Richard J Bold

University of California, Davis, Davis, California, United States

Are you Richard J Bold?

Claim your profile

Publications (158)550.33 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Pancreatic ductal adenocarcinoma has proven to be one of the most chemo-resistant among all solid organ malignancies. Several mechanisms of resistance have been described, though few reports of strategies to overcome this chemo-resistance have been successful in restoring sensitivity to the primary chemotherapy (gemcitabine) and enter the clinical treatment arena.Methods We examined the ability of cellular arginine depletion through treatment with PEG-ADI to alter in vitro and in vivo cytotoxicity of gemcitabine. The effect on levels of key regulators of gemcitabine efficacy (e.g. RRM2, hENT1, and dCK) were examined.ResultsCombination of PEG-ADI and gemcitabine substantially increases growth arrest, leading to increased tumor response in vivo. PEG-ADI is a strong inhibitor of the gemcitabine-induced overexpression of ribonucleotide reductase subunit M2 (RRM2) levels both in vivo and in vitro, which is associated with gemcitabine resistance. This mechanism is through the abrogation of the gemcitabine-mediated inhibitory effect on E2F-1 function, a transcriptional repressor of RRM2.Conclusion The ability to alter gemcitabine resistance in a targeted manner by inducing metabolic stress holds great promise in the treatment of advanced pancreatic cancer.
    Journal of experimental & clinical cancer research : CR. 12/2014; 33(1):102.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate readmission rates and associated factors to identify potentially preventable readmissions.
    Annals of surgery. 10/2014; 260(4):583-591.
  • Erin G. Brown, Robert J. Canter, Richard J. Bold
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objectives Serial levels of CA 19-9 are correlated with treatment response and survival; however, little is known about CA 19-9 kinetics in the absence of therapy. We hypothesize that preoperative CA 19-9 kinetics predict rate of resectability as well as survival.Methods Retrospective review of 72 patients with radiographically resectable pancreatic adenocarcinoma with two pre-operative CA 19-9 levels prior to planned pancreaticoduodenectomy. Primary outcome measures were resectability and overall survival.ResultsForty-seven out of 72 patients (65%) had resectable disease. Unresectable patients had higher absolute change in CA 19-9 than patients with resectable disease (97 U/ml vs. −34 U/ml) as well as higher rate of change (4 U/ml/day vs. −1 U/ml/day). Receiver operating characteristic curves identified predictive thresholds for absolute (≥50 U/ml) and rate of CA 19-9 change (≥1 U/ml/day) that accurately identified unresectable patients. Survival analysis revealed that a change in CA 19-9 <50 U/ml and a rate of change <1 U/ml/day predicted improved survival (P = 0.04, P = 0.02); however, for patients with resectable disease, CA 19-9 changes did not predict survival.Conclusions Preoperative kinetics of CA 19-9 predict resectable disease for pancreatic cancer. These variables also predict overall survival; however, these do not predict survival for those with resectable disease. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 10/2014; · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Practice patterns vary with the planning and delivery of post mastectomy radiation therapy (PMRT). Our investigation examines practice patterns in the use of chest wall bolus and a boost among the Athena Breast Health Network (“Athena”). Methods Athena is a collaboration among the five University of California Medical Centers that aims to integrate clinical care and research [1]. From February 2011 to June 2011, all physicians specializing in the multidisciplinary treatment of breast cancer were invited to take a web-based practice patterns survey. Sixty-two of the 239 questions focused on radiation therapy practice environment, decision making processes, and treatment management, including the use of a bolus or boost in PMRT. Results Ninety-two percent of the radiation oncologists specializing in breast cancer completed the survey. All of the responders use a material to increase the surface dose to the chest wall during PMRT. Materials used included brass mesh, commercial bolus, and custom designed wax bolus. Fifty percent used tissue equivalent superflab bolus. Fifty-five percent of the respondents routinely use a boost to the chest wall in PMRT. Eighteen percent give a boost depending on the margin status, and 3/11 (27%) do not use a boost. Conclusions Our investigation documents practice pattern variation for the use of a PMRT boost and the use of chest wall bolus among the University of California breast cancer radiation oncologists. Further understanding of the practice pattern variation will help guide clinicians in our cancer centers to a more uniform approach in the delivery of PMRT.
