Zhongyuan Yin

Radiation induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: a review of new avenues in its management

Temporal lobe necrosis (TLN) is the most debilitating late-stage complication after radiation therapy in patients with nasopharyngeal cancer (NPC). The bilateral temporal lobes are inevitably encompassed in the radiation field and are thus prone to radiation induced necrosis. The wide use of 3D conformal and intensity-modulated radiation therapy (IMRT) in the treatment of NPC has led to a dwindling incidence of TLN. Yet, it still holds great significance due to its incapacitating feature and the difficulties faced clinically and radiologically in distinguishing it from a malignancy. In this review, we highlight the evolution of different imaging modalities and therapeutic options. FDG PET, SPECT and Magnetic Spectroscopy are among the latest imaging tools that have been considered. In terms of treatment, Bevacizumab remains the latest promising breakthrough due to its ability to reverse the pathogenesis unlike conventional treatment options including large doses of steroids, anticoagulants, vitamins, hyperbaric oxygen and surgery.

MicroRNA-574-5p promotes metastasis of non-small cell lung cancer by targeting PTPRU.

Dysregulation of microRNAs (miRNAs) has been associated with malignant behavior in a variety of cancers. Our previous study demonstrated that miRNA expression profiles are predictors for patients with advanced non-small cell lung cancer (NSCLC). We also showed that miRNAs are involved in small-cell lung cancer metastasis. Here, we used qRT-PCR to re-analyze our previous microarray results using serum samples from 75 patients with NSCLC. Surprisingly, we found that miR-574-5p and miR-874 were overexpressed in patients with metastatic advanced NSCLC but not in patients with non-metastatic advanced NSCLC. Additionally, miR-574-5p expression was correlated between matched serum and tissue samples from 68 patients. However, these 2 miRNAs are not prognostic factors for NSCLC. Transwell and wound-healing assays showed that miR-574-5p promotes the migration and invasion of NSCLC cells. Furthermore, miR-574-5p enhanced the tyrosine phosphorylation of β-catenin by repressing PTPRU expression in vitro. In conclusion, this study explored the expression of miR-574-5p in clinical samples and its molecular mechanisms in the metastasis of advanced NSCLC.

Gefitinib-Induced Hepatotoxicity in Patients Treated for Non-Small Cell Lung Cancer

Background: Although epidermal growth factor receptor (EGFR)-specific tyrosine kinase inhibitors (TKIs) are widely used in the management of advanced non-small cell lung cancer (NSCLC), gefitinib-induced hepatotoxicity has been underappreciated and rarely reported. Case Report: The medical records of 92 NSCLC patients, who were admitted to our cancer center in the past 5 years, were reviewed retrospectively. All patients received treatment with gefitinib (250 mg/day), during which liver function was monitored. Of the 92 NSCLC patients, 6 (6.5%) developed mild to moderate hepatotoxicity during gefitinib treatment. The time of onset of hepatotoxicity ranged from 7 days to 6 months after gefitinib administration. 1 patient (1.1%) suffered from grade 2 hepatotoxicity, and gradually recovered her normal liver function after reduction of the gefitinib dose. The other 5 patients with grade 1 hepatic impairment tolerated gefitinib well without requiring dose reductions or drug cessation. Conclusion: Gefitinib-induced hepatotoxicity is not uncommon. Although the extent of this toxicity is generally mild in nature and most patients tolerate gefitinib well, meticulous monitoring is mandatory to avoid severe hepatic impairment.

