Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing “wax-and-wane” transformation

BACKGROUND: Small-cell lung cancer with epidermal growth factor receptor (EGFR) gene mutation typically manifests as a transformation occurring after EGFR tyrosine kinase inhibitor therapy for adenocarcinoma with EGFR mutation, whereas primary small-cell lung cancer showing EGFR mutation is extremely rare. Second biopsy of EGFR-mutated tumor has been broadly recognized as necessary, but is not always performed in daily practice, mainly due to the imbalance between the potential risk of the diagnostic procedure and the therapeutic impact of the biopsy result. CASE PRESENTATION: A 70-year-old woman who had never smoked was referred to our hospital with chief complaints of cough and back pain. Transbronchial lung biopsy from the primary tumor of the left upper lobe revealed combined small-cell lung cancer and adenocarcinoma, a subtype of small-cell lung cancer. EGFR L861Q mutation was detected in both small-cell lung cancer and adenocarcinoma components. Given the staging of cT2aN3M1b (Stage IV) and histological diagnosis, first-line chemotherapy with cisplatin plus irinotecan was initiated, and partial response was achieved. Seven months after initial diagnosis, the primary tumor enlarged again, and a second biopsy from the enlarged lesion detected only adenocarcinoma with the L861Q mutation. Erlotinib was started, but multiple brain metastases and enlarged mediastinal lymph nodes subsequently appeared. Whole-brain radiation therapy was performed, and endobronchial ultrasonography-guided transbronchial biopsy from the lymph node revealed reverse transformation to small-cell lung cancer with the L861Q mutation. Amrubicin therapy achieved partial response after two cycles, with the shrinkage lasting for eight months. Serum sialyl Lewis X antigen level increased when the adenocarcinoma component was dominant, whereas plasma pro-gastrin-releasing peptide level increased when the small-cell lung cancer component became dominant. CONCLUSIONS: Transformation of the tumor correlates with the difference between small-cell lung cancer and adenocarcinoma in sensitivity to therapies, so repeated biopsies are beneficial for choosing appropriate treatments. Noninvasively obtainable parameters such as tumor markers can support the need for biopsy

Nuclear magnetic resonance study on rotational dynamics of water and benzene in a series of ionic liquids: Anion and cation effects.

The rotational correlation times (τ(2R)) for polar water (D(2)O) molecule and apolar benzene (C(6)D(6)) molecule were determined in ionic liquids (ILs) by means of the (2)H (D) NMR spin-lattice relaxation time (T(1)) measurements. The solvent IL was systematically varied to elucidate the anion and cation effects separately. Five species, bis(trifluoromethylsulfonyl)imide (TFSI(-)), trifluoromethylsulfonate (TfO(-)), hexafluorophosphate (PF(6) (-)), chloride (Cl(-)), and formate (HCOO(-)), were examined for the anion effect against a fixed cation species of 1-butyl-3-methyl-imidazolium (bmim(+)). Four species, bmim(+), N-methyl-N-butylpyrrolidinium (bmpy(+)), N,N,N-trimethyl-N-propylammonium (N(1,1,1,3) (+)), and P,P,P-trihexyl-P-tetradecylphosphonium (P(6,6,6,14) (+)), were employed for the cation effect against a fixed anion species of TFSI(-). The τ(2R) ratio of water to benzene, expressed as τ(W∕B), was used as a probe to characterize the strength of Coulombic solute-solvent interaction in ILs beyond the hydrodynamic limit based on the excluded-volume effect. The τ(W∕B) value was found to strongly depend on the anion species, and the solute dynamics are sensitive not only to the size but also to the chemical structure of the component anion. The cation effect was rather weak, in contrast. The largest and most hydrophobic P(6,6,6,14) (+) cation was exceptional and a large τ(W∕B) was observed, indicating a unique solvation structure in [P(6,6,6,14) (+)]-based ILs

Pathways and Kinetics of Anisole Pyrolysis Studied by NMR and Selective 13C Labeling. Heterolytic Carbon Monoxide Generation

By applying [13]C and [1]H NMR spectroscopy the pyrolysis of site-selectively [13]C-enriched (H3[13]CO[12]C6H5) and normal anisole compounds was studied in the dark at 0.001–1.0 M (M, mol dm[−3]) and at 400–600 °C (supercritical conditions). Conversion of the [13]C-labeled methyl group was confined to the methoxy-originated fragments, [13]CO and [13]CH4, and the reactive intermediate, H[13]CHO*. The normal phenyl group, [12]C6H5– was converted to benzene, [12]C6H6 and phenol, [12]C6H5OH without ring disintegration. The pyrolysis consists of two elementary steps: (1) the rate-determining unimolecular ether-bond fission (k1) to generate the fragmented product C6H6 and energized intermediate H[13]CHO* through the intramolecular proton transfer from the methoxy group to the phenyl, and (2) the fast bimolecular disproportionation (k2) through the intermolecular proton/hydride transfer from H[13]CHO* to H3[13]COC6H5 to produce [13]CO, [13]CH4, and C6H5OH. CO is generation by the heterolytic (ionic) mechanism in contrast to the homolytic (radical) one via the phenoxy radical intermediate (C6H5O•) in the literature despite the agreement of the rate constant (k1) and the activation energy

Prospects for a personalized peptide vaccine against lung cancer

Introduction: The tumor characteristics and immunological status of the host should be carefully considered for the successful development of cancer peptide vaccines. Recently, personalized peptide vaccines (PPV) that individually select antigens for each patient are being developed for lung cancer. Areas covered: Novel PPV, in which appropriate vaccine antigens are selected in each patient by assessing preexisting immunity to a panel of vaccine peptide candidates, have been attempted with promising results in early-phase clinical trials for lung cancer. Additionally, PPV targeting neo-antigens derived from genetic mutations have been currently attempted with high anticipation of success in various cancers, because they can be recognized as foreign by the host immune system. In this review, we present an overview of the current progress and future directions of such PPV for patients with lung cancer. Expert opinion: Both genetic characterization of tumor cells and assessment of the immune responses to potential tumor antigens might be a key component for facilitating successful cancer vaccine development. In addition, not only selection of immunogenic epitopes, but also appropriate modulation of the host immunological status should be considered; clinical trials combining neo-antigen vaccines and anti-PD-1 antibodies for lung cancer are currently ongoing and their results are awaited

Pneumothorax during Pemetrexed Treatment in a Patient with Non-Small Cell Lung Cancer: A Case Report and Literature Review

Pemetrexed is a multitargeted antifolate that has demonstrated antitumor activity in non-small cell lung cancer. A 70-year-old male presented with a stage IV non-small cell lung cancer. The patient was treated with pemetrexed as third-line chemotherapy. However, a pneumothorax occurred 16 days after the administration of the second cycle of pemetrexed. The pneumothorax was slight and the patient was observed without undergoing any additional treatment. Twenty-four days after its initial occurrence, the pneumothorax had improved. This is the first case of pneumothorax that has been observed during pemetrexed treatment. Pneumothorax during chemotherapy is rare; however, it is a life-threatening complication and should not be overlooked