major causes of spontaneous drug and radiation resistance in patients with lung adenocarcinomas (LADC). 53BP1 is a mediator that relays signals from DNA damage sensors and ...activates various effectors for the DNA repair and cell survival. In this study we investigated the clinical and biological significance of 53BP1. Expression of 53BP1 was detected by immunoblotting and immunohistochemistry. Our data showed that 53BP1 was detected in 166 (75.8%) of 219 LADC patients. Expression of 53BP1 correlated with tumor stage, cigarette smoking, lymphovascular invasion and poor clinical outcome. In vitro, increased 53BP1 expression elevated drug resistance, and silencing of 53BP1 expression reduced cisplatin resistance. Our results suggest that 53BP1 expression plays an important role in cisplatin resistance and predicts the prognosis for LADC.
By using mRNA differential display to examine specimens of non-small cell lung cancer (NSCLC), we have identified overexpression of dihydrodiol dehydrogenase (DDH) that was not detected in the ...corresponding normal lung tissue. Normally DDH is associated with catalysis of polycyclic aromatic hydrocarbons (PAHs) in the liver; in NSCLC cells, DDH expression would implicate an association with disease progression. In this study we investigated the prognostic significance of DDH expression in patients with NSCLC. By using immunohistochemistry, we measured DDH expression in 381 patients with NSCLC. The relationship between DDH expression and clinicopathological parameters (age, gender, smoking history, mitotic index, histological type, stage, cell differentiation, and lymphovascular invasion) was analyzed by chi2 analysis. Survival curves were plotted with the method of Kaplan-Meier, and statistical difference of survivals between different groups was compared by a log-rank test. Our results showed that DDH overexpression could be detected in 317 (83.2%) of 381 pathological sections and in 77.9% (60 of 77) of metastatic lymph nodes. Expression of DDH was confirmed by immunoblotting. Compared with patients with DDH overexpression in tumors, patients with low DDH expression had significantly lower incidence of early tumor recurrence and distant organ metastasis (46.7 versus 29.7%; P = 0.045). Interestingly, survival was also significantly better in patients with low DDH expression than in those with DDH overexpression (P = 0.0017). Using univariate analysis, we correlated three important factors, DDH overexpression, tumor stages, and gender, with poor prognosis for NSCLC patients. Nevertheless, biological function and involvement of DDH in the disease progression of NSCLC require additional studies.
We used suppression subtractive hybridization (SSH) and oligonucleotide microarray to differentiate expression profiles of metastasis-related genes and to evaluate their clinical significance in ...patients with invasive oral cancer (OCa). Overexpression of the specific genes was confirmed by reverse transcription-PCR (RT-PCR). Cells expressing the gene were identified by immunohistochemistry in pathology specimens. Clinical correlation and significance were analyzed statistically. Using these methods, we detected increased expressions of MMP-1, -3, -7, -9, -10 and interleukin (IL)-8 in invasive OCa. Moreover, our data showed that overexpressions of MMP-1, -3, -7, -10 and IL-8 were associated with reduced survival.
Previous reports have indicated that patients with severe acute respiratory syndrome (SARS)-associated coronavirus infection could develop atypical pneumonia with fulminant pulmonary edema. However, ...the target cells of SARS viral infection have not been characterized in detail. We report the pathologic findings of the lung in 3 cases of SARS. Chest radiographs at 2 to 3 weeks of infection revealed an atypical pneumonia with pulmonary consolidation, a clinical characteristic of SARS infection. The presence of the SARS virus was determined by nested reverse transcription-polymerase chain reaction (RT-PCR), and the infected cells were identified by in situ hybridization in open-lung biopsy and postmortem necropsy specimens. Expression of SARS virus-encoded RNA was detected in all 3 cases by RT-PCR, and the SARS viral signal was localized in pneumocytes by using in situ hybridization.
nm23-H1, a nucleoside diphosphate kinase (NDPK), enhances drug sensitivity and has antimetastatic activity, whereas focal adhesion kinase (FAK) is closely associated with cell migration and tumour ...spreading. The relationship between these two proteins, however, is not well elucidated. In this study, we investigate their correlation in patients with non-small cell lung cancer (NSCLC). Expressions of nm23-H1 and FAK were examined by reverse transcription-polymerase chain reaction and immunoblotting in surgical resections. The relationship between these two genes was assessed statistically. Patients were classified into four groups according to the expression of nm23-H1 and FAK by immunohistochemistry: FAK-negative/nm23-H1-positive, FAK-negative/nm23-H1-negative, FAK-positive/nm23-H1-positive and FAK-positive/nm23-H1-negative. Although the causal correlation is still uncertain, our results showed that protein expression of nm23-H1 was inversely correlated with that of FAK. The combined analysis of nm23-H1 and FAK protein expression in the same tumour specimens revealed that patients with FAK-negative/nm23-H1-positive tumours survived the longest, 56 months, among those with nm23-H1 and FAK features (P<0.001). Our data indicate that expressions of nm23-H1 and FAK are inversely correlated. These results suggest that the status of nm23-H1 and FAK protein expression may help in predicting the aggressive behavior of NSCLC. However, further studies are warranted to clarify the impact of FAK on the function of nm23-H1 as an anti-metastatic gene.
