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S Advani

Publications and source records attributed to S Advani.

At least 55 records · Page 3Linked to original sources
PubMed1995

Chromosome investigations & clinical outcome in patients with myelodysplastic syndromes.

A total of 25 patients with primary myelodysplastic syndrome (p-MDS) were cytogenetically investigated. The incidence of abnormal karyotypes was higher, detected in 88 per cent of the patients and the most frequent abnormality was a terminal deletion of chromosome 7 (45% of the patients with abnormal karyotypes) followed by an i (17q) (18%), +21(14%), -5/5q (9%), del (11) (q22) (9%). Cytogenetic analysis after therapy/after leukaemic transformation indicated either stable clones (2 patients) or emergence of new clones such as inv(5) (q32q36), del (17) (p13), +20, +22 (1 patient each). It is to be noted that of the 8 patients with leukaemic transformation, 5 had del (7q). The leukaemic transformation (32% of the patients) was not related to the percentage of abnormal karyotypes not to the percentage of blasts at the time of the MDS presentation. Chromosome instability was shown by 10 (45%) patients. Our data indicate that higher frequency of chromosomal aberrations with involvement of chromosome 7 may be the result of underlying disease.

Adolescent↗
PubMed1994

Differential phosphorylation in normal and leukemic granulocytes in response to phorbol 12-myristate 13-acetate.

Granulocytes from the peripheral blood of patients with chronic myeloid leukemia (CML) exhibit a number of functional defects. To explore the relationship of these aberrations to signal transduction, granulocytes from normal subjects and CML patients were labelled with 32Pi, stimulated with phorbol myristate acetate (PMA) and the phosphoproteins (Pps) in the unstimulated and stimulated cells analyzed by 2D-SDS-PAGE followed by autoradiography. Results show that there are six distinct reproducibly phosphorylated proteins referred to as Pp1-Pp6 identifiable in the basal patterns of the resting granulocytes. Amongst these, Pp1 and Pp5 are more intensely phosphorylated and Pp3 is very faint or absent in unstimulated CML cells, relative to the normal granulocytes. On stimulation of normal cells with PMA, Pp1, Pp3, Pp4 and Pp6 exhibit distinct patterns of phosphorylation-dephosphorylation. In the CML cells, however, Pp1 and Pp4 are unresponsive to PMA. We conclude that PKC-mediated functions involving Pp1, Pp3 and Pp4 are most probably defective in CML cells.

Autoradiography↗
PubMed1992

Decreased expression of Fc gamma RIII mRNA in leukemic granulocytes.

Morphologically mature granulocytes from patients with chronic myeloid leukemia show significant impairment in their ability to internalize aggregated IgG, a ligand that is rapidly phagocytosed by normal human granulocytes. With a view to understand the molecular basis of this defect, normal and leukemic granulocytes were examined for the steady-state levels of mRNA for Fc gamma RIII, a membrane-associated receptor that initially binds and traps the IgG-opsonized antigens. Northern blot analyses revealed that the level of the specific mRNA in CML granulocytes was between 0.08 and 0.69 times that seen in the normal granulocytes. This could be one of the contributory factors for the observed endocytic defect in the leukemic granulocytes.

Blotting, Northern↗
PubMed1992

Cisplatin-based (PVB+M) chemotherapy in good-risk and poor-risk nonseminomatous germ cell tumors.

Twenty-seven patients with metastatic nonseminomatous germ cell tumors were treated with Cisplatin, vinblastine, bleomycin, and low-dose methotrexate (PVB+M) combinations. Patients were divided into good-risk and poor-risk groups. All seven patients (100%) with good-risk factors achieved complete response, and all are alive disease free at a median of 70 months. In the poor-risk group, only 10 of 20 patients (50%) achieved complete response, and seven (35%) are alive disease free at a median of 58 months. Eight patients, 4 in each group, were required to undergo surgery for removal of postchemotherapy residual masses. The results confirm that Cisplatin-based chemotherapy protocols are adequate to cure most patients with good-risk factors, and newer approaches are needed for patients at poor risk.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Differential phosphorylation--cause for defective internalization of aggregated IgG by chronic myeloid leukemic granulocytes?

