Invasion Of Adjacent Tissues Research Articles

Oncocitoma renal na gravidez – uma forma invulgar de hipertensão secundária

IntroductionRenal oncocytoma accounts for 5-7% of primary renal neoplasms. It is usually diagnosed in asymptomatic patients and is characterized by a benign behavior without invasion of adjacent tissues or metastasis. Diagnosis during pregnancy is uncommon and to date there have been only a few cases reported in the literature. Case reportThe authors present the case of a 32-year-old nulliparous woman with uncontrolled hypertension diagnosed at seven weeks gestation. She was referred to our institution at 24 weeks with superimposed pre-eclampsia complicated by acute pulmonary edema and hemodynamic instability requiring mechanical ventilatory support, fetal growth restriction and stillbirth. Etiological study of the hypertensive disorder performed in the postpartum period was consistent with renal oncocytoma. ConclusionThe clinical behavior of renal oncocytoma remains poorly characterized during pregnancy and may lead to an adverse maternal and fetal outcome despite its theoretically benign behavior. It is essential to exclude a possible secondary cause of hypertension in cases that are difficult to control.

Pilot Feasibility Study of Neoadjuvant Chemoradiotherapy with S-1 in Patients with Locally Advanced Gastric Cancer Featuring Adjacent Tissue Invasion or JGCA Bulky N2 Lymph Node Metastases

To improve the prognosis of locally advanced gastric cancer, clinical trials of neoadjuvant chemotherapy (NAC) are being performed. Although neoadjuvant chemoradiotherapy (NACRT) generally achieves superior local tumor control to NAC, its efficacy for locally advanced gastric cancers remains unclear. Therefore, a prospective trial was conducted to explore the feasibility and safety of NACRT with oral S-1 in a series of cases. Patients who had Japanese Gastric Cancer Association (JGCA) cStage IIIB gastric cancer were enrolled onto this study and received oral S-1 (65 mg/m(2)/day) administration and 50-Gy radiotherapy followed by radical surgery. The primary end points were completion of therapy and safety. Between October 2005 and September 2008, 12 eligible patients were enrolled. Two could not complete the chemotherapy because of grade 3 toxicity. R0 resections were performed in 11 patients (91.7 %) (95 % confidence interval 61.5-99.8). Although operative morbidity was observed in two cases, there were no postoperative deaths. A pathologic response was observed in 10 patients (83.3 %). In five (62.5 %) of eight gastric cancers with invasion to adjacent structures, microscopic tumor deposits were not found in the affected organs. The 3-year survival rate was 58.3 % during a median follow-up period of 36 months. Although this study is preliminary, the present regimen seems to be feasible and safe as a treatment for locally advanced gastric cancers featuring adjacent tissue invasion or JGCA bulky N2 disease. This treatment approach should now be tested using the new tumor, node, metastasis staging system in a large clinical trial.

Unexpected Dramatic Response of Pretreated Invasive Thymic Malignancies on Pemetrexed-Case Report and Review of Current Treatment Modalities

Thymomas are rare and usually slowly growing tumors, originating from the epithelial layer of the thymus. Prognosis depends on the extent of invasion of adjacent tissues whereby multimodality treatment including surgery with or without adjuvant chemoradiotherapy is the preferred approach for locally advanced thymomas. For metastatic thymomas, only few chemotherapeutic options are available. We report 2 cases of patients with metastatic thymic malignancies with a dramatic response on pemetrexed treatment. The choice for this antifolate therapy is based upon a small series. Because metastatic thymic neoplasm is a rare disease, large randomised trials are not feasible. Case reports on the treatment of these malignancies are very important and can provide readers with the opportunity to deal with rare dis- eases.

Parathyroid Carcinoma

Hyperparathyroidism is a common endocrine disease with several causes. Of these etiologies, parathyroid carcinoma is very rare, occurring in less than 1% of patients with primary hyperparathyroidism. Parathyroid carcinoma can be diagnosed by unequivocal evidence of capsular or vascular invasion or invasion of adjacent tissues or organs. The diagnosis of malignancy can be challenging in the absence of clear-cut invasion. This article presents the clinical and histopathologic characteristic of parathyroid carcinoma, its differential diagnosis, and ways to approach problematic cases. Some useful ancillary studies are also discussed.

