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Pedro G. Santiago-Cardona

Pedro G. Santiago-Cardona
Ponce Health Sciences University-Ponce Research Institute · Basic Sciences Department, Biochemistry & Cancer Biology Divisions

PhD

About

54
Publications
2,215
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275
Citations
Additional affiliations
August 2006 - May 2016
Ponce School of Medicine and Health Sciences
Position
  • Professor (Associate)

Publications

Publications (54)
Chapter
In an era of precision medicine important treatment decisions are dictated by expression of clinically informative tumor protein biomarkers. These biomarkers can be detected by immunohistochemistry (IHC) performed in tumor tissue sections obtained from biopsies or resections. Like all experimental procedures, IHC needs optimization for several of i...
Chapter
The cancer phenotype is usually characterized by deregulated activity of a variety of cellular kinases, with consequent abnormal hyper-phosphorylation of their target proteins. Therefore, antibodies that allow the detection of phosphorylated versions of proteins have become important tools both preclinically in molecular cancer research, and at the...
Book
This detailed book serves as a laboratory manual containing vital protocols and in-depth discussion involving commonly used experimental approaches for the characterization of several aspects of lung tumor biology. Beginning with an extensive section on biomarker detection, the volume continues with chapters on the genetic and molecular characteriz...
Article
Full-text available
Lung cancer patients with mutations in epidermal growth factor receptor (EGFR) benefit from treatments targeting tyrosine kinase inhibitors (TKIs). However, both intrinsic and acquired resistance of tumors to TKIs are common, and EGFR variants have been identified that are resistant to multiple TKIs. In the present study, we characterized selected...
Article
Full-text available
Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a bi...
Data
Detailed description of the TMA LC241C, including histological tumor type, average scoring for phospho-Rb S249, phospho-Rb T821 and p39, and the accompanying clinical data for each patient. The scores were averaged from the independent scores of 3 pathologists and the Aperio system. (DOCX)
Data
The TGFβ-induced EMT signature is capable of segregating patients based on metastasis free survival, overall survival and time to metastasis in a tissue microarray cohort of 150 NSCLC patients (TMA5). The TGFβ-EMT signature was used to separate TMA5 into EMT-positive and EMT-negative patient populations. Using the EMT-positive population we then ve...
Data
NSCLC patients whose AC tumors show a TGFβ-induced EMT gene expression signature also show high p39 expression. The TGFβ-EMT signature was used to separate TMA5 into EMT-positive and EMT-negative patient populations. A t-test showed a statistically significant difference in p39 expression between patients with the TGFβ-EMT signature and those witho...
Data
Detailed description of the TMA LC488, including histological tumor type, average scoring for phospho-Rb S249, phospho-Rb T821 and p39, and the accompanying clinical data for each patient. The scores were averaged from the independent scores of 3 pathologists and the Aperio system. (DOCX)
Data
Detailed description of the TMA T041, including histological tumor type, average scoring for phospho-Rb S249 and the accompanying clinical data for each patient. (DOCX)
Article
Lung cancer is characterized by its aggressiveness and proclivity for early metastasis. A predictor of metastasis of NSCLC rely on post-resection evaluation of tumor histology, which is a severe limitation since only 15% of the patients are diagnosed with resectable disease. Hence, there is a need to characterize biomarkers with metastasis-predicti...
Conference Paper
Introduction: Hispanics are projected to constitute 23% of the U.S. population by 2050. However, large-scale sequencing projects, such as The Cancer Genome Atlas (TCGA), provide little information on this ethnic population. In fact, only seven out of over 500 lung adenocarcinoma tumors sequenced in the TCGA database are reported to be Hispanic. To...
Chapter
The retinoblastoma protein (pRb) is an important tumor suppressor and cell cycle repressor. pRb is a phosphoprotein whose function is regulated primarily at the level of phosphorylation, and therefore, detecting pRb’s phosphorylation status in human tissue samples can be clinically informative. Unfortunately, detection of phosphorylated pRb residue...
Chapter
The retinoblastoma tumor suppressor protein (pRb) is a preeminent tumor suppressor that acts as a cell cycle repressor, specifically as an inhibitor of the G1–S transition of the cell cycle. pRb is a phosphoprotein whose function is repressed by extensive phosphorylation in several key residues, and therefore, pRb’s phosphorylation status has becom...
