Abdul R. Khokhar

Holy Family Hospital

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Zahid H. Siddik

The University of Texas MD Anderson Cancer Center

Román Pérez-Soler

Montefiore Medical Center

Salaam Al-Baker

The University of Texas at Austin

Kenton H. Whitmire

Rice University

Miles P. Hacker

University of Toledo

Gregg J. Lumetta

Pacific Northwest National Laboratory

S. Shamsuddin

The University of Texas MD Anderson Cancer Center

Sheryl L. Doran

Anderson Hospital

Quanyun Xu

Scripps MD Anderson Cancer Center

Mohammad S. Ali

Roger Williams Medical Center

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

101

The University of Texas Health Science Center at Houston

Anderson Hospital

The University of Texas at Austin

University of Houston

Baylor College of Medicine

The University of Texas System

Rice University

University College London

University of Florida

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Thin layer chromatography of N-thiobenzoylamino acid anilides

Journal of Chromatography A (1969)

G. C. Barrett Abdul R. Khokhar

Residue (chemistry)

Amino Acid Analysis

Thin layers

10.1016/s0021-9673(01)97974-9

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Citations (17)

Abstract 2507: Defective Chk2 expression in cisplatin-resistant ovarian tumor cells impedes wild-type p53 function

Cancer Research (2010)

Ismail M. Meraz Abdul R. Khokhar Zahid H. Siddik

Abstract The p53 tumor suppressor in its wild-type state correlates with sensitivity of tumor cells to cisplatin, and mutant p53 with resistance. However, resistance is also a significant impediment in tumors harboring wild-type p53. Identifying the mechanism preventing wild-type p53 from inducing cell death becomes vital in understanding resistance. Our studies in an isogenic sensitive-resistant pair of wild-type p53 ovarian tumor models demonstrate that unlike sensitive A2780 cells, the ∼25-fold resistant 2780CP variant cells do not upregulate p21 at 24 hr in response to cisplatin (1 or 5 µM). Since defects in wild-type p53 and chk2 are reported to be mutually exclusive and Chk2 defects are known to impact p53 function, we investigated chk2 expression in the model pair. By immunoblot analysis, A2780 cells robustly expressed Chk2, whereas levels were undetectable in resistant cells. Real-time PCR demonstrated an absence of Chk2 transcripts in resistant cells, and since chronic exposure to decitabine (1 or 5 µM for 5, 7 or 9 days) failed to upregulate Chk2, this suggested that loss of Chk2 expression in 2780CP cells is likely due to a non-epigenetic mechanism. In order to test whether loss of Chk2 indeed contributes to loss of p53 function and also loss of sensitivity to cisplatin, A2780 cells were exposed to Chk2 siRNA (100 nM for 5 hr), which reduced Chk2 levels by >75%. Exposure of siRNA-treated cells to cisplatin (1.0 µM) followed by immunoblot analysis 24 hr later demonstrated an attenuated p21 expression. Similarly, cytotoxic assessment by the MTT assay provided evidence that Chk2-knockdown in A2780 cells increased resistance to cisplatin by about 2-fold. Since the level of cisplatin resistance in 2780CP cells and other similar models is much greater than those seen in resistant cells harboring mutant- or null-p53, we tested the concept that p53 knockdown by siRNA in Chk2-deficient 2780CP cells may actually sensitize these cells. Support for this was provided by a 2-fold decrease in the IC50 of cisplatin. In contrast, the IC50 of cisplatin increased by about 2-fold in p53-knockdown A2780 cells. If Chk2-deficiency contributes to cisplatin resistance in tumor cells harboring wild-type p53, then specific non-cross-resistant platinum analogs must be activating p53 and inducing cell killing in a Chk2-independent manner. This was confirmed by the demonstration that the platinum(IV) analog DAP increased levels of p21 in Chk2-knockdown A2780 cells without loss of cytotoxic potency, and that knockdown of p53 in either sensitive or resistant cells increased resistance to the analog by about 2- to 3-fold. These results demonstrate the relative significance of Chk2 in the mode of action of cisplatin and the analog DAP. (Supported by NCI RO1 CA127263). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2507.

