Paraoxonase-1: Characteristics and Role in Atherosclerosis and Carotid Artery Disease.

Paraoxonase-1 (PON-1) is a calcium-dependent enzyme that is synthesized in the liver and then secreted in blood where it is bound to high density lipoprotein (HDL). PON-1 is a hydrolase with a wide range of substrates, including lipid peroxides. It is considered responsible for many of the antiatherogenic properties of HDL. PON-1 prevents low density lipoprotein (LDL) oxidation, a process that is considered to contribute to the initiation and development of atherosclerosis. PON-1 activity and levels are influenced by gene polymorphisms; of the 2 common variants, one is in position 192 (Q192R) and one in position 55 (M55L). Also, many drugs affect PON-1 activity. The role of PON-1 in carotid atherosclerosis is inconsistent. Some studies show an association of PON-1 polymorphisms with carotid plaque formation, whereas others do not. The aim of this review is to summarize the characteristics of PON-1, its interactions with drugs and its role in atherosclerosis and especially its relationship with carotid artery disease.

Iodine intake and chronic autoimmune thyroiditis: a comparative study between coastal and mainland regions in Greece.

INTRODUCTION: The purpose of this study was to evaluate the relationship between iodine intake and autoimmune thyroiditis in Chios, an island located in the North East Aegean Sea, in comparison to mainland regions in South Western Greece (SWG). MATERIALS AND METHODS: Urine iodine concentration (UIC), thyroid function (serum TSH, thyroid autoantibodies: anti-TPO and anti-Tg), and thyroid U/S were assessed in 200 subjects (150 females and 50 males) from Chios and 322 subjects (255 females and 67 males) from several mainland regions in SWG. All participants were recruited from outpatient clinics and were diagnosed as euthyroid. RESULTS: Median UIC in Chios was significantly higher compared to SWG (136.1 vs. 104.5 µg/L, p < 0.001), indicating that both regions are iodine sufficient according to World Health Organization (WHO) criteria. The prevalence of thyroid autoimmunity was 66.5% in Chios and 27% in SWG, significantly higher in females (46.7%) than in males (26.5%). Furthermore, individuals with increased levels of thyroid autoantibodies either anti-TPO or anti-Tg (TAbs) showed increased median UIC levels compared to those / subjects / patients with normal levels (126.7 vs. 108.95 µg/L, p < 0.001). Serum TSH mean values (mIU/L) were greater in females (mean = 2.1 ± 1.41) compared to males (mean = 1.82 ± 1.26) (p = 0.04) and decreased with age. CONCLUSIONS: In conclusion, in the present study, we clearly indicate that increased thyroid autoimmunity is positively associated with increased iodine intake, as well as with the female gender. Moreover, iodine intake and thyroid autoimmunity appear to be significantly higher in a coastal region (Chios) than in mainland Greece (SWG). Additional environmental factors, apart from iodine, should be investigated in future studies. Mean TSH values were increased in females and decreased with age. The latter is probably due to the presence of autonomous goiter in older Greek populations, as a result of long-term status of iodine deficiency in the past.

Current clostridium difficile treatments: Lessons that need to be learned from the clinical trials.

Clostridium difficile infection (CDI) is the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. Judging from the clinical trials on drugs used in CDIs, no approved treatment for recurrences exists, possibly indicating that a combination of treatment approaches are mandatory especially in severe infections, with current studies not being fully representative. Among the new strategies researched intensively fidaxomicin is presented, which demonstrates reduced CDI recurrences. Moreover, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally monoclonal antibodies against C. difficile toxins which offer protection against recurrences. Careful interpretation of the results based on lessons learned from previous trials conducted seems crucial. Questions are raised regarding how the results of future studies regarding new strategies researched will be managed and interpreted especially with regard to recurrence management as relevant data must be monitored for at least 30 days after end of treatment.

Minimally invasive management of hepatic cysts: indications and complications.

