BACKGROUND & AIMS: :Results of a study on the relative frequencies of tumors in American black and Nigerian children were compared with data from the Childhood Cancer Registries in Manchester, United Kingdom, and Kampala, Uganda. The American black child living in Washington, D.C. and the Caucasian child living in Manchester had similar high frequencies for leukemia and glioma, whereas the incidence of lymphoma and retinoblastoma was low. African children living in Nigeria or Uganda had the opposite frequency patterns. These differences in frequencies of tumors between two ethnologically related population groups, American black and Nigerian, suggested the influence of environmental factors in the etiology of these tumors, even though exposure to environmental carcinogens was short. The rarity of Ewing's sarcoma and testicular tumors in American black and Nigerian children suggested a genetic influence.

背景与目标： ：将一项关于美国黑人和尼日利亚儿童肿瘤相对频率的研究结果与来自英国曼彻斯特和乌干达坎帕拉的儿童癌症登记处的数据进行了比较。居住在华盛顿特区的美国黑人孩子和居住在曼彻斯特的白人孩子白血病和神经胶质瘤的发病率相似，而淋巴瘤和视网膜母细胞瘤的发病率却很低。生活在尼日利亚或乌干达的非洲儿童的频率模式相反。在两个与人种学相关的人口群体（美国黑人和尼日利亚人）之间，这些肿瘤发生频率的差异表明，即使短期暴露于环境致癌物，环境因素也影响了这些肿瘤的病因。在美国黑人和尼日利亚儿童中，尤因肉瘤和睾丸肿瘤的罕见性表明有遗传影响。

BACKGROUND & AIMS: INTRODUCTION:Apoptosis (programmed cell death) is the best described mode of physiological cell death. During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is external protein signal originating from other cell--also named as "death signal". Another one is specific cell reaction for external stress factors. Blood concentration of proteins regulating both pathways of apoptosis may be useful in early diagnosis and staging of thyroid tumors. The aim of study was evaluation of p53 and sFasL blood concentration in patients with benign follicular adenoma and follicular thyroid cancer. MATERIALS AND METHODS:The study population was composed of 28 patients: 14 with thyroid carcinoma and 14 patients with follicular neoplasm (NF). All patients underwent surgical treatment. P53 and sFasL levels were evaluated before surgery and related to the histopathological diagnosis obtained post-surgery. RESULTS:The analysis revealed high sFasL blood concentration in patients with follicular thyroid cancer in comparison with the group with follicular adenoma. There was no statistically significant difference between levels of p53 in both groups. CONCLUSIONS:Evaluation of sFasL serum level concentration may be useful in preoperative diagnosis of follicular thyroid tumors.

背景与目标： 简介：细胞凋亡（程序性细胞死亡）是描述性的生理性细胞死亡方式。在胚胎发育和形态发生过程中，可能通过两种途径诱导细胞凋亡。第一个是源自其他细胞的外部蛋白质信号-也称为“死亡信号”。另一个是针对外部应激因素的特异性细胞反应。调节细胞凋亡的两种途径的蛋白质的血药浓度可能对甲状腺肿瘤的早期诊断和分期有用。研究的目的是评估良性滤泡性腺瘤和滤泡性甲状腺癌患者的p53和sFasL血药浓度。
材料与方法：研究人群由28例患者组成：14例甲状腺癌和14例滤泡性肿瘤（NF）。所有患者均接受手术治疗。在手术前评估P53和sFasL水平，并与手术后获得的组织病理学诊断有关。
结果：分析显示，与滤泡性腺瘤相比，滤泡性甲状腺癌患者的sFasL血药浓度较高。两组中p53水平之间无统计学差异。
结论：血清sFasL水平的评估可能对甲状腺滤泡性肿瘤的术前诊断有帮助。

BACKGROUND & AIMS: :The transphenoidal procedure has become the preferred approach in the surgical management of sellar/parasellar tumors. Nevertheless, specific indications remain for the transcranial approach and the objective of this review is to evaluate the available data on outcomes following transcranial or transphenoidal approaches to sellar/parasellar tumors. We assess the indications used for each approach and parameters that favor one over the other. Factors such as tumor size, consistency and configuration are important variables in choosing the transcranial approach. Other important considerations include persistent visual loss after incomplete decompression via the transphenoidal route, ectatic midline carotid arteries, co-existent intracranial aneurysms and sphenoid sinusitis. We review the data on visual and endocrinological outcomes following the transcranial or transphenoidal approach and provide an argument that, while there appears to be a trend towards greater visual improvement after transcranial surgery for large-to-giant pituitary adenomas, this benefit is offset by a greater risk of postoperative pituitary dysfunction. There is no difference in the rate of recurrence between the two procedures in the published literature. Overall, craniotomies will continue to play a role in the management of patients with sellar/parasellar tumors, although patient selection and careful preoperative evaluation are key elements in choosing the most appropriate approach.

