Fluorinated porous organic frameworks for improved CO2 and CH4 capture.

A porous 3D selectively fluorinated framework (F-PAF1), robust yet flexible and with a surface area of 2050 m2 g-1, was synthesised by condensation of an ad hoc prepared fluorinated tetraphenylmethane (TPM) monomer to ensure homogenously distributed C-F dipoles in the swellable architecture. Tetradentate TPM was also the comonomer for the reaction with fluorinated difunctional monomers to obtain frameworks (FMFs) with a controlled amount of regularly spaced reorientable C-F dipoles. The isosteric heat of adsorption of CO2 was increased by 53% by even moderate C-F dipole insertion, with respect to the non-fluorinated frameworks. CO2/N2 selectivity was also increased up to a value of 50 for the difluoro-containing comonomer. Moreover, methane shows optimal interaction energies of 24 kJ mol-1.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Role of exon-16-deleted HER2 in breast carcinomas.

A splice variant of the human gene HER2, lacking exon-16 (DeltaHER2) which encodes a small extracellular region, has been described. This altered receptor forms disulfide bond-stabilized homodimers. We report here that the DeltaHER2 splice variant represents about 9% of the HER2 mRNA obtained from most of the 46 breast carcinoma samples with HER2 expression levels ranging from 3+ to 0 by HercepTest. Analysis of human cells transfected with DeltaHER2 or wild-type (WT) cDNA revealed no growth of WT cells in nude mice, whereas clones expressing 10-fold less DeltaHER2 were tumorigenic. Unlike WT transfectants, DeltaHER2-expressing cells showed low sensitivity to two new therapeutic drugs targeting receptors of the HER family (ZD1839 and Trastuzumab), whereas an inhibitor of the HER2 tyrosine kinase domain (Emodin) blocked activation of both DeltaHER2 and WT transfectants. Taken together, our findings indicate that the DeltaHER2 transcript encodes the transforming form of the oncoprotein. It is plausible that malignant transformation arises when a critical threshold of DeltaHER2 is reached in HER2-overexpressing tumors. Specific inhibitors of HER2 catalytic activity represent a promising approach to therapy of HER2-overexpressing tumors.

The 67 kDa laminin receptor increases tumor aggressiveness by remodeling laminin-1.

The association between expression of the 67 kDa laminin receptor (67LR) and tumor aggressiveness has been convincingly demonstrated although the exact function of this molecule in the metastatic process has remained unclear. In this study, we tested whether the laminin-1, upon interaction with 67LR, promotes tumor cell aggressiveness; the investigation was based on: (i) the previous demonstration that soluble 67LR, as well as a 20-amino-acid peptide corresponding to the 67LR laminin binding site, changes the conformation of laminin upon interaction with this adhesion molecule and (ii) the known relevance of microenvironment remodeling by the tumor, leading to structural modification of extracellular matrix components in tumor progression. MDAMB231 breast carcinoma cells plated on peptide G-treated laminin-1 exhibited a polygonal array of actin filament bundles compared with cells seeded on native laminin-1 which presented the actin bundles organized as multiple cables parallel to margins. Furthermore, in cells seeded on peptide G-treated laminin-1, 67LR was distinct from the alpha6 integrin subunit in filopodia protrusions in addition to colocalizing with this integrin in focal adhesion plaques as it occurs when cells are plated on native laminin-1. In addition to differences in tumor cell adhesion and migration found in cells exposed to peptide G-treated vs native laminin-1, breast carcinoma cells seeded on modified laminin-1 showed a 6-fold increase in invasion capability compared with cells seeded on unmodified laminin-1. Alterations in actin organization as well as adhesion, migration and especially invasion observed in MDAMB231 cells in the presence of peptide G-treated laminin-1 were even found in MDAMB231 cells that, after selection for 67LR high expression, were seeded on native laminin-1. As the 67LR shedding is proportional to its expression level, these findings indicate a role for 67LR in changing laminin structure. Expression analysis of 97 genes encoding proteins that mediate cell matrix interactions, revealed significant differences between cells exposed to modified vs unmodified laminin-1 in 19 genes, 17 of which--including those encoding alpha3 integrin, extracellular matrix protein 1, proteolytic enzymes (such as MT1-MMP, stromelysin-3 and cathepsin L) and their inhibitors--were up-modulated in cells treated with modified laminin-1. Zymogram analysis clearly indicated a significant increase in the activity of the gelatinolytic enzyme MMP-2 in the culture supernatant from cells exposed to modified laminin-1, without an increase in mRNA abundance as observed in microarray analysis. Invasiveness of tumor cells conditioned by modified laminin-1, evaluated as the capability to cross Matrigel basement, was significantly more inhibited by MMPinhibitor TIMP-2 than invasiveness induced by native laminin-1. Taken together, our findings indicate that the role of 67LR in tumor aggressiveness rests in its ability to modify laminin-1 thereby activating proteolytic enzymes that promote tumor cell invasion through extracellular matrix degradation.

