High ERCC1 expression is thought to be related with resistance to chemotherapy based on platinum. The aim of this study was to present our institutional observations regarding to the association of ...ERCC1 and overall survival (OS) of the lung adenocarcinoma patients who received chemotherapy based on platinum.
A total of 253 lung adenocarcinoma patients in all TNM stages were retrospectively investigated. The diagnosis was based on small biopsy samples obtained during bronchoscopy. Depending on the TNM stage of the disease and clinical condition, patients received only the chemotherapy based on platinum, or in combination with radiotherapy or surgery. Tissue sample for ERCC1 immunohistochemical analysis was sufficient in 129 patients. Low from high ERCC1 expression was separated by the semi-quantitative H-score median.
High ERCC1 expression was found in 47.3% patients, and was correlated with higher TNM (p = 0.021), tumor enlargement (p = 0.002), positive lymph nodes (p = 0.001), positive distant metastasis (p = 0.005), and higher relative risk of death (p < 0.001). Furthermore, significance association was observed for low ERCC1 expression and better performance status (ECOG) (p = 0.023). Longer OS was strongly associated with a low ERCC1 expression, not only in the group of patients in TNM stage I-III, who were treated with combination of chemotherapy with surgery or radiotherapy (p = 0.002), but also in the group of patients in TNM stage IV who received only chemotherapy based on platinum (p < 0.001), compared with the patients in the same TNM stage and high ERCC1 expression.
ERCC1 expression in lung adenocarcinoma is a useful prognostic marker and moreover, a useful predictive marker in patients receiving chemotherapy based on platinum in all stages of the disease.
BACKGROUND The present study was carried out in order to evaluate our institutional experience with small biopsy in diagnosis and molecular testing of lung adenocarcinoma. Few specific and predictive ...markers have been evaluated and correlated with clinicopathologic characteristics and survival in patients with lung adenocarcinoma who received platinum-based chemotherapy. There have not been such reports from Croatia. MATERIAL AND METHODS A total of 142 cases of lung adenocarcinoma were retrospectively investigated in small biopsies for the immunohistochemical expression of TTF-1, napsin A, ERCC1, ALK, and the EGFR mutation by real-time polymerase chain reaction (rtPCR). RESULTS TTF-1, napsin A, and ERCC1 expression was found in 81%, 78%, and 69% of patients, respectively, and the expressions were not significantly associated with subtype. Expression of ALK was found in 4% and EGFR mutation in 10% of patients. Exon 19 deletions were the most common. Longer survival was significantly associated with TTF-1 positivity (p=0.007) and napsin A positivity (p=0.026). Higher relative risk of death significantly correlated with positive expression of ERCC1 (p=0.041). CONCLUSIONS Positive TTF-1 and napsin A expressions in lung adenocarcinoma tissues were useful diagnostic and favorable prognostic parameters. Positive ERCC1 expression was identified as a negative prognostic marker in patients treated with platinum-based chemotherapy. The percentages of EGFR and ALK mutations corresponded to those in previously published reports for Caucasians.
The aim of the study was to explore possible differences in DNA flow cytometric characteristics, particularly differences in distribution of DNA indices of aneuploid clones, between male and female ...breast cancers. We retrospectively analyzed 31 male breast cancers. Clinicopathological and DNA flow cytometric characteristics of male breast cancers (patient age, tumor size, histological type, histological grade, axillary lymph node status, hormone receptor expression, ploidy, and S-phase fraction) were compared with that of the control group of matched female breast cancers. Hormone receptors and HER-2/neu were investigated immunohistochemically with additional chromogenic in situ hybridization (CISH) analysis of HER-2/neu 2+ cases. Ploidy and S-phase fraction were determined by DNA flow cytometry. Comparison with clinicopathological features was made using
χ
2
and
t
test. Aneuploidy was found in 78 % of the cases, with the predomination of hypotetraploid clones (39 %), followed by tetraploid (23 %) and hypertetraploid clones (16 %). We found higher frequency of hypertetraploidy in male breast cancers (16 and 6 %, respectively) than in the control group of matched female breast cancers. Clinicopathological features of hypertetraploid male breast cancers did not differ from that of non-hypertetraploid cancers. Higher frequency of hypertetraploidy among male breast cancers might indicate different cytogenetical evolutionary pathway between male and female breast cancer.