背景与目标： ：经蝶突手术已成为蝶鞍/鞍旁肿瘤手术治疗的首选方法。然而，经颅入路的具体指征仍然存在，本综述的目的是评估经颅或经蝶入路治疗鞍/鞍旁肿瘤后可获得的结局数据。我们评估了每种方法所使用的适应症和参数，它们相互之间有利。肿瘤大小，一致性和构型等因素是选择经颅入路的重要变量。其他重要的考虑因素包括经蝶窦途径减压不完全后持续的视力丧失，直肠中线颈动脉，并存的颅内动脉瘤和蝶窦炎。我们回顾了经颅或经蝶入路方法后的视觉和内分泌结果的数据，并提出了一个观点，即对于大到大的垂体腺瘤，经颅手术后似乎有更大的视觉改善趋势，但这种益处被术后垂体功能障碍的风险更大。在已发表的文献中，这两种方法的复发率没有差异。总体而言，开颅手术将继续在蝶鞍/鞍旁肿瘤患者的治疗中发挥作用，尽管患者选择和仔细的术前评估是选择最合适方法的关键因素。

BACKGROUND & AIMS: All patients referred to the Institute of Radiotherapy and Nuclear Medicine in Peshawar (IRNUM) during 1990 to 1994 were analyzed. There were 1655 children with biopsy-proven cancers; 1290 were from the North West Frontier Province (NWFP), and the remaining 365 were Afghan refugees. Male children from the NWFP were 67% and females were 33%. Among Afghan children, 69% were males and 31% were females. Patients whose histopathologies were doubtful or not available were excluded from the study. The most common tumors in children in the NWFP were lymphoid leukemia, lymphoma, myeloid leukemia, Wilms tumor, tumors of the central nervous system (CNS), soft tissue sarcoma, bone tumors, retinoblastoma, neuroblastoma, and testicular tumors. Among Afghan children the most common cancers were lymphoma, lymphoid leukemia, myeloid leukemia, Wilms tumor, retinoblastoma, tumors of soft tissue, bone tumors, CNS tumors, testicular tumors, and neuroblastoma.

背景与目标： 分析了1990年至1994年间转诊至白沙瓦放射与核医学研究所（IRNUM）的所有患者。有1655名儿童经活检证实为癌症。 1290名来自西北边境省（NWFP），其余365名是阿富汗难民。 NWFP的男性儿童为67％，女性为33％。在阿富汗儿童中，男性占69％，女性占31％。组织病理学可疑或无法获得的患者被排除在研究之外。 NWFP儿童中最常见的肿瘤是淋巴样白血病，淋巴瘤，髓样白血病，Wilms肿瘤，中枢神经系统（CNS）肿瘤，软组织肉瘤，骨肿瘤，视网膜母细胞瘤，神经母细胞瘤和睾丸肿瘤。在阿富汗儿童中，最常见的癌症是淋巴瘤，淋巴样白血病，髓样白血病，威尔姆斯瘤，视网膜母细胞瘤，软组织肿瘤，骨肿瘤，中枢神经系统肿瘤，睾丸肿瘤和神经母细胞瘤。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的研究结果表明，缺氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，这导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性特征。

BACKGROUND & AIMS: :Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.

背景与目标： ：最近在肺腺癌中，主要在东亚患者中，报道了HER2基因的酪氨酸激酶结构域中的活化突变。我们的研究旨在评估白人患者肺腺癌中HER2突变的发生率和性质。通过PCR单链构象多态性分析和外显子19和20的直接测序，评估了403例肺腺癌中HER2基因的突变状态。我们发现9例（2.2％）病例中存在HER2突变。突变中的七个（78％）位于776-779位密码子（YVMA）的框架重复/插入中，另外两个为碱基取代，导致氨基酸变化。先前发现在776-779碱基处的热点突变是亚洲患者中最常见的HER2突变。在传统的肺腺癌（CLA）和具有支气管肺泡特征（ABAFs）的肺腺癌之间，突变的分布存在显着差异。 113个ABAF中有7个（6.2％）和290个CLA中有2个（0.7％）被突变了（p = 0.0025）。此外，HER2突变的频率在女性（4.1％）比男性（1.8％）和从不吸烟者（3.1％）要高出吸烟者（1.9％），但差异无统计学意义。还研究了该系列肿瘤的EGFR和K-ras突变。在43（10.7％）例中观察到EGFR突变，在110（27.3％）例中观察到K-ras突变。发现EGFR，HER2和K-ras突变是相互排斥的事件。 HER2突变在一部分肺腺癌患者中的存在增加了用HER2特异性激酶抑制剂治疗这些患者的希望。

