抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m 2 on day 1 plus docetaxel (75 mg/m 2 on day 1) or gemcitabine (1250 mg/m 2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m 2 or AUC 5 with gemcitabine 1000 mg/m 2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tematica de Investigacion Cooperativa en Cancer.

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Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

CA : A Cancer Journal for Clinicians

Background Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non–small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. Methods After screening tumor samples from approximately 1500 patients with non–small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. Results Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. Conclusions The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

/pdf/anaplastic-lymphoma-kinase-inhibition-in-non-small-cell-lung-4chlx92dsn.pdf

Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

Asymmetric total synthesis of a potent antifungal and cytostatic 9-methoxystrobilurin K was achieved by developing a convergent and versatile synthetic route.

Asymmetric Total Synthesis of 9-Methoxystrobilurin K.

A young male of hemorrhagic cerebral infarction associated with finasteride and minoxidil Tomoyuki Kuno, M.D., Yuto Uchida, M.D., Toshihiko Usami, M.D., Susumu Kobayashi, M.D., Koji Takada, M.D., Ph.D., Masahiro Oomura, M.D., Ph.D., and Noriyuki Matsukawa, M.D., Ph.D. Department of Neurology, Toyokawa City Hospital Department of Neurology, Nagoya City University Graduate School of Medical Sciences Department of Radiology, Toyokawa City Hospital We report a young male of hemorrhagic cerebral infarction associated with finasteride and minoxidil. He had undertaken 0.4 mg of finasteride and 4 mg of minoxidil daily for 8 months. During his exercising, he suddenly presented with a headache, followed by visual disorder. On admission, his brain MRI showed hemorrhagic cerebral infarction in the right occipital lobe. However, our examinations that revealed the cause of his cerebral infarction showed no abnormalities. Thereafter, we suspected adverse effects of finasteride and minoxidil and discontinued these medications. He never had recurrent stroke since then. We emphasize the importance of a detailed interview including unusual medications to investigate the cause of cerebral infarction.

/pdf/a-young-male-of-hemorrhagic-cerebral-infarction-associated-1jpry0nkct.pdf

A young male of hemorrhagic cerebral infarction associated with finasteride and minoxidil

Optically active silyl and stannyl substituted cyclopropylmethanols were effectively obtained by the catalytic and enantioselective cyclopropanation of γ-silyl and γ-stannyl substituted allylic alcohols with Et 2 Zn and CH 2 I 2 in the presence of chiral N,N′-bis(p-nitrobenzenesulfonyl)-1,2-cyclohexanediamine in good enantioselectivites. The absolute configurations of the resulting metallocyclopropanes were unambiguously established.

First Catalytic and Enantioselective Synthesis of Silyl‐ and Stannyl‐ Substituted Cyclopropylmethanols.

症例は53歳 男性. 平成4年7月 より痛風腎による腎不全のため, 慢性維持透析を開始した. 平成7年5月13日 に突然上腹部痛が出現, GOT/GPT 132/60IU/lと 高値で, 超音波検査にて胆嚢内に高吸収の内容物を認めた. 15 日総ビリルビン6.6mg/dl, 血清K 7.5mEq/lと 高値で, 透析後緊急開腹術を行った. 胆嚢は著明に緊満 しており, 摘出後切開すると, 壁の炎症肥厚を認め, 内部は凝血塊で充満 しており, 慢性胆嚢炎に伴う胆嚢出血と診断された. 総胆管内にも血腫を認め, これが閉塞性黄疸の原因と考えられた. Tチ ューブ ドレナージを留置し, 閉腹 した. 術 後経過は順調で1か 月後, 退院, 現在外来透析に通院中である. 慢性透析患者における胆嚢出血はこれまで1剖 検 例の報告のみであるが, 早期に適切な治療を行えば予後良好であり, 透析患者の急性腹症の鑑別診断のひとつとし て念頭におくべき疾患と考えられた.

https://www.jstage.jst.go.jp/article/jsdt1994/29/2/29_2_149/_pdf

Susumu Kobayashi

Papers

Asymmetric Total Synthesis of 9-Methoxystrobilurin K.

A young male of hemorrhagic cerebral infarction associated with finasteride and minoxidil

First Catalytic and Enantioselective Synthesis of Silyl‐ and Stannyl‐ Substituted Cyclopropylmethanols.

A case of hemorrhagic cholecystitis in a patient on maintenance hemodialysis

Stereocontrolled synthesis of an ene-carbapenem antibiotic (-)-asparenomycin c