FOLFOX activity in a rare case of metastatic colonic adenocarcinoma of the tongue: A case report

Abstract Background Adenocarcinomas of the oral cavity are rare neoplasms, and only four cases of primary colonic adenocarcinoma of the tongue have ever been described in literature. Very few information about chemotherapy sensitiveness of this type of neoplasia is available, with only one regimen that showed some activity in a metastatic patient. Case presentation We describe the case of a patient bearing a metastatic colonic adenocarcinoma of the tongue submitted to a first-line chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX regimen). After chemotherapy the patient obtained the complete disappearance of the primitive neoplasia located in the body of the tongue, and a tumor size reduction > 50% of liver and lung metastases. Conclusions This case demonstrated the activity of the combination of oxaliplatin and 5-fluorouracil in this very rare neoplasia. The FOLFOX regimen might be considered either in advanced and especially in the neoadjuvant setting, when the reduction of the primary tumor is highly needed

Unacylated Ghrelin Promotes Skeletal Muscle Regeneration Following Hindlimb Ischemia via SOD-2-Mediated miR-221/222 Expression

BACKGROUND: Surgical treatment of peripheral artery disease, even if successful, does not prevent reoccurrence. Under these conditions, increased oxidative stress is a crucial determinant of tissue damage. Given its reported antioxidant effects, we investigated the potential of unacylated‐ghrelin (UnAG) to reduce ischemia‐induced tissue damage in a mouse model of peripheral artery disease. METHODS AND RESULTS: We show that UnAG but not acylated ghrelin (AG) induces skeletal muscle regeneration in response to ischemia via canonical p38/mitogen‐actived protein kinase signaling UnAG protected against reactive oxygen species–induced cell injuries by inducing the expression of superoxide dismutase‐2 (SOD‐2) in satellite cells. This led to a reduced number of infiltrating CD68(+) cells and was followed by induction of the myogenic process and a reduction in functional impairment. Moreover, we found that miR‐221/222, previously linked to muscle regeneration processes, was up‐regulated and negatively correlated with p57(Kip2) expression in UnAG‐treated mice. UnAG, unlike AG, promoted cell‐cycle entry in satellite cells of mice lacking the genes for ghrelin and its receptor (GHSR1a). UnAG‐induced p38/mitogen‐actived protein kinase phosphorylation, leading to activation of the myogenic process, was prevented in SOD‐2–depleted SCs. By siRNA technology, we also demonstrated that SOD‐2 is the antioxidant enzyme involved in the control of miR‐221/222–driven posttranscriptional p57(Kip2) regulation. Loss‐of‐function experiments targeting miR‐221/222 and local pre–miR‐221/222 injection in vivo confirmed a role for miR‐221/222 in driving skeletal muscle regeneration after ischemia. CONCLUSIONS: These results indicate that UnAG‐induced skeletal muscle regeneration after ischemia depends on SOD‐2–induced miR‐221/222 expression and highlight its clinical potential for the treatment of reactive oxygen species–mediated skeletal muscle damage

Unacylated ghrelin prevents mitochondrial dysfunction in a model of ischemia/reperfusion liver injury

