記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内分泌外科学会  

<p>乳癌は臨床病理学的サブタイプ分類に基づく治療が行われている。近年ではOncotypeDX^®を用いてより正確なサブタイプ分類の判定や治療が可能となった。また，トラスツズマブの抗体薬物複合体であるトラスツズマブデルクステカンの登場によりHER2低発現という新しいサブタイプが登場した。さらに，ER陽性乳がんに対する治療耐性への克服として<i>ESR1</i>変異に基づく治療戦略や，PI3K/AKT経路の阻害薬であるカピバセルチブの登場，homologous recombination repair deficiency（HRD）に対する治療戦略など，分子診断に基づく治療がさらに細分化されつつある。今後も乳がん診療は遺伝子変異に基づいた個別治療が広がっていくだろう。</p>

DOI： 10.11226/ojjaes.41.2_127

CiNii Research

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内分泌外科学会  

<p>甲状腺腫瘍診療ガイドラインが大幅に改訂され2024年版が発刊された。薬物療法については近年のがんゲノム医療の普及に伴い甲状腺がんの領域ではドライバー遺伝子異常に紐づいた複数の選択的チロシンキナーゼ阻害薬が使用可能となり，再発・転移甲状腺がん患者の治療選択肢は増加している。一方で，複数のコンパニオン診断薬とがん遺伝子パネル検査（comprehensive genome profile：CGP）が存在することで臨床の現場では混乱が予想される。本稿では，再発・転移甲状腺がんに対する薬物療法におけるガイドラインの改訂の目的と補足すべき点について概説した。</p>

DOI： 10.11226/ojjaes.41.2_100

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Breast Cancer  

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

DOI： 10.1007/s12282-023-01505-x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内分泌外科学会  

<p>当科においては中リスク甲状腺乳頭癌に対する外科治療方針を2000年以降全摘（TT）＋D3→TT＋両側D1→片葉切除（IL）＋患側D1へde-escalationしてきた。このde-escalationに伴う治療成績を検証することにより中リスク乳頭癌に対する最適な治療方針を検討した。de-escalationしたことにより，未郭清領域である対側の気管周囲リンパ節には約５分の１の症例でリンパ節転移の存在が推測された。しかし，経過観察期間（中央値約６年）において臨床的な再発は患側外側リンパ節の１例であり，生命予後に影響する様な再発はきたしていない。甲状腺全摘を行わないことにより術後放射性ヨウ素治療も行っていないが，予後には影響していないようである。よって，経過観察期間がまだ短いが, 中リスク群に対するIL＋患側D1郭清は妥当な方針と考えられた。</p>

DOI： 10.11226/ojjaes.40.3_140

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内分泌外科学会  

<p>日本では，標準治療が終了した，もしくは終了見込みの固形癌患者を対象として2019年６月より包括的がんゲノムプロファイリング（CGP）検査が保険適用されている。加えて，甲状腺癌に対しては，2022年２月に<i>RET</i>陽性甲状腺癌に対するセルペルカチニブが薬事承認された。甲状腺癌に対するがんゲノム医療が広がりつつある一方で，その治療へのアクセスのしやすさなどまだ課題が残る。</p>

DOI： 10.11226/ojjaes.40.1_18

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nutrients  

(1) Background: Protein stimulates the secretion of glucagon (GCG), which can affect glucose metabolism. This study aimed to analyze the metabolic effect of a high-protein diet (HPD) in the presence or absence of proglucagon-derived peptides, including GCG and GLP-1. (2) Methods: The response to HPD feeding for 7 days was analyzed in mice deficient in proglucagon-derived peptides (GCGKO). (3) Results: In both control and GCGKO mice, food intake and body weight decreased with HPD and intestinal expression of Pepck increased. HPD also decreased plasma FGF21 levels, regardless of the presence of proglucagon-derived peptides. In control mice, HPD increased the hepatic expression of enzymes involved in amino acid metabolism without the elevation of plasma amino acid levels, except branched-chain amino acids. On the other hand, HPD-induced changes in the hepatic gene expression were attenuated in GCGKO mice, resulting in marked hyperaminoacidemia with lower blood glucose levels; the plasma concentration of glutamine exceeded that of glucose in HPD-fed GCGKO mice. (4) Conclusions: Increased plasma amino acid levels are a common feature in animal models with blocked GCG activity, and our results underscore that GCG plays essential roles in the homeostasis of amino acid metabolism in response to altered protein intake.

