An unusual presentation of adenoid cystic carcinoma of the minor salivary glands with cranial nerve palsy: a case study

<p>Abstract</p> <p>Background</p> <p>Adenoid Cystic Carcinoma (ACC) is a rare tumor entity and comprises about 1% of all malignant tumor of the oral and maxillofacial region. It is slow growing but a highly invasive cancer with a high recurrence rate. Intracranial ACC is even more infrequent and could be primary or secondary occurring either by direct invasion, hematogenous spread, or perineural spread. We report the first case of the 5^thand 6^thnerve palsy due to cavernous sinus invasion by adenoid cystic carcinoma.</p> <p>Case presentation</p> <p>A 49-year-old African American female presented to the emergency room complaining of severe right-sided headache, photophobia, dizziness and nausea, with diplopia. The patient had a 14 year history migraine headaches, hypertension, and mild intermittent asthma. Physical examination revealed right lateral rectus muscle palsy with esotropia. There was numbness in all three divisions of the right trigeminal nerve. Motor and sensory examination of extremities was normal. An MRI of the brain/brain stem was obtained which showed a large mass in the clivus extending to involve the nasopharynx, pterygoid plate, sphenoid and right cavernous sinuses.</p> <p>Biopsy showed an ACC tumor with a cribriform pattern of the minor salivary glands. The patient underwent total gross surgical resection and radiation therapy.</p> <p>Conclusion</p> <p>This is a case of ACC of the minor salivary glands with intracranial invasion. The patient had long history of headaches which changed in character during the past year, and symptoms of acute 5^thand 6^thcranial nerve involvement. Our unique case demonstrates direct invasion of cavernous sinus and could explain the 5^thand 6^thcranial nerve involvement as histopathology revealed no perineural invasion.</p

Frequent downregulation of 14-3-3 σ protein and hypermethylation of 14-3-3 σ gene in salivary gland adenoid cystic carcinoma

14-3-3 σ, a target gene of the p53 tumour suppressor protein, has been shown to regulate the cell cycle at the G2/M checkpoint. Recent studies have demonstrated that 14-3-3 σ is downregulated by hypermethylation of the CpG island in several types of cancer. In this study, we investigated the expression and methylation status of 14-3-3 σ in human salivary gland adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Immunohistochemical analysis revealed that the positive expression rate of 14-3-3 σ in ACC (one out of 14) was markedly lower than that in MEC (ten out of 10). Since most of the ACCs carried the wild-type p53 protein, downregulation of 14-3-3 σ in ACC may not be due to the dysfunction of p53 pathway. Microdissection–methylation-specific PCR revealed that frequent hypermethylation of the 14-3-3 σ gene was observed in ACC when compared to that in MEC. In cultured-ACC cells, we confirmed the downregulation of 14-3-3 σ via hemimethylation of the gene by sequencing analysis after sodium bisulphite treatment. Furthermore, re-expression of 14-3-3 σ in the ACC cells was induced by the treatment with DNA demethylating agent, 5-aza-2′-deoxycytidine. Irradiation apparently induced the enhanced expression of 14-3-3 σ and G2/M arrest in normal salivary gland cells; however, in the ACC cells, neither induction of 14-3-3 σ nor G2/M arrest was induced by irradiation. These results suggest that downregulation of 14-3-3 σ might play critical roles in the neoplastic development and radiosensitivity of ACC

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug

ADP is the Dominant Controller of AMPactivated Protein Kinase Activity Dynamics in Skeletal Muscle during Exercise

Exercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that AMPK activity dynamics are determined principally by ADP and not AMP. We then used the model to predict the effects of two additional direct-binding activators of AMPK, ZMP and Compound 991, further validating the model and demonstrating its applicability to understanding AMPK pharmacology. The relative effects of direct-binding activators can be understood in terms of four properties, namely their concentrations, binding affinities for AMPK, abilities to enhance AMPK phosphorylation, and the magnitudes of their allosteric activation of AMPK. Despite AMP’s favorable values in three of these four properties, ADP is the dominant controller of AMPK activity dynamics in skeletal muscle during exercise by virtue of its higher concentration compared to that of AMP

Dynamic models for bird community in farming landscapes

International audienc

PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BackgroundCetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC.Patients and methodsPREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety.ResultsA total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies.ConclusionsECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients

Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial†

International audienceBACKGROUND:The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC).PATIENTS AND METHODS:Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT.RESULTS:The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively.CONCLUSION:CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings.EUDRA CT NO:2007-007029-38