Rapid Local Invasion Research Articles

Epigenomic integrative analysis pinpoint master regulator transcription factors associated with tumorigenesis in squamous cell carcinoma of oral tongue.

Head and Neck Cancer (HNC) is a heterogeneous group of cancers, which includes cancers arising in the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. Epidemiological studies have revealed that several factors such as tobacco and alcohol use, exposure to environmental pollutants, viral infection, and genetic factors are risk factors for developing HNC. The squamous cell carcinoma of oral tongue (SCCOT), which is significantly more aggressive than the other forms of oral squamous cell carcinoma, presents a propensity for rapid local invasion and spread, and a high recurrence rate. Dysregulation in the epigenetic machinery of cancer cells might help uncover the mechanisms of SCOOT tumorigenesis. Here, we used DNA methylation changes to identify cancer-specific enhancers that were enriched for specific transcription factor binding sites (TFBS), and potential master regulator transcription factors (MRTF) associated with SCCOT. We identified the activation of MRTFs associated with increased invasiveness, metastasis, epithelial-to-mesenchymal transition, poor prognosis, and stemness. On the other hand, we found the downregulation of MRTFs associated with tumor suppression. The identified MRTFs should be further investigated to clarify their role in oral cancer tumorigenesis and for their potential use as biological markers.

Long non‑coding RNA MIR4713HG aggravates malignant behaviors in oral tongue squamous cell carcinoma via binding with microRNA let‑7c‑5p.

Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive pathological types of head and neck squamous cell carcinoma, and presents with rapid local invasion and metastasis. The present study confirmed that the long non-coding (lnc) RNA MIR4713HG was markedly upregulated in both OTSCC tissues and cell lines and associated with poor survival. The present study performed a series of experiments to investigate the impact of MIR4713HG on OTSCC and revealed that upregulation of MIR4713HG had a crucial role in promoting cell proliferation and metastasis of OTSCC cell lines both in vitro and in vivo. By applying bioinformatics analyses, micro RNA let-7c-5p was observed to physically bind with MIR4713HG, and the knockdown of let-7c-5p could counteract the influence of MIR4713HG on OTSCC. Furthermore, the present study demonstrated that let-7c-5p performed its regulating role in OTSCC via affecting the expression level of transmembrane channel like 7 (TMC7). In conclusion, the present study demonstrated that lncRNA MIR4713HG acted as a pro-tumor factor facilitating cell proliferation and metastasis of OTSCC via affecting the let-7c-5p/TMC7 signaling pathway, which presents as a promising therapeutic target in OTSCC.

Renal Artery Embolization Before Radical Nephrectomy for Complex Renal Tumour: Which are the True Advantages?

IntroductionRenal artery embolization is performed before radical nephrectomy (RN) for renal mass in order to induce preoperative infarction and to facilitate surgical intervention through decrease of intraoperative bleeding. Moreover, in metastatic renal cancer it seems to stimulate tumour-specific antibodies, even if no established benefits in clinical response or survival have been reported. The role of preoperative renal artery embolization (PRAE) in management of renal masses has been often debated and its real benefits are still unclear. Nevertheless, in huge and complex renal masses, which are often characterized by a high and anarchic blood supply and rapid local invasion, radical nephrectomy can be challenging even for skilled surgeons. The aim of this prospective randomized study was to evaluate the effectiveness and safety of PRAE in complex masses by comparing perioperative outcomes of RN with and without PRAE.Materials and methodsFrom December 2015 to May 2018 we enrolled prospectively 64 patients who underwent RN for localized (T2a-b) or locally advanced (T3 and T4) or advanced (N+, M+) renal cancers. Patients were divided in two groups. The first group included 30 patients who underwent PRAE; in the second group we enrolled 34 patients who did not undergo RN without PRAE. Perioperative outcomes in terms of operative time, blood loss, transfusion rate and length of hospitalization were evaluated. Statistical analysis was performed using GraphPad Prism 6.0 software.ResultsMedian blood loss was 250 ml (50-500) and 400 ml (50-1000) in the first and second group, respectively, with a statistically significant difference (p=0.0066). Median surgical time was 200 min (90-390) and 240 min (130-390) in PRAE and No-PRAE group (p=0.06), respectively. No major complications occurred after embolization. Overall complication rate in Group 1 and 2 was 46.7% (14/30) and 50% (17/34), respectively (p=0.34). No major complications occurred in both groups. The mean follow up was 21,5 months.ConclusionsOur results prove PRAE to be a safe procedure with low complications rate. To our experience, PRAE seems to be a useful tool in surgical management of a large mass and advanced disease.

Surfactant Variations in Porous Media Localize Capillary Instabilities during Haines Jumps.

We use confocal microscopy to measure velocity and interfacial tension between a trapped wetting phase with a surfactant and a flowing, invading nonwetting phase in a porous medium. We relate interfacial tension variations at the fluid-fluid interface to surfactant concentration and show that these variations localize the destabilization of capillary forces and lead to rapid local invasion of the nonwetting fluid, resulting in a Haines jump. These spatial variations in surfactant concentration are caused by velocity variations at the fluid-fluid interfaces and lead to localization of the Haines jumps even in otherwise very uniform pore structure and pressure conditions. Our results provide new insight into the nature of Haines jumps, one of the most ubiquitous and important instabilities in flow in porous media.

