Camilo Jimenez

University of Houston, Houston, Texas, United States

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Publications (84)363.11 Total impact

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    ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in ACC has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of ACC. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human ACC samples was positively associated with cancer-related biological processes including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of ACC cells with exogenous HCG resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacological inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in ACC growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 08/2015; DOI:10.1158/0008-5472.CAN-14-3707 · 9.33 Impact Factor
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    ABSTRACT: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that is usually large (>5 cm) at time of diagnosis. Delayed diagnosis significantly worsens survival. We describe adrenal gland morphology prior to ACC diagnosis and discern potential causes of delayed diagnosis. ACC patients seen at The University of Texas MD Anderson Cancer Center between 1998 and 2014 who had cross-sectional body imaging ≥3 months prior to their diagnosis. We conducted a detailed review of clinical and radiological features in these patients prior to ACC diagnosis. Of 439 patients with ACC, 25 had imaging preceding ACC diagnosis (5 with normal adrenal glands and 20 with preexisting masses). On the first available images, the median mass size was 2.8 cm (range 0-9) with median precontrast density of 36 Hounsfield units (range 17-43) and became 9 cm (range 1-18) at the time of ACC diagnosis. The median interval between first available image and ACC diagnosis was 20 months (range 3-89). In the 5 patients whose initial images showed normal adrenal glands, the time between the last normal scan and ACC diagnosis ranged from 5 to 36 months. The most common reason for delayed ACC diagnosis was the presumed benign status of the preexisting mass (n = 13, 65 %). Radiologically suspicious adrenal masses can precede ACC diagnosis and have variable growth patterns. ACC can also develop de novo within a few months in a radiologically documented normal adrenal gland. The presumed benignancy of preexisting masses based on size is the main reason for delayed ACC diagnosis.
    Endocrine 07/2015; DOI:10.1007/s12020-015-0694-7 · 3.88 Impact Factor
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    ABSTRACT: Mutation of the genes encoding the succinate dehydrogenase (SDH) subunits A, B, C, or D, or the SDHAF2 protein, cause the SDHx-hereditary paraganglioma syndromes. Hereditary susceptibility to metastatic sympathetic pheochromocytomas and paragangliomas is most commonly due to germline mutations in the SDHB gene. Individuals with SDHD mutations occasionally present with metastatic disease, while conversely malignant paragangliomas are rarely observed in SDHC carriers. A 43 year-old woman presented with an abdominal paraganglioma metastatic to the skeleton and multiple lymph nodes. The tumor produced excessive amounts of noradrenaline causing hypertension and symptoms of catecholamine excess. The patient underwent surgical resection of the primary tumor and lymph node metastases. Loss of SDHB protein expression in the primary tumor was demonstrated by immunohistochemistry. Germline sequencing and deletion testing revealed a large allelic deletion of exons 1-6 in SDHC, and no mutations or deletions were detected in SDHB or SDHD. The patient's mother died because of kidney cancer. Hereditary pheochromocytomas and paragangliomas may be associated with a deletion of the SDHC gene. These patients may present with malignant sympathetic paragangliomas.
    Familial Cancer 07/2015; DOI:10.1007/s10689-015-9821-0 · 1.98 Impact Factor
  • Camilo Jimenez · Steven G Waguespack
    Endocrine 06/2015; 50(1). DOI:10.1007/s12020-015-0672-0 · 3.88 Impact Factor
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    ABSTRACT: Pheochromocytomas (PHs) and sympathetic paragangliomas (PGs) are tumors that produce catecholamines, predisposing patients to cardiovascular disease and gastrointestinal effects such as constipation. 1. Determine the prevalence of constipation, its risk factors, and its impact on survival. 2. Identify whether a systematic combination of fiber, water, and laxatives, was effective for treatment of constipation. We retrospectively studied 396 patients with PH/PG diagnosed in 2005-2014. The study population was patients with constipation as a presenting symptom; the control group, patients without constipation as a presenting symptom. The MD Anderson Symptom Inventory was used to assess constipation and quality of life. Twenty-three patients (6%) had constipation. Constipation was associated with headaches, palpitations, diaphoresis, weight loss, and excessive noradrenaline production (p<0.0001). Eighteen of these patients had non-metastatic primary tumors larger than 5 cm and/or extensive metastases. No statistically significant differences in age, sex, and genotype were noted between the study and control groups. In patients without metastases, resection of the primary tumor led to symptom disappearance. A systematic combination of fiber, water, and laxatives was associated with symptom improvement. Two patients who presented unmanaged constipation died because of sepsis from toxic megacolon. Constipation is a rare and potentially lethal complication in patients with PH/PGs. Severe constipation can be prevented by recognizing and treating mild symptoms.
