Jeffrey E. Lee

Bio: Jeffrey E. Lee is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Epidermal growth factor & Receptor. The author has an hindex of 11, co-authored 13 publications receiving 7201 citations. Previous affiliations of Jeffrey E. Lee include Genentech.

Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells

Abstract: The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted v-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains. A single transmembrane region of 23 amino acids separates the extracellular EGF binding and cytoplasmic domains. The receptor gene is amplified and apparently rearranged in A431 cells, generating a truncated 2.8-kilobase mRNA which encodes only the extracellular EGF binding domain.

Borderline Resectable Pancreatic Cancer: Definitions, Management, and Role of Preoperative Therapy

Abstract: With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of "borderline resectability." In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180 degrees of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.

Borderline resectable pancreatic cancer: the importance of this emerging stage of disease.

Abstract: Background Patients with borderline resectable pancreatic adenocarcinoma (PA) include those with localized disease who have tumor or patient characteristics that preclude immediate surgery. There is no optimal treatment schema for this distinct stage of disease, so the role of surgery is undefined. Study Design We defined patients with borderline resectable PA as fitting into one of three distinct groups. Group A comprised patients with tumor abutment of the visceral arteries or short-segment occlusion of the Superior Mesenteric Vein. In group B, patients had findings suggestive but not diagnostic of metastasis. Group C patients were of marginal performance status. Patients were treated initially with chemotherapy, chemoradiation, or both; those of sufficient performance status who completed preoperative therapy without disease progression were considered for surgery. Results Between October 1999 and August 2006, 160 (7%) of 2,454 patients with PA were classified as borderline resectable. Of these, 125 (78%) completed preoperative therapy and restaging, and 66 (41%) underwent pancreatectomy. Vascular resection was required in 18 (27%) of 66 patients, and 62 (94%) underwent a margin-negative pancreatectomy. A partial pathologic response to induction therapy ( Conclusions This is the first large report of borderline resectable PA and includes objective definitions for this stage of disease. Our neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.

Preoperative Gemcitabine-Based Chemoradiation for Patients With Resectable Adenocarcinoma of the Pancreatic Head

Abstract: Purpose We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy (PD) for stage I/II pancreatic adenocarcinoma. Patients and Methods Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous (IV) infusions of gemcitabine (400 mg/m 2 IV over 30 minutes) plus radiation therapy (30 Gy in 10 fractions over 2 weeks). Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and, in the absence of disease progression, were taken to surgery. Results The study enrolled 86 patients. At the time of restaging, disease progression or a decline in performance status precluded 13 patients from surgery. Seventy-three (85%) of 86 patients were taken to surgery, extrapancreatic disease was found in nine, and 64 (74%) of 86 underwent a successful PD. Median overall survival (86 patients) was 22.7 months with a 27% 5-year survival. Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients (P .001). The 5-year survival for those who did and did not undergo PD was 36% and 0%, respectively. Conclusion Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets: patients likely to benefit from PD (n 64) and those in whom surgery would be unlikely to provide clinical benefit (n 22). Furthermore, the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer. J Clin Oncol 26:3496-3502. © 2008 by American Society of Clinical Oncology

Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma

Abstract: Objective: To better understand the impact of a microscopically positive margin (R1) on patterns of disease recurrence and survival after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. Summary Background Data: A positive resection margin after PD is considered to be a poor prognostic factor, and some have proposed that an R1 margin may be a biologic predictor of more aggressive disease. The natural history of patients treated with contemporary multimodality therapy who underwent a positive margin PD has not been described. Methods: We analyzed our experience from 1990 to 2004, which included the prospective use of a standardized system for pathologic analysis of all PD specimens. All patients who underwent PD met objective computed tomographic criteria for resection. Standard pathologic evaluation of the PD specimen included permanent section analysis of the final bile duct, pancreatic, and superior mesenteric artery (SMA) margins. First recurrences (all sites) were defined as local, regional, or distant. Survival and follow-up were calculated from the date of initial histologic diagnosis to the dates of first recurrence or death and last contact, respectively. Results: PD was performed on 360 consecutive patients with pancreatic adenocarcinoma. Minimum follow-up was 12 months (median, 51.9 months). The resection margins were negative (R0) in 300 patients (83.3%) and positive (R1) in 60 (16.7%); no patients had macroscopically positive (R2) margins. By multivariate analysis (MVA), high mean operative blood loss and large tumor size were independent predictors of an R1 resection. Patients who underwent an R1 resection had a median overall survival of 21.5 months compared with 27.8 months in patients who underwent an R0 resection. After controlling for other variables on MVA, resection status did not independently affect survival. By MVA, only lymph node metastases, major perioperative complications, and blood loss adversely affected survival. Conclusions: There was no statistically significant difference in patient survival or recurrence based on R status. However, this series is unique in the incorporation of a standardized surgical technique for the SMA dissection, the prospective use of a reproducible system for pathologic evaluation of resection margins, the absence of R2 resections, and the frequent use of multimodality therapy. (Ann Surg 2007;246: 52‐60)

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene

Abstract: The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...

The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.

Abstract: In recent years, members of the protein kinase family have been discovered at an accelerated pace. Most were first described, not through the traditional biochemical approach of protein purification and enzyme assay, but as putative protein kinase amino acid sequences deduced from the nucleotide sequences of molecularly cloned genes or complementary DNAs. Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.