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2% [1/57], p less then 0.001). Extraperitoneal recurrence occurred during 2008-2016 in the pleura/lungs and the para-aortic lymph nodes above the renal vessels. Cox proportional hazards regression analysis revealed that treatment period (HR 0.49, 95% CI 0.34-0.71, p less then 0.001) and bevacizumab use (HR 0.58, 95% CI 0.39-0.87, p = 0.009) were independently associated with intraperitoneal recurrence; stage IV disease (HR 1.87, 95% CI 1.14-3.06, p = 0.034) was independently associated with extraperitoneal recurrence. Conclusion Aggressive surgery reduced intraperitoneal recurrence and prolonged time to recurrence, contributing to better patient survival.We previously reported that the metastasis-associated in colon cancer-1 (MACC-D1) is overexpressed in colon cancer. However, so far, only a few effective MACC-1 inhibitors have been identified. To discover novel transcriptional inhibitors of MACC-1, we performed a luciferase reporter-based high-throughput screening (HTS). This strategy discovered rottlerin as an inhibitor of MACC-1 transcription was able to reduce cell motility in colon cancer in time- and dose-dependent manners. Wound healing assay indicated that 48-h treatment with 2.5 μM rottlerin impairs wound closure compared to the controls. Electrophoretic mobility shift assays showed that rottlerin inhibits the binding of the transcriptional activators Sp1 and c-Jun with human MACC-1 promoter. A combination of Western blot assays and expression analyses by qRT-PCR ruled out that rottlerin may act indirectly through inhibition of c-Jun or Sp1 expression to decrease MACC-1 expression in human colon cancer cell lines SW620. Rather, these results support that rottlerin restricts the binding of MACC-1 promoter directly by c-Jun and Sp1 in colon cancer cells. Thus, as a small-molecule inhibitor of MACC-1, rottlerin may benefit colon cancer patients by suppressing MACC-1-dependent tumor growth and metastasis.Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), the first immune checkpoint to be targeted clinically, has provided an effective treatment option for various malignancies. However, the clinical advantages associated with CTLA-4 inhibitors can be offset by the potentially severe immune-related adverse events (IRAEs), including autoimmune thyroid dysfunction. To investigate the candidate genes and signaling pathways involving in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy, integrated differentially expressed genes (DEGs) were extracted from the intersection of genes from Gene Expression Omnibus (GEO) datasets and text mining. The functional enrichment was performed by gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) network, module enrichment, and hub gene identification were constructed and visualized by the online Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. A total of 22 and 17 integrated human DEGs in hypothyroidism and hyperthyroidism group related to anti-CTLA-4 therapy were identified, respectively. Functional enrichment analysis revealed 24 GO terms and 1 KEGG pathways in the hypothyroid group and 21 GO terms and 2 KEGG pathways in the hyperthyroid group. After PPI network construction, the top five hub genes associated with hypothyroidism were extracted, including ALB, MAPK1, SPP1, PPARG, and MIF, whereas those associated with hyperthyroidism were ALB, FCGR2B, CD44, LCN2, and CD74. learn more The identification of the candidate key genes and enriched signaling pathways provides potential biomarkers for autoimmune thyroid dysfunction related to anti-CTLA-4 therapy and might contribute to the future diagnosis and management of IRAEs for cancer patients.Corrections are needed to the original version of this article.Background Immune checkpoint blockade therapy may lead to thyroid dysfunction in 3-7% of treated patients. Alemtuzumab is a CD52 inhibitor leading to thyroid dysfunction in approximately 40% of patients. A female patient was affected by multiple sclerosis (MS) and subclinical hyperthyroidism due to an autonomously functioning thyroid nodule (AFTN). After alemtuzumab treatment, she developed aggressive clinical hyperthyroidism consistent with Marine-Lenhart syndrome. Case presentation A 36-year-old woman presented in July 2019 with symptoms of hyperthyroidism and eye complaints. Three years earlier, she was diagnosed with MS. Subclinical hyperthyroidism was diagnosed in April 2017. Thyroid scintigraphy showed an intranodular distribution of 99mTc-pertechnatate consisting of an AFTN in the right lobe of the thyroid. In June 2018, because of the MS, she was treated with alemtuzumab. In November 2018, she was started on methimazole treatment because of the symptoms of hyperthyroidism. In December 2018, thyroid function was normal under methimazole treatment. In June 2019, the patient received a second round of alemtuzumab administration. One month later, she developed symptoms of hyperthyroidism. These symptoms were accompanied by diplopia. Blood tests showed severe hyperthyroidism. Thyroid scintigraphy showed a diffuse distribution of 99mTc-pertechnatate and the presence of a "cool" area in the right lobe of the thyroid, confirmed by ultrasonography. The nodule was diagnosed as a low-risk indeterminate lesion. Conclusion We present a case of Graves' disease with active, moderate-to-severe Graves' ophthalmopathy in a patient with pre-existing AFTN presenting with a coexisting, rare case of Marine-Lenhart syndrome associated with immune reconstitution after alemtuzumab treatment.Diabetes mellitus (DM) is a chronic multisystem disease. Diabetic nephropathy (DN) is one of its significant microvascular complications, associated with increased morbidity and mortality. The aim of this article is to review the literature regarding the latest advances in the management of type 2 DM (T2DM) in patients with chronic kidney disease (CKD). We initially refer to the screening guidelines, the diagnostic tests used, the need for novel biomarkers in DN, the recent advances in high-risk patient identification, the recommended glycemic targets, and concerns regarding the accuracy of HbA1c in these patients. Then, a detailed explanation of the appropriate medical management based on evidence from recent trials is presented, analyzed, and discussed. All patients with T2DM should be screened for albuminuria at initial diagnosis and annually thereafter. Proteomics and metabolomics today represent promising diagnostic tools. Optimal glycemic control, with individualized HbA1c targets, is fundamental for reduced onset or delayed progression of DN and microvascular complications, in general.