[Male contraception]. / La contraccezione maschile.

The only safe method of male contraception is vasectomy, with high reversibility secured by microsurgery. Italy, however, suffers from a lack of regulations on this subject. Hormonal treatment (testosterone plus progestational hormones) is far from providing reliability and safety, while some perspectives, theoretical only for the time being, are offered by studies on functional infertility induced by either speeding up (ganglioplegic, sympathomimetic, parasympatholytic, oxytocin, endothelin, angiotensin) or inhibiting (sympatholytic) the sperm transport through the epididymis, or altering the epididymal environment (alpha-chloridin, chlorodeoxyglucose).

Semen cryopreservation from oncological patients: the Italian experience.

The aim of the study is to summarize official data on semen cryopreservation for oncological patients in Italy. The first private semen bank for oncological patients in Italy was founded by Colpi in 1983 in Milan. In 1987, the first public semen bank was established in "Macedonio Melloni" Hospital (Milan) by Ragni. Normal semen samples are usually present in only 40% of oncological patients. The rate of semen sample use for assisted reproduction techniques is similar to international data (5%). At present, semen cryopreservation is possible only in about 20 Italian centers.

Study on anaerobic and aerobic degradation of different non-ionic surfactants.

Six alcohol ethoxylates (C5E2, C6E4, C7E4, C8E2, C8E4, C10E4) and two fatty acid esters were tested at lab-scale for degradation in anaerobic and aerobic conditions and oxygen uptake rate (OUR). Anaerobic removal of C5E2, C6E4 and C7E4 improved with increasing number of ethoxy groups (E) and decreasing length of the alkyl chain (C). Their aerobic removal was also great but lower than the anaerobic values. C8E2, C8E4 and C10E4 were adsorbed on sludge but not degraded in anaerobic conditions, while they were efficiently removed under aerobiosis. The fatty acid esters were removed to a level between the two alcohol ethoxylates groups in both anaerobiosis and aerobiosis. The measured OUR confirmed the different behaviours of the three groups of compounds.

HER2 as a prognostic factor in breast cancer.

HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. HER2-positive tumors also contain p53 abnormalities, tend to be hormone receptor and bcl-2 negative, have lymphoid infiltration (LI) and a high mitotic index. Patients with LI who are HER2 positive have a better prognosis than those who are HER2 negative, whereas HER2-positive patients without LI have a significantly worse prognosis than HER2-negative patients. Morphological and biological alterations appear to identify two categories of breast tumor. Two hypotheses may explain the progression to two tumor types: (1) atypical ductal hyperplasia (ADH) is a precursor of ductal carcinoma in situ (DCIS), which is a precursor of invasive ductal carcinoma (IDC); or (2) ADH is a precursor of HER2-negative IDC whereas DCIS is a precursor of HER2-positive IDC. The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.

Nerve growth factor cooperates with p185(HER2) in activating growth of human breast carcinoma cells.

