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1.  Report of chronic myelogenous leukemia in chronic phase from, Asian Institute of Oncology, Mumbai, 2002-2010 
Chronic myeloid leukemia (CML) has paradigm shift in its treatment modality after the discovery of targeted therapy Imatinib. At our centre we collected data of 100 consecutive patients over a period of 8 years. The interesting finding in our study was difference in the survival of patients presenting in early chronic phase (81%) versus late chronic phase (16%). Also the patients with primary resistance did poorly compared to the patients who developed secondary resistance to Imatinib.
PMCID: PMC3902615  PMID: 24516300
Chronic myeloid leukemia; chronic phase; veenat; Glivec
2.  Targeting mTOR pathway: A new concept in cancer therapy 
This article highlights the current knowledge of mTOR biology and provides new insights into the role of mTOR in different cancers. An active mTOR coordinates a response in cell growth directly through its effects on cell cycle regulators and indirectly by sustaining nutrient supply into the cell through the production of nutrient transporters and also through the promotion of angiogenesis. A primary way that mTOR exerts its regulatory effects on cell proliferation is by controlling the production of cyclin D1. mTOR increases the translation of hypoxia-inducible factor 1 (HIF-1)/HIF-2. The HIF transcription factors drive the expression of hypoxic stress response genes, including angiogenic growth factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor β (PDGF-β), and transforming growth factor a (TGF-α). mTOR also increases the surface expression of nutrient transporters proteins. An increase in these proteins results in greater uptake of amino acids and other nutrients by the cell leading to adequate nutrient support to abnormal cell growth and survival. There is also emerging evidence that mTOR activation may play a role in promoting cell survival through the activation of antiapoptotic proteins that contribute to tumor progression. Given that the mTOR pathway is deregulated in a number of cancers, it is anticipated that mTOR inhibitors will have broad therapeutic application across many tumor types. Until now, no treatment demonstrated Phase III evidence after disease progression on an initial VEGF-targeted therapy in advanced renal cell carcinoma. Everolimus is the first and only therapy with Phase III evidence after failure of VEGF-targeted therapy. Everolimus is a once-daily, oral inhibitor of mTOR (mammalian target of rapamycin) indicated for the treatment of advanced renal cell carcinoma in patients, whose disease has progressed on or after treatment with VEGF-targeted therapy.
PMCID: PMC3089921  PMID: 21584218
Angiogenesis; bioenergetics; everolimus
3.  Granulocyte colony-stimulating factor (filgrastim) in chemotherapy-induced febrile neutropenia 
The use of granulocyte colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is well accepted. To assess whether administration of filgrastim along with standard empiric antibiotic therapy is beneficial for patients with chemotherapy-induced febrile neutropenia (FN), we conducted an open, non-randomized clinical trial.
Materials and Methods:
This was a prospective, open, Phase IV clinical trial in patients receiving chemotherapy for histologically confirmed cancer, with an oral temperature of >38.2°C and absolute neutrophil count (ANC) of <500/mm 3. Filgrastim was administered subcutaneously in a dose of 5 mcg/kg/day, 24 hours after administration of cytotoxic therapy, for up to two weeks or until the ANC reached 10,000 cells/mm 3. The parameters of assessment included duration of neutropenia, fever, hospitalization and antibiotic usage.
All 24 evaluable patients recovered from neutropenia, fever and FN in a median duration of two days. This result is similar to that reported in earlier studies with filgrastim. Despite the acceleration in recovery from neutropenia and fever, it also reduced the duration of hospital stay and usage of intravenous (IV) antibiotic. Only two adverse events were reported, which were of mild nature.
Filgrastim, when used in patients with chemotherapy-induced neutropenia, exhibited efficacy in accelerating the recovery from neutropenia and fever comparable to that reported with filgrastim in literature. The data from this study suggest that filgrastim is effective in the treatment of chemotherapy-induced neutropenia and is well tolerated by Indian patients.
PMCID: PMC3009438  PMID: 21206712
Febrile neutropenia; filgrastim; granulocyte colony-stimulating factor
4.  Natural killer and lymphokine activated killer cell functions in Hodgkin's disease. 
British Journal of Cancer  1990;62(2):205-208.
We report the natural killer (NK) and lymphokine activated killer (LAK) cell activities in peripheral blood lymphocytes (PBL) from untreated patients with Hodgkin's disease (HD) and from healthy donors. The frequency of LAK cell precursors was also studied using limiting dilution analysis (LDA). About 75% of the HD patients had normal NK activity. There was a higher percentage of low NK responders (mean percent NK activity of healthy donors--2 SD) in patients with lymphocyte depletion histologic grade of the disease and those who were in clinical stage IV, suggesting a correlation of decrease in NK activity with poor prognosis. We found efficient LAK activity against the NK-sensitive K562 cells and NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumour targets in both low and normal NK responder HD patients, irrespective of the histopathological grade and clinical stage of the disease. In concordance with their good LAK cell activity, HD patients showed a frequency distribution of LAK cell progenitors in the PBL comparable to that of healthy donors.
PMCID: PMC1971824  PMID: 2386735
7.  Concanavalin A induced suppressor cell activity and autorosette forming cells in chronic myeloid leukemia patients. 
British Journal of Cancer  1983;48(6):783-790.