OBJECTIVE: Liver cysts are divided into congenital and acquired. Congenital cystic lesions include polycystic liver disease, simple cysts, duct related and ciliated hepatic foregut cysts. Acquired cystic lesions are divided into infectious and non-infectious. The infectious cysts are the hydatid cyst, the amoebic abscess, and the pyogenic abscess, whereas the non-infectious cysts are neoplastic cysts and false cysts. While modern medicine provides a lot of minimally invasive therapeutic modalities, there has emerged a pressing need for understanding the various types of liver cysts, the possible minimal therapeutic options along with their indications and complications. We aim is to clarify the role of minimally invasive techniques in the management of hepatic cysts. MATERIALS AND METHODS: A literature review was performed using the MEDLINE database. The search terms were: liver cyst, minimally invasive, laparoscopic, percutaneous, drainage and fenestration. We reviewed 82 English language publications articles, published until October 2017. RESULTS: Minimally invasive management of liver LC is an emerging field including many therapeutic modalities ranging from the percutaneous aspiration of pyogenic abscesses to laparoscopic hepatectomy for hepatic cystadenomas. The most used techniques are percutaneous drainage, laparoscopic fenestration, and laparoscopic hepatectomy. CONCLUSIONS: The application of the various minimally invasive approaches, as well as their indication and complications, depend on the type of the cystic lesion, its size and its position in the liver. Percutaneous drainage is mostly used in simple cysts, hydatid cysts, pyogenic abscesses and bilomas. Laparoscopic fenestration is mostly used in simple cysts and polycystic liver disease. Finally, laparoscopic hepatectomy is mostly used in polycystic liver disease, hydatid cysts, and cystadenomas.

Postoperative deep wound dehiscence of thoracotomy with isolation of Corynebacterium tuberculostearicum: surgical site infection or colonization?

OBJECTIVE: Infections with Corynebacterium tuberculostearicum are very rare as in most of the cases its isolation is associated with tissue colonization rather than infection. CASE REPORT: An 80-year old female patient was sent to the consultation hour of thoracic surgery for evaluation of a symptomatic persistent unilateral pleural effusion of her right lung. The differential diagnosis included either the presence of a chronic pleural empyema or the presence of malignancy. After excluding a malignancy, a decortication of the middle and lower lobe was performed, as the two lobes could not significantly re-expand. The course was further complicated by the presence of two-times deep wound dehiscence, which made necessary a rethoracotomy. The microbiologic results of the biopsies revealed the presence of only Corynebacterium tuberculostearicum with an initially questionable clinical relevance. As soon as the antibiotic treatment for Corynebacterium tuberculostearicum began, together with the use of vacuum-assisted therapy (VAC), the closure of the thoracotomy was accelerated. CONCLUSIONS: Clinically relevant surgical site infections with Corynebacterium species in thoracic surgery are difficult to distinguish. Nevertheless, its combined surgical and antibiotic treatment is warranted when its relevance is questionable due to its resistance to broad-spectrum antibiotics as well as to its potential for the complicated clinical course.

HIV patient with pseudomyxoma peritonei of extra-appendiceal origin is disease-free and alive 9 years after complete cytoreductive surgery.

OBJECTIVE: Pseudomyxoma peritonei (PMP) is a clinical syndrome that is mainly characterized by the presence of mucinous ascites that results from the rupture of a mucin-producing neoplasm. No reports exist so far regarding the management of this syndrome in HIV patients. CASE REPORT: A 54-year old male patient with a diagnosed atypical colitis developed additionally over time a complicated diverticulitis which was initially treated conservatively with antibiotics. Due to septic complication, the patient received a Hartmann resection. Six months after the first surgery a Hartmann reversal was tried; it, however, revealed peritoneal implants and a significant stenosis of the colon stump. Resection of these lesions confirmed histopathologically the presence of a low-grade pseudomyxoma peritonei. Five months later, a second try for a Hartmann reversal was performed. In the view of the slightly enlarged paracolic lymph nodes, a low anterior resection was performed with a primary descendorectostomy. Histopathological examination revealed no more signs of the tumor, which confirmed the completeness of the cytoreductive surgery by the first try for a Hartmann reversal. CONCLUSIONS: Completeness of cytoreductive surgery and low grade histology seem to be the most important factors for the prognosis in pseudomyxoma peritonei in immunocompromised patients as suggested by the long overall and progression free survival of the present patient.

Nestin and CD146 expression in metaplastic breast cancer: stem-cell therapy in need? Lessons reported from a male patient.

OBJECTIVE: Metaplastic breast carcinomas represent a rare subtype of breast cancer exhibiting aggressive clinical features. They appear as highly chemoresistant tumors, therefore showing poor outcome and high rates of local recurrence or distant metastasis. CASE REPORT: A 37-year-old greek man was referred to our hospital for evaluation of a locally advanced, ulcerated, fixed, irregular and hard in consistency mass covering his left breast and chest wall. Further work out with CT and biopsy of the tumor revealed a triple negative metaplastic breast cancer classified as cT4cN3cM1. The patient received first line chemotherapy and afterward a palliative resection of the tumor. The histology revealed the presence of a combined triple negative adenocarcinoma with a predominant metaplastic squamous carcinoma and a spindle cell (sarcomatoid) carcinoma of the breast. In the tissue sample stem cell markers, nestin and CD146 (MCAM) were expressed, enhancing the theory that cancer cells of this tumor could possibly harbor stem cell properties. The patient received several chemotherapy regimens but died 6 months after the initiation of treatment. CONCLUSIONS: Metaplastic breast cancer consists of cells with stem cell properties. New targeted therapies are warranted in the view of the tumor's high resistance to conventional chemotherapy. Targeting nestin and CD146 might be a promising therapy as they seem to be implicated in the EMT pathway.

Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis.

BACKGROUND: In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear. MATERIAL AND METHODS: We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters. RESULTS: TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes. DISCUSSION: This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research.

Comparison Between Minimally Invasive and Open Gastrectomy for Gastric Cancer in Europe: A Systematic Review and Meta-analysis.

AIMS: We compared laparoscopic and robotic gastrectomies with open gastrectomies and with each other that were held for gastric cancer in Europe. METHODS: We searched for studies conducted in Europe and published up to 20 February 2015 in the PubMed database that compared laparoscopic or robotic with open gastrectomies for gastric cancer and with each other. RESULTS: We found 18 original studies (laparoscopic vs open: 13; robotic vs open: 3; laparoscopic vs robotic: 2). Of these, 17 were non-randomized trials and only 1 was a randomized controlled trial. Only four studies had more than 50 patients in each arm. No significant differences were detected between minimally invasive and open approaches regarding the number of retrieved lymph nodes, anastomotic leakage, duodenal stump leakage, anastomotic stenosis, postoperative bleeding, reoperation rates, and intraoperative/postoperative mortality. Nevertheless, laparoscopic procedures provided higher overall morbidity rates when compared with open ones, but robotic approaches did not differ from open ones. On the contrary, blood loss was less and hospital stay was shorter in minimally invasive than in open approaches. However, the results were controversial concerning the duration of operations when comparing minimally invasive with open gastrectomies. Additionally, laparoscopic and robotic procedures provided equivalent results regarding resection margins, duodenal stump leakage, postoperative bleeding, intraoperative/postoperative mortality, and length of hospital stay. On the contrary, robotic operations had less blood loss, but lasted longer than laparoscopic ones. Finally, there were relatively low conversion rates in laparoscopic (0%-6.7%) and robotic gastrectomies (0%-5.6%) in most studies. CONCLUSION: Laparoscopic and robotic gastrectomies may be considered alternative approaches to open gastrectomies for treating gastric cancer. Minimally invasive operations are characterized by less blood loss and shorter hospital stay than open ones. In addition, robotic procedures have less blood loss, but last longer than laparoscopic ones.

Incidence of inactive allele CYP2D6*4 among Greek women suffering from hormone-sensitive breast cancer.

BACKGROUND: The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The aim of the present study is to estimate the incidence of CYP2D6*4, in the Greek population and more precisely among females suffering from breast cancer. MATERIALS AND METHODS: Eighty unrelated mainland Greek female volunteers suffering from hormone-sensitive breast cancer were recruited during their primary handling or follow-up examination in order to provide samples for purification and polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) of genomic DNA derived from buccal swabs. RESULTS: The incidence of individuals with at least one present allele*4 within the Hellenic population was estimated to be as high as 30% (n = 24/80), with a 95% confidence interval of 20% to 40%. From the statistical point of view, it can be securely stated that incidence of *4 among Greek women is over 20%. The incidence of homozygous carriers of *4 in the present sample occurred in 8.75%, while the incidence of allele*4 haplo-type occurred in 19.4% (n=160). CONCLUSION: Although the outcoming results for Greek women are actually in line with existing data for other European nations, it should be noted, that a routine CYP2D6 testing of women suffering from breast cancer is formally not recommended, as the clinical significance of CYP2D6 phenotype in treatment and outcome of breast cancer remains unclear.

Platelet indices and netrophil to lymphocyte ratio in adults with acute appendicitis.

