City of Hope Medical Center
City of Hope Medical Center
Williams L.,City of Hope Medical Center
Medical Physics | Year: 2012
Tissue absorbed dose (D) is a computed result for internal emitters. For fixed geometries, D is calculated by a matrix (S) multiplication of the integrated activity vector (Ã). The last quantity is usually measured by nuclear imaging of activity in various source organs and performing a temporal integration. Ã is the same as the total number of source decays. Dose is computed for a number of target organs — some of which will be the same as the source organs. The D = S*Ã relationship is general in that the same formula may also be used for voxels within organs or even down to the cellular level. Finding the activity (A) in source tissues may be done by a number of methods of which 6 are described. The most common clinical technique is the geometric mean (GM) image of an organ. Uncertainties in the GM method are ≈ +/− 30%. If one can do quantitative SPECT, PET or CAMI imaging, the variation is reduced to around +/− 6%. These last three techniques, however, require fusion of anatomic (e.g. CT) and nuclear images. The S matrix is generated via Monte Carlo methods and may be used in two formats. The most common is a set of phantom‐derived values for regulatory or scientific considerations. An example is the OLINDA program from Vanderbilt University. In this case, the corresponding animal or patient Ã value must be normalized using blood flow arguments. A second format is modification of a phantom's S values for a particular patient using the latter's geometry as found in CT or MRI scans. Corrections in such cases may be 2‐fold or more because of patient organ size variability. These variations may be due to genetic reasons and/or disease. Two caveats to the use of the above dose formulation should be mentioned. One exception is that the geometry may vary during tissue irradiation; e.g., by tumor size decrease due to immediate radiation dose effects. In this case, the standard formula is replaced by its differential form: dD/dt = S(t)*A(t). Dose rate may also be an important biological factor in assessing tissue response. A second important biological consideration is that effects — such as tumor regression — may depend upon higher powers of D than the first. Thus, the tissue response may not be a linear function of D, but would exhibit a sigmoid shape. One would anticipate such responses due to saturation of a biological system. Learning Objectives: 1. Knowing the general formula for internal emitter absorbed dose estimation. 2. Understanding the various methods used to measure activity, at depth, in source organs in a living animal or patient. 3. Realizing that two types of dose may be computed: one for a phantom and a second type for an individual patient. S values must be modified accordingly for these two computations. 4. Estimating uncertainties — including those in both Ã and S ‐ involved in the dose estimation process. © 2012, American Association of Physicists in Medicine. All rights reserved.
Stein C.A.,City of Hope Medical Center |
Castanotto D.,City of Hope Medical Center
Molecular Therapy | Year: 2017
Oligonucleotides (oligos) have been under clinical development for approximately the past 30 years, beginning with antisense oligonucleotides (ASOs) and apatmers and followed about 15 years ago by siRNAs. During that lengthy period of time, numerous clinical trials have been performed and thousands of trial participants accrued onto studies. Of all the molecules evaluated as of January 2017, the regulatory authorities assessed that six provided clear clinical benefit in rigorously controlled trials. The story of these six is given in this review. © 2017 The American Society of Gene and Cell Therapy
Inghirami G.,University of Turin |
Inghirami G.,New York University |
Inghirami G.,New York Medical College |
Chan W.C.,City of Hope Medical Center |
Pileri S.,University of Bologna
Immunological Reviews | Year: 2015
Summary: T-cell lymphoproliferative disorders are a heterogeneous group of neoplasms with distinct clinical-biological properties. The normal cellular counterpart of these processes has been postulated based on functional and immunophenotypic analyses. However, T lymphocytes have been proven to be remarkably capable of modulating their properties, adapting their function in relationship with multiple stimuli and to the microenvironment. This impressive plasticity is determined by the equilibrium among a pool of transcription factors and by DNA chromatin regulators. It is now proven that the acquisition of specific genomic defects leads to the enforcement/activation of distinct pathways, which ultimately alter the preferential activation of defined regulators, forcing the neoplastic cells to acquire features and phenotypes distant from their original fate. Thus, dissecting the landscape of the genetic defects and their functional consequences in T-cell neoplasms is critical not only to pinpoint the origin of these tumors but also to define innovative mechanisms to re-adjust an unbalanced state to which the tumor cells have become addicted and make them vulnerable to therapies and targetable by the immune system. In our review, we briefly describe the pathological and clinical aspects of the T-cell lymphoma subtypes as well as NK-cell lymphomas and then focus on the current understanding of their pathogenesis and the implications on diagnosis and treatment. © 2015 John Wiley & Sons A/S.
