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To describe 7 patients with paraproteinemic keratopathy and to highlight the clinical and pathologic diversity of this rare entity and the importance of timely, systemic evaluation.Retrospective, multicenter collaborative case series.Seven patients with paraproteinemic keratopathy.Clinical and pathologic records were reviewed to identify patients with well-documented corneal immunoglobulin deposits. Detailed ophthalmologic and medical histories were assembled. In 6 patients, corneal tissue was evaluated histochemically and immunohistochemically; in selected cases, corneal tissue was evaluated by in situ hybridization and ultrastructurally.Visual acuity and anterior segment examination at presentation and follow-up; local therapy; systemic diagnosis and management; and histopathologic, immunohistochemical, in situ hybridization, and ultrastructural findings.Seven patients were identified with corneal immunoglobulin deposition. In addition to previously reported crystalline, nummular, patch-like, and lattice-like corneal opacities, prominent corneal vascularization was present in 2 patients mimicking interstitial keratitis and limbal stem cell deficiency. All patients had evidence of paraproteinemia in a setting of monoclonal gammopathy of undetermined significance, smoldering plasma cell myeloma, or Waldenström macroglobulinemia. Corneal findings were the first manifestation of systemic disease in 4 patients, and the diagnosis was not suspected in 3 of these patients. Pathologic evaluation of biopsied corneal and conjunctival tissues demonstrated immunoglobulin deposits. Previously unreported ultrastructural patterns in the cornea were noted: large scroll-like immunotactoid deposits, immune complex-like deposits, and randomly arranged fibrils morphologically intermediate between amyloid and immunotactoid deposits. Surgical intervention to improve vision was performed in 4 patients, with recurrence of deposits in 3 patients. Three patients underwent systemic therapy with diminution of the deposits and improvement in vision in 1 patient.The clinical and pathologic expressions of corneal immunoglobulin deposits are protean and present a diagnostic challenge. Early recognition of this rare entity is important to address the potentially serious associated systemic disease.

Several gender-specific differences in cardiovascular diseases are known and pharmacokinetics of β-blockers shows relevant sex-specific differences. The plasma levels of metoprolol, for example, are higher in women compared to men. However, randomized studies have shown that metoprolol has little or no greater reduction in the mortality of women following myocardial infarction. We tested the hypothesis that metoprolol might have significant gender-specific effects in patients with chronic angina pectoris. Body weight of women was slightly (–9%) less than that of men and the daily dose of metoprolol was similar in both groups. Thus, according to pharmacokinetics women should have obtained higher plasma levels of this drug and the ensuing pharmacologic effects of metoprolol should have been greater. Our results do not confirm this assumption. Metoprolol reduced the frequency of angina episodes and the consumption of nitroglycerin tablets to a similar extent in both sexes. However, the pretreatment hemodynamic profiles confirmed the existence of gender-specific differences: women had significantly higher heart rate and blood pressure both at rest and during exercise. Since both groups were comparable in age, comorbidities, and medications, the existing difference is likely to be due to gender-specificity. The hemodynamic differences persisted during therapy with metoprolol: resting heart rate, blood pressure and rate pressure product were reduced to a greater extent in men. During cycloergometry, there was a slight difference in the time of onset of ST depression and time of onset of angina, which were slightly higher in men, but probably because of the limited number of cases, the difference between men and women did not reach significance. On the other hand, with metoprolol the duration of exercise and, in parallel, the number of metabolic equivalents was significantly greater in males than in females. Thus in spite of a presumed greater plasma concentration of metoprolol in women, we found a significant difference in anti-ischemic effect in favor of men. We conclude that metoprolol might exert a significantly greater therapeutic effect on stress-induced angina pectoris in men than in women and this difference should be taken into account when prescribing this β-blocker.

Purpose: The chimeric T84.66 (cT84.66) minibody is a novel engineered antibody construct (VL-linker-VH-CH3; 80 kDa) that demonstrates bivalent and high affinity (4 × 1010 m−1) binding to carcinoembryonic antigen (CEA). The variable regions (VL and VH) assemble to form the antigen-combining sites, and the protein forms dimers through self-association of the CH3 domains. In animal models, the minibody demonstrated high tumor uptake, approaching that of some intact antibodies, substantially faster clearance than intact chimeric T84.66, and superior tumor-to-blood ratios compared with the cT84.66 F(ab′)2 fragment, making it attractive for further evaluation as an imaging and therapy agent. The purpose of this pilot clinical study was to determine whether 123I-cT84.66 minibody demonstrated tumor targeting and was well tolerated as well as to begin to evaluate its biodistribution, pharmacokinetics, and immunogenicity in patients with colorectal cancer.Experimental Design: Ten patients with biopsy-proven colorectal cancer (6 newly diagnosed, 1 pelvic recurrence, 3 limited metastatic disease) were entered on this study. Each received 5–10 mCi (1 mg) of 123I-labeled minibody i.v. followed by serial nuclear scans and blood and urine sampling over the next 48–72 h. Surgery was performed immediately after the last nuclear scan.Results: Tumor imaging was observed with 123I-labeled minibody in seven of the eight patients who did not receive neoadjuvant therapy before surgery. Two patients received neoadjuvant radiation and chemotherapy, which significantly reduced tumor size before surgery and minibody infusion. At surgery, no tumor was detected in one patient and only a 2-mm focus was seen in the second patient. 123I-labeled minibody tumor targeting was not seen in either of these pretreated patients. Mean serum residence time of the minibody was 29.8 h (range, 10.9–65.4 h). No drug-related adverse reactions were observed. All 10 patients were evaluated for immune responses to the minibody, with no significant responses observed.Conclusion: This pilot study represents one of the first clinical efforts to evaluate an engineered intermediate-molecular-mass radiolabeled antibody construct directed against CEA. cT84.66 minibody demonstrates tumor targeting to colorectal cancer and a faster clearance in comparison with intact antibodies, making it appropriate for further evaluation as an imaging and therapy agent. The mean residence time of the minibody in patients is longer than predicted from murine models. We therefore plan to further evaluate its biodistribution and pharmacokinetic properties with minibody labeled with a longer-lived radionuclide, such as 111In.

