Smarajit Pal

Chittaranjan National Cancer Institute | CNCI · Clinical Biochemistry

Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune functions. We have observed that an immunomodulator, neem leaf glycoprotein (NLGP), inhibits tumor-resident MDSCs and enhances antitumor CD8+ T cell immunity. NLGP inhibits the number as well as functions of tumor-resident MDSCs (Gr1±CD11b±) and enhances antitumor CD8± T cell immuni...

We have generated a polyclonal antibody against a novel immunomodulator, neem leaf glycoprotein (NLGP) that can react to a specific 47Kd subunit of NLGP. Generated anti-NLGP antibody (primarily IgG2a) was tested for its anti-tumor activity in murine carcinoma (EC, CT-26), sarcoma (S180) and melanoma (B16Mel) tumor models. Surprisingly, tumor growth...

Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated...

Tolerogenic dendritic cells (DCs) are a subset of DCs characterized by abundant indoleamine 2, 3 dioxygenase (IDO) expression. IDO may be co-operatively induced in DCs by regulatory T (Tregs) cells and various DC maturation agents. Tregs are markedly amplified in the physiological system of cancer patients, inducing over tolerance in DCs that leads...

We have evaluated the toxicity profile of a unique immunomodulator, neem leaf glycoprotein (NLGP) on different physiological systems of Swiss mice and Sprague Dawley rats. NLGP injection, even in higher doses than effective concentration caused no behavioral changes in animals and no death. NLGP injection increased the body weights of mice slightly...

Background & objectives: Interferon alpha 2b (IFNα2b) has been reported to regulate several immune functions efficiently to enhance the cytotoxic activity of NK and T cells towards various forms of tumours. The objective of the present study was to evaluate the efficacy of IFNα2b in overcoming disease induced and/or treatment associated imunosuppre...

In an aim to rectify dysregulated CC chemokine receptor (CCR5)/ligand (RANTES, MIP-1α, MIP-1β) status of monocytes/macrophages in tongue squamous cell carcinoma (TSCC; n = 12) patients, we have tested interferon α2b (IFNα2b), a novel immunomodulator with wide use in the management of several forms of cancer. IFNα2b can upregulate reduced CCR5 expre...

Despite being a pleiotropic cytokine, the therapeutic potential of interferon α2b (IFNα2b) is debatable. Thus, the need for identifying predictive marker(s) for patients who are most likely to benefit from the treatment is pivotal for avoiding the exposure of nonresponsive patients to the toxicity of the treatment. To account for the attenuated eff...

Myeloid-derived dendritic cells (DCs) generated from monocytes obtained from stage IIIB cervical cancer (CaCx IIIB) patients show dysfunctional maturation; thus, antitumor T cell functions are dysregulated. In an objective to optimize these dysregulated immune functions, the present study is focused on the ability of neem leaf glycoprotein (NLGP),...

Previous studies have shown that the CC chemokine receptor CCR5 is downregulated on monocyte/macrophage (MO/Mphi) surfaces in head and neck squamous cell carcinoma (HNSCC) patients (stage IIIB). Ligands (RANTES, MIP-1alpha and MIP-1beta) of this chemokine receptor were also secreted in lesser quantity from MO/Mphi of HNSCC patients in comparison wi...

Expression of STAT3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differe...

AIM: Cyclophosphamide (CP) is one of the most widely used alkylating antineoplastic agents that damage normal cells while killing cancerous cells in vivo. The use of CP in treating cancer patients is limited due to its severe toxicities induced mainly by oxidative stress. Diphenylmethyl selenocyanate is a synthetic organoselenium compound shown to...

We have demonstrated augmentation of the CD3-CD56+ natural killer (NK) and CD8+CD56_ T-cell-mediated tumor cell cytotoxicity by neem leaf glycoprotein (NLGP). These NK and T cells were isolated from the peripheral blood of head and neck squamous cell carcinoma patients with a state of immunosuppression. NLGP induces TCRalphabeta-associated cytotoxi...

