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Pilot Study to Determine the Prevalence of CYP2B6*6(C.516G>T), CYP2C19*2 (C.681G>A) and CYP2C19*3 (C.636G>A) in Breast Cancer Patients versus Normal Healthy Controls among Three Major Ethnic Groups in Singapore 测定新加坡三个主要民族乳腺癌患者与正常健康对照中CYP2B6*6(C.516G>T)、CYP2C19*2 (C.681G>A)和CYP2C19*3 (C.636G>A)患病率的初步研究
Pub Date : 2022-01-01 DOI: 10.16966/2381-3318.154
S. Gh, Koo Sh, Tanrykuliev Pt, Lee Ls, Tham Ck, H. M, Tan Sm
Background: Breast cancer is the top cancer suffered by women worldwide and is the leading cause of cancer mortality for women living in Singapore. Unfortunately, most of breast cancer cases are detected at a later stage of disease development and cripple the outcome of the therapy. This is a study to identify potential breast cancer susceptibility gene polymorphisms.
背景:乳腺癌是世界范围内女性患的头号癌症,也是新加坡女性癌症死亡率的主要原因。不幸的是,大多数乳腺癌病例在疾病发展的后期才被发现,从而削弱了治疗的效果。这是一项确定潜在乳腺癌易感基因多态性的研究。
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引用次数: 0
Factors Affecting Colorectal Cancer Screening Among African-Born Immigrants in the United States: A Cross-Sectional Study 影响美国非洲裔移民结直肠癌筛查的因素:一项横断面研究
Pub Date : 2022-01-01 DOI: 10.16966/2381-3318.152
Chibundu C, Beatty F, Akwafuo S
Objectives: Early detection of colorectal cancer through periodic screening has proved to be effective in reducing the incidence rate and mortality from colorectal cancer. Available records indicate racial and ethnic disparities in colorectal cancer screening in the United States. In this paper, a retrospective cross-sectional study to examine how family income, health insurance status, language of interview, length of stay in the US, perceived health status, level of education, and having a usual place for medical care affect colorectal cancer screening among African-born immigrants in the United States is presented.
目的:通过定期筛查,及早发现结直肠癌,可有效降低结直肠癌的发病率和死亡率。现有记录表明,在美国,结直肠癌筛查存在种族和民族差异。在本文中,一个回顾性的横断面研究,以检查如何家庭收入,健康保险状况,采访语言,在美国逗留的时间长短,感知健康状况,教育水平,并有一个通常的医疗场所影响结肠直肠癌筛查在美国的非洲出生的移民提出。
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引用次数: 1
Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases 没有进展的前期转移性乳腺癌再活检检测激素受体/HER2状态是否有任何理由?2箱
Pub Date : 2021-01-01 DOI: 10.16966/2381-3318.148
Duman Bb, Cil T
Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.
生物标志物的改变在乳腺癌局部复发或转移中被充分证明是由于肿瘤的异质性和生物学的变化。有一些关于原发和转移部位之间不一致的数据。同时,激素、受体的状态在新辅助治疗后和复发时也会发生变化。靶向联合化疗后无进展或复发的转移性乳腺癌,在人表皮生长因子受体2 (HER2)过表达阳性激素受体阳性或三阴性患者化疗后进行计划维持治疗。在指南中,如果活检的时间通常是在肿瘤进展之后,则重新活检的时间没有确切的时间。我们提出的病例中,我们检测到不同的激素受体状态,从一开始没有进展,并决定维持治疗之前。这一课题对于乳腺癌等异质性肿瘤的治疗具有重要意义。重审时间的重要决定是辩论。在这方面,这两个病例都是重要的例子,对于这类患者来说,肿瘤异质性是乳腺癌中最广为人知的实体之一。我们发现两例患者,其中一例在诊断时为雌激素孕激素受体HER2 3阴性(+++),另一例在诊断时为三阴性,在再活检中激素受体阳性,无进展。我们的目的是讨论肿瘤的异质性和重新活检的时间在乳腺癌的两个病例的光。
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引用次数: 0
Could a Growth Inhibitory Factor, Present Only during Pregnancy, be Made Available to Treat Cancer in Adults? A Commentary 一种仅在怀孕期间存在的生长抑制因子能否用于治疗成人癌症?一篇评论
Pub Date : 2021-01-01 DOI: 10.16966/2381-3318.149
Mizejewski Gj
