About

Carlos Carrera is a Clinical Professor of Medicine at UCSD, with a research focus on molecular biology, cancer therapy, and programmed cell death. His work includes investigating mechanisms of chemotherapy toxicity, DNA damage, and apoptosis in cancer cells, particularly in relation to methylthioadenosine phosphorylase (MTAP) deficiency and T-cell acute lymphoblastic leukemia. Carrera has contributed to understanding the genetic deletions in lung cancers and the development of targeted therapies using agents like alanosine and deoxyadenosine analogs. His research activities have been funded by NIH grants, and he has authored numerous publications in the fields of molecular biology, hematology, and oncology. Carrera's work emphasizes the biochemical and genetic basis of cancer and explores novel therapeutic strategies, including salvage therapy and apoptosis induction, to improve treatment outcomes. His contributions have advanced knowledge in cancer genetics, drug resistance, and targeted molecular therapies.

Research topics

• Biology
• Chemistry
• Biochemistry
• Molecular biology
• Medicine

Selected publications

• Prevalencia de los subtipos de leucemia aguda en pacientes atendidos en el área de hematología del Hospital de especialidades Eugenio Espejo desde agosto del 2015 a agosto del 2018

  Reflexiones · 2022-03-19 · 1 citations

  article1st authorCorresponding

  Introducción: La leucemia es una neoplasia hematológica, caracterizada por la proliferación de células hematopoyéticas inmaduras, se clasifican en agudas y crónicas. Objetivo: Establecer la prevalencia de los subtipos de leucemia aguda (LA) en pacientes atendidos en Hematología del hospital de Especialidades Eugenio Espejo (HEEE), desde agosto 2015 a agosto 2018. Diseño: Estudio descriptivo, retrospectivo, con, 401 pacientes con diagnóstico LA, registrados en la historia clínica, posterior a la autorización del Comité de Bioética del HEEE. Resultados: En el periodo de 2015 a 2018 se identificaron 401 pacientes con diagnóstico de LA, 230 (57%) hombres divididos en leucemia mieloide aguda (LMA) 93 (23%) y leucemia linfoide aguda (LLA) 137 (34%), y 171(43%) mujeres, con LMA 16% y 106 LLA 106. El sub tipo de LMA, Mieloblástica con diferenciación (M2) de mayor presentación, 40 pacientes (25%), 22 hombres y 18 mujeres, seguida de Mieloblástica con mínima diferenciación (M1) diagnosticada en 35 (22%) pacientes, 20 (13%) hombres y 15 (9%) mujeres. La promielocítica (M3), se diagnosticaron 31 (20%) pacientes, 16 hombres, y en 15 mujeres, entre los 20 a 29 años. Y la LLA, de tipo B, 233 (96%) casos, el sub tipo B común con 173 (71%), 91 hombres y 82 mujeres. El sub tipo preT, 10 (4%) casos, 5 (2%) en hombres y mujeres. Conclusiones: De las LA su mayor prevalencia fue LLA en los subtipos B común. Y los casos de LMA en los tipos M1 y M2 la mayoría de los casos en hombres y mujeres.

  PublisherDOI

• GUÍA DE RECOMENDACIONES EN PACIENTES CON DIABETES MELLITUS EN FASE DE CONFINAMIENTO O ENFERMEDAD AGUDA POR SARS-COV-2 (COVID-19)

  Redalyc (Universidad Autónoma del Estado de México) · 2020-01-01

  article

  "La pandemia por síndrome respiratorio agudo severo por infección del coronavirus 19 (SARS-COVID19) representa un gran reto para los sistemas de salud mundiales. El distanciamiento social y la cuarentena han afectado la forma del cuidado de pacientes con diabetes mellitus. La adaptación ante la pandemia hace necesario proveer una guía del cuidado adecuado de estos pacientes a nivel local con nuestros recursos para lograr en ellos un adecuado control glicémico."

  Publisher

• Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment

  JAMA · 2017-07-11 · 150 citations

  articleOpen access

  IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

  PublisherOA PDFDOI

• Marrow Suppression Produced by Repeated Doses of Cladribine

  Acta Haematologica · 2009-02-18 · 43 citations

  articleSenior author

  2-Chlorodeoxyadenosine (cladribine, Leustatin) is being used extensively in the treatment of hematologic malignancies, but relatively little is known regarding its toxicity to the normal marrow. Long-term serial hematologic observations have been made on 29 patients with multiple sclerosis undergoing experimental therapy with monthly courses of cladribine, each of which consisted of 0.087-0.1 mg/kg per day for 7 days. The characteristic hematologic responses of the patients consisted of acute transient monocytopenia, prolonged, profound lymphopenia especially of CD4-positive cells, and modest lowering of the granulocyte count and hemoglobin with development of long-lasting macrocytosis. Two patients developed severe aplastic anemia, requiring transfusion both of red cells and platelets. One of these had previously received extensive therapy with chlorambucil, while the other had received carbamazepine (Tegretol) and was ingesting phenytoin (Dilantin) at the time of cladribine therapy. Both patients recovered after several months of marrow suppression.

