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S Advani

Publications and source records attributed to S Advani.

At least 37 records · Page 2Linked to original sources
PubMed1999

Essential drugs for cancer therapy: a World Health Organization consultation.

The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible.

Antineoplastic Agents↗
PubMed1999

Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus.

Malignant gliomas remain incurable with current interventions. Encouraging investigational approaches include the use of genetically modified herpes simplex-1 (HSV-1) viruses as direct cytotoxic agents. Combining attenuated HSV-1 with standard therapy, human U-87 malignant glioma xenografts grown in the hind limb or intracranially in athymic nude mice were exposed to ionizing radiation, inoculated with genetically modified HSV R3616, or received both virus and radiation. The combination of virus with fractionated ionizing radiation suggests a synergistic action and results in reduced tumor volumes and longer survivals when compared with treatment with either modality alone.

Animals↗
PubMed1998

Avascular necrosis of bone--a complication of aggressive therapy for acute lymphoblastic leukemia.

The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The median period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awareness of this complication is important in order to have an early diagnosis so as to limit disability.

Adolescent↗
PubMed1998

Comparative incidence of the rearrangements of TEL/AML1 and ALL1 genes in pediatric precursor B acute lymphoblastic leukemias in India.

The TEL/AML1 translocation, which is specific for pre B-cell leukemias is predictive of a favorable treatment outcome. In contrast, translocations involving the ALL1 locus which are associated with both B and non B leukemias predict a poor outcome. To determine the relative distribution of high and low risk molecular subtypes of ALL in India, we analyzed the relative frequencies of these two translocations. The study included a random selection of 46 newly diagnosed patients of childhood ALL from the Tata Memorial Hospital, Bombay, India. Similar to the frequency observed in other world regions, we found an All1 rearrangement in less than 7% (3/46) of pre B-ALL patients. In contrast to the 25% frequency reported for other regions the low risk molecular subtype characterized by the TEL/AML1 translocation represented a comparatively smaller fraction (4/46) in this study. These results provide a preliminary support for a lower frequency of molecular subgroup of leukemias with a potential for favorable clinical outcome in precursor B-ALL from India.

Adolescent↗
PubMed1997

Decreasing the apoptotic threshold of tumor cells through protein kinase C inhibition and sphingomyelinase activation increases tumor killing by ionizing radiation.

Approximately 30% of cancer deaths result from the failure to control local and regional tumors. The goal of radiotherapy is to maximize local and regional tumor cell killing while minimizing normal tissue destruction. Attempts to enhance radiation-mediated tumor cell killing using halogenated pyrimidines, antimetabolites, and other DNA-damaging agents or sensitizers of hypoxic tumor cells have met with only modest clinical success. In an unique strategy to modify tumor radiosensitivity, we used an inhibitor of the protein kinase C group A and B isoforms, chelerythrine chloride (chelerythrine), to enhance the killing effects of ionizing radiation (IR). Protein kinase C activity plays a central role in cellular proliferation, differentiation, and apoptosis. Chelerythrine increases sphingomyelinase activity and enhances IR-mediated cell killing through induction of apoptotic tumor cell death in a radioresistant tumor model both in vitro and in vivo. Although previous reports have suggested that IR-mediated apoptosis correlates with tumor volume reduction, we demonstrate for the first time that lowering the apoptotic threshold increases tumor cell killing in vivo.

Alkaloids↗
PubMed1997

Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice.

