Melanoma contains CD133 and ABCG2 positive cells with enhanced tumorigenic potential

The failure to eradicate most cancers and in particular melanoma may be as fundamental as a misidentification of the target. The identification of cancer stem/initiating cells within the tumour population with a crucial role for tumour formation may open new pharmacological perspectives. Our data show three main novelties for human melanoma: firstly, melanoma biopsy contains a subset of cells expressing CD133 (CD133+) and the latter is able to develop a Mart-1 positive tumour in NOD-SCID mice. Secondly, the WM115, a human melanoma cell line, has been found to express both CD133 and ABCG2 markers. This cell line grows as floating spheroids, expresses typical progenitors and mature neuronal/oligodendrocyte markers and is able to transdifferentiate into astrocytes or mesenchymal lineages under specific growth conditions. As in xenografts generated with CD133+ biopsy melanoma cells, those produced by the cell line displayed lower levels of CD133 and ABCG2. Thirdly, the WM115 cells express the most important angiogenic and lymphoangiogenic factors such as notch 4, prox1 and podoplanin which can cooperate in the development of the tumourigenic capability of melanoma in vivo. Therefore, in this study, we demonstrate the presence of stem/initiating subsets in melanoma both in biopsy and in an established melanoma cell line grown in vitro and in xenografts. Interestingly, considering that melanoma gives metastasis primarily through lymphatic vessels, herein, we demonstrated that a melanoma cell line expresses typical lymphoangiogenic factors

Mesenchymal Stromal Cells Primed with Paclitaxel Provide a New Approach for Cancer Therapy

BACKGROUND: Mesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived stromal cells to Doxorubicin led them to acquire anti-proliferative potential towards co-cultured haematopoietic stem cells (HSCs). We thus hypothesized whether freshly isolated human bone marrow Mesenchymal stem cells (hMSCs) and mature murine stromal cells (SR4987 line) primed in vitro with anti-cancer drugs and then localized near cancer cells, could inhibit proliferation. METHODS AND PRINCIPAL FINDINGS: Paclitaxel (PTX) was used to prime culture of hMSCs and SR4987. Incorporation of PTX into hMSCs was studied by using FICT-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by PTX primed hMSCs (hMSCsPTX) was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of hMSCsPTX and PTX primed SR4987(SR4987PTX), while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting hMSCsPTX and SR4987PTX with cancer cells in mice. Nevertheless, despite a loss of cells due to chemo-induced apoptosis, both hMSCs and SR4987 were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. PTX primed cells acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, hMSCsPTX and SR4987PTX co-injected with human cancer cells (DU145 and U87MG) and mouse melanoma cells (B16) in immunodeficient and in syngenic mice significantly delayed tumor takes and reduced tumor growth. CONCLUSIONS: These data demonstrate, for the first time, that without any genetic manipulation, mesenchymal stromal cells can uptake and subsequently slowly release PTX. This may lead to potential new tools to increase efficacy of cancer therapy

Relationship between birth weight and retinal microvasculature in newborn infants

Objective: The purposes of this study were to determine the normal retinal microvasculature measurements in human infants who are born at term and to determine whether birth weight influences measurements of retinal microvasculature. Study Design: Retinal arteriole and venule measurements were obtained in a cohort of 24 infants who were born at term. Digital images of both the retinas were obtained using a digital retinal camera after pupillary dilation. Result: In all, 24 newborn infants born at term (12 females and 12 males) were analyzed in this study. The measured retinal arteriole diameters were from 66.8 to 147.8 μm (mean, 94.2±19.6 μm), and the venule diameters were from 102.0 to 167.8 μm (mean, 135.2±19.1 μm). Seven babies in the sample had low birth weight (LBW), while 17 babies were born with normal weight. Babies with lower birth weights had larger arteriole (113.1±17.9 μm vs 86.4±14.4 μm; P=0.0009) and venule diameters (151.7±14.9 μm vs 128.4±16.9 μm; P=0.0040). Conclusion: Retinal venules and arterioles in LBW babies are larger compared with those of normal-birth-weight babies. We postulate that the difference observed in our study was due to in utero pathophysiological changes that occurred in the cerebral circulation of growth-restricted fetuses

Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation

Here, we identify CD44(+)CD90(+)CD73(+)CD34(−)CD45(−) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes

Impatto clinico del monitoraggio digitale delle perdite aeree dopo resezione polmonare

Scopo del lavoro: valutazione dell'impatto clinico del monitoraggio digitale delle perdite aeree dopo resezione polmonare nel contesto della gestione pianificata del drenaggio toracico; studio prospettico randomizzato, controllato con intento di trattament

Termoablazione con microonde versus lobectomia polmonare: studio con propensity match

Sebbene la chirurgia resti il trattamento di prima scelta nel tumore polmonare non a piccole cellule (NSCLC) in stadio iniziale, la terapia locale (radioterapia, termoablazione) ha acquistato un ruolo rilevante nei pazienti affetti da NSCLC localizzato che non possono essere sottoposti a chirurgia per et\ue0 avanzata o per ridotta funzione cardio-respiratoria. Il presente studio \ue8 indirizzato alla valutazione della non inferiorit\ue0 della termoablazione con microonde (MW) rispetto alla lobectomia polmonare nel trattamento di lesioni primitive in I stadio o secondarie del polmone

Thoracoscopic versus conventional lobectomy : comparable short-term results associated to lower systemic impact

Videotoracoscopy has emerged as an alternative to the conventional technique in thoracic surgery. We compared the outcomes after VTS and coventional lobectomies, in terms of postoperative pain, systemic inflammation and pulmonary function.From October 2010 and May 2011, 57 patients underwent pulmonary lobectomy. Among them, 15 patients received VTS lobectomy and 42 received open lobectomy. 15 patients were selected from the \u201copen\u201d group and used as controls.Operative times differed between the two groups (VTS 238.5 vs open 191.6 min, p 0.01), but we found no difference when we compared chest tube stay (POD 6.0 \ub1 2.83 vs 5.1 \ub1 2.94, NS). Perceived postoperative pain (NRS scale) was the same (POD1 3.1 vs 2.7, POD2 2.2 vs 2.2, POD3 1.5 vs 1.3, NS) and the total amount of analgesics per patient, expressed as mg of morphine/Kg, was also not statistically different (4 vs 4.8, NS). Furthermore, no statistical difference was observed in postoperative WBC and CRP between the two groups, although we believe this to be mainly due to the small population size. The average CRP was 7.6 vs. 11.6 on POD3 and 5.07 vs. 8.15 on POD5, in the VTS group and open group respectively. We didn\u2019t have any major complications, but 4 patients who had undergone VTS lobectomy had a late pleural effusion requiring thoracentesis, despite the usual postoperative management. Moreover, a patient in the same group had postoperative pneumonia: we consider it to be related to an underlying HIV-related immunosuppression, rather than to the surgical technique itself. One patient in the \u201copen\u201d group experienced severe postoperative pain. One patient in each group had prolonged air-leaks and after that the \u201cfissureless\u201d technique was introduced when thoracoscopic lobectomies were performed.We believe VTS lobectomy to be a safe technique, associated to a lower systemic impact on the patient compared to the conventional technique