Clear cell sarcoma of the tendons and aponeuroses (CCSTA) are rare aggressive soft tissue tumors with tendency for lymph nodes dissemination. Lymph node involvement is a correlate for prognosis. We present three patients with CCSTA in whom simultaneous sentinel lymph biopsy (SLNB) and resection was performed. Sentinel lymph node mapping may have a role in clear cell sarcoma from a prognostic standpoint. Further investigations are needed for validation.

BACKGROUND Esophageal carcinoma is a particularly interesting tumor because of the dramatic difference in its incidence and geographic distribution among populations of similar ethnic origin. Epidemiologic data have suggested that many environmental exposures may be associated with an increased risk of its formation. METHODS In this study, 92 samples of esophageal squamous cell carcinoma (ESCC) were collected from patients who resided in 2 geographic areas in China with different incidences of ESCC: Linxian and Zhejiang. Overexpression and mutations of the p53 tumor-suppressor gene were examined by using immunohistochemistry, single-strand conformation polymorphism analysis, and direct sequencing. RESULTS The rates of point mutation and overexpression of p53 in the ESCC specimens studied were 30.4% (29 of 92 specimens) and 51.1% (47 of 92 specimens), respectively. The overexpression of p53 was associated with tumor metastasis and with 5-year case fatality. Significant differences were found in the rates of overexpression and mutations in patients with clinical T2 tumors between the specimens from Linxian, which is a high-incidence geographic area, and the specimens from Zhejiang, which is a low-incidence area. Furthermore, different mutational spectra were found in the tumor samples from these two geographic areas: In tumor samples from Linxian, the most common substitution mutation was a transversion in exon 5, whereas the most common mutations in tumor samples from Zhejiang were transitions in exon 7. CONCLUSIONS The data suggest that the mutation and overexpression of p53 may play important roles in the development of ESCC. The changes in p53 may reflect environmental exposure to the different combinations of mutagenic factors and genetic instability demonstrated by the populations in Linxian and Zhejiang. The overexpression of p53 protein may have significance as a prognostic factor for patients with esophageal carcinoma. Cancer 2004. © 2004 American Cancer Society.

Background Use of extirpative surgery in the setting of recurrent rectal cancer is controversial given the poor overall outcome of such patients and the morbidity associated with exenteration. Methods A retrospective review of patients treated for recurrent rectal cancer from 1990 to 2002 was performed. Results Twenty-two patients underwent pelvic exenteration. Seventeen underwent potentially curative resection, 5 were for palliation only. There was 1 operative death. Fifteen suffered at least 1 complication; 9 suffered multiple complications. Ten patients required readmission to the hospital. The overall disease-free interval was 11 months. Potentially curative and palliative resections resulted in median survivals of 20.4 and 8.4 months, respectively ( P = 0.049). Conclusions While patients may derive oncologic and palliative benefits from exenteration, the price in terms of operative morbidity remains high. Newer measures of operative morbidity are necessary to better appraise the value of this radical approach to recurrent rectal cancer.

PURPOSE/OBJECTIVES To describe a program of research related to outcomes of palliative surgery and focus on one phase of this research involving decision making by patients and surgeons considering surgery for advanced disease. DESIGN Descriptive. SAMPLE 10 patients undergoing surgery and 3 oncology surgeons. METHODS Qualitative interviews were conducted with patients and their surgeons pre- and postoperatively. Transcripts were content analyzed to identify major themes in patient and surgeon interviews based on study questions. MAIN RESEARCH VARIABLES Decision making, palliative surgery, quality of life. FINDINGS The study findings highlight the issues of greatest concern to patients and surgeons considering palliative surgery. This phase was an important component of the overall program of palliative surgery research. CONCLUSIONS Comprehensive care for patients with advanced cancer seeks to achieve a balance of providing aggressive care, ensuring optimum symptom management, and maintaining a focus on comfort. Further study of palliative surgery as an aspect of interdisciplinary care is warranted. IMPLICATIONS FOR NURSING Patients undergoing surgery for advanced disease require expert nursing care to address quality-of-life concerns. Further research is needed in this area.

