An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD⁺/NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.     

A water-soluble aminatedβ1-3D-glucan derivative causes regression of solid tumors in mice

Meth A sarcoma, when inoculated in the skin, grew progressively in hybrid CB6 Fl(Balb/c×C57B1/6) mice. When water-soluble aminated 1-3D-glucan (AG) was injected intravenously or intraperitoneally on day 7 of tumor growth, the tumors underwent complete regression. When the injection was performed on day 3 there was regression of tumors in only about half of the cases. When the injection was performed on day 14 there was no apparent effect on tumor growth. Tumors in thymectonized animals did not appear to respond to treatment with AG on day 7. The relatively simple chemistry and low toxicity of AG, together with its solubility in biological fluids, makes it a promising tool in experimental—and possibly clinical—tumor therapy.Abbreviation AG aminated glucan     

环状RNA在胃癌中的研究现状与策略

环状RNA (circRNA)是一种共价闭合的非编码RNA,可以调节真核生物中的基因表达.最近应用高通量RNA测序和生物信息学方法揭示人类细胞中存在大量circRNA.许多circRNA具有一定的组织和时序特异性,且与生理发育和各种肿瘤等疾病密切相关. circRNA被证明在细胞质中富集和稳定,表明其具有作为肿瘤生物标志物的潜力.胃癌(gastric carcinoma,GC)是一种常见的恶性肿瘤,在全球癌症相关死亡原因中排第3位.尽管该疾病在诊断和治疗方面取得了许多进展,但GC患者的预后仍然很差,大多数国家的5年总生存率低于30%.因此,寻找能调节GC发生发展和评估预后的新分子机制和治疗靶标至关重要.近年来circRNA在胃癌中的研究不断增多,其在胃癌的发生发展、诊断、治疗及预后过程中扮演重要角色.本文就circRNA产生机制及一般特征、生物学功能、在胃癌中的研究进展及研究中存在的问题作一综述.     

Concomitant sertoli and leydig cell tumor of the testis: a case report

A rare intratubular gonadal stromal tumor was present in the testis of a 45-year-old man who was admitted to our hospital with the chief complaint of gradual enlargement of the left testis. Tumoral markers were negative and no extension was observed. The tumor comprised an intratubular mixture of two types of tumor cells with intercellular junctions: the predominant tumor cells were consistent with a Sertoli cell origin and cells comprising the minor population consistent with a Leydig cell origin. The patient is disease free after 6-month follow-up. The case is considered to be a testicular mixed tubular Sertoli-Leydig cell tumor. It highlights a rare type of primary tumor of the testis that features a good prognosis.     

Modeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting

1. Download high-res image (243KB)
2. Download full-size image

     

DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study

We evaluated the association between methylation of 9 genes, SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1, and SFN in tumor samples from 720 breast cancer cases with clinicopathological features of the tumors and survival. Logistic regression was used to estimate odds ratios (OR) of methylation and Cox proportional hazards models to estimate hazard ratios (HR) between methylation and breast cancer related mortality. Estrogen receptor (ER) and progesterone receptor (PR) positivity were associated with increased SCGB3A1 methylation among pre- and post-menopausal cases. Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1–19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4–39.9; Stage III/IV OR = 5.6, 95% CI: 1.1–29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1–0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1–0.8; Stage III/IV OR = 0.6, 95% CI: 0.1–3.4). Among postmenopausal women, methylation of SYK was associated with increased tumor size (OR = 1.7, 95% CI: 1.0–2.7) and higher nuclear grade (OR = 2.0, 95% CI 1.2–3.6). Associations between methylation and breast cancer related mortality were observed among pre- but not post-menopausal women. Methylation of SCGB3A1 was associated with reduced risk of death from breast cancer (HR = 0.41, 95% CI: 0.17–0.99) as was BRCA1 (HR = 0.41, 95% CI: 0.16–0.97). CCND2 methylation was associated with increased risk of breast cancer mortality (HR = 3.4, 95% CI: 1.1–10.5). We observed differences in methylation associated with tumor characteristics; methylation of these genes was also associated with breast cancer survival among premenopausal cases. Understanding of the associations of DNA methylation with other clinicopathological features may have implications for prevention and treatment.     

