BACKGROUND & AIMS: :Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

背景与目标： 基质金属蛋白酶（MMPs）的表达与妇科肿瘤的侵袭性有关。这项研究的目的是确定子宫内膜恶性肿瘤中MMP-2，MMP-7和MMP-9以及金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2的表达及其与临床和组织学参数的关系。用特异性单克隆抗体对1999年至2004年间接受治疗的50例子宫内膜癌患者的福尔马林固定，石蜡包埋的肿瘤样品进行染色。根据FIGO分类将肿瘤分组。将染色结果与组织学和临床数据进行比较。 MMP和TIMP表达的半定量分析显示，根据组织学亚型，TIMP-2表达存在显着差异（P = 0.03），并且MMP-9表达也呈现差异的趋势（P = 0.05）。随着组织学分级的升高，MMP-2表达增加而TIMP-2表达下降（分别为P = 0.0007，P <0.0001）。 MMP-2表达与淋巴结转移相关（P = 0.04），而TIMP-2表达与肌层浸润深度（P = 0.01），血管淋巴管受累（P = 0.02）和淋巴结转移（P = 0.0003）相关）。这些结果支持MMP和TIMP参与子宫内膜肿瘤的生长和进展。 MMP-2的高表达和TIMP-2的低表达是子宫内膜肿瘤最有效的标志物，具有局部和远处扩散的高风险。

BACKGROUND & AIMS: :The phenotypic response of rat liver to a carcinogenic protocol involving initiation/selection and promotion with and without phenobarbital (PB) feeding was studied in pubertal and adult male rats. Considering the early presence of preneoplastic nodular areas, it appeared that pubertal rats, initiated at 6-7 weeks, presented a higher susceptibility to the protocol than adult rats initiated at 9-10 weeks. Altered liver phenotype was characterized by: (1) gamma-glutamyl-transpeptidase (GGT) and glutathione S-transferase (GST) activities; (2) the expression of two forms of cytochrome P-450; de novo PB-inducible P-450 II B 1,2 and P-450 II C 7 normally expressed in 45-day-old rats and PB-inducible, and (3) the expression of albumin and alpha-fetoprotein cDNAs. In the absence of PB, the susceptibility of pubertal rat liver to hepatocarcinogenesis was related to a special metabolic phenotype enriched in GGT and GST activities by comparison with the quasi-normal expression of both P-450s. Adult rat liver presented a less altered pattern closer to that of noninitiated rat liver. During PB promotion, the loss of PB inducibility of P-450 II C 7 in pubertal rat liver suggested that the hormonal status of the animals could interact with initiation to modulate specific gene expression. The late phase of PB promotion revealed the loss of highly differentiated functions (P-450s, albumin), whereas enzymatic markers associated with preneoplastic foci showed a persistent high expression.

背景与目标： ：在青春期和成年雄性大鼠中研究了大鼠肝脏对涉及开始/选择和促进（有或没有苯巴比妥（PB）喂养）致癌方案的表型反应。考虑到肿瘤前结节区域的早期存在，看来与在9-10周龄开始的成年大鼠相比，在6-7周龄开始的青春期大鼠对方案的敏感性更高。肝表型改变的特征是：（1）γ-谷氨酰转肽酶（GGT）和谷胱甘肽S-转移酶（GST）活性； （2）两种形式的细胞色素P-450的表达；从头开始PB诱导的P-450 II B 1,2和P-450 II C 7在45天大的大鼠中正常表达，并且在PB诱导中正常表达，以及（3）白蛋白和甲胎蛋白cDNA的表达。在没有PB的情况下，与两个P-450的准正常表达相比，青春期大鼠肝脏对肝癌发生的敏感性与富含GGT和GST活性的特殊代谢表型有关。成年大鼠肝脏的变化较小，与未启动大鼠肝脏的变化更接近。在PB促进过程中，青春期大鼠肝脏中P-450 II C 7的PB诱导性丧失，这表明动物的荷尔蒙状态可能与启动相互作用，从而调节特定的基因表达。 PB促进的晚期阶段揭示了高度分化的功能（P-450s，白蛋白）的丧失，而与肿瘤前病灶相关的酶标记物显示了持续的高表达。

BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.