    European Journal of Endocrinology 06/2015; 173(3). DOI:10.1530/EJE-15-0456 · 4.07 Impact Factor
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    ABSTRACT: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor deriving from the thyroid parafollicular cell. Thyroidectomy continues to serve as the primary initial treatment for this cancer. Because standard cytotoxic chemotherapy has proven ineffective, reoperation and external beam radiation therapy had been the only tools to treat recurrences or distant disease. The discovery that aberrant activation of RET, a receptor tyrosine kinase, is a primary driver of MTC tumorigenesis led to clinical trials using RET-targeting tyrosine kinase inhibitors. The successes of those trials led to the approval of vandetanib and cabozantinib for treating patients with progressive or symptomatic MTC. The availability of these drugs, along with additional targeted therapies in development, requires a thoughtful reconsideration of the approach to treating patients with unresectable locally advanced and/or metastatic progressive MTC.
    04/2015; 1(2):203-216. DOI:10.2217/ije.14.26
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    ABSTRACT: Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least 1/3 of paragangliomas are related to germline mutations in 1 of 17 genes. Although these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for <0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of 15 patients with cardiac paragangliomas was performed to determine clinical presentation, genetic background, diagnostic workup, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 patients (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen patients (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; 1 additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to co-morbidities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, the investigators extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 03/2015; 115(12). DOI:10.1016/j.amjcard.2015.03.020 · 3.28 Impact Factor
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    ABSTRACT: Context: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAFV600E mutation. Objective: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial. Design: Retrospective review at MD Anderson Cancer Center. Methods: Best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0. Results: We identified 17 patients with advanced PTC harboring the BRAFV600E mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47%) and stable disease (SD) in 8/15(53%) patients. The rate of durable response (PR plus SD ≥ 6 months) was 67%. Median time to treatment failure was 13 months. There was no association between change in thyroglobulin and tumor size. Drug discontinuation, drug interruptions, and dose reductions were needed in 5(29%), 13 (76%), and 10 (59%) patients, respectively. Most common AEs were fatigue (71%), weight loss (71%), anorexia (65%), arthralgias (59%), hair loss (59%), rash (59%), hand-foot syndrome (53%), calluses (47%), diarrhea (47%), fever (41%), dry mouth (35%), nausea (35%), and verrucous keratosis (35%). Grade≥3 AEs were present in 8 (47%) patients. Conclusions: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAFV600E mutation. Our results are similar to those reported in a phase II clinical trial and support the potential role of vemurafenib in this patient population.
    Journal of Clinical Endocrinology &amp Metabolism 10/2014; 100(1):jc20142246. DOI:10.1210/jc.2014-2246 · 6.21 Impact Factor
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    Maria E Cabanillas · Mimi I Hu · Camilo Jimenez
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    ABSTRACT: Context: Medullary thyroid cancer (MTC) is a rare form of thyroid cancer comprising approximately 4% of all thyroid cancers. The majority of patients have a relatively good prognosis; however, a subgroup of patients will require systemic therapy. Large phase III randomized trials led to the approval of two drugs--vandetanib and cabozantinib--for progressive or symptomatic MTC. The decision regarding which drug to initiate first is not entirely clear and is a common concern amongst treating physicians. Evidence acquisition and synthesis: A review of the literature in English was conducted, and data were summarized and integrated into a decision matrix. Conclusions: The decision regarding which drug to initiate first for progressive MTC should be based on a careful review of the medical history, physical examination findings, medication list, electrocardiogram, laboratory results, and tumor characteristics. It is necessary to consider the relative contraindications when choosing which drug to initiate first.