    Clinical Breast Cancer 08/2014; · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone-associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments.
    Proceedings of the National Academy of Sciences 08/2014; · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The relationship between procedural relative value units (RVUs) for surgical procedures and other measures of surgeon effort are poorly characterized. We hypothesized that RVUs would poorly correlate with quantifiable metrics of surgeon effort.
    Journal of Surgical Research 05/2014; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Changes in health care reimbursement policy have led to an era in which hospitals are motivated to improve quality of care while simultaneously reducing costs. Research demonstrating the most efficient means to target costs may have a positive effect on patient quality of life and the overburdened health care system. OBJECTIVE To evaluate the effect of hospital length of stay (LOS) and the occurrence of postoperative complications on total charges in patients undergoing elective pancreaticoduodenectomy. DESIGN, SETTING, AND PATIENTS We performed a retrospective review of 89 cases identified in an institutional database of patients who underwent elective pancreaticoduodenectomy at an academic tertiary care center from December 1, 2007, through May 31, 2012. MAIN OUTCOMES AND MEASURES Occurrence of postoperative and inpatient complications, LOS, incidence of readmission within 60 days of discharge, and hospital charges from initial postoperative hospitalization. Linear regression analysis was performed comparing LOS with hospital charges. RESULTS Thirty-four of 89 patients (38%) developed postoperative complications. Mean and median LOSs were 12 and 8 days, respectively. The LOS was significantly related to postoperative complications. Of the 34 patients who developed complications, the mean LOS was 19 days compared with 7 days for those patients not developing complications (P < .001). Only 2 of 55 patients (4%) without complications were readmitted to the hospital, whereas 13 of 34 patients (38%) with complications required readmission. Perioperative hospital charges were significantly related to LOS (R2 = 0.840, R = 0.917). For those patients without complications, linear regression demonstrated a daily hospital charge of $11 612 (R2 = 0.923, R = 0.961). However, for those patients with complications, the optimal relationship between LOS and hospital charges was exponential (R2 = 0.832). CONCLUSIONS AND RELEVANCE Prolonged LOS is associated with increased total charges, but given the exponential increase in charges, the complication itself has an effect on increased charges above and beyond that of a prolonged hospitalization. The drive to reduce LOS after pancreaticoduodenectomy has minimal effect on overall charges to the patient. Efforts should be directed instead at reducing complications because this has a much more significant effect on financial outcomes.
    JAMA surgery. 05/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective This study aims to estimate and test temporal differences in mental health (MH) need and service use among adult cancer survivors nationally before and after important policy recommendations for psychosocial cancer care.Methods Adults (n = 58,585) from the National Health Interview Survey, 2005 and 2010, were categorized as having (1) no chronic disease, (2) chronic disease other than cancer, (3) cancer without other chronic disease, and (4) cancer with other chronic disease. In these groups, we compared psychological distress, MH visits, and unmet need for MH services. Survey-weighted logistic regression was used to model these variables as functions of disease status and sociodemographic covariates and the interactions of disease status and survey year.ResultsWhereas the proportion of individuals with psychological distress and MH visits was significantly higher in 2010 versus 2005 for the no chronic disease group, the only group with significantly lower unmet need in 2010 versus 2005 was the cancer with other chronic disease group (5.3% vs. 3.0%, p < 0.05). In adjusted models, cancer survivors with other chronic disease had significantly lower odds of unmet need in 2010 (odds ratio 1.38; 95% confidence interval 0.85, 2.25) than in 2005 (odds ratio 3.32; 95% confidence interval 2.28, 4.83).Conclusions We find evidence of MH care quality improvement among cancer survivors between 2005 and 2010, a period that coincides with policy and clinical attention to psychosocial cancer care. These efforts may have reduced, but not eliminated, unmet need for MH services among cancer survivors. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 05/2014; · 3.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aim: The Akt signaling pathway mediates a potent anti-apoptotic signal in pancreatic cancer and inhibition of this pathway has become an attractive mechanism to increase the efficacy of traditional chemotherapies. Autophagy is a lysosomal catabolic pathway by which eukaryotic cells recycle macromolecules and organelles. Although autophagy may function as a survival mechanism under metabolic stress conditions, it also serves as an alternate route to programmed cell death distinct from apoptosis. In the present study, we examined the role of autophagy in Akt-mediated regulation of cell death in pancreatic cancer. Mia-PaCa-2 and PANC-1 human pancreatic cancer cell lines were used in our experiments. The small-molecule inhibitor A-443654 was used to inhibit Akt, and rapamycin was used to inhibit mTOR. Autophagy was inhibited with Chloroquine and 3-methyladenine. Autophagy was assessed by immunoblotting for light chain-3 (LC-3) processing as well as fluorescence microscopy for autophagosome formation following transfection with a LC-3/GFP construct. Cell death was determined by fluorescence-activated cell sorting (FACS) with quantitation of the sub-G0 content. Inhibition of either Akt or mTOR induced autophagy; inhibition of Akt but not of mTOR led to traditional caspase-mediated apoptosis. When autophagy was inhibited, cell death was abrogated following Akt, but not mTOR, inhibition. The Akt signaling pathway regulates both autophagy and apoptosis through divergent pathways; mTOR mediates autophagy signaling but appears to be un-involved in cell death. Autophagy appears to play a role in the regulation of cell survival by Akt, but only when proximal signaling pathways not involving mTOR are simultaneously activated.
    Anticancer research 02/2014; 34(2):631-7. · 1.71 Impact Factor
  • Clinical Breast Cancer 10/2013; · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the modern era of esophagectomy, we hypothesized that perioperative morbidity and mortality from cervical or thoracic sites of anastomoses would not be different. We used the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who underwent esophagectomy for lower esophageal or gastroesophageal (GE) junction malignancies from 2005 to 2010. Patients were categorized as having either a cervical or thoracic anastomosis based on CPT codes. There were 601 (66%) cervical and 308 (34%) thoracic anastomoses. Cervical anastomoses were associated with greater than 2 units of blood transfusion in a higher proportion of patients (10% vs. 3%, P = 0.001), and higher superficial surgical site infections (13% vs. 7%, P = 0.003). There were no difference in rates of organ/space infections (6% vs. 7%, P = 0.70), overall morbidity (38% vs. 39%, P = 0.84), or mortality (3% vs. 4%, P = 0.34). Median length of stay was similar (11.5 days cervical vs. 11 days thoracic, P = 0.89), even among patients with organ/space infections (18 days cervical vs. 21 days thoracic, P = 0.49). On multivariate analysis thoracic anastomosis was not a significant predictor of increased overall morbidity (OR 1.13: 95%CI 0.83-1.54). After esophagectomy, the site of anastomosis does not predict an increased risk of perioperative morbidity or mortality. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 09/2013; · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We sought to characterize the extent of extremity soft tissue tumor (ESTT) resections among surgical specialties, hypothesizing that substantial variation exists in the number of ESTT resections performed by specialty. We queried the UHC-AAMC database for data from 85 institutions for years 2007-2009. We abstracted data on total number of musculoskeletal (MSK) procedures, number of subcutaneous (SQ), deep, and malignant ESTT resections, and anatomic site of resection. Data were available for 4,682 practitioners including the following specialties: general surgery (GS, N = 2,195), plastic surgery (PS, N = 792), surgical oncology (SO, N = 533), general orthopedics (GO, N = 1,079), and orthopedic oncology (OO, N = 83). The mean number of all MSK procedures performed per year was 19.0 ± 2.3 GS, 179.6 ± 3.0 PS, 32.4 ± 6.2 SO, 798.6 ± 115.4 GO, and 482.9 ± 6.5 OO (P = 0.001). SQ ESTT resections per year were similar among specialties (1.7 ± 0.3 GS, 2.7 ± 0.3 PS, 2.4 ± 0.4 SO, 1.7 ± 0.5 GO, 4.7 ± 0.2 OO), while deep and malignant resections were more likely performed by OO (combined deep and malignant: 0.9 ± 0.1 GS, 2.0 ± 0.4 PS, 9.9 ± 0.6 SO, 5.8 ± 0.3 GO, and 63.6 ± 8.1 OO, P = 0.001). Adjusting for number of physicians in the database, of the total deep and malignant ESTT resections, 9.4% were performed by GS, 7.7% by PS, 26.0% by SO, 30.8% by GO, and 26.0% by OO. Nearly 50% of deep and malignant ESTT resections are performed by non-oncology-designated surgeons. Approximately 17% are performed by practitioners who complete an average of one to two of these procedures per year. These findings may have significant implications for quality of care in soft tissue tumor surgery. J. Surg. Oncol. 