Nerve growth factor (NGF) is known to exert a mitogenic effect on human breast cancer cells through proto-TrkA activation. Reverse transcriptase-PCR analysis of proto-TrkA expression in human breast carcinoma specimens and cell lines revealed trkA transcript in 12 of 14 human breast carcinoma specimens and in all of four cell lines tested. While cytofluorimetric and Western blot analysis indicated proto-TrkA expression in three of the four cell lines, NGF stimulated growth in only two of the three positive cell lines. Inhibition of NGF-induced MAPK activation by an antibody directed against the extracellular domain of TrkA but not by an inhibitor of TrkA phosphorylation demonstrated the requirement of NGF binding but not of proto-TrkA kinase activity for MAPK activation, suggesting the recruitment of another kinase for transmission of the mitogenic signaling. Indeed, NGF induced tyrosine phosphorylation and stimulated kinase activity of p185(HER2), a kinase receptor of the HER family. A TrkA phosphorylation inhibitor did not affect this activation. Moreover, the two receptors were coprecipitated by antibodies directed against proto-TrkA and p185(HER2). Down-modulation of p185(HER2) expression in a breast carcinoma line transfected with a construct containing an anti-p185(HER2) antibody sequence and expressing proto-TrkA impaired NGF-induced MAPK activation and proliferation. Together these data show that in cells expressing low levels of TrkA such as breast carcinoma cells, NGF must recruit other overexpressed receptors such as p185(HER2) in order to generate a biological signal that can induce breast cancer cell growth.

Production of a monoclonal antibody directed against the high-affinity nerve growth factor receptor.

The high-affinity nerve growth factor receptor corresponds to the tyrosine protein kinase encoded by the proto-oncogene trkA. Different findings suggest that nerve growth factor (NGF) can be operative in the growth modulation of tumor cell lines possessing high-affinity binding sites for this molecule. Using as immunizing material the SKNBE neuroblastoma cell line transfected with proto-trkA we produced a monoclonal antibody (MAb) able to recognize the high-affinity nerve growth factor receptor. The selected MAb, designated MGR12, is directed against an epitope present on the extracellular domain of the receptor since it showed reactivity on living trkA-expressing cells and was able to immunoprecipitate the proto-trkA molecule. The MGR12 MAb is directed against a non-functional epitope since it neither inhibited NGF binding nor induced receptor internalization. This new reagent appears to be an appropriate tool for analyzing the expression of high-affinity nerve growth factor receptor in tumors of different origin and for elucidating its involvement in tumor progression.

[Agranulocytosis caused by dipyrone. Case reports]. / Agranulocitosi da dipirone: contributo casistico.

Two cases of dipyrone-induced agranulocytosis are described. In the first one, the disease was due to a single administration, in the second one, to prolonged therapy. The possible pathogenic mechanism is discussed, which can be immunologic and/or toxic. The effectiveness of some of the drugs and general supportive measures applied is discussed. Health education of the patient, in conjunction with careful attention by the physician, may play an important role in the prevention of this pathological condition.

[Indications for cerebral revascularization surgery (author's transl)]. / Indicazioni agli interventi di rivascolarizzazione cerebrale.

Cerebrovascular diseases are among the most widespread. In the USA alone there is at any time a population of 1.6 million people with current stroke syndrome or the sequelae thereof. The most effective weapon to combat this disease is prevention, and here reference is made in particular to surgical prevention, especially through endoarterectomy of the extracranial internal carotid, and to vertebrobasilar circulatory failure.

[Radiotherapy of tumors of the bladder and urethra]. / Radioterapia dei tumori della vescica e dell'uretra.

With regard to vesica tumors, a remarkable difficulty for the interpretation of statistical data is often given by the different classifications that the different authors use. Therefore we have reported a comparative table always for being faithful to what we wished at the beginning of this work that has be useful to the doctor above all by a clinical point of view. In synthesis all the Authors think that radiotherapy is not the elective treatment for tumors in O or A stage, while it can be efficient in the therapy of vesica neoplasies in B1, B2 and C stages. The most Authors seem less favourable to preoperating irradiation of tumor above all for the unexact intraoperating valuation of "staging" that is inevitable after this treatment. Postoperating radiotherapy (5000-6000 R in 20-30 days) can be more useful in the cases of incomplete surgical exeresis although there is the problem of possible radiolesions of eventual uretero-intestinal anastomosis let alone of intestine. In the end urethra tumors are sensitive to radiotherapy for their superficiality and excellent tolerance of membrum to radiations that permits also the giving of 6000-7000 R in 4-6 days.