    Journal of Clinical Endocrinology &amp Metabolism 09/2014; 99(12):jc20142811. DOI:10.1210/jc.2014-2811 · 6.21 Impact Factor
  • Libero Santarpia · Camilo Jimenez
    08/2014; 1(1):7-10. DOI:10.2217/ije.14.7
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    ABSTRACT: Mestastatic pheochromocytoma and paraganglioma (MPP) present clinicians with three major challenges: scarcity, complexity of characterization, and heterogeneous behavior and prognosis. As with the treatment of all neuroendocrine tumors, the control of hormonal symptoms and tumor growth are the main therapeutic objectives in MPP patients. A significant number of MPP patients still die from uncontrolled hormone secretion. In addition, the management of MPP remains palliative. Steps forward include proper characterization of MPP patients at large cancer referral centers with multidisciplinary teams; improved strategies to stratify patients prognostically; and implementation of trials within national and international networks. Progress in the molecular characterization and staging of MPP constitutes the basis for significant treatment breakthroughs.
    European Journal of Endocrinology 06/2014; 171(3). DOI:10.1530/EJE-14-0113 · 4.07 Impact Factor
  • Mimi I Hu · Anita K Ying · Camilo Jimenez
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    ABSTRACT: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer, demonstrating variable behavior from indolent disease to highly aggressive, progressive disease. There are distinguishing phenotypic features of sporadic and hereditary MTC. Activation or overexpression of cell surface receptors and up-regulation of intracellular signaling pathways in hereditary and sporadic MTC are involved in the disease pathogenesis. There has been an exponential rise in clinical trials with investigational agents, leading to approval of 2 medications for progressive, advanced MTC. Developments in understanding the pathogenesis of MTC will hopefully lead to more effective and less toxic treatments of this rare but difficult to treat cancer.
    Endocrinology & Metabolism Clinics of North America 06/2014; 43(2):423-442. DOI:10.1016/j.ecl.2014.02.004 · 3.40 Impact Factor
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    ABSTRACT: Sorafenib has proven efficacy in advanced differentiated thyroid cancer (DTC), but many patients must reduce the dose or discontinue treatment because of toxicity. The tolerability and efficacy of lower starting doses of sorafenib for DTC remain largely unstudied.Methods.We retrospectively examined overall survival, time to treatment failure, time to progression, discontinuation rates, and dose-reduction and interruption rates in patients with metastatic DTC treated with first-line sorafenib outside of a clinical trial. Two patient groups were compared; group 1 received the standard starting dose of 800 mg/day, and group 2 received any dose lower than 800 mg/day.Results.We included 75 adult patients, with 51 in group 1 and 24 in group 2. Mean age at diagnosis was 54 years, and 56% were male. The most common histologies included 43% papillary thyroid cancer of the conventional type, 15% papillary thyroid cancer of the follicular variant, and 15% Hürthle cell carcinoma. Time to treatment failure was 10 months (95% confidence interval [CI]: 5.6-14.3) in group 1 and 8 months (95% CI: 3.4-12.5) in group 2 (p = .56). Median overall survival was 56 months (95% CI: 30.6-81.3) in group 1 and 30 months (95% CI: 16.1-43.8) in group 2 (p = .08). Rates of discontinuation due to disease progression were 79% in group 1 and 91% in group 2, and 21% in group 1 and 9% in group 2 (p = .304) stopped treatment because of toxicity. Dose-reduction rates were 59% and 43% (p = .29), and interruption rates were 65% and 67% (p = .908) in group 1 and group 2, respectively.Conclusion.Efficacy and tolerability of sorafenib in treatment-naïve DTC patients does not appear to be negatively influenced by lower starting daily doses.