Metabolic regulation of ferroptosis in the tumor microenvironment

Ferroptosis is an iron-dependent, nonapoptotic form of regulated cell death triggered by impaired redox and antioxidant machinery and propagated by the accumulation of toxic lipid peroxides. A compendium of experimental studies suggests that ferroptosis is tumor-suppressive. Sensitivity or resistance to ferroptosis can be regulated by cell-autonomous and non-cell-autonomous metabolic mechanisms. This includes a role for ferroptosis that extends beyond the tumor cells themselves, mediated by components of the tumor microenvironment, including T cells and other immune cells. Herein, we review the intrinsic and extrinsic factors that promote the sensitivity of cancer cells to ferroptosis and conclude by describing approaches to harness the full utility of ferroptotic agents as therapeutic options for cancer therapy.     

Stromal biology of pancreatic cancer

The genetic paradigm of cancer, focused largely on sequential molecular aberrations and associated biological impact in the neoplastic cell compartment of malignant tumors, has dominated our view of cancer pathogenesis. For the most part, this conceptualization has overlooked the dynamic and complex contributions of the surrounding microenvironment comprised of non-tumor cells (stroma) that may resist, react to, and/or foster tumor development. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease in which a prominent tumor stroma compartment is a defining characteristic. Indeed, the bulk of PDAC tumor volume consists of non-neoplastic fibroblastic, vascular, and inflammatory cells surrounded by immense quantities of extracellular matrix, far exceeding that found in most other tumor types. Remarkably, little is known about the composition and physiology of the PDAC tumor microenvironment, in particular, the role of stroma in tumor initiation and progression. This review attempts to define key challenges, opportunities and state-of-knowledge relating to the PDAC microenvironment research with an emphasis on how inflammatory processes and key cancer pathways may shape the ontogeny of the tumor stroma. Such knowledge may be used to understand the evolution and biology of this lethal cancer and may convert these insights into new points of therapeutic intervention.     

单个肿瘤细胞测序研究进展

肿瘤是机体在各种致癌因素作用下,遗传物质受损导致特定细胞失去对正常生长调控,引起其克隆性异常增生而形成的恶性赘生物。随着单细胞分离技术及单细胞测序技术日益成熟,单个肿瘤细胞全基因组测序已成为肿瘤研究的一个崭新的领域。该文就对单个肿瘤细胞的获取及单个肿瘤细胞测序研究进展进行综述。     

Although Abundant in Tumor Tissue,Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors

1. Download high-res image (251KB)
2. Download full-size image

     

Tumor immune microenvironment: sanctuary of tumor and target for immunotherapy

The tumor immune microenvironment (TIME) is the cellular environment in which tumors exist. This includes: surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules, immune checkpoint proteins and the extracellular matrix (ECM). The TIME plays a critical role in cancer progression and regulation. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. The molecules and cells in the TIME influence disease outcome by altering the balance of suppressive versus cytotoxic responses in the vicinity of the tumor. Having a better understanding of the tumor immune microenvironment will pave the way for identifying new targets for immunotherapies that promote cancer elimination.     