English

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Therefore, the present study is aimed at detecting the highly expressed genes, responsible for lung cancer through Serial Analysis of Genome Expression (SAGE) Genie at Cancer Genome Anatomy Project (CGAP). IGL@ (Immunoglobulin lambda locus) gene is predominantly highly expressed in the lung cancer and is considered to be a new target for the Cancerous diseases. The protein was retrieved from the Swissprot/Uniprot KB with accession number Q6GMX3 and was modelled using MODELLER9v7 for predicting the 3D structure of the IGL @ protein which provides an accurate and efficient module to build loops and side chains, found to be identical in sequence. Modelled structure revealed appreciable measures when subjected to structure verification and evaluation using PROCHECK. Ramachandran plot signified the present work undertaken through conformational parameters ᶲ (phi) and ψ (psi) angles calculated from model with 93.4% residues in most favoured region. Further, PROCHECK results confirmed acceptance of model through main and side)chain values. Root mean square distance of planarity was found below 0.02. Hence the model was revealed to have good stereochemistry. Structure of IGL@ Protein can be important tool for future endeavours towards structure based drug designing techniques to impel the search of new efficient inhibitors. Keywords ) SAGE, Lung Cancer, Highly Expressed Genes, Comparative Modeling, PROCHECK

Extramedullary Plasmacytoma of the Nasopharynx: A Rare Tumour with 7-Year Follow Up

Objective: To report a case of extramedullary plasmacytoma, a rare localized tumour involving
 the head and neck region in a 56-year -old gentleman.
 
 Methods:
 Design: Case Report
 Setting: Tertiary University Referral Center
 Patient: One
 
 Result: The patient presented with a 5-month history of right-sided nasal obstruction and intermittent epistaxis in 2003. Nasal endoscopy revealed a friable, dark red mass arising from the roof of the nasopharynx, occluding the right choana. No invasion of adjacent tissues or cervical lymphadenopathy was evident. A biopsy of the mass was diagnosed as plasmacytoma. Serum and urine electrophoresis failed to detect any monoclonal bands. All other screening tests to rule out multiple myeloma were negative. These findings confirmed the diagnosis of extramedullary plasmacytoma. He recieved radiotherapy to the nasopharynx of 50 Gy for a total of 23 fractions. No recurrence was noted at 7-year follow-up.
 
 Conclusion: Extramedullary plasmacytoma of the nasopharynx represents a tumour with good prognosis but requires long term follow up in anticipation of local recurrence and progression to Multiple Myeloma.
 
 Keywords: extramedullary, plasmacytoma, nasopharynx

An analysis of the magnetic resonance imaging and pathology of intracal lymphoplasmacyte-rich meningioma

To discuss the MRI features of the intracranial lymphoplasmacyte-rich meningioma and the correlation between the MRI features and pathology. Review retrospectively the MRI and pathologic data of seven patients with lymphoplasmacyte-rich meningioma which were confirmed by surgery and pathology. The seven cases of lymphoplasmacyte-rich meningioma were solitary, six cases demonstrated flat growth along the meninges, five cases had not yet formed specific nodules, and two cases exhibited irregular lobulation. Seven cases had no clear boundary, peritumoral brain edema was obvious and adjacent brain tissues were invaded to varying degrees. After plain MRI scans, the focuses of seven cases exhibited lower-isointense signal in T1WI, five cases revealed higher-isointense signal and two cases showed lower-isointense signal in T2WI. Enhancement scans demonstrated marked enhancement in seven cases, and the meninges in six cases thicken irregularly and extensively. Pathology showed the richness and diversity of cells, an infiltration containing plasma cells and lymphocytes, as well as the unequal areas of neoplastic spindle cells and meninge epithelial cells. Lymphoplasmacyte-rich meningioma is a subtype meningioma of WHO I-grade, which is seldom seen and whose imaging appearances are varied from ordinary meningioma. Its features include growing flat along the meninges, irregular forms, unclear boundary, obvious edema, notable strengthening effect, usual invasion of adjacent brain tissues, and similar inflammation.

