A lung squamous carcinoma patient with ROS1 rearrangement sensitive to crizotinib.

It is widely known that ROS1 rearrangement mostly occurs in the adenocarcinoma subtype of non-small-cell lung cancer. Patients with squamous cell carcinoma harboring ROS1 rearrangement are extremely rare. This is a case report of a squamous cell carcinoma patient with ROS1 rearrangement. An 84-year-old Chinese woman with a about 6.6 cm mass in the right middle lobe and right pleural effusion, enlarged mediastinal and hilar lymph nodes was diagnosed with stage IIIB lung squamous cell carcinoma harboring ROS1 rearrangement is highly sensitive to crizotinib in the first treatment setting. This is the first time to report lung squamous carcinoma patient with ROS1 rearrangement sensitive to crizotinib. We hope that oncologists will notice this phenomenon and it will help the lung squamous cell carcinoma patient to get longer overall survival time.

MicroRNA Signature of Lung Adenocarcinoma with EGFR Exon 19 Deletion.

The findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and some of them can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer. In this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual microRNAs was validated by qRT-PCR assays. Moreover, we detected the microRNAs expression in plasma of lung adenocarcinoma patients with EGFR exon 19 deletion and wild-type. Lastly, we explored the function of the positive microRNA in EGFR tyrosine kinase inhibitors (EGFR-TKIs ) resistance using MTT and Annexin V-APC assays. The expression of 1,732 microRNAs was evaluated, and we found that microRNAs expression was different between these two groups. Hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were up-regulated and hsa-miR-3196 was down-regulated in the EGFR exon 19 deletion group compared with wild-type group. The detection of circulating microRNAs showed that miR-3196 was down-regulated in lung adenocarcinoma patients with EGFR exon 19 deletion compared with wild-type. And then the MTT assay results showed that miR-3196 had no effect on the sensitivity of erlotinib. The results of apoptosis analysis showed that inhibition of miR-3196 and erlotinib induced more apoptosis in H1299 cells than erlotinib alone, and overexpressed miR-3196 and erlotinib induced less apoptosis in PC9 cells than erlotinib alone (P<0.05). It is suggested that microRNAs associate with EGFR exon 19 deletion and miR-3196 may be further explored as a potential predictor and targeted biomarker when it is difficult to get the tumors.

Isolated brain metastasis as a late recurrence of completely resected non-small cell lung cancer.

The brain is one of the most common sites for non-small cell lung cancer (NSCLC) metastasis; however, late isolated brain metastasis as a recurrence of NSCLC is rare. The present study describes a case of isolated solitary brain metastasis as a late recurrence of NSCLC, which occurred >2 years following the successful resection of the primary tumor, and was identified by magnetic resonance imaging. To the best of our knowledge, this is the first report of isolated brain metastasis as a postoperative recurrence of NSCLC. The aim of the present study was to highlight that, despite its rarity, such recurrence should be considered possible, and particular attention to the treatment of such patients should be paid.

EGFR, KRAS and ROS1 variants coexist in a lung adenocarcinoma patient.

The c-ros oncogene 1 (ROS1) fusion is almost mutually exclusive to epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in non-small cell lung cancer (NSCLC), and it is not seen in the literature for patients to exhibit three mutations. The present study reported a case of a 53-year-old male diagnosed with adenocarcinoma, exhibiting combined EGFR, KRAS mutations and ROS1 rearrangement. At the first line therapy, the patient was treated with crizotinib because of the KRAS mutation that is a known resistant factor of EGFR-TKI resistance, but no responsive. At the second line therapy, EGFR-TKI Icotinib revealed a good response until now. To the best of to our knowledge, this is the first case report of a patient with concurrent EGFR, KRAS mutations and ROS1 fusion. This patient had an excellent response to Icotinib but not crizotinib, suggesting that the EGFR mutation was the oncogenic driver but ROS1 fusion and KRAS mutation not.

Inhibition of IGF-IR increases chemosensitivity in human colorectal cancer cells through MRP-2 promoter suppression.

