Neu Treatment Research Articles

Effects of bacterial strains isolated from the ectomycorrhizal roots of Laccaria parva on sporocarp production by the fungus in vitro

Abstract The effects of bacteria isolated from ectomycorrhizas on sporocarp production of Laccaria parva were examined in vitro. Three bacterial strains of Bradyrhizobium were selected on the basis of their affinity for L. parva LL02 in previous confrontation tests: a positive or a negative strain that significantly increased or decreased hyphal extension areas, and a neutral strain that did not have significant effects on them. Mycelia of LL02 and a suspension of each bacterial strain were inoculated onto a surface-sterilized pine seedling in a glass bottle and then incubated for 3 mo in an illuminated incubator. Plant biomass did not differ significantly among the treatments, but the level of ectomycorrhizal colonization was low in the treatment inoculated with a negative strain (Neg treatment). The frequency with which mature sporocarps occurred was higher in treatments inoculated with positive (Pos treatment) or neutral strains (Neu treatment) compared with control and Neg treatments. The ratio of biomass accounted for by mature sporocarps was low in control and Neg treatments, and high in Pos and Neu treatments. These results indicate that bacteria colonizing ectomycorrhizas affect the production of sporocarps and that the affinity between fungi and bacteria is likely to underlie this interaction.

Expression of Estrogen Receptors (ER), Progesterone Receptors (PR) and HER-2/neu receptors in Endometrial Carcinoma and their associations with histological types, grades and stages of the tumor.

Objective:To study and detect immunohistochemical expression of Estrogen Receptors, Progestrone Receptors and HER-2/neu Receptors in Endometrial Carcinoma (EC) and to find their associations with histological types, grades and stages of the tumor.Methods:A cross sectional study of one year duration from January 2016 to January 2017 was conducted at Histopathology department of Army Medical College, Rawalpindi. A non-probability purposive sampling technique was used to include 56 cases of EC. The specimens were tested for ER, PR and HER-2/neu expression using immunohistochemical analysis. Data was analyzed in SPSS and the significance of association of expression of the receptors with histological types, grades and stages of the tumor was assessed.Results:Significant association of Her-2/neu overexpression with histological types and grades of EC was seen, whereas the association of ER and PR expression with histological types, grades and stage of EC was statistically insignificant.Conclusion:It is suggested that EC showing over expression of HER2/neu with immunohistochemistry may be treated with anti HER-2/neu treatment with better chances of survival and decreased post-treatment morbidity.

P1-12-26: Global Patterns of Care for HER2/Neu Overexpressing Breast Cancer.

Abstract Background: Her2/neu overexpression is an independent adverse prognostic factor present in approximately 25% of invasive breast cancers. HER2−overexpressing breast cancer is particularly common in younger patients and therefore poses a significant public health burden. Anti-Her2/neu adjuvant trastuzumab significantly reduces the risk of recurrence as well as improves survival. In view of the serious potential ramifications of not receiving anti-Her2/neu therapy when appropriate, we undertook this international project to determine clinical access to Her2/neu testing and treatment patterns for women with HER2/neu-positive early breast cancer. Methods: A web-based survey was sent to 386 physicians from 33 countries who participated in the “TEACH” trial, a double blind placebo-controlled phase III study of a novel anti-Her2/neu therapy, lapatinib, in women with primary Her2/neu-positive breast cancer. The survey contained 27 questions addressing physician and patient demographics, access to Her-2/Neu testing in everyday clinical practice, and anti-Her2/neu treatment options in a variety of clinical scenarios. Results: One hundred and fifty one participants (39%) from 28 countries answered the survey. Ninety eight percent of the participants reported having Her2/neu tumor expression routinely measured for clinical practice in their institutions by immunohistochemistry (83%), FISH (78%) and other methods (17%). Among Asian physicians, 18% did not have routine testing available and sent primary tumors for central testing for TEACH eligibility. Forty eight percent of physicians surveyed reported instances when they had recommended adjuvant Her2-directed therapy to a patient who eventually did not receive it. The proportion of physicians from developing countries that reported patients not receiving therapy was higher than those from developed countries (68% vs. 38%, respectively). The main reason for not receiving trastuzumab was cost in developing countries, while in more developed countries patient refusal and co-morbidities were the main reasons. Discussion: This survey reflects availability of HER2 breast tumor testing and anti-Her2/neu therapy among physicians from 28 countries worldwide who participated in an anti-Her2/neu therapy clinical trial of a free anti-Her2/neu therapy. These results indicate that a high proportion of women with Her2/neu-overexpressing breast cancer may not receive standard anti-Her2/neu adjuvant therapy especially in developing countries, the barrier to treatment being cost of therapy. We are extending our access to care survey project to a more unselected diverse group of physicians in developing countries. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-26.

