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Although alectinib is effective for relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) and has a favorable safety profile, its role as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the role of allo-HSCT itself in this setting are unknown. A 35-year-old man with ALK-positive ALCL experienced relapse after first-line therapy with CHOP. Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed. However, disease progressed 15 months after transplantation, and alectinib was initiated. Complete response (CR) was achieved after three months of treatment, and alectinib was continued for 5 months. After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate. The post-transplant course was unremarkable except for grade I acute GVHD. The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.

Palladium-catalyzed direct arylation polycondensation of 3,4-ethylenedioxythiophene (EDOT) with dibromocarbazole was investigated by varying heating conditions and microwave heating conditions. The polycondensation of EDOT with 3,6-dibromocarbazole resulted in the alternating copolymer (Mn = 6600) in high yield. In contrast, 2,7-dibromocarbazole shows low reactivity and the polycondensation of EDOT with 2,7-dibromocarbazole resulted in an oligomeric product (Mn< 4000) in low yield. [ABSTRACT FROM AUTHOR]

Studies on the isolation and molecular mechanisms of phytochemicals with anti-tumor or anti-inflammatory properties are important to developing new drugs for cancer and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. In the course of a study to screen bioactive isoflavones from Erythrina poeppigiana (Leguminosae), we isolated an isoflavone with potent apoptosis-inducing activity against human leukemia HL-60 cells. It was designated erypoegin K. The studies demonstrated an enantiomer, (S)-erypoegin K, displayed selective cytotoxic activity, was a novel inhibitor of topoisomerase II, and possessed anti-tumor activity both in vitro and in vivo. We identified other apoptosis-inducing isoflavones with the ability to inhibit glyoxalase I. Dimeric acridone alkaloids, carbazole alkaloids, and coumarin and quinoline derivatives-all obtained mainly from plants in the family Rutaceae-induced apoptosis of HL-60 cells via the production of reactive oxygen species and mitochondrial dysfunction. We also identified terpenoid coumarins, carbazole quinones, rotenoid derivatives, and quinolone alkaloids with anti-inflammatory activities. These compounds reduced nitric oxide (NO) production from RAW264.7 macrophage cells stimulated with lipopolysaccharides and interferon-γ. Some of the compounds displayed neuroprotective activity by reducing NO production. This review primarily describes our recent studies on erypoegin K, and other compounds with apoptosis-inducing and anti-inflammatory activities.

An 89-year-old female who had been clinically diagnosed with primary lung cancer underwent right upper lobectomy and lymph node dissection(ND2a-2). Postoperative pathological staging revealed a stage ⅡA(pT1bN1M0)adenocarcinoma that was negative for an EGFR mutation. Nineteen months after surgery, the patient developed a mediastinal lymph node metastasis, and radiotherapy was prescribed. Thirty-eight months later, she developed new mediastinal/hilar lymph node metastases and was prescribed pemetrexed(500 mg on day 1 of each of 3 weeks)as the first-line therapy. A complete response was evident after 10 courses. However, she developed grade 3 nausea, and pemetrexed was discontinued. During 10 months of follow-up, no new lesion appeared; therefore, follow-up was discontinued. Ninety-three months after surgery, she was referred to our hospital because an abnormal shadow was apparent on chest roentgenography. A thorough examination revealed pleural dissemination, pulmonary metastases, mediastinal/hilar lymph node metastases, an adrenal metastasis, and bone metastases. Although her performance status(PS)was poor(grade 4), as the diagnosis was ALK fusion gene-positive adenocarcinoma, alectinib(600 mg once daily)was commenced as the second-line therapy. Complete response was achieved 14 months later(ie, 108 months after surgery and 89 months after postoperative recurrence). Thus, an octogenarian patient with poor PS and ALK fusion gene-positive adenocarcinoma exhibited a complete response after treatment with alectinib.

Few cases of lung mucoepidermoid carcinomas with anaplastic lymphoma kinase (ALK) fusion have been reported. A 35-year-old woman was found to have an abnormal chest X-ray. A tumor and obstructive pneumonitis in her left upper lobe was detected using computed tomography (CT). She was admitted to our hospital, and was diagnosed with mucoepidermoid carcinoma by transbronchial biopsy. Left pneumonectomy and lymphadenectomy were performed for lung mucoepidermoid carcinoma and a mediastinal lymph node metastasis (pT2aN2M0, stage ⅢA). Postoperative radiotherapy (50 Gy) to the mediastinum and chemotherapy were performed followed by several radiotherapies for cervical and mediastinal lymph node and right ischium metastases. Since then, further radiotherapy was impossible. However, we detected ALK fusion in the resected specimen and the cancer responded to alectinib hydrochloride.

The prognosis of Parkinson's disease (PD) has been improved with developing anti-parkinsonian agents. Recently the re-evaluation of L-dopa and dopamine agonists is the topic in the world based on focusing non motor side effects of dopamine agonists such as sudden uncontrollable somnolence and valvulopathy in place of motor complication. The development of anti-parkinsonian drugs based on the new mechanism has been progressed such as CEP-1347, AAV-neuturin, AAV-GAD, and AAV-DDC. The most reliable new drug is zonisamide which is originally synthesized in Japan for epilepsy. A nation-wide randomized double blind study showed that Zonisamide improves motor function of advanced PD patients. Long-term efficacy was also shown. The mechanism of zonisamide for PD is the increase of dopamine synthesis and moderate inhibition of monoamine oxydase B activity. Inhibitatory effects of sodium channel and T-type calcium channel may also affects. Zonisamide has neuroprotective effects though inhibition of quinoprotein and increasing the levels of GSH and Mn SOD. Up to now we have no agents with clinically evidenced neuroprotective effects for PD. Base on the results of ELLDOPA study and "delayed start" clinical trials the most important concept for neuroprotection may be the early dopaminergic support for the degenerating dopaminergic system.

FAB Cooperative Group has cited 3 or higher percentage in the peroxidase (PO) activity as one of criteria for the diagnosis of acute myeloid leukemia. We have previously reported in two cases of acute myelomonocytic leukemia (M4) that there was a great difference between 3,3'-diaminobenzidine (DAB) and 3-amino 9-ethyl carbazole (3AC) as substrates for PO reaction. In order to confirm the previous result, we extended the cases and compared the PO activities in blood films taken from several leukemic subjects, which were fixed with various kinds of fixatives, using DAB and 3AC as substrates. Their peroxidase activities were also determined through electron microscopy (EM-PO). There were no differences among fixatives and substrates in staining normal granulocytic cells (neutrophils and monocytes) and cells in 13 cases of leukemia, except for two cases, one with M4 and the other with relapse of M2. These showed the highest PO activity with 3AC staining and 10% formaldehyde acetone buffer for fixation. Besides, all types manifested the highest positivity in EM-PO, except for the relapse of M2 that showed a higher positivity in the peroxidase stain by 3AC staining, 10% formaldehyde acetone buffer fixation than the EM-PO. Unlike other leukemic blasts PO reaction products of blast cells of the two cases showed a scattered distribution of microscopic granules. These findings suggested the difference, which was seen in the previous reports, of the PO stain between two substrates might be due not only to sensitivity for staining but to the presence of some heterogeneity such as isoenzyme in the myeloperoxidase.