PRECLINICAL TESTING OF GALECTIN-3C FOR MULTIPLE MYELOMA

The American Cancer Society expects that there will be more than 20,000 new cases of multiple myeloma (MM) in the US in 2011 and despite the new treatments now available, the median survival rate is only 5 years. Galectin-3C (Gal-3C) is a human lectin involved in cellular processes including cellular differentiation, apoptosis, neoplastic transformation, and metastasis. Gal-3C contains the carbohydrate recognition domain (CRD) of galectin-3 and is thought to act as a dominant negative inhibitor of galectin-3-mediated cross-linking. Gal-3C is a proprietary truncated, inhibitory form of galectin-3. Results showed that in a subcutaneous U266 cell NOD/SCID mouse model of human MM, treatment with an N-terminally truncated form of galectin-3, termed Gal-3C significantly inhibited tumor growth. Furthermore, in vitro data indicated that Gal-3C acts by inhibition of angiogenesis, MM cell migration and invasion, and NF-kB activation. Moreover, Gal-3C facilitates the antitumor activity of bortezomib, a proteasome inhibitor for MM treatment. Gal-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. The delivery of Gal-3C to patients will be via a pump during initial clinical trials. In the long-term, the plan is to develop a formulation of Gal-3C for sustained release to increase survival for patients with MM

Ecotoxicology of nanomaterials: the role of invertebrate testing

Engineered nanomaterials represent a new and expanding class of chemicals whose environmental hazard is actually poorly determined. The peculiar behavior of nanomaterials makes them much more similar to new chemicals than to the corresponding bulk materials; this feature imposes reliable and standardized evaluation protocols for toxicity and ecotoxicity assessments. General rules for assessing nanotoxicity and the state of the art are periodically published in reports by control agencies. This review highlights the role of invertebrates as valuable and validated test organisms for assessing ecotoxicity of new and/or untested chemicals. The general scarcity of experimental data, their unequal distribution among the different nanomaterials and environmental conditions, the difficulties in manipulating nanomaterials and obtaining stable and homogeneous suspensions, the confusion arising from a not well defined metrics are discussed

Sperm protein 17 is highly expressed in endometrial and cervical cancers

<p>Abstract</p> <p>Background</p> <p>Sperm protein 17 (Sp17) is a highly conserved mammalian protein in the testis and spermatozoa and has been characterized as a tumor-associated antigen in a variety of human malignancies. Many studies have examined the role of Sp17 in tumorigenesis and the migration of malignant cells. It has been proposed as a useful target for tumor-vaccine strategies and a novel marker to define tumor subsets and predict drug response. This study aimed to investigate the expression of Sp17 in endometrial and cervical cancer specimens, its possible correlation with the pathological characteristics, and its value in the diagnosis and immunotherapy of the related cancers.</p> <p>Methods</p> <p>The monoclonal antibodies against human Sp17 were produced as reagents for the analysis and immunohistochemistry was used to study two major kinds of paraffin-embedded gynecological cancer specimens, including 50 cases of endometrial cancer (44 adenous and 6 adenosquamous) and 31 cases of cervical cancer (15 adenous and 16 squamous). Normal peripheral endometrial and cervical tissues were used as controls.</p> <p>Results</p> <p>Sp17 was found in 66% (33/50) of the patients with endometrial cancer and 61% (19/31) of those with cervical cancer. Its expression was found in a heterogeneous pattern in the cancer tissues. The expression was not correlated with the histological subtype and grade of malignancy, but the staining patterns were different in endometrial and cervical cancers. The hyperplastic glands were positive for Sp17 in the normal peripheral endometrial and cervical tissues in 10% (8/81) of the patients.</p> <p>Conclusions</p> <p>Sp17 is highly expressed in human endometrial and cervical cancers in a heterogeneous pattern. Although the expression frequency of Sp17 is not correlated with the histological subtype, the staining pattern may help to define endometrial and cervical cancers. Sp17 targeted immunotherapy of tumors needs more accurate validation.</p

Comment on 'Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area'