BACKGROUND Costs associated with the provision of medical care continue to escalate. Therefore, providers must evaluate the cost-effectiveness and benefit to individual healthcare practices. The authors evaluated the immediate and short-term resource utilization needs of patients undergoing surgical intervention with curative or palliative intent. METHODS Three hundred two patients undergoing surgery with therapeutic intent were observed from the time of admission for intervention until the time of death or until 6 months from the time of the surgical procedure. Surgeons preoperatively identified each case as either curative or palliative in intent. Demographic information, as well as the nature of all interactions with the cancer center, was recorded. RESULTS Surgeons identified 58 (19%) procedures as palliative and 244 (81%) as curative in intent. Demographic characteristics between the two groups were similar, although recurrent or metastatic disease was more often present in palliative rather than curative patients (P = 0.0078) and palliative intent patients were more likely to have received previous therapy. During the 6-month period, 4690 encounters occurred with the cancer center. The mean number of encounters per patient in each group was similar, although curative intent patients were more likely to have visits with therapeutic intent including chemotherapy administration (P = 0.01), radiation (P = 0.003), or repeat surgical procedures (P = 0.006). In contrast, palliative patients were more likely to be admitted for management of symptoms (P = 0.0001) and had fewer hospital-free days than did curative patients (P = 0.0069). CONCLUSIONS The average number of encounters for patients undergoing treatment of disease was not significantly different, suggesting that patients undergoing surgery with palliative intent do not require a greater amount of resources than curative intent patients. The nature of the interactions, however, was different, suggesting that resource needs are different and may need to be anticipated in the assessment of how better quality outcomes can be achieved in the palliative surgery setting. Cancer 2003. © 2003 American Cancer Society.

Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC).A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates.Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P =.01). Lower stage was associated with higher adenoma recurrence rates (P =.04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates.The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.

Liver metastasis from colorectal cancer remains an oncological challenge. Hepatic chemotherapy has been used; however, rigorous quality of life (QOL) measurements are lacking. The aim of this study was to describe unique QOL issues to formulate a specific tool for this population.A purposive sample was identified of patients treated with intrahepatic chemotherapy. Consenting patients completed a demographic tool and the City of Hope QOL Scale/Cancer Patient survey. An in-depth interview on QOL concerns was conducted, taped, and transcribed verbatim. The data from the interviews were coded to identify recurrent themes.Sixteen patients participated. Physical well-being was maintained. Significantly lower subscale scores were noted for psychological, social, and spiritual domains compared with nonpatient norms (City of Hope volunteers; n = 169). Patients found intrahepatic chemotherapy convenient but were unable to pursue vigorous activity, and their sleep habits changed. Psychologically, patients felt reassured to receive specific therapy to their liver.Pilot evaluation of QOL in this population revealed changes in physical, psychological, social, and spiritual dimensions. Both disease- and treatment-specific concerns were identified, and the results provide evidence for items to include in a QOL questionnaire specific to this population.

For periampullary cancer,intraoperative radiation therapy (IORT) administered to the site with the highest locoregional recurrence risk carries the rationale to improve tumor control. An IORT effect on survival remains unclear. IORT impact on postoperative outcomes after pancreatectomy for adenocarcinoma was analyzed, with a specific attempt to correct for the nonrandom IORT treatment assignment, and to account for treatment group imbalances in the interpretation of outcome differences. A propensity-score-adjusted analysis, based on variable selection by logistic regression, was used to rebalance treatments. Between 1989 and 1999, 61 patients underwent partial or total pancreatectomy for a primary periampullary adenocarcinoma at the City of Hope National Medical Center. Diagnoses included pancreatic (n = 36), duodenal (n = 11), ampullary (n = 10), and bile duct cancer (n = 4). Thirty patients received IORT to the resection area, with a median dose of 15 Gy (range: 10-20), followed by postoperative external beam radiation (n = 24). Mortality was 0%, the complication rate 61%. Of 33 patients with a documented recurrence, 6 had an isolated locoregional recurrence only (1 IORT versus 5 no IORT, = 0.05); the systemic recurrence pattern differed as well (IORT 94%, no IORT 67%; = 0.04). IORT had no significant impact on hospital stay (overall median: 17 days), disease-free survival (16 months), and overall survival (23 months) when adjusted for those most relevant variables reflecting IORT treatment group assignment propensity. After adjustment for relevant propensity factors, IORT was not linked to a significantly increased risk for complications, hospital stay, or survival hazard. The recurrence pattern may be affected in some patients, but systemic recurrences predominate. We continue to explore IORT in combination with systemic chemotherapy.

Background: We prospectively evaluated the effectiveness of major surgery in treating symptoms of advanced malignancies. Methods: Fifty-nine patients were evaluated for major symptoms of intent to treat and were followed up until death or last clinical evaluation. Surgeons identified planned operations before surgery as either curative or palliative and estimated patient survival time. An independent observer assessed symptom relief. A palliative surgery outcome score was determined for each symptomatic patient. Results: Surgeons identified 22 operations (37%) as palliative intent and 37 (63%) as curative intent. The median overall survival time was 14.9 months and did not differ between curative and palliative operations. Surgical morbidity was high but did not differ between palliative (41%) and curative (44%) operations. Thirty-three patients (56%) were symptomatic before surgery, and major symptom resolution was achieved after surgery in 26 (79%) of 33. Good to excellent palliation, defined as a palliative surgery outcome score >70, was achieved in 64% of symptomatic patients. Conclusions: Most symptomatic patients with advanced malignancies undergoing major operations attained good to excellent symptom relief. Outcome measurements other than survival are feasible and can better define the role of surgery in multimodality palliative care. A new outcome measure to evaluate major palliative operations is proposed.