BACKGROUND: A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. METHOD: Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with histologically proven acute appendicitis upon admission, and of 50 healthy adults (20 men and 30 women). The parameters for white blood cells and platelets were compared between the two groups, and for each gender separately. RESULTS: A higher white blood cell count, neutrophil count, neutrophil percentage, neutrophil to lymphocyte ratio and lower lymphocyte percentage was reported in patients with acute appendicitis than that in the healthy controls, with high areas under the curve (AUC), sensitivities, specifi cities, positive predictive values (PPVs) and moderate negative predictive values (NPVs). The lymphocyte count was lower in patients than it was in the healthy controls. The platletcrit was lower in the female patients than that in the female controls, whereas a difference was not detected in the male participants. Differences were not detected with regard to platelet count, mean platelet volume and platelet distribution width for both genders. CONCLUSION: The neutrophil to lymphocyte ratio increases and lymphocyte percentage decreases in acute appendicitis, and can be used as an additional diagnostic marker. Plateletcrit, and therefore total platelet mass, is reduced in women with acute appendicitis, indicating the involvement of platelets in its pathophysiology. However, it is neither a reliable predictor or excluder of the disease.

Elevated Farnesoid X Receptor (FXR) and Retinoid X Receptors (RXRs) expression is associated with less tumor aggressiveness and favourable prognosis in patients with pancreatic adenocarcinoma.

UNLABELLED: Farnesoid X Receptor (FXR) and its co-partners Retinoid X Receptors (RXRs) are considered to participate in crucial biochemical and cellular processes, being involved in the pathogenesis of several diseases, including cancer. The present study aimed to evaluate the clinical significance of FXR alone and in conjunction with RXRs expression, in pancreatic adenocarcinoma. FXR, RXR-α, -ß and -γ protein expression was assessed immunohistochemically on tumoral samples of 55 pancreatic adenocarcinoma cases and was statistically analyzed with clinicopathological characteristics, tumor proliferative capacity and patients' survival. Enhanced FXR expression was borderline associated with earlier histopathological stage (p=0.054). Concomitant elevated FXR/RXR-α expression was significantly associated with decreased tumor histological grade (p=0.017), while concomitant enhanced FXR/RXR-ß and FXR/RXR-γ expression with earlier histopathological stage (p=0.017 and p=0.004, respectively) and smaller tumor size (p=0.037 and p=0.005, respectively). Concomitant enhanced FXR/RXR-γ expression was additionally significantly associated with the absence of lymph node metastases (p=0.018). Pancreatic adenocarcinoma patients with enhanced FXR, FXR/RXR-ß or -γ expression showed significantly longer survival times compared to those with low expression (p=0.013, p=0.021 and p<0.001, respectively). In multivariate analysis, FXR and FXR/RXR-γ expression were identified as independent prognostic factors (p=0.044 and p=0.001, respectively). CONCLUSION: The present study suggested that FXR and RXRs were implicated in pancreatic malignant disease progression, reinforcing their utility as clinical markers for patients' management and prognosis, as well as targets for potential therapeutic interventions. KEYWORDS: FXR, RXR, pancreatic adenocarcinoma, immunohistochemistry, clinicopathological parameters, patients' survival.

Pneumocystis jirovecii pneumonia in liver transplant recipients: a systematic review.

BACKGROUND: Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients. METHODS: We searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms "liver transplantation" and "pneumocystis." Our search yielded 60 articles, 35 of which were used for our review. RESULTS: P. jirovecii pneumonia (PJP) has an incidence of 1%-11% in liver transplant recipients without prophylaxis and mortality rates of 7%-88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%-3%. The duration of its use varies from 3 months to 1 year after the liver transplantation. CONCLUSIONS: PJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.

Platelet-activating factor (PAF) receptor expression is associated with histopathological stage and grade and patients' survival in gastric adenocarcinoma.

Platelet activating factor (PAF) has been considered as potent inflammatory lipid mediator that exerts its actions by binding to PAF receptor (PAFR). PAF/PAFR system has been implicated in several pathophysiological states, including tumor progression, angiogenesis and metastasis. The present study aimed to evaluate the clinical significance of PAFR expression in gastric adenocarcinoma. PAFR protein expression was assessed immunohistochemically on 54 gastric adenocarcinoma tissue samples and was analyzed in relation with clinicopathological parameters, tumor proliferative capacity and patients' survival. PAFR was abundantly expressed in all gastric adenocarcinoma cases examined. Increased PAFR expression was significantly more frequently observed in well/moderately compared to poorly differentiated gastric adenocarcinoma cases (p=0.011). PAFR expression was significantly increased in intestinal- compared to diffuse-type cases (p=0.020). Elevated PAFR expression was significantly associated with smaller tumor size, absence of lymph node and organ metastasis and low tumor histopathological stage (p=0.025, p<0.001, p=0.009 and p<0.001, respectively). Additionally, patients presenting elevated PAFR expression had significantly longer survival times compared to those with low PAFR expression (log-rank test, p<0.001). These results support an important potential role of PAFR signalling in gastric malignant disease progression and render further research in this field a necessity.

