Clinical analysis of NSCLC patients reveals lack of association between EGFR mutation and TET1 downregulation.

Lung cancer is one of the leading causes of death from cancer worldwide, with a poor prognosis in advanced cases. In the past decade, epidermal growth factor receptor (EGFR) inhibitors have shown significant efficacy towards treatment for EGFR mutant lung cancer. Expanding our knowledge of oncogenic EGFR signaling pathways is therefore of highly importance for the cancer field. Recently it has been proposed that mutant EGFR transcriptionally silences the TET1 (ten-eleven translocation methylcytosine dioxygenase 1) gene in cellular and animal models of lung cancer. Since TET1 is a known DNA demethylase, EGFR-mediated TET1 silencing therefore downregulates demethylation of tumor suppressor genes, which then leads to tumor growth inhibition, potentiating the role of TET1 as a tumor suppressor gene in NSCLC. In our study, we examined the role of EGFR-TET1 silencing in NSCLC patient samples. By independently analyzing the TCGA (The Cancer Genome Atlas) NSCLC data set as well as a cohort of patient samples from our hospital and a data set from publicly deposited databases, we did not observe the aforementioned mutant EGFR silencing of TET1. Conversely, in our cohort, TET1 expression levels were significantly elevated in EGFR mutant samples (P=0.007). Patients with higher TET1 levels showed a trend of better response rates to EGFR inhibitors compared to low TET1 staining levels, although the result was not significant (P=0.08). Furthermore, we did not observe a correlation between TET1 expression levels and patient survival. We conclude that while oncogenic EGFR suppression of TET1 is established in cellular and animal models of lung cancer, its role in patient outcome and prognosis remains inconclusive and warrants further investigation.

Successful treatment of erlotinib-induced acute hepatitis and acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review.

Erlotinib, a kind of epidermal growth factor receptor tyrosine kinase inhibitor, is a target therapy and approved for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced pancreatic cancer. Among these EGFR-TKI agents, including gefitinib and erlotinib, the common dose-limiting toxicities are diarrhea, mucositis and skin rash (Acneform eruptions). In addition to the above adverse effects, infrequent but potentially fatal and lethal entity complications include acute interstitial lung disease (ILD) and acute hepatitis. The incidence of EGFR-TKI agents (gefitinib and erlotinib) induced acute hepatitis is rare and hepatotoxicity of EGFR-TKI agent was rarely discussed. The treatment of EGFR-TKI agents induced acute hepatitis remains uncertain and cessation medication is current policy. Here we reported a case of erlotinib induced interstitial pneumonitis and acute hepatitis with clinical appearance of hypoxemia and general weakness, treated with high dose pulse therapy and showed good recovery.

Successful treatment of gallbladder neuroendocrine carcinoma with combined chemo-radiotherapy: a case report and literature review.

Neuroendocrine tumors (NETs) occur in the bronchopulmonary system. Extrapulmonary NETs are rare and are considered to ac count for 2.5 - 5% of all NETs, with more than 60% of these tumors occurring along the gastro intestinal tract, including primary NET of the gall bladder. Pri mary NETs of the gall bladder have been classified as carcinoid, neuroendocrine carcinoma or heterogeneous carcinoma. Currently, the main treatment of neuroendocrine car ci noma re mains surgery. The role of radiotherapy and chemotherapy is undefined be cause of the paucity of data. In advanced cases, chemotherapy has been prescribed with such effective agents as cisplatin, carboplatin, etoposide and paclitaxel. Here we re port a case of a 64-year-old Taiwanese male patient with neuroendocrine carcinoma of the gall bladder who received combined chemoradiotherapy (CCRT) with cisplatin, 5- fluorouracil and leucovorin (PFL) from June 2009 un til now, and whose disease is stable. CCRT with PFL may be a possible reg i men for high-grade neuroendocrine carcinoma of the gall bladder.

Acute interstitial pneumonitis in a patient receiving a FOLFOX-4 regimen plus cetuximab treated with pulse therapy.

