To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α6β4integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α6β4were examined by Western blotting and flow cytometry in certain human pancreatic cancer cell lines. The human cell line BxPC-3 was used for α6β4-positive and a mouse cell line, A4, was used for negative counterpart. We labeled antibody against α6β4with Indium-111 ((111)In) or indocyanine green (ICG). After injection of(111)In-labeled probe to tumor-bearing mice, biodistribution, SPECT, autoradiography (ARG), and immunohistochemical (IHC) studies were conducted. After administration of ICG-labeled probe, in vivo and ex vivo NIR imaging and fluorescence microscopy of tumors were performed. BxPC-3 tumor showed a higher radioligand binding in SPECT and higher fluorescence intensity as well as a delay in the probe washout in NIR imaging when compared to A4 tumor. The biodistribution profile of(111)In-labeled probe, ARG, and IHC confirmed the α6β4specific binding of the probe. Here, we propose that α6β4is a desirable target for the diagnosis of pancreatic cancer and that it could be detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG-labeled α6β4antibody.
© The Author(s) 2016.

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The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 Å resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.

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On April 1, 2016 BioWa, Inc. ("BioWa") reported that it was relocating its office from La Jolla, California to Princeton, New Jersey, and appointment of Mr. Takeshi Masuda, as the President and CEO for the next stage of corporate development (Press release, Kyowa Hakko Kirin, APR 1, 2016, View Source [SID:1234510289]).

Mr. Masuda has also served as President of Kyowa Kirin USA Holdings, Inc. the holding company of Kyowa Hakko Kirin’s US pharmaceutical subsidiaries.

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BioWa develops partnerships with pharmaceutical companies and biotechs through the licensing of proprietary therapeutic antibody technologies POTELLIGENT and COMPLEGENT. These technologies were developed by Kyowa Hakko Kirin, Co. Ltd. and BioWa will be continuing a role as the exclusive worldwide licensor of those technologies after relocation to Princeton.

Cancer is a serious disease that causes many deaths every year. We urgently need to design effective treatments to cure this disease. Tumor suppressor genes (TSGs) are a type of gene that can protect cells from becoming cancerous. In view of this, correct identification of TSGs is an alternative method for identifying effective cancer therapies. In this study, we performed gene ontology (GO) and pathway enrichment analysis of the TSGs and non-TSGs. Some popular feature selection methods, including minimum redundancy maximum relevance (mRMR) and incremental feature selection (IFS), were employed to analyze the enrichment features. Accordingly, some GO terms and KEGG pathways, such as biological adhesion, cell cycle control, genomic stability maintenance and cell death regulation, were extracted, which are important factors for identifying TSGs. We hope these findings can help in building effective prediction methods for identifying TSGs and thereby, promoting the discovery of effective cancer treatments.

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Neuroendocrine tumors (NETs) are malignant solid tumors arising in hormone-secreting tissue. They have historically been very difficult to treat, and advanced NETs are considered incurable. Surgery is the only potentially curative treatment option, though research is ongoing, investigating the efficacy of targeted therapies combined with more traditional chemotherapies. Frequent bowel movements and episodes of flushing are the most common symptoms.
The present study reports data from an anonymous patient survey of 663 eligible NET patients, identified with the assistance of patient advocacy groups. This study investigated the impact of treatment (surgery alone; surgery plus somatostatin analogue; other treatments) on quality of life (QOL). Finally, we investigate whether recurrent disease results in poorer QOL compared to disease treated curatively with surgery and remaining in remission.
Results suggest that increased frequency of bowel movements and presence of any flushing symptoms are correlated with decreased quality of life. Treatment groups differed on most Patient Reported Outcomes Measurement Information System (PROMIS) global health and PROMIS-29 scores, including physical function, fatigue, pain, social function, and general physical and mental health, with the surgery group reporting significantly better scores than the other groups (effect size of differences ranged from 0.28 to 0.54). This may be possibly due to effective symptom control reached for these patients through surgery alone. After adjustment for carcinoid syndrome, the association with the treatment group disappeared for all domains except physical functioning. In terms of disease status, patients with recurrent disease reported poorer physical, social, and mental functions. Depression scores were similar between groups; however, patients with recurrent disease reported significantly higher anxiety compared to those with no current NET. Physical functioning was even more markedly different between groups, with recurrent NET patients reporting significantly impaired overall physical function, impaired sleep, and significant fatigue compared to those with no current NET. To our knowledge, this is the first study to comprehensively examine the effect of treatment group, disease status, and symptom burden on the quality of life in NET patients in a large sample. Limitations and future research directions are discussed.

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