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Monoclonal antibodies binding the EGFR, such as cetuximab and panitumumab, have been extensively used as targeted therapy for the treatment of mCRC. However, in clinical practice, it has been found that these treatment options have some limitations and fail to fully exploit their immunoregulatory activities. Meanwhile, because of the limited effects of current treatments, immunotherapy is being widely studied for patients with mCRC. However, previous immunotherapy trials in mCRC patients have had unsatisfactory outcomes as monotherapy. Thus, combinatorial treatment strategies are being researched. The authors retrieved relevant documents of combination therapy for mCRC from PubMed and Medline. This review elaborates on the knowledge of immunomodulatory effects of anti-EGFR therapy alone and in combination with immunotherapy for mCRC. Although current treatment options have improved median overall survival (OS) for advanced disease to 30 months, the prognosis remains challenging for those with metastatic disease. More recently, the combination of anti-EGFR therapy with immunotherapy has been shown activity with complementary mechanisms. Hence, anti-EGFR therapy in combination with immunotherapy may hold the key to improving the therapeutic effect of refractory mCRC. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis (PC) is an advanced malignancy that is not sensitive to systemic conventional chemotherapy. Treatment options for PC are usually palliative rather than curative. Cytoreductive surgery and hyperthermic intraperitoneal (IP) chemotherapy are associated with limited efficacy in patients with PC. However, the peritoneum can produce effective immunity by inducing T-lymphocyte recruitment and proliferation, and the unique immune environment of the peritoneum provides the rationale for IP immunotherapy in PC. The authors retrieved relevant documents of IP immunotherapy for PC from PubMed and Medline. This review elaborates on the knowledge of the peritoneal immune microenvironment and IP immunotherapy for PC covering immune stimulators, radioimmunotherapy, catumaxomab, cancer vaccines, chimeric antigen receptor (CAR)-T cells, and immune checkpoint inhibitors. The prognosis of PC is poor. However, the peritoneal cavity is a unique immune compartment with abundant immune cells which can produce effective immunity. IP immunotherapy may be a promising strategy in patients with PC. [ABSTRACT FROM AUTHOR]

Inhibitors of COMT are clinically used for the treatment of Parkinson's disease. Here, we report the first natural pentacyclic triterpenoid-type COMT inhibitors and their structure-activity relationships and inhibition mechanism. The most potent compounds were found to be oleanic acid, betulinic acid and celastrol with IC50 values of 3.89–5.07 μM, that acted as mixed (uncompetitive plus non-competitive) inhibitors of COMT, representing a new skeleton of COMT inhibitor. Molecular docking suggested that they can specifically recognise and bind with the unique hydrophobic residues surrounding the catechol pocket. Furthermore, oleanic acid and betulinic acid proved to be less disruptive of mitochondrial membrane potential (MMP) compared to tolcapone, thus reducing the risk of liver toxicity. These findings could be used to produce an ideal lead compound and to guide synthetic efforts in generating related derivatives for further preclinical testing. [ABSTRACT FROM AUTHOR]

In December 2009, within just weeks of the issuance of several controversial (and arguably ultra vires) tax circulars by the Ministry of Finance (MOF) and by the State Administration of Taxation (SAT), the SAT promulgated a seminal regulation governing informal rulemaking activities of all tax authorities in China. This regulation took effect on 1 July 2010 and promises to significantly improve the clarity, transparency, predictability and quality of rulemaking on taxation in the PRC. Ironically, it can also be seen as a rebuke to a cynical view that is rather prevalent among Chinese tax practitioners and reinforced by the recent problematic tax circulars: namely, that because the PRC government does not care about creating order in tax administration and taxpayers are unwilling or are unable to enforce their rights, informal rules issued by the government should be given full weight even if they contradict laws created by higher authority and/or are inconsistent with each other. The new SAT regulation on informal rulemaking is just one illustration of the dynamic development of the rule of law in taxation in China. This article uses the enactment of the new regulation as an occasion for examining the question: what is the 'law' in Chinese tax administration? [ABSTRACT FROM AUTHOR]

The present study investigated the possible clinical significance of serum CA125 levels in patients with non-Hodgkin's lymphoma (NHL) and the mechanism of secretion. Serum CA125 levels in 335 patients with NHL were measured by enzyme-linked immunosorbent assay. The tissue CA125 expression in 22 patients with NHL was performed on paraffin section by immunohistochemical methods. One hundred and ninety-eight cases (59.1%) were found to have elevated serum CA125 levels. Serum CA125 levels were associated with clinical stage, effusions, high serum lactate dehydrogenase and β2-M levels, and response to therapy. Microscopically, immunohistochemical staining revealed that malignant tumor cells demonstrated negative CA125 expression in all of the 22 cases. Our results suggested that serum CA125 levels could be an interesting tumor marker in NHL. The immunohistochemical study suggested that CA125 appeared not to be secreted by lymphoma cells directly. [ABSTRACT FROM AUTHOR]