Concurrent presence of diabetes affects the GLUT3 programming of glucose metabolism in glioblastoma.

OBJECTIVE: Diabetes mellitus (DM)-mediated impaired glucose metabolism increase in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An integral membrane transport protein, glucose transporter 3 (GLUT3) facilitates glucose transport into GB tumor cells. We aimed to explore the regulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospectively analyzed. Of the total, 15 patients were concurrently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evaluated by analyzing its correlation with Ki67, P53 expression, MALAT1 expression, and peripheral blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and metformin to modulate GLUT3. The RNA expression of GLUT3, SOX2, and MALAT1 was analyzed by real-time qPCR. The lactate levels of T98G cells were measured by Cobas c502 analyzer. A scratch wound assay was performed to investigate the migration rate of T98G cells. RESULTS: GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and peripheral blood glycated hemoglobin (HbA1c) levels were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagliflozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-mediated GLUT3 suppression induced SOX2 and MALAT1 expressions and influenced the migration capacity of T98G cells. CONCLUSIONS: Our findings suggest that the low GLUT3 expression of the tumors of GB-DM patients may induce the production of adenosine triphosphate (ATP) from cellular energy sources other than glucose metabolism. However, further studies are warranted to confirm these results.

The inmunohistochemical expression of c-Met is an independent predictor of survival in patients with lioblastoma multiforme

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care (AU)

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The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme.

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.

A comparison of Ki 67 proliferative index in primary tumor and axillary metastatic lymph nodes with length of survival in patients with breast cancer.

OBJECTIVE: The aim of the present study was to investigate the possibility to predict the histopathological features of breast and metastatic lymph nodes and survey and prognosis of patients and likelihood of being a predictive factor for treatment by using Ki67 immunohistochemical stain. MATERIALS AND METHODS: 95 patients who were admitted to Uludag University Medical Faculty, Department of General Surgery with a diagnosis of stage II-III breast cancer between dates May 1997 and December 2002 were retrospectively evaluated with respect to breast cancer related prognostic factors treatments and last-control related data. Ki67 immunohistochemical staining was performed to appropriate specimens using Streptavidin-biotin technique. Ki67 was reported as the proliferation index, and the number of stained nuclei were stated to be / 1000. RESULTS: In the evaluation of the lymph node by univariate analysis, we ascertained that duration of survival is shorter above the 227 cut-off value for Ki67 proliferative index. Length of survival of patients with tumor Ki67 proliferative index below 141 and with no distant metastasis was established to be better. Ki67 proliferative index in the lymph node was detected to increase more with increasing histological and nuclear grade, estrogen and progesterone receptor negativity and at stage III. CONCLUSION: Since numerous factors are effective on breast cancer, each patient and tumor behaves differently. A lot of prognostic factors are taken into account while treatment choice is determined. We may have information on the biological behavior of the tumor in patients who underwent sentinel lymph node biopsy or axillary dissection in staining with Ki67 pattern (Tab. 5, Fig. 3, Ref. 13).

Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats.

The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group 3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical studies were performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5 (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; p<0.05). There was higher expression of caspase-3 proteins in Group 2 (2.28+/-0.95) compared to Group 5 (1.50+/-0.83; p<0.05). Bax proteins were also increased in Group 2 (1.85+/-1.06) compared to Group 5 (0.40+/-0.54) and in Group 4 (2.00+/-0.00) compared to Group 5 (0.40+/-0.54; p<0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29+/-0.96) compared to Group 5 (0.20+/-0.44) (p<0.05); Group 3 (1.00+/-0.70) compared to Group 5 (0.20+/-0.44; p<0.05); and Group 4 (3.00+/-0.00; p<0.05) compared to Group 5 (0.40+/-0.54; p<0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.

Effective treatment of relapsing idiopathic nodular panniculitis (Pfeifer-Weber-Christian disease) with mycophenolate mofetil.

Relapsing idiopathic nodular panniculitis is the term used to describe a group of diseases that presents as subcutaneous inflammatory nodules, fever and systemic symptoms and histopathologically displays inflammation within the fat lobules. There is no specific test for diagnosis and extensive investigations are required to exclude systemic causes of panniculitis. No uniform effective therapy is available and various drugs used include mainly corticosteroids alone or in combination with other immunosuppressive agents. Presented in this paper is an intractable case of idiopathic nodular panniculitis whose corticotherapy failed and could not be continued because of serious adverse effects. The rapid and good therapeutic response of the patient to mycophenolate mofetil monotherapy is discussed.

Factors influencing cosmetic results after breast conserving management (Turkish experience).

