Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2) and malignancy in brain tumors

<p>Abstract</p> <p>Background</p> <p>Small heat shock proteins are molecular chaperones that protect proteins against stress-induced aggregation. They have also been found to have anti-apoptotic activity and to play a part in the development of tumors. Recently, we identified a new small heat shock protein, Hsp16.2 which displayed increased expression in neuroectodermal tumors. Our aim was to investigate the expression of Hsp16.2 in different types of brain tumors and to correlate its expression with the histological grade of the tumor.</p> <p>Methods</p> <p>Immunohistochemistry with a polyclonal antibody to Hsp16.2 was carried out on formalin-fixed, paraffin-wax-embedded sections using the streptavidin-biotin method. 91 samples were examined and their histological grade was defined. According to the intensity of Hsp16.2 immunoreactivity, low (+), moderate (++), high (+++) or none (-) scores were given.</p> <p>Immunoblotting was carried out on 30 samples of brain tumors using SDS-polyacrylamide gel electrophoresis and Western-blotting.</p> <p>Results</p> <p>Low grade (grades 1–2) brain tumors displayed low cytoplasmic Hsp16.2 immunoreactivity, grade 3 tumors showed moderate cytoplasmic staining, while high grade (grade 4) tumors exhibited intensive cytoplasmic Hsp16.2 staining. Immunoblotting supported the above mentioned results. Normal brain tissue acted as a negative control for the experiment, since the cytoplasm did not stain for Hsp16.2. There was a positive correlation between the level of Hsp16.2 expression and the level of anaplasia in different malignant tissue samples.</p> <p>Conclusion</p> <p>Hsp16.2 expression was directly correlated with the histological grade of brain tumors, therefore Hsp16.2 may have relevance as becoming a possible tumor marker.</p

GHRH antagonists reduce the invasive and metastatic potential of human cancer cell lines \u3ci\u3ein vitro\u3c/i\u3e

We investigated the effect of a GHRH antagonist, MIA-602 on the metastatic cascade in vitro of three human cancers, DBTRG-05 glioblastoma, MDA-MB-468 estrogen-independent breast, and ES-2 clear cell ovarian cancer. GHRH receptors and their main splice variant, SV1 were detected on all three cell lines. After treatment with MIA-602, the cell viability decreased significantly, significant inhibition of cell invasion was observed and the release of MMPs was significantly decreased. The attachment of cancer cells to fibronectin and matrigel was severely hindered. Wound-healing experiments demonstrated a reduced cellular motility in all three cell lines. The up regulation of caveolin-1 and E-cadherin, and the powerful down regulation of NF-ĸB and β-catenin was detected. Our study suggests that the clinical application of highly potent GHRH antagonists in cancer therapy would be desirable since they inhibit proliferation and metastasis development as well

GHRH antagonists reduce the invasive and metastatic potential of human cancer cell lines in vitro

We investigated the effect of a GHRH antagonist, MIA-602 on the metastatic cascade in vitro of three human cancers, DBTRG-05 glioblastoma, MDA-MB-468 estrogen-independent breast, and ES-2 clear cell ovarian cancer. GHRH receptors and their main splice variant, SV1 were detected on all three cell lines. After treatment with MIA-602, the cell viability decreased significantly, significant inhibition of cell invasion was observed and the release of MMPs was significantly decreased. The attachment of cancer cells to fibronectin and matrigel was severely hindered. Wound-healing experiments demonstrated a reduced cellular motility in all three cell lines. The upregulation of caveolin-1 and E-cadherin, and the powerful downregulation of NF-κB and β-catenin was detected. Our study suggests that the clinical application of highly potent GHRH antagonists in cancer therapy would be desirable since they inhibit proliferation and metastasis development as well

Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2) and malignancy in brain tumors-2

<p><b>Copyright information:</b></p><p>Taken from "Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2) and malignancy in brain tumors"</p><p>http://www.biomedcentral.com/1471-2407/7/233</p><p>BMC Cancer 2007;7():233-233.</p><p>Published online 21 Dec 2007</p><p>PMCID:PMC2234428.</p><p></p>ar Hsp16.2 immunoreactivity, whereas no immunoreactivity in the cytoplasm. . Pilocytic astrocytoma. Strong intranuclear immunopositivity but no intracytoplasmic staining was detected. . Grade 2 astrocytoma shows intensive intranuclear labeling as well as mild cytoplasmic staining. . Grade 3 astrocytoma exhibits strong Hsp 16.2 positivity intranuclearly and moderate Hsp16.2 positivity in the cytoplasm. Grade 1 meningeoma showing high expression of Hsp16.2 intranuclearly and mild expression in the cytoplasm. . Grade 3 meningeoma displayed strong intranuclear and moderate cytoplasmic staining for Hsp16.2. Grade 2 ependymoma with strong intranuclear and moderate cytoplasmic immunopositivity. Grade 3 oligodendroglioma exhibiting intensive intranuclear and moderate cytoplasmic immunoreactivity. . Grade 4 glioblastoma showing strong Hsp16.2 positivity intranuclearly and intracytoplasmically alike. . Grade 4 PNET with intensive staining in the nucleus as well as in the cytoplasm

Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer

The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3-year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC

Retrospective study of cancer patients’ predictive factors of care in a large, Hungarian tertiary care centre

Objectives To identify predictive factors of multiple emergency department (ED) visits, hospitalisation and potentially preventable ED visits made by patients with cancer in a Hungarian tertiary care centre.Design Observational, retrospective study.Setting A large, public tertiary hospital, in Somogy County, Hungary, with a level 3 emergency and trauma centre and a dedicated cancer centre.Participants Patients above 18 years with a cancer diagnosis (International Classification of Diseases, 10th Revision codes of C0000–C9670) who visited the ED in 2018, who had received their diagnosis of cancer within 5 years of their first ED visit in 2018 or received their diagnosis of cancer latest within the study year. Cases diagnosed with cancer at the ED (new cancer diagnosis-related ED visits) were also included, constituting 7.9% of visits.Primary outcome measures Demographic and clinical characteristics were collected and the predictors of multiple (≥2) ED visits within the study year, admission to inpatient care following the ED visit (hospitalisation), potentially preventable ED visits and death within 36 months were determined.Results 2383 ED visits made by 1512 patients with cancer were registered. Predictive factors of multiple (≥2) ED visits were residing in a nursing home (OR 3.09, 95% CI 1.88 to 5.07) and prior hospice care (OR 1.87, 95% CI 1.05 to 3.31). Predictive factors for hospitalisation following an ED visit included a new cancer diagnosis-related visit (OR 1.86, 95% CI 1.30 to 2.66) and complaint of dyspnoea (OR 1.61, 95% CI 1.22 to 2.12).Conclusions Being a resident of a nursing home and receiving prior hospice care significantly increased the odds of multiple ED visits, while new cancer-related ED visits independently increased the odds of hospitalisation of patients with cancer. This is the first study to report these associations from a Central-Eastern European country. Our study may shed light on the specific challenges of EDs in general and particularly faced by countries in the region