BACKGROUND & AIMS: :Following surgery, the hormone dependence of breast tumors is exploited for therapy using antagonists such as tamoxifen, although occasional hormone-resistant clones do appear. Another chemotherapeutic strategy uses microtubule inhibitors such as taxanes. Unfortunately, these agents elicit toxicities such as leukocytopenia, diarrhea, alopecia, and peripheral neuropathies and are also associated with the emergence of drug resistance. We have previously described a tubulin-binding, natural compound, noscapine, that was nontoxic and triggered apoptosis in many cancer types albeit at 10 mumol/L or higher concentrations depending on the cell type. We now show that a synthetic analogue of noscapine, 9-bromonoscapine, is approximately 10-fold to 15-fold more potent than noscapine in inhibiting cell proliferation and induces apoptosis following G2-M arrest in hormone-insensitive human breast cancers (MDA-MB-231). Furthermore, a clear loss of mitochondrial membrane potential, release of cytochrome c, activation of the terminal caspase-3, and the cleavage of its substrates such as poly(ADP-ribose) polymerase, suggest an intrinsic apoptotic mechanism. Taken together, these data point to a mitochondrially mediated apoptosis of hormone-insensitive breast cancer cells. Human tumor xenografts in nude mice showed significant tumor volume reduction and a surprising increase in longevity without signs of obvious toxicity. Thus, our data provide compelling evidence that 9-bromonoscapine can be useful for the therapy of hormone-refractory breast cancer.

背景与目标： ：手术后，尽管偶尔出现激素抵抗性克隆，但利用他莫昔芬等拮抗剂开发了乳腺肿瘤的激素依赖性疗法。另一种化学治疗策略是使用微管抑制剂，例如紫杉烷类。不幸的是，这些药物引起毒性，例如白细胞减少，腹泻，脱发和周围神经病，并且还与耐药性的出现有关。先前我们已经描述了微管蛋白结合的天然化合物Noscapine，尽管在10μmol/ L或更高的浓度（取决于细胞类型）下，但在许多类型的癌症中均无毒并引发细胞凋亡。我们现在显示，Noscapine的合成类似物9-bromonoscapine在抑制细胞增殖方面比Noscapine的效力高约10倍至15倍，并在激素不敏感的人类乳腺癌（MDA-MB）中引起G2-M阻滞后诱导凋亡-231）。此外，线粒体膜电位的明显损失，细胞色素c的释放，末端caspase-3的活化以及其底物（如聚（ADP-核糖）聚合酶）的裂解表明了内在的凋亡机制。综上所述，这些数据表明了激素不敏感的乳腺癌细胞由线粒体介导的凋亡。裸鼠中的人类肿瘤异种移植物显示出明显的肿瘤体积减少和寿命的惊人增加，而没有明显的毒性迹象。因此，我们的数据提供了令人信服的证据，表明9-溴莫可可碱可用于治疗激素难治性乳腺癌。

BACKGROUND & AIMS: STUDY DESIGN:A cross-sectional study of the spine in 40 young adults after solid organ transplantation in childhood. OBJECTIVE:To evaluate the impact of organ transplantation and long-term immunosuppressive treatment on growing spine using magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA:A review of the current literature reveals no systematic evaluation of the spine after transplantation in childhood. METHODS:A total of 40 adult patients (mean age 22.1 years, range, 16.0-27.0), who received either kidney, liver, or heart transplant as children, were evaluated. Mean follow-up after transplantation was 11.2 years (range 3.0-18.0). All patients filled in a questionnaire, underwent an interview and physical examination, as well as had MRI of the spine. Standing spinal radiographs were taken from patients with a rib hump > or = 6 degrees. RESULTS:There were 8 (20%) patients who had a history of vertebral fracture. Eleven (28%) patients reported frequent back pain at rest. There were 15 (38%) patients who had scoliosis > 10 degrees (range 10 degrees -69 degrees ). On MRI, narrowed disc spaces were noted in 32 (80%) patients, and irregular endplates were noted in 24 (60%). There were 14 (35%) patients who had at least 1 compressed or wedged vertebra (> 20%). Patients treated for acute rejection had wedged vertebrae, speckled or black disc spaces, and irregular endplates more often than patients without rejections. Males had wedged vertebrae more often than females (P = 0.0067). CONCLUSIONS:Back pain, scoliosis, wedged vertebrae, and narrowed, degenerated disc spaces are common after solid organ transplantation in childhood.

