N N Teng

Stanford University, Palo Alto, CA, United States

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Publications (122)508.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the clinic. Drugs that were once effective against naïve disease subsequently prove ineffective against recurrent disease, which often exhibits an MDR phenotype. MDR can be attributed to many factors; often dominating among these is the ability of a cell to suppress or block drug entry through upregulation of membrane-bound drug efflux pumps. Efflux pumps exhibit poly-specificity, recognizing and exporting many different types of drugs, especially those whose lipophilic nature contributes to residence in the membrane. We have developed a general strategy to overcome efflux-based resistance. This strategy involves conjugating a known drug that succumbs to efflux-mediated resistance to a cell-penetrating molecular transporter, specifically, the cell-penetrating peptide (CPP), D-octaarginine. The resultant conjugates are discrete single entities (not particle mixtures) and highly water-soluble. They rapidly enter cells, are not substrates for efflux pumps, and release the free drug only after cellular entry at a rate controlled by linker design and favored by target cell chemistry. This general strategy can be applied to many classes of drugs and allows for an exceptionally rapid advance to clinical testing, especially of drugs that succumb to resistance. The efficacy of this strategy has been successfully demonstrated with Taxol in cellular and animal models of resistant cancer and with ex vivo samples from patients with ovarian cancer. Next generation efforts in this area will involve the extension of this strategy to other chemotherapeutics and other MDR-susceptible diseases.
    Molecular Pharmaceutics 05/2014; · 4.57 Impact Factor
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    ABSTRACT: Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.
    Journal of the National Comprehensive Cancer Network: JNCCN 02/2014; 12(2):248-80. · 5.11 Impact Factor
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    ABSTRACT: These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.
    Journal of the National Comprehensive Cancer Network: JNCCN 10/2013; 11(10):1199-209. · 5.11 Impact Factor
  • Yi Chen, Marcia M Bieber, Nelson N H Teng
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    ABSTRACT: A major challenge of successful chemotherapy in ovarian cancer is overcoming intrinsic or acquired multi-drug resistance caused by active drug efflux mediated by ATP-binding cassette (ABC) transporters. Regulation of these transporters in ovarian cancer is poorly understood. We have found that abnormal expression of the hedgehog (Hh) signaling pathway transcription factor Gli1 is involved in the regulation of ABC transporters ABCB1 and ABCG2 in ovarian cancer. Hh is a known regulator of cancer cell proliferation and differentiation in several other types of invasive and metastatic malignancies. Our work has demonstrated that Gli1 is abnormally activated in a portion of ovarian cancers. Inhibition of Gli1 expression decreases ABCB1 and ABCG2 gene expression levels and enhances the response of ovarian cancer cells to certain chemotherapeutic drugs. The underlying mechanism is a direct association of Gli1 with a specific consensus sequence located in the promoter region of ABCB1 and ABCG2 genes. This study provides new understanding of ABC gene regulation by Hh signaling pathway, which may lead to the identification of new markers to detect and to anticipate ovarian cancer chemotherapy drug sensitivity. © 2013 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 02/2013; · 4.27 Impact Factor
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    ABSTRACT: These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline). See "Updates" in the NCCN Guidelines for Ovarian Cancer for a complete list of all the recent revisions.
    Journal of the National Comprehensive Cancer Network: JNCCN 11/2012; 10(11):1339-1349. · 5.11 Impact Factor
  • Gynecologic Oncology 10/2012; 127(1):S9. · 3.93 Impact Factor
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    ABSTRACT: Multidrug resistance is the major cause of failure of many chemotherapeutic agents. While resistance can arise from several factors, it is often dominated by drug efflux mediated by P-glycoprotein (P-gp), a membrane-bound polysubstrate export pump expressed at high levels in resistant cells. While co-administration of pump inhibitors and a drug could suppress efflux, this two-drug strategy has not yet advanced to therapy. We recently demonstrated that the reversible attachment of a guanidinium-rich molecular transporter, polyarginine, to a drug provides a conjugate that overcomes efflux-based resistance in cells and animals. This study is to determine whether this strategy for overcoming resistance is effective against human disease. Tumor samples from ovarian cancer patients, both malignant ascites cells and dissociated solid tumor cells, were exposed to Taxol-oligoarginine conjugates designed to release free drug only after cell entry. Cell viability was determined via propidium-iodide uptake by flow cytometry. To analyze bystander effect, toxicity of the drug conjugates was also tested on peripheral blood leucocytes. Human ovarian carcinoma specimens resistant to Taxol in vitro demonstrated increased sensitivity to killing by all Taxol-transporter conjugates tested. These studies also show that the drug conjugates were not significantly more toxic to normal human peripheral blood leukocytes than Taxol. These studies with human tumor indicate that oligoarginine conjugates of known drugs can be used to overcome the efflux-based resistance to the drug, providing a strategy that could improve the treatment outcomes of patients with efflux-based drug-resistance.
