Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer.

Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn’s disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.

Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.

We compared the efficacy and the safety of a carboplatin plus etoposide regimen (CE) vs split doses of cisplatin plus etoposide (SPE) in elderly or poor-risk patients with extensive disease small-cell lung cancer (ED-SCLC). Eligibility criteria included: untreated ED-SCLC; age X70 and performance status 0 -2, or age o70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m À2 IV on days 1 -3. The SPE arm received cisplatin 25 mg m À2 IV on days 1 -3 and etoposide 80 mg m À2 IV on days 1 -3. Both regimens were given with granulocyte colony-stimulating factor support in a 21 -28 day cycle for four courses. A total of 220 patients were randomised. Median age was 74 years and 74% had a PS of 0 or 1. Major grade 3 -4 toxicities were (%CE/%SPE): leucopenia 54/51, neutropenia 95/90, thrombocytopenia 56/16, infection 7/6. There was no significant difference (CE/SPE) in the response rate (73/73%) and overall survival (median 10.6/9.9 mo; P ¼ 0.54). Palliation scores were very similar between the arms. Although the SPE regimen is still considered to be the standard treatment in elderly or poor-risk patients with ED-SCLC, the CE regimen can be an alternative for this population considering the risk -benefit balance.

p73 is a p53-related tumor suppressor but is also induced by oncogene products such as E2F-1, raising a question as to whether p73 is a tumor suppressor gene or oncogene. Unlike p53, p73 has several variants, including ⌬Np73, which lacks the NH 2 -terminal transactivation domain. Although, in developing neurons, ⌬Np73 is expressed abundantly and seems to inhibit the proapoptotic function of p53, the role of p73 and ⌬Np73 and their regulatory mechanism in cell growth and differentiation are poorly understood. Here we report that p73, but not p53, directly activates the transcription of endogenous ⌬Np73 by binding to the p73-specific target element located at positions ؊76 to ؊57 within the ⌬Np73 promoter region. The activation of ⌬Np73 promoter by p63 was marginal. ⌬Np73 was associated with p73␣, p73␤, and p53, as demonstrated by immunoprecipitation assays, and inhibited their transactivation activities when we used reporters of Mdm2, Bax, or ⌬Np73 itself in SAOS-2 cells. Furthermore, induction or overexpression of ⌬Np73 promoted cell survival by competing with p53 and p73 itself. Thus, our results suggest that the negative feedback regulation of p73 by its target ⌬Np73 is a novel autoregulatory system for modulating cell survival and death.

The clinical efficacy of a combination of adalimumab and azathioprine at WWeek 26 did not differ from that of adalimumab monotherapy in patients with Crohn's disease naïve to both medications.