Ischemia/reperfusion (I/R) injury is a common cause of liver dysfunction during hepatectomy, liver transplantation procedures and in generalized shock. Although effort has been dedicated to rescuing tissue damage in these clinical settings, there is still an urgent need for an effective treatment to protect the liver from the burden of I/R injury. In this study, we have investigated the potential clinical impact of unacylated-ghrelin (UnAG) in a liver I/R rat model. Particular attention has been paid to mitochondria. We demonstrate that UnAG was able to reduce the lag-phase time in response to ADP administration and increase oxygen consumption in ex vivo experiments using liver mitochondria recovered from rats subjected to I/R. Moreover, we found that UnAG rescued the expression of a key regulator of mitochondrial morphology and electron transport chain function; the optic atrophy 1 (Opa1) protein. Cytochrome c oxidase (COX), ATP synthase (complex V) activity and mitochondrial permeability transition pore (mPTP) opening were also affected by UnAG administration in vivo. An in vitro, hepatic I/R model was used to validate these data. We demonstrate that UnAG upregulates the expression of Cox subunit IV (CoxIV) and increases cellular ATP content. This results in Bcl-2 upregulation and protection against apoptosis. Opa1 silencing shows that Opa1 is crucial for a UnAG-induced increase in cellular ATP content, apoptosis resistance, Bcl-2 and CoxIV expression. Finally, we show that UnAG improves Opa1's interaction with MIC60 in the I/R setting, hinting at its role in cristae shape regulation. Our results demonstrate that UnAG administration rescues the intrinsic mitochondrial pathway triggered by I/R damage. Opa1's contribution in mediating this effect is also reported. This suggests that UnAG can interfere with mitochondrial dysfunction, via Opa1, in a preclinical liver I/R model. We therefore provide the rationale for exploiting UnAG as an alternative means to rescuing mitochondrial damage and organ dysfunction

Channel sounding and indoor radio channel characteristics in the W-band

This work presents directional radio channel measurements in the W-band using a commercial versatile channel sounder based on a vector network analyzer (VNA), capable of measuring scattering parameters from 75 to 500 GHz with frequency converters. The commercial setup has been modified by increasing the distance for one of the converters using precision coaxial cables and avoiding the use of amplifiers. Firstly, initial distance-dependent single-input single-output (SISO) measurements of indoor radio channels are presented to assess the validity of the setup in the 75 110 GHz frequency band with highly directive horn antennas. Then, single-input multiple-output (SIMO) radio channels were measured at 94 GHz using one directional and one omnidirectional antenna mounted on two positioners. Initial channel characterization is presented comprising root mean square (rms) delay spread, rms angular spread, K-factor, and path loss in an indoor environment at 94 GHz.This work was supported by MINECO, Spain (TEC2013-47360-C3-2-P TEC2013-47360-C3-3-P) and by European FEDER funds.Martínez Inglés, M.; Gaillot, D.; Pascual-García, J.; Molina-García-Pardo, JM.; Rodriguez Rodriguez, JV.; Rubio Arjona, L.; Juan Llacer, L. (2016). Channel sounding and indoor radio channel characteristics in the W-band. EURASIP Journal on Wireless Communications and Networking. 30:1-8. doi:10.1186/s13638-016-0530-7S1830D Zico, Ultra-wideband and 60 GHz communications for biomedical applications. Springer. http://link.springer.com/book/10.1007%2F978-1-4614-8896-5 .L Jofre, J Romeu, S Capdevila, J Abril, E Nova, M Alonso, The “challenging” world of Terahertz radiation and imaging. Proceedings of the 5th European Conference on Antennas and Propagation (EUCAP), 2011, pp. 3470–3475M Kawase, “Non-destructive evaluation method of pharmaceutical tablet by terahertz-time-domain spectroscopy: application to sound-alike medicines”, J. Infrared Millimeter Terahertz Waves, 34(9), 566–571KD Anderson, 94 GHz propagation in the evaporation duct. IEEE Trans. Antennas Propag. 38(5), 746–753 (1990)K Aydin, Y-M Lure, Millimeter wave scattering and propagation in rain: a computational study at 94 and 140 GHz for oblate spheroidal and spherical raindrops. IEEE Trans. Geosci. Remote Sens. 29(1), 593–601 (1991)C Gloaguen, An experiment for propagation studies at 94 GHz. Eighth Int. Conf. Antennas Propagation 1, 406–409 (1993)A Kajiwara, “Indoor propagation measurements at 94 GHz,” personal, indoor and mobile radio communications, 1995. Sixth IEEE Int. Symp PIMRC’95. Wireless Merging Inf. Superhighway 3, 1026 (1995)J Helminger, J Detlefsen, H Groll, Propagation properties of an indoor-channel at 94 GHz. Int. Conf. Microw Millimeter Wave Technol.Proc 98, 9–14 (1998)R Piesiewicz, R Geise, M Jacob, J Jemai, T Kurner, “Indoor channel measurements of point-to-point ultra broadband short range links between 75 GHz and 110 GHz”, in International Symposium Antennas and Propagation Society, 2008, pp. 1–4A Brizzi, A Pellegrini, Y Hao, “Experimental characterization of the propagation on the human torso at W band”, in Radio Science Meeting (Joint with AP-S Symposium), USNC-URSI, 2013, p. 39K Haneda, J Järveläinen, A Karttunen, M Kyro, J Putkonen, Indoor short-range radio propagation measurements At 60 and 70 GHz, in EuCAP 2014, The Hague, The Netherlands, 2014, pp. 1–4S Promwong, J Takada, Free space link budget estimation scheme for ultra wideband impulse radio with imperfect antennas. IEICE Electronics Express 1(7), 188–192 (2004)NL Johnson, S Kotz, N Balakrishnan, Continuous univariate distributions, vol. 1 (Wiley-Interscience, Hoboken, 1993)A Richter, Estimation of radio channel parameters: models and algorithms (Dr.-Ing. dissertation, TU Ilmenau, Ilmenau, Germany, 2005