The heterogeneity of meningioma revealed by multiparameter analysis: infiltrative and non-infiltrative clinical phenotypes

Tumor invasion or infiltration of adjacent tissues is the source of clinical challenges in diagnosis as well as prevention and treatment. Among brain tumors, infiltration of the adjacent tissues with diverse pleiotropic mechanisms is frequently encountered in benign meningiomas. We assessed whether a multiparametric analysis of meningiomas based on data from both clinical observations and molecular analyses could provide a consistent and accurate appraisal of invasive and infiltrative phenotypes and help determine the diagnosis of these tumors. Tissue analyses of 37 meningiomas combined enzyme-linked immunosorbent assay (ELISA) and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) assays of two different protein biomarkers (thrombospondin 1 and a phosphorylated form of vimentin) as well as gene expression analyses with oligonucleotide micro-arrays. Up to four different clinical and molecular parameters were then examined for tumor classification. From this study, we were able to cluster 36 out of the 37 tumors into two different subsets corresponding to infiltrative/invasive and non-infiltrative tumors. In addition, meningiomas that invade brain and those that infiltrate the neighboring skull bone exhibited no distinguishable molecular features. Our multi-parameter analysis that combines clinical data, transcriptomic and molecular assays clearly reveals the heterogeneity of meningiomas and distinguishes the intrinsically infiltrative/invasive tumors from the non-infiltrative meningiomas.

Using ex vivo proton magnetic resonance spectroscopy to reveal associations between biochemical and biological features of meningiomas

The goal in this study was to determine if proton ((1)H) MR spectroscopy can differentiate meningioma grade and is associated with interpretations of biological behavior; the study was performed using ex vivo high-resolution spectra indicating metabolic characteristics. Sixty-eight resected tissue samples of meningiomas were examined using ex vivo (1)H MR spectroscopy. Of these meningiomas, 46 were WHO Grade I, 14 were WHO Grade II, and 8 were WHO Grade III. Fifty-nine were primary meningiomas and 9 were recurrences. Invasion of adjacent tissue (dura mater, bone, venous sinus, brain) was found in 32 cases. Thirty-nine meningiomas did not rapidly recur (as defined by expansion on MR imaging within a 5-year follow-up period), whereas rapid recurrence was confirmed in 24 meningiomas, and follow-up status was unknown in 5 cases. The absolute concentrations of total alanine and creatine were decreased in high-grade compared with low-grade meningiomas, as was the ratio of glycine to alanine (all p < 0.05). Additionally, alanine and the glycine/alanine ratio distinguished between primary and recurrent meningiomas (all p < 0.05). Finally, the absolute concentrations of alanine and creatine, and the glycine/alanine and choline/glutamate ratios were associated with rapid recurrence (p < 0.05). These data indicate that meningioma tissue can be characterized by metabolic parameters that are not typically identified by histopathological analysis alone. Creatine, glycine, and alanine may be used as markers of meningioma grade, recurrence, and the likelihood of rapid recurrence. These data validate a previous study of a separate group of Grade I meningiomas.

Expression of E-cadherin, Snail and Hakai in epithelial cells isolated from the primary tumor and from peritumoral tissue of invasive ductal breast carcinomas

Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epithelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.

Histopathology reporting of breast cancer in Queensland: the impact on the quality of reporting as a result of the introduction of recommendations

Recommendations for the pathology reporting of breast cancer were released in Australia to ensure detailed communication of important prognostic features and good patient management. An audit of the reporting of invasive breast cancer in Queensland was conducted to determine how well these guidelines were utilised in 2004. A random sample of reports was audited for inclusion of recommended criteria. The proportion of reports meeting each of the criteria was determined and compared across whether the report was in a synoptic report template or in a free text format. Comparison was made with published data from prior to the release of the recommendations. Of the 419 reports in the sample, at least 90% of reports included lesion size, histological type, histological grade, lymph node involvement, margins of excision, lymphovascular invasion, and changes in adjacent breast tissue individually, and 74% included all seven of these essential criteria. Synoptic reports accounted for 76% of the sample and were significantly more likely to have documented grade (p < 0.001), quadrant (p = 0.003), calcification (p < 0.001), lymphovascular invasion (p < 0.001), changes in non-neoplastic breast (p < 0.001) and ductal carcinoma in situ criteria (p < 0.001) compared with free text report format. The most notable improvements since the implementation of the recommendations were in documentation of adjacent breast tissue (92% versus 49%) and lymphovascular invasion (97% versus 54%). Breast cancer reporting in Queensland has improved since the implementation of the recommendations, however further improvements would likely be seen if there is more widespread utilisation of a synoptic report format.