  PublisherDOI

• Sistemática de elevación de seno maxilar con abordaje lateral mediante trefinas específicas

  Revista española odontoestomatológica de implantes · 2008-01-01

  article

  El objetivo del presente trabajo es la presentacion de una nueva tecnica quirurgica de abordaje lateral del seno maxilar para la colocacion de implantes dentales, ya sea realizada en una o dos fases quirurgicas. El motivo de tal tecnica es ofrecer mayor seguridad y rapidez en la abertura lateral del antro sinusal. Para ello se han utilizado trefinas de corta longitud con topes de seguridad y de profundidad de corte programable disenadas especificamente para ello.

  Publisher

• EFA (9-β-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine

  Blood · 2005-10-19 · 15 citations

  articleOpen access

  The deficiency of methylthioadenosine phosphorylase (MTAP) in T-cell acute lymphoblastic leukemia (T-ALL) and other cancers, while constitutively expressed in normal cells, allows for selective therapy using L-alanosine, an inhibitor of de novo AMP synthesis. We demonstrate that MTAP- T-ALL cells obtained at relapse are as sensitive to L-alanosine toxicity as diagnosis samples. The therapeutic index of L-alanosine can be increased by the use of a MTAP substrate, which protects MTAP+ normal cells. Since MTAP substrates MTA and 5'deoxyadenosine are prone to toxicities associated with adenosine, we synthesized and evaluated a potentially nontoxic MTAP substrate, 9-beta-D-erythrofuranosyladenine (EFA). The cytotoxicity of EFA to hematopoietic progenitors erythroid burst-forming units (BFU-Es) and granulocyte-macrophage colony-forming units (CFU-GMs) was at least 26- to 41-fold less than that of MTA. In addition, EFA selectively rescued MTAP+ MOLT-4 cells from L-alanosine toxicity at 25 microM with negligible toxicity even at 100 microM. As for MTA, significant, albeit incomplete, rescue was achieved at 12.5 microM, but higher concentrations were toxic. EFA at 20 microM or less rescued primary MTAP+ T-ALL cells and normal lymphocytes from L-alanosine toxicity. Collectively, these data indicate that EFA is an effective agent for salvaging MTAP+ cells from L-alanosine toxicity and is superior to MTA due to lower cytotoxicity.

  PublisherOA PDFDOI

• La escama blanca del mango Aulacaspis tubercularis y medidas integradas para su manejo

  2004-01-01

  article

  A. tubercularis conocida como la escama blanca del mango, cochinilla, piojillo blanco o pelabolsillo, es uno de las principales plagas del mango. esta presente en Ecuador en todas las areas cultivadas con mango y fue identificado en 1997. Posee dimorfismo sexual, es decir que hembras y machos tienen diferentes aspectos. Los frutos afectados son rechazados durante la recoleccion en el campo y en las empacadoras, en donde aceptan solamente entre 1 a 2 lesiones de escamas por fruto. Una hembra deposita entre 32 y 197 huevecillos durante su vida, pudiendo un solo insecto infectar todos los frutos de un pedunculo, de alli la importancia de realizar muestreos o evaluaciones permanentes desde el inicio de floracion a la cosecha. El muestreo del insecto se realiza fregando con las yemas de los dedos las colonias de escamas machos para observar si estan vivas o muertas; estan vivas cuando en los dedos queda una substancia amarillo anaranjada. Para un control integrado se debe realizar practicas culturales como podas de despunte y de raleo, para eliminar poblaciones que quedan despues de las cosechas; aplicar productos de baja toxicidad como aceites minerales y vegetales, desde el inicio de la floracion, amarre y formacion de frutos. Los productos y dosis que reducen las poblaciones de hembras y ninfas son: Oleatos vegetales (Cochibiol) 2l; Aceite mineral (Aceite agricola) 2,5 l; Acidos grasos y triacilgliceridos (Babaoil) 2,5 l; Polisulfuro azadirachtina (Pestone) 3 l; Triacilgliceroles, acidos grasos (Ecofrut) 4 l; Sales potasicas de acidos grasos (Impide) 2 l; Aceite vegetal (Aceite comestible emulsificado) 4 l. Con la aplicacion de estos productos se favorece la presencia de enemigos naturales como adultos y larvas de Coccidophilus sp y larvas de Chrysopa sp, principales predatores de la escama blanca del mango. Se pueden utilizar en el estrato inferior de los arboles trampas transparentes untadas con pegamento o stiken para la captura de los machos que tienen alas

  Publisher

• Nucleotide Requirements for the in Vitro Activation of the Apoptosis Protein-activating Factor-1-mediated Caspase Pathway