A serum microRNA signature as a prognostic factor for patients with advanced NSCLC and its association with tissue microRNA expression profiles

The aim of the present study was to detect microRNA (miRNA) signatures in advanced non-small cell lung cancer (NSCLC), and to study the association between miRNA expression levels in serum and tissue. A cohort of patients who had previously been diagnosed with advanced NSCLC was enrolled in the present study. miRNAs associated with prognosis, which had previously been detected in early stage NSCLC samples, were measured in the serum of the patient groups using a cross-validation method. In addition, serum miRNAs associated with progression-free survival (PFS) were detected in paired fresh tissue samples, in order to analyze the correlation between serum and tissue expression levels. A risk-score analysis was used to develop a four-miRNA signature to predict PFS. miR-1, miR-30d, miR-221 and miR-486 were identified as having a significant correlation with PFS in advanced NSCLC. miR-221 and miR-486 exhibited significant positive correlations between serum and tissue expression. Furthermore, overexpression of miR-221 and reduced expression of miR-486 increased cell proliferation, migration and invasion in vitro. In conclusion, the miRNA signature identified in the present study may be considered an independent prognostic factor of PFS in advanced NSCLC. In addition, the expression levels of miR-221 and miR-486 were significantly correlated between serum and tissue. miR-221 was identified as an oncogenic risk factor, whereas miR-486 exerted protective effects against cancer cell proliferation, migration and invasion.

CDP138 silencing inhibits TGF- β /Smad signaling to impair radioresistance and metastasis via GDF15 in lung cancer

CDP138, a CDK5 binding partner, regulates cell proliferation and migration. However, the mechanisms by which CDP138 functions in these processes remain unclear. In this study, we show that CDP138 is frequently overexpressed and that high levels of CDP138 are correlated with lymph node metastasis in lung cancer. Furthermore, we provide evidence that CDP138-depleted lung cancer cells exhibit enhanced radiosensitivity as well as reduced migration and invasion. Mechanistically, we identify GDF15, a member of the TGF-β superfamily, as a key downstream effector of CDP138. CDP138 silencing attenuates TGF-β/Smad signaling activation at least in part through the downregulation of GDF15. More importantly, the observed phenotypes caused by CDP138 knockdown are partially dependent on GDF15 inhibition. Together, our findings demonstrate that CDP138 positively modulates the TGF-β/Smad signaling pathway via GDF15 to promote radioresistance and metastasis, suggesting CDP138 as a potential oncogenic biomarker and a promising therapeutic target in the treatment of lung cancer.

Temporal lobe necrosis: a dwindling entity in a patient with nasopharyngeal cancer after radiation therapy

IntroductionOur objective was to report a case of misdiagnosed temporal lobe necrosis (TLN) in a patient with nasopharyngeal cancer (NPC) after radiation therapy.Case PresentationWe report a case of a 45 years old Chinese woman who developed moderate to severe headache and dizziness 1 year after 2D radiation therapy for NPC. Subsequent MRI scanning revealed a big enhancing mass in the right temporal lobe. The initial diagnosis was metastatic or intracranial extension of NPC, or a primary intracranial malignancy. She was referred to the neurosurgery department where a maximal surgical resection of the lesion was performed. A diagnosis of TLN was made according to the final histology.ConclusionTLN still matters in the IMRT era. The diagnostic quagmire of TLN lies in its close resemblance to neoplasm on clinical presentation and imaging. Reviewing the patients treatment plan to scrutinize the dose to the temporal lobes is an important prerequisite for diagnosis.

Immune thrombocytopenia as a paraneoplastic syndrome in patients with nasopharyngeal cancer

Nasopharyngeal cancer (NPC) presenting with thrombocytopenia is rare. This report details 2 cases of NPC with grade III thrombocytopenia as a paraneoplastic syndrome.

LZTS2 inhibits PI3K/AKT activation and radioresistance in nasopharyngeal carcinoma by interacting with p85

Phosphoinositide 3-kinase (PI3K) activity is aberrantly activated in nasopharyngeal carcinoma. However, the underlying mechanisms remain unclear. Here, we found that Leucine zipper tumor suppressor 2 (LZTS2) was downregulated and predicted poor prognosis in nasopharyngeal carcinoma patients. Furthermore, we identified the PI3K subunit p85 as a novel LZTS2-interacting protein using an unbiased proteomics approach. Moreover, we demonstrated that LZTS2 competes with p110 for p85 binding and inhibits activation of the PI3K/AKT signaling pathway. Functionally, we showed that LZTS2 suppresses tumorigenesis and radioresistance in nasopharyngeal carcinoma in a p85-dependent manner. Taken together, our results not only provide understanding of the molecular mechanisms by which PI3K/AKT signaling is activated but also suggest that targeting the LZTS2/PI3K/AKT signaling axis is a promising therapeutic strategy for radiosensitization of nasopharyngeal carcinoma.