背景与目标： 研究设计：儿童实体器官移植后对40位年轻人的脊柱进行的横断面研究。
目的：利用磁共振成像（MRI）评估器官移植和长期免疫抑制治疗对生长中脊柱的影响。
背景资料摘要：对当前文献的回顾表明，儿童期移植后没有对脊柱进行系统评价。
方法：总共评估了40名成年患者（平均年龄22.1岁，范围16.0-27.0），他们从小就接受了肾脏，肝脏或心脏移植手术。移植后的平均随访时间为11.2年（范围3.0-18.0）。所有患者均填写了问卷，接受了访谈和体格检查，并对脊柱进行了MRI检查。肋骨隆起>或= 6度的患者拍摄站立式脊柱X光片。
结果：有8例（20％）有椎体骨折病史。 11名（28％）患者报告休息时经常出现背痛。脊柱侧弯> 10度（范围10度-69度）的患者为15（38％）。在MRI上，发现32例（80％）患者的椎间盘间隙变窄，发现24例（60％）的不规则端板。有14名（35％）患者至少有1块受压或楔入的椎骨（> 20％）。接受急性排斥反应的患者比没有排斥反应的患者更经常出现椎体楔形，斑点或黑色椎间盘间隙以及不规则的终板。男性比女性更经常楔住椎骨（P = 0.0067）。
结论：儿童实体器官移植后，背部疼痛，脊柱侧弯，椎骨楔形和椎间盘狭窄变窄是常见的。

BACKGROUND & AIMS: PURPOSE:To demonstrate the utility of a new concept of intraoperative use of high frequency ultrasound (hfioUS) in maximizing the extent of resection (EOR) of intracerebral high-grade tumors. MATERIALS AND METHODS:22 Patients harboring an intracerebral high-grade tumor were retrospectively included in this study (14 primary tumors, 8 metastasis). 14 of them had a perilesional edema equal or greater to lesion volume, 3 had previously received radiotherapy. Following macroscopic tumor debulking, the small (11 × 31 mm) L15 - 7io (Philips, Bothell, USA) high-frequency probe (7 - 15 MHz) was introduced into the resection cavity and its walls were meticulously scanned to search for tumor remnants. Postoperative MR scan was evaluated by a board-certified independent neuroradiologist, who assessed the EOR. RESULTS:Gross total resection was achieved in 21 patients (95.5 %). One patient had a small tumor remnant (6 × 4 × 3 mm) of a very large (80 × 60 × 74 mm) anaplastic astrocytoma, detected in the postoperative MR scan. A permanent postoperative hemiparesis was diagnosed in one patient with a metastasis in the motor area, while the other patients recovered without permanent neurological deficits from the surgery. CONCLUSION:The hfioUS probe allowed in this study a precise detection of the tumor and a detailed discrimination between normal, pathological and edematous tissue in all 22 cases. :ZIEL:: Darstellung eines neuen intraoperativen Konzepts basierend auf Hochfrequenz-Ultraschall (hfioUS) zur Maximierung der Resektion hochgradiger intrazerebraler Tumoren. MATERIAL UND METHODEN:22 Patienten mit hochgradigen intrazerebralen Tumoren (14 primäre Tumoren, 8 Metastasen) wurden retrospektive in diese Studie eingeschlossen. 14 dieser Patienten zeigten ein perifokales Ödem gleich oder größer als das Läsionsvolumen, 3 Patienten erhielten präoperativ bereits Radiotherapie. Nach der makroskopischen Tumorentfernung wurde die hfioUS-Messsonde L15 – 7io (Philips, Bothell, USA) mit einer Größe von 11 × 31 mm in die Tumorhöhle eingeführt und die Wände dieser nach Tumorresten untersucht. Postoperative MRTs wurden von einem unabhängigen Neuroradiologen bezüglich Resektionsgrad ausgewertet. ERGEBNISSE:Eine makroskopische Totalresektion wurde bei 21 Patienten (95.5 %) erreicht. Ein Patient mit einem großen anaplastischen Astrozytom (80 × 60 × 74 mm) zeigte einen kleinen Resttumor (6 × 4 × 3 mm) im postoperativen MRT. Eine permanente postoperative Hemiparese zeigte sich bei einem Patient mit einer Metastase im motorischen Areal, die restlichen Patienten erholten sich postoperative ohne permanentes neurologisches Defizit von der Operation. SCHLUSSFOLGERUNG:In dieser Studie erlaubte die hfioUS-Messsonde bei allen 22 Fällen eine präzise Darstellung des Tumors und eine detaillierte Unterscheidung zwischen regelrechtem, pathologischem und ödematösem Hirnparenchym.