In the present paper attempts have been made to investigate suppressor cell activity in CML patients in first and subsequent remissions in order to study the relationship between suppressor cell activity and progression of the disease. For this purpose, the ability of Con A activated suppressor cells from peripheral blood of CML patients in 1st, 2nd and 3rd remission to suppress PHA response of autologous lymphocytes is investigated and compared with that of normal healthy donors. The ability of Con A activated cell population to form rosettes with autologous RBCs (ARFC) is also investigated. The results indicate that lymphocytes from CML patients in 1st (61.8 +/- 6.1%), 2nd (62.6 +/- 3.0%) and 3rd (55.3 +/- 4.8%) remissions show significantly high suppressor cell activity than normal healthy donors (36.5 +/- 1.9%) when activated with Con A. Similarly, generation of spontaneous suppressor cell activity was also higher in 1st (23.3 +/- 4.7%) and 2nd (25.3 +/- 4.2%) remission lymphocytes than controls (10.1 +/- 2.5%). In the 3rd remission however, the spontaneous suppressor cell activity (14.5 +/- 3.2%) was comparable to controls. Thus it appears that a higher suppressor cell precursor population is present in CML patients in remission. However, this could not be correlated with the progression of the disease. CML patients in 1st remission also revealed an increased percentage of ARFC which correlated with the suppressor cell function. The ARFC activity tested in a few patients in subsequent remissions was comparable with controls although functional suppressor activity was increased.
PMCID: PMC2011565  PMID: 6228243
8.  In vitro generation of lymphocytotoxicity to autochthonous leukaemic cells in chronic myeloid leukaemia. 
British Journal of Cancer  1981;43(1):13-18.
Lymphocytes from 13 chronic myeloid leukaemia (CML) patients in remission were tested for their ability to differentiate in vitro into a cell population cytotoxic to autochthonous target leukaemic cells. CML remission lymphocytes were cultured in vitro with autochthonous leukaemic cells and allogeneic normal lymphocytes from an unrelated donor, singly or in combination. The cytotoxic lymphocytes obtained after 7 days of culture were tested for their ability to kill autochthonous leukaemic cells in a 3h 51Cr-release assay. It was found that with the allogeneic stimulus alone, cytotoxicity was generated in 5/13 cases, whilst stimulation of lymphocytes with autochthonous leukaemic cells alone induced cytotoxicity in 7/13 cases. In contrast, anti-leukaemic cytotoxicity was shown in 12/13 cases when responder lymphocytes were stimulated with both autochthonous leukaemic and unrelated allogeneic normal lymphocytes. The specificity of cytotoxicity was confirmed using other targets such as autochthonous PHA-transformed lymphoblasts and mouse L1210 cells. In 1/5 cases, CML remission lymphocytes stimulated with autochthonous leukaemic cells showed cytotoxicity to PHA-transformed autochthonous normal lymphoblasts, whilst 1/4 patients showed nonspecific cytotoxicity to L1210 cells when lymphocytes were cultured in MLC or MLTC, as well as in a 3-cell assay.
PMCID: PMC2010486  PMID: 6450603
9.  Cellular sensitization in chronic myeloid leukaemia patients to leukaemic blast antigens. 
British Journal of Cancer  1979;40(3):391-396.
Sixteen chronic myeloid leukaemia (CML) patients in remission were tested with solubilized membrane antigens from CML leukaemic cells, CML blasts, AML blasts and ALL blasts for cellular immunity in vitro by lymphocyte transformation (LT) and leucocyte migration inhibition (LMI) assays. Twelve CML patients in remission were tested with allogeneic PHA-transformed normal lymphoblasts. As controls, peripheral-blood leucocytes from 9 healthy persons were tested with the same antigen preparations. It was seen that 8/16 (50%) CML patients responded to CML antigens by both LT and LMI assays, while 5/16 (31%) patients reacted to CML blasts and 44% (7/16) patients reacted to AML blast antigens. It was interesting to note that 5/11 (45%) CML patients reacted to ALL blast antigens by both assays. One out of 12 patients reacted to PHA-transformed lymphoblasts. None of the healthy controls reacted to leukaemia-associated antigens. The results suggest the sharing of antigens between myeloid leukaemic cells, myeloid blasts and lymphoid blasts.
PMCID: PMC2010056  PMID: 292450
10.  Demonstration of cellular immunity in chronic myeloid leukaemia using leucocyte migration inhibition assay. 
British Journal of Cancer  1976;33(3):267-272.
Peripheral blood leucocytes from chronic myeloid leukaemia patients in remission were tested for inhibition of migration in presence of solubilized membrane antigens from leukaemic cells in 15 cases. Eight out of 9 autochthonous combinations (88-8%) and 35/49 allogenic combinations (71-4%) showed inhibition of migration. Antigens prepared from relapse leukaemic cell samples in 4 cases showed inhibition of migration of autochthonous as well as allogeneic remission leucocytes. The same batch of CML antigens inhibited migration of normal leucocytes at the level of 22-2%. The difference between inhibition of migration shown by remission leucocytes and normal leucocytes in presence of CML antigens was statistically significant. Solubilized antigens, similarly prepared from normal leucocytes, showed inhibition of migration of remission leucocytes to the extent of 15% only. The difference between the reactivity of CML remission leucocytes to normal and CML antigens was also statistically significant. No enhancement of migration of remission leucocytes was seen with CML antigens.
PMCID: PMC2024985  PMID: 1063589

Results 1-10 (10)