Oxidation of 2-methoxy phenol derivatives in the presence of methanol provides dearomatized oxygenated intermediates.

The importance of visualizing and measuring cerebrospinal fluid flow dynamics of patients in the upright position is described. Recent observations from the FONAR Upright® Weight-Bearing Multi-Positio

Peak ground acceleration is a very important factor that must be considered in construction site for examining the potential damage resulting from earthquake. The actual records by seismometer at stations related to the site may be taken as a basis, but a reliable estimating method may be useful for providing more detailed information of the strong motion characteristics. Therefore, the purpose of this study was by using back-propagation neural networks to develop a model for estimating peak ground acceleration at two main line sections of Kaohsiung Mass Rapid Transit in Taiwan. Additionally, the microtremor measurements with Nakamura transformation technique were taken to further validate the estimations. Three neural networks models with different inputs including epicentral distance, focal depth and magnitude of the earthquake records were trained and the output results were compared with available nonlinear regression analysis. The comparisons exhibited that the present neural networks model did have a better performance than that of the other methods, as the calculation results were more reasonable and closer to the actual seismic records. Besides, the distributions of estimating peak ground acceleration from both of computations and measurements might provide valuable information from theoretical and practical standpoints.

purpose: Pain syndromes resulting from recurrent or metastatic cancer require careful evaluation to determine the cause of the pain and the appropriate and judicious use of antitumor treatment. The choice of therapy must integrate the type of pain, its function, the overall disease burden of the patient, and psychological aspects of the cancer. As a general rule, opioid analgesics are the mainstay of treatment in patients with cancer-related pain. When pharmacologic pain control is insufficient or is associated with intolerable side effects, the surgical management of pain can be considered. overview: In this article, we review the options, indications, and side effects of the interventional and surgical methods available for the treatment of cancer-related pain. clinical implications: Planning surgical treatment for cancer-related pain after a patient's lack of response to therapy with opioid analgesics requires an understanding of sensory innervation as well as a realistic expectation of survival, anesthetic risk, or possibility of incomplete pain relief. As such, surgical interventions must be tailored to the individual patient. Clinicians should keep in mind the surgical alternatives for the effective control of pain when it becomes apparent that medical therapy is ineffective.

Although most human cancers display a single histology, there are unusual cases where two or more distinct tissue types present within a primary tumor. One such example is metaplastic breast carcinoma. Metaplastic breast carcinoma is a rare but aggressive cancer with a heterogenous histology, including squamous, chondroid, and spindle cells. Metaplastic carcinomas often contain an admixed conventional ductal invasive or in situ mammary carcinoma component, and are typically triple-negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER-2) amplification/overexpression. An unanswered question is the origin of metaplastic breast cancers. While they may arise independently from their ductal components, their close juxtaposition favors a model that postulates a shared origin, either as two derivatives from the same primary cancer, or one histology as a clonal outgrowth of the other. Understanding the mechanism of development of these tumors may inform clinical decisions. We performed exome sequencing for paired metaplastic and adjacent conventional invasive ductal carcinomas in eight patients and created a pipeline to identify somatic variants and predict their functional impact in these samples, without having matched normal tissue. We then determined the genetic relationships between the histologically distinct compartments. In each case, the tumor components have nearly identical landscapes of somatic variation, implying that the differing histologies do not derive from genetic clonal divergence, suggesting that epigenetic or noncoding changes mediate the metaplastic phenotype. This indicates that alternative therapeutic approaches, including epigenetic therapies, may render metaplastic breast cancers susceptible to current and future therapies. Citation Format: Bracha E. Avigdor, Katie Beierl, Christopher D. Gocke, Daniel J. Zabransky, Karen Cravero, Kelly Kyker-Snowmana, Berry Button, David Chu, Sarah Croessmann, Rory L. Cochran, Roisin M. Connolly, Ben H. Park, Ashley Cimino-Mathews, Sarah J. Wheelan. Whole exome sequencing of metaplastic breast carcinoma indicates monoclonality with associated ductal carcinoma component [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-278. doi:10.1158/1538-7445.AM2017-LB-278

Background: Estrogen receptor alpha (ERα), encoded by the ESR1 gene, is expressed in approximately 70% of breast cancers. Recent studies conducted by us and others have shown that somatic mutations in ESR1 gene play a key role in conferring endocrine resistance in ER+ breast cancer. These hotspot mutations mainly occur on the ligand binding domain of ERα, leading to poor outcomes in 25-30% of patients with ER+ metastatic breast cancer in clinic. The mechanisms behind the potential enhanced metastasis of these mutations have become an urgent issue to be addressed, but they are not well understood due to a lack of ESR1 mutant models. Methods: We generated and characterized genome-edited T47D and MCF7 breast cancer cell lines with the two most common ESR1 mutations (Y537S and D538G), using CRIPSR/Cas9 and rAAV systems respectively. Multiple clones for each mutant were sorted and the mutation frequencies were detected using digital droplet PCR (ddPCR). We subsequently performed an RNA-sequencing to deeply differentiate the gene expression patterns in these mutants. The growth of these pooled mutant-cells was determined in both 2D and 3D plates. The cell-matrix adhesions were measured based on ECM array, and 84-ECM adhesion related genes were further tested by qPCR array. IncuCyte real-time image system was used to monitor the cell migration based on the wound-scratching assay. Results: We first identified the robust mutation frequencies at both RNA and DNA levels in our cell models. The RNA-seq exhibits multiple ligand-independent genes overlapping between either cell lines or mutants, which were further conformed by qPCR. We also found that both Y537S and D538G mutants present ligand-independent growth in 2D and 3D ultra-low attachment plates. Using wound-scratching assay, we observed significant higher migration rate in D538G mutant of T47D cell lines on both matrigel and type I collagen, indicating a cell-line and mutant-specific phenotype. We also detected lower attachment of both mutants on type I collagen in both cell lines, and our qPCR array revealed that alterations in the MMP pathways could be one of the major mechanism causing this phenotype. Conclusion: In sum, our study presents the first in-depth metastatic functional analysis of the biology of ESR1 mutations in genomic knock-in cell models, pointing out the enhanced migration and decreased cell-matrix adhesion as a potential novel gain-of-function of the Y537S and D538G mutant-cells. These findings suggest the potential role of enhanced metastasis of these ESR1 mutations through remodeling of transcriptional profiles, shedding lights towards the development of efficient therapies of ESR1 mutant breast cancer. Citation Format: Zheqi Li, Amir Bahreini, Peilu Wang, Kevin Levine, Nilgun Tasdemir, David Chu, Ben Ho Park, Adrian Lee, Steffi Oesterreich. ESR1 mutations confer novel metastatic functions in genome-edited breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1001. doi:10.1158/1538-7445.AM2017-1001

This paper presents a recognition scheme for fine-grain gestures. The scheme leverages directional antenna and short-range wireless propagation properties to recognize a vocabulary of action-oriented gestures from the American Sign Language. Since the scheme only relies on commonly available wireless features such as Received Signal Strength (RSS), signal phase differences, and frequency subband selection, it is readily deployable on commercial-off-the-shelf IEEE 802.11 devices. We have implemented the proposed scheme and evaluated it in two potential application scenarios: gesture-based electronic activation from wheelchair and gesture-based control of car infotainment system. The results show that the proposed scheme can correctly identify and classify up to 25 fine-grain gestures with an average accuracy of 92% for the first application scenario and 84% for the second scenario.

The PIK3CA gene encodes for the p110 alpha isoform of PI3 kinase and is one of the most frequently mutated oncogenes in human cancers. However, the mechanisms by which PIK3CA mutations activate cell signaling are not fully understood. Here we used a phosphoproteomic approach to compare differential phosphorylation patterns between human breast epithelial cells and two isogenic somatic cell knock in derivatives, each harboring a distinct PIK3CA mutation. We demonstrated differential phosphorylation patterns between isogenic cell lines containing a PIK3CA helical domain mutation (E545K) compared to cells with a PIK3CA kinase domain mutation (H1047R). In particular, the receptor tyrosine kinase, HER3, showed increased phosphorylation at tyrosine 1328 in H1047R cells versus E545K cells. Genetic studies using shRNA demonstrated that H1047R cells have a profound decrease in growth factor independent proliferation upon HER3 knock down, but this effect was attenuated in E545K cells. In addition, HER3 knock down led to reductions in both PI3 kinase and MAP kinase pathway activation in H1047R cells, but in E545K cells only PI3 kinase pathway diminution was observed. These studies demonstrate the power of using paired isogenic cell lines for proteomic analysis to gain new insights into oncogenic signal transduction pathways.

In this panel, the panel members will discuss future research trends in mobile augmented reality. In particular, we will focus on the design challenges of mobile augmented reality (MAR) platform e.g. real-time augmented reality that can help vulnerable populations; augmented reality in medical surgery and applications, and use of MAR in education. We will discuss research issues such as security and privacy of wearable devices like Google Glass, integration of multiple mobile applications within the MAR platform.

Playing games on mobile devices is very popular. Recently, cloud gaming – where datacenter servers execute the games on behalf of thin clients that merely transmit UI input events and display output rendered by the servers – has emerged as an interesting alternative to traditional clientside game execution. Cloud Gaming-as-a-Service (GaaS) offers several advantages salient to mobile clients. First, users with low end devices can get the same high quality experience as users with high end devices. Second, mobile game developers avoid two challenges that arise with the huge diversity of mobile devices: platform compatibility headaches and per-platform performance tuning. Third, upgrading servers (e.g., for bug fixes, game updates, etc.) becomes far easier than redeploying new software to clients. Finally, players can select from a vast library of games and instantly play any of them. However, GaaS on mobile devices faces a key technical dilemma: how can players attain real-time interactivity in the face of wide-area latency? Real-time interactivity means client input events should be quickly reflected on the client display. User studies have shown that players are sensitive to as little as 60 ms latency, and are aggravated at latencies in excess of 100 ms [1]. A further delay degradation from 150 ms to 250 ms lowers user engagement by 75% [2]. Instead, we propose to mitigate wide-area latency via speculative execution. We present DeLorean a system that delivers real-time gaming interactivity as fast as traditional local client-side execution, despite with network latencies. DeLorean’s basic approach combines input prediction with speculative execution to render mulitple possible frame outputs which could occur RTT milliseconds in the future. DeLorean employs the following techniques to accomplish this.