The Metastatic Process: Methodological Advances and Pharmacological Challenges

The metastatic spread of cancer is still the major barrier to the treatment of this disease. Understanding the molecular mechanisms underlying the metastatic process is of crucial importance to tune novel therapeutic strategies aimed at contrasting the dissemination of cancer. Metastasis is a sequential multistep process that ultimately leads to the cancer's outgrowth in a different organ from which it had originated. This clinically and experimentally involves the following steps: invasion of adjacent tissues, intravasation, transport of cancer cells through the circulatory system, arrest at a secondary site, extravasation and growth in a secondary organ. Additionally, tumor growth and metastasis depend on the ability of the tumor to induce its own blood supply through angiogenesis. Each of these steps can potentially be targeted by therapeutic agents, but the limited knowledge regarding the molecular events of metastasis makes most therapeutic strategies largely inefficient. However, important methodological advances have recently led to further insights into the biology of metastasis, thus raising the possibility of designing more appropriate pharmacological strategies to contrast the specific steps of the metastatic process. A variety of pharmacological approaches including inhibition of tumor invasion, angiogenesis, signal transduction pathways, and most recently the targeting of tumor stroma, are now under fervent development. Benefits and limits of these approaches, as well as, new therapeutic opportunities are herein discussed. Agents that limit any phase of the metastatic process may be therapeutically useful. Therefore, the future pharmacological challenge will be to combine drugs that target different aspects of this complex multistep process.

Perioperative Factors Affecting Long-Term Outcomes of 473 Consecutive Patients Undergoing Hepatectomy for Hepatocellular Carcinoma

The aim of this study was to evaluate the long-term outcomes of liver resection for hepatocellular carcinoma (HCC). Between January 1993 and December 2002, a total of 473 patients underwent hepatectomy for HCC at a medical center in Taiwan. Clinicopathological and surgical characteristics were studied to identify prognostic factors influencing survival. There were 379 men (80.1%) with mean +/- standard deviation age of 53.1 +/- 13.1 years. The etiology of HCC was hepatitis B (n = 277), hepatitis C (n = 90), coinfection with hepatitis B and C (n = 47), and non-B or C hepatitis (n = 50). The blood loss was 282.3 +/- 370.5 ml, and 411 patients (86.9%) did not require perioperative blood transfusion. On univariate analysis, the statistically significant independent factors for disease-free survival were alfa-fetoprotein (AFP) levels of >400 ng/ml, indocyanine green retention of >10%, Pringle maneuver, blood transfusion, tumor diameter >5 cm, bilateral tumors, microvascular invasion, adjacent tissue invasion, daughter nodules and cirrhotic liver. The univariate factors influencing overall survival were similar to those influencing disease-free survival except for AFP. Independent factors that statistically significantly affected overall survival on multivariate analysis included Pringle maneuver, blood transfusion, tumor diameter >3 cm, microvascular invasion, daughter nodules, and liver cirrhosis. The 1-, 5-, and 10-year disease-free survival were 75.3, 43.3, and 22.3%, respectively. The 1-, 5-, and 10-year overall survival were 86.7, 55, and 33.7%, respectively. AFP, indocyanine green retention of >10%, blood transfusion, Pringle maneuver, tumor diameter of >3 cm, bilateral tumors, microvascular invasion, adjacent tissue invasion, daughter nodules, and liver cirrhosis influence survival.