肿瘤干细胞与肿瘤相关巨噬细胞的相互作用

肿瘤微环境(tumor microenvironment,TME)不仅促进了肿瘤的早期形成和远处转移,而且随着肿瘤的进展,其自身也不断地发生变化。作为TME的重要组成部分,肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)可通过分泌多种细胞因子激活IL-6/STAT3、TGF-β、Wnt/β-catenin等信号通路促进肿瘤干细胞(cancer stem cells,CSCs)的存活、自我更新和化疗耐药等。同时,CSCs也可通过分泌多种细胞因子和趋化因子等募集巨噬细胞,并将其诱导为TAMs重塑CSCs特定的生态位,维持CSCs表型并促进肿瘤进展。TAMs与CSCs的相互作用在促进肿瘤生长、转移及化疗耐药等方面发挥了重要作用。本文对TME中CSCs与TAMs相互作用的研究进行综述,并总结了以CSCs与TAMs相互作用为靶点在新型癌症治疗以及增强化疗效果等方面的重要潜力。     

Effects of 2.45-GHz microwave radiation and phorbol ester 12-O-tetradecanoylphorbol-13-acetate on dimethylhydrazine-induced colon cancer in mice

The purpose of this study was to investigate the effects of 2.45 GHz microwave (MW) radiation on dimethylhydrazine (DMH)-induced colon cancer in mice. The subjects were 115 Balb/c mice 4 weeks of age. The animals were divided into group A (control), group B (DMH), group C (DMH + MW), and group D [DMH + 12-O-tetradecanoylphorbol-13-acetate (TPA)]. Radiation (10 mW/cm²) was delivered dorsally with the E field parallel to the mouse's long body axis in an anechoic chamber. Radiations were administered 3 hr daily, 6 days per week, over a period of 5 months. The average SAR was estimated to be 10–12 W/kg. During the course of radiation treatments, DMH was injected once per week. The tumor promoter TPA was administered once per week for 10 weeks, from the third week on, after the initial treatment. The incidence of tumors did not significantly differ between the three test groups (groups B, C, and D; P > 0.25). However, the number of tumors, the size of the tumors, and the incidence of protuberant and infiltrative types in tumor-bearing animals were higher in group D compared to groups B and C (P < 0.05). No difference was found between groups B and C (P > 0.25). The study indicates that 2.45 GHz microwave radiation at 10 mW/cm² power density did not promote DMH-induced colon cancers in young mice. The study also showed that TPA could accelerate colon tumor production if a tumor was initiated. © 1994 Wiley-Liss, Inc.     

Cancer stem cells,a fuzzy evolving concept: A cell population or a cell property?

The cancer stem cells (CSC) hypothesis represents a pathological extrapolation of the physiological concept of embryonic and somatic stem cells. In its initial definition, it encompassed the hypothesis of a qualitatively distinct population of immortal cancer cells originating from somatic stem cells, which generate in xenotransplants by a deterministic irreversible process, the hierarchy of more differentiated finite lifespan derived cells, which constitute, themselves, the bulk of the cancer. These CSC would express specific biomarkers and gene expressions related to chemo- and radioresistance, stemness, epithelial–mesenchymal transition, etc.

No convincing congruence of several of these properties in one cell population has been demonstrated. The concept has greatly evolved with time and with different authors (“the plasticity of cancer stem cells”), leading to a minimal definition of cells generating a hierarchy of derived cells. In this article these concepts are analyzed. It is proposed that stemness is a property, more or less reversible, a hallmark of some cells at some time in a cancer cell population, as immortality, dormancy, chemo- or radioresistance, epithelial–mesenchymal transition etc. These phenotypic properties represent the result of independent, linked, or more or less congruent, genetic, epigenetic, or signaling programs.     