Human alpha-fetoprotein (AFP) is well-known as the “gold standard” biomarker for liver and germ cell tumors. It has also been utilized as a pregnancy screening analyte for neural tube defects as well as Down syndrome, when combined with other gestational-age dependent biomarkers. However, a lesser known and recognized property of AFP is its role in the maintenance and monitoring of fetal growth during ontogenetic development in man. Although a major function of AFP during pregnancy involves the serum transport of estrogens, fatty acids, retinoid, and other compounds, the positive and negative regulation of fetal growth is a vital additional function of AFP. Human AFP largely functions as a growth promoting agent; however, the fetal protein is able to temporarily convert to a growth inhibitory factor in stress and shock environments in the fetal milieu. The development of a transient form of AFP or its derived peptides could be harnessed for use as an adjunct therapeutic agent to treat cancer in adults.
人甲胎蛋白(AFP)被认为是肝脏和生殖细胞肿瘤的“金标准”生物标志物。当与其他胎龄相关的生物标志物结合使用时,它也被用作神经管缺陷和唐氏综合症的妊娠筛查分析物。然而,AFP的一个鲜为人知和公认的特性是它在人类个体发育过程中维持和监测胎儿生长的作用。虽然甲胎蛋白在妊娠期间的主要功能包括雌激素、脂肪酸、类维生素a和其他化合物的血清转运,但对胎儿生长的积极和消极调节是甲胎蛋白的重要附加功能。人AFP主要起促生长作用;然而,胎儿蛋白能够在胎儿环境中的应激和休克环境中暂时转化为生长抑制因子。一种瞬时形式的甲胎蛋白或其衍生肽的发展可以作为辅助治疗剂用于治疗成人癌症。
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引用次数: 0
Disintegrin-Like Peptides Derived from Naturally-Occurring Proteins: A Proposed Adjunct Treatment for Cancer Therapy: A Commentary 来自天然蛋白质的崩解素样肽:一种建议的辅助治疗癌症:评论
Pub Date : 2021-01-01 DOI: 10.16966/2381-3318.147
Mizejewski Gj
Disintegrins constitute a group of small proteins or peptides (45-85 amino acids) that function as natural antagonists of integrin receptor-dependent cell activities. The integrins themselves comprise a superfamily of hetero-dimeric (alpha and beta chains) transmembrane cell surface receptors whose functions include cell adhesion, growth, migration, and angiogenesis. In contrast, the disintegrins comprise groups of two types of molecules, namely, a) short proteins or peptides comprising insect and animal venoms; and b) intrinsic sub domain sequence fragments or short motifs present on large mammalian metalloprotease enzymes. Certain disintegrins bind specifically to tri-amino acid sequences (RGD, LGD etc) located on integrins beta-1 and beta-3 chains of the hetero complex receptors. Binding at such sites can inhibit or block cell migration, angiogenesis, metastasis, and platelet aggregation. Recently, small disintegrin-like peptides from naturally-occurring proteins have likewise been reported to inhibit growth and adhesion functions associated with integrin-dependent cell activities. The present report describes examples of such disintegrin-like peptides and provides support for their proposed use in adjunct cancer therapy.
崩解素由一组小蛋白质或肽(45-85个氨基酸)组成,作为整合素受体依赖性细胞活性的天然拮抗剂。整合素本身包含一个异二聚体(α链和β链)跨膜细胞表面受体超家族,其功能包括细胞粘附、生长、迁移和血管生成。相反,分解素由两种类型的分子组成,即a)含有昆虫和动物毒液的短蛋白或肽;b)存在于大型哺乳动物金属蛋白酶上的内在亚结构域序列片段或短基序。某些崩解素特异性结合位于杂合体受体的整合素β -1和β -3链上的三氨基酸序列(RGD, LGD等)。这些位点的结合可以抑制或阻断细胞迁移、血管生成、转移和血小板聚集。最近,来自天然蛋白质的小的崩解素样肽同样被报道抑制与整合素依赖性细胞活性相关的生长和粘附功能。本报告描述了这种崩解素样肽的例子,并为其在辅助癌症治疗中的应用提供了支持。
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引用次数: 2
Assessment of Knowledge, Attitude and Practice of Breast Self-Examination among Reproductive Age Females in Altekaina Village, Sudan July 2018 2018年7月苏丹Altekaina村育龄妇女乳房自检知识、态度和行为评估
Pub Date : 2020-01-01 DOI: 10.4172/1948-5956-C12-156
A. Wb, A. Nm, Bashir Ba
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引用次数: 0
Androgen Receptor as a Potential Target for Treatment of Breast Cancer. 雄激素受体作为治疗乳腺癌的潜在靶点。
Pub Date : 2017-04-01 Epub Date: 2016-10-06 DOI: 10.16966/2381-3318.129
Y Wu, J V Vadgama

