Daniel Henriques de Menezes - Academia.edu (original) (raw)

Papers by Daniel Henriques de Menezes

Revista Eclesiástica Brasileira, 2019

Bagoas Estudos Gays Generos E Sexualidades, Nov 26, 2012

Journal of Experimental Therapeutics and Oncology, 2003

We studied the possibility of increasing sensitization of drug-resistant MDA435/LCC6 multidrug-re... more We studied the possibility of increasing sensitization of drug-resistant MDA435/LCC6 multidrug-resistant (MDR) human breast cancer cells to doxorubicin (DOX) by increasing cellular drug retention with P-glycoprotein (P-gp) inhibitor PSC833 in combination with induction of cell death through down-regulation of Bcl-2 protein using Bcl-2 antisense (G3139). In in vitro cytotoxicity assays, the combination of G3139 with DOX exhibited 40% increased cytotoxicity in both wild-type (WT) and MDR cells. PSC833 increased the cytotoxicity of DOX and Taxol with complete and partial reversal of the resistance of MDR cells to DOX and Taxol, respectively. The presence of G3139 did not increase the cytotoxicity of PSC833 combined with DOX or Taxol in both cell lines. In vivo studies with WT and MDR cell lines transplanted into severely combined immunodeficientmicedemonstrated that G3139(5 mg/kg) was able to suppress the growth of both WT and MDR tumors to an equivalent extent. PSC833 (100 mg/kg) partially restored the sensitivity of resistant tumors to DOX, and the combination of G3139 and PSC833 with liposomal DOX showed maximum growth suppression of MDR tumors compared with individual treatments. The improved efficacy of this treatment was attributed to Bcl-2 antisense-induced apoptosis, combined with cellular retention of DOX in tumor cells via P-gp blockade.

$Research paper thumbnail of A phase I dose-finding study of combined treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer$

Clinical cancer research : an official journal of the American Association for Cancer Research, 2001

Bcl-2 is a negative prognostic indicator in prostate cancer, implicated in the development of and... more Bcl-2 is a negative prognostic indicator in prostate cancer, implicated in the development of androgen independence and treatment resistance, and is overexpressed in hormone-refractory prostate cancer (HRPC). Genasense is a phosphorothioate antisense oligonucleotide complementary to the bcl-2 mRNA open reading frame that in preclinical studies has shown significant activity in inhibiting expression of Bcl-2, delaying androgen independence, and improving chemosensitivity in prostate and other cancer models. In this dose escalation study, we evaluated the combination of Genasense and mitoxantrone, a standard chemotherapy for patients with HRPC. Twenty-six patients with HRPC were treated at seven dose levels receiving Genasense at a dose ranging from 0.6 to 5.0 mg/kg/day and mitoxantrone from 4 mg/m(2) to 12 mg/m(2). Genasense was administered as a 14-day i.v. continuous infusion every 28 days with mitoxantrone given as an i.v. bolus on day 8. No dose-limiting toxicities were observed....

Clinical cancer research : an official journal of the American Association for Cancer Research, 2000

Bcl-2 is a key apoptosis-regulating protein that has been implicated in mechanisms of chemoresist... more Bcl-2 is a key apoptosis-regulating protein that has been implicated in mechanisms of chemoresistance for a variety of malignancies by blocking programmed cell death. This study investigated the activity of the Bcl-2 antisense oligodeoxynucleotide (AS ODN) G3139 combined with free doxorubicin (F-DOX) or sterically stabilized liposomal doxorubicin (SL-DOX) to determine the role that drug pharmacodistribution properties may have on antitumor activity using a Bcl-2-expressing human breast solid tumor xenograft model. Administration of G3139 was able to delay the growth of MDA435/LCC6 cells compared with control ODN-treated animals; however, in all of the cases, tumors reestablished after AS ODN treatment. Western blot analyses of Bcl-2 levels of solid tumors showed a sequence-specific down-regulation of the Bcl-2 protein after four daily doses of G3139, which correlated with histological evidence of tumor cell death. Interestingly, the expression of Bcl-2 returned to pretreatment level...

Targeting of Drugs 6, 1998

... 1992; Zu et al. 1993; Forssen et al. 1996; Unezaki et al. 1996). ... 1985; Courtenay-Luck et ... more ... 1992; Zu et al. 1993; Forssen et al. 1996; Unezaki et al. 1996). ... 1985; Courtenay-Luck et al. 1986; Phillips and Dahman 1995). The use of humanized or chimerized antibodies or antibody fragments may reduce this immunogenicity (Harding et al. 1997). ...