Magnetic Resonance Imaging of Cystic and Endocrine Pancreatic Neoplasms

This article describes the appearance of miscellaneous cystic and endocrine neoplasms using magnetic resonance imaging (MRI). Magnetic resonance imaging is a useful diagnostic modality in the assessment of various pancreatic neoplasms. Pancreatic endocrine tumors are moderately low in signal intensity on T1-weighted fat-suppressed images and moderately high in signal intensity on T2-weighted fat-suppressed images and demonstrate homogeneous, ring, or diffuse heterogeneous enhancement on immediate postgadolinium gradient echo images. Cystic pancreatic neoplasms, including intraductal papillary mucinous neoplasm, are well demonstrated and subcategorized according to their characteristic cystic configurations on MRI and MR cholangiopancreatography images. Microcystic serous cystadenomas are demonstrated as a honeycombed appearance on T2-weighted images and have a central stellate scar. Mucinous cystic neoplasms usually appear as multilocular cystic masses, with benign forms of macrocystic tumors possessing uniform thickness septations and malignant forms exhibiting irregular septations and tumor nodules. The presence of tumor stroma, invasion of adjacent tissue, or liver metastases can be assessed by MRI. The connection between the pancreatic duct and the cystic tumor is usually well shown on MR cholangiopancreatography images.

A Case of Fibromatosis Occurring in the Levator Scapulae

Fibromatosis is a benign tumor arising from the musculoaponeurotic tissues of the body. The natural history of fibromatosis is slow, progressive growth with invasion of adjacent tissues but this tumor has no malignant or metastatic potential. Complete surgical excision is the mainstay of treatment. However, it is often difficult due to the complex anatomy, close proximity of vital structures in the head and neck region. Preoperative core needle biopsy and MR images can make it possible to diagnose preoperatively and outline the tumor extent, which are very important to treat patients with fibromatosis. In this report, a rare case of fibromatosis occurring in the levator scapulae muscle is presented with a review of literatures. Korean J Otorhinolaryngol-Head Neck Surg 2009;52:1001-4 Key WordZZFibromatosis.

Urban Malignancy: Similarity in the Fractal Dimensions of Urban Morphology and Malignant Neoplasms

All contemporary landscapes on the planet feature the aggressive growth of cities and other urbanizations. In 1990, we suggested that the similarity between urban forms and malignant lesions could be studied with the use of fractal geometry. Two separate disciplines have emerged since then: the study of urban morphology using various fractal analyses, and “oncological mathematics,” the study of malignant lesions using fractal analysis. Several mathematical techniques are used in both fields to conduct these studies. From the point of view of a physician, the expanding, invasive, colonizing urban form with highly irregular borders resembles a malignant lesion. Malignant neoplasms have at least four major characteristics: rapid, uncontrolled growth; invasion and destruction of adjacent normal tissues (ecosystems); metastasis (distant colonization); and de-differentiation. Many urban forms are almost identical in general appearance, a characteristic that would qualify as “de-differentiation.” Large urban settlements display “rapid, uncontrolled growth” expanding in population and area occupied at rates of from 5 to 13% per year. We propose a null hypothesis that “there is no similarity or correlation in the fractal dimension of urban forms and malignant neoplasms.”

A Novel Role for Tissue Factor Pathway Inhibitor-2 in the Therapy of Human Esophageal Carcinoma

Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI-2 in the development of esophageal carcinoma. Western blotting revealed that TFPI-2 was downregulated in 75% of esophageal carcinomas and in most esophageal carcinoma cell lines. Immunohistochemistry revealed that TFPI-2 was significantly downregulated in tumor tissues and in lymph node metastases. Experimental overexpression of TFPI-2 in KYSE450, KYSE510, YES2, and EC9706 cells significantly inhibited their invasive ability. Overexpression of TFPI-2 in EC9706 cells inhibited xenograft tumor growth and invasion into surrounding tissues, as well as reduced lung metastasis. Further studies demonstrated that recombinant TFPI-2 protein significantly inhibited the activity of matrix metalloproteinases and tumor-related angiogenesis. Parenteral treatment with recombinant TFPI-2 protein significantly suppressed xenograft growth and metastasis. Together, these data indicate that TFPI-2 inhibits tumor invasion and angiogenesis both in vitro and in vivo, and suggest a potentially important therapeutic role for recombinant TFPI-2 in the treatment of malignant esophageal carcinomas.

