Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 -3.74, P = 0.01). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the "HIF-1α -strong and TERT -strong" and the "HIF-1α -weak and TERT -weak" patient subgroups, as evaluated by Kaplan-Meier analysis (P = 0.005). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.

Our study proves that MIB-1 LI is not dependent on factors like age and sex and is solely dependent on histological grade. Though the average level of MIB-1 LI varies considerably in the different grades of astrocytomas, considerable overlap can be observed between them. MIB-1 LI is a very useful adjunct to the histopathological diagnosis and can be of great help in situations where the clinical and radiological findings do not correlate with histological diagnosis.

Background: The aim of this study was to analyze the clinicopathological and immunohistochemical features of primary central nervous system lymphoma (PCNSL) cases occurring in Indian patients and also study the utility of the crush smear preparation in intraoperative diagnosis. Materials and Methods: The immune status, clinical, radiological details, immunohistochemical profile, histopathological findings and cytological features in smear preparation of 32 cases of PCNSL were analyzed. Patients with systemic NHL and skull-base lymphomas were excluded. Results: The mean age of our patients was 52 years with a male: female ratio 1:1. A periventricular location was found in 62.5% of patients. None of our PCNSL cases were associated with AIDS. All cases except one were diffuse large B-cell lymphomas. Intraoperative diagnosis using crush smears allowed correct prediction in 93% of cases. Conclusions: Our study shows that PCNSL is seen predominantly in immunocompetent patients in India .The age of presentation is relatively young as compared to the West. Our study also stresses the utility of crush smear preparation in establishing an intraoperative diagnosis.

Pleomorphic xanthoastrocytoma has been considered as an astrocytic tumor with relatively favorable prognosis. It corresponds to WHO Grade-II neoplasm. Recently, several patterns with relatively poor prognosis have been recorded and a new concept of "PXA with anaplastic features" has been proposed. The present case is about a 9-year-old girl who presented with symptoms of recurrent headache, seizures and poor academic performance. MRI revealed left fronto-parietal irregular enhancing mass lesion with callosal involvement and right mid-brain arteriovenous malformation. Clinical and radiological examination was suggestive of a high grade glial neoplasm/PNET. A diagnosis of high grade glial neoplasm was rendered on the squash smears submitted for frozen sections based on the presence of spindle cells, admixed with pleomorphic bizarre, giant cells with multilobated nuclei showing few atypical mitosis and abundant eosinophilic cytoplasm. Frontal craniotomy with debulking of the tumor was performed and permanent sections revealed a biphasic glial neoplasm with spindle cells arranged in fascicles admixed with bizarre multinucleated giant cells showing abundant vacuolated and lipidized cytoplasm, nuclear hyperchromasia with intranuclear inclusions. Eosinophilic granular bodies, mitosis of 7/10 HPF, micro vascular proliferation, necrosis and invasion into the underlying brain parenchyma were noted. With these histomorphological findings a diagnosis of pleomorphic xanthoastrocytoma with anaplastic features was rendered.

Thymosin β4 (Tβ4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tβ4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tβ4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tβ4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.