The objective of this study was to determine the acute effects of glucocorticoids on in vivo levels of bone collagen synthesis in neonatal mice. Mice were injected with vehicle or dexamethasone at the start of the experiment. At 22 h, mice were given a 10 microCi injection of [3H]proline. At 24 h, the mice were sacrificed and the incorporation of [3H]proline into collagenase-digestible CDP labeling) and noncollagen (NCP labeling) protein in calvariae were determined by digestion with bacterial collagenase. Calvarial RNA was analyzed for COL 1A1 and osteocalcin mRNA levels by Northern blotting. After 24 h, vehicle-treated mice showed a 9.8 +/- 1.0% weight gain while dexamethasone-treated mice (1 mg/kg) had a 7.4 +/- 0.8% weight loss. Dexamethasone (1 mg/kg) decreased CDP and NCP labeling in calvariae by 51 +/- 4% and 17 +/- 4%, respectively (13 experiments). The inhibitory effect on protein labeling was selective for collagen since dexamethasone decreased the percent collagen synthesis from 25.4 +/- 1.6% to 16.6 +/- 1.0% (13 experiments). Dexamethasone at 3 mg/kg also decreased CDP labeling and the percent collagen synthesis in calvariae. There was a 30% reduction in COL1A1 mRNA levels and a 67% decrease in osteocalcin mRNA levels. To determine the reversibility of the inhibition of collagen synthesis, mice were given a single injection of dexamethasone (1 mg/kg) and then injected with [3H]proline 2 h prior to sacrifice at 24, 48, or 72 h. The reduction in CDP labeling observed at 24 h was fully reversed by 48-72 h. Moreover, by 72 h, the-rate of weight gain by dexamethasone-treated mice was similar to vehicle-treated controls. These data show that administration of dexamethasone to neonatal mice leads to a selective decrease in bone collagen synthesis within 24 h that is accompanied by down-regulation of osteocalcin and COL1A1 mRNA levels. This model will be useful in determining mechanisms by which high dose glucocorticoids inhibit bone formation in vivo.

Analysis of Variance↗
PubMed1997

Preliminary report of an intensified, short duration chemotherapy protocol for the treatment of pediatric non-Hodgkin's lymphoma in India.

BACKGROUND: In the past, the results of the treatment of non-Hodgkin's lymphomas (NHL) in Indian children have been poor, due to inadequate chemotherapy and poor supportive care. In an attempt to overcome these problems, we conducted a clinical trial in Bombay with a new protocol, MCP842. PATIENTS AND METHODS: Seventy-four previously untreated patients < 25 years were entered on study at the Tata Memorial Hospital, Bombay. Patients with lymphoblastic lymphoma (LL) (38) without bone marrow involvement and all patients with small noncleaved cell lymphoma (SNCL) (18) and large cell lymphoma (LCL) (18) were eligible. Treatment consisted of alternating cycles of two regimens, A and B. Patients with St. Jude stages I and II received six cycles, and those with stages III or IV received eight cycles. A cycles included cyclophosphamide, adriamycin, vincristine and ara-C, and B cycles, etoposide, vincristine, methotrexate, ifosfamide and mesna. RESULTS: Complete response was achieved in 67 (91%) of patients. Event free survival (EFS) for all patients was 58%; 68% for patients with SNCL and LCL combined, and 48% for patients with LL. There was no significant difference in EFS by histology (LL versus non-LL), or stage. There were nine (12%) toxic deaths, two during induction and seven in patients in remission; six occurred in patients with LL. CONCLUSIONS: These results are better than past results in Bombay. Unlike earlier CCG protocols, in which the outcome between patients with LL and non-LL differed, this was not so in MCP842. Even patients with extensive LL without bone marrow disease received only eight cycles of therapy, suggesting that short duration therapy is curative in as many as half of such patients--an important observation in a country with limited resources.

Adolescent↗
PubMed1997

Non-Hodgkin's lymphoma: cytotoxic T lymphocyte mediated activity correlated with histopathological classification and staging.

Non-Hodgkin's lymphomas (NHLs) constitute a heterogeneous group of lymphoid tumors and a majority of them in India are of B-cell phenotype. It has been postulated that immunoregulatory dysfunctions may be involved in the pathogenesis of NHL. Hence, peripheral blood mononuclear cells obtained from twenty six untreated patients were assessed for cytotoxic T lymphocyte mediated (CTL) activity in 51Cr release assay. Patients were classified according to Revised European American Lymphoma classification. B-cell small lymphocytic lymphoma patients showed lower CTL activity than NHL patients of other histopathological subtypes and healthy individuals. Diffuse large B cell lymphomas showed CTL activity comparable to healthy individuals. However, within the same histopathological subgroup, the CTL activity did not correlate with the stage of the patients.

