Therapeutic intervention of glioma with the novel antineoplastic agent T11TS: the story so far.

The disease relevance of novel therapeutic agent T11TS, established first by the authors' group, was shown to ameliorate experimental glioma through multimodal mechanistic activities. T11TS reverses immunosuppression in glioma, causing profound effects on immune potentiation via peripheral, intracranial and hematopoietic cells. T-cell signaling in glioma is reversed by T11TS, modulating cytokine levels and favoring apoptotic killing of glioma cells.

Akt Phosphorylation Orchestrates T11TS Mediated Cell Cycle Arrest in Glioma Cells.

The novel anti-neoplastic glycopeptide T11TS retards glioma both in clinical samples and models. This study investigates the correlation between altering the glioma microenvironment with glioma arrest and death. Flow cytometry, immunoblotting, ELISA, and co-immunoprecipitation were employed to investigate glioma cell arrest and death.

Regulation of key molecules of immunological synapse by T11TS immunotherapy abrogates Cryptococcus neoformans infection in rats.

Cryptococcus neoformans infects and disseminates in hosts with diminished T cell responses. The immunomodulator T11TS (T11 target structure) had profound potential in glioma as well as C. neoformans infected model for disease amelioration.

Unravelling the apoptotic mechanisms in T-lymphocytes in an animal model for pollen induced airway allergy and studying the impact of specific immunotherapy.

Asthma is a chronic inflammatory disorder of the airways, increasing in prevalence worldwide. Reduced T cell apoptosis may interfere with the down-regulation of an immune response resulting in T cell accumulation contributing to the chronic inflammation of asthma. Most studies focused so far on apoptosis of eosinophils but the detailed role of T lymphocytes apoptosis in allergic diseases is unclear yet.

T11TS immunotherapy augments microglial and lymphocyte protective immune responses against Cryptococcus neoformans in the brain.

Cryptococcus neoformans, the encapsulated yeast acquired through inhalation, remains localized in lungs, but harbours the CNS in immunocompromised individuals. Several treatment regimes have failed combating this disease totally, but long-term usage of drugs leads to organ damage. As T11-target structure (T11TS) has documented profound immune potentiation, we aimed to investigate the role of microglia, pivotal immune cells of brain in ameliorating cryptococcosis, with T11TS immunotherapy.

Allergen immunotherapy modulates sensitivity of Treg cells to apoptosis in a rat model of allergic asthma.

Aim: To study the apoptosis of Foxp3 Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy.

Materials & Methods: Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed.

T11TS immunotherapy repairs PI3K-AKT signaling in T-cells: Clues toward enhanced T-cell survival in rat glioma model.

Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway.

Modulation of regulatory T cells by intranasal allergen immunotherapy in an experimental rat model of airway allergy.

Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a "procrustean paradigm" as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T-cell homeostasis and in the maintenance of peripheral tolerance to allergens.

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells.

Combating gliomagenic global immunosuppression is one of the emerging key for improving prognosis in malignant glioma. Apoptosis plays a pivotal role within the adult hematopoietic system particularly in regulating the cells of immune system. Gliomagenic regulation of apoptotic mediators within bone marrow milieu has not been elucidated.

Use of Prothrombin Complex Concentrate for Warfarin Reversal Before the Performance of an Epidural Blood Patch in a Patient With Cortical Vein Thrombosis and Subdural Hematoma: A Case Report.

Compared to conventional therapy, several studies with prothrombin complex concentrate (PCC) have recently demonstrated its superior efficacy in rapidly replacing vitamin K-dependent factors for patients with life-threatening hemorrhage. We present a novel use of PCC in a patient with intracranial hypotension, who had received warfarin for treatment of cortical vein thrombosis. However, after anticoagulation, she proceeded to develop bilateral subdural hematomas with descent of cerebellar tonsils.

Microglial Contribution to Glioma Progression: an Immunohistochemical Study in Eastern India.

Human glioma, arising from glial cells of the central nervous system, accounts for almost 30%of all brain tumours , neoplasms with a poor prognosis and high mortality rates worldwide. In the present study we assessed tissue architectural modifications associated with macrophage lineage cells, controversial major immune effector cells within the brain, in human glioma tissue samples from eastern India. Ethically cleared post-operative human glioma samples from our collaborative neurosurgery unit with respective CT/MRI and patient history were collected from the Nodal Centre of Neurosciences in Kolkata, over 9 months.

T11TS Treatment Augments Apoptosis of Glioma Associated Brain Endothelial Cells, Hint Toward Anti-Angiogenic Action in Glioma.

Malignant glioma continues to be a clinical challenge with an urgent need for developing curative therapeutic intervention. Apoptosis induction in tumor-associated endothelial cells represent a central mechanism that counteracts angiogenesis in glioma and other solid tumors. We previously demonstrated that intraperitoneal administration of sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) in rodent glioma model inhibits PI3K/Akt pathway and Raf/MEK/ERK signaling in glioma-associated brain endothelial cells.

Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect.

Disease relevance of T11TS-induced T-cell signal transduction through the CD2-mediated calcineurin-NFAT pathway: Perspectives in glioma immunotherapy.