背景与目标： 目的：证明术中使用高频超声（hfioUS）这一新概念在最大限度地扩大脑内高级别肿瘤的切除范围（EOR）方面的实用性。
材料与方法：本研究回顾性纳入了22例脑内高度肿瘤患者（14例原发肿瘤，8例转移瘤）。其中14例病灶周围水肿等于或大于病灶体积，3例以前接受过放射治疗。在宏观肿瘤消灭之后，将小的（11×31 mm）L15-7io（Philips，Bothell，USA）高频探头（7-15 MHz）引入切除腔，并对其壁进行仔细扫描以寻找肿瘤残留物。术后MR扫描由经董事会认证的独立神经放射科医生评估，该医师评估了EOR。
结果：21例患者全切除了（95.59％）。一名患者在术后MR扫描中发现了一个很小的肿瘤残留（6××4××3×mm）很大的（80××60××74×mm）间变性星形细胞瘤。一名患有运动区转移的患者被诊断出永久性术后偏瘫，而另一名患者则因手术而没有永久性神经功能缺损而康复。
结论：在本研究中，hfioUS探针可对所有22例患者的肿瘤进行精确检测，并对正常，病理和水肿组织进行详细区分。
：ZIEL :: Darstellung eines neuenneuopern Konzepts basierend auf Hochfrequenz-Ultraschall（hfioUS）zur Maximierung der Resektion hochgradiger intrazerebraler Tumoren。
材料和方法：22顽固性复发性脑卒中患者是图斯雷布雷伦·图莫伦（14 primture Tumoren，8 Metastasen）。 14位患者的抗癌药和放射线治疗的3位患者的放射治疗。 US-Messsonde L15 – 7io（菲利普斯，美国，博塞尔）的Nach der makroskopischen Tumorentfernung战争发生在Tumorhöhleeingeführt和Wände死者中。术后的MRT会引起神经放射。
ERGEBNISSE：21位患者（Eat makroskopische Totalresektion wurde bei）（95.5％）erreicht。术后进行MRT时，患者应接受astroplasttom（80×60×74 mm）和zeigte einen kleinen Resttumor（6×4×3 mm）的手术。永久性手术后半永久患者的脑部转移，再进行永久性患者永久性神经外科手术后永久性手术。
SCHLUSSFOLGERUNG：在Dieser Studie erlaubte die HfioUS-Messsonde bei allen中，在肿瘤与细节研究方面的进展，以及在病理学和病理学上的发展。

BACKGROUND & AIMS: OBJECTIVES:Pancreatic endocrine tumors (PETs) share numerous features with gastrointestinal neuroendocrine (carcinoid) tumors. Targets of novel therapeutic strategies previously assessed in carcinoid tumors were analyzed in PETs (44 cases). METHODS:Activating mutations in EGFR, KIT, and PDGFRA and nonresponse mutations in KRAS were evaluated. Copy number of EGFR and HER-2/neu was quantified by fluorescence in situ hybridization. Expression of EGFR, PDGFRA, VEGFR1, TGFBR1, Hsp90, SSTR2A, SSTR5, IGF1R, mTOR, and MGMT was measured immunohistochemically. RESULTS:Elevated EGFR copy number was found in 38% of cases but no KRAS nonresponse mutations. VEGFR1, TGFBR1, PDGFRA, SSTR5, SSTR2A, and IGF1R exhibited the highest levels of expression in the largest percentages of PETs.Anticancer drugs BMS-754807 (selective for IGF1R/IR), 17-(allylamino)-17-demethoxygeldanamycin (17-AAG, targeting Hsp90), and axitinib (directed toward VEGFR1-3/PDGFRA-B/KIT) induced growth inhibition of human QGP-1 PET cells with IC50 values (nM) of 273, 723, and 743, respectively. At growth-inhibiting concentrations, BMS-754807 inhibited IGF1R phosphorylation; 17-AAG induced loss of EGFR, IGF1R, and VEGFR2; and axitinib increased p21(CDKN1A) expression without inhibiting VEGFR2 phosphorylation. CONCLUSIONS:Results encourage further research into multidrug strategies incorporating inhibitors targeting IGF1R or Hsp90 and into studies of axitinib combined with conventional chemotherapeutics toxic to tumor cells in persistent growth arrest.