背景与目标： ：Etanercept是一种重组人类可溶性肿瘤坏死因子（TNF-alpha）受体融合蛋白，可抑制TNF-alpha（一种在移植物抗宿主病（GVHD）发病机理中的主要介体）。我们的研究目的是评估依那西普治疗21例激素抵抗性急性GVHD（aGVHD）（n = 13）和慢性GVHD（cGVHD）（n = 8）患者的安全性和有效性。每周两次皮下给予Etanercept 25 mg，持续4周，然后每周25 mg，持续4周。依那西普开始治疗时，有14例皮肤，13例胃肠，5例肝，5例肺，4例经口受累。 12名患者（57％）完成了12剂治疗。总体上，21例患者中有11例（52％）对依那西普治疗有反应，其中6例（46％）患有aGVHD [n = 4完全缓解（CR），n = 2部分缓解（PR）]和5例（62 ％）和cGVHD（n = 1 CR，n = 4 PR）。临床反应最常见于顽固性肠aGVHD患者，其中55％的患者为CR，9％的患者为PR。 CMV重新激活发生在48％的患者中，细菌感染发生在14％的患者中，而真菌感染发生在19％的患者中。自依那西普开始接受中位随访429天（71-1007天）后，有14名患者（67％）还活着。 7例患者死亡，3例感染，2例难治性aGVHD死亡，2例疾病进展。总之，我们的初步数据表明，依那西普耐受性好，在类固醇难治性aGVHD和cGVHD患者中可引起较高的应答率，特别是在胃肠道受累的情况下。

BACKGROUND & AIMS: :Differential killing of the patient's cancer cells versus normal cells is a necessity for chemotherapy. Advantage can be taken of close regulations of gene expression and of enzyme activity that are essential for normal cell functioning, and that are altered during tumor progression. Summarized here is our research on four such progression changes of cancer cells; some deregulate proliferation control and others decrease programmed death (apoptosis). These processes will be illustrated with examples of potential chemotherapies based on them. Methods for discovery of such changes include Differential Display and microarrays.

背景与目标： ：与正常细胞相比，不同程度地杀死患者的癌细胞是化疗的必要条件。可以利用基因表达和酶活性的紧密调节，这些调节对于正常的细胞功能是必不可少的，并且在肿瘤进展过程中会改变。这里总结了我们对癌细胞的四个这样的进展变化的研究。一些人放松了对增殖的控制，而另一些人减少了程序性死亡（细胞凋亡）。这些过程将以基于它们的潜在化学疗法为例进行说明。发现这种变化的方法包括差异显示和微阵列。

BACKGROUND & AIMS: CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in vitro and cause regression of tumor in vivo. The role of various host immune cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by adoptive transfer of anti-tumor T cell clones to recipients that were selectively depleted of individual immune cell types. By these means, macrophages and NK cells were found to be required for tumor killing. Depletion of host CD4+ T cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by anti-tumor T cells. An essential role for antigen receptor-negative NK cells is likely dependent upon secretion of IFN-gamma from NK cells since treatment of tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and tumor challenge abrogated T cell killing, resulting in progressive tumor growth. Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell surface MHC class II expression was induced in tumor cells by exposure to IFN-gamma. In addition, tumor cells were isolated from tumor-bearing animals by absorption using anti-MHC class II antibody, demonstrating that 13762 tumor expresses cell surface MHC class II antigens in situ. However, if hosts were depleted of NK cells before tumor challenge, MHC class II+ tumor was not recovered. Collectively these results suggest that adenocarcinoma 13762 is eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