Raz D.J.,City of Hope Medical Center |
Nelson R.A.,City of Hope Medical Center |
Grannis F.W.,City of Hope Medical Center |
Kim J.Y.,City of Hope Medical Center
Chest | Year: 2015
Background: The natural history of typical pulmonary carcinoid tumors has not been described and has important implications for counselingelderly patients or patients with high operative-risk about surgical resection. Methods: Data from the Surveillance, Epidemiology, and End Results Program were used to identify 4,111 patients with biopsy specimen-proven lymph node-negative typical carcinoid tumor of the lung between 1988 and 2010; 306 had no resection, 929 underwent sublobar resection, and 2,876 underwent lobectomy. Overall survival and disease-specific survival (DSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of survival. Results: Five-year overall survival in patients who underwent lobectomy, sublobar resection, or no surgery was 93%, 92%, and 69%, respectively (P <.0001); 5-year DSS was 97%, 98%, and 88%, respectively (P <.0001). Among T1 tumors, DSS was 98% for patients who underwent lobectomy and sublobar resection and 92% for no surgery; among T2 tumors, DSS was 97%, 100%, and 87%, respectively, and among T3 and T4 tumors, it was 96%, 100%, and 75%, respectively. On multivariate analysis, nonoperative management was associated with an increased risk for disease-specific mortality compared with lobectomy (hazard ratio, 2.14; 95% CI, 1.35-3.40; P =.0013). Conclusions: In this population-based cohort, surgical resection of lymph node-negative carcinoid tumors is associated with a survival advantage over nonoperative treatment. However, the DSS at 5 years was still high without any treatment, suggesting that observation of asymptomatic peripheral typical carcinoid tumors orendoscopic management of symptomatic central carcinoid tumors may be considered in patients at high risk for surgical resection. © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS.
Groot Koerkamp B.,Rotterdam University |
Fong Y.,City of Hope Medical Center
Journal of Surgical Oncology | Year: 2014
The biliary malignancies that are reviewed here are gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (IHC), and perihilar cholangiocarcinoma (PHC). The focus is on outcomes after potentially curative resection of biliary malignancies. Key outcomes are postoperative mortality, median and 5-year overall survival (OS), recurrence-free survival, and recurrence patterns. Poor prognostic factors for recurrence and survival as well as prognostic models are also discussed. The incidence of biliary malignancies in the United States is about 5 in 100,000. Postoperative mortality for resection of GBC and IHC is similar to that of liver resections for other indications. However, 90 day postoperative mortality after liver resection for PHC is about 10%. For GBC, median OS depends strongly on the T-stage and ranges from 8 months (pT3) to 79 months (pT1b). Median OS after resection for IHC is about 30 months, and for PHC about 38 months. The majority of patients with biliary malignancies develop a recurrence after resection. Patients with GBC recur early with a median time to recurrence of 12 months, versus about 20 months for IHC and PHC. In patients with resected IHC or PHC locoregional recurrence was the only site of recurrence in about 60% of patients, versus 15% in patients with GBC. Poor prognostic factors after resection of all biliary malignancies include the presence of lymph node metastasis, a positive surgical resection margin, and moderate or poor tumor differentiation. Several prognostic nomograms have been developed to predict long-term outcomes of biliary cancer resection. © 2014 Wiley Periodicals, Inc.