The emergence of multidrug resistance (MDR) in cancer cells has made many of the currently available chemotherapeutic agents ineffective. However, the mechanism involved in mediating this effect is not yet fully understood. Here, we found the overexpression of type I insulin-like growth factor receptor (IGF-IR) in established colorectal MDR cells. Specific siRNA of IGF-IR decreases cell proliferation, exert synergistic effect with anticancer drugs. The downstream signaling of IGF-IR, PI3K/AKT pathway, was altered upon IGF-IR silencing. The expression of multidrug-resistance-associated protein 2 (MRP-2) was suppressed due to the nuclear translocation of nuclear factor-like 2 (Nrf2). Then the intracellular drug concentration was increased and the drug-resistant phenotype was reversed. Our findings improve current understanding of the biology of IGF-IR and MDR and have significant therapeutic implications on colorectal MDR cancer.

[Prognostic analysis of advanced non small cell lung cancer treated by sequential chemo-radiation therapy combined with traditional Chinese medicine: a report of 54 cases].

OBJECTIVE: To evaluate the influence of fewer courses and prolonged intervals of chemotherapy on survival rate of advanced non small cell lung cancer (NSCLC) patients treated by sequential chemo-radiation therapy combined with traditional Chinese medicine (TCM). METHODS: From Jan. 2000 to Dec. 2001, 54 untreated advanced NSCLC patients (2 stage IIIa, 18 stage IIIb, 34 stage IV) were treated by sequential chemo-radiation therapy combined with TCM. The courses of chemotherapy were reduced and the intervals of chemotherapy were longer than that of the standard regimen. The efficacy and survival rate were documented and the prognostic factors were analyzed. RESULTS: Complete remission (CR) was observed in 1 case and partial remission (PR) in 20 cases. The overall objective response rate was 40.4%. Median survival was 15.3 months, 1-, 2- and 3-year survival rate were 53.7%, 28.9% and 9.6% respectively. The median survival of stage III and IV were 21.8 months and 12.5 months respectively. The 1-, 2-, and 3-year survival rates of stage III were 65.0%, 49.5%, 24.7% and that of stage IV were 47.0%, 23.3%, 0%, respectively. The quality of life was improved in most of the patients. Cox's proportional hazards regression showed that improved quality of life and treatment of TCM were the significant prognostic factors of overall survival. CONCLUSION: Chemotherapy and radiotherapy combined with TCM is beneficial to extending the interval of chemotherapy, improving the quality of life, and increasing the survival rate of advanced NSCLC patients.

[Effects of Yifei Kangliu Oral Liquid on cell cycle and protein-nucleic acid synthesis of experimental lung cancer].

OBJECTIVE: To explore the effect of the traditional Chinese medicine Yifei Kangliu (YFKL) Oral Liquid on the proliferation, cell cycle and protein-nucleic acid synthesis of murine Lewis lung cancer cell and human lung adenocarcinoma cell line SPC-A-1. METHODS: The inhibiting rates of tumor growth were calculated by weighing the weight of tumor inoculated in vivo, combined by counting cancer cells in vitro. The ratio of the cell cycle and exponents of DNA, RNA, and protein were measured by flow cytometry (FCM). RESULTS: The inhibiting rate of tumor growth in the treated group with YFKL Oral Liquid was 30.38% (P<0.05). The proportion of cells in S phase of the treated groups with YFKL Oral Liquid was lower than that of the control group. In the group with most significant result, 72% of the cells were stagnated in G0/G1 phase. The inhibiting rates of DNA, RNA and protein in murine Lewis lung cancer were 7.4%, 23.73% and 23.31% respectively. In SPC-A-1 cell line, the inhibiting rates were 9.3%, 10.1% and 14.7% respectively, demonstrating amplified effects on lower levels. CONCLUSION: YFKL Oral Liquid significantly inhibited the proliferation of murine Lewis lung cancer cell and human lung adenocarcinoma cell line SPC-A-1 by blocking the cancer cells entering the proliferative phase resulted from its inhibition of DNA.