Adult↗
PubMed1997

Auto-tumor reactive cytotoxic T-cell responses in B-cell non-Hodgkin's lymphoma.

We have generated cytotoxic T-lymphocytes (CTLs) from the peripheral blood (PB) of eight B-cell non-Hodgkin's lymphoma (NHL) patients by in vitro coculture with autologous fresh tumor cells. Their functional activity was assessed in 51Cr release assay and was found to be MHC class I restricted. Our results indicate the presence of T-cells cytotoxic for autologous tumor cells in the PB of these patients but these were relatively small numbers in small lymphocytic lymphomas (SLLs). Treatment of fresh tumor cells with rIFN-gamma and rTNF-alpha alone, or in combination significantly increased their susceptibility in 4/5 cases of SLLs, and a case of diffuse large cell lymphoma and Burkitt lymphoma (BL), while, B-cell lymphoma, rich in T-cells, did not show any appreciable increase. Fresh tumor cells were also analysed for MHC class I and ICAM-1 antigens by flow cytometry, in 5/8 cases before and after cytokine treatment. Significant upregulation of MHC class I antigens but with no detectable change in ICAM-1 observed in a case of SLL and BL, correlated with enhanced susceptibility. These findings suggest the possible role of MHC class I antigens in the cytotoxic susceptibility of autologous tumor cells in B-cell NHL.

Cytotoxicity, Immunologic↗
PubMed1996

Pattern of second primary neoplasms following breast cancer.

BACKGROUND: Second primary neoplasms (SPN) have been seen with diseases such as breast cancer and Hodgkin's disease. Therapeutic agents used for their treatment have been found responsible for the development of SPN in some cases. In addition, genetic factors are known to contribute to their development. METHODS: A retrospective study of 15 patients who had primary breast cancer and developed SPN concurrently or sequentially was conducted. RESULTS: Of 15 patients analysed in this study, five had haematological SPN, four had ovarian cancer, and six had different types of non-haematological SPN. Familial clustering was found in two patients. A peculiar abnormality of chromosome 5 and 7 was detected in one patient with haematological SPN, suggesting therapy-related leukaemia. CONCLUSIONS: It is postulated that alkylating agents with or without p53 gene inactivation may predispose to leukaemia, whereas ovarian tumors following breast cancer could be related to BRCA 1 gene inactivation.

Adult↗
PubMed1996

Fc gamma RII and Fc gamma RIII on normal leukaemic granulocytes: a flow cytometry and northern analysis.

Morphologically mature granulocytes from patients with chronic myeloid leukaemia (CML) exhibit a defect in internalization of heat-aggregated IgG. In order to investigate this defect at the molecular level and, in turn, the discordant maturation of these granulocytes, we compared the expression of Fc gamma RII and Fc gamma RIII, the two receptors for IgG on the surface of granulocytes, in normal and CML samples. Our flow cytometric data show that the number of granulocytes expressing Fc gamma RIII is lowered in CML patients to near half that in normal individuals, with a simultaneous decrease in the steady-state levels of the mRNA for Fc gamma RIII. Mean fluorescence intensity (MFI), an indicator of the number of receptors per cell, varies widely for Fc gamma RIII in normal individuals whereas it is more localized and lowered in granulocytes from CML patients. The number of granulocytes positive for Fc gamma RII is also significantly lowered in CML samples compared to the normals, which exhibit a wide variation in the number of cells positive for the receptor, even though their nRNA levels do not vary much. The CML granulocytes, in general, exhibit lowered levels of the steady-state mRNA for Fc gamma RII. The MFI for the surface expression of Fc gamma RII is only marginally different between the two cell types. Our data indicate that the morphologically homogeneous population of CML granulocytes actually consists of at least two types of cells, one which expresses the Fc receptors and one which does not.