    The Oncologist 04/2014; 19(5). DOI:10.1634/theoncologist.2013-0409 · 4.87 Impact Factor
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    ABSTRACT: Objective: To describe and compare the clinical, biochemical, radiologic, and pathologic features of adrenal pheochromocytoma-ganglioneuroma (PC-GN) composites with the features of isolated pheochromocytomas (PCs) and adrenal ganglioneuromas (AGNs).Methods: We reviewed data for PC-GN composite cases seen at a single tertiary center between 1993 and 2012 and compared them with isolated AGN and relatively similar median-size PC.Results: Nine PC-GN composites were included. Median age at diagnosis was 52 yr (range, 28-83 yr) for PC-GN compared with 55 yr (range, 24-78) for PC patients and 40 yr (range 18-64) for AGN. Similar to PCs, all PC-GNs composites were associated with catecholamine overproduction while AGNs were non-functioning. On pathology, the median tumor sizes were 7 cm (range, 2.5-13 cm) for PC-GN tumors, 6.5 cm (range, 3.5-7 cm) for PCs, and 8 cm (range, 3.2-20) for AGNs. On CT imaging, PC-GN composites and PCs were heterogeneous, with both having significantly higher post-contrast density values than did AGNs, which typically looked homogeneous and had a progressive enhancement pattern without contrast washout in most cases.Conclusions: The presence of a PC component significantly increased tumor heterogeneity and post-contrast density values. CT imaging could be very helpful in distinguishing AGNs from both PC-GN and PC tumors, but only pathologic examination can yield the diagnosis. Clinically and radiologically, PC-GN composites were indistinguishable from PCs and need to be managed similarly.
    Endocrine Practice 03/2014; 20(9):1-19. DOI:10.4158/EP14010.OR · 2.81 Impact Factor
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    ABSTRACT: Context: Sorafenib, a tyrosine kinase inhibitor, is a common first line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem. Objective: To determine the efficacy of salvage therapy after first-line sorafenib failure. Design: Retrospective review at MD Anderson Cancer Center from January 2005 to May 2013. Patients: Patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). Patients who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS). Outcome Measures: Progression-free survival (PFS), best response, and median OS. Results: Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients was 37 months; median OS was significantly longer with salvage therapy compared to sorafenib alone (58 vs. 28 months, p = 0.013). In group 2, 17 patients were evaluable for best response, although 2 patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response (PR) in 2/15 (13%), stable disease (SD) in 10/15 (67%), and progressive disease (PD) in 3/15 (20%) patients. With salvage therapy, PRs were seen in 7/17 (41%) and SD in 10/17 (59%) patients. Median PFS was 7.4 months with first-line sorafenib only and 11.4 months with salvage therapy. Salvage therapy included sunitinib (4), pazopanib (3), cabozantinib (4), lenvatinib (3), and vemurafenib (3). Conclusions: Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.