背景与目标： 与大鼠腺癌13762反应的CD4抗肿瘤T细胞在体外杀死肿瘤并在体内引起肿瘤消退。通过将抗肿瘤T细胞克隆过继转移到选择性清除了个体免疫细胞类型的受体上，研究了各种宿主免疫细胞在体内CD4 T细胞介导的肿瘤消除中的作用。通过这些手段，发现杀死肿瘤需要巨噬细胞和NK细胞。宿主CD4 T细胞，CD8 T细胞或嗜中性白细胞的耗竭对抗肿瘤T细胞对肿瘤的消除没有影响。抗原受体阴性NK细胞的重要作用可能取决于NK细胞分泌IFN-γ，因为在过继转移和肿瘤攻击之前用抗IFN-γ抗体治疗肿瘤受体可以消除T细胞杀伤，从而导致进行性肿瘤生长。体外用IFN-γ或抗IFN-γ抗体治疗不会影响腺癌13762或抗肿瘤T细胞的存活率，但通过暴露于IFN-γ诱导了肿瘤细胞的细胞表面MHC II类表达。另外，通过使用抗MHC II类抗体的吸收从荷瘤动物中分离出肿瘤细胞，表明13762肿瘤原位表达细胞表面MHC II类抗原。但是，如果宿主在肿瘤攻击前已耗尽NK细胞，则无法恢复MHC II类肿瘤。这些结果共同表明，通过直接杀死肿瘤，MHC II类限制性CD4 T细胞可消除13762腺癌。

BACKGROUND & AIMS: PURPOSE:A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN:Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. RESULTS:Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (

BACKGROUND & AIMS: :Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.

背景与目标： ：野生型（WT）序列p53肽是广泛应用的癌症疫苗的诱人候选物。这项研究的目的是评估肝细胞癌（HCC）患者基于WT p53的免疫治疗方法的潜力。通过在24 HCC中使用肽/HLA-A2.1四聚体直接在外周血中鉴定出对WT p53（149-157）和WT p53（264-272）HLA-A * 0201限制性表位具有特异性的循环CD8 T细胞耐心。 WT p53肽特异性刺激后的细胞毒性T淋巴细胞（CTL）活性通过使用实时定量聚合酶链反应测定的颗粒酶B和干扰素-γmRNA转录分析来评估。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中p53的状态，主要组织相容性复合体（MHC）的表达和共刺激分子。与健康对照相比，HCC患者表现出明显更高的WT p53特异性记忆CD8 T细胞频率和更强的WT p53特异性CTL活性。 p53特异性CD8 T细胞的频率增加及其活性与选择性HLA-A2等位基因缺失和肿瘤细胞共刺激分子表达降低有关。此外，p53特异性T细胞数量的增加与肿瘤细胞中II类MHC的高表达相吻合，但与肿瘤淋巴结转移分期系统的T状态呈负相关。我们的结果表明，在肝癌患者中存在自然免疫监视和肿瘤免疫逃避，涉及针对WT p53肿瘤抗原的T细胞应答。这些发现可能对癌症疫苗的未来发展具有重要意义。

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。我们的发现表明，低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细胞中的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，从而导致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。

BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.

背景与目标： ：肿瘤浸润基质细胞（TISC）以及肿瘤本身都被认为与肿瘤相关的免疫抑制有关，这是肿瘤逃避免疫监视的关键机制之一。然而，由于在已建立的肿瘤中TISC的比例很小，因此TISC的制备是困难的。因此，通常被认为与肿瘤相关的免疫抑制有关的细胞是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中，我们开发了一种从已建立的肿瘤中直接制备TISC的方法，以分析其功能。使用绿色荧光蛋白（GFP）转基因（Tg）小鼠和移植有GFPTg小鼠骨髓（BM）细胞的C57BL / 6小鼠，我们检测到TISC的三个亚群：一个与源自BM的未成熟髓样细胞（ImC）相容。其他两个亚群CD11b（）细胞和CD11b（-）细胞并非源自BM。在存在GM-CSF的情况下与肿瘤培养后，TISC包括这些亚群，但并非每个亚群独立地抑制由抗CD3诱导的T细胞增殖。在我们的系统中，肿瘤并未直接抑制T细胞反应，但来自肿瘤的未知因素影响了TISC的免疫抑制。

BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标： 背景：我们检查了膀胱癌中P53基因的杂合性（LOH）缺失，并研究了P53基因在乳头状瘤恶性进展中的作用。另外，检查了复发性膀胱癌的克隆性。
方法：分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定，石蜡包埋的组织中提取DNA，在P53基因的3个多态性位点处通过聚合酶链反应（PCR）进行扩增，并通过非放射性同位素单链构象多态性（Non-RI SSCP）分析。
结果：在40个信息量样本中，在13个样本中检测到LOH，其中3个7级中有4个（57％），2个23级中有9个（39％），1个10级中没有10个（10％）。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明，3例（60％）在原发性肿瘤中显示LOH，2例在复发性肿瘤中显示LOH。 ，与LOH在19例（16％）的3例中未显示出恶性进展的情况相反。 4例异时复发表现为LOH。在复发性肿瘤中2个，仅在初始肿瘤中1个，在两个肿​​瘤中1个。
结论：P53基因的改变被认为与肿瘤的分级有关，并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。

