28 research outputs found
Valproic Acid Synergizes With Cisplatin and Cetuximab in vitro and in vivo in Head and Neck Cancer by Targeting the Mechanisms of Resistance
Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a
devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus
cetuximab (CX) is one of the standard first-line treatments in this disease. However, this
therapeutic regimen is often associated with high toxicity and resistance, suggesting that
new combinatorial strategies are needed to improve its therapeutic index. In our study,
we evaluated the antitumor effects of valproic acid (VPA), a well-known antiepileptic
agent with histone deacetylase inhibitory activity, in combination with CDDP/CX doublet
in head and neck squamous cell carcinoma (HNSCC) models. We demonstrated, in
HNSCC cell lines, but not in normal human fibroblasts, that simultaneous exposure to
equitoxic doses of VPA plus CDDP/CX resulted in a clear synergistic antiproliferative and
pro-apoptotic effects. The synergistic antitumor effect was confirmed in four different
3D-self-assembled spheroid models, suggesting the ability of the combined approach
to affect also the cancer stem cells compartment. Mechanistically, VPA enhanced
DNA damage in combination treatment by reducing the mRNA expression of ERCC
Excision Repair 1, a critical player in DNA repair, and by increasing CDDP intracellular
concentration via upregulation at transcriptional level of CDDP influx channel copper
transporter 1 and downregulation of the ATPAse ATP7B involved in CDDP-export.
Valproic acid also induced a dose-dependent downregulation of epidermal growth factor
receptor (EGFR) expression and of MAPK and AKT downstream signaling pathways
and prevent CDDP- and/or CX-induced EGFR nuclear translocation, a well-known
mechanism of resistance to chemotherapy. Indeed, VPA impaired the transcription
of genes induced by non-canonical activity of nuclear EGFR, such as cyclin D1 and thymidylate synthase. Finally, we confirmed the synergistic antitumor effect also
in vivo in both heterotopic and orthotopic models, demonstrating that the combined
treatment completely blocked HNSCC xenograft tumors growth in nude mice. Overall,
the introduction of a safe and generic drug such as VPA into the conventional treatment
for R/M HNSCC represents an innovative and feasible antitumor strategy that warrants
further clinical evaluation. A phase II clinical trial exploring the combination of VPA and
CDDP/CX in R/M HNSCC patients is currently ongoing in our institute
Un raro caso di osteomalacia ipofosforemica oncogenica associata ad iperparatiroidismo terziario
Clinical-pathological features in HER2-positive advanced gastric cancer: Italian data of the Reggio Emilia Clinical Cancer Centre.
Breast cancer in systemic sclerosis: Results of a cross-linkage of an Italian Rheumatologic Center and a population-based Cancer Registry and review of the literature.
OBJECTIVE: Increased frequency of few types of cancer in systemic sclerosis (SSc) has been reported in the literature; in particular, breast carcinoma has been proposed as one of the most frequent malignancy in SSc patients, even though data are not univocal. The aim of the present study was to retrospectively evaluate the prevalence of breast cancer in our SSc series, compared with sex-/age-matched general population of the same geographical area, and the possible correlations with SSc features, including X-ray exposure for clinical investigations. A review of the world literature about this topic was also done.
METHODS: Clinical records of 318 consecutive SSc patients, 31 M and 287 F, age 51.5\ub114.5 SD years, disease duration 10\ub16.5 SD years, referred to our Rheumatology Unit between January 2002 and December 2012 were evaluated.
RESULTS: Twelve (3.8%) cases of breast cancer were recorded, including 11/287 females (3.8%) and 1/31 (3.2%) male patients. Considering the subgroup of 202 SSc patients resident in the Province of Modena compared with data of the local Tumor Registry, the incidence of breast cancer observed in our SSc series is significantly higher than expected (SIR 2.1; 95% interval of confidence: 1.13-3.90; p<0.01). On the whole, the comparison between SSc patients with cancer and those without did not show any significant differences with regard to SSc clinical features, including the X-ray exposure. Of note is the relatively shorter disease duration at the time of breast cancer detection (median 2.5years, range 1-21; disease duration of mean 10\ub16.5 SD years in the entire cohort). The review of the literature revealed that the observed incidence of breast cancer in our case series is comparable to the few studies reporting the highest percentages of this malignancy.
CONCLUSIONS: A significant increase of breast cancer incidence compared to sex-age-matched general population from the same geographic area was observed. Moreover, a close temporal relationship between SSc and breast cancer onset was found, independently from clinical, serological, and instrumental features of SSc. The possible pathogenetic link between this systemic autoimmune disease and complicating breast cancer, as well as the results of previous studies, are discussed
Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a population-based study
Although surgery alone represents a curative approach for patients with pT3N0M0 colon cancer, about 15\ue2\u80\u9320\uc2 % of these patients develop a relapse of disease. Microsatellite instability (MSI) is one of the most important molecular markers in colorectal cancer. The aim of this study was to investigate the prognostic relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the Province of Modena\ue2\u80\u94(Northern Italy) within the 2002\ue2\u80\u932006 period in patients who showed a relapse of disease during the 5-year period of follow-up (59 cases). They were compared to 59 controls similar in clinical and pathological features but with good prognosis. None of the subjects received adjuvant chemotherapy. MSI status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled mononucleotide markers. The overall prevalence of MSI was 12.7\uc2 % (15 of 118 cases). MSI was detected mainly in mucinous adenocarcinoma (p\uc2 
Intracellular recording of human cardiac action potentials on market-available multielectrode array platforms
High quality attenuated intracellular action potentials from large cell networks can be
recorded on multi-electrode arrays by means of 3D vertical nanopillars using electrical
pulses. However,most of the techniques require complex 3D nanostructures that prevent
the straightforward translation into marketable products and the wide adoption in the
scientific community. Moreover, 3D nanostructures are often delicate objects that cannot
sustain several harsh use/cleaning cycles. On the contrary, laser optoacoustic poration
allows the recording of action potentials on planar nanoporous electrodes made of
noble metals. However, these constraints of the electrode material and morphology may
also hinder the full exploitation of this methodology. Here, we show that optoacoustic
poration is also very effective for porating cells on a large family of MEA electrode
configurations, including robust electrodes made of nanoporous titanium nitride or
disordered fractal-like gold nanostructures. This enables the recording of high quality
cardiac action potentials in combination with optoacoustic poration, providing thus
attenuated intracellular recordings on various already commercial devices used by a
significant part of the research and industrial communities
Low rectal cancer and distance from anal sphincter before and after preoperative therapy
Preoperative therapy increased the distance of the low rectal cancer from the anal sphincter until the near 50% of cases and can make possible or facilitate an anal preserving operation