Revista Brasileira de Coloproctologia, 2007

Ainda não esta comprovada a eficácia dos derivados morfínicos ao nível de receptores opióides per... more Ainda não esta comprovada a eficácia dos derivados morfínicos ao nível de receptores opióides periféricos. Estudos procuram demonstrar o poder da droga em interferir na intensidade da dor quando infiltrada em nervos periféricos. Avaliamos, então, a infiltração local de morfina associada à anestesia local em cirurgias orificiais proctológicas. Nesse estudo foram analisados 61 pacientes, independentemente do gênero, sendo divididos aleatoriamente em dois grupos: a um grupo foi associada morfina ao anestésico local enquanto ao outro houve a administração do anestésico local sem a droga morfínica. Os pacientes de ambos os grupos foram submetidos à sedação e analgesia pós-operatória padronizadas. Foram avaliados: a intensidade da dor, a analgesia pós-operatória e a morbidade. A intensidade da dor, no momento de seu surgimento, foi semelhante nos dois grupos; o tempo de analgesia pós-operatória foi maior no grupo em que a morfina foi administrada, entretanto, não se mostrou estatisticamen...

Journal of Liposome Research, 1999

Page 1. JOURNAL OF LIPOSOME RESEARCH, 9(2), 199-228 (1999) CELLULAR TRAFFICKING AND CYTOTOXICITY ... more Page 1. JOURNAL OF LIPOSOME RESEARCH, 9(2), 199-228 (1999) CELLULAR TRAFFICKING AND CYTOTOXICITY DOXORUBICIN IN B LYMPHOMA CELLS? OF ANTI-CD19-TARGETED LIPOSOMAL Daniel E. Lopes de ...

Journal of Controlled Release, 1996

In the last few years a number of advances took place in development of methodologies for prepara... more In the last few years a number of advances took place in development of methodologies for preparation of polyethylene glycol (PEG)-grafted immunoliposomes. Several new end-group functionalized PEG lipids were introduced for this purpose. These include pyridyldithiopropionate-PEG-and hydrazide-PEG-PE derivatives, which incorporate well into liposomes and are used for covalent attachment of antibodies to extremities of the liposome-grafted polymeric chains. Methods previously known for linking antibodies to classical liposomes are in some cases applicable to preparation of PEG-grafted immunoliposomes. In these methods antibodies are fixed directly to the lipid bilayer through reactive residues on the polar headgroups of lipids. Attributes of the new methods and their comparison to the traditional methods for preparation of immunoliposomes are the main focus of this manuscript. Particular attention is paid to reactivities, potential and observed complications as well as to the relationship between the conjugation chemistry and biological activity. It is clear that having numerous possible pathways for generating long-circulating immunoliposomes is of great value, since some antibodies tend to be sensitive to different chemical conditions. The current state of the field should facilitate rapid accumulation of in vivo results, which are critical for determination of the true value of this technology.

Clinical Orthopaedics and Related Research, 2005

We reviewed 155 consecutive patients who were treated with a proximal femoral nail from 1997 to 2... more We reviewed 155 consecutive patients who were treated with a proximal femoral nail from 1997 to 2001 to determine the rate of implant specific complications. Results were stratified according to fracture type and surgeon experience to determine which problems occurred in these groups. One year postoperative followup was available for 129 of 132 surviving patients (98%). Failure of fixation occurred in three patients (2%), and a femoral shaft fracture occurred in one patient (0.7%). Fixation failures included one cutout, one delayed fracture healing, and one lateral displacement of the antirotation screw. The total reoperation rate was high (12%) mainly because of hardware removals, which occurred in 13 patients (8.6%). Stratification of results showed that hematomas and iliotibial tract irritation occurred more commonly with lesser surgical experience. General complications and intraoperative problems were seen more often with subtrochanteric fractures. Because the high reoperation rate with the proximal femoral nail is a concern, extramedullary devices continue to be the preferred implants for treatment of stable trochanteric fractures. The low rates of femoral shaft fractures and failure of fixation suggest the proximal femoral nail is useful for treatment of unstable trochanteric and subtrochanteric fractures. Level of Evidence: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Clinical Orthopaedics & Related Research, 2011

