Abstract：
BACKGROUND:Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis, as a majority of patients present with advanced disease. Current adjuvant strategies for metastatic patients include mitotane or other cytotoxic agents and carry a significant morbidity as well as a low (<10 %) 5-year survival. Withanolides, including withaferin A, are novel chemotherapeutic agents with potent targeted effects in medullary thyroid cancer and a number of solid malignancies with low toxicity in vivo. We hypothesize that novel naturally derived withanolides will have potent targeted anti-cancer activity against ACCs. METHODS:In vitro cell viability of ACC cell lines (Y1 and SW13) was measured using MTS cell proliferation assay. Cell cycle and apoptotic analysis studied using annexin V/propidium iodide staining on flow cytometry (FC) and targeted molecular mechanisms of withanolide cytotoxicity were assessed using standard Western blot analysis. RESULTS:All the withanolides potently reduced ACC cell viability on MTS assay with 7- to 185-fold higher selectivity than normal fibroblasts. Cell cycle analysis demonstrated a shift in cell cycle arrest from G1/G0 to G2/M with induction of apoptosis at nanomolar concentrations of withanolides. Unlike current ACC therapeutics, withanolides modulated expression of several key oncogenic pathway proteins in ACCs by Western blot, including Jagged 1, MAPK, and Akt/mTOR pathway proteins in a dose-dependent manner after 24 h drug treatment of SW13 cells. CONCLUSION:These results demonstrate the first evidence of the anticancer efficacy of withanolides in ACC cells and provide support for future translational evaluation of these compounds as novel therapeutic agents for ACC patients.
journal_name
World J Surgjournal_title
World journal of surgeryauthors
Subramanian C,Zhang H,Gallagher R,Hammer G,Timmermann B,Cohen Mdoi
10.1007/s00268-014-2532-0subject
Has Abstractpub_date
2014-06-01 00:00:00pages
1343-52issue
6eissn
0364-2313issn
1432-2323journal_volume
38pub_type
杂志文章abstract：BACKGROUND:The clinical importance of papillary thyroid microcarcinoma (PTMC) remains controversial, with current guidelines suggesting that thyroid lobectomy alone is sufficient. The purpose of this study was to identify population-level treatment patterns in the USA for PTMC. METHODS:Patients with PTMC in SEER (1998...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-014-2602-3
更新日期：2014-09-01 00:00:00
abstract：BACKGROUND:We analyzed perioperative platelet counts as a potential clinical marker for survival after transthoracic en bloc resection for esophageal cancer. Recent data described preoperative thrombocytosis in malignancies to be associated with poor prognosis. METHODS:A retrospective analysis from a prospective datab...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-010-0707-x
更新日期：2010-11-01 00:00:00
abstract：BACKGROUND:Surgical resection remains the treatment of choice for carotid body tumors (CBTs). Although perioperative complications such as carotid artery injury and neurological deficits occur infrequently, they can be devastating. The aim of this study was to evaluate whether clinical factors or preoperative imaging f...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-015-3058-9
更新日期：2015-08-01 00:00:00
abstract：:The geographic distribution of duodenal ulcer and its characteristics in rural areas of high incidence in developing countries are reviewed. The choice of surgical procedures is discussed in light of the bulky diet and nutritional problems of these countries. A vagotomy procedure is advised for duodenal ulcer and a B...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/BF01654731
更新日期：1977-01-01 00:00:00
abstract：BACKGROUND:We investigated the implications of HER2 amplification in Asian women with small, node-negative breast cancer in low- and middle-income countries (LMCs). METHODS:We reviewed the charts patients treated between 1989 and 2009 with breast conservation therapy for node-negative breast cancers measuring ≤ 2 cm. ...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-011-1353-7
更新日期：2012-02-01 00:00:00
abstract：BACKGROUND:The treatment of acute limb ischemia (ALI) has barely changed over the last years. However, the progressive implementation of anticoagulants, antiplatelet agents or statins within the population might have modified the profile and prognosis of patients suffering an ALI. The aim of this study was to evaluate ...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-018-4511-3
更新日期：2018-08-01 00:00:00
abstract：BACKGROUND:Frailty is a customized marker of biological age that helps to gauge an individual's functional physiologic reserve and ability to react to stress and is associated with increased postoperative morbidity and mortality. In order to mitigate frailty preoperatively, the concept of prehabilitation has entered th...