背景与目标： 目的：胰腺内分泌肿瘤（PET）与胃肠道神经内分泌（类癌）肿瘤具有许多特征。以前在类癌肿瘤中评估过的新治疗策略的靶标已在PET（44例）中进行了分析。
方法：评估EGFR，KIT和PDGFRA的激活突变以及KRAS的无应答突变。通过荧光原位杂交定量EGFR和HER-2 / neu的拷贝数。免疫组织化学法检测EGFR，PDGFRA，VEGFR1，TGFBR1，Hsp90，SSTR2A，SSTR5，IGF1R，mTOR和MGMT的表达。
结果：38％的病例发现EGFR拷贝数升高，但没有KRAS无反应突变。 VEGFR1，TGFBR1，PDGFRA，SSTR5，SSTR2A和IGF1R在最大百分比的PET中表现出最高的表达水平。抗癌药BMS-754807（对IGF1R / IR选择性），17-（烯丙胺基）-17-去甲氧基格尔德霉素（17-靶向Hsp90的AAG和axitinib（针对VEGFR1-3 / PDGFRA-B / KIT）诱导人QGP-1 PET细胞的生长抑制，IC50值（nM）分别为273、723和743。在抑制生长的浓度下，BMS-754807抑制了IGF1R磷酸化。 17-AAG诱导的EGFR，IGF1R和VEGFR2丢失；阿昔替尼在不抑制VEGFR2磷酸化的情况下增加p21（CDKN1A）的表达。
结论：结果鼓励对结合靶向IGF1R或Hsp90的抑制剂的多药策略和阿昔替尼与常规化学治疗药物联合治疗对持续生长停滞有毒的肿瘤细胞进行进一步研究。

BACKGROUND & AIMS: :Infectious pancreatic necrosis virus (IPNV), a type species of aquabirnaviruses in the family Birnaviridae, is an etiological agent of infectious pancreatic necrosis and has been isolated from epizootics of cultured salmonids. In the present study, an epithelioma papulosum cyprini (EPC) cell line persistently infected with IPNV (PI-EPC) was experimentally established by subculturing EPC cells surviving IPNV infection, and was characterized. PI-EPC cells were morphologically indistinguishable from EPC, but continued to grow and yield IPNV. PI-EPC cells showed no cytopathic effect due to IPNV inoculation, and susceptibility of PI-EPC cells against heterologous viruses was not different from that of EPC cells. Only one cell of 10(3.5) PI-EPC cells produced IPNV at approximately 10(0.5) 50% tissue culture infectious dose (TCID50)/cell/day, which was approximately 1,000 times lower than that of normal EPC cells. PI-EPC cells that did not yield IPNV (N-PI-EPC) were screened. The IPNV genome was detected from both PI-EPC and N-PI-EPC cells, and the IPNV VP2 structural protein was detected from both cell lines, but no other IPNV proteins were observed by Western blot analysis with anti-IPNV serum. Thus, multiplication of IPNV in PI-EPC cells was regulated by some host cell factors, except interferon.

背景与目标： ：传染性胰腺坏死病毒（IPNV）是Birnaviridae家族中一种水痘病毒的类型物种，是传染性胰腺坏死的病原体，已从养殖鲑鱼的流行病中分离出来。在本研究中，通过继代培养在IPNV感染后存活的EPC细胞，通过实验建立了持续感染IPNV（PI-EPC）的塞浦路斯青皮上皮细胞（EPC）细胞系，并对其进行了表征。 PI-EPC细胞在形态上与EPC没有区别，但继续生长并产生IPNV。 PI-EPC细胞没有因IPNV接种而引起的细胞病变作用，并且PI-EPC细胞对异源病毒的敏感性与EPC细胞没有什么不同。 10（3.5）PI-EPC细胞中只有一个细胞以约10（0.5）50％组织培养物感染剂量（TCID50）/细胞/天产生IPNV，这比正常EPC细胞低约1,000倍。筛选不产生IPNV的PI-EPC细胞（N-PI-EPC）。从PI-EPC和N-PI-EPC细胞中都检测到IPNV基因组，并且从两个细胞系中都检测到了IPNV VP2结构蛋白，但用抗IPNV血清进行的蛋白质印迹分析未观察到其他IPNV蛋白。因此，除干扰素外，PI-EPC细胞中IPNV的增殖受某些宿主细胞因子的调节。

BACKGROUND & AIMS: :We carried out the first meta-analysis comparing the technical success and clinical outcomes of endoscopic ultrasound-guided drainage (EUD) and conventional transmural drainage (CTD) for pancreatic pseudocysts. We searched PubMed, Embase, Scopus, and the Cochrane library to identify relevant prospective trials. The technical success rate, short-term (4-6 weeks) success, and long-term (at 6 months) success in symptoms and the radiologic resolution of pseudocysts, complication rates, and death rates were compared. Two eligible randomized-controlled trials and two prospective studies including 229 patients were retrieved. The technical success rate was significantly higher for EUD than for CTD [risk ratio (RR)=12.38, 95% confidence interval (CI): 1.39-110.22]. When CTD failed because of the nonbulging nature of pseudocysts, a crossover was carried out to EUD (n=18), which was successfully performed in all these cases. All patients with portal hypertension and bleeding tendency were subjected to EUD to avoid severe complications. EUD was not superior to CTD in terms of short-term success (RR=1.03, 95% CI: 0.95-1.11) or long-term success (RR=0.98, 95% CI: 0.76-1.25). The overall complications were similar in both groups (RR=0.98, 95% CI: 0.52-1.86). The most common complications were bleeding and infection. There were two deaths from bleeding after CTD. The short-term and long-term treatment success of both methods is comparable only if proper drainage modality is selected in specific clinical situations. For bulging pseudocysts, either EUD or CTD can be selected whereas EUD is the treatment of choice for nonbulging pseudocysts, portal hypertension, or coagulopathy.