Malignant glioma is the most lethal of a wide array of CNS neoplasms. Its onset and progression are markedly associated with profound immunosupression and paralysis of T-cell survival and proliferation. Myriad immunotherapeutic strategies are presently used to target such T-cell anomalies in glioma.

A mathematical model to elucidate brain tumor abrogation by immunotherapy with T11 target structure.

T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma) and the immune system interactions, which aims in designing efficacious brain tumor therapy.

T11 target structure induced modulations of the pro-inflammatory and anti-infammatorycytokine expressions in experimental animals for glioma abrogation.

Glioma angiogenesis is the result of the interaction between cancer cells with endothelial cells, and the surrounding inflammatory cells. This interaction plays a crucial role in directing the neo-formation of blood vessels. In the carcinogenic milieu, inflammatory cytokines secreted from inflammatory cells affect endothelial cell functions that are indispensable for tumor growth and metastatic propagation.

The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation.

T-cell-mediated immune responses are typically low in conditions of malignant glioma which has been known to cause marked immunesuppression and dysregulate major T-cell signaling molecules. Thus, T-cell-based immunotherapies are currently in vogue in the treatment of malignant glioma. The novel glycopeptide, T11TS/S-LFA-3/S-CD58 has previously been shown by our group to be highly efficacious in glioma abrogation in in vivo and in vitro conditions.

T11TS inhibits glioma angiogenesis by modulation of MMPs, TIMPs, with related integrin αv and TGF-β1 expressions.

During glioma development, angiogenesis plays a crucial role in growth and vascularization of primary brain tumors. T11 target structure (T11TS), a bioactive molecule, has been documented as an anti-neoplastic agent in glioma-induced rats and also in human glioma in vitro. This novel molecule induces apoptosis of tumor cells by way of immune potentiation and impairs the glioma cell cycle, but its role in glioma angiogenesis has not been worked out in detail.

Significant modulation of macrophages associated cytokines TNF-α, VEGF and apoptotoic protein Bax, Bcl2 abrogates tumor cells.

T11 target structure (T11TS), a membrane glycoprotein has been documented with anti neoplastic activity in glioma bearing animal model in our lab. In this study, we have evaluated the phagocytic potential, expression of VEGF, TNF-α in T11TS treated and untreated macrophages in all four grades of glioma. The data indicates the significant enhancement of phagocytosis in T11TS treated macrophages of grades I and II glioma.

T11TS impedes glioma angiogenesis by inhibiting VEGF signaling and pro-survival PI3K/Akt/eNOS pathway with concomitant upregulation of PTEN in brain endothelial cells.

The crucial role of angiogenesis in malignant glioma progression makes it a potential target of therapeutic intervention in glioma. Previous studies from our lab showed that sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) has potent anti-neoplastic and immune stimulatory effects in rodent glioma model. In the present study we investigated the anti-angiogenic potential of T11TS and deciphered the underlying molecular mechanism of its anti-angiogenic action in malignant glioma.

Therapeutic profile of T11TS vs. T11TS+MiADMSA: a hunt for a more effective therapeutic regimen for arsenic exposure.

Arsenic exposure is a serious health hazard worldwide. We have previously established that it may result in immune suppression by upregulating Th2 cytokines while downregulating Th1 cytokines and causing lymphocytic death. Treatment modalities for arsenic poisoning have mainly been restricted to the use of chelating agents in the past.

Immunomodulatory role of TIITS in respect to cytotoxic lymphocytes in four grades of human glioma.

T11 target structure (T11TS), a membrane glycoprotein has been documented with antineoplastic activity in animal model in our lab. Previously, in animal study we have documented T11TS induced cytotoxic abrogation of tumor cells. Encouraged by these established findings by our group and as prerequisite for clinical trial, this study has been designed to assess the cytotoxic potential of the patient's lymphocytes in in vitro study of autologous human glioma as modulated by T11TS.

Asystole during pulmonary artery catheter insertion under general anesthesia.

In spite of ongoing debate for the past 40 years, pulmonary artery catheters remain in use for invasive hemodynamic monitoring and management of critically ill patients. We describe a case of a sudden onset of asystolic cardiac arrest during the placement of a pulmonary artery catheter, while under general anesthesia. A brief review of the literature highlighting arrhythmic complications associated with pulmonary artery catheterization is also presented.

Comparative evaluation of T11 target structure and its deglycosylated derivative nullifies the importance of glycan moieties in immunotherapeutic efficacy.

Sheep red blood cell (SRBC), a non-specific biological response modifier that has long been used as a classical antigen, has been shown to exert an immunomodulatory and anti-tumor activities in experimental animals. The active component of SRBC, which is responsible for such effects, was found to be a cell surface acidic glycoprotein molecule, known as T11 target structure (T11TS). In the present study, T11TS was isolated and purified to homogeneity using a five-step protocol involving isolation of sheep erythrocyte membrane from packed cell volume, 20% ammonium sulfate cut of the crude membrane proteins mixture, immunoaffinity purification using mouse anti-sheep CD58 mAb (L180/1) tagged matrix, preparative gel electrophoresis, and gel electroelution process.