The role of ThinPrep cytology in the investigation of ki-67 index, p53 and HER-2 detection in fine-needle aspirates of breast tumors.

PURPOSE: The aim of the current study was to compare the immunocytochemical expression of ki-67, HER-2 and p53 on ThinPrep (TP)-processed smears, obtained by preoperative fine-needle aspiration (FNA) biopsies from primary breast carcinoma with the immunohistochemical results obtained on the corresponding surgical samples. METHODS: FNA biopsies were collected from 119 female patients during a 31-month period. Subsequently, these patients underwent surgical resection of the tumors. RESULTS: The overall accuracy (OA) of the TP cytology for ki-67, p53 and HER-2 expression was 96, 99 and 97%, respectively. There was a strong positive correlation between immunohistochemistry and immunocytochemistry results for ki-67 (Spearman's test 0.875) for p53 (Cramer's phi test 0.965) and HER-2 (Kendall's tau test 0.891). CONCLUSION: This pilot study demonstrates that it is possible to monitor multiple molecular markers by using the TP cytology. Sample collection and storage is simple and permits the assortment of the FNA sample for both morphologic diagnosis and ancillary studies. The accuracy of TP technique in the evaluation of ki-67, p53 and HER-2 expression is comparable to those of the histological evaluation, and could be of paramount importance for the preoperative planning of treatment.

Management of cystic and solid pancreatic incidentalomas: a review analysis.

Incidentally discovered pancreatic lesions that are asymptomatic have become much more common in recent years. It is important to characterize these lesions and to determine which patients can be safely observed and which should undergo an operation, as a substantial proportion of them might be malignant or premalignant. This review focus on the diagnostic approach and management of the different types of cystic and solid incidental pancreatic lesions based on appropriate clinical input, imaging screening and histological criteria. The task of developing guidelines to deal with an incidentally found pancreatic lesion, however, is much more complex and controversial than with other organs incidentalomas. In most series, pancreatic incidentalomas (PIs) <2 cm and of cystic appearance are likely to be benign, whereas those >2 cm are usually premalignant or malignant. Serous cystadenomas can reach very large size and are usually benign lesions. The presence of a solid mass or a mural nodule in a cystic lesion along with main pancreatic duct dilatation, thick septations and biliary obstruction are considered features suspicious of malignancy. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are malignant or lesions of malignant potential and need surgical exploration. Solid lesions are much more likely to be premalignant or malignant and most of patients will undergo resection. The decision to operate rather than follow a solid lesion is a matter of tumor size and of clinical judgment based on the age and patient comorbidities. The present study should serve as a general guide and not applied as strict principles. Key words: cystic pancreatic incidentalomas, diagnostic approach, management, solid pancreatic incidentalomas.

Focal nodular hyperplasia and hepatocellular adenoma: current views.

Focal Nodular Hyperplasia (FNH) is a rare benign hepatic lesion believed to generate upon a hyperplastic response of the hepatocyte. Hepatocellular Adenoma (HA) occurs predominantly in young women receiving oral contraceptive medication. These two lesions have drawn significant attention throughout the recent years due to their specific clinical and pathological features as well as their challenging management. Although Focal Nodular Hyperplasia is managed conservatively in the majority of cases, it can albeit pose a difficult diagnostic dilemma. On the other hand, Hepatocellular Adenoma can be complicated with catastrophic hemorrhage or malignant transformation and therefore mandates surgical excision in many cases. The aim of this work is to review the current literature pertaining to these two clinical entities regarding their pathogenesis, diagnostic approach and genetics, as well as to shed light on specific differential diagnostic issues arising in many cases these lesions are encountered.

Clinical significance of Src expression and activity in human neoplasia.

Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the human genome and member of the Src protein tyrosine kinases family (SFK). As described by Martin and Rous, a genetic recombination between c-src and the RSV oncogene of Rous sarcoma virus results in a modified Src protein, with increased intrinsic activity and transforming potential in animal and human tissues. Several in vitro and in vivo studies supported this theory providing insight in the signalling pathways involved. Accumulating evidence from studies on clinical samples supported the role of Src in the process of carcinogenesis and disease progression in several human malignancies. Some studies have further reinforced the significance of the kinase in malignacy by correlating its expression and/or activity with important clinicopathological parameters, such as tumour stage, histopathological grade, proliferative capacity and most importantly patient's survival. This review is a comprehensive report of the published evidence on the expression and clinical significance of Src in human malignancy, which constitutes the background of the current studies and clinical trials on the use of Src inhibitors as novel potent antineoplastic strategy.