Granulocytes from the peripheral blood of patients with chronic myeloid leukemia (CML) are known to exhibit a defect in internalization of aggregated IgG relative to normal cells. As this aberration may arise due to defective transmembrane signalling, this study was undertaken to analyze alterations, if any, in protein phosphorylation between the two cell types. Normal and CML granulocytes were labeled with 32P-sodium orthophosphate and then stimulated with aggregated IgG. The phosphoproteins in the unstimulated and stimulated cells were analyzed by 2D-SDS-PAGE followed by autoradiography. The results show that there are five distinctly identifiable, reproducibly phosphorylated proteins referred to as Pp1-Pp5. In the unstimulated normal cells, Pp1 is less phosphorylated than Pp3, while in CML cells, Pp1 is more intense than Pp3. On stimulation of normal cells, with aggregated IgG, intensity of Pp1 increases while that of Pp3 decreases. In CML cells this response is reversed. We conclude that one of the causes for the defective internalization of IgG by CML granulocytes may probably be the observed differences in the phosphorylation of the proteins under study.

Granulocytes↗
PubMed1991

Production of interleukin-1 and tumour necrosis factor in non-Hodgkin's lymphoma patients.

Peripheral blood monocytes from non-Hodgkin's lymphoma (NHL) patients were assessed for the monocyte functions with respect to their ability to secrete interleukin-1 and tumour necrosis factor (TNF) and their cytotoxic potential to tumour target WEHI 164 clone 13. Our results indicate comparable levels of interleukin-1 and TNF production by NHL patients. The cytotoxic potential by monocytes was also not depressed in these patients. The data obtained suggest normal monocyte functions in NHL patients.

Adult↗
PubMed1991

The anomaly of pyridine nucleotide synergism in carbon tetrachloride metabolism.

Carbon tetrachloride metabolism was examined in hepatic microsomes isolated from control and phenobarbital-treated Sprague-Dawley rats to determine the mechanism of pyridine nucleotide synergism. An NADPH generator increased metabolism two fold as determined by lipid peroxidation. Addition of NADH to the reaction system did not alter the maximum velocity, but did decrease the Km for NADPH from 61 microM to 7.6 microM in control and from 21 microM to 6.3 mM PB microsomes. Addition of NAD+ produced an increase in metabolism similar to NADH. Substrates and competitive inhibitors of nucleotide pyrophosphatase also enhanced CCl4 metabolism. A high correlation (r = 0.947) was indicated between the percent inhibition of nucleotide pyrophosphatase and the percent synergism of NADPH-catalyzed CCl4 metabolism. Thus, pyridine nucleotide synergism in CCl4 metabolism appears to result from the increased availability of NADPH produced by a decreased degradation of the NADPH by the nucleotide pyrophosphatase.

Animals↗
PubMed1991

Amelioration of doxorubicin resistance by pentoxifylline in human chronic myeloid leukemia cells in vitro.

Doxorubicin (DOX) is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Pentoxifylline (PTX) is a non-toxic methylxanthine used clinically for the treatment of intermittent claudication. It is an active haemorheological agent, used for the treatment of defective microcirculation. In the present study, we employed PTX as a drug response modulator in combination with DOX to achieve increased cytotoxicity in human chronic myeloid leukemia (CML) cells. Inhibition of 3H-TdR incorporation was used as a measure of cytotoxicity. PTX at 100 microM concentration significantly (P less than 0.001) potentiated DOX-mediated DNA biosynthesis inhibition in CML cells in vitro. Significant synergistic inhibition was seen in 13 out of 22 CML samples. Decreased DOX accumulation is a characteristic feature of DOX resistant tumor cell lines. Drug accumulation studies demonstrated that PTX significantly (P less than 0.02) increased the intracellular accumulation of DOX in the CML cells. The enhanced DOX accumulation can be a mechanism of increased cytotoxicity by DOX-PTX combination.

Doxorubicin↗
PubMed1991

Single and combination treatment with vitamin K3 and adriamycin: in vitro effects on cell survival and DNA damage in human chronic myeloid leukemia cells.

Utility of drug response modulators to increase therapeutic:toxic ratio of anticancer drugs in the treatment of refractory malignancies is becoming desirable. In this study, we have attempted to potentiate the tumor cell killing ability of Adriamycin (ADR) against chronic myeloid leukemia cells (CML), in the presence of vitamin K3. Cell growth was evaluated by the MTT assay and the 3H-thymidine incorporation inhibition assay. A highly significant (p less than 0.001) inhibition of cell survival and 3H-thymidine incorporation was effected in CML cells exposed to the combination of ADR and vitamin K3. When the CML cells were treated with ADR and vitamin K3 simultaneously, a greater fragmentation of the intact DNA was revealed as observed by the enhanced formation of DNA single strand breaks. Results demonstrate the therapeutic significance of employing vitamin K3 as an adjuvant in CML chemotherapy with ADR.