SERUM LEVELS OF SHED HER2/NEU PROTEIN IN MEN WITH PROSTATE CANCER CORRELATE WITH DISEASE PROGRESSION

We determined the association between serum levels of shed Her-2/neu protein and disease progression in men with prostate cancer. Serum from 279 patients enrolled in a prospective serum bank and database at New York University Medical Center was analyzed using the Food and Drug Administration approved Immuno-1 Her-2/neu assay. Patients were classified by the Prostate-Specific Antigen Working Group model into 5 groups, namely group 1-no evidence of cancer in 60, group 2-clinically localized disease in 67, group 3-prostate specific antigen increasing after therapy and no clinical metastases in 77, group 4-clinical metastases and castration sensitivity in 42, and group 5-clinical metastases and castration resistance in 33. A cutoff of 14 ng/ml for normal serum Her-2/neu was established based on the 95th order statistic in group 1. Of 279 patients 37 (13.3%) had increased serum Her-2/neu, that is 5%, 11.9%, 10.4%, 16.7% and 33.3% in groups 1 to 5, respectively. There was a significant difference between patients with (groups 4 and 5) and without (groups 2 and 3) clinical metastases (p = 0.006). In group 5 patients serum Her-2/neu was significantly higher than in group 2 patients (p <0.02). The risk of cause specific death increased significantly with each unit increase in serum Her-2/neu (p <0.001). Increased serum Her-2/neu correlates with the presence of metastatic disease and it may indicate an increased risk of death in patients with castrate, metastatic prostate cancer. The detection of serum Her-2/neu is a minimally invasive alternative to tumor sampling for identifying potential candidates for anti-Her-2/neu treatment strategies. Further studies are needed to optimize this assay for application in the clinical setting.

Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours.

To correlate the expression of a series of apoptotic and oncogene markers (including p53, Bcl-2, BAX, Bcl-XL, p21WAF,1/CIP1, cyclin D1, HER-2/neu) in thymic epithelial tumours with histological type, stage and resectability and to determine whether the information on HER-2/neu would be valuable in identifying patients who are eligible for anti-HER-2/neu treatment. Immunohistochemical stains were performed on 16 cases of non-neoplastic thymus, 63 thymomas and 17 thymic carcinomas. Fluorescence in-situ hybridization (FISH) for HER2 was performed to validate the gene amplification. Eighteen thymomas were positive for p53 and 14 of them were low-expressors, with positive cells below 10%. All thymic carcinomas revealed over-expression of p53 with positive cells either between 10% and 50% or >50%. The expression of p53 correlated with histological type and stage in thymoma. In both thymoma and thymic carcinoma, there was a statistically significant correlation between p53 status and resectability, with low expressors having a higher likelihood of being resectable. Thymic carcinomas, regardless of the histological subtypes, uniformly expressed Bcl-2, while thymomas showed no or only weak cytoplasmic immunoreactivity. Most thymomas and thymic carcinomas were negative for Bcl-XL, p21WAF,1/CIP1 and cyclin D1. The expression of BAX was inconsistent among different histological types. Nine thymic carcinomas revealed membranous positivity for HER-2/neu, but no HER2 gene amplification could be demonstrated by FISH in any of the cases. p53 and Bcl-2 are more implicated in the development of thymic carcinoma than thymoma. The higher level of p53 expression and the strong immunopositive pattern of Bcl-2 in thymic carcinomas have potential value in the differential diagnosis and prediction of aggressiveness and resectability. On account of the absence of HER2 amplification, patients would probably not benefit from anti-HER-2/neu treatment.

A new method for tolerance induction: busulfan administration followed by intravenous injection of neuraminidase-treated donor bone marrow.

The portal venous (p.v.) administration of foreign cells induces donor-specific tolerance. Recently, we have demonstrated that the p.v. administration of donor cells elicits donor-specific tolerance across major histocompatibility complex barriers. In the present study, utilizing the intrahepatic tolerance-inducing system, we have established a new method for organ transplantation using both busulfan ([Bu] to provide a sufficient "space" for the donor hematopoietic cells to expand in the recipient) and neuraminidase ([Neu] to enhance the trapping of i.v.-injected cells in the liver). Radiolabeled bone marrow cells (BMCs) were found to exclusively accumulate in the livers of the recipients as a result of the Neu treatment. Furthermore, hematopoietic progenitors (forming hematopoietic foci) in the accumulated BMCs were retained in the recipient livers for at least 18 days. C57BL/6 (B6) mice that had been transplanted with skins of BALB/c mice immediately after the injection of BALB/c BMCs showed a 90% skin graft survival rate over 400 days as a result of using the combination of injecting 50 mg/kg Bu into the B6 mice and treatment of the BALB/c BMCs with 0.25 U/ml Neu (50 Bu + 0.25 Neu). However, the survival rate significantly decreased when either the Bu or Neu treatment was omitted. In tolerant recipients, microchimerism was observed in the various hematolymphoid organs. T cells collected from the tolerant recipients suppressed proliferative responses to the donor-alloantigens but enhanced the production of Th2 and Th3 cytokines. These findings suggest that the enhanced retention of donor BMCs in the recipient livers as a result of the Bu and Neu treatments efficiently induces tolerance induction. Therefore, this "single-day protocol" would be of great advantage for human organ transplantation.

New method for thyroid transplantation across major histocompatibility complex barriers using allogeneic bone marrow transplantation.