Background The transfemoral approach is an extensile surgical approach that is performed routinel... more Background The transfemoral approach is an extensile surgical approach that is performed routinely to facilitate cement and implant removal and improve exposure for revision stem implantation. Previous studies have looked at clinical results of small patient groups. The factors associated with fixation failure of cementless revision stems when using this approach have not been examined. Questions/purposes We determined (1) the clinical results and (2) complications of the transfemoral approach and (3) factors associated with fixation failure of revision stems when using the transfemoral approach. Patients and Methods We retrospectively examined all our patients in whom femoral stem revision was performed through a transfemoral approach between December 1998 and April 2004 and for whom a minimal followup of 2 years was available. One hundred patients were available for this study. The mean (± SD) postoperative followup was 5 years (± 1.64 years). Results The average Harris hip score improved from 45.2 (± 14.02) preoperatively to 83.4 (± 11.86) at final followup. Complete radiographic bony consolidation of the osteotomy site was observed in 95% of patients. Dislocations occurred in 9% of patients. Four revision stem fixation failures were observed, all occurring in patients with primary three-point fixation. Three-point fixation was associated with short osteotomy flaps and long revision stems. Conclusions The transfemoral approach is associated with a high rate of osteotomy flap bony healing and good clinical results. When using the transfemoral approach, a long osteotomy flap should be performed and the shortest possible revision stem should be implanted. Level of Evidence Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. This work was performed at Polyclinique Sévigné.

Cancer Chemotherapy and Pharmacology, 2002

To evaluate the pharmacokinetic (PK) properties of Bcl-2 antisense oligodeoxynucleotide G3139 whe... more To evaluate the pharmacokinetic (PK) properties of Bcl-2 antisense oligodeoxynucleotide G3139 when combined with the anthracycline anticancer drug doxorubicin (DOX) in a model of MDA435/LCC6 human breast cancer in severely compromised immunodeficient (SCID) mice. An orthotopic model of MDA435/LCC6 solid breast tumors was developed by bilateral implantation of passaged cells in female SCID-RAG2 mice. The G3139 plasma profile was compared for two common routes of administration (i.v. or i.p.) in single and multiple dose treatment regimens of 5 mg/kg G3139 alone or with simultaneous DOX (5 mg/kg) administration. At selected times, plasma and major organs were assayed for [3H]G3139 using scintillation counting and DOX determined using HPLC. The molecular integrity of G3139 was analyzed using SDS-PAGE. The PKs of G3139 and DOX were evaluated using a two-compartment model. G3139 administered i.v. at 5 mg/kg revealed a biexponential plasma concentration-time curve with a Cmax of 99.9 microg/ml and elimination half-lives of 0.03 h and 9.8 h, respectively, which resulted in an area under the concentration-time curve (AUC) of 15.9 microg x h/ml. G3139 administered i.p. showed a plasma absorption, distribution and elimination profile typical of this route of administration, characterized by half-lives of 0.03 h, 0.2 h and 8.9 h, respectively and a Cmax of 8.6 microg/ml. Based on AUC comparisons, the bioavailability of G3139 injected i.p. was 84% compared to i.v. administration. Subtle changes were observed in G3139 PKs after three prior i.p. doses of G3139. Specifically, a six-fold slower absorption rate, lower Cmax (6.9 microg/ml), increased Tmax (0.2 h), and an AUC of 17.4 microg x h/ml were observed, consistent with concentrations approaching saturation levels in tissue sites to which G3139 distributes. Coadministration of DOX had significant effects on the PK properties of G3139, manifested by an increased Cmax (11.2 microg/ml), higher AUC (19.7 microg x h/ml), and ninefold lower plasma clearance for single-dose G3139 administration. G3139 in plasma remained largely intact (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 17% degraded in plasma over 4 h), and increased plasma protein association occurred as a function of time. G3139 was detected in both healthy and tumor tissue after i.v. and i.p. administration. The highest tissue levels of G3139 were observed in the kidneys (40 microg/g), and low levels (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 2 microg/g) were detected in lung, heart and muscle. The rate of accumulation of G3139 in organs was dependent upon G3139 levels in plasma and the presence of coadministered DOX. Significant accumulation of G3139 was observed in solid tumors, with peak levels of approximately 5 microg G3139/g tumor, and approximately a two-to threefold tumor/muscle AUC ratio. The kinetics of G3139 accumulation in tumor tissue increased with increasing circulating G3139 concentration. The tissue distribution properties of DOX were also altered in the presence of coadministered G3139: in the presence of G3139, tumor exposure to DOX increased two-to threefold without alteration in plasma DOX PKs. These findings indicate that drug-drug interactions between G3139 and DOX are modest and favorable in that elevated tumor DOX levels are achieved without compromising G3139 tumor uptake or significantly altering plasma drug concentrations.