Loss-of-heterozygosity (LOH) analysis of archival tumor tissue can aid in determining the clinical significance of BRCA variants. Here we describe an approach for assessing LOH in formalin-fixed, paraffin-embedded (FFPE) tissues using variant-specific probes and droplet digital polymerase chain reaction (ddPCR). We evaluated LOH in 2 related breast cancer patients harboring a rare missense BRCA2 variant of unknown clinical significance (c.6966G>T; M2322I). Conventional PCR followed by Sanger sequencing suggested a change in allelic abundance in the FFPE specimens. However, we found no evidence of LOH as determined by the allelic ratio (wild type-variant) for BRCA2 in both patients' archival tumor specimens and adjacent normal control tissues using ddPCR. In summary, these experiments demonstrate the utility of ddPCR to quickly and accurately assess LOH in archival FFPE tumor tissue.

Background:Malignant bowel obstruction (MBO) secondary to peritoneal carcinomatosis carries a grave prognosis. We evaluated clinicopathologic factors that predict outcomes after palliative operations for MBO. Methods:Data on patients undergoing laparotomy for palliation of gastrointestinal MBO at City of Hope between 1995 and 2000 were retrospectively collected. Successful palliation was defined as the ability to tolerate solid food (TSF). Results:Sixty-three patients underwent operative treatment. In 20 patients, MBO was the first presentation of disease; for others, the median disease-free interval was 15 months. The complication rate was 44%, and postoperative mortality was 15%. The median length of stay was 12 days. Twenty-nine patients (45%) were discharged from the hospital on a regular diet; 22 (76%) continued to eat until their last follow-up. Median survival was 90 days. Univariate factors for longer survival were TSF on discharge, colorectal primary, and nonmetastatic status at first diagnosis. Patients with ascites and whose cancer first presented with MBO had an inferior survival. Noncolorectal primary remained a multivariate predictor for decreased survival. TSF was predicted by the absence of ascites, an obstruction not involving the small bowel, and a preoperative albumin of >3.0 mg/dl. Multiple logistic regression analysis yielded presence of ascites and small-bowel obstruction as predictors of inability to TSF. Conclusions:Only one third of patients with MBO from peritoneal carcinomatosis will have prolonged postoperative palliation with significant, but acceptable, treatment-related morbidity. TSF at discharge is a useful predictor of continued palliation for most patients. Patients with colorectal cancer may have superior survival outcome and better palliation; others are at risk for poor outcomes, especially in the presence of ascites and MBO of small bowel. In these patients, highly selective use of laparotomy is recommended.

Background: Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral prophylactic mastectomy (CPM) at the time of unilateral mastectomy for breast cancer. The purpose of this study is to evaluate the efficacy of CPM in preventing CBC. Methods: sixty-four patients undergoing CPM and a control group of 182 patients not undergoing CPM and matched for age, stage, surgery, chemotherapy, and hormonal therapy were retrospectively compared for CBC rate, disease-free survival, and overall survival. Results: Thirty-six CBCs occurred in the control group. In the CPM group, 3 CBCs were found at the time of prophylactic mastectomy, but none occurred subsequently (P = 0.005). Disease-free survival at 15 years in the CPM group was 55% (95% confidence interval [CI] 38% to 69%) versus 28% (95% CI 19% to 36%) in the control group (P = 0.01). Overall survival at 15 years was 64% (95% CI 45% to 78%) CPM versus 48% (95% CI 39% to 58%) in controls (P = 0.26). Conclusions: CPM prevented CBC and significantly prolonged disease-free survival. Future studies will need to address risk assessment and contralateral breast cancer prevention in patients treated for early breast cancer.

