Luis E De Las Casas

University of Toledo, Toledo, Ohio, United States

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Publications (44)93.73 Total impact

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    ABSTRACT: The p21-activated serine-threonine kinase (PAK1) regulates cell motility and adhesion. We have previously shown that the prolactin (PRL)-activated tyrosine kinase JAK2 phosphorylates PAK1 in vivo and in vitro and identified tyrosines 153, 201, and 285 in PAK1 as sites of JAK2 tyrosyl phosphorylation. Here, we further investigate the role of the tyrosyl phosphorylated PAK1 (pTyr-PAK1) in regulation of cell adhesion. We use human breast cancer T47D cell lines that stably overexpress PAK1 wild type or PAK1 Y3F mutant in which these 3 JAK2 phosphorylation sites were mutated to phenylalanine. We demonstrate that PRL/JAK2-dependent phosphorylation of these tyrosines promotes a motile phenotype in the cells upon adhesion, participates in regulation of cell adhesion on collagen IV, and is required for maximal PAK1 kinase activity. Down-regulation of PAK1 abolishes the effect of PAK1 on cell adhesion. We show that the tyrosyl phosphorylation of PAK1 promotes PAK1 binding to β-PAK1-interacting guanine-nucleotide exchange factor (βPIX) and G protein-coupled receptor kinase-interacting target 1 (GIT1), phosphorylation of paxillin on Ser273, and formation and distribution of adhesion complexes. Using phosphospecific antibodies (Abs) directed to single phosphorylated tyrosines on PAK1, we identified Tyr285 as a site of PRL-dependent phosphorylation of PAK1 by JAK2. Furthermore, using PAK1 Y285F mutant, we provide evidence for a role of pTyr285 in cell adhesion, enhanced βPIX/GIT1 binding, and adhesion turnover. Our immunohistochemistry analysis demonstrates that pTyr285- PAK1 may modulate PAK1 signaling during tumor progression.-Hammer, A., Oladimeji, P., Casas, L. E. D. L., Diakonova, M. Phosphorylation of tyrosine 285 of PAK1 facilitates βPIX/GIT1 binding and adhesion turnover. © FASEB.
    The FASEB Journal 12/2014; DOI:10.1096/fj.14-259366 · 5.48 Impact Factor
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    ABSTRACT: Autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea not responsive to a gluten free diet and must be distinguished from refractory sprue. It is associated with circulating autoantibodies against goblet cells and enterocytes. AIE mainly involves the small intestines, with very few cases reported in adults. Because of the paucity of cases, the epidemiology of the disease remains unclear, and treatment is based on the cases found in the literature. Of the 35 adult cases reported, only 4 involved the colon. Because of the low number of cases, there have been no clear recommendations on treatment modalities with most reports heavily emphasizing steroids as the mainstay of treatment. We present the case of adult female patient who developed postpartum AIE and colopathy with profuse diarrhea successfully treated with adalimumab and a review of the literature. To the best of our knowledge, this case is only the fourth case of a tumor necrosis factor alpha antagonist being used in the treatment of AIE and the first case of adalimumab being used.
    American Journal of Therapeutics 11/2014; DOI:10.1097/MJT.0000000000000119 · 1.13 Impact Factor
  • The Journal of Urology 10/2014; 193(1). DOI:10.1016/j.juro.2014.10.047 · 3.75 Impact Factor
  • Diagnostic Cytopathology 08/2014; DOI:10.1002/dc.23205 · 1.52 Impact Factor
  • Gastrointestinal Endoscopy 05/2013; 77(5):AB557. DOI:10.1016/j.gie.2013.03.966 · 4.90 Impact Factor
  • Gastrointestinal Endoscopy 04/2012; 75(4):AB446. DOI:10.1016/j.gie.2012.03.1205 · 4.90 Impact Factor
  • Journal of Gastrointestinal Cancer 12/2011; DOI:10.1007/s12029-011-9354-1
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    ABSTRACT: Kaposi sarcoma is a vascular tumor manifesting as nodular lesions on skin, mucous membranes, or internal organs. This is a case of a 42-year-old human immunodeficiency virus- (HIV) positive bisexual male, not on highly active antiretroviral therapy (HAART) since diagnosis four years ago. He presented with a three-day history of abdominal pains, fever, vomiting, and a one-week history of melena stools. Endoscopy revealed Kaposi sarcoma in the stomach and duodenum. Postendoscopy, he developed acute abdomen. Exploratory laparotomy revealed extensive Kaposi sarcoma of the gastrointestinal tract with appendiceal involvement. The patient underwent appendectomy and had an uneventful recovery. A review of the literature discusses appendiceal Kaposi sarcoma with appendicitis, a rare but critical manifestation of gastrointestinal Kaposi sarcoma.