Background: This study examines the usefulness of thallium-201 single photon emission computed tomography (201Tl SPECT) in differentiating pulmonary malignancies from benign lesions by using dual ...phase 201Tl scintigraphy. Methods: One hundred and six patients with thoracic lesions and confirmed diagnoses were assessed by 201Tl chest SPECT examinations; of these 106 enrolled thoracic lesions, 59 were malignancies and 47 were benign lesions. Dual phase 201Tl SPECT was performed with an early image acquired at 10–20 min and a delayed image at 2–3 h after intravenous injection of 2–3 mCi of 201Tl. The results of 201Tl SPECT images were classified as either malignant or benign lesions by visual interpretation: the lesion was interpreted as positive for malignancy if the uptake of 201Tl in the lung lesion in the delayed phase was increased or persistent as compared with that in the early phase image; otherwise, it was considered as a benign lesion. Simultaneously, the traditional method of retention index (RI) was also calculated to help in the differential diagnosis of pulmonary lesions. Then, both methods of dual phase 201Tl SPECT, visual reading and traditional RI, were compared to differentiate pulmonary malignancies from benign lesions. Results: Analyzing the image results, we found that dual phase 201Tl SPECT could differentiate pulmonary malignancies from benign lesions with a sensitivity of 83%, a specificity of 91% and an accuracy of 87%. Moreover, by using the traditional RI method of 201Tl SPECT, it could differentiate pulmonary malignancy from benign lesions with a sensitivity of 79.3%, a specificity of 80.8% and an accuracy of 80%. Conclusions: We conclude that using dual phase 201Tl SPECT with visual interpretation is a simpler and potentially more effective method for differentiating pulmonary malignancies from benign lesions, with results compatible with the traditional RI method of 201Tl SPECT.
An 18‐year‐old girl who had severe headaches in the left temporal and facial regions was found to have a small enhanced dural‐based parietal convexity mass. On magnetic resonance imaging (MRI), this ...mass was homogeneously enhanced with “dural tail sign,” and was similar to a meningioma. This mass was completely removed surgically, and pathology proved it to be a cavernous angioma without previous hemorrhages. The patient's facial pain was dramatically relieved after surgery. A small dural mass causing severe facial pain is an unusual situation. The lack of hemosiderin in the extra‐axial cavernous angioma often leads to the preoperative diagnosis of meningioma.
Intravesical adjuvant chemotherapy and neoadjuvant chemotherapy has been respectively administered for superficial transitional cell carcinoma (TCC) of urinary bladder and advanced TCC for years. ...However, the therapeutic efficacy is limited. Recently, overexpression of aldo-keto reductase (AKR) in lung, esophageal, uterine cervical and ovarian cancers was shown to be closely associated with disease progression and drug resistance. In this study, we used immunohistochemistry to determine AKR expression in pathological specimens of 347 patients with urinary bladder cancer (UBC). Some of these patients were from areas with a high risk of black foot disease (BFD), a disease that is closely associated with arsenic contamination of drinking water. The presence of AKR was confirmed by immunoblotting, matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF) and reverse transcription-polymerase chain reaction (RT-PCR). AKR isotype was determined by cDNA sequencing. Our results showed overexpression of AKR1C2 in 226 (65.1%) patients. BFD areas had a higher frequency of patients expressing AKR1C2 in UBC. Among AKR1C2-positive UBC, 148 (65.5%) were invasive, 70 (31.0%) were non-invasive and 8 (3.5%) were carcinoma in situ (CIS). These data indicated that AKR1C2 expression could be significantly associated with cancer invasiveness (p<0.001) and disease progression. Because BFD has been closely related to arsenic ingestion, our results suggested that continual intake of arsenic in drinking water might provoke AKR1C2 expression that could in turn induce drug resistance in UBC, and AKR1C2 could be a tumor marker for UBC.
We reported an extremely rare case of undifferentiated endometrial stromal sarcoma imaged with gallium-67 scintigraphy. This previously healthy 32-year-old woman presented with cough and dyspnea for ...days. Unexpectedly, the pathology of the opacity in the right pulmonary hilar region demonstrated metastatic high-grade epithelioid sarcoma. Gallium scintigraphy performed to detect possible origin showed abnormal uptake in the right supraclavicular region, chest region and pelvic region. Computed tomography-guided biopsy of the pelvic mass revealed undifferentiated endometrial stromal sarcoma. This case demonstrated the usefulness of gallium-67 scintigraphy in the detection of the primary disease and the evaluation of the metastatic disease.
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