2013; 108:142-147. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 09/2013; 108(3):142-7. · 2.64 Impact Factor
  • Source
    Richard J Bold
    Annals of Surgical Oncology 04/2013; · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND DATA: Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established. AIMS: To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases. METHODS: 84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors. RESULTS: Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm(2) was an independent predictor for NSLN metastases and extranodal disease. CONCLUSION: Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 03/2013; · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy is an intracellular recycling mechanism that helps cells to survive against environmental stress and nutritional starvation. We have recently shown that prostate cancers undergo metabolic stress and caspase-independent cell death following exposure to arginine deiminase (ADI, an enzyme that degrades arginine in tissue). The aims of our current investigation into the application of ADI as a novel cancer therapy are to identify the components mediating tumor cell death, and to determine the role of autophagy (stimulated by ADI and/or rapamycin) on cell death. Using advanced fluorescence microscopy techniques including 3D deconvolution and superresolution structured-illumination microscopy (SIM), we show that prostate tumor cells that are killed after exposure to ADI for extended periods, exhibit a morphology that is distinct from caspase-dependent apoptosis; and that autophagosomes forming as a result of ADI stimulation contain DAPI-stained nuclear material. Fluorescence imaging (as well as cryo-electron microscopy) show a breakdown of both the inner and outer nuclear membranes at the interface between the cell nucleus and aggregated autophagolysosomes. Finally, the addition of N-acetyl cysteine (or NAC, a scavenger for reactive oxygen species) effectively abolishes the appearance of autophagolysosomes containing nuclear material. We hope to continue this research to understand the processes that govern the survival or death of these tumor cells, in order to develop methods to improve the efficacy of cancer pharmacotherapy.
    Proc SPIE 02/2013;
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: There are conflicting data regarding improvements in postoperative outcomes with perioperative epidural analgesia. We sought to examine the effect of perioperative epidural analgesia vs. intravenous narcotic analgesia on perioperative outcomes including pain control, morbidity, and mortality in patients undergoing gastric and pancreatic resections. METHODS: We evaluated 169 patients from 2007 to 2011 who underwent open gastric and pancreatic resections for malignancy at a university medical center. Emergency, traumatic, pediatric, enucleations, and disseminated cancer cases were excluded. Clinicopathologic data were reviewed among epidural (E) and non-epidural (NE) patients for their association with perioperative endpoints. RESULTS: One hundred twenty patients (71 %) received an epidural and 49 (29 %) did not. There were no significant differences (P > 0.05) in mean pain scores at each of the four days (days 0-3) among the E (3.2 ± 2.7, 3.2 ± 2.3, 2.3 ± 1.9, and 2.1 ± 1.9, respectively) and NE patients (3.7 ± 2.7, 3.4 ± 1.9, 2.9 ± 2.1, and 2.4 ± 1.9, respectively). Within each of the E and NE patient groups, there were significant differences (P < 0.0001) in mean pain scores from day 0 to day 3 (P < 0.0001). Of the E patients, 69 % also received intravenous patient-controlled analgesia (PCA). Ileus (13 % E vs. 8 % NE), pneumonia (12 % E vs. 8 % NE), venous thromboembolism (6 % E vs. 4 % NE), length of stay [11.0 ± 12.1 (8, 4-107) E vs. 12.2 ± 10.7 (7, 3-54) NE], overall morbidity (36 % E vs. 39 % NE), and mortality (4 % E vs. 2 % NE) were not significantly different. CONCLUSIONS: Routine use of epidurals in this group of patients does not appear to be superior to PCA.