BACKGROUND & AIMS: BACKGROUND:Brain tumors (BT) are second only to acute lymphoblastic leukemia as the most prevalent form of pediatric cancer, with BT 5-year survival rates approaching 70%. With increased survival, quality of life has emerged as an essential health outcome. This investigation examines the internal consistency reliability and construct validity of the Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module. METHODS:The PedsQL 4.0 Generic Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Brain Tumor Module were administered to 99 families. The average age of the 56 boys and 43 girls was 9.76 years (range=2-18 years). The sample included children with tumors located in the posterior fossa/brainstem (N=62, 62.6%), supratentorial (N=15, 15.2%), and midline (N=22, 22.2%). Children were on treatment (N=46, 46.5%), off treatment<12 months (N=19, 19.2%), or off treatment>12 months/long-term survivor (N=34, 34.3%). Treatment included radiation (N=61, 61.6%), surgery (N=83, 83.8%), chemotherapy (N=87, 87.9%), and bone marrow transplant (N=5, 5.1%). RESULTS:Internal consistency reliability was demonstrated for the 24-item PedsQL Brain Tumor Module (average alpha=0.78-0.92, parent proxy-report, n=99; average alpha=0.76-0.87, child self-report, n=51). Construct validity for the PedsQL Brain Tumor Module was supported through an analysis of the intercorrelations with the Generic Core Scales and Fatigue Scale. CONCLUSIONS:The findings provide support for the measurement properties of the PedsQL Brain Tumor Module.

背景与目标： 背景：脑肿瘤（BT）仅次于急性淋巴细胞白血病，是儿童癌症的最普遍形式，其BT 5年生存率接近70％。随着生存率的提高，生活质量已成为一种必不可少的健康结果。这项研究检查了儿童生命质量量表（PedsQL）脑肿瘤模块的内部一致性可靠性和构建效度。
方法：将PedsQL 4.0通用核心量表，PedsQL多维疲劳量表和PedsQL脑肿瘤模块应用于99个家庭。 56名男孩和43名女孩的平均年龄为9.76岁（范围= 2-18岁）。样本包括肿瘤位于后颅窝/脑干（N = 62，62.6％），幕上（N = 15，15.2％）和中线（N = 22，22.2％）的儿童。儿童正在接受治疗（N = 46，46.5％），未接受治疗<12个月（N = 19，19.2％）或接受过治疗> 12个月/长期幸存者（N = 34，34.3％）。治疗包括放疗（N = 61，61.6％），手术（N = 83，83.8％），化学疗法（N = 87，87.9％）和骨髓移植（N = 5，5.1％）。
结果：24项PedsQL脑肿瘤模块具有内部一致性可靠性（平均α= 0.78-0.92，父母代理报告，n = 99；平均α= 0.76-0.87，孩子自我报告，n = 51）。通过分析通用核心量表和疲劳量表之间的相互关系，支持了PedsQL脑肿瘤模块的构建效度。
结论：这些发现为PedsQL脑肿瘤模块的测量特性提供了支持。

BACKGROUND & AIMS: :In addition to their role in cellular homeostasis, pathways that regulate autophagy affect both tumorigenesis and tumor response to treatment. Therefore, understanding the regulation of autophagy in treated cancer cells is relevant to the discovery of molecular targets for the development of anti-cancer drugs. Our recent report points to radiation-induced inactivation of the mTOR pathway as an underlying mechanism of radiation-induced autophagy in the human breast cancer cell line MCF-7. Most importantly, radiation-induced inactivation of this pathway was detrimental to cell survival and was associated with reversal of mitochondrial ATPase activity and mitochondrial hyperpolarization, decreased level of eukaryotic initiation factor 4G (eIF4G) and increased phosphorylation of p53. Future analysis of the interrelationship among these events and the role each of them plays in cell survival following radiation will increase our ability to employ the mTOR pathway in anti-cancer therapy.