Article
Introduction: To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. Methods: This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was s...
Article
Lung cancer is characterized by its poor prognosis, aggressiveness, and proclivity for early metastasis. Non-small cell lung cancer (NSCLC) it’s the most common type of lung cancer with a five-year survival rate of 18%. Most predictors of metastasis and recurrence of NSCLC rely on post-resection evaluation of tumor histology, which is a severe limi...
Article
Full-text available
In spite of recent therapeutics advances and early detection, lung cancer is still the leading cause of cancer-associated deaths worldwide. The five-year survival rates for its two major subtypes, small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are estimated to be 6% and 18%, respectively. This high mortality is due to its aggr...
Article
Lung cancer remains the leading cause of cancer deaths among men and women worldwide. Its five-year survival rate (17.8%) is by far the lowest among the most common cancers such as colon (65.4%), breast (90.5%), and prostate (99.6%). Early detection and screening still remain challenging, and despite the many recent breakthroughs in lung cancer tre...
Article
Full-text available
We previously characterized the retinoblastoma tumor suppressor protein (Rb) as a regulator of adherens junction assembly and cell-to-cell adhesion in osteoblasts. This is a novel function since Rb is predominantly known as a cell cycle repressor. Herein, we characterized the molecular mechanisms by which Rb performs this function, hypothesizing th...
Article
Barriers persist in the development and delivery of effective cancer therapies to under-represented minority populations. In Puerto Rico, cancer is the second leading cause of death, yet cancer research awareness and training opportunities remain somewhat limited on the island. These limitations hinder progress toward decreasing the cancer health d...
Article
Full-text available
Hispanic/Latinos (H/L) are expected to grow to over 24% of the USA population by 2050 and lung cancer is the number one cause of cancer death among H/L men. Due to the information that is becoming available via genetic testing, lung cancer molecular profiling is allowing for increasing application of personalized lung cancer therapies. However, to...
Article
Full-text available
RB1 was the first tumor suppressor gene discovered. Over 4 decades of work have revealed that the Rb protein (Rb) is a master regulator of biological pathways influencing virtually every aspect of intrinsic cell fate including cell growth, cell-cycle checkpoints, differentiation, senescence, self-renewal, replication, genomic stability, and apoptos...
Article
Osteosarcomas (OS) and small cell lung carcinomas (SCLC) are poorly differentiated, highly aggressive tumors, with an early proclivity to metastasize. Prognosis is poor for both, with only 10-20% of patients achieving long-term disease-free intervals. Still, OS and SCLC aggressivity remain to be molecularly explained. Interestingly, these cancer ty...
Article
Full-text available
pRb is known as a classic cell cycle regulator whose inactivation is an important initiator of tumorigenesis. However, more recently, it has also been linked to tumor progression. This study defines a role for pRb as a suppressor of the progression to metastasis by upregulating integrin α10. Transcription of this integrin subunit is herein found to...
Article
Osteosarcomas (OS) are highly aggressive neoplasms of osteoblastic origin. Evidencing their early proclivity to metastasize, at the time of diagnosis most OS are already classified as high grade and poorly differentiated malignancies and about 20% have detectable metastases. Prognosis is very poor with only about 10% of patients achieving long-term...
Data
Gene Set Enrichment Analysis (GSEA, one module of SAM). GSEA was performed using GO Project database. Results again indicated that pRb knockout would significantly affect adhesion related processes. (0.01 MB XLS)
Data
pRb deficiency dramatically affects the expression of genes involved in cell adhesion pathways in osteoblasts. MetaCore cellular pathway analysis in conjunction with the Canonical Pathway database from GeneGO Inc. were used to determine which canonical pathways are statistically affected by pRb deficiency. This analysis allowed us to determine the...
Data
Cell Adhesion Related Genes Positively Regulated by Rb. Gene Ontology database prioritization for cell adhesion genes yielded 1719 individual probe-sets corresponding to genes designated to be involved directly or indirectly in cell adhesion. This table shows those that were positively regulated by pRb. For these 1719 individual probesets, tests fo...
Data