We report a case of acute interstitial pneumonitis and respiratory failure occurring in a 69-year-old, previously healthy patient receiving FOLFOX regimen plus cetuximab for colon cancer. Association between this chemotherapy regimen and interstitial pneumonitis is rarely reported in the literature. We treated the patient with pulse steroid therapy, and improvement in respiratory function and decreased pulmonary infiltrations demonstrated good response to steroids use. However, the patient ultimately expired from respiratory complications after 98 days from admission, possibly due to secondary infection. Both oxaliplatin and cetuximab have rarely been associated with interstitial pneumonitis, and our case may serve as an important reference for physicians notice in patients receiving these chemotherapeutic agents.

Malignant ovarian germ cell tumors.

OBJECTIVES: Fifty patients with malignant ovarian germ cell tumors, which accounts for 10.8% of all ovarian malignancies, were treated from 1977 through 1994. Their cases are reviewed. METHODS: The histology includes endodermal sinus tumor (EST) in 15 patients, immature teratoma in 14, dysgerminoma in 13, and mixed germ cell tumor in eight. The mean age at presentation was 21.5 years and mean primary tumor diameter was 16 cm. All patients underwent surgery as the initial treatment, and 10 received more than one operation. Postoperative adjuvant chemotherapy was not given to cases with stage Ia immature teratoma and dysgerminoma. VAC (vincristine, actinomycin D, cyclophosphamide) and BVP (bleomycin, vinblastine, cisplatin) regimens were utilized in early 1980s for EST and advanced-stage tumors of immature teratoma and dysgerminoma. BEP (bleomycin, etoposide, cisplatin) and EP (etoposide, cisplatin) regimens were applied in advanced-stage disease and some stage I disease since 1990. VIP (VP-16, ifosfamide, cisplatin) regimen was employed as salvage regimen in cases where other combinations failed. RESULTS: alpha-Fetoprotein (AFP) was elevated in every tumor containing endodermal sinus element, and AFP served as a good indicator for prediction of tumor recurrence. The follow-up time ranged from 5 to 144 months with the mean of 54.5 months. CONCLUSIONS: The survival rate for EST was 54%, that for immature teratoma and dysgerminoma was 85% and 90%, respectively.

Factors contributing to the accuracy in diagnosing ovarian malignancy by color Doppler ultrasound.

OBJECTIVE: To determine whether resistance index values obtained by color Doppler ultrasound contribute to the accuracy in diagnosing ovarian malignancies. METHODS: Four hundred ten patients with ovarian neoplasms referred for color Doppler ultrasound evaluation were enrolled, excluding patients examined during the luteal phase. Resistance index of the intra-tumor arteries was measured by color Doppler ultrasound. The corresponding clinical and histopathologic information was recorded. For statistical determinations, we used the Yates corrected chi 2 analysis, Fisher exact test, Student t test, and linear regression analysis. RESULTS: Satisfactory intra-tumor artery waveforms were obtained in 96.1% (99 of 103) of ovarian malignancies. Resistance index values varied at 0.23-0.82. Regression analysis of resistance index values on tumor size and amount of ascites demonstrated a linear association (R = 0.498 and 0.362, respectively; P < .01 in both). If we regard a resistance index of 0.4 as a cutoff value, the overall sensitivity and specificity in detecting malignancy were 68.0 and 97.4%, respectively. Primary ovarian malignancies exhibited significantly more false negatives (30 of 79) than malignancies metastasized to the ovary (three of 24) (P = .018). Malignancies containing mainly cystic components exhibited more false negatives (20 of 41) than did tumors with primarily solid components (13 of 62) (P < .01). Significantly more false negatives were encountered in malignancies with larger diameters (greater than 10 cm) compared to smaller ones (27 of 63 versus six of 40; P < .01), and in malignancies accompanied by considerable ascites (greater than 1000 mL) (13 of 25 versus 20 of 78; P < .05). CONCLUSIONS: Tumor origin, size, component nature, and amount of ascites contributed to the accuracy in diagnosing ovarian malignancies using resistance index values obtained by color Doppler ultrasound.