Breast Cancer Research and Treatment, 2000

We have investigated the effects of transient Bcl-2 down-regulation induced by the Bcl-2 antisens... more We have investigated the effects of transient Bcl-2 down-regulation induced by the Bcl-2 antisense oligodeoxynucleotide (ODN) G3139 (Genta Incorporated) in high Bcl-2 protein expressing, estrogen receptor (ER) positive MCF-7 and low Bcl-2 expressing, ER negative MDA435/LCC6 human breast cancer cells. Treatment with Bcl-2 antisense ODN in vitro caused &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 80% reduction of Bcl-2 protein levels in a sequence specific manner for both cell lines. Maximum mRNA reduction was achieved within 24 h of the first antisense ODN exposure whereas full protein down-regulation required antisense exposure over 48 h. This Bcl-2 reduction was associated with 80-95% loss of viable cells compared to untreated cells. Similar cytotoxic effects were observed in both cell lines despite a nine-fold intrinsic difference in Bcl-2 protein expression suggesting that the relative degree of down-regulation of Bcl-2 is more important than the absolute reduction. Cell death associated with G3139 exposure exhibited properties indicative of apoptosis such as mitochondrial membrane depolarization and caspase activation. Combined treatment with G3139 and cytotoxic agents resulted in additive cytotoxicity in both cell lines. However, under most conditions studied, the direct cytotoxic activity of G3139 antisense was not synergistic with the cytotoxic agents. These results suggest that while Bcl-2 clearly constitutes an attractive therapeutic target due to its role in regulating apoptosis in breast cancer cells, additional mechanisms are important in the control of apoptosis arising from exposure to anticancer agents in vitro.

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2000

Circulating malignant CD19 B cells have been implicated in the pathogenesis and relapse of multip... more Circulating malignant CD19 B cells have been implicated in the pathogenesis and relapse of multiple myeloma (MM). This study investigated the therapeutic applicability of using long-circulating liposome-encapsulated doxorubicin (DXR) targeted against the internalizing CD19 antigens present on human MM cells. In vitro binding studies using the CD19 MM cell line ARH77 demonstrated that CD19-directed immunoliposomes (SIL[anti-CD19]) specifically attached to these cells. Formulations of immunoliposomal doxorubicin (DXR-SIL[anti-CD19]) showed a higher association with, and higher cytotoxicity against, ARH77 cells than did non-targeted liposomal doxorubicin (DXR-SL) or isotype-matched controls (DXR-NSIL[IgG2a]). By using the pH-sensitive fluorophore, 1-hydroxypyrene-3,6,8-trisulfonic acid, binding of SIL[anti-CD19] to CD19 antigens was shown to trigger receptor-mediated internalization of the antibody^antigen complexes into endosomes. Targeting of SIL[anti-CD19] to CD19 B cells was also demonstrated in a heterogeneous mixture of peripheral blood mononuclear cells (PBMC) from MM patients. A decrease in cellular DNA (which is an indicator of apoptosis) caused by the cytotoxicity of DXR-SIL[anti-CD19] to myeloma PBMC was determined by using flow cytometry. While PBMC treatment with free DXR resulted in non-specific cytotoxicity to both B and T cells, DXR-SL were only minimally cytotoxic to either. In contrast, DXR-SIL[anti-CD19] were selectively cytotoxic for B cells in PBMC, indicating that this treatment may be effective in eliminating circulating malignant B cells in MM patients.

Advanced Drug Delivery Reviews, 1997

Advanced Drug Delivery Reviews, 1995

... Article Outline. References. advanced drug delivery reviews ELSEVIER Advanced Drug Delivery... more ... Article Outline. References. advanced drug delivery reviews ELSEVIER Advanced Drug Delivery Reviews 16 (1995) 267284 Pharmacokinetics of longcirculating liposomes Theresa M. Alien*,Christian B. Hansen, Daniel E. Lopes de Menezes Department of Pharmacology ...

A cultura cafeeira ocupa papel de destaque no cenário econômico brasileiro, sendo responsável pel... more A cultura cafeeira ocupa papel de destaque no cenário econômico brasileiro, sendo responsável pelo rendimento de U $4, 7 bilhões em 2008. A grande incidência de pragas e doenças diminui a capacidade produtiva da cultura, aumentando os custos de produção, ...