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Collision tumor of the kidney composed of clear cell carcinoma and collecting duct carcinoma: report of a case with unusual morphology and clinical follow-up

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Chinese Journal of cancer 2014年第7期33卷 351-355页

作者： Rhonda Burch-Smith Nizar M Tannir Erika Resetkova Pheroze Tamboli Priya Rao department of Pathology MD Anderson Cancer Center department of Geni-tourinary Medical Oncology MD Anderson Cancer Center

We report the case of a 67-year-old female who presented with a large renal mass. Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that invaded into the renal sinus and perinephric fat. Histologic examination revealed two distinct tumor types. The first type was a conventional(clear cell) renal cell carcinoma that was of low nuclear grade and comprised the minority of the overall tumor. The second type was a high-grade collecting duct carcinoma with glandular/tubular differentiation and composed the majority of the tumor. Immunohistochemical studies demonstrated distinctive patterns of the two tumor types, thus confirming two distinct lineages. Five months postoperatively, the patient developed metastasis to the lungs and right hilar lymph node region. A fine needle aspiration of a lung nodule demonstrated a metastatic, poorly differentiated carcinoma, similar to the collecting duct carcinoma component in the kidney. Collision tumors of the kidney are rare with fewer than 10 cases reported in the literature. Our report further expands the spectrum of this rare phenomenon.

关键词：集合管肾细胞肾脏肿瘤病例报告癌组织学检查随访

Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade

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World Journal of Gastrointestinal Oncology 2017年第9期9卷 354-362页

作者： Travis Edward Grotz Richard E Royal Paul F Mansfield Michael James Overman Gary N Mann Kristen Ashlee Robinson Karen A Beaty Safiea Rafeeq Auerlio Matamoros Michelle W Taggart Keith Francis Fournier department of Surgical Oncology at the University of Texas md anderson cancer center department of Medical Oncology at the University of Texas md anderson cancer center department of Radiology at the University of Texas md anderson cancer center department of Pathology at the University of Texas md anderson cancer center department of SurgicalOncology at the University of Texas md anderson cancer center

AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards *** There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms.

关键词： Hyperthermic intraperitoneal chemotherapy Pseudomyxoma peritonei Histology Grade Prognostic Outcomes

A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses

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Cell Research 2007年第5期17卷 435-440页

作者： Seon Hee Chang Unit 906 Houston USA TX 77030 7455 Fannin department of immunology md anderson cancer center

CD4+ helper T (TH) cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed TH,TH17 or inflammatory TH (THi), has been identified as critical mediators of tissue inflammation. These cells produceIL-17 (also called IL-17 A) and IL-17F, two most homologous cytokines sharing similar regulations. Here we reportthat when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which wename as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17Fhomodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 andKC (CXCL1) as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent onIL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatoryresponses and may serve as a novel target for treating various immune-mediated diseases.

关键词： inflammation IL-17 T cells

Hippo signaling and epithelial cell plasticity in mammalian liver development, homeostasis, injury and disease

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Science China(Life Sciences) 2019年第12期62卷 1609-1616页

作者： Randy L.Johnson department of cancer Biology University of Texas MD Anderson Cancer Center

A traditional view of cellular differentiation is unidirectional: progenitor cells adopt specific fates in response to environmental cues resulting in deployment of cell-specific gene expression programs and acquisition of unique differentiated cellular properties such as production of structural and functional proteins that define individual cell types. In both development and in tissue repair stem and progenitor cells are thought to both self-renew to maintain the pool of precursors and to expand to give rise to transient amplifying and differentiated cell types. Recently, however, it has become appreciated that differentiated cell types can be reprogrammed to adopt progenitor and stem cell properties. In the case of epithelial cells in the mammalian liver, hepatocytes and biliary epithelial cells there is a significant degree of plasticity between these lineages that has been implicated in mechanisms of tissue repair and in liver pathologies such as cancer. Recent studies have highlighted the role of Hippo signaling, an emerging growth control and tumor suppressor pathway, in regulating epithelial cell plasticity in the mammalian liver and in this review, the role of cellular plasticity and Hippo signaling in regulating normal and abnormal tissue responses in the mammalian liver will be discussed.