    Journal of Gastrointestinal Surgery 01/2013; · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Postoperative venous thromboembolism (VTE) is increasingly viewed as a quality of care metric, although risk-adjusted incident rates of postoperative VTE and VTE after hospital discharge (VTEDC) are not available. We sought to characterize the predictors of VTE and VTEDC to develop nomograms to estimate individual risk of VTE and VTEDC. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified 471,867 patients who underwent inpatient abdominal or thoracic operations between 2005 and 2010. We excluded primary vascular and spine operations. We built logistic regression models using stepwise model selection and constructed nomograms for VTE and VTEDC with statistically significant covariates. RESULTS: The overall, unadjusted, 30-d incidence of VTE and VTEDC was 1.5% and 0.5%, respectively. Annual incidence rates remained unchanged over the study period. On multivariate analysis, age, body mass index, presence of preoperative infection, operation for cancer, procedure type (spleen highest), multivisceral resection, and non-bariatric laparoscopic surgery were significant predictors for VTE and VTEDC. Other significant predictors for VTE, but not VTEDC, included a history of chronic obstructive pulmonary disease, disseminated cancer, and emergent operation. We constructed and validated nomograms by bootstrapping. The concordance indices for VTE and VTEDC were 0.77 and 0.67, respectively. CONCLUSIONS: Substantial variation exists in the incidence of VTE and VTEDC, depending on patient and procedural factors. We constructed nomograms to predict individual risk of 30-d VTE and VTEDC. These may allow more targeted quality improvement interventions to reduce VTE and VTEDC in high-risk general and thoracic surgery patients.
    Journal of Surgical Research 01/2013; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is little information about the use of text messaging (texting) devices among resident and faculty physicians for patient-related care (PRC). To determine the prevalence, frequency, purpose, and concerns regarding texting among resident and attending surgeons and to identify factors associated with PRC texting. E-mail survey. University medical center and its affiliated hospitals. Surgery resident and attending staff. Prevalence, frequency, purpose, and concerns regarding patient-related care text messaging. Overall, 73 (65%) surveyed physicians responded, including 45 resident (66%) and 28 attending surgeons (62%). All respondents owned a texting device. Majority of surgery residents (88%) and attendings (71%) texted residents, whereas only 59% of residents and 65% of attendings texted other faculty. Most resident to resident text occurred at a frequency of 3-5 times/d (43%) compared with most attending to resident texts, which occurred 1-2 times/d (33%). Most resident to attending (25%) and attending to attending (30%) texts occurred 1-2 times/d. Among those that texted, PRC was the most frequently reported purpose for resident to resident (46%), resident to attending (64%), attending to resident (82%), and attending to other attending staff (60%) texting. Texting was the most preferred method to communicate about routine PRC (47% of residents vs 44% of attendings). Age (OR: 0.86, 95% CI: 0.79-0.95; p = 0.003), but not sex, specialty/clinical rotation, academic rank, or postgraduate year (PGY) level predicted PRC texting. Most resident and attending staff surveyed utilize texting, mostly for PRC. Texting was preferred for communicating routine PRC information. Our data may facilitate the development of guidelines for the appropriate use of PRC texting.