Caspase-dependent proteolytic cleavage of STAT3alpha in ES cells, in mammary glands undergoing forced involution and in breast cancer cell lines.

BACKGROUND: The STAT (Signal Transducers and Activators of Transcription) transcription factor family mediates cellular responses to a wide range of cytokines. Activated STATs (particularly STAT3) are found in a range of cancers. Further, STAT3 has anti-apoptotic functions in a range of tumour cell lines. After observing a proteolytic cleavage in STAT3alpha close to a potential apoptotic caspase protease cleavage site we investigated whether STAT3alpha might be a caspase substrate. METHODS: STAT3alpha status was investigated in vitro in several cell systems:- HM-1 murine embryonic stem (ES) cells following various interventions; IOUD2 murine ES cells following induction to differentiate along neural or adipocyte lineages; and in a number of breast cancer cell lines. STAT3alpha status was also analysed in vivo in wild type murine mammary glands undergoing controlled, forced involution. RESULTS: Immunoblotting for STAT3alpha in HM-1 ES cell extracts detected amino and carboxy terminal species of approximately 48 kDa and 43 kDa respectively--which could be diminished dose-dependently by cell treatment with the nitric oxide (NO) donor drug sodium nitroprusside (SNP). UV irradiation of HM-1 ES cells triggered the STAT3alpha cleavage (close to a potential caspase protease cleavage site). Interestingly, the pan-caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (z-VAD-FMK) and the JAK2 tyrosine kinase inhibitor AG490 both inhibited cleavage dose-dependently, and cleavage was significantly lower in a heterozygous JAK2 knockout ES cell clone. STAT3alpha cleavage also occurred in vivo in normal murine mammary glands undergoing forced involution, coinciding with a pulse of phosphorylation of residue Y705 on full-length STAT3alpha. Cleavage also occurred during IOUD2 ES cell differentiation (most strikingly along the neural lineage) and in several human breast cancer cell lines, correlating strongly with Y705 phosphorylation. CONCLUSION: This study documents a proteolytic cleavage of STAT3alpha into 48 kDa amino and 43 kDa carboxyl terminal fragments in a range of cell types. STAT3alpha cleavage occurs close to a potential caspase site, and can be inhibited dose-dependently by SNP, AG490 and z-VAD-FMK. The cleavage seems to be caspase-dependent and requires the phosphorylation of STAT3alpha at the Y705 residue. This highly regulated STAT3alpha cleavage may play an important role in modulating STAT3 transcriptional activity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are