We comment on the recent study by Sideras et al (2015) that combines tissue microarrays (TMAs) and immunohistochemistry to investigate the expression pattern of 15 antigens belonging to different categories, including cancer-testis antigens and oncofetal proteins in hepatocellular carcinoma (HCC). Because current therapies for HCC are far from ideal (Ilan, 2014) and immunotherapy has been suggested as a potential therapeutic option, the Authors aimed at identifying a panel of biologically relevant tumour antigens with broad expression in a western European population of HCC patients and specific expression in the tumour tissue with no, or little, expression in surrounding non- tumoral tissue (Sideras et al., 2015)

Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance.</p> <p>Methods</p> <p>Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910.</p> <p>Results</p> <p>We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin.</p> <p>Conclusion</p> <p>HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy.</p

Funzionalizzazione di Nanoparticelle con mAbSp17 per la cura del carcinoma ovarico

Nonostante l\u2019avvento di nuovi agenti chemioterapici nella terapia contro il carcinoma ovarico, la mortalit\ue0 causata da questo tumore maligno rimane invariata. Il problema maggiore \ue8 che il tumore viene diagnosticato in fase tardiva e la sopravvivenza, a 5 anni dalla diagnosi, \ue8 del 27% contro il 45,6% se la diagnosi \ue8 precoce. Sperm Protein 17 (SP17) \ue8 una proteina altamente conservata nei mammiferi ed \ue8 implicata nel legame dello spermatozoo alla zona pellucida. SP17 fa parte della famiglia dei cancer testis antigen ed \ue8 considerato un possibile target per l\u2019immunoterapia. La presenza di questa proteina \ue8 stata osservata nelle linee cellulari di OC umano, considerandolo come un possibile biomarker per questo tumore. Studi pre-clinici, in modello murino con OC, hanno dimostrato che la proteina SP17 funziona come vaccino prevenendo la formazione del tumore. Lo scopo di questo lavoro \ue8 quello di legare l\u2019anticorpo monoclonale contro SP17 (mAbSP17) a nanoparticelle di ossido di ferro (Fe3O4NP), iniettare il sistema in un modello murino con carcinoma ovarico umano, per valutare se l\u2019anticorpo legato direzioni le NP verso il tumore. In parallelo si vuole anche valutare la biodistribuzione delle Fe3O4NP. A tale scopo, le Fe3O4NP sono state rivestite con amminopropiltrietossisilano (APTES) e coniugate all'anticorpo, usando EDC (1-Etil-3-(3-dimetilamminopropil)-carbodiimmide cloridrato) e NHS (N-idrossisulfosuccinimide). Il legame covalente dell\u2019APTES con le NP \ue8 stato confermato mediante spettroscopia FT-IR, mentre il legame dell\u2019anticorpo alle NP \ue8 stata determinata mediante saggio ELISA. La capacit\ue0 di internalizzazione del sistema [email protected] \ue8 stata valutata, mediante microscopio confocale, trattando la linea cellulare di carcinoma ovarico umano (SKOV3). I sistemi, NP@APTES-mAbSP17 e [email protected], sono stati testati in vivo su modello murino con carcinoma ovarico indotto da SKOV3. NP@APTES-mAbSP17 e [email protected] sono stati iniettati, per via intraperitoneale, dopo 7 giorni dall\u2019induzione del tumore. Nelle immagini acquisite, utilizzando lo strumento IVIS-LUMINA (Caliper, LifeSciences), si osserva una forte fluorescenza nella zona tumorale, che indica che le [email protected] sono localizzate nel tumore. La nostra ipotesi ancora da confermare \ue8 che le NP siano state internalizzate dalle cellule tumorali, come gi\ue0 dimostrato in vitro. Per quanto riguarda il sistemaNP@APTES-mAbSP17, il lavoro \ue8 ancora in corso. Ad oggi si ha solo una valutazione macroscopica del fenomeno, ma le NP non sembrano aver causato risposta immunitaria o tossicit\ue0. Ovaio, polmone e fegato verranno valutati sia, per via immunoistochimica, per verificare la presenza di SP17 e quindi del tumore, che analizzati al TEM per osservare l\u2019eventuale presenza delle NP

Sperm protein 17 is expressed in human nervous system tumours

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells