cis-Diamminedichloroplatinum(II)-induced cell death through apoptosis in sensitive and resistant human ovarian carcinoma cell lines.

Abstract:

:We have studied the effects of the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-platin) on three human ovarian carcinoma cell lines - one sensitive to the drug (CH1), one with acquired resistance (CH1cisR) and one with intrinsic resistance (SKOV-3). Previous work has shown that the 50% inhibitory concentrations (IC50 values) after a 2-h exposure to the drug are: CH1, 2.5 microM; CH1cisR, 7.5 microM; and SKOV-3, 33 microM. Despite the variation in sensitivity, the amount of Pt bound to DNA and the rate of removal of Pt was similar for the three lines. There were significant differences in the rates of formation of DNA cross-links but these were not large enough to account for the high resistance of the SKOV-3 line. We have reported that in the L1210 murine leukaemia cell line there are two mechanisms of cisplatin-induced cell death - one of which involves apoptosis. In this paper, we report on an investigation into whether sensitivity to apoptosis played a role in the resistance of these ovarian lines toward cisplatin. After a 2-h incubation with the drug, cells from the three lines showed evidence of death through apoptosis. The cells detached from the culture dish in a time- and dose-dependent fashion. These cells morphologically were quite distinctive from the attached cells and showed changes in their chromatin structure indicative of apoptosis. Their DNA had not been degraded into oligonucleosomal fragments (200 bp and multiples thereof) but had been cut into larger fragments (30 kilobase pairs, kbp) of a size associated with chromatin domains (chromatin loops). At equitoxic doses of drug, the quantity of cells undergoing apoptosis was similar for the three cell lines. The most prominent effect on cell-cycle kinetics was a slowdown in S-phase transit during which the cells underwent apoptosis. Cells that successfully completed the S phase subsequently suffered a temporary G2 block. We propose that the sensitivity of these cell lines to cisplatin was governed by their ability to handle damage caused by platination of the DNA and that the major mechanism of cisplatin-induced cell death in all three cell lines was the induction of apoptosis.

authors

Ormerod MG,O'Neill C,Robertson D,Kelland LR,Harrap KR

doi

10.1007/s002800050413

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

463-71

issue

5

eissn

0344-5704

issn

1432-0843

journal_volume

37

pub_type

杂志文章
  • Adjuvant oral razoxane (ICRF-159) in resectable colorectal cancer.

    abstract::One hundred and seventy six patients (81 controls, 95 receiving treatment) have entered a prospective randomized trial of long-term oral adjuvant razoxane (ICRF-159) following removal of a colorectal cancer. The median follow-up is 34 months. The treated patients in Dukes' groups B and C have a significantly longer di...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00254053

    authors: Gilbert JM,Hellmann K,Evans M,Cassell PG,Stoodley B,Ellis H,Wastell C

    更新日期:1982-01-01 00:00:00

  • Dosing sequence-dependent pharmacokinetic interaction of oxaliplatin with paclitaxel in the rat.

    abstract:BACKGROUND:In a phase I clinical trial of oxaliplatin (OPT) in combination with paclitaxel (PXL), a pharmacokinetic interaction was observed when OPT was given as a 2-h i.v. infusion followed by a 1-h i.v. infusion of PXL. The purpose of this study was to use a rat model to evaluate whether the pharmacokinetic interact...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0531-6

    authors: Liu J,Kraut EH,Balcerzak S,Grever M,D'Ambrosio S,Chan KK

    更新日期:2002-12-01 00:00:00

  • Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration.

    abstract::The pharmacokinetics of hexamethylmelamine (HMM) and its first metabolite (hydroxymethylpentamethylmelamine: HMPMM) following IP bolus dose of 200 mg/kg were studied in mice. The drug concentrations were determined by a sensitive reversed-phase HPLC assay. Thus, for the first time, HMM major hydroxylated and demethyla...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00273391

    authors: Dubois J,Atassi G,Hanocq M,Abikhalil F

    更新日期:1986-01-01 00:00:00

  • Pharmacokinetics and safety of erlotinib and its metabolite OSI-420 in infants and children with primary brain tumors.

    abstract:PURPOSE:Erlotinib (Tarceva®), a potent small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, has been evaluated to treat infants and children with primary brain tumors. The pharmacokinetics of erlotinib and its primary metabolite OSI-420 were characterized and exposure-safety associations we...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/s00280-019-03921-3

    authors: Reddick SJ,Campagne O,Huang J,Onar-Thomas A,Broniscer A,Gajjar A,Stewart CF

    更新日期:2019-10-01 00:00:00

  • Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study.

    abstract:PURPOSE:Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. METHODS:We evaluated ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s00280-002-0443-5

    authors: Martell RE,Peterson BL,Cohen HJ,Petros WP,Rai KR,Morrison VA,Elias L,Shepherd L,Hines J,Larson RA,Schiffer CA,Hurwitz HI

    更新日期:2002-07-01 00:00:00

  • Prophylactic intravesical instillation therapy with adriamycin and mitomycin C in patients with superficial bladder cancer.

    abstract::Intravesical instillation of adriamycin (ADM) or mitomycin C (MMC) was carried out for the purpose of preventing the recurrence of superficial bladder cancers (Ta and T1) after transurethral resection or transurethral coagulation. First, eligible patients were divided into two groups (solitary and multiple) and then t...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00262491

    authors: Tsushima T,Matsumura Y,Ozaki Y,Yoshimoto J,Ohmori H

    更新日期:1987-01-01 00:00:00

  • A phase I trial of amsalog (CI-921) administered by intravenous infusion using a 5-day schedule.

    abstract:PURPOSE:Amsalog, a derivative of 9-aminoacridine, is an inhibitor of topoisomerase II. Early studies of intravenous amsalog administered either once weekly, or daily for 3 days repeated every 3 weeks, showed that myelosuppression is the dose-limiting toxicity (DLT). Phase II studies showed only limited activity in brea...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s002800000216

    authors: Fyfe D,Price C,Langley RE,Pagonis C,Houghton J,Osborne L,Woll PJ,Gardner C,Baguley BC,Carmichael J,Cancer Research Campaing Phase I\/II Trials Committee.

    更新日期:2001-04-01 00:00:00

  • In vitro succinate dehydrogenase chemosensitivity of gastric carcinoma--relationship to DNA content.

    abstract::Relationships between in vitro chemosensitivity and cell nuclear DNA content were investigated in malignant cells from 41 patients exhibiting advanced gastric carcinoma. The chemosensitivity was evaluated by measuring the succinate dehydrogenase (SD) activity in drug-exposed cancer cells and the DNA content was micros...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686250

    authors: Saito A,Korenaga D,Maehara Y,Baba H,Okamura T,Sugimachi K

    更新日期:1992-01-01 00:00:00

  • Therapeutic evaluation of five nitrosoureas in a human melanoma xenograft system.

    abstract::The development of nitrosoureas has switched from more lipophilic derivatives to congeners with higher water-solubility, since this property was presumably associated with a decrease in myelosuppression. We have compared the therapeutic efficacy of clinically well-known lipophilic nitrosoureas BCNU, CCNU, and MeCCNU w...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00254194

    authors: Osieka R,Glatte P,Pannenbäcker R,Schmidt CG

    更新日期:1983-01-01 00:00:00

  • Protein expression profiling identifies differential modulation of homologous recombination by platinum-based antitumor agents.

    abstract:PURPOSE:Oxaliplatin and satraplatin demonstrate activity against cisplatin-resistant tumor cells. Although the two platinum analogs are structurally-related, oxaliplatin is more active. Therefore, studies focusing on protein expression profiling were undertaken to identify the molecular mechanism for the difference in ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-020-04085-1

    authors: He G,Xie X,Siddik ZH

    更新日期:2020-06-01 00:00:00

  • Prophylactic intravesical instillation chemotherapy against recurrence after a transurethral resection of superficial bladder cancer: a randomized controlled trial of doxorubicin plus verapamil versus doxorubicin alone. The Kyushu University Urological On

    abstract:PURPOSE:We investigated whether verapamil (VR), a known chemosensitizing agent of P-glycoprotein-mediated multidrug resistance, could enhance the preventative effect of doxorubicin (Adriamycin, ADM) on both intravesical recurrence and disease progression after transurethral resection (TUR) of superficial bladder cancer...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s002800050831

    authors: Naito S,Kotoh S,Omoto T,Osada Y,Sagiyama K,Iguchi A,Ariyoshi A,Hiratsuka Y,Kumazawa J

    更新日期:1998-01-01 00:00:00

  • A comparison of the quality of informed consent for phase I oncology trials over a 30-year period.

    abstract:PURPOSE:Efforts are underway in improving the informed consent process. The success of these efforts to improve quality of informed consent forms (ICFs) for phase I oncology trials has not been previously measured. METHODS:We reviewed and compared ICFs of all phase I trials for metastatic cancer conducted between 1986...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-018-3673-x

    authors: Malik L,Cooper J

    更新日期:2018-11-01 00:00:00

  • CDDO-Me, a synthetic triterpenoid, inhibits expression of IL-6 and Stat3 phosphorylation in multi-drug resistant ovarian cancer cells.

    abstract::Previous studies have identified interleukin 6 (IL-6) as an important cytokine with prognostic significance in ovarian cancer. Activation of the IL-6-Stat3 pathway contributes to tumor cell growth, survival and drug resistance in several cancers, including ovarian cancer. To explore potential therapeutic strategies fo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0785-8

    authors: Duan Z,Ames RY,Ryan M,Hornicek FJ,Mankin H,Seiden MV

    更新日期:2009-03-01 00:00:00

  • Platinum drug effects on the expression of genes in the polyamine pathway: time-course and concentration-effect analysis based on Affymetrix gene expression profiling of A2780 ovarian carcinoma cells.

    abstract:PURPOSE:As a follow-up to our previous findings that platinum drugs induce a key enzyme in polyamine catabolism, gene expression profiling and mathematical modeling were used to define the effects of cisplatin and oxaliplatin on the expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma cells....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0325-3

    authors: Varma R,Hector S,Greco WR,Clark K,Hawthorn L,Porter C,Pendyala L

    更新日期:2007-05-01 00:00:00

  • Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid.

    abstract::DDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in mye...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00254043

    authors: Alberto P,Peytremann R,Medenica R,Beretta-Piccoli M

    更新日期:1978-01-01 00:00:00

  • Chemotherapy for the carcinoid syndrome.

    abstract::Patients with carcinoid syndrome usually die from carcinomatosis, rather than the pharmacological effects of the tumour. Functioning carcinoid tumours are resistant to radiotherapy. Twenty-four different cytotoxic drugs or combinations have been used to treat the carcinoid syndrome, but only actinomycin D, cyclophosph...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00258469

    authors: Harris AL

    更新日期:1981-01-01 00:00:00

  • Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101.

    abstract:PURPOSE:To determine the maximum tolerated dose and the toxicity profile of the PDGF receptor pathway inhibitor SU101 in pediatric patients with refractory solid tumors, and to define the plasma pharmacokinetics of SU101 and its active metabolite SU0020 in children. EXPERIMENTAL DESIGN:Patients between 3 and 21 years ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-004-0769-2

    authors: Adamson PC,Blaney SM,Widemann BC,Kitchen B,Murphy RF,Hannah AL,Cropp GF,Patel M,Gillespie AF,Whitcomb PG,Balis FM

    更新日期:2004-06-01 00:00:00

  • Phase II study of adriamycin with sequential methotrexate and 5-fluorouracil (AMF) in gastric carcinoma.

    abstract::The purpose of this study was to evaluate the response rate, methotrexate plasma levels, and toxicity of a three-drug regimen in patients with gastric carcinoma. A total of 37 patients with advanced measurable adenocarcinoma of the stomach were treated with Adriamycin, methotrexate, and 5-fluorouracil (AMF). Adriamyci...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00254103

    authors: Ajani JA,Goudeau P,Levin B,Faintuch JS,Abbruzzese JL,Boman BM,Kanojia MD

    更新日期:1989-01-01 00:00:00

  • Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study.

    abstract::A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02897298

    authors: Whitehead VM,Bernstein ML,Vega R,Vats T,Dyment P,Vietti TJ,Krischer J

    更新日期:1990-01-01 00:00:00

  • Lack of effect of cisplatin on i.v. L-PAM plasma pharmacokinetics in ovarian cancer patients.

    abstract::Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t 1/2 beta), plasma clearance (Clp), and volume of distribution (Vd beta) of L-PAM were, respectively: 46.4 +/- 6.7 min, 20.5...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00254189

    authors: Zucchetti M,D'Incalci M,Willems Y,Cavalli F,Sessa C

    更新日期:1988-01-01 00:00:00

  • A comparative study of bisantrene given by two dose schedules in patients with metastatic breast cancer.

    abstract::Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m2 (37 patients) or an injection of 80 mg/m2 daily for 5 days (D x 5) (35 patients) every 3-4 weeks after stratification by performance status...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00262287

    authors: Holmes FA,Esparza L,Yap HY,Buzdar AU,Blumenschein GR,Hortobagyi GN

    更新日期:1986-01-01 00:00:00

  • Folinic acid, 5-fluorouracil and mitomycin C in metastatic breast cancer patients previously treated with at least two chemotherapy regimens.

    abstract:PURPOSE:To assess the activity and safety of combined folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC) in metastatic breast cancer patients previously treated with at least two chemotherapy regimens. PATIENTS AND METHODS:A total of 104 consecutive patients were enrolled for treatment with FA 100 mg/m(2) ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-002-0495-6

    authors: Francini G,Petrioli R,Messinese S,Pozzessere D,Marsili S,Correale P,Sabatino M,Fiaschi AI

    更新日期:2002-10-01 00:00:00

  • Phase I study of anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers.

    abstract:PURPOSE:Anti-angiogenic agents combined with histone deacetylase inhibitors act synergistically in vitro and in vivo. We conducted a phase I study of the combination of the anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers. METHODS:Bevacizumab w...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-014-2384-1

    authors: Wheler JJ,Janku F,Falchook GS,Jackson TL,Fu S,Naing A,Tsimberidou AM,Moulder SL,Hong DS,Yang H,Piha-Paul SA,Atkins JT,Garcia-Manero G,Kurzrock R

    更新日期:2014-03-01 00:00:00

  • Cisplatin efflux, binding and intracellular pH in the HTB56 human lung adenocarcinoma cell line and the E-8/0.7 cisplatin-resistant variant.

    abstract:PURPOSE:Many cell lines resistant to cisplatin (DDP) have reduced DDP accumulation. We postulated that reduced accumulation of DDP in resistant cells might be due to decreased intracellular DDP binding, leading to increased passive efflux. METHODS:The total cellular ([T-DDP]), intracellular ultrafiltrable ([F-DDP]) an...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050967

    authors: Chau Q,Stewart DJ

    更新日期:1999-01-01 00:00:00

  • Carboplatin-based combination chemotherapy for advanced carcinoma of the cervix.

    abstract::A combination of carboplatin, vincristine, methotrexate and bleomycin (COMB) was given to 29 patients with locally advanced, metastatic or recurrent cervical carcinoma. A total of 85 cycles of chemotherapy were given, with half of the patients receiving greater than 3 cycles. Both the response rate (32.1%) and the med...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685165

    authors: Junor E,Davies J,Habeshaw T,Kaye S,Paul J,Rankin E,Reed N,Symonds RP

    更新日期:1991-01-01 00:00:00

  • Antitumor activity and cytotoxicity of a new ankinomycin derivative, 3'-,11-dibutyryl ankinomycin.

    abstract::Ankinomycin is a new antitumor antibiotic found in the culture broth of Streptomyces sp. SF2587. Ankinomycin showed marked cytotoxicity and antitumor activity against some murine leukemias, but the activity against murine solid tumors was rather weak because of its strong acute toxicity. We synthesized ankinomycin acy...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685831

    authors: Ishii S,Satoh Y,Tsuruo T

    更新日期:1993-01-01 00:00:00

  • UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer.

    abstract:PURPOSE:Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients. METHODS:Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1485-8

    authors: Sunakawa Y,Ichikawa W,Fujita K,Nagashima F,Ishida H,Yamashita K,Mizuno K,Miwa K,Kawara K,Akiyama Y,Araki K,Yamamoto W,Miya T,Narabayashi M,Ando Y,Hirose T,Saji S,Sasaki Y

    更新日期:2011-08-01 00:00:00

  • Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine.

    abstract::Mercaptopurine (6MP) has been the standard drug for maintenance therapy of acute lymphoblastic leukemia. In a multicenter study we investigated whether thioguanine (6TG), which is converted more directly to the cytotoxic thioguanine nucleotides (TGN), offers a therapeutic advantage over 6MP. In this study (COALL-92), ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1007/s002800050816

    authors: Erb N,Harms DO,Janka-Schaub G

    更新日期:1998-01-01 00:00:00

  • Pharmacokinetics of lenalidomide during high cut-off dialysis in a patient with multiple myeloma and renal failure.

    abstract:INTRODUCTION:High cut-off dialysis, increasingly used in multiple myeloma patients, is susceptible to influence anticancer drug elimination. We report about lenalidomide disposition in a patient on high cut-off dialysis for renal failure secondary to myeloma cast nephropathy. METHODS:The patient received a higher dosa...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-3219-z

    authors: Dao K,Lu Y,Peer CJ,Figg WD,Stadelmann R,Burnier M,Buclin T,Kissling S

    更新日期:2017-01-01 00:00:00

  • Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies.

    abstract:PURPOSE:Imatinib is an inhibitor of the Bcr-Abl tyrosine kinase; however, resistance is common. Flavopiridol, a cyclin-dependent kinase (CDK) inhibitor, down-regulates short-lived anti-apoptotic proteins via inhibition of transcription. In preclinical studies, flavopiridol synergizes with imatinib to induce apoptosis. ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-012-1839-5

    authors: Bose P,Perkins EB,Honeycut C,Wellons MD,Stefan T,Jacobberger JW,Kontopodis E,Beumer JH,Egorin MJ,Imamura CK,Douglas Figg W Sr,Karp JE,Koc ON,Cooper BW,Luger SM,Colevas AD,Roberts JD,Grant S

    更新日期:2012-06-01 00:00:00