    Gynecologic Oncology 04/2012; 126(1):118-23. · 3.93 Impact Factor
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    ABSTRACT: CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.
    Proceedings of the National Academy of Sciences 03/2012; 109(17):6662-7. · 9.81 Impact Factor
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    ABSTRACT: This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy. Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts. Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients. Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.
    Haematologica 01/2012; 97(1):30-7. · 5.94 Impact Factor
  • Histopathology 12/2011; 59(6):1274-7. · 2.86 Impact Factor
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    ABSTRACT: Ovarian cancer has very heterogeneous histological classification, and response to therapy of the same grade and type varies. We studied genes in the Wnt and hedgehog (Hh) pathways, which are essential for embryonic development and which play critical roles in proliferation in a variety of human cancers. Variations in these pathway genes causing proliferation could play a role in the variation in tumor progression and response to therapy. Using real-time polymerase chain reaction, we studied 16 primary grade 3 International Federation of Gynecology and Obstetrics stage III serous ovarian cancer samples for expression of the Wnt pathway gene AXIN2, fibroblast growth factor 9, and Hh pathway gene expressions of glioma-associated oncogene 1, glioma-associated oncogene 2, patched homolog 1, patched homolog 2, Indian Hedgehog (HH), sonic HH, and Smoothened, a G protein-coupled receptor protein. Normal ovary epithelial cell line was used as control. We found wide variation of up-regulation of pathway component and target genes in the primary tumor samples and apparent cross talk between the pathways. AXIN2, a Wnt target gene, showed increased expression in all serous ovarian cancer samples. Fibroblast growth factor 9 was also overexpressed in all tumors with greater than 1000-fold increase in gene expression in 4 tumors. Expression of Hh pathway genes varied greatly. More than half of the tumor samples showed involvement of Hh signaling or pathway activation either by expression of transcription factors and Hh ligands or by overexpression of Indian HH/sonic HH and the receptor-encoding patched homolog 1/patched homolog 2. We found a wide variation in fold expression of genes involved in the Wnt and Hh pathway between patient samples.
    International Journal of Gynecological Cancer 06/2011; 21(6):975-80. · 1.94 Impact Factor
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    ABSTRACT: Squamous cell carcinoma (SCC) is the most common type of malignant transformation in mature cystic teratoma (MCT) of the ovary. The SCC is difficult to preoperatively diagnose. We conducted a retrospective study to seek the possible risk/prognostic factors and treatments for SCC arising from MCT of the ovary. Using an institutional database, we identified 3 women treated for SCC arising from an MCT of the ovary at the Kaohsiung Veteran General Hospital. A retrospective chart review was conducted, with information obtained from radiographs, operative reports, pathology reports, and radiation oncology records. A total of 1551 cases of MCT were diagnosed at Kaohsiung Veteran General Hospital from 1990 to 2009, of which, malignant teratoma SCC type was noted in 3 cases (0.19%). The median age of the subjects was 39 years. Abdominal fullness was the most common symptom (3/3 cases). The mean diameter of the ovarian tumor was 17.3 cm, ranging from 16 to 18 cm. All 3 patients received simple right salpingo-oophorectomy or debulking surgery. Two of the patients reached stage IIIC and died. : With our review as basis, we recommend being cautious of the following risk factors: patient age, tumor size, ultrasound characteristics, sonar tumor vessel wave form, computed tomography, and levels of SCC and CA125 tumor markers. We suggest that patients have regular ovarian ultrasound examination. Based on our literature review, stage IA patients who undergo standardized operational procedures do well without adjuvant treatment, but such patients must be confirmed accurately with complete surgical staging to be in stage IA before undergoing conservative management. The optimal approach to the management of patients with advanced stage and recurrent disease is unclear. Surgical cytoreduction with proper staging, adjuvant therapy with platinum-based or paclitaxel-based chemotherapy, and concurrent whole pelvic radiation have been recommended as possible methods of treatment.