    Southern medical journal 04/2011; 104(4):278-81. DOI:10.1097/SMJ.0b013e31820dc210 · 1.12 Impact Factor
  • Cytopathology 11/2010; 22(6):418-20. DOI:10.1111/j.1365-2303.2010.00826.x · 1.47 Impact Factor
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    ABSTRACT: To the best of our knowledge, there are currently no recorded cytologic features of any effusion from rheumatoid peritonitis showing cytologic findings linked to rheumatoid pleural disease, although rheumatoid nodules have been described in the peritoneum. A 75-year-old man with longstanding, poorly controlled rheumatoid arthritis was seen in our hospital after a motor vehicle collision. Computed tomography showed free fluid in the abdominal cavity. Laparoscopic examination revealed a large amount of nonhemorrhagic ascitic fluid and no traumatic intraabdominal injuries. Abdominal and peritoneal surfaces appeared completely normal. The ascitic fluid was aspirated through the laparoscope and sent for cytologic examination. Cytospin preparations revealed histiocytes and loosely cohesive clusters of small cytologically bland epithelioid cells amid acute inflammatory cells and granular necrotic debris. Cell block material displayed transected fibroconnective tissue fragments lined by hyperplastic mesothelium with squamous metaplasia. Immunohistochemical studies revealed that the mesothelial cells were positive for calretinin, cytokeratin 5/6, and p63. The ascites was attributed to peritoneal disease from rheumatoid arthritis, based on the cytologic findings, immuno-profile, exclusion of other possible causes (i.e., cirrhosis, nephrotic syndrome, protein-losing enteropathy, or drugs), and patient's clinical setting.
    Acta cytologica 01/2010; 54(6):1123-6. · 1.56 Impact Factor
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    Olga L Bohn, Luis E De las Casas, Marino E Leon
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    ABSTRACT: Metastatic disease to thyroid gland is a rare event. Although renal cell carcinoma (RCC) has been reported to metastasize the thyroid gland, metastatic RCC to a thyroid neoplasm is very unusual. We report a case of a 68-year-old man with history of RCC who presented with a 2.5-cm thyroid nodule. Histologic examination demonstrates a renal cell carcinoma metastatic to a papillary carcinoma of the thyroid. The clinicopathologic features of metastatic disease into a thyroid gland neoplasm are shown, and a review of the literature is presented.
    Head and Neck Pathology 12/2009; 3(4):327-30. DOI:10.1007/s12105-009-0147-9
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    ABSTRACT: A 52-year-old woman presented with recurrent episodes of chest pain, shortness of breath, palpitations, and fatigue for three months. Her past medical history was significant for chronic anemia. Physical examination revealed a pansystolic murmur radiating to the left axilla. Her admission workup showed microcytic anemia. Her serum creatinine and iron studies were within normal limits and her hemoglobin electrophoresis pattern was that of beta thalassemia minor. Two-dimensional echocardiography showed a multilobulated mobile mass attached to the mitral annulus at the base of the anterior mitral valve leaflet. The patient underwent surgical resection of the mass. Pathology examination revealed a cardiac myxoma with conspicuous foci of extramedullary hematopoiesis.
    Southern medical journal 06/2009; 102(7):769-71. DOI:10.1097/SMJ.0b013e3181a8240c · 1.12 Impact Factor
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    ABSTRACT: Intraoperative cytologic evaluation of brain tumors has been used either to render a preliminary interpretation or more often as a complement to frozen section examination. Central neurocytoma is a intraventricular neoplasm, typically located in the region of the foramen of Monro, affecting mostly young to middle age adults. Histologically, central neurocytomas are characterized by monotonous cells with round nuclei and neuronal differentiation within a rich capillary network. Their distinction during intraoperative consultations from oligodendroglioma, ependymoma (mainly clear cell ependymoma), and non-Hodgkin lymphoma can be a diagnostic challenge. We report a case of a 19-year-old female with an intraventricular tumor where imprint cytology preparations were crucial for the intraoperative diagnosis of central neurocytoma. Imprint cytology preparations show a round cell neoplasm associated with neuropil clumps and short straight capillaries admixed with tumor cell clusters. To the best of our knowledge, only a few cases describing the cytologic findings of central neurocytomas have been reported in the medical literature. The differential diagnosis, tissue correlation, clinical-radiologic features, and ancillary studies are discussed.