背景与目标： ：我们进行了首次荟萃分析，比较了胰腺假性囊肿的内镜超声引导引流术（EUD）和常规透壁引流术（CTD）的技术成功率和临床结果。我们搜索了PubMed，Embase，Scopus和Cochrane库，以确定相关的前瞻性试验。比较了技术上的成功率，短期（4-6周）成功率和长期（6个月时）症状的成功率以及假性囊肿的放射学分辨率，并发症发生率和死亡率。检索了两项合格的随机对照试验和两项前瞻性研究，其中包括229例患者。 EUD的技术成功率显着高于CTD [风险比（RR）= 12.38，95％置信区间（CI）：1.39-110.22]。当CTD由于假性囊肿的非膨隆性而失败时，便与EUD进行了交叉（n = 18），在所有这些情况下均成功进行了交叉。所有患有门静脉高压症和出血倾向的患者均应接受EUD治疗，以避免严重的并发症。就短期成功率（RR = 1.03，95％CI：0.95-1.11）或长期成功率（RR = 0.98，95％CI：0.76-1.25）而言，EUD并不优于CTD。两组的总并发症相似（RR = 0.98，95％CI：0.52-1.86）。最常见的并发症是出血和感染。 CTD后有两人因出血死亡。仅当在特定的临床情况下选择了适当的引流方式时，这两种方法的短期和长期治疗成功率才具有可比性。对于隆起的假性囊肿，可以选择EUD或CTD，而EUD是不隆起的假性囊肿，门脉高压或凝血病的治疗选择。

BACKGROUND & AIMS: PURPOSE:Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). METHODS:The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. RESULTS:Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). CONCLUSIONS:These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

背景与目标： 目的：糖尿病是怀疑为胰腺癌的危险因素，但有关它是该疾病的危险因素还是结果仍存在疑问。这项研究从NCI胰腺癌队列联合会（PanScan）收集的数据中前瞻性地检查了糖尿病与胰腺腺癌风险之间的关联。
方法：汇集的数据包括使用嵌套病例对照研究设计的来自十二个队列的1,621例胰腺腺癌病例和1,719例匹配的对照。所有分析均排除在胰腺癌诊断时间（<2年）内被诊断出患有糖尿病的受试者。所有分析均根据年龄，种族，性别，研究，饮酒，吸烟，BMI和胰腺癌家族史进行了调整。
结果：自我报告的糖尿病与胰腺癌风险增加40％相关（OR = 1.40，95％CI：1.07，1.84）。该关联因糖尿病持续时间而异；持续时间为2-8年的患者风险最高（OR = 1.79，95％CI：1.25，2.55）;糖尿病9年没有相关性（OR = 1.02，95％CI：0.68，1.52）。
结论：这些发现为糖尿病与胰腺癌风险之间的关系提供了支持。糖尿病持续时间最长的患者缺乏相关性可能反映了低胰岛素血症，需要进一步研究。

BACKGROUND & AIMS: :Objective: To determine the effect of electro-acupuncture (EA) treatment on serum levels of interferon-γ (IFN-γ) in rats with 7,12-dimethylbenz(α)anthracene (DMBA)-induced breast tumors. Methods: Twenty five female Wistar rats were divided randomly into 5 groups: normal group (N; neither DMBA-induced nor treated with EA); control group (C; DMBA-induced only); EA 3 days : (DMBA-induced + EA for 3 days); EA 5 days: (DMBA-induced + EA for 5 days); EA 10 days: (DMBA-induced + EA for 10 days) group. Animals were acclimatized from day 1 to day 7. Subcutaneus injections of DMBA 10mg/kg BW was administered every second day, from days 7 to 35. Acupuncture was performed every second day from day 42. Rats were sacrificed on the second day after the last acupuncture, breast tumors excised and stained histological sections were analysed by light microscopy. At sacrifice, blood was extracted from the heart for measurement of serum IFN-γ by ELISA. Results: All of the DMBA-induced rats developed tumors. Electro-acupuncture significantly increased IFN-γ levels in DMBA induced rats, when compared to control group. Conclusions: Our findings suggest that EA significantly increases IFN-γ levels in DMBA-induced breast tumors.