    International Journal of Gynecological Cancer 04/2011; 21(3):466-74. · 1.94 Impact Factor
  • Renata R Urban, Nelson N H Teng, Daniel S Kapp
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    ABSTRACT: We report a case of uterine cancer and invasive cervical cancer, detected incidentally during the female-to-male sex reassignment surgery. The management of these patients is presented. Such individuals may not be receiving regular gynecologic care appropriate to their remaining genital organs; symptoms of malignant disease may be missed.
    American journal of obstetrics and gynecology 02/2011; 204(5):e9-e12. · 3.28 Impact Factor
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    ABSTRACT: Ovarian neoplasms consist of several histopathologic entities, and treatment depends on the specific tumor type. Epithelial ovarian cancer comprises most malignant ovarian neoplasms (∼ 80%)(1); however, other less-common pathologic subtypes must be considered in treatment guidelines. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer discuss epithelial ovarian cancer (including borderline or low malignant potential) and less-common histopathologies, including malignant germ cell neoplasms, carcinosarcomas (malignant mixed Müllerian tumors of the ovary [MMMT]), and sex cord-stromal tumors. The guidelines also discuss fallopian tube and primary peritoneal cancers, which are less-common neoplasms that are managed similarly to epithelial ovarian cancer. However, the less-common histologies of ovarian cancer are managed differently. Information on the less-common ovarian histopathologies are not published in this issue of JNCCN, but can be found online at www.NCCN.org. Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and the country's fifth most common cause of cancer mortality in women. In 2010, an estimated 21,900 new diagnoses and 13,900 deaths will occur from this neoplasm in the United States; fewer than 40% of women with ovarian cancer are cured.(2,3) The incidence of ovarian cancer increases with age and is most prevalent in the eighth decade of life, with a rate of 57 per 100,000 women. The median age at diagnosis is 63 years, and 70% of patients present with advanced disease.(4) Epidemiologic studies have identified risk factors for ovarian cancer. A 30% to 60% decreased risk of cancer is associated...
    Journal of the National Comprehensive Cancer Network: JNCCN 01/2011; 9(1):82-113. · 5.11 Impact Factor
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    Joseph M Bay, Bruce K Patterson, Nelson N H Teng
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    ABSTRACT: The constitutive proliferation and resistance to differentiation and apoptosis of neoplastic cervical cells depend on sustained expression of human papillomavirus oncogenes. Inhibition of these oncogenes is a goal for the prevention of progression of HPV-induced neoplasias to cervical cancer. SiHa cervical cancer cells were transfected with an HPV-16 promoter reporter construct and treated with leukemia inhibitory factor (LIF), a human cytokine of the interleukin 6 superfamily. SiHa and CaSki cervical cancer cells were also assessed for proliferation by MTT precipitation, programmed cell death by flow cytometry, and HPV E6 and E7 expression by real-time PCR. LIF-treated cervical cancer cells showed significantly reduced HPV LCR activation, reduced levels of E6 and E7 mRNA, and reduced proliferation. We report the novel use of LIF to inhibit viral oncogene expression in cervical cancer cells, with concomitant reduction in proliferation suggesting re-engagement of cell-cycle regulation.
    Infectious Diseases in Obstetrics and Gynecology 01/2011; 2011:463081.
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    ABSTRACT: Overview An estimated 12,200 new cases of cervical cancer will be diagnosed in the United States in 2010, and 4200 people will die of the disease.(1) Cervical cancer rates are decreasing among women in the United States, although incidence remains high among Hispanic/Latino, black, and Asian women.(2-5) However, cervical cancer is a major world health problem for women. The global yearly incidence of cervical cancer for 2002 was 493,200; the annual death rate was 273,500. It is the third most common cancer in women worldwide,(6,7) with 78% of cases occurring in developing countries, where cervical cancer is the second most frequent cause of cancer death in women. Persistent human papillomavirus (HPV) infection is regarded as the most important factor contributing to the development of cervical cancer. A relationship seems to exist between the incidence of cervical cancer and the prevalence of HPV in the population. The prevalence of chronic HPV in countries with a high incidence of cervical cancer is 10% to 20%, whereas its prevalence in low-incidence countries is 5% to 10%.(6) Immunization against HPV prevents infection with certain types of HPV and, thus, is expected to prevent specific HPV cancer in women (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Cervical Cancer Screening, in this issue; to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org).(8-12) Other epidemiologic risk factors associated with cervical cancer are a history of smoking, parity, contraceptive use, early age at onset of coitus, larger number...