A 61-year-old woman presented with an isolated, painless, slightly enlarged right laterocervical lymph node without any other signs and symptoms of disease. Laboratory test including hematological ...and biochemical parameters were normal. A cervical ultrasonography demonstrated one lymph node (10 mm) on the right laterocervical side and one small reactive lymph node on the left laterocervical side. The fine needle aspiration (FNA) smears revealed a polymorphic population of cells composed of lymphocytes, histiocytes, epitheloid cells, plasma cell, tingible body macrophages and macrophages infiltrated with Leishmania amastigotes. Treatment was initiated with Stiboglukonat Na (Pentostam) and led to a full recovery.
Zaštita žrtava kaznenih djela Borovec, Krunoslav; Burazer, Marina
Policija i sigurnost,
09/2007, Letnik:
16, Številka:
1-2
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U kritici trenutačnog stanja, kad je u pitanju odnos prema žrtvama i svjedocima kaznenih djela i drugim strankama kojima policija pruža svoje usluge, prepoznajemo potrebu nužnih promjena u odnosu ...policije prema spomenutim kategorijama građana. Preduvjet za to je kreiranje novih strategija koje će u konačnici doprinijeti učinkovitijem suzbijanju kriminaliteta, kvalitetnijem obavljanju poslova u policiji, ali i većem povjerenju građana u policiju. Da bi ispunila određene ciljeve, svaka organizacija, pa tako i policija mora imati viziju svoje budućnosti koja počiva na čvrstim temeljima. Nju treba prenositi svim zainteresiranim stranama, prije svega vlastitim zaposlenicima. Oni moraju osjetiti kako organizacija «diše» i u kojem se smjeru razvija, a nadasve se moraju osjećati sastavnim i bitnim dijelom sustava. Dakle, ovim naglašavamo važnost svakog pripadnika policije u provedbi pojedinih projekata, kako bi oni u končanici zaživjeli kao općeprihvaćene metode rada, a ne kao obveza pojedinca. Naša spremnost da objektivno i kritički shvatimo trenutno stanje u području zaštite žrtava kaznenog djela daje nam za pravo vjerovati kako su sazrijeli uvjeti za nove projekte koji će predstavljati pravu i istinsku reformu. Kako bi u usvajanju novih metoda rada i odnosa prema žrtvama i svjedocima kaznenih djela bili uspješni te planirane reforme proveli učinkovito, moramo, prije svega, poraditi na vlastitim stavovima o novoj ulozi policije, kao i na pripremi svakog našeg policajca za novu drugačiju ulogu. Redefiniranje rang-liste prioriteta policijskog djelovanja preduvjet je koji moramo ispuniti ako želimo biti policija koja će se transformirati u javni servis građana.
A 61-year-old woman presented with an isolated, painless, slightly enlarged right laterocervical lymph node without any other signs and symptoms of disease. Laboratory test including hematological ...and biochemical parameters were normal. A cervical ultrasonography demonstrated one lymph node (10 mm) on the right laterocervical side and one small reactive lymph node on the left laterocervical side. The fine needle aspiration (FNA) smears revealed a polymorphic population of cells composed of lymphocytes, histiocytes, epitheloid cells, plasma cell, tingible body macrophages and macrophages infiltrated with Leishmania amastigotes. Treatment was initiated with Stiboglukonat Na (Pentostam) and led to a full recovery.
The aim of this study was to identify short digestion-resistant peptides (SDRPs) released by pepsin digestion of the whole cow’s milk and examine their IgE reactivity and allergenicity. Raw milk was ...subjected to simulated gastric digestion. SDRPs were fractionated from the digests and identified by MS. Milk SDRPs were evaluated for aggregability, propensity to compete for IgE binding with individual milk allergens, and ability to bind IgG4 from allergic and milk-tolerant individuals. The majority of milk SDRPs originated from caseins (97% of peptides) and overlapped with the known IgE epitopes of cow’s milk allergens. SDRPs competed with milk proteins for binding to human IgE and readily formed aggregates. The average peptide length was 10.6 ± 3.5 amino acids. The ability to provoke allergenic in vivo responses was confirmed by skin-prick testing (SPT) in five milk-allergic subjects. This was attributed to the peptide ability to aggregate into non-covalent complexes. SDRPs are able to induce response in SPT, but only in 50% of the sera SDRPs were able to inhibit IgG4 binding to caseins. Hence, SDRPs corresponding to the mainly continuous epitopes of milk proteins induce allergenic in vivo responses in milk-allergic subjects due to aggregation.
► Actinidin represents a mixture of active and inactive enzyme in kiwifruit extract. ► Thermally inactivated actinidin showed IgG and IgE reactivity in vitro. ► Thermally inactivated actinidin ...revealed in vivo reactivity in skin prick test. ► Thermally processed kiwifruit may induce clinical symptoms in allergic patients.
Actinidin, an abundant cysteine protease from kiwifruit, is a specific biomarker of isolated allergy to kiwifruit. This study evaluates the IgE-binding properties of biologically active and thermally inactivated actinidin. Employing two different activity assays (caseinolytic assay and zymogram with gelatin) we showed that actinidin obtained from kiwifruit extract under native conditions represents a mixture of inactive and active enzyme. The structural integrity of actinidin was confirmed by SDS–PAGE, Edman degradation, mass fingerprint and Western blot with polyclonal antibodies. Although it was capable of inducing positive skin prick test reactions, we failed to detect IgE reactivity of active actinidin in Western blot with patient sera. Thermally inactivated actinidin exhibited IgE reactivity both in vivo and in vitro, indicating that heat processed kiwifruit products may induce clinical reactivity. These findings imply that apart from the allergenic epitopes on its surface, actinidin also contains hidden epitopes inside the protein which become accessible to IgE upon thermal treatment.
Background: Kiwi fruit allergy, as well as its association with hypersensitivity to other foods and to pollen, has been extensively reported in the last few years. Several IgE-binding components have ...been detected in kiwi extract, but only one 30-kd allergen has been isolated; it was identified as actinidin (Act c 1). Recently, we have reported a 24-kd kiwi protein to be a potential major allergen in a group of patients with oral allergy syndrome (OAS). Objective: The aim of this study was to purify and characterize the 24-kd kiwi allergen biochemically. Methods: Seven polysensitized patients with OAS to kiwi were used in this study. The kiwi allergen was isolated by using a combination of gel permeation, ion exchange, and immobilized metal ion affinity chromatography. Its biochemical characterization included determination of its isoelectric point, molecular weight, N-terminal sequencing, concanavalin A –binding ability, digestibility in simulated gastric fluid, and antifungal activity. Western blotting, 2-dimensional PAGE immunoblotting, and skin prick tests were performed to characterize the isolated protein immunochemically. Results: All 7 patients recognized the isolated 24-kd kiwi protein as an allergen. The isolated protein consisted of 2 isoforms with isoelectric points of 9.4 and 9.5 migrated as one protein band of 20 kd after SDS-PAGE under nonreducing conditions or at 24 kd under reducing conditions. The partial N-terminal sequence revealed that it is a thaumatin-like protein (TLP) with concanavalin A –binding ability. The protein showed antifungal activity toward Saccharomyces carlsbergensis , and Candida albicans . The protein was degraded by the simulated gastric fluid within 1 minute. Both isoforms bound IgE from a pool of sera in a 2-dimensional PAGE immunoblot. The TLP elicited positive skin prick test responses in 4 (80 %) of 5 patients with OAS. Conclusion: This study reported isolation and full characterization of a new kiwi allergen, TLP (isoelectric points of 9.4 and 9.5 and molecular weight of 24 kd), which belongs to the family of pathogenesis-related proteins. The isolated protein expressed antifungal activity toward S carlsbergensis and C albicans . (J Allergy Clin Immunol 2002;110:805-10.)
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