Multidrug resistance (MDR) is still a major threat to successful clinical application of cancer chemotherapy. Copper plays an important role in biological systems, and copper is also involved in carcinogenesis. In the present investigation, we addressed the question whether metal copper might be involved in drug resistance of murine and human tumor...

We have studied the immunomodulatory effects of interferon-alpha2b (IFN-alpha2b) in rectification of the dysregulated IFN-gamma-dependent chemokines and their receptor CXCR3 splice variants in head and neck squamous cell carcinoma-peripheral blood mononuclear cells (HNSCC-PBMC). CXCR3 expression was upregulated in HNSCC-PBMC, with the demonstration...

Interaction between CXCL10 and CXCR3 is dysregulated in head and neck squamous cell carcinoma (HNSCC) and hampers chemotaxis of cytotoxic cells at tumor site. In continuation of the demonstration of significant immunomodulatory effects of neem leaf preparation (NLP), the active ingredient of NLP is characterized as a glycoprotein (NLGP). NLGP is re...

We assessed the immunological status of stage III and IV head and neck squamous cell carcinoma (HNSCC) patients and age-matched healthy individuals. In HNSCC patients, the total leukocyte count was lower and the proliferating ability of PBMCs against phytohemagglutinin (PHA) was significantly downregulated. These cells showed lower expression of th...

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or overexpression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is act...

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is ac...

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and...

Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG). Herein, we have determined the efficacy of CuNG in overcoming multidrug-resistant cancer using drug-resistant murine and human cancer cell lines. Action of CuNG following single i.m. administration (5 mg/kg body weight) was...

A murine monoclonal anti-idiotype (Id) antibody, 3H1 has been developed and characterized previously. Anti-Id 3H1 mimics a specific epitope of carcinoembryonic antigen (CEA) and can be used as a surrogate antigen for CEA. 3H1 induced anti-CEA immunity in different species of animals as well as humans and showed promise as a potential vaccine candid...

We have examined the role of interferon alpha2b (IFNalpha2b) in augmentation of the suppressed immune functions and cytotoxicity of tobacco-related head and neck squamous cell carcinoma (HNSCC) patients. The suppressed killing activity of PBMC of HNSCC patients towards KB, MCF7 and K562 cell lines could be restored by in vitro treatment of PBMC wit...

In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone) glycinate (CuNG) has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effe...

Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hu...

The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protoco...

The antineoplastic activity of a platinum complex K4 (Pt Cl2 ATP) (Pt-ATP) has been investigated in transplantable tumors, both in an ascitic and solid (Ehrlich ascites carcinoma) tumor model. It has been observed that the drug at the total dose of 10 mg/kg body weight successfully inhibited the tumor burden both in ascitic and solid tumor system a...

Glutaminase is a hematotoxic anti-tumor agent, and copper-ATP complex (Cu-ATP) is both anti-neoplastic and hematostimulatory. Combination chemotherapy with these two agents has been performed in mice bearing Ehrlich ascites carcinoma, to elucidate whether this could result in augmented tumor inhibition with reduced hematotoxicity. Glutaminase-Cu-AT...

The hematologic effect of [Cu3(ATP)(2)6H2O]2-, a synthetic copper-ATP complex (Cu-ATP) having antitumor activity, was investigated in normal and Ehrlich ascites carcinoma-bearing mice. Cu-ATP (25 mg/kg) induced appreciable tumor inhibition and prolonged host survival which were accompanied by elevated levels of hemoglobin, platelet and lymphocytes...

The anti-neoplastic activity of bacterial glutaminase on Ehrlich ascites tumor-bearing mice was studied by determining the reduction in the tumor cell count and extension of life span of the host after therapy. The therapeutic effect of glutaminase in relation to change in activity of glutaminolytic enzymes (glutamine amidohydrolase (GNase) and glu...

Phosphate-dependent glutaminase activity in spleen, kidney, brain and liver is increased after tumor cell inoculation and this activity gradually increases with the progression of the tumor. The increase in enzyme activity in the liver is significant. Studies of the response of liver glutaminase after Cu-ATP treatment reveals that Cu-ATP is capable...