    Journal of Surgical Education 01/2013; 70(6):826-834. · 1.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer is the leading form of malignancies among men in the U.S. While surgery carries a significant risk of impotence and incontinence, traditional chemotherapeutic approaches have been largely unsuccessful. Hormone therapy is effective at early stage, but often fails with the eventual development of hormone-refractory tumors. We have been interested in developing therapeutics targeting specific metabolic deficiency of tumor cells. We recently showed that prostate tumor cells specifically lack an enzyme (argininosuccinate synthase, or ASS) involved in the synthesis of the amino acid arginine(1). This condition causes the tumor cells to become dependent on exogenous arginine, and they undergo metabolic stress when free arginine is depleted by arginine deiminase (ADI)(1,10). Indeed, we have shown that human prostate cancer cells CWR22Rv1 are effectively killed by ADI with caspase-independent apoptosis and aggressive autophagy (or macroautophagy)(1,2,3). Autophagy is an evolutionarily-conserved process that allows cells to metabolize unwanted proteins by lysosomal breakdown during nutritional starvation(4,5). Although the essential components of this pathway are well-characterized(6,7,8,9), many aspects of the molecular mechanism are still unclear - in particular, what is the role of autophagy in the death-response of prostate cancer cells after ADI treatment? In order to address this question, we required an experimental method to measure the level and extent of autophagic response in cells - and since there are no known molecular markers that can accurately track this process, we chose to develop an imaging-based approach, using quantitative 3D fluorescence microscopy(11,12). Using CWR22Rv1 cells specifically-labeled with fluorescent probes for autophagosomes and lysosomes, we show that 3D image stacks acquired with either widefield deconvolution microscopy (and later, with super-resolution, structured-illumination microscopy) can clearly capture the early stages of autophagy induction. With commercially available digital image analysis applications, we can readily obtain statistical information about autophagosome and lysosome number, size, distribution, and degree of colocalization from any imaged cell. This information allows us to precisely track the progress of autophagy in living cells and enables our continued investigation into the role of autophagy in cancer chemotherapy.
    Journal of Visualized Experiments 01/2013;
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Current guidelines suggest consideration of sentinel lymph node biopsy (SLNB) for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy. Our objective was to identify factors influencing the utilization of SLNB in this population. METHODS: We used the Surveillance Epidemiology and End Results database to identify all women with breast DCIS treated with mastectomy from 2000 to 2008. We excluded patients without histologic confirmation, those diagnosed at autopsy, those who had axillary lymph node dissections performed without a preceding SLNB, and those for whom the status of SLNB was unknown. We used multivariate logistic regression reporting odds ratios (OR) and 95 % confidence intervals (CI) to evaluate the relationship of patient- and tumor-related factors to the likelihood of undergoing SLNB. RESULTS: Of 20,177 patients, 51 % did not receive SLNB. Factors associated with a decreased likelihood of receiving a SLNB included advancing age (OR 0.66; 95 % CI 0.62-0.71), Asian (OR 0.75; CI 0.68-0.83) or Hispanic (OR 0.84; 95 % CI 0.74-0.96) race/ethnicity, and history of prior non-breast (OR 0.57; 95 % CI 0.53-0.61). Factors associated with an increased likelihood of receiving a SLNB included treatment in the east (OR 1.28; 95 % CI 1.17-1.4), intermediate (OR 1.25; 95 % CI 1.11-1.41), high (OR 1.84; 95 % CI 1.62-2.08) grade tumors, treatment after the year 2000, and DCIS size 2-5 cm (OR 1.54; 95 % CI 1.42-1.68) and >5 cm (OR 2.43; 95 % CI 2.16-2.75). CONCLUSIONS: SLNB is increasingly utilized in patients undergoing mastectomy for DCIS, but disparities in usage remain. Efforts at improving rates of SLNB in this population are warranted.
    Annals of Surgical Oncology 09/2012; · 4.12 Impact Factor

Publication Stats

2k Citations
550.33 Total Impact Points


  • 1993–2014
    • University of California, Davis
      • • Division of Surgical Oncology
      • • Department of Surgery
      • • Center for Biophotonics Science and Technology
      • • Department of Internal Medicine
      Davis, California, United States
  • 1998–2013
    • California State University, Sacramento
      Sacramento, California, United States
    • Oakland University
      • Department of Surgery
      Rochester, MI, United States
  • 1997–2002
    • University of Texas MD Anderson Cancer Center
      • • Department of Cancer Biology
      • • Department of Surgical Oncology
      Houston, TX, United States
  • 1993–1998
    • University of Texas Medical Branch at Galveston
      • Department of Surgery
      Galveston, TX, United States
  • 1996
    • Lincoln University California
      Oakland, California, United States