    The Journal of Clinical Endocrinology and Metabolism 03/2014; 99(6):jc20133588. DOI:10.1210/jc.2013-3588 · 6.21 Impact Factor
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    ABSTRACT: Background: Age-related risk of medullary thyroid carcinoma (MTC) development in presymptomatic carriers of lower risk germline RET mutations is uncertain; such data may aid counseling patients regarding timing of thyroidectomy. Methods: From an institutional database and an exhaustive literature review, we identified 679 patients with American Thyroid Association (ATA) level A or B mutations who were identified because of family screening (index cases of MTC were excluded to minimize selection bias). We evaluated age at thyroidectomy or last evaluation if no thyroidectomy, preoperative calcitonin level (elevated or not), the mutated codon, and outcome (MTC vs. no MTC after thyroidectomy or no clinical evidence of MTC if thyroid intact). Data were used to estimate the cumulative prevalence of MTC and/or assess likelihood of MTC stratified by codon. After exclusion of cases with missing data or small representation, 503 patients with mutations in codons 533, 609, 611, 618, 620, 791, and 804 were analyzed. Results: 236 patients had MTC. Cumulative prevalence and median time to MTC varied by codon and within ATA risk levels (p<0.0001). Patients with a codon 620 mutation were 2.8-6.9 times more likely to have MTC than other level B mutation carriers, and 5.1-21.7 times more likely than level A mutation carriers included in our focus population. The youngest median time to MTC was 19 years for codon 620 and the oldest was 56 years for codon 611. Cumulative prevalence of MTC by age 20 was 10% or lower for codons 533, 609, 611, 791, and 804. By age 50, it ranged from 18% for codon 791 to 95% for codon 620. An elevated preoperative calcitonin level strongly predicted MTC on final pathology, though false-negative rates varied by codon (p<0.0001). Positive predictive values ranged from 76% to 100% by codon with an overall positive predictive value of 87% across codons. Conclusions: This study offers a better understanding of the age-related development of MTC in lower risk RET mutation carriers, provides evidence of further distinctions between lower risk mutations within ATA subgroups, and clarifies the clinical significance of codon 791 mutations. The data support individualized "codon-based" management approaches coupled with clinical data such as calcitonin levels.
    Thyroid: official journal of the American Thyroid Association 03/2014; 24(7). DOI:10.1089/thy.2013.0620 · 4.49 Impact Factor
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    ABSTRACT: Subdiaphragmatic paraganglioma is a rare neuroendocrine tumor for which scarce data exist regarding long-term patient outcome following resection. The aim of this study was to determine the association of surgical resection with survival. A retrospective study at a tertiary care center was performed. Demographics, genetics, histology, and operative details were reviewed. Patients were grouped according to margin status (R0, R1, or R2) and survival calculated. A total of 50 patients with subdiaphragmatic paragangliomas underwent primary resection from 1999 to 2012. Median age at operation was 46 years, with a median tumor size of 6.0 cm. Of these patients, 30 (60 %) had a R0 resection, 11 (22 %) had a R1 resection, and 9 (18 %) had a R2 resection. There was no operative mortality, and 17 (34 %) patients had metastatic disease. Six (12 %) patients died, four (8 %) of whom had metastatic disease. Univariate analysis identified that age >50 years (p = 0.02) and undergoing a R2 resection (p = 0.03) were associated with a shorter overall survival (OS). Those with metastases at some point after their initial diagnosis had a shorter disease-free survival (DFS) than those without metastases (p = 0.04). Of 27 patients tested, 12 (44 %) had a germline succinyl dehydrogenase B (SDHB) mutation. SDHB immunohistochemistry identified 18 patients (of 27 who underwent staining) who had loss of SDHB expression in which 7 of 11 patients (63 %) who underwent genetic testing had a genetic mutation. Surgical resection of subdiaphragmatic paraganglioma is safe. Survival was longest in patients who were younger, with no metastases, or had a R0 or R1 resection. Patients who test negative for a germline mutation should undergo SDHB immunostaining to identify potential hereditary carriers missed by current genetic testing.
    World Journal of Surgery 01/2014; 38(3). DOI:10.1007/s00268-013-2443-5 · 2.64 Impact Factor

Publication Stats

1k Citations
363.11 Total Impact Points


  • 2010–2014
    • University of Houston
      Houston, Texas, United States
  • 2004–2014
    • University of Texas MD Anderson Cancer Center
      • • Endocrine Neoplasia and Hormonal Disorders
      • • Department of Surgical Oncology
      Houston, Texas, United States
  • 2005–2012
    • Baylor College of Medicine
      • Division of Diabetes, Endocrinology and Metabolism
      Houston, Texas, United States
    • Jackson Memorial Hospital
      Miami, Florida, United States