  Journal of Biological Chemistry · 2000-01-01 · 164 citations

  articleOpen access

  Adenine deoxynucleosides, such as 2-chlorodeoxyadenosine (2CdA) and fludarabine, induce apoptosis in quiescent lymphocytes, and are thus useful drugs for the treatment of indolent lymphoproliferative diseases. We previously demonstrated that that the 5'-triphosphate metabolite of 2CdA (2CdATP), similar to dATP, can cooperate with cytochrome c and apoptosis protein-activating factor-1 (APAF-1) to trigger a caspase pathway in a HeLa cell-free system. We used a fluorometry-based assay of caspase activation to extend the analysis to several other clinically relevant adenine deoxynucleotides in B-chronic lymphocytic leukemia extracts. The nucleotide-induced caspase activation displayed typical Michaelis-Menten kinetics. As estimated by the V(max)/K(m) ratios, the relative efficiencies of different nucleotides were Ara-ATP > 9-fluoro-9-beta-D-arabinofuranosyladenine 5'-triphosphate > dATP > 2CdATP > 9-beta-D-arabinofuranosylguanine 5'-triphosphate > dADP > ATP. In contrast to dADP, both ADP and its nonhydrolyzable alpha, beta-methylphosphonate analog were strong inhibitors of APAF-1-dependent caspase activation. The hierarchy of nucleotide activation was confirmed in a fully reconstituted system using recombinant APAF-1 and recombinant procaspase-9. These results suggest that the potency of adenine deoxynucleotides as co-factors for APAF-1-dependent caspase activation is due both to stimulation by the 5'-triphosphates and lack of inhibition by the 5'-diphosphates. The capacity of adenine deoxynucleoside metabolites to activate the apoptosome pathway may be an additional biochemical mechanism that plays a role in the chemotherapy of indolent lymphoproliferative diseases.

  PublisherDOI

• Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria

  Blood · 2000-11-15 · 265 citations

  article

  Adenine deoxynucleosides induce apoptosis in quiescent lymphocytes and are thus useful drugs for the treatment of indolent lymphoproliferative diseases. To explain why deoxyadenosine and its analogs are toxic to a cell that is not undergoing replicative DNA synthesis, several mechanisms have been proposed, including the direct binding of dATP to the pro-apoptotic factor Apaf-1 and the activation of the caspase-9 and -3 pathways. In this study it is shown, by means of several assays on whole cells and isolated mitochondria, that 2-chloro-2'-deoxyadenosine (2CdA) and 2-choloro-2'-ara-fluorodeoxyadenosine (CaFdA) disrupt the integrity of mitochondria from primary chronic lymphocytic leukemia (B-CLL) cells. The nucleoside-induced damage leads to the release of the pro-apoptotic mitochondrial proteins cytochrome c and apoptosis-inducing factor. The other adenine deoxynucleosides tested displayed comparable DNA-damaging potency but did not affect mitochondrial function. Interference with mitochondrial integrity, thus, may be a factor in the potent cytotoxic effects of 2CdA and CaFdA toward nondividing lymphocytes.

  PublisherDOI

• Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria

  Blood · 2000-11-15 · 239 citations

  article

  Abstract Adenine deoxynucleosides induce apoptosis in quiescent lymphocytes and are thus useful drugs for the treatment of indolent lymphoproliferative diseases. To explain why deoxyadenosine and its analogs are toxic to a cell that is not undergoing replicative DNA synthesis, several mechanisms have been proposed, including the direct binding of dATP to the pro-apoptotic factor Apaf-1 and the activation of the caspase-9 and -3 pathways. In this study it is shown, by means of several assays on whole cells and isolated mitochondria, that 2-chloro-2′-deoxyadenosine (2CdA) and 2-choloro-2′-ara-fluorodeoxyadenosine (CaFdA) disrupt the integrity of mitochondria from primary chronic lymphocytic leukemia (B-CLL) cells. The nucleoside-induced damage leads to the release of the pro-apoptotic mitochondrial proteins cytochrome c and apoptosis-inducing factor. The other adenine deoxynucleosides tested displayed comparable DNA-damaging potency but did not affect mitochondrial function. Interference with mitochondrial integrity, thus, may be a factor in the potent cytotoxic effects of 2CdA and CaFdA toward nondividing lymphocytes.

  PublisherDOI

Recent grants

• NIH Grant R29CA054892

  NIH · $486k · 1996

• NIH Grant R21CA068260

  NIH · $273k · 1999

• NIH Grant K08CA001100

  NIH · $167k · 1990

• NIH Grant P60AR040770

  NIH · $11.1M · 2002

Frequent coauthors

• Dennis A. Carson

  University of California, San Diego

  94 shared

• D B Wasson

  Institute on Aging

  43 shared

• Howard B. Cottam

  University of California, San Diego

  25 shared

• Lawrence D. Piro

  Sapienza University of Rome

  25 shared

• Erik H. Willis

  Bio-Rad (United States)

  21 shared

• Shiro Seto

  Shizuoka Children's Hospital

  20 shared

• Masaru Kubota

  Columbia University

  20 shared

• Ernest Beutler

  19 shared