Pathology of conjunctival melanocytic neoplasms

Abstract Purpose To describe the classification, grading and staging of conjunctival melanocytic proliferation. Methods We have audited our experience with conjunctival melanomas, using a novel mapping system and have found shortcomings in the current Tumour Node Metastasis (TNM) staging system. We have also reviewed our cases of intra‐epithelial melanocytic neoplasia and confirmed other authors’ impressions that conjunctival ‘primary acquired melanosis with atypia’ is histologically similar to cutaneous in situ melanoma. To improve objectivity in the reporting of conjunctival intra‐epithelial melanocytic neoplasia, we propose a scoring system based on pattern of melanocytic infiltration, density of melanocytes &amp; degree of cellular atypia. Results The term ‘conjunctival melanosis’ should be used only to describe the slit‐lamp appearance of hyperpigmentation. Histologically, this abnormality should be categorized as ‘hypermelanosis’ or ‘melanocytosis’. Hypermelanosis can either be primary or secondary to ocular or systemic disease. Benign melanocytosis comprises conjunctival melanocytic hyperplasia and naevi. Malignant melanocytosis is essentially melanoma, which is primary (in situ or invasive) or secondary (i.e., spreading to conjunctiva from adjacent tissues) or rarely metastatic. We suggest that the TNM staging system for conjunctival melanoma should be revised to: (1) include a Tis stage; (2) take account of superficial extent, invasion of adjacent tissues and caruncular involvement, in stages TI to TIII; and (3) to sub‐categorize TIV disease so that there is better correlation with likely mortality. Conclusion We have revised the classification of conjunctival melanocytic proliferations &amp; improved the grading and staging of melanoma. These developments should be useful in treatment &amp; research.

TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression

Esophageal cancer is characterized by rapid clinical progression and poor prognosis due to adjacent tissue invasion and distant organs metastasis at a very early stage. TM4SF3 (transmembrane 4 superfamily 3), a member of tetraspanin family, has been reported as a metastasis associated gene in many types of tumors. Herein, we described new properties of TM4SF3 in tumor metastasis, which suggested that this gene might be involved in esophageal carcinoma metastasis. Western blotting revealed that TM4SF3 was overexpressed in 57.1% (8/14) of esophageal carcinomas and esophageal carcinoma cell lines with high-invasive potential. Exogenous expression of TM4SF3 in two low-invasive esophageal carcinoma cell lines, KYSE150 and EC9706, significantly promoted cell migration and invasion. Upregulating TM4SF3 expression in EC9706 cells promoted xenograft tumor invading into surrounding tissues, enhanced lung metastasis, and shortened the lifespan of mice (median survival EC9706-TM4SF3 106.5 days versus EC9706-Vector 169.0 days, P < 0.0001) in a spontaneous metastasis model. Further studies demonstrated that ADAM12m was upregulated by TM4SF3 overexpression in vitro and in vivo. Abrogating up-expression of ADAM12m by siRNA significantly suppressed TM4SF3-mediated invasion. Together, these data from our studies indicated that overexpression of TM4SF3 in esophageal cancer conferred advantage to the invasion and metastasis of this destructive disease. Upregulated expression of ADAM12m by TM4SF3 might play a key role in TM4SF3-mediated invasion and metastasis. TM4SF3 and ADAM12m might be potential targets of esophageal carcinoma for anti-metastasis therapy.

90 INVITED Signal transduction pathways in colorectal cancer (CRC)

Neuroendocrine tumors (NETs) are heterogeneous neoplasms with respect to molecular characteristics and clinical outcome. Although slow-growing, NETs are often late diagnosed, already showing invasion of adjacent tissues and metastases. Precise knowledge of NET biological and molecular features has opened the door to the identification of novel pharmacological targets. Therapeutic options include somatostatin analogs, alone or in combination with interferon-α, multi-targeted tyrosine kinase inhibitors (e.g. sunitinib) or mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus). Antiangiogenic approaches and anti insulin-like growth factor receptor (IGFR) compounds have been also proposed as combination therapies with the aforementioned compounds. This review will focus on recent studies that have improved therapeutic strategies in NETs, discussing management challenges such as drug resistance development as well as focusing on the need for predictive biomarkers to design distinct drug combinations and optimize pharmacological control.