Wild type

10.1158/1538-7445.am10-2507

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Effects on the Monocyte-Macrophage System and Antitumor Activity Against L1210 Leukemia of <italic>cis-bis</italic>-Cyclopentenecarboxylato-<italic>trans-R,R</italic>-1,2-Diaminocyclohexane-Platinum (II) Encapsulated in Multilamellar Vesicles<xref ref-type="fn" rid="FN2">2</xref>

JNCI Journal of the National Cancer Institute (1986)

R Perez-Soler Abdul R. Khokhar PJ Claringbold Leela P. Kasi Gabriel Lopez‐Berestein

Multilamellar vesicles (MLVs) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a molar ratio of 7:3 were used as carriers of cis-bis-cyclopentenecarboxylato-trans-R,R-1,2-diaminocyclohexane-p latinum (II) (CPDP). The encapsulation efficiency of liposomal CPDP (L-CPDP) was 87.6%, and its stability in normal saline at 14 days was 94.4%. The in vitro and in vivo effects on the function of the monocyte-macrophage system and the antitumor activity against L1210 leukemia were investigated in CD-1 and (C57BL/6J X DBA/2J)F1 mice. L-CPDP and cisplatin (CDDP) caused a comparable inhibition of murine-resident peritoneal macrophage (PM) protein and RNA synthesis and superoxide anion release. PM-mediated tumor cell cytotoxicity was completely inhibited at a concentration of 10 micrograms CDDP and L-CPDP/ml but not at concentrations of 1 and 5 micrograms/ml. The differences in plasma clearance of 99mTc-labeled MLV and phagocytic capacity of the liver among animals pretreated with the maximum tolerated doses of L-CPDP (25 mg/kg), empty liposomes, or CDDP (10 mg/kg) were not statistically significant (plasma clearance % of control: 105, 110, and 100, respectively: P greater than .05; liver uptake % of control: 87, 96, and 104, respectively: P greater than .05). At the maximum tolerated doses, the antitumor activity of L-CPDP against L1210 leukemia was similar to that of CDDP when a single dose was administered [median survival of treated mice/median survival of control mice X 100 (%T/C): 181 vs. 175] and slightly higher with the use of a triple-dose schedule (%T/C: 275 vs. 225). L-CPDP is easy to prepare, has a high-encapsulation efficiency and stability, is not more toxic than CDDP to the monocyte-macrophage system, and is at least as effective as CDDP against L1210 leukemia.

Monocyte

10.1093/jnci/77.5.1137

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Chemical and Biological Studies on a Series of Novel (trans-(1R,2R)-, trans-(1S,2S)-, and cis-1,2-Diaminocyclohexane)platinum(IV) Carboxylate Complexes

Journal of Medicinal Chemistry (1997)

Abdul R. Khokhar Salam Al-Baker S. Shamsuddin Zahid H. Siddik

A series of novel platinum(IV) complexes of the type DACH-PtIV-trans-(Y)2-cis-X (where DACH = trans-(1R,2R)-, trans-(1S,2S)-, or cis-1,2-diaminocyclohexane; X = diacetate, oxalate, malonate, methylmalonate, cyclobutanecarboxylate (CBCA), or 1,1-cyclobutanedicarboxylate (CBDCA); and Y = acetate or trifluoroacetate) has been synthesized and characterized by elemental analysis, IR, and 195Pt-NMR spectroscopy. The compounds have been tested against cisplatin-sensitive L1210/0 leukemia, cisplatin-resistant L1210/DDP leukemia, and M5076 reticulosarcoma cell lines in vivo. Most of these analogs displayed reasonable activity against L1210/0 cells (%T/C = 135 to >700). There were no gross differences in activity between analogs containing isomers of DACH. Selected compounds were evaluated against L1210/DDP tumor models in which they demonstrated reduced but significant activity compared with activity in the L1210/0 model. Interestingly, complex 20, PtIV(trans-1R,2R-DACH)-trans-(acetate)2methylmalonate, was highly active against M5076, although it had no activity against the L1210 lines. The results demonstrate that specific combinations of axial and equatorial carboxylate ligands, together with the DACH carrier ligand, can favorably modulate the antitumor properties of platinum complexes and enhance circumvention of cisplatin resistance.

Malonate

Carboxylate

L1210 cells

10.1021/jm960587l

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Seasonal variation in trachoma prevalence among children, District Dera Ghazi Khan of Punjab, Pakistan

Journal of the Pakistan Medical Association (2020)

Abdul R. Khokhar Tehseen Iqbal Mujahid Hussain Qurrat-ul Ain Rehman

The study objective was to estimate trachoma prevalence in relation to seasonal variation among children.Study Design was cross sectional and data was collected during all seasons of the year. After randomization of population units, 10% of them were identified by lottery and 5% of them were selected and examined for active trachoma case detection by simple random sampling technique. Total number of study participants were nine thousand seven hundred and ten (n=9710) from both urban and rural population units. The study was conducted during January -December 2018 during all three seasons of the year. After clinical examination, data was entered into a questionnaire Performa, which was used as tool for data collection. A Chi-square test was applied to compare trachoma cases among different seasons and among both boys and girls.Maximum burden of disease (62.4%) was reported during spring and winter season. Both spring and winter seasons have six months duration. During summer season, 70(37.6%) cases were reported. A highly significant (<0.01) relationship was reported between summer and spring seasons and trachoma prevalence (p < 0.01). A high prevalence was noted among female children.Higher prevalence of active trachoma was noted during summer season.