Autophagy influences the low-dose hyper-radiosensitivity of human lung adenocarcinoma cells by regulating MLH1

Abstract Purpose: To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Materials and methods: Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. Results: A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR). Conversely, the radiosensitivity of H460 cells, which express high levels of MLH1, conformed to the linear-quadratic (LQ) model. After down-regulating MLH1 expression, A549 cells showed increased HRS and inhibition of autophagy, whereas H460 cells exhibited HRS/IRR. The levels of mTOR, p-mTOR, and BNIP3 were reduced in cells harboring MLH1 shRNA, and the changes in the mTOR/p-mTOR ratio mirrored those in MLH1 expression. Conclusions: Low MLH1-expressing A549 cells may exhibit HRS. Both the mTOR/p-mTOR and BNIP3/Beclin-1 signaling pathways were found to be related to HRS, but only mTOR/p-mTOR is involved in the regulation of HRS via MLH1 and autophagy.

Risk factors of complications after CT-guided percutaneous needle biopsy of lumps near pulmonary hilum

The factors influencing the incidence of common complications (pneumothorax and pulmonary hemorrhage) of CT-guided percutaneous needle biopsy of lumps near pulmonary hilum were investigated. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum was performed on 48 patients. The complications of pneumothorax and pneumorrhagia as well as the contributing factors were analyzed statistically. The major complications associated with CT-guided needle biopsy included pneumothorax (13 cases, 27.1%) and pulmonary hemorrhage (14 cases, 20.24%). χ2 test revealed that pneumothorax was associated with the lesion size and depth of needle penetration, and pulmonary hemorrhage with the depth of needle penetration and needle retention time with a significant P value. Pneumothorax was observed in 7 cases (17.5%) out of 40 cases with diameter of mass greater than 3 cm, and in 6 cases (60%) out of 10 cases with depth of needle penetration greater than 4 cm. Additionally, pulmonary hemorrhage was identified in 12 cases (41.4%) out of 29 cases with needle retention time longer than 15 min, and pulmonary hemorrhage in 7 cases (70%) out of 10 cases with depth of needle penetration greater than 4 cm. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum is safe and effective. The key factors to prevent the complications include correct evaluation of lesion size, depth of needle penetration and the needle retention time before the operation.SummaryThe factors influencing the incidence of common complications (pneumothorax and pulmonary hemorrhage) of CT-guided percutaneous needle biopsy of lumps near pulmonary hilum were investigated. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum was performed on 48 patients. The complications of pneumothorax and pneumorrhagia as well as the contributing factors were analyzed statistically. The major complications associated with CT-guided needle biopsy included pneumothorax (13 cases, 27.1%) and pulmonary hemorrhage (14 cases, 20.24%). χ2 test revealed that pneumothorax was associated with the lesion size and depth of needle penetration, and pulmonary hemorrhage with the depth of needle penetration and needle retention time with a significant P value. Pneumothorax was observed in 7 cases (17.5%) out of 40 cases with diameter of mass greater than 3 cm, and in 6 cases (60%) out of 10 cases with depth of needle penetration greater than 4 cm. Additionally, pulmonary hemorrhage was identified in 12 cases (41.4%) out of 29 cases with needle retention time longer than 15 min, and pulmonary hemorrhage in 7 cases (70%) out of 10 cases with depth of needle penetration greater than 4 cm. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum is safe and effective. The key factors to prevent the complications include correct evaluation of lesion size, depth of needle penetration and the needle retention time before the operation.