Abstract 3061: AS-10: a new small molecule with promising activity against pancreatic cancer

Abstract Patients with pancreatic cancer (PC) have a median survival of only 6 months and a five-year survival of less than 5%, hence making PC one of the deadliest cancer. Severity of PC is due to its identification at late stages, rapid local invasion, early metastases, and meager response to current chemotherapeutic agents. Current therapies result in minimal survival advantage and are linked with multiple adverse events and drug resistance. Hence, there is an urgent need for novel agents which are less toxic and offer greater benefits over conventional therapy. There is ample evidences in literature demonstrating that inflammation plays a critical role in PC growth and promotion. Nuclear factor κB (NF-κB) pathway, one of the major inflammatory pathway, is well known for its inflammatory response, cell proliferation, and resistance to apoptosis. It has been demonstrated that activation of NF-κB in PC is also responsible for resistance towards first line chemotherapeutic agent, gemcitabine, in PC. Through extensive structure-activity relationship studies, we have recently identified a novel small molecule, AS-10, which was lethal to PC cells. We sought to evaluate the mechanism of action of AS-10 responsible for inhibiting the growth of PC cells. In vitro, AS-10 reduced PC cell growth with an EC50, in the range of 2.5 to 5 μM. Growth arrest was confirmed by cell cycle studies, which showed that AS-10 induced G1 and G2 cell cycle arrest. The cell cycle arrest was associated with an increase of cell cycle inhibitory markers like p21 and p27. Effect of AS-10 on cell cycle was translated into activation of apoptosis, confirmed by caspase 3/7 activity, PARP cleavage and Annexin V staining. Due to its structural characteristics, we evaluated the effect of AS-10 on inflammatory NF-κB pathway. Our studies, in Panc-1 cells, showed that AS-10 inhibited NF-κB DNA binding activity as well as NF-κB translocation to the nuclei in the presence of inflammatory stimuli (tumor necrosis factor (TNFα)). Since, up regulation of NF-κB activity has been known to be responsible for gemcitabine resistance in PC, we evaluated the activity of our NF-κB inhibitor AS-10 in combination with gemcitabine, and showed that AS-10 synergistically potentiated gemcitabine activity in PC cells. Taken together, these results suggest that AS-10, may represent a potentially promising therapeutic agent for PC. Detailed investigations regarding the efficacy and mechanism of action of these compounds will be presented. Citation Format: Deepkamal Karelia, Manoj K. Pandey, Daniel Plano, Shantu Amin, Arun K. Sharma. AS-10: a new small molecule with promising activity against pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3061.

Multimodal treatment of sporadic and inherited neuroendocrine tumors of the thymus

Neuroendocrine tumors of the thymus (NETT) are a rare tumor entity of the anterior mediastinum. They belong to the category of foregut carcinoids and are often associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome. Approximately 180 cases have been reported since their first description. NETT reveal an aggressive behavior leading to rapid local invasion and metastatic spread. An aggressive surgical approach may achieve long-term survival. Patients presenting from 1990 to 2005 at the Department of Surgery and the Department of Gastroenterology of the Philipps-University Marburg with neuroendocrine tumors were enrolled in a prospective database with a follow-up until 2005. Fifty MEN1-patients were enrolled in a study and screening program. These databases were retrospectively reviewed identifying all patients with NETT. The clinical features, therapeutical approaches and the outcome were analyzed. Six patients were found with NETT, 4 patients suffered from metastases at the time of presentation. All patients were male, with a median age of 41.3 years at presentation. Four out of these 6 patients revealed MEN1 syndrome. All patients underwent tumor resection via sternotomy. Three patients underwent parathyreoidectomy and transcervical thymectomy before the NETT was diagnosed. Median survival was 53 months (range, 24-109). Given a frequent association between MEN1 and NETT, all patients with NETT should be screened for MEN1. Since transcervical thymectomy does not prevent all MEN1 patients from developing NETT, existing surveillance guidelines for MEN1 should consider CT scan of the thorax on a regular basis.

Local activity of matrix metalloproteinases in a case of botryoid sarcoma

The aim of the study was to assess the activities of the collagenases type IV (matrix metalloproteinase type 2 [MMP-2] and matrix metalloproteinase type 9 [MMP-9]), also known as gelatinases, and the local activity of interstitial collagenase (matrix metalloproteinase type I[MMP-1]) in tissue extracts from a case of the botryoid sarcoma, a rare and very malignant tumour of the female genital tract. Zymography revealed that botryoid sarcoma does not express the 92-kDa form of type IV collagenase activity in Triton extract and only weak activity in Heat extract when compared to values found in extracts from striated muscle and fibroma uteri. MMP-1 appeared in the latent form only in the Triton extract of botryoid sarcoma and its activity was lower than those found in the control tissues. These results indicate that the very rapid local invasion and systemic metastases associated with botryoid sarcoma do not depend on the activity of tumour-derived gelatinases.

Primary sarcomas of the temporal bone.

Primary sarcomas of the temporal bone are rare. Symptoms include otorrhea, bleeding, hearing loss, and frequently facial paralysis. The undifferentiated type and the rhabdomyosarcomas are the most common. The neoplasms are highly malignant with rapid local invasion destroying the petrous apex, mastoid, middle ear, and often eroding into the bony and membranous labyrinth. Extension may occur to the middle and posterior cranial fossae. Metastasis is early, usually to the lungs and bones. Combined surgery, irradiation, and chemotherapy have produced the best results in treatment; however, the prognosis is usually poor.