Knock-down of endogenous pRb in pRb-expressing osteoblasts disrupts adherens junctions. A DNA construct encoding a short hairpin-interfering RNA targeting the mouse RB gene (RB-shRNA) was cloned into an expression vector. pRb-expressing MC3T3 cells were then transfected with this construct followed by selection of stable transfectants. (a). Phase c...
Data
pRb regulates merlin folding in human osteoblasts. To determine if pRb expression is necessary and sufficient to promote merlin activation, we investigated merlin-tubulin interactions in the pRb-deficient osteosarcoma cell line Saos-2. Saos-2 cells were transfected with either control vector (CV) or with a vector transducing pRb. Cells transfected...
Data
Gene Set Analysis (GSA, one module of SAM). GSA was performed using GO Project database. Results indicated that pRb knockout would significantly affect adhesion related processes. (0.01 MB XLS)
Data
pRb-deficient osteoblasts show traits of the transformed phenotype. (a) To determine if pRb-deficient MC3T3 osteoblasts are able to form tumors in vivo, 1×106 cells were injected subcutaneously into SCID/NCr BALB/C mice. Three weeks after injection, mice injected with pRb-deficient MC3T3 osteoblasts developed highly vascularized tumors (arrow), whi...
Data
Blocking Rac1 activity reestablishes adherens junction formation and contact-dependent growth arrest. In these experiments, pRb-expressing osteoblasts stably expressing dnCdk5 were transfected with either a control vector or a dominant negative Rac1 (RacN17), followed by selection of stable transfectants. A–B. Phase contrast photomicrographs at 4×...
Data
Cell Adhesion Related Genes Negatively Regulated by Rb. Description for this table is the same as for Table S2, except that this table highlights genes repressed by pRb. (0.33 MB XLS)
Data
GeneGo Analysis. Analyses based on the GO database from the GO project confirmed the results from the Canonical Pathway Database shown in table S1 by ranking a cell-adhesion process with the second best P value among a total of 3752 GO functional processes. These data demonstrate, in an arbitrary fashion, that cell adhesion processes are among thos...
Article
Full-text available
The retinoblastoma protein (pRb) is a cell cycle regulator inactivated in most human cancers. Loss of pRb function results from mutations in the gene coding for pRb or for any of its upstream regulators. Although pRb is predominantly known as a cell cycle repressor, our data point to additional pRb functions in cell adhesion. Our data show that pRb...
Article
s: First AACR International Conference on Frontiers in Basic Cancer Research--Oct 8–11, 2009; Boston MA Alterations involving loss or gain of function of components of the retinoblastoma (RB1) tumor suppressor pathway are observed in a wide range of human cancers. They include loss of p16INK4a expression in melanomas and overexpression of cyclin D...
Article
A tumor suppressor commonly targeted in human cancers is the retinoblastoma (pRb) protein, a regulator of the G1/S phase transition of the cell cycle. pRb itself is inactivated with a frequency of over 90% in a subset of human tumors such as retinoblastomas, osteosarcomas, and small cell lung carcinomas. Ours studies suggest a novel role of pRb as...
Article
s: First AACR International Conference on Frontiers in Basic Cancer Research--Oct 8–11, 2009; Boston MA Disruption of the retinoblastoma (pRb) pathway is observed in most cancers. Mutational inactivation of pRb itself is observed at high frequencies in retinoblastomas, osteosarcomas, and small cell lung carcinoma. pRb blocks cell cycle progression...
Article
Endometriosis is a gynecological disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity. This condition is characterized by chronic pelvic pain, pain during intercourse (dyspareunia), painful periods (dysmenorrhea) and infertility. We and others have shown increased expression of lysyl oxidases--a family of...
Article
We have previously characterized the first invertebrate homolog of serum amyloid A (SAA) proteins in the sea cucumber Holothuria glaberrima, where its expression is associated with intestinal regeneration, suggesting a possible involvement of SAA proteins in intestinal morphogenesis. Here we show that bacterial lipopolysaccharides (LPS) trigger a c...
Article
Serum amyloid A (SAA) proteins comprise a family of highly conserved apolipoproteins found in all mammals thus far investigated, and also in ducks and salmonid fishes. However, no invertebrate SAA homologues have been detected to date. Here we report the characterization of the first SAA homologue in a nonvertebrate deuterostome, the echinoderm Hol...
Article
The Echinodermata is a unique animal group forming an early branch in the deuterostomes phylogenetic tree. In echinoids and asteroids a single Hox cluster with nine cognates of the vertebrate Hox paralogous groups has been reported, but no data are available from other echinoderm classes. We report here nine Hox-type sequences from the sea cucumber...

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