    Journal of the National Comprehensive Cancer Network: JNCCN 12/2010; 8(12):1388-416. · 5.11 Impact Factor
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    ABSTRACT: To describe and review the incidence of para-aortic (PA) nodal metastasis in completely staged endometrial cancer patients who are negative for pelvic nodal metastasis. Using an institutionally maintained database, we identified all patients with endometrial cancer from 2002 to 2006 who had both pelvic and aortic nodal dissections and determined the rate of isolated para-aortic nodal metastasis in non-malignant (i.e. negative) pelvic nodes. 201 endometrial cancer patients were surgically treated at our institution from 2002 to 2006. 171 patients had both pelvic and PA nodes removed during surgery, and specimens examined by a pathologist. Only 2 (1.2%) had PA nodes that tested positive for malignance (i.e. positive PA nodes) with pelvic nodes that tested negative for malignance (i.e. negative pelvic nodes). The final International Federation of Gynecology and Obstetrics (FIGO) grade for the endometrial tumor cells in the two patients was "G1" with endometrioid adenocarcinoma and "G3" with endometrioid adenocarcinoma and mucinous differentiation, respectively. Based on the very low incidence of patients inflicted with endometrial cancer that have positive para-aortic lymph nodes (PALNs) with negative pelvic nodes found both in our literature review (1.5%) and in our own study (1.2%), the addition of PA lymphadenectomy in all patients was found to have minimal diagnostic and therapeutic value. At the present, the role of complete PA lymphadenectomy in all patients with endometrial cancer should be re-examined. Individualized algorithms should be developed based on risk factors and status of pelvic nodes.
    Gynecologic Oncology 12/2010; 121(1):122-5. · 3.93 Impact Factor
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    ABSTRACT: Overview Despite a significant decrease in the incidence and mortality of cervical carcinoma in the United States, an estimated 12,200 women will be diagnosed with the disease in 2010, with 4210 expected deaths.(1) High-risk groups include women without access to health care and those who have immigrated to the United States from countries where cervical cancer screening is not routinely performed.(2) Because cervical cytology screening is the current method for early detection of this neoplasm, the purpose of these guidelines is to provide direction for the evaluation and management of cervical cytology. These guidelines include recommendations on screening techniques, initiation, and frequency of screening, and management of abnormal screening results including colposcopy. Cervical cytology screening techniques include liquid-based cytology or conventional Papanicolaou (Pap) smears. Unless specifically noted, these techniques are collectively referred to as cervical cytology in this discussion. Human papillomavirus (HPV) DNA testing for primary cervical cancer has been approved by the FDA; several diagnostic tests are available (e.g., HPV high-risk and HPV 16/18 DNA tests, Hybrid Capture 2 HPV DNA test). However, HPV DNA testing is not recommended in women younger than 21 years.(3) HPV DNA testing for high-risk virus types can also be used as a component of both primary screening and workup of abnormal cytology results; it is not useful to test for low-risk virus types.(3) (See HPV DNA Testing on page 1378 for more detail about these tests.) Colposcopy, along with colposcopically directed biopsies, is the primary method for evaluating women with abnormal cervical cytologies....
    Journal of the National Comprehensive Cancer Network: JNCCN 12/2010; 8(12):1358-86. · 5.11 Impact Factor
  • Journal of the National Comprehensive Cancer Network: JNCCN 06/2009; 7(5):498-531. · 5.11 Impact Factor
  • Fuel and Energy Abstracts 01/2009; 75(3).

Publication Stats

2k Citations
508.87 Total Impact Points

Institutions

  • 1987–2013
    • Stanford University
      • • Department of Obstetrics and Gynecology
      • • Department of Radiation Oncology
      • • Division of Rheumatology
      • • Department of Anesthesia
      Palo Alto, CA, United States
  • 1984–2012
    • Stanford Medicine
      • • Department of Obstetrics and Gynecology
      • • Division of Gynecologic Oncology
      Stanford, California, United States
  • 2010–2011
    • VGHKS Kaohsiung Veterans General Hospital
      • Department of Obstetrics and Gynaecology
      Kaohsiung, Kaohsiung, Taiwan
  • 2007–2011
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, California, United States
    • Morehouse School of Medicine
      • Department of Obstetrics and Gynecology
      Atlanta, GA, United States
  • 2004–2008
    • University of Alabama at Birmingham
      • Comprehensive Cancer Center
      Birmingham, AL, United States
  • 2006
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
  • 1992
    • University of California, Davis
      • Department of Obstetrics and Gynecology
      Davis, CA, United States
  • 1991
    • University of California, San Diego
      • Department of Medicine
      San Diego, CA, United States
  • 1990
    • David Grant USAF Medical Center
      Sacramento, California, United States