关键词： liver homeostasis plasticity regeneration cancer Hippo pathway

Peli： a family of signal-responsive E3 ubiquitin ligases mediating TLR signaling and T-cell tolerance

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Cellular & Molecular immunology 2012年第2期9卷 113-122页

作者： Wei Jin Mikyoung Chang Shao-Cong Sun immunology Program Memorial Sloan-Kettering Cancer CenterNew YorkNYUSA department of immunology The University of Texas MD Anderson Cancer CenterNew YorkNY 10065USA

E3 ubiquitin ligases play a crucial role in regulating immune receptor signaling and modulating immune homeostasis and activation. One emerging family of such E3s is the Pelle-interacting （Peli） proteins, characterized by the presence of a cryptic forkhead-associated domain involved in substrate binding and an atypical RING domain mediating formation of both lysine （K） 63- and K48-1inked polyubiquitin chains. A well-recognized function of Peli family members is participation in the signal transduction mediated by Toll-like receptors （TLRs） and IL-1 receptor. Recent gene targeting studies have provided important insights into the in vivofunctions of Pelil in the regulation of TLR signaling and inflammation. These studies have also extended the biological functions of Pelil to the regulation of T-cell tolerance. Consistent with its immunoregulatory functions, Peli I responds to different immune stimuli for its gene expression and catalytic activation. In this review, we discuss the recent progress, as well as the historical perspectives in the regulation and biological functions of Peli.

关键词： Peli Pellino ubiquitination NF-kB TLR T-cell tolerance

Dynamic Behavior and Function of Foxp3^+ Regulatory T Cells in Tumor Bearing Host

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Cellular & Molecular immunology 2009年第1期6卷 3-13页

作者： F. Xiao-Feng Qin department of immunology The University of TexasMD Anderson Cancer Center The University of Texas Graduate School of Biomedical Sciences at Houston

Regulatory T cells （Tregs） expressing forkhead/winged-helix transcription factor Foxp3 represent a distinct lineage of lymphocytes which play a central role in protecting the host from autoimmune diseases. However, Tregs also pose a major problem to anti-tumor immunity. Growing body of evidence from both laboratory and clinical investigations has demonstrated that expansion and accumulation of these immunosuppressive cells correlates with advanced tumor growth and predicts poor disease prognosis. How tumor development subverts normal self-tolerance function of Tregs thereby thwarts host anti-tumor immunity remains elusive. This review will discuss our current knowledge in understanding the dynamics and plasticity of Foxp3~ Treg activation and induction in tumor bearing hosts and their interaction with various antigen presenting cells （APCs） in tumor microenvironment leading to the establishment of active local and systemic immune suppression. Cellular ＆ Molecular immunology.

关键词： Treg APC tumor microenvironment immune suppression anti-tumor immunity

Epigenetic alterations in gastric carcinogenesis

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Cell Research 2005年第4期15卷 247-254页

作者： In-Seon CHOI,Tsung-Teh WU department of Pathology The University of Texas md anderson cancer center Houston Texas USA department of Pathology The University of Texas md anderson cancer center Houston Texas USA

Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogeneoverexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a varietyof methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play impor-tant roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpGisland methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesisand its relevance of clinical implications.

关键词： epigenetic alterations gastric carcinogenesis chronic gastritis intestinal metaplasia dysplasia/adenoma adenocarcinoma.

Predictive biomarkers in precision medicine and drug development against lung cancer

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Chinese Journal of cancer 2015年第7期34卷 295-309页

作者： Bingliang Fang Reza J Mehran John V Heymach Stephen G Swisher department of Thoracic and Cardiovascular Surgery The University of Texas MD Anderson Cancer Center department of Thoracic and Head/Neck Medical Oncology The University of Texas MD Anderson Cancer Center

The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been *** agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer ***,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted ***,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug *** review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug *** identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition ***,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.

关键词：生物标志物药物开发预测肺癌医学受体酪氨酸激酶表皮生长因子受体治疗药物

Hypoxia inducible factor(HIF) in the tumor microenvironment：friend or foe？

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Science China(Life Sciences) 2017年第10期60卷 1114-1124页

作者： Yanqing Huang Daniel Lin Cullen M.Taniguchi The University of Texas at md anderson Department of Experimental Radiation Oncology MD Anderson Cancer Center Houston TX 77030 USA The University of Texas at md anderson Division of Radiation Oncology MD Anderson Cancer Center Houston TX 77030 USA

Hypoxia acts as an important regulator of physiological and pathological processes. Hypoxia inducible factors(HIFs) are the central players involved in the cellular adaptation to hypoxia and are regulated by oxygen sensing EGLN prolyl *** affects many aspects of cellular growth through both redox effects and through the stabilization of HIFs. The HIF isoforms likely have differential effects on tumor growth via alteration of metabolism, growth, and self-renewal and are likely highly context-dependent. In some tumors such as renal cell carcinoma, the EGLN/HIF axis appears to drive tumorigenesis,while in many others HIF1 and HIF2 may actually have a tumor suppressive role. An emerging role of HIF biology is its effects on the tumor microenvironment. The EGLN/HIF axis plays a key role in regulating the function of the various components of the tumor microenvironment, which include cancer-associated fibroblasts, endothelial cells, immune cells, and the extracellular matrix(ECM). Here, we discuss hypoxia and the diverse roles of HIFs in the setting of tumorigenesis and the maintenance of the tumor microenvironment as well as possible future directions of the field.

关键词： hypoxia HIF tumor microenvironment cellular homeostasis mouse model