背景与目标： ：除了在细胞稳态中的作用外，调节自噬的途径还影响肿瘤发生和肿瘤对治疗的反应。因此，了解在治疗的癌细胞中自噬的调控与发现抗癌药物的分子靶标有关。我们最近的报告指出，辐射诱导的mTOR途径失活是人类乳腺癌细胞系MCF-7辐射诱导的自噬的潜在机制。最重要的是，此途径的辐射诱导失活对细胞存活有害，并且与线粒体ATPase活性和线粒体超极化的逆转，真核起始因子4G（eIF4G）的水平降低以及p53磷酸化的增加有关。进一步分析这些事件之间的相互关系以及它们各自在放射后的细胞存活中所起的作用，将提高我们在抗癌治疗中采用mTOR途径的能力。

BACKGROUND & AIMS: BACKGROUND:Transanal resection of benign and selected malignant rectal tumors is a well accepted surgical technique. The use of a stereoscopic microsurgical technique, as originally described by Buess et al in 1984, has been shown to improve the results of standard transanal resection by allowing precise, full thickness resections up to 24 cm from the anal verge. Transanal endoscopic microsurgery (TEM) has failed to gain widespread popularity for two reasons: The proprietary instrument set is expensive and complex ($68,000 and 30 components), and the procedure is difficult to master technically. We present our results with a modification of the TEM instrument that incorporates a standard laparoscope and video camera as well as standard laparoscopic instruments.

METHODS:Four surgeons have been trained to date. Details of the training curriculum are presented. The technique of videoendoscopic transanal tumor resection (VTEM) is described. A prospective data base was maintained of all VTEM cases. This was reviewed for this study to determine indications, operative times, complications and outcomes.

RESULTS:Four surgeons performed 27 VTEM cases between August 1994 and June 1996. The average age was 69 years and the majority (16) of patients were ASA III. Pre-op diagnosis was benign polyp in 25 patients and adenocarcinoma in 2. Average operating time was 127 minutes (49 to 280 minutes), and was longer during a surgeon's first 5 cases and for lesions more than 16 cm from the anal verge. Operative problems were rare (4%) and post-op complications (incontinence 2, late bleeding 1, adenoma recurrence 1) were seen in 15%.

CONCLUSIONS:VTEM can be taught successfully to GI and colorectal surgeons using a format similar to that used for advanced laparoscopic courses. The use of already available laparoscopes and instruments decreases the initial costs of the set-up. Results are good, with low rates of complications and recurrence and a very short hospital stay. The patient benefits from an effective, minimally invasive alternative to open surgery.

背景与目标： 背景：经肛门切除良性和恶性直肠肿瘤是一种广为接受的手术技术。如Buess等人在1984年最初描述的，使用立体显微外科技术已显示可通过允许距肛门边缘长达24 cm的精确，全层切除来改善标准经肛门切除的结果。经肛门内窥镜显微外科手术（TEM）未能获得广泛的普及，其原因有两个：专有的器械套件昂贵且复杂（68,000美元，包含30个组件），并且该过程在技术上难以掌握。我们通过修改TEM仪器（结合标准腹腔镜和摄像机以及标准腹腔镜仪器）展示我们的结果。

方法：到目前为止，已经培训了四名外科医生。介绍了培训课程的详细信息。描述了视频内镜经肛门肿瘤切除术（VTEM）的技术。保留了所有VTEM病例的前瞻性数据库。

结果：1994年8月至1996年6月，四名外科医生进行了27例VTEM病例。平均年龄为69岁。年，大多数（16）患者为ASA III。术前诊断为良性息肉25例，腺癌2例。平均手术时间为127分钟（49至280分钟），在外科医生的前5例中以及距肛门边缘16厘米以上的病变中，手术时间更长。手术中很少有手术问题（4％），术后并发症（尿失禁2，晚期出血1，腺瘤复发1）占15％。

结论：可以教VTEM使用类似于高级腹腔镜课程的格式成功地向胃肠道和结直肠外科医生使用。使用已经可用的腹腔镜和仪器可降低安装的初始成本。结果良好，并发症和复发率低，住院时间很短。患者可以从有效，微创的替代开放手术中受益。