Clinical studies have shown that the androgen receptor (AR) is ubiquitously expressed in breast cancers and this could provide prognostic implication in the diagnosis and treatment of breast cancers. Data from Nurse's Health Study on women with invasive breast cancer suggest that a significant number of tumors were AR-positive as defined by immunohistochemistry. In addition, the distribution of AR among different breast cancer subtypes varies significantly, and the biological reasons for this variation are not well understood. Despite strong histochemical evidence, the AR status is not applied for assessing pathological findings and disease outcome in clinical practice. AR antagonists are not currently used as therapy in breast cancer. This is in part due to conflicting results from early clinical trials with first generation of AR antagonists together with the complexity in breast cancer heterogeneity. In addition, role of AR in breast cancer is not fully understood. Here we will review the role of AR in different subtypes of breast cancers and elucidate its mechanisms. We will also discuss some recent interesting findings on the second generation of AR antagonists for treatment of breast cancer.

临床研究表明雄激素受体(AR)在乳腺癌中普遍表达,这可能为乳腺癌的诊断和治疗提供预后意义。来自护士健康研究的浸润性乳腺癌患者的数据表明,免疫组织化学定义的ar阳性肿瘤数量显著增加。此外,AR在不同乳腺癌亚型中的分布差异很大,造成这种差异的生物学原因尚不清楚。尽管有强有力的组织化学证据,但在临床实践中,AR状态并未用于评估病理表现和疾病结局。AR拮抗剂目前尚未用于乳腺癌的治疗。部分原因是由于第一代AR拮抗剂的早期临床试验结果相互矛盾,以及乳腺癌异质性的复杂性。此外,AR在乳腺癌中的作用尚不完全清楚。在这里,我们将回顾AR在不同亚型乳腺癌中的作用并阐明其机制。我们还将讨论最近关于第二代AR拮抗剂治疗乳腺癌的一些有趣发现。
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引用次数: 7
Hematopoietic Stem Cell-derived Adipocytes Promote Tumor Growth and Cancer Cell Migration. 造血干细胞来源的脂肪细胞促进肿瘤生长和癌细胞迁移。
Pub Date : 2017-01-01 Epub Date: 2017-03-08 DOI: 10.16966/2381-3318.130
Y Xiong, D L Russell, L T McDonald, L A Cowart, A C LaRue

Adipocytes, apart from their critical role as the energy storage depots, contribute to the composition of the tumor microenvironment. Our previous studies based on a single hematopoietic stem cell (HSC) transplantation model, have revealed a novel source of adipocytes from HSCs via monocyte/macrophage progenitors. Herein, we extend these studies to examine the role of HSC-derived adipocytes (HSC-Ad) in tumor progression. When cultured under adipogenic conditions, bone marrow-derived monocytic progenitors differentiated into adipocytes that accumulated oil droplets containing triglyceride. The adipokine array and ELISAs confirmed secretion of multiple adipokines by HSC-Ad. These adipocytes underwent further development in vivo when injected subcutaneously into C57Bl/6 mice. When co-injected with melanoma B16F1 cells or breast cancer E0771 cells into syngeneic C57Bl/6 mice, HSC-Ad not only accelerated both melanoma and breast tumor growth, but also enhanced vascularization in both tumors. Conditioned media from HSC-Ad supported B16F1 and E0771 cell proliferation and enhanced cell migration in vitro. Among the HSC-Ad secreted adipokines, insulin-like growth factor 1 (IGF-1) played an important role in E0771 cell proliferation. Hepatocyte growth factor (HGF) was indispensable for B16F1 cell migration, whereas HGF and platelet-derived growth factor BB (PDGF-BB) collectively contributed to E0771 cell migration. Expression levels of receptors for IGF-1, HGF, and PDGF-BB correlated with their differential roles in B16F1 and E0771 cell proliferation and migration. Our data suggest that HSC-Ad differentially regulate tumor behavior through distinct mechanisms.