Cell Survival↗
PubMed1991

Expression of the multidrug transporter P-glycoprotein and in vitro chemosensitivity: correlation with in vivo response to chemotherapy in acute myeloid leukemia.

Thirty four patients with acute myeloid leukemia (AML) (30 de novo and 4 relapsed) were evaluated for P-glycoprotein (P-gp) expression, and in vitro chemosensitivity. The P-gp expression was evaluated by immunohistochemical method using JSB-1 monoclonal antibody and the results were visualized by peroxidase-antiperoxidase goat antimouse antibody and the in vitro chemosensitivity was measured by the semiautomated MTT colourimetric assay method. Depending upon the percent cells expressing P-gp and the intensity of P-gp staining, the samples were graded as absent, mild or strong for the relative P-gp expression, which was further correlated with the in vitro chemosensitivity and the clinical response of the tumors. Expression of P-gp was seen in 17 of the 30 de novo AML cases and all four relapse cases. Patients with no P-gp expression showed in vitro chemosensitivity while those with strong P-gp expression were resistant in vitro. Patients with mild P-gp expression showed varied chemosensitivity. P-gp expression correlated with clinical response to chemotherapy. Seven out of 11 patients with no P-gp achieved complete remission (C.R.). The other four died early in induction. Of five patients who expressed strong P-gp, four had resistant disease and the autopsy study of the remaining patient who died in induction revealed persistent disease. Of the 10 de novo AML patients who had mild P-gp expression, five achieved C.R. while one had resistant disease and four died in induction. All the four relapsed AML showed mild P-gp expression.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia.

DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.

Blotting, Northern↗
PubMed1990

Sensitization of chronic myeloid leukemia cells to adriamycin cytotoxicity by clofibrate.

Clofibrate (CPIB), an antihyperlipidemic agent, was employed as a drug response modulator in this study to evaluate its action, if any, on adriamycin (ADR) cytotoxicity in adriamycin insensitive chronic myeloid leukemia (CML) cells in vitro. Inhibition of (3H)-thymidine incorporation was used as a measure of DNA biosynthesis inhibition. A marginally toxic concentration of CPIB [0.001% (v/v)] was utilized to evaluate the cytotoxicity in CML cells exposed to ADR 5 and 10 micrograms/ml. A heterogeneous response was observed in 16 different CML blood samples, 9 samples displaying a synergistic, 3 an additive and 4 a less than additive inhibition of DNA biosynthesis when exposed to the combination of ADR and CPIB. The cytotoxic effect induced by ADR alone and in combination with CPIB was found to be irreversible. The data suggest that the cell membrane modulating drug CPIB is effective as an adjuvant to enhance the antiproliferative action of ADR.

Clofibrate↗
PubMed1990

Quantitative variations in A, B, Ht1 and Ht2 antigens on erythrocytes in leukemia and lymphoma.

Using an immunoradiometric assay, A, B, Ht1 and Ht2 antigens on erythrocyte membranes were quantitated in 192 leukemia and 23 lymphoma patients. A and B antigens were reduced in 37% and 50% of leukemia cases respectively. A wide range of antigenic reduction was observed for A antigen, while B antigenic reduction was generally 16-20%. Passive absorption of Ht1 antigen from plasma onto erythrocytes was greater in leukemic compared to normal subjects. Among patients with reduced A and B antigens, 27% had increased and 37% decreased Ht2 antigens. Incidence of reduction in antigens was significantly higher (p less than 0.001) in untreated compared to treated patients.

ABO Blood-Group System↗
PubMed1990

Bepridil enhances adriamycin-induced DNA biosynthesis inhibition in human myeloid leukemia cells.