Animals↗
PubMed1995

Experimental tests for protrusion and undulation pressures in phospholipid bilayers.

Theoretical treatments predict that strong entropic pressures between adjacent bilayer membranes can arise from out of plane motions caused by either thermally induced bending undulations of the entire bilayer [Harbich, W., & Helfrich, W. (1984) Chem. Phys. Lipids 36, 39-63; Evans, E. A., & Parsegian, V. A. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7132-7136] or protrusions of individual lipid molecules from the bilayer surface [Israelachvili, J. N., & Wennerström, H. (1992) J. Phys. Chem. 96, 520-531]. To determine the relative contributions of these motions to the repulsive pressure between phospholipid bilayers, the osmotic stress/X-ray diffraction method was used to measure the range and magnitude of the total repulsive pressure, and micropipet methods were used to measure the bending moduli of phosphatidylcholine bilayers containing lysophosphatidylcholine and polyunsaturated diarachidonoylphosphatidylcholine (DAPC) bilayers. In the gel phase, incorporation of equimolar lysophosphatidylcholine into phosphatidylcholine bilayers caused the hydrocarbon chains from apposing monolayers to interdigitate, but did not appreciably change the equilibrium fluid spacing in excess buffer from its control value of 12 A. In contrast, the incorporation of equimolar lysophosphatidylcholine into liquid-crystalline phase phosphatidylcholine bilayers markedly increased the range of the repulsive pressure so that equilibrium fluid separation increased from 15 to 28 A, and also decreased the bilayer bending modulus from 5.1 x 10(-13) to 1.3 x 10(-13) erg. Liquid-crystalline DAPC bilayers had intermediate values of both equilibrium fluid separation (20 A) and bending modulus (2.8 x 10(-13) erg). Analysis of these data indicates that (1) the relative importance of entropic pressures compared to the hydration pressure depends strongly on the composition and structure of the bilayer, (2) the protrusion pressure may contribute to the total repulsive pressure at large pressures or small fluid spacings, and (3) the repulsive undulation pressure, together with the attractive van der Waals pressure, is a primary factor in determining the fluid spacing at low and/or zero applied pressures in liquid-crystalline bilayers.

Electrons↗
PubMed1995

Protein 1a: a major wheat germ agglutinin binding protein on the surface of human granulocytes associated with the cytoskeleton.

Lectin-receptors on leukocyte and endothelial surfaces are becoming more important in the light of increasing evidence which implicates lectin-carbohydrate interactions in diverse physiological phenomena. This study reports the identification of a major 118 kDa granulocyte surface protein, (Protein 1 a) which binds the lectin wheat germ agglutinin (WGA), and is distinctly different from reported WGA binding granulocyte membrane proteins. Protein 1 a has been isolated from the Triton-soluble and Triton-insoluble lysates of normal individuals and patients with Chronic Myeloid Leukemia (CML) using a combination of differential solubilization, lectin affinity, ion exchange chromatography and HPLC. The protein from the detergent lysates of both normal and CML granulocytes has similar pI values, lectin affinities, and hydrophobicity. However, its solubility in Triton is different in the two cell types. In 71% of CML cases examined, Protein 1 a exhibits decreased Triton solubility suggesting its increased association with the cytoskeleton (CSK). Stimulation of normal granulocytes with WGA leads to the translocation of the soluble form of Protein 1 a to the Triton-insoluble fraction. This cytoskeletal recruitment of Protein 1 a is sustained only under conditions of excess WGA and occupied receptor. The CSK disruptive agent dihydrocytochalasin B (H2CB) releases the insoluble form of the receptor into the Triton-soluble fraction. Investigation of a CSK-involving process such as ligand internalization revealed that CML granulocytes exhibit slower kinetics of internalization of fluorescent WGA molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1995

Decreased expression of both Fc gamma RII and Fc gamma RIII mRNA in leukemic granulocytes.