We aimed to determine predictive factors affecting cosmetic results after breast conserving management in breast cancer. Data on 96 patients with 97 breast cancer cases, who had been admitted to Uludag University M.A. Radiotherapy Center between October 1995 and December 1998 and managed with breast-conserving treatment, were analysed to determine the factors affecting cosmetic outcome. Possible factors affecting cosmesis were grouped as patient-related, tumor-related and treatment-related. Mann-Whitney U test was used in univariate analyses whereas logistic regression was used in multivariate analyses. Median follow-up time was 29.5 months ranging between 11 and 53 months and median age at admission was 50 (range 22-84). Cosmetic results were grouped in five categories; excellent; good; fair; poor and, very poor, using criteria, such as presence of fibrosis, telangiectasia, shape of breast, asymmetry, status of areola, pigmentation. Treated breasts were scored by the patients, three radiation oncologists and a breast surgeon independently. In the analysis performed using scores given by the patients, cases with scores 3 and above (unsatisfactory) were compared with cases with scores below 3 (satisfactory). Eighty-two patients (84%) considered cosmetic result as satisfactory (excellent/good) whereas 15 patients (16%) considered unsatisfactory (fair/poor/very poor). In univariate analysis using Mann-Whitney U test, type of surgery (P=0.0655) was the statistically significant factors affecting cosmetic results. In multivariate analysis using logistic regression, tumor quadrant (P=0.0060) and elapsed radiation therapy days (P=0.0090) were the most significant factors. Median values were taken into consideration for the scores given by the physicians and cases with scores 3 and above (unsatisfactory) were compared with cases with scores below 3 (satisfactory). Eighty-two cases were evaluated as satisfactory (84%) whereas 15 cases were unsatisfactory (16%). In this set of data, patient age (P=0.0144), menopausal status (P=0.0111), institution which surgery was performed (P=0.0045), type of surgery (P=0.0044), placement of metallic clips (P=0.0083) and skin fibrosis (P=0.038) were found to be significant in univariate analysis using Mann-Whitney U test. In multivariate analysis using logistic regression, institution where surgery took place (P=0.0015), menopausal status (P=0.0087) and telangiectasia (P=0.0657) were the most significant factors.

Airway remodeling and serum total immunoglobulin E (IgE) levels in a murine model of asthma.

A murine model of allergen-induced airway inflammation, epithelial phenotypic changes, and total immunoglobulin E (IgE) levels is described. Mice were sensitized to ovalbumin without adjuvant and challenged by multiple intratracheal instillations of ovalbumin by a nonsurgical technique. After repeated challenges, the basement membrane of the airway epithelium showed fibrosis, inflammatory cell infiltration at peribronchial and perivascular sites, and goblet cell hyperplasia. In addition, total IgE levels were found to be increased significantly. Further studies which will evaluate the contribution of each feature of remodeled airway to the natural history of asthma are definitely needed.

A case of primary spinal intramedullary lymphoma.

A 41-year-old male presented to our clinic with a 1-month history of left hemiparesis. He had marked left arm weakness. The diagnostic work-up revealed an intramedullary mass at spinal level C2-4. Laminectomies were performed at C2-3-4 and the tumor was subtotally resected. Histological examination identified the mass as a non-Hodgkin's diffuse B-cell lymphoma. The patient was treated with corticosteroids, chemotherapy, and adjuvant radiotherapy. The residual tumor tissue had completely disappeared by 6 months of follow-up; however, the patient presented with intraventricular metastasis at 11 months postsurgery.

Minimally invasive craniotomy using the Steiner-Lindquist stereotaxic guide.

Thirty-three obscure intracranial lesions were located using the Steiner-Lindquist microsurgical stereotaxic guide and then surgically resected. Seventeen of the lesions were located in the parietal region, six in the frontal region, three in the parietooccipital region, three in the temporoparietal region, one in the thalamic region, one in the centrum semiovale, one in the brainstem, and one in the third ventricle. Twenty-three lesions were in subcortical or cortical locations. In 28 cases, the lesion was totally removed, while in 5 the lesion was subtotally resected. Pathological examinations confirmed glial tumor in eight patients, metastasis in seven, meningioma in two, cavernous angioma in eight, arteriovenous malformation (AVM) in four, hematoma in two, dysembryoblastic neuroepithelial tumor in one, and septum pellucidum cyst in one. Two patients developed transient complications postsurgery. Mean lesion size was 23 +/- 0.97 mm. The hospitalization period ranged from 1 to 6 days (mean 3.4 +/- 1.3 days). Surgeries were performed under general anesthesia, or under local anesthesia with the patient awake. The Steiner-Lindquist microsurgical stereotaxic guide is useful for pinpointing small lesions, especially those in the subcortical and deep areas. Knowing the precise location of the lesion facilitates removal through a small craniotomy incision. This minimally invasive procedure reduces the number of postoperative neurological complications, and also cuts costs by shortening the hospital stay.

Spinal subarachnoid hemorrhage attributable to schwannoma of the cauda equina.

BACKGROUND: Cauda equina syndrome occurring as a result of spontaneous spinal subarachnoid hemorrhage (SAH) from a spinal tumor is reported to be rare. CASE DESCRIPTION: A 28-year-old woman presented at our clinic with a history of severe back pain for 10 days, progressive paraparesis, and urinary retention. Her physical examination revealed a mass located intradurally at the level of L1-2 and a massive SAH. An L1-L2, laminectomy and a hemilaminectomy from D9 to D12 were performed and the SAH was evacuated and the cord was decompressed. CONCLUSION: At the first year follow-up, her restricted dorsal and plantar flexion continued. Post-gadolinium magnetic resonance imaging revealed no mass.

Giant lymphoid hamartoma of mediastinum (Castleman's disease).

The giant lymphoid hamartoma is known as a rare, benign, large, solitary, encapsulated mass of lymphoid tissue. It frequently involves mediastinum or pulmonary hilum. It may also occur in other various locations. Few of the patients may have general symptoms. The disease has been divided into two variants according to microscopic structure. These are hyaline vascular type and plasma-cell type. The hyaline vascular type is benign but the plasma-cell type meets malignancy criteria, so that the plasma-cell type has been subject to discussion whether it is suited to chemotherapy or not. Our case was a 55-year-old male with persistent cough. There was a mass having a size of 6 centimeters on left pulmonary hilum on chest radiograph. Left thoracotomy was performed and a hilar lymphoid mass removed. The biopsy finding was "hyaline vascular type giant lymphoid hamartoma". No other therapy was done. Patient is well six months after the operation.