journal_title：World journal of surgery
pub_type： 杂志文章,评审
doi：10.1007/s00268-020-05658-0
更新日期：2020-11-01 00:00:00
abstract：BACKGROUND:The change in the route of food passage after pancreaticoduodenectomy (PD) is quite similar to the change after gastric bypass surgery; both procedures bypass the duodenum and directly connect to the distal jejunum. Moreover, both procedures result in resolution of type 2 diabetes mellitus. Therefore, more d...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-015-3157-7
更新日期：2015-11-01 00:00:00
abstract：OBJECT:The massive typhoon Haiyan (Yolanda) ripped across the central Philippines on November 8, 2013, and damaged infrastructure including hospitals. The Israeli Defense Forces field hospital was directed by the Philippine authorities to Bogo City in the northern part of the island of Cebu, to assist the damaged local...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-016-3692-x
更新日期：2017-02-01 00:00:00
abstract：BACKGROUND:Recurrent laryngeal nerve palsy (RLNP) is one of the most common complications after thyroidectomy. We aim to evaluate the role of intraoperative corticosteroids in preventing or treating postoperative RLNP. MATERIALS AND METHODS:We conducted a prospective study of 295 patients who underwent either total lo...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-005-0399-9
更新日期：2006-03-01 00:00:00
abstract：BACKGROUND:Few guidelines exist for the initial management of wounds in disaster settings. As wounds sustained are often contaminated, there is a high risk of further complications from infection, both local and systemic. Healthcare workers with little to no surgical training often provide early wound care, and where r...
journal_title：World journal of surgery
pub_type： 杂志文章,评审
doi：10.1007/s00268-014-2663-3
更新日期：2015-04-01 00:00:00
abstract：BACKGROUND:The splintering of general surgery into subspecialties in the past decade has brought into question the relevance of a continued emphasis on traditional general surgical training. With the majority of trainees now expressing a preference to subspecialise early, this study sought to identify if the requiremen...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-014-2890-7
更新日期：2015-02-01 00:00:00
abstract：:We sought to determine whether early eschar excision en masse (EEE) at one operation would be effective in the prevention and treatment of postburn organ dysfunction (OD) and multiple organ dysfunction syndrome (MODS). A total of 60 patients, with total body surface burned area over 35% and a third degree burn area ov...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s002689900661
更新日期：1999-12-01 00:00:00
abstract：BACKGROUND:Gastroesophageal reflux is the main risk factor for esophageal adenocarcinoma, but there is no strong support for a protective effect of antireflux surgery. We tested the hypothesis that esophageal adenocarcinoma that develops with long latency after antireflux surgery might be due to persistent postoperativ...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-006-0386-9
更新日期：2007-03-01 00:00:00
abstract：BACKGROUND:The reported high incidence of 30-60% postoperative pain after an elective day surgical orchidopexy is undesirable. We evaluated the efficacy of our analgesic regimen for unilateral orchidopexy in preschool children performed as a day surgical procedure. METHODS:Between January 2004 and December 2006, 247 c...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-008-9847-7
更新日期：2009-03-01 00:00:00
abstract：:Transsphenoidal pituitary surgery has radically modified the management of pituitary-dependent hypercortisolism (Cushing's disease). Bilateral adrenalectomy may, however, represent the ultimate treatment in some cases of hypercortisolism. In the present study we report our experience of bilateral adrenalectomy in 82 p...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s002689900118
更新日期：1996-09-01 00:00:00
abstract：:This prospective study was instituted to assess whether the use of the on-pump method or the off-pump method affects changes in health-related quality of life (QOL) as evaluated a year after coronary artery bypass graft (CABG) surgery. Data including preoperative risk factors and postoperative morbidity up to discharg...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-004-7486-1
更新日期：2004-10-01 00:00:00
abstract：:Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis ...