It has been shown that allogeneic bone marrow transplantation (BMT) after lethal irradiation elicits donor-specific tolerance for organ or tissue transplantation across major histocompatibility complex (MHC) barriers. Recently, we have demonstrated that the portal venous (p.v.) administration of donor bone marrow cells (BMCs) elicits donor-specific tolerance across MHC barriers by only two administrations of an immunosuppressant (CsA or FK-506). In our study, using the central and intrahepatic tolerance-inducing system, we have established a new method for thyroid transplantation with BMT that would be more applicable to humans. In addition to sublethal (6-5 Gy) irradiation, recipient B6 (H-2b) mice received injections i.p. with the myeloablative drug busulfan (BU) on day -2 to provide a sufficient "space" for the donor hematopoietic cells to expand in the recipients. To induce the intrahepatic tolerance, donor BALB/c (H-2d) BMCs were treated with neuraminidase (Neu), which enhances the trapping of i.v. injected BMCs in the liver. After the injection of Neu-treated BMCs, the thyroid organs from the BALB/c mice were engrafted under the renal capsules. A 90% graft survival rate was obtained over 100 days by a combination of BU administration, 6 Gy irradiation, and i.v. injection of Neu-treated BMCs [BU+6 Gy+(Neu) i.v.], and a 70% graft survival rate was obtained by [BU+5 Gy+(Neu) i.v.]. However, the graft survival rate significantly decreased when either the BU or Neu treatment was omitted. T cells collected from the tolerant recipients suppressed the proliferative responses to donor alloantigens. Using both BU and Neu treatments, we have succeeded in inducing long-term tolerance and preventing the rejection of thyroid allografts by the single-day protocol.

Relation Between Development of Leukemia and Duration of &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-ethylurea Treatment in DONRYU Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;

N-Nitroso-N-ethylurea (NEU; CAS: 759-73-9) is a strong leukemogen that induces erythroblastic leukemia in inbred DONRYU rats. In the present experiments, relationships between development of leukemia, duration of NEU treatment, and sequential changes in the hematopoietic organs during carcinogen administration were examined. In experiment 1, groups of rats were given a 400-ppm NEU solution for 0, 2, 4, 6, 8, or 10 weeks, and the resultant incidence of leukemias was 0, 26, 40, 75, 95, and 100%, respectively. Of the various types of leukemia, the erythroblastic type was observed in 0, 0, 20, 40, 95, and 90% of rats, respectively. The average latent period showed an inverse correlation with the duration of NEU treatment. In experiment 2 the animals were divided into carcinogen-treated and control groups, and rats were sacrificed periodically for histopathologic examination. In the experimental group, the bone marrow became hypoplastic soon after commencement of NEU treatment and at the 6th week became severely aplastic, thereafter recovering slightly. At the 10th week, 2 rats out of 5 examined were leukemic. Relationships between incidence of leukemia, duration of NEU treatment, and sequential changes of the bone marrow during carcinogen administration are discussed.

Low temperature inhibition on binding, transport, and incorporation of leucine, arginine, methionine, and histidine in Escherichia coli

A multiple amino acid auxotroph and a wild type of Escherichia coli K12 were used to study the effects of near minimum growth temperatures on the binding, transport, and cellular incorporation of selected amino acids. Both strains of the bacterium showed the same minimum growth temperature (8 degrees C) when previously grown at 15 degrees C. At 8 degrees C and above, the auxotroph exhibited an overall greater ability to bind and transport amino acids than did the wild type. Below the minimum growth temperature, transport and cellular incorporation including respiration ((uptake) were significantly lower for either organism. The NEU and HEPPEL osmotic shock treatment indicated the removal of the specific histidine-binding protein and the ability to bind histidine was not recovered by further incubation below 8 degrees C. At 8 degrees C and above, the cells recovered their ability to bind histidine within one hour. The evidence presented indicates a direct relationship between the auxotroph's minimum growth temperature and its ability to bind amino acids, specifically methionine.

The multiple-cluster mutation complex in mutagenesis with higher plants

After treatment of dry and pre-soaked seeds of barley with gamma-rays, EMS, NEU and EI, the frequency of multiple mutations (multimutations) was higher with EMS and NEU treatment, while cluster mutations appeared in greater numbers following treatment with gamma rays and NEU. Pre-soaking the seeds led to a reduction in the frequency of total mutations, cluster mutations and multimutations. This has been explained as a result of the application of lower doses and the induction of mutations at a relatively later stage in ontogenetic development in the case of pre-soaked seeds.Some new mutation types in barley have been described and some of the old types have been given names representing the mutation characters more precisely.The compound mutation frequency of different seedling mutation types, when taken separately, was found to be independent of the mutagen employed and the stage of treatment. The size of mutated chimeras in M 1 plants, as indicated by the segregation ratio of mutants in M 2, was largest in albina, xantha, chlorina, albina-tigrina, chl-terminalis and eceriferum, and lowest in viridis, viridoalbina etc. This could be expected if the unstable premutations induced by mutagenic treatment are resolved into mutations at different intervals after their initiation, or it can be explained by the induction of dominant mutations, or lethal changes together with visible mutations.