    Diagnostic Cytopathology 01/2009; 38(3):202-7. DOI:10.1002/dc.21179 · 1.52 Impact Factor
  • Soheila Korourian, Luis De Las Casas
    Clinical Obstetrics: The Fetus & Mother, Third Edition, 01/2008: pages 33 - 58; , ISBN: 9780470753293
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    ABSTRACT: Low-grade fibromyxoid sarcoma is an uncommon, deceptively bland mesenchymal neoplasm that typically occurs in the deep soft tissues of the proximal extremities of young to middle-aged patients. Intra-abdominal low-grade fibromyxoid sarcomas are distinctly rare. We describe the first reported example of this sarcoma involving the ovary. The 42-year-old patient presented with progressing abdominal pain and urinary frequency. Computed tomographic imaging of the abdomen and pelvis showed a 14-cm left-sided pelvic mass. The patient underwent surgical resection and, intraoperatively, a left ovarian mass was identified that extended to both the left hypogastric artery and the left ureter. The resected specimen consisted of a 17-cm tan, fleshy mass containing grossly recognizable nodules of gelatinous, myxoid tissue and a small rim of normal ovary. Microscopic examination of the neoplasm revealed a cytologically bland spindle cell proliferation set in a collagenized stroma that abruptly transitioned to nodules of a myxoid stroma with a well-formed capillary vasculature, features characteristic of low-grade fibromyxoid sarcoma. On the basis of the diagnosis, the patient was clinically staged as a retroperitoneal sarcoma with secondary ovarian involvement. The patient has stable residual disease 11 months postoperatively. This case adds to the literature of intra-abdominal low-grade fibromyxoid sarcoma and expands the list of malignant mesenchymal neoplasms that may involve the ovary.
    International Journal of Gynecological Pathology 05/2007; 26(2):173-6. DOI:10.1097/01.pgp.0000228145.36807.43 · 1.63 Impact Factor
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    ABSTRACT: Chorioamnionitis is the maternal and fetal response to an ascending intrauterine infection. The fetal response is manifested by funisitis and chorionic vasculitis, or as neutrophils within pulmonary spaces. Human hematopoiesis occurs in the liver primarily during the 6th to 22nd weeks of gestation. To establish the relationship between the presence of an intrauterine infection and the degree of fetal hepatic myelopoiesis in second- and third-trimester fetuses. Liver and lungs from 49 fetal autopsies, 20 to 41 weeks of gestational age, and their associated placentas and membranes were analyzed for evidence of intrauterine infection and hepatic myelopoiesis. Hematoxylin-eosin-stained sections from fixed tissues were evaluated for the presence of amnionic fluid infection, defined by the presence of acute chorioamnionitis or funisitis. The degree of portal hematopoiesis, myelopoiesis and intra-alveolar neutrophils was assessed semiquantitatively with hematoxylin-eosin-stained sections and immunohistochemically with antimyeloperoxidase. The Kruskal-Wallis 1-way analysis of variance and the Wilcoxon-Mann-Whitney test were used to determine the significance of any observed difference. The degree of portal and lobular myelopoiesis was significantly greater with the presence of inflammation in both the membranes and umbilical cord, and correlated with the presence of intra-alveolar neutrophils (P < .001). A high correlation between the hematoxylin-eosin and immunohistochemistry assessment of myeloid cells was noted. There is increased portal and lobular myelopoiesis in 20-week to 41-week gestational age fetal livers that is associated with intrauterine ascending infection. The presence of increased portal or lobular myelopoiesis suggests the presence of an active fetal response to an intrauterine ascending infection.
    Archives of pathology & laboratory medicine 12/2006; 130(12):1786-91. DOI:10.1043/1543-2165(2006)130[1786:MITLOS]2.0.CO;2 · 2.88 Impact Factor