journal_title：World journal of surgery
pub_type： 杂志文章,评审
doi：10.1007/s002680010228
更新日期：2000-11-01 00:00:00
abstract：:The aim of this study was to clarify the role of ganglion cells in the development and recurrence of sigmoid volvulus. We analyzed 9 samples obtained from 9 patients who had undergone sigmoidectomy for sigmoid volvulus, and, for comparison, 18 samples from 18 patients who had undergone sigmoidectomy or low anterior re...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-004-7462-9
更新日期：2005-01-01 00:00:00
abstract：BACKGROUND:Enhanced recovery (ERAS) guidelines do not differentiate between left- and right-sided colectomies, but differences in recovery have been reported for the two procedure types. We aimed to compare compliance with the ERAS protocol and outcomes after right versus left colectomy. METHODS:Between June 2011 and ...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-016-3563-5
更新日期：2016-10-01 00:00:00
abstract：PURPOSE:The aim of the study was to evaluate risk factors for small bowel obstruction (SBO) in early postoperative period after anterior resection for rectal cancer. METHODS:Patients who underwent anterior resection (AR) [high AR (HAR) or low AR (LAR)] for rectal cancer between January 2009 and April 2016 were enrolle...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-017-4152-y
更新日期：2018-01-01 00:00:00
abstract：:In a double-blind placebo-controlled study we investigated the effect of recombinant human erythropoietin (r-HuEPO), on the perioperative hemoglobin concentration and the use of blood transfusions in patients undergoing elective colorectal surgery with a preoperative hemoglobin level
journal_title：World journal of surgery
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002689900561
更新日期：1999-01-01 00:00:00
abstract：:Congenital short colon (CSC) is a condition in which the colon is replaced, wholly or partially, by a dilated pouch together with anorectal malformation and a colourinary fistula. Most of the reported series have been from northern India where this malformation is frequent. This paper details the management of 108 pat...
journal_title：World journal of surgery
pub_type： 临床试验,杂志文章
doi：10.1007/s002689900019
更新日期：1996-01-01 00:00:00
abstract：BACKGROUND:Frequent use of computed tomography (CT) in trauma patients results in frequent detection of non-trauma-related incidental findings (IFs). Inpatient documentation and disclosure at discharge are infrequent, even when they are potentially serious. We aimed to not only identify the incidence of IFs but also to...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-013-2092-8
更新日期：2013-09-01 00:00:00
abstract：BACKGROUND:The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 ± 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of post...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-016-3584-0
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND:Surgical care is critical to establish effective healthcare systems in low- and middle-income countries, yet the unmet need for surgical conditions is as high as 65% in Ugandan children. Financial burden and geographical distance are common barriers to help-seeking in adult populations and are unmeasured in ...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-018-4691-x
更新日期：2018-11-01 00:00:00
abstract：BACKGROUND:The extent to which obesity and genetics determine postoperative complications is incompletely understood. METHODS:We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and ...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-019-05202-9
更新日期：2020-01-01 00:00:00
abstract：BACKGROUND:Binding of the lectin Helix pomatia agglutinin (HPA) has been shown to be associated with poor prognosis in many human cancers, but not in thyroid cancer. The aims of the present study were to assess alteration in cellular glycosylation, detected by HPA binding, in thyroid tumors; to determine if such altere...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-011-1196-2
更新日期：2011-10-01 00:00:00
abstract：BACKGROUND:Africa's health workforce crisis has recently been emphasized by major international organizations. As a part of this discussion, it has become apparent that the workforce required to deliver surgical services has been significantly neglected. METHODS:This paper reviews some of the reasons for this relative...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s00268-008-9473-4
更新日期：2008-06-01 00:00:00
abstract：:This study compares the findings of conventional computed tomography (CT) and ultrasound (US) imaging in the preoperative evaluation of patients with abdominal aortic aneurysm (AAA). It also assesses the impact of preoperative CT-derived information on operative strategy. A prospective study was conducted of 96 patien...
journal_title：World journal of surgery
pub_type： 杂志文章
doi：10.1007/s002689900626
更新日期：1999-10-01 00:00:00