Background: Because inflammatory breast cancer (IBC) has been viewed as a malignancy with a poor likelihood of longterm survival, few women have been offered esthetic reconstruction after mastectomy for IBC. Recent advances in multimodality therapy have improved the outcomes for women with this disease. The purpose of this review was to assess the results of esthetic breast reconstruction in the population with IBC. Study Design: Review of medical records at the City of Hope National Medical Center for the 10-year period ending in May 1997, revealed 23 women who underwent elective esthetic breast reconstruction after mastectomy for IBC. The records of these patients were reviewed retrospectively. Patients requiring reconstruction for large surgical chest wall defects were not included in the review. Results: Treatment for IBC included mastectomy in all patients, chemotherapy in 22, and chest wall radiation therapy in 14. Immediate reconstruction was performed at the time of mastectomy (n = 14) or was delayed (n = 9). The types of reconstruction included transverse rectus abdominis musculocutaneous flap (n = 18), latissimus dorsi flap (n = 2), or prosthetic mammary implant reconstruction (n = 3). Seven women chose to undergo additional reconstruction procedures (ie, nipple reconstruction) after their initial reconstruction. With a median followup of 44 months for survivors, 16 patients developed recurrence after reconstruction. Of these, 6 were local recurrences and 10 were distant failures. Seven patients are currently alive with no evidence of disease, 4 are currently alive with disease, and 12 have died as a result of breast cancer. The median disease-free survival after reconstruction was 19 months. The median overall survival after reconstruction for all patients was 22 months. The only negative predictor of survival was a positive surgical margin at mastectomy. Conclusions: The significant emotional and esthetic benefits of breast reconstruction should be available to women with IBC. In light of the improving prognosis of IBC with current aggressive multimodality treatment, reconstructive procedures should be offered as part of comprehensive therapy.

Inflammatory breast cancer is a locally advanced tumor with an aggressive local and systemic course. Treatment of this disease has been evolving over the last several decades. The aim of this study was to assess whether current therapies, both surgical and chemotherapeutic, are providing better local control (LC) and overall survival (OS). We also attempted to identify clinical and pathologic factors that may be associated with improved OS, disease-free survival (DFS), and LC.A 25-year retrospective review performed at the City of Hope National Medical Center identified 90 patients with the diagnosis of inflammatory breast cancer.Of the 90 patients identified with inflammatory breast cancer, 33 received neoadjuvant therapy (NEO) consisting of chemotherapy followed by surgery with radiation (n = 26) and without radiation (n = 7). Fifty-seven patients received other therapies (nonNEO). Treatments received by the nonNEO group consisted of chemotherapy, radiation, mastectomy, adrenalectomy, and oophorectomy, alone or in combination. The median follow-up was 28.9 months for the NEO group and 17.6 months for the nonNEO group. Borderline significant differences in the OS distributions between the two groups were found (P = .10), with 3- and 5-year OS for the NEO group of 40.0% and 29.9% and for the nonNEO group of 24.7% and 16.5%, respectively. DFS and LC were comparable in the two groups. Lower stage was associated with an improved OS (P.05). The 5-year OS for stage IIIB was 30.9%, compared to 7.8% for stage IV. In those patients with stage III disease who were treated with mastectomy and rendered free of disease, margin status was identified by univariate analysis to be a prognostic indicator for OS (P.05). The 3-year OS, DFS, and LC for patients with negative margins were 47.4%, 37.5%, and 60.3%, respectively, compared to 0%, 16.7%, and 31.3% in patients with positive margins.This study suggests that in patients with inflammatory breast cancer and nonmetastatic disease, an aggressive surgical approach may be justified with the goal of a negative surgical margin. Achievement of this local control is associated with a better overall outcome for this subset of patients. The ability to obtain negative margins may further identify a group of patients with a less aggressive tumor biology that may be more responsive to other modalities of therapy.

A 41 year old female with type I cryoglobulinemia, refractory to methylprednisolone, rituximab, and cyclophosphamide complicated by a rising serum viscosity was treated with alemtuzumab. After a cumulative dose of 1,085 mg of alemtuzumab, her serum viscosity decreased to normal. Treatment toxicity was limited to fungal esophagitis responsive to topical therapy. This case demonstrates the potential use of alemtuzumab in the treatment of refractory cryoglobulinemia.

Location is a core component of today's mobile devices and apps. While GPS is widely used, it continues to perform poorly when satellite visibility is obscured, e.g. in urban canyons. This paper explores the potential benefits of cloud- and crowd-assisted GPS for tackling urban canyons. Specifically, we present early results on utilizing high resolution environment scans such as Digital Surface Models (DSMs) to aid GPS calculations. Second, we suggest initial designs for leveraging location corrections from other mobile device users to enhance noisy GPS readings.

This paper investigates the development of accurate and efficient classifiers to identify misbehaving users (i.e., "flashers") in a mobile video chat application. Our analysis is based on video session data collected from a mobile client that we built that connects to a popular random video chat service. We show that prior image-based classifiers designed for identifying normal and misbehaving users in online video chat systems perform poorly on mobile video chat data. We present an enhanced image-based classifier that improves classification performance on mobile data. More importantly, we demonstrate that incorporating multi-modal mobile sensor data from accelerometer and the camera state (front/back) along with audio can significantly improve the overall image-based classification accuracy. Our work also shows that leveraging multiple image-based predictions within a session (i.e., temporal modality) has the potential to further improve the classification performance. Finally, we show that the cost of classification in terms of running time can be significantly reduced by employing a multilevel cascaded classifier in which high-complexity features and further image-based predictions are not generated unless needed.

Online video chat services such as Chatroulette and Omegle randomly match users in video chat sessions and have become increasingly popular, with tens of thousands of users online at anytime during a day. Our interest is in examining user behavior in the growing domain of mobile video, and in particular how users behave in such video chat services as they are extended onto mobile clients. To date, over four thousand people have downloaded and used our Android-based mobile client, which was developed to be compatible with an existing video chat service. The paper provides a first-ever detailed large scale study of mobile user behavior in a random video chat service over a three week period. This study identifies major characteristics such as mobile user session durations, time of use, demographic distribution and the large number of brief sessions that users click through to find good matches. Through content analysis of video and audio, as well as analysis of texting and clicking behavior, we discover key correlations among these characteristics, e.g., normal mobile users are highly correlated with using the front camera and with the presence of a face, whereas misbehaving mobile users have a high negative correlation with the presence of a face.