DOI： 10.3390/nu14050975

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13691-021-00520-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Reports  

The platelet isoform of phosphofructokinase (PFKP) is one of the key enzymes in the glycolytic pathway. PFKP is highly expressed in several cancers, and it has been reported to be involved in the progression of cancer cells. However, its oncological role in breast cancer (BC) remains unclear. The present study aimed to evaluate the function of PFKP in BC cells and its expression level in patients with BC. Firstly, the mRNA and protein expression of PFKP was evaluated in BC and non‑cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to evaluate the correlation between PFKP and 84 cancer‑related genes. Then, PFKP knockdown was conducted using small interfering RNA, and cell proliferation, invasiveness and migration were analyzed. Furthermore, the association between PFKP mRNA expression and clinicopathological factors was inves‑ tigated in 167 patients with BC. PFKP was highly expressed in estrogen receptor‑negative and human epidermal growth factor receptor 2‑negative BC cell lines. PCR array analysis demonstrated that the expression level of PFKP was signifi‑ cantly correlated with that of transforming growth factor‑β1 and MYC proto‑oncogene. PFKP knockdown significantly decreased the proliferation and invasiveness of MCF7, SK‑BR‑3, and MDA‑MB‑231 cells. Furthermore, cell migra‑ tion was inhibited in SK‑BR‑3 and MDA‑MB‑231 cells. In the clinical specimens, patients with T2/T3/T4, lymph node metastasis, or stage II/III/IV exhibited higher expression of PFKP mRNA than patients with less severe disease. In conclu‑ sion, the present findings indicated that PFKP is involved in promoting tumor‑progressive oncological roles in BC cells across different subtypes and is considered a possible novel therapeutic target for BC.

DOI： 10.3892/or.2021.8220

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13691-021-00515-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13691-021-00517-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Current Oncology  

Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients’ clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. Results: Among 13 BC cell lines, estrogen receptor (ER)positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ERpositive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ERnegative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways.

DOI： 10.3390/curroncol28050346

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Surgery Today  

Purpose: Papillary thyroid cancer (PTC) is generally associated with a favorable prognosis. However, some patients have fatal disease, with locally infiltrating tumors or progressive distant metastases; yet few studies have investigated the characteristics of the tumor-progressive gene expression profile in advanced PTC. We conducted this study to clarify the gene expression status in advanced PTC and identify candidate molecules for prognostic biomarkers. Methods: We analyzed 740 tumor-progressive gene expression levels from formalin-fixed paraffin-embedded blocks of samples from six patients with low-risk PTC and six patients with high-risk PTC, using the nCounter PanCancer Progression panel. Then, we investigated the association between the expression levels of focused genes and pathological factors in PTC patients in The Cancer Genome Atlas (TCGA) database. Results: The expression levels of 14 genes in the high-risk PTC specimens were more than two-fold those in the low-risk PTC specimens. In the TCGA database, expression levels of four genes (CCL11, COL6A3, INHBA, and SRPX2) were significantly higher in patients with advanced PTC. Among the patients with advanced PTC, those with high SRPX2 expression levels had poor disease-free survival. Univariate and multivariate analyses revealed that high SRPX2 expression was an independent prognostic factor. Conclusion: Based on the findings of this study, CCL11, COL6A3, INHBA, and SRPX2 are potential biomarkers that indicate advanced PTC. SRPX2, in particular, is considered a prognostic biomarker.

DOI： 10.1007/s00595-021-02262-0

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本内分泌学会  

DOI： 10.1507/endocrine.97.s.update_31

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.annonc.2021.05.764

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nagoya Journal of Medical Science  

The standard chemotherapy regimen for unresectable or recurrent biliary tract cancer is gemcitabine combined with cisplatin (GC). To evaluate the effectiveness and safety of chemotherapy in patients with unresectable or recurrent biliary tract cancer in the real world, we retrospectively analyzed the clinical courses of patients who underwent chemotherapy with GC from January 2015 to November 2019. Forty-eight patients underwent the GC regimen. One patient (2.1%) achieved a complete response, seven patients (14.6%) achieved a partial response, 26 patients (54.2) achieved stable disease, 11 patients (22.9%) achieved progressive disease, and 3 patients (6.3%) were not evaluable. The overall response rate was 16.7%. The median overall survival was 14.2 months (95% CI: 13.8–14.6), and the median progression-free survival was 7.7 months (95% CI: 4.2–11.2). Thirty-nine patients (81.3%) experienced grade 3 or higher severe adverse events as follows: 54.2% experienced neutropenia, 20.8% experienced anemia, 12.5% experienced thrombocytopenia and 20.8% experienced biliary tract infection. As a second-line chemotherapy, S-1 was used in seventeen patients, and stable disease was achieved in three patients (17.6%). The GC regimen for biliary tract cancer is effective and safe for unresectable or recurrent biliary tract cancer in routine clinical practice.

DOI： 10.18999/nagjms.82.4.725

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Letters  

Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, MZB1 mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. MZB1 mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of MZB1 mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker.

DOI： 10.3892/ol.2020.12059

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Letters  

Breast cancer (BC) is the most frequently diagnosed malignant tumor in women worldwide, and the development of new molecules associated with BC is essential for the management of this disease. RAS and EF-hand domain-containing (RASEF) encodes the GTPase enzyme that belongs to the Rab family. Although the effects of this gene have been reported in several malignant tumor types, the role of RASEF in BC has not been completely elucidated. The aim of the present study was to investigate the importance of RASEF expression in BC. RASEF mRNA expression levels were evaluated in BC and non-cancerous mammary cell lines. The association between RASEF mRNA expression levels and clinicopathological factors in 167 patients with BC were then determined. Among the 13 examined BC cell lines, ER-negative/HER2-negative cell lines expressed lower RASEF mRNA levels, when compared with the other examined cell lines (P=0.014). Of the 167 patients examined, patients with negative hormone receptor status exhibited significantly lower RASEF mRNA expression levels (P<0.001). In addition low RASEF expression in BC tissues was associated with negative estrogen receptor status (P<0.001), negative progesterone receptor status (P<0.001), and triple-negative status (P<0.001). Additionally, although the differences were not statistically significant, patients with low RASEF expression levels exhibited poorer disease-free survival (P=0.123) and overall survival (P=0.086) than other patients. The results of the present study indicate that RASEF mRNA expression levels are associated with hormone receptor status in BC.

DOI： 10.3892/ol.2018.9542

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Nuclear Medicine  

Background Age is a prognostic factor for recurrent differentiated thyroid carcinoma (DTC) and may be related to radioactive iodine (RAI) nonavidity. Indications for molecular-targeted drugs (MTDs) are currently limited to RAI-refractory DTC. Demonstrating refractoriness to RAI, mainly indicated by RAI nonavidity, may be a barrier to the introduction of MTDs for elderly patients. The present study was conducted to evaluate the impact of age and histological type on the RAI avidity of recurrent lesions of DTC. Methods Two hundred fifty-eight patients (189 patients with classic papillary thyroid carcinoma [cPTC], 8 patients with follicular variant of papillary thyroid carcinoma, and 61 patients with follicular thyroid carcinoma), who underwent their first RAI whole-body scanning for recurrent DTC at our institution between 2004 and 2013, were retrospectively studied. Radioactive iodine uptake was determined by visible uptake by metastatic lesion(s) in a diagnostic RAI-whole-body scan. Results The prevalence of RAI-avid lung metastases in cPTC indicated a significant, inverse correlation with age (<55 years, 36.2%; ≥55 years, 3%; P < 0.001). By contrast, for follicular thyroid carcinoma, the prevalence of RAI avidity was not influenced by age. Similar tendencies were observed for lymph node metastases. Conclusions Radioactive iodine avidity by metastatic lesions of cPTC in elderly patients, especially those older than 55 years, was seldom demonstrated. Adherence to a strategy of restricting MTD administration after confirmation of RAI refractoriness should be revisited for elderly patients. A strategy of omitting RAI treatment should be taken into account when considering age and histological type.

DOI： 10.1097/RLU.0000000000002078

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nagoya Journal of Medical Science  

Laparoscopic adrenalectomy is the gold standard procedure for most adrenal tumors. Obesity is considered as a risk factor for surgical complications. This study aimed to evaluate whether obesity affects peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy using body mass index (BMI). This retrospective study included 98 patients who underwent transabdominal laparoscopic adrenalectomy between January 2011 and December 2016. We divided the patients into 2 groups: non-obese group (BMI < 25 kg/m2) and obese group (BMI ≥ 25 kg/m2). We assessed perioperative outcomes and postoperative complications between the groups. A total of 98 patients were analyzed (70 without obesity and 28 with obesity). There were no significant differences between the non-obese and obese groups regarding operative time (111 vs 107 min; p = 0.795), blood loss (3.5 vs 3.5 ml; p = 0.740), rate of placement of additional trocars (14.3% vs 17.9%; p = 0.657), rate of open conversion (2.6% vs 3.6%; p = 0.853), and postoperative length of hospital stay (6 vs 5 days; p = 0.237). Furthermore, obesity was not a significant risk factor for postoperative complications (postoperative bleeding, wound infection, and pneumonia). There are no significant differences in peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy in patients with obesity compared with those without obesity. Transabdominal laparoscopic adrenalectomy is feasible and safe for patients with obesity.

DOI： 10.18999/nagjms.80.1.21

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40792-017-0408-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Reports  

Breast cancer (BC) is the most common malignant tumor among women worldwide. Development of novel molecular targets is important to improve prognosis of BC patients. Derlin 3 (DERL3) gene is a member of derlin family, and its coding protein is critical to the endoplasmic reticulumassociated degradation mechanism. However, its oncological role in breast cancer remains unclear. This study evaluated DERL3 expression and function in BC. We analyzed DERL3 mRNA in 13 BC and two non-cancerous cell lines, and explored effects of DERL3 knockdown on BC proliferation, invasion and migration. We also evaluated correlation of DERL3 mRNA expression levels with clinicopathological factors and prognosis in 167 BC patients. DERL3 mRNA expression was detected in five (38%) BC cell lines. Inhibiting DERL3 expression significantly decreased proliferation and invasion in BC cells. Specimens from patients with lymph node metastasis had higher DERL3 mRNA expression than those without (P=0.030). Patients in the highest quartile for DERL3 mRNA expression (n=42) were more likely to experience shorter overall survival than other patients (P=0.032). These findings indicate that DERL3 promotes malignant phenotype in BC cells. DERL3 may serve as a potential prognostic marker and therapeutic target for BC.

DOI： 10.3892/or.2017.5800

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncology Letters  

Breast cancer (BC) is the most common malignancy among women. Identifying novel biomarkers to predict prognosis accurately is important in managing this disease. The regulatory factor X1 (RFX1) gene is a member of the regulatory factor X gene family. Its protein reportedly downregulates the proto-oncogene c-myc, but its role in BC has been unclear. In this study, expression and methylation status of RFX1 were determined in BC cell lines. We then evaluated RFX1 mRNA expression levels with regard to clinicopathological factors including postoperative prognosis in 167 patients with BC. Expression of RFX1 was heterogeneous among cell lines, and we found no DNA methylation at the RFX1 promoter region. Patients were categorized into groups with high or low RFX1 expression, based on ratio of RFX1 mRNA expression in BC and adjacent non-cancerous tissues. The high RFX1 group was significantly associated with low T factor (P=0.028), earlier disease stage (P=0.015), positive expression of estrogen receptor (P=0.005) and progesterone receptor (P=0.011), negative expression of human epidermal growth factor receptor 2 (P=0.001). The high RFX1 group experienced more favorable disease-free survival (P=0.007) and overall survival (P=0.013). In multivariate analysis, RFX1 expression was an independent prognostic factor for disease-free survival. Our findings indicate that RFX1 may serve as a prognostic marker for BC.

DOI： 10.3892/ol.2017.6005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

<p>気管内腔までの浸潤を伴う甲状腺癌は稀ではあるが，血痰，喀血，呼吸困難などの症状を伴って患者を死に至らしめる重篤な病態である。症例の絶対数が少ないので，切除範囲に対する考え方，気管再建法，周術期管理などについて臨床試験を行うことはほぼ不可能で，比較的症例数が多い施設からの報告があるのみである。ここでは当科における甲状腺癌気管浸潤例に対する気管合併切除および再建の経験を踏まえて，特に膜様部温存気管端々吻合を重点的に紹介する。周到な術前評価，確実な手技，適切な周術期管理により端々吻合再建は安全に施行でき，患者のQOL維持に有用であると考えられる。</p>

DOI： 10.11226/jaesjsts.34.2_98

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

Animal models with defective glucagon action show hyperplasia of islet α-cells, however, the regulatory mechanisms underlying the proliferation of islet endocrine cells remain largely to be elucidated. The Gcg^gfp/gfp mice, which are homozygous for glucagon/green fluorescent protein knock-in allele (GCGKO), lack all proglucagon-derived peptides including glucagon and GLP-1. The present study was aimed to characterize pancreatic neuroendocrine tumors (panNETs), which develop in the GCGKO mice. At 15 months of age, macroscopic GFP-positive tumors were identified in the pancreas of all the GCGKO mice, but not in that of the control heterozygous mice. The tumor manifested several features that were consistent with pancreatic neuroendocrine tumors (panNETs), such as organoid structures with trabecular and cribriform patterns, and the expression of chromogranin A and synaptophysin. Dissemination of GFP-positive cells was observed in the liver and lungs in 100% and 95%, respectively, of 15-month-old GCGKO mice. To elucidate the regulatory mechanism for tumor growth, PanNET grafts were transplanted into subrenal capsules in GCGKO and control mice. Ki-67 positive cells were identified in panNET grafts transplanted to GCGKO mice 1 month after transplantation, but not in those to control mice. These results suggest that humoral factors or conditions specific to GCGKO mice, are involved in the proliferation of panNETs. Taken together, GCGKO mice are novel animal model for studying the development, pathogenesis, and metastasis panNETs.

DOI： 10.1371/journal.pone.0133812

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