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    ABSTRACT: Overexpression of the epidermal growth factor type II receptor HER-2/neu has been associated with resistance to chemotherapy and poor survival in several human tumors. In the current study, the authors have determined the frequency and clinical significance of HER-2/neu gene amplification in uterine serous papillary endometrial carcinoma (USPC), a highly aggressive variant of endometrial carcinoma. Fluorescence in situ hybridization (FISH) assay was used to analyze gene amplification in paraffin blocks from 30 women harboring Stage IA-IV USPC treated at the University of Arkansas for Medical Sciences (Little Rock, AR) from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. USPC patient survival in relation to HER-2/neu gene amplification was analyzed using Kaplan-Meier curves in conjunction with the log-rank test. Amplification of the HER-2/neu gene by FISH was observed in 14 of the 30 (47%) cases. Heterogeneity was noted in 4 of 14 cases in the amplification of the HER-2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. Patients with USPC harboring tumors with HER-2/neu gene amplification had a significantly shorter survival time from diagnosis to disease-related death when compared with FISH-negative patients (P = 0.0008). African-American (AA) patients were found to have a poorer prognosis compared with Caucasian (C) women (P = 0.01) and to harbor USPC with significantly higher levels of HER-2/neu gene amplification (P = 0.02). HER-2/neu gene amplification in USPC was found to be an important prognostic indicator for poor outcome that occurs more frequently in AA when compared with C patients. Determination of HER-2/neu gene amplification may guide clinical management of patients with USPC and may have important implications for the implementation of novel treatment strategies.
    Cancer 11/2005; 104(7):1391-7. DOI:10.1002/cncr.21308 · 4.90 Impact Factor
  • Luis E. De Las Casas
    Diagnostic Cytopathology 08/2005; 33(2):144-144. DOI:10.1002/dc.20286 · 1.52 Impact Factor
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    ABSTRACT: To evaluate and compare HER2/neu protein overexpression and gene amplification in uterine serous papillary endometrial cancer (USPC). Immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) assays were used to analyze and compare HER2/neu protein expression and gene amplification, respectively, in paraffin blocks from 26 women harboring stage IA to IV USPC treated at the University of Arkansas for Medical Sciences from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. Moderate-to-strong expression of HER2/neu protein was noted in 16 (62%) of 26 USPC samples evaluated, with 7 (27%) samples showing moderate staining (2+) and 9 (35%) showing strong staining (3+) for HER2/neu. Amplification of the ERBB2 gene by FISH was observed in 11 of the 26 (42%) cases. Protein overexpression and gene amplification were found to correlate in 100% (9 of 9) of the 3+ positive tumors and 2 out of 7 (29%) of the 2+ positive tumors. Heterogeneity was noted in 3 cases in the amplification of the HER2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. None of the 10 USPC cases scored by IHC as 0 or 1+ was found positive for ERBB2 amplification by FISH. Amplification of the HER2/neu oncogene represents a common finding in USPC. FISH analysis should be used for confirmation of gene amplification in USPC showing 2+ expression of HER2/neu. Prior screening and selection of appropriate immunohistochemistry-positive areas may be beneficial in the selection of some USPC patients undergoing FISH analysis.
    Gynecologic Oncology 08/2005; 98(1):24-30. DOI:10.1016/j.ygyno.2005.03.041 · 3.69 Impact Factor

Publication Stats

342 Citations
93.73 Total Impact Points

Institutions

  • 2011–2014
    • University of Toledo
      Toledo, Ohio, United States
  • 2010–2014
    • Medical University of Ohio at Toledo
      • Department of Medicine
      Toledo, Ohio, United States
  • 2008
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, Maryland, United States
  • 2002–2005
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2004
    • University of Arkansas for Medical Sciences
      • Department of Surgery
      Little Rock, Arkansas, United States
  • 2003
    • University of Missouri - Kansas City
      • Department of Pathology
      Kansas City, MO, United States
  • 2000–2001
    • University of Wisconsin–Madison
      • Department of Pathology and Laboratory Medicine
      Madison, Wisconsin, United States
  • 1999
    • East Carolina University
      • Department of Pathology & Laboratory Medicine
      North Carolina, United States
  • 1998
    • University of South Carolina School of Medicine - Greenville
      Greenville, South Carolina, United States