脂肪细胞除了作为能量储存库的关键作用外,还有助于肿瘤微环境的组成。我们之前的研究基于单一造血干细胞(HSC)移植模型,揭示了通过单核细胞/巨噬细胞祖细胞从HSC中获得脂肪细胞的新来源。在此,我们扩展了这些研究,以检查hsc来源的脂肪细胞(HSC-Ad)在肿瘤进展中的作用。当在成脂条件下培养时,骨髓来源的单核祖细胞分化为脂肪细胞,脂肪细胞积累含有甘油三酯的油滴。脂肪因子阵列和elisa证实HSC-Ad分泌多种脂肪因子。当皮下注射到C57Bl/6小鼠体内时,这些脂肪细胞在体内进一步发育。当将HSC-Ad与黑色素瘤B16F1细胞或乳腺癌E0771细胞共注射到同基因C57Bl/6小鼠体内时,HSC-Ad不仅加速了黑色素瘤和乳腺肿瘤的生长,而且增强了两种肿瘤的血管化。HSC-Ad条件培养基支持B16F1和E0771细胞体外增殖和增强细胞迁移。在HSC-Ad分泌的脂肪因子中,胰岛素样生长因子1 (IGF-1)在E0771细胞增殖中起重要作用。肝细胞生长因子(HGF)对于B16F1细胞迁移是必不可少的,而HGF和血小板衍生生长因子BB (PDGF-BB)共同促进E0771细胞迁移。IGF-1、HGF和PDGF-BB受体的表达水平与其在B16F1和E0771细胞增殖和迁移中的不同作用相关。我们的数据表明,HSC-Ad通过不同的机制对肿瘤行为进行差异调节。
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引用次数: 19
Preclinical Assessment of Low Doses of Cisplatin in the Management of Acute Promyelocytic Leukemia 低剂量顺铂治疗急性早幼粒细胞白血病的临床前评估
Pub Date : 2015-10-01 DOI: 10.16966/2381-3318.113
Shaloam Dasari, Venkatramreddy Velma, C. Yedjou, P. Tchounwou
Cis-diamminedichloroplatinum (II) (cisplatin) is the most widely used chemotherapeutic drug for various cancers, but its effectiveness is limited by tumor cell resistance and the severe side effects it causes. Since high level of cisplatin is cytotoxic to both cancer and normal cells, the goal of the present study was to explore the effectiveness of prolonged low doses of cisplatin in the management of leukemia. To achieve our goal, human leukemia (HL-60) cells were treated with different doses (1, 2, or 3 µM) of cisplatin for 24, 48, 72 and 96 hours. Cell viability was assessed by MTS assay. Both oxidative stress damage and genotoxicity were estimated by antioxidants, lipid peroxidation, and comet assays, respectively. Data obtained from the MTS assay demonstrated that cisplatin treatment decreased the number of viable tumor cells by direct cell killing or by simply decreasing the rate of cellular proliferation in a dose- and time-dependent fashion. The results of the lipid peroxidation showed a significant increase (p<0.05) of malondialdehyde levels with increasing cisplatin doses. Results obtained from super oxide dismutase and catalase assays showed a gradual increase in antioxidant enzyme activity in cisplatin-treated cells compared to control cells. Data generated from the Comet assay demonstrated a significant dose-dependent increase in genotoxicity with respect to DNA damage as a result of cisplatin treatment. Taken together, our research demonstrated that cisplatin-induced cytotoxicity in HL-60 cells is mediated at least in part via induction of oxidative stress and oxidative damage.
顺式二胺二氯铂(顺铂)是目前广泛应用于各种癌症的化疗药物,但肿瘤细胞耐药和严重的副作用限制了其疗效。由于高剂量的顺铂对癌细胞和正常细胞都有细胞毒性,因此本研究的目的是探讨长时间低剂量顺铂在白血病治疗中的有效性。为了实现我们的目标,用不同剂量(1、2或3µM)的顺铂治疗人类白血病(HL-60)细胞24、48、72和96小时。MTS法测定细胞活力。氧化应激损伤和遗传毒性分别通过抗氧化剂、脂质过氧化和彗星测定来估计。从MTS试验中获得的数据表明,顺铂治疗通过直接杀死细胞或简单地以剂量和时间依赖的方式降低细胞增殖率来减少活的肿瘤细胞的数量。脂质过氧化结果显示,丙二醛水平随顺铂剂量的增加而显著升高(p<0.05)。超氧化物歧化酶和过氧化氢酶测定结果显示,与对照细胞相比,顺铂处理细胞的抗氧化酶活性逐渐增加。Comet试验产生的数据表明,顺铂治疗对DNA损伤的遗传毒性有显著的剂量依赖性增加。综上所述,我们的研究表明,顺铂诱导的HL-60细胞毒性至少部分是通过诱导氧化应激和氧化损伤介导的。
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引用次数: 9
Soluble gC1qR in Blood and Body Fluids: Examination in a Pancreatic Cancer Patient Cohort. 血液和体液中的可溶性 gC1qR:胰腺癌患者队列研究
Pub Date : 2015-10-01 Epub Date: 2015-09-03 DOI: 10.16966/ijcrmm.110
Ellinor Ib Peerschke, Ricardo Jmge Brandwijk, Francine R Dembitzer, Yayoi Kinoshita, Berhane Ghebrehiwet