Morphologically mature granulocytes from patients with chronic myeloid leukemia exhibit a defect in internalization of heat-aggregated IgG. In this study, we investigate the status of the steady-state levels of the mRNA for the two receptors for IgG, Fc gamma RII and Fc gamma RIII, as a step towards understanding the molecular basis of the defect and in turn the discordant maturation of the leukemic cells. Our data show that the mRNA for both receptors is lower in the leukemic cells relative to the normal cells. This may be one of the causes for the defective endocytosis.

Blotting, Northern↗
PubMed1995

Temperature dependence of the repulsive pressure between phosphatidylcholine bilayers.

Bilayer structure and interbilayer repulsive pressure were measured from 5 to 50 degrees C by the osmotic stress/x-ray diffraction method for both gel and liquid crystalline phase lipid bilayers. For gel phase dibehenoylphosphatidylcholine (DBPC) the bilayer thickness and pressure-distance relations were nearly temperature-independent, and at full hydration the equilibrium fluid spacing increased approximately 1 A, from 10 A at 5 degrees C to 11 A at 50 degrees C. In contrast, for liquid crystalline phase egg phosphatidylcholine (EPC), the bilayer thickness, equilibrium fluid spacing, and pressure-distance relation were all markedly temperature-dependent. As the temperature was increased from 5 to 50 degrees C the EPC bilayer thickness decreased approximately 4 A, and the equilibrium fluid spacing increased from 14 to 21 A. Over this temperature range there was little change in the pressure-distance relation for fluid spacings less than approximately 10 A, but a substantial increase in the total pressure for fluid spacings greater than 10 A. These data show that for both gel and liquid crystalline bilayers there is a short-range repulsive pressure that is nearly temperature-independent, whereas for liquid crystalline bilayers there is also a longer-range pressure that increases with temperature. From analysis of the energetics of dehydration we argue that the temperature-independent short-range pressure is consistent with a hydration pressure due to polarization or electrostriction of water molecules by the phosphorylcholine moiety. For the liquid crystalline phase, the 7 A increase in equilibrium fluid spacing with increasing temperature can be predicted by an increase in the undulation pressure as a consequence of a temperature-dependent decrease in bilayer bending modulus.

Gels↗
PubMed1995

Immunophenotype and ultrastructural studies in blast crisis of chronic myeloid leukemia.

Thirty-four patients with chronic myeloid leukemia in blast crisis (CML-BC) were evaluated for lineage differentiation with immunological markers and the presence of ultrastructural peroxidase. Eighteen (52.9%) were found to have myeloid blast crisis. Cytochemically, myeloperoxidase (MPO) could be detected only in six patients on light microscopy while in the remaining 12 patients, myeloid differentiation was confirmed only by demonstration of MPO either at ultrastructural level or by the reactivity with anti myeloperoxidase (anti MPO) antibody. Six (17.6%) had lymphoid blast crisis as identified by lymphoid specific markers (CD19; CD10; CD7; CD4) along with the absence of myeloid markers. Heterogenous blast cell populations with mixed lineage differentiation were seen in 4 (11.7%) patients. These cases showed both lymphoid (CD19, CD10) and myeloid (anti MPO and ultrastructural MPO) characteristics. A single case of megakaryoblastic blast crisis was identified with positivity for CD41 and CD42 along with the presence of platelet peroxidase at the ultrastructural level. Five cases (14%) of CML blast crisis remained unclassifiable. These results suggest that blast crisis in CML show an arrest of differentiation at an early stage when compared to de novo acute leukemias. This is particularly evident from the fact that MPO could only be demonstrated ultrastructurally or with anti MPO antibody in the majority of patients with myeloid differentiation. It is expected that utilisation of molecular studies including immunoglobulin and T-cell receptor gene rearrangement and m-RNA expression for myeloperoxidase will provide a better insight into the level of differentiation for the presently unclassifiable cases of CML-blast crisis.

Antigens, CD↗