Surgical oncology as a distinct field of expertise is fairly young. The current study was designed to gain a better understanding of the attitude of practicing physicians toward the field of surgical oncology.Three hundred twenty-seven physicians in the San Gabriel Valley (a suburban area adjacent to Los Angeles) responded to an anonymous survey of opinions regarding surgical oncology. Responses were placed into a computerized database.Of those responding, 179 were primary care physicians, 52 were general surgeons, 78 were gynecologists, and 18 were medical oncologists. Overall, 89% of physicians were familiar with the field of surgical oncology, but only 47% had ever heard of The Society of Surgical Oncology (SSO). Ninety-four percent of the respondents felt that a surgical oncologist should care for patients with complex cancer, and 63% of respondents felt that surgical oncologists should care only for patients with complex cancer. Familiarity with the field of surgical oncology and with the SSO correlated with the percentage of the physicians practice that was cancer related. Only 22% of physicians felt that the field of surgical oncology is redundant to the general surgical specialties.Results of the survey indicate that there is considerable recognition of the unique expertise of the surgical oncologist by the medical community. Unfortunately, many physicians are not familiar with the SSO. Educating physicians in the community about the SSO may help to further expand the role of the surgical oncologist in the care of the patient with cancer, standardize the expectations of the skills and training of a surgical oncologist, and set a benchmark for the surgical subspecialty.

e18231Background: CINV is among the most debilitating and feared consequences of cancer treatment. It is therefore imperative to determine if patients are achieving similar response rates in practice as demonstrated in trials. This study evaluated the real world effectiveness of palonosetron, an NK-1 inhibitor, and dexamethasone in patients receiving HEC for prevention of CINV according to international antiemetic guidelines (ASCO, MASCC, NCCN). Methods: A phase IV prospective, multi-center observational study was conducted in which 107 patients were enrolled and treated in accordance with standard of care. All medications were commercially available and the decision to treat was made by the primary physician prior to and independent of participation in the study. The primary outcome for analysis was complete response (CR) defined as no emetic episodes and no use of rescue medication for CINV. CR was classified as acute- (0-24 hours), delayed-phase ( > 24-120 hours), and overall (0-120 hours). Nausea, vom...

The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.

Face recognition has many challenges. For instance, the illumination, various facial expression and different viewpoints add difficulties to identify the same person from a bunch of images. Searching over a huge set of images will only amplify such difficulties. We introduce the location aware face recognition framework for mobile-taken photos to alleviate the hardness. With the help of location sensor on the mobile devices, we collect images with location information. We propose an algorithm to reduce the search space of face recognition and therefore achieve better accuracy. Photos are clustered by locations on the server. Each location is then associated with a face classifier. Every client can send a "Who is Here" type query to the server by uploading an image with the location. The algorithm on the server will search over the given location and identify the person on the image. Experiments are conducted on mobile devices. The results are quite promising that higher accuracy is achieved and the query can be answered in near real-time.

A growing number of mobile apps are exploiting smartphone sensors to infer user behavior, activity, or context. Inference requires training using labeled ground truth data. Obtaining labeled data for new apps is a "chicken-egg" problem. Without a reasonable amount of labeled data, apps cannot provide any service. But until an app provides useful service it is not worth installing and has no opportunity to collect user data. This paper aims to address this problem. Our intuition is that even though users are different, they exhibit similar patterns on certain sensing dimensions. For instance, different users may walk and drive at different speeds, but certain speeds will indicate driving for all users. These common patterns could be used as "seeds" to model new users through semi-supervised learning. We prototype a technique to automatically extract the commonalities to seed personalized inference models for new users. We evaluate the proposed technique through example apps and real world data.

Many context aware applications can benefit from using high-level sensing results with semantic meanings (e.g, busy/idle). This paper proposes a platform design that provides high-level "virtual sensor" abstractions and enables new virtual sensors to be bootstrapped from existing ones.

As mobile apps become more closely integrated into our everyday lives, mobile app interactions ought to be rapid and responsive. Unfortunately, even the basic primitive of launching a mobile app is sorrowfully sluggish: 20 seconds of delay is not uncommon even for very popular apps.We have designed and built FALCON to remedy slow app launch. FALCON uses contexts such as user location and temporal access patterns to predict app launches before they occur. FALCON then provides systems support for effective app-specific prelaunching, which can dramatically reduce perceived delay.FALCON uses novel features derived through extensive data analysis, and a novel cost-benefit learning algorithm that has strong predictive performance and low runtime overhead. Trace-based analysis shows that an average user saves around 6 seconds per app startup time with daily energy cost of no more than 2% battery life, and on average gets content that is only 3 minutes old at launch without needing to wait for content to update. FALCON is implemented as an OS modification to the Windows Phone OS.