Pullarkat V.,City of Hope Medical Center
Advances in Hematology | Year: 2010
Recipients of hematopoietic stem cell transplantation (HSCT) frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study. © 2010 Vinod Pullarkat.
Ferrell B.,City of Hope Medical Center
Nursing Science Quarterly | Year: 2010
The focus of this column is to describe a body of research on palliative care and end-of-life that has been the focus of Dr. Betty Ferrell's career and her work at the City of Hope. The impact of this work on the nursing workforce is described and research resources for nurses are included. © The Author(s) 2010.
Glackin C.A.,City of Hope Medical Center
Maturitas | Year: 2014
Breast cancer is the leading cause of cancer-related deaths in the United States with over 232,000 new diagnoses expected in 2014 and almost 40,000 deaths. While treatment of primary breast cancer is often well-managed with surgery and radiation, metastatic breast cancer (MBC) that has spread to the brain, bones, liver, and lungs is often incurable. One of the major challenges in the treatment of breast cancer is the presence of a subpopulation of cancer cells that are chemoresistant and metastatic. Given that metastasis is the driving force behind mortality for breast cancer patients, it is essential to identify the characteristics of these aberrant cancer cells that allow them to spread to distant sites in the body and develop into metastatic tumors. Understanding the metastatic mechanisms driving cancer cell dispersal will open the door to developing novel therapies that prevent metastasis and improve long-term outcomes for patients. In this review we assess the feasibility of targeting the Twist and Wnt signaling pathways in breast cancer. These pathways mediate epithelial-mesenchymal transition (EMT), a process that can give rise to chemoresistance. We review potential treatment strategies for targeting EMT and drug resistance as well as the problems that may arise with these targeted delivery therapeutic approaches. Finally, we examine recent advances in the field, including nanoparticle delivery and small interfering RNA (siRNA) technology, and discuss the impact that these approaches may have on translating much needed therapeutic approaches into the clinic, for the benefit of patients battling MBC. © 2014 Elsevier Ireland Ltd.
California Institute of Technology and City Of Hope Medical Center | Date: 2012-11-17
Embodiments in accordance with the present invention relate to packed-column nano-liquid chromatography (nano-LC) systems integrated on-chip, and methods for producing and using same. The microfabricated chip includes a column, flits/filters, an injector, and a detector, fabricated in a process compatible with those conventionally utilized to form integrated circuits. The column can be packed with supports for various different stationary phases to allow performance of different forms of nano-LC, including but not limited to reversed-phase, normal-phase, adsorption, size-exclusion, affinity, and ion chromatography. A cross-channel injector injects a nanolitre/picolitre-volume sample plug at the column inlet. An electrochemical/conductivity sensor integrated at the column outlet measures separation signals. A self-aligned channel-strengthening technique increases pressure rating of the microfluidic system, allowing it to withstand the high pressure normally used in high performance liquid chromatography (HPLC). On-chip sample injection, separation, and detection of mixture of anions in water is successfully demonstrated using ion-exchange nano-LC.
Pullarkat V.,City of Hope Medical Center |
Aldoss I.,City of Hope Medical Center
Critical Reviews in Oncology/Hematology | Year: 2015
Early assessment of disease response to induction chemotherapy is important in acute myeloid leukemia (AML) in order to plan future therapy and identify chemorefractory disease. Such assessment is customarily performed by examining the bone marrow at around day 14 after initiation of chemotherapy. However, criteria for assessment of residual leukemia in day 14 bone marrow specimens as well as the significance of partial response on long term outcomes remain unclear. Clinical practices vary regarding the therapeutic intervention for residual disease and include readministration of the original induction therapy or use of a different reinduction regimen. In this article, we critically examine the prognostic significance of residual disease detected on interim bone marrow examination as well as data on reinduction therapy with the original induction regimen versus an alternate regimen. We emphasize the need for standardizing reporting of interim bone marrow assessment as well as evaluating new technologies and biomarkers for early assessment of disease response and chemosensitivity in AML. © 2015 Elsevier Ireland Ltd.