Background: gC1qR is a multifunctional cellular protein that has been linked to inflammation and cancer. gC1qR is highly upregulated in adenocarcinomas as compared to normal tissue counterparts, and soluble gC1qR (sgC1qR) has been detected in vitro in the pericellular milieu of proliferating malignant cells.

Aim: The present study explored the tissue expression of gC1qR in pancreatic cancer by immunohistochemistry, and the presence of sgC1qR in vivo, by examining blood and malignant effusions from patients with metastatic pancreatic adenocarcinoma.

Methods: Tissue expression of gC1qR by pancreatic adenocarcinoma was visualized by immunohistochemistry. SgC1qR was quantified in serum from healthy volunteers (n=20) and pancreatic cancer patients (n=34), as well as in malignant pleural (n=23) and peritoneal effusions (n=27), using a newly developed, sensitive immunocapture sandwich ELISA.

Results: Overexpression of gC1qR was confirmed in pancreatic adenocarcinoma compared to nonmalignant pancreatic tissue. Moreover, increased serum levels of sgC1qR (0.29 ± 0.22 ng/ml) were noted in patients with metastatic pancreatic cancer compared to healthy controls (0.15 ± 0.10 ng/ml) (mean ± S.D.) (p=0.035). In 11 of 16 patients for whom sequential samples were available, serum sgC1qR levels rose with disease progression, and paralleled changes in tumor biomarkers, CEA and CA19.9. In addition to blood, sgC1qR was detected in malignant pleural (0.55 ± 0.47 ng/ml) and peritoneal effusions (0.57 ± 0.38 ng/ml).

Conclusion: This study provides the first evidence for the presence of sgC1qR in vivo. The ability to detect sgC1qR in blood and body fluids will enable further studies to elucidate its pathophysiology in malignancy.

背景:gC1qR是一种多功能细胞蛋白,与炎症和癌症有关。与正常组织相比,gC1qR在腺癌中高度上调,而且在体外增殖的恶性细胞的细胞周环境中检测到了可溶性gC1qR(sgC1qR)。目的:本研究通过免疫组化方法探讨了胰腺癌组织中 gC1qR 的表达情况,并通过检测转移性胰腺腺癌患者的血液和恶性渗出物,探讨了 sgC1qR 在体内的存在情况:方法:通过免疫组织化学方法观察胰腺癌组织中 gC1qR 的表达。采用新开发的灵敏的免疫捕获夹心酶联免疫吸附试验,对健康志愿者(20 人)和胰腺癌患者(34 人)的血清以及恶性胸腔积液(23 人)和腹腔积液(27 人)中的 SgC1qR 进行了定量分析:结果:与非恶性胰腺组织相比,gC1qR在胰腺腺癌中被证实过度表达。此外,与健康对照组(0.15 ± 0.10 ng/ml)(平均值 ± S.D.)相比,转移性胰腺癌患者血清中的 sgC1qR(0.29 ± 0.22 ng/ml)水平升高(p=0.035)。在有连续样本的 16 位患者中,有 11 位患者的血清 sgC1qR 水平随着疾病的进展而升高,并与肿瘤生物标志物 CEA 和 CA19.9 的变化同步。除血液外,恶性胸腔积液(0.55 ± 0.47 ng/ml)和腹腔积液(0.57 ± 0.38 ng/ml)中也检测到了 sgC1qR:该研究首次证明了体内存在sgC1qR。结论:本研究首次证明了 sgC1qR 在体内的存在,在血液和体液中检测 sgC1qR 的能力将有助于进一步研究阐明其在恶性肿瘤中的病理生理学。
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引用次数: 0
期刊
International journal of cancer research and molecular mechanisms
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