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 One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy.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

Eighteen patients experienced recurrence after resection of carcinoma of the head of the pancreas which were confirmed imaging methods were subjected to a study evaluating diagnostic modalities for recurrence, patterns of recurrence, treatment and prognosis after recurrence. Both ultrasonography (US) and computed tomography (CT) were excellent modalities for diagnosis of recurrence in the liver, however, for diagnosis of local recurrence, CT was more valuable than US and positron emission tomography (PET) was usefull for early detection of local recurrence. Lesions were apt to be detected early after operation in patients with recurrence in the liver compared with in those with local recurrence. The therapuetic effect for recurrence in the liver, cannot be expected but in patients with local recurrence detected over two years after the resection, radiation therapy prolonged period of survival. Prognosis after recurrence of patients in whom local recurrence was identified initially was significantly better than that of patients in whom recurrence in the liver was seen initially. In patients developed recurrence after resection of carcinoma of the head of the pancreas, prolonged survival cannot be expected at the time when hepatic recurrence occurs, however, therapeutic effects can be attained if the recurrence remains in the local region. The importance of correct diagnosis of local recurrence for better prognosis should be emphasized.

Clinical study on recurrence after resection for carcinoma of the head of the pancreas

A case of psoas abscess associated with diabetes mellitus (DM) is reported. The 64-year-old male patient with untreated DM was admitted to the hospital because of pain in the left lower side of his back and in the left leg. White blood cell, CRP, blood glucose and HbAIC were elevated. Abdominal ultrasonography demonstrated an ehco free space and abdominal CT scan revealed a low density area with un irregular border in the left psoas muscle, indicative of psoas abscess. Ultrasonography-guided percutaneous drainage was performed and thick, white pus was obtained. Group B β-Streptococcus was detected by culture. The patient's condition was improved with the pus drainage, administration of antibiotics and treatment of diabetic status by intermittent insulin injection, but a hard mass developed subsequently in the left groin region. Pus that was similar to that previously drained from the psoas abscess was also collected by an incision of the mass. The amount of pus drainage gradually decreased over the course of days, and the patient was discharged from the hospital. Though the process of infection and the development of the abscess were unclear in this case, they seemed to have been induced by advanced DM as a fundamental complication.

https://www.jstage.jst.go.jp/article/ringe1998/61/6/61_6_1622/_pdf

Psoas abscess with diabetes mellitus treated by ultrasonography-guided percutaneous drainage-a case report-

二次性副甲状腺機能亢進症患者より摘出した副甲状腺における, preproPTH, c-myc, オルニチン脱炭酸酵素遺伝子 (ODC) mRNAの発現をノーザンブロット法で調べ, 術前に投与した1,25(OH)2D3(D3) の影響を検討した. 3例11個の副甲状腺においてpreproPTHの発現は最小の発現量を1とした場合最大約2倍程度の多寡が見られたものの, 副甲状腺の大きさや組織型の多様性と相関した変化ではなかった. c-mycの発現は1例の4個の副甲状腺のうち2個で発現増大が認められた. しかしこれらの副甲状腺の大きさや組織型には際立った特徴はなく, その発現増大の原因は明らかではなかった. ODC mRNAの発現量はすべての副甲状腺においてほぼ一定であった. D3は4μgを4例に対して術前3.5-48時間に経口投与した. 摘出した13個の副甲状腺の遺伝子発現を検討した結果, preproPTH, c-myc, ODCいずれの発現も3例の非投与例と差が認められなかった. したがって副甲状腺摘出術の適応となるような二次性副甲状腺機能亢進症においては, D3 4μg投与では, これらの遺伝子発現は抑制されないものと考えられた.

Susumu Kobayashi

Papers

Clinical study on recurrence after resection for carcinoma of the head of the pancreas

Psoas abscess with diabetes mellitus treated by ultrasonography-guided percutaneous drainage-a case report-

mRNA expression of preproPTH and growth-related genes in secondary hyperparathyroidism in chronic renal failure patients