The utilization of drug response modulators, based on their physico-chemical properties to augment the cytotoxic response of anticancer drugs is now gaining importance. We present in this communication, investigations performed to assess the antitumor activity of Adriamycin (ADR), on chronic myeloid leukemia (CML) cells, and the effect of bepridil, a calcium channel blocker on the ADR cytotoxicity. Inhibition of 3H-thymidine incorporation into DNA was used as an index of the cytotoxic effects of drugs when utilised alone or in combination. The combination of bepridil (1 and 5 micrograms/ml) and ADR (5 and 10 micrograms/ml) indicated a significant (P less than 0.001) enhancement in the DNA biosynthesis inhibition in CML cells, as compared to those samples exposed to ADR alone. The observed inhibition of DNA biosynthesis was found to be totally reversible, partially reversible and completely irreversible when the CML cells were exposed to bepridil alone, ADR alone and ADR plus bepridil, respectively. Bepridil was found to be highly lipid soluble at physiological pH, and this property could be responsible for the modulation of the ADR activity observed in this study. Results obtained, though preliminary due to the small sample size, clearly indicate a necessity for a detailed evaluation of bepridil effects, which would lead to higher therapeutic gains in anticancer chemotherapy in the clinic.

Bepridil↗
PubMed1990

Studies on natural killer cells in chronic myeloid leukemia patients in remission.

In our earlier studies, the natural killer (NK) cell mediated cytotoxicity was found to be impaired in 55% of chronic myeloid leukemia (CML) patients in remission (low NK responders), while the rest exhibited normal range of cytotoxicity (normal NK responders). In the present investigations probable factors contributing to the impaired NK activity of low NK responder CML patients have been analyzed. Peripheral blood lymphocytes (PBL) from both low and normal NK responder CML patients possessed normal percentages of HNK-1+, CD3+ and CD8+ cells. The proportion of HNK-1+ cells and CD8+ cells in low density fractions (LDF) and high density fractions (HDF) respectively of Percoll separated PBL from low and normal NK responder CML patients and healthy donors was comparable. However, the NK activity of LDF cells of low NK responder CML patients was much lower. Also, HDF cells from low NK responder CML patients exhibited a regulatory effect on NK cytotoxicity of PBL from healthy donors. Therefore, it is likely that the presence of suppressor cells and perhaps an intrinsic inability of HNK-1+ cells may together contribute to the impaired NK cytotoxicity of low NK responder CML patients.

Antigens, Differentiation↗
PubMed1989

Modulation of natural killer and antibody-dependent cellular cytotoxicity by interferon and interleukin-2 in chronic myeloid leukemia patients in remission.

Our earlier studies demonstrated that about 55% of chronic myeloid leukemia (CML) patients in remission exhibited impaired natural killer (NK) cytotoxicity (low NK responders) while antibody-dependent cellular cytotoxicity (ADCC) of these patients, on chicken red blood cells as targets, was within normal range. In this paper, we have attempted to modulate the NK cytotoxicity of CML patients in remission with interferon (IFN) and interleukin-2 (IL-2) singly or together. ADCC using K562 target-directed monoclonal antibody (MAb) 4.6E10 was also modulated by treating the effectors with IFN or IL-2. Pretreatment of nonadherent mononuclear cells from peripheral blood (NAPBMNC) with IFN or IL-2 was found to result in 20 and 21% increase in target cell lysis in case of healthy donors, 79 and 98% increase in case of CML normal NK responders, and 164 and 159% increase in case of CML low NK responders. Combined use of IFN and IL-2 potentiated further the lymphocytotoxicity to 25% in healthy donors, 135% in normal NK responder CML patients and 283% in low NK responder CML patients. This treatment resulted in restoration of cytotoxicity of the latter group of patients to a normal level. The augmentation was seen in 80-100% CML patients. Although ADCC with chicken red blood cells as targets was within normal range, ADCC mediated with MAb to K562 cells was significantly lower in CML low NK responders (24.5%) than CML normal NK responders (42.4%) and healthy donors (65.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

Non-Hodgkin's lymphoma: natural cell-mediated cytotoxicity correlated with histological classification and prognosis.

Non-Hodgkin's lymphoma (NHL) patients classified according to the Rappaport classification system had depressed natural killer (NK) and NK cytotoxic factor activities, antibody-dependent cellular cytotoxicity, active killing potential as well as recycling capacity. The suppression of these activities was not related to the favorable or unfavorable prognosis of the patients. Paramaters of the NK cytotoxic status of the NHL patients did not correlate with the histology or prognosis of the disease.

Antibody-Dependent Cell Cytotoxicity↗