背景与目标： ：目的：确定电针治疗对血清中干扰素-γ（IFN-γ）水平的影响
在患有7,12-二甲基苯并（α）蒽（DMBA）诱导的乳腺肿瘤的大鼠中。方法：25名女性Wistar
将大鼠随机分为5组：正常组（N；既不是DMBA诱导的，也不是用EA治疗的）。控制
组（C；仅DMBA诱导）； EA 3天：（DMBA诱导的EA 3天）； EA 5天：（DMBA诱导的EA
5天）; EA 10天：（DMBA诱导的EA 10天）组。从第1天到第7天使动物适应环境。
从第二天到第7天至第35天，皮下注射DMBA 10mg / kg体重。
从第42天起每隔第二天进行一次。最后一次针刺后第二天将大鼠处死，
通过光学显微镜分析切除的肿瘤和染色的组织学切片。牺牲时，血液被抽出
从心脏通过ELISA测定血清IFN-γ。结果：所有DMBA诱导的大鼠均出现肿瘤。
与对照组相比，电针显着增加了DMBA诱导的大鼠的IFN-γ水平。
结论：我们的发现表明，EA可以显着增加DMBA诱导的乳腺肿瘤中的IFN-γ水平。

BACKGROUND & AIMS: BACKGROUND:The ideal neoadjuvant treatment protocol for patients with pancreatic cancer (PDAC) remains unclear. We evaluated the efficacy and safety of neoadjuvant hypofractionated chemoradiotherapy with S-1 for patients with resectable (R) and borderline resectable (BR) PDAC. METHODS:Eligibility criteria included patients with R and BR PDAC, performance status 0-1, and age 20-85 years. Hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) was delivered 5 days/week for 2 weeks prior to pancreatectomy. RESULTS:Fifty-seven patients were enrolled in this study, including 33 R and 24 BR [19 BR tumors with portal vein contact (BR-PV) and 5 BR tumors with arterial contact (BR-A)]. The total rates of protocol treatment completion and resection were 91% (50/57) and 96% (55/57), respectively. Seven patients failed to complete S-1 due to cholangitis (n = 5) or neutropenia (n = 2). The most common grade 3 toxicities [Common Terminology Criteria for Adverse Events (CTCAE) version 4.0] were anorexia (7%), nausea (5%), neutropenia (4%), and leukopenia (4%). No patient experienced grade 4 toxicity. Pathologically negative margins (R0) were achieved in 54 of 55 patients (98%) who underwent pancreatectomy. Pathological response was classified as Evans grade I in 8 patients (15%), IIa in 31 patients (56%), IIb in 14 patients (25%), III in 1 patient (2%), and IV in 1 patient (2%), and operative morbidity (Clavien-Dindo grade IIIb or less) was observed in 4 patients (8%). The 1- and 2-year overall survival (OS) rates were 91 and 83% in R patients, respectively, and 77 and 58% in BR patients, respectively (p = 0.03). CONCLUSION:Neoadjuvant S-1 with concurrent hypofractionated radiotherapy is tolerable and appears promising for patients with R and BR PDAC.

背景与目标： 背景：胰腺癌（PDAC）患者理想的新辅助治疗方案尚不清楚。我们评估了可切除（R）和边缘可切除（BR）PDAC患者使用S-1的新辅助超分割放化疗的疗效和安全性。
方法：入选标准包括R和BR PDAC，表现状态0-1和20-85岁的患者。在胰腺切除术之前的2周中，每周5天，每次S-5（60 mg / m2）进行次分割放射束放射疗法（10份30 Gy）。
结果：57例患者入选本研究，包括33例R和24例BR [19例门静脉接触的BR肿瘤（BR-PV）和5例动脉接触的BR肿瘤（BR-A）]。方案治疗完成和切除的总比率分别为91％（50/57）和96％（55/57）。由于胆管炎（n = 5）或中性粒细胞减少症（n = 2），七名患者未能完成S-1。最常见的3级毒性[不良事件通用术语标准（CTCAE）4.0版]为厌食症（7％），恶心（5％），中性粒细胞减少症（4％）和白细胞减少症（4％）。没有患者经历过4级毒性。 55例接受胰腺切除术的患者中有54例（98％）达到了病理学阴性切缘（R0）。病理反应分为Evans I级：8例（15％），IIa≥31例（56％），IIb≥14例（25％），IIIb≥1例（2％），IV≥1例（2 ％），并且在4例患者（8％）中观察到了手术发病率（Clavien-Dindo IIIb级或更低）。 R患者的1年和2年总生存率（OS）分别为91％和83％，BR患者分别为77％和58％（p = 0.03）。
结论：新辅助S-1联合并发次分割放疗是可以耐受的，对于R和BR PDAC的患者似乎很有希望。