10.47391/jpma.874

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TASTE BLINDNESS AMONG MEDICAL STUDENTS

Abdul R. Khokhar Tehseen Iqbal Naveed Atif Yousafi Malik Shah Zaman Latif

Introduction: Modern research has reported variations in taste that results in food and beverageÂÂÂÂ consumption. This is true that 15â€“25% of population is born with taste blindness to phenylthiocarbamide (PTC). This study aimed to see frequency of taste-blindness among the medical students of DG Khan Medical College, Pakistan. Methods: A cross-sectional study was conducted in which simple random sampling technique was applied. Medical students of DG Khan Medical College participated. Out of 381 students, 151 consented (78 female, 73 male) were evaluated for taste blindness. Age range was 17â€“23 years. A drop of 0.5% PTC solution was placed on the tongue and participants were asked to state the taste perceived. Results: Among males 13.70% and 14.10% females were taste blind to PTC respectively. On regional basis, 13.50% students of upper Punjab and 11.96% students of South Punjab were non-taster to PTC. Conclusion: So, 12.58% population of Punjab is taste blind. Pak J Physiol 2014;10(3-4):10â€“1

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Preparation, characterization, and antitumor activity of new cisplatin analogues with 1-methyl-4-(methylamino)piperidine: Crystal structure of [PtII(1-methyl-4-(methylamino) piperidine)(oxalate)]

Journal of Inorganic Biochemistry (2003)

Uday Mukhopadhyay J.H. Thurston Kenton H. Whitmire Zahid H. Siddik Abdul R. Khokhar

Piperidine

Monoclinic crystal system

Cyclohexane conformation

10.1016/s0162-0134(02)00614-1

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Citations (15)

Synthesis and Characterization of A Series of Platinum(II) and Palladium(II) Complexes Containing the Bidentate Ligandmeso-1,2-Diphenylethylenediamine ORmeso-1,2-Bis(4-Chlorophenyl) Ethylenediamine

Journal of Coordination Chemistry (1989)

Abdul R. Khokhar Gregg J. Lumetta

Abstract The bidentate ligands meso-1,2-diphenylethylenediamine (stein) and meso-1,2-bis(4-chlorophenyl) ethylenediamine (4-Cl-st) have been prepared and spectroscopically characterized. Complexes of the type [MX2(N N)] (where M α Pd or Pt; X α Cl or X2 α oxalate or 1,1-cyclobutanedicarboxylate; N N α stein or 4-Cl-st) have been synthesized. These complexes have been characterized by infrared and NMR spectroscopic techniques.

Ethylene diamine

10.1080/00958978909408835

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Citations (8)

Synthesis, characterization and antitumor activity of a series of N-substituted iminodiacetato(diammine) platinum(II) complexes

Inorganica Chimica Acta (1988)

Abdul R. Khokhar Gregg J. Lumetta Roberta A. Newman Sheryl L. Doran

10.1016/s0020-1693(00)90807-7

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Citations (11)

SYNTHESIS AND CHARACTERIZATION OF NEW ANTITUMORTRANS-R,R-, TRANS-S,S- ANDCIS-1,2-DIAMINOCYCLOHEXANE PLATINUM (IV) COMPLEXES

Journal of Coordination Chemistry (1994)

Salaam Al-Baker Zahid H. Siddik Abdul R. Khokhar

Abstract A series of isomeric 1, 2-diaminocyclohexane platinum (IV) complexes of the type DACH-PtIV-trans(X)2 cis(Y) (where DACH = trans-R,R-, trans-S,S- or cis-1,2-diaminocyclohexane, X = chloro, bromo, acetato, or trifluoroacetato, and Y = dichloro, dibromo, 1,1-cyclobutanedicarboxylato, tartronato, ketomalonato, or methylmalonato) has been synthesized. The isomeric DACH-PtIV-trans(X)2 cis(Y) complexes were prepared by first oxidizing the corresponding DACH-dihaloplatinum(II) or DACH-dicarboxylato-platinum(II) [DACH-PtIIY] with hydrogen peroxide to DACH-PtIV-trans(OH)2Y, and then replacing the axial hydroxo groups with chloro, bromo, or monocarboxylato ligands. These complexes were characterized by elemental analysis, and infrared and nuclear magnetic resonance (195Pt{1H}) spectroscopic techniques. Key Words: Platinum1,2-diaminocyclohexaneisomercarboxylatesynthesis

Oxidizing agent

Cis–trans isomerism

10.1080/00958979408024206

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Citations (21)