放射性粒子碘125插置组织间治疗晚期肿瘤的临床疗效

目的:探讨放射性粒子碘125插置组织间治疗晚期肿瘤的疗效。方法:选择2008年7月至2011年4月经我院收治的晚期肿瘤患者95例,全部患者均经放射性粒子碘125插置组织间治疗,观察患者疗效、不良反应、免疫指标及肿瘤标志物水平,并随访6-24月观察患者生存率。结果:95例患者临床有效率为83.15%,其中CR 23例(24.21%),PR 56例(58.94%),PD 9例(9.47%),SD 7例(7.37%)。在碘125插置过程中出现7例气胸,术后出现2例咳血、1例排便困难和3例出现发热并伴穿刺处疼痛。全部患者治疗前后IgG、IgA和IgM水平无显著性变化(P0.05),而治疗后4周各病种晚期肿瘤患者相应肿瘤标志物水平显著低于治疗前,差异有统计学意义(P0.05)。53例肺癌患者中,半数生存期为20个月,术后1、2年生存率分别为86.79%和41.51%;而同期行姑息手术且未接受放射性粒子碘125插置组织间治疗的40例肺癌患者,半数生存期仅为12个月,术后1、2年生存率分别为57.50%和22.50%,两组比较,差异有统计学意义(P0.05)。结论:放射性粒子碘125插置组织间治疗晚期肿瘤具有适应症广、安全性高、临床效果好和不良反应少等优点,还可提高晚期肿瘤患者的生存期。     

细胞衰老与肿瘤治疗

人口老龄化是全世界都面临的重大挑战,随着老年人口的增加,肿瘤等衰老相关疾病发病率随之升高.流行病学调查结果显示,大约2/3的新增肿瘤患者为65岁以上的老年人,并且这一比例在不断攀升.细胞衰老是指在DNA损伤或癌基因失调等一系列条件下引起的稳定的细胞周期阻滞,并伴有形态、生化及表观遗传的改变.大量研究证明细胞衰老对抑制潜在癌细胞增殖具有重要作用.然而,目前研究认为除了抑制肿瘤发生,细胞衰老也可能促进肿瘤的演进,细胞衰老对肿瘤发挥了双刃剑作用.因此,深入了解细胞衰老与肿瘤之间的联系,充分利用细胞衰老对肿瘤抑制功能,规避其对肿瘤的促进作用可为肿瘤的治疗提供更多可能的选择.     

胃癌发生中的独特肿瘤标记物—LI-cadherin

LI-cadherin,也被称为cadherin-17,是肠上皮细胞中一种贯穿细胞膜的、钙依赖性的、介导细胞间连接的糖蛋白。与经典钙黏蛋白相比,LI-cadherin是一种具备独特结构和功能的新型钙黏蛋白。LI-cadherin由7个胞外重复序列和一个只包含20个氨基酸残基的较短的胞质尾区组成。在人体中,LI-cadherin特异性的位于肝细胞和肠细胞中的底外侧区。而LI-cadherin介导细胞连接时,既不与链蛋白结合,也不导致β-catenin的上调。一些研究发现,在胃癌中LI-cadherin的过度表达与CDX-2显著相关,而且在肠化生中CDX-2的表达总是与LI-cadherin呈现很强的成对性。最新的研究认为LI-cadherin的表达与胃癌的发生、发展、转移及预后均有关系。在针对胃癌的临床处理方面,LI-cadherin将会是有用的肿瘤标记物。     

Alteration of WWOX in human cancer,a clinical view

WWOX gene is located in FRA16D, the highly affected chromosomal fragile site. Its tumor suppressor activity has been proposed on a basis of numerous genomic alterations reported in chromosome 16q23.3–24.1 locus. WWOX is affected in many cancers, showing as high as 80% loss of heterozygosity in breast tumors. Unlike most tumor suppressors impairing of both alleles of WWOX is very rare. Despite cellular and animal models information on a WWOX role in cancer tissue is limited and sometimes confusing. This review summarizes information on WWOX in human tumors.     

胰腺癌相关微生物标志物研究进展

在所有消化系统肿瘤中,胰腺癌的恶性程度很高,患者生存率极低,而胰腺癌发病的具体机制尚不明确。随着近年来包括肠道菌群在内的人体微生物研究的迅速发展,微生物在胰腺癌的潜在发病机制也成为研究热点。本文介绍了与胰腺癌相关的微生物标志物,并分析各种微生物标志物对胰腺癌的作用机制以及微生物形成的肿瘤微环境对胰腺癌的影响,为微生物与胰腺癌关系的进一步研究提供参考,有利于学界未来利用微生物相关技术开展胰腺癌的早期检查、早期预防和临床治疗。