Papers by andres carranza
Peptides, Dec 1, 2012
The last decades have seen no significant progress in extending the survival of lung cancer patie... more The last decades have seen no significant progress in extending the survival of lung cancer patients and there is an urgent need to improve current therapies. The substance P (SP)/neurokinin-1 receptor (NK-1R) system plays an important role in the development of cancer: SP and NK-1R antagonists respectively induce cell proliferation and inhibition in human cancer cell lines. No study of the involvement of this system in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells has been carried out in depth. Here, we demonstrate the involvement of the SP/NK-1R system in human H-69 (SCLC) and COR-L23 (NSCLC) cell lines: (1) they express isoforms of the NK-1R and mRNA for the NK-1R; (2) they overexpress the tachykinin 1 gene; (3) the NK-1R is involved in their viability; (4) SP induces their proliferation; (5) NK-1R antagonists (Aprepitant (Emend), L-733,060, L-732,138) inhibit the growth of both cell lines in a concentration-dependent manner; (6) the specific antitumor action of these antagonists against such cells occurs through the NK-1R; and (7) lung cancer cell death is due to apoptosis. We also demonstrate the presence of NK-1Rs and SP in all the human SCLC and NSCLC samples studied. Our findings indicate that the NK-1R may be a promising new target in the treatment of lung cancer and that NK-1R antagonists could be new candidate antitumor drugs in the treatment of SCLC and NSCLC.
Placenta, Jul 1, 2010
A role for Substance P (SP) in human placenta is not known, although is possible that regulates p... more A role for Substance P (SP) in human placenta is not known, although is possible that regulates placental physiology through the Neurokinin (NK)-1 receptor. Ten human normal placenta tissues were studied by immunohistochemistry to demonstrate the localization of NK-1 receptor and SP. An immunostaining pattern for NK-1 receptor and SP was observed in the endothelium and myocytes of fetal blood vessels, decidua and trophoblast. The SP is located in both the cytoplasm and the nucleus whereas NK-1 receptor in cytoplasmic. These findings reported here for the fist time, suggest a role for the SP and NK-1 receptor in the placental physiology.
Annals of Oncology, 2012
ABSTRACT Background Preclinical models and randomized clinical trials suggest a protective role f... more ABSTRACT Background Preclinical models and randomized clinical trials suggest a protective role for estrogens against colorectal cancer (CRC). ER-β is the prevalent estrogen receptor in normal colonic mucosa, while its expression is significantly reduced in CRC. An increased ER-α/β ratio has been documented in colon carcinomas and this is associated with increased proliferation and decreased apoptosis. The aim of our study was to evaluate the expression of activated ER-α and its prognostic implications in a series of patients with surgically resected stage II-III CRC. Methods Phosphorylated ER-α [Ser167] expression was evaluated by immunohistochemistry (IHC) in tissue microarrays (TMA) of 218 CRC paraffin-embedded tumor samples. A pER-α score was calculated for each sample according to staining intensity and proportion of stained cells assessed by two pathologists blinded to the clinical data. Univariate and multivariate analyses were performed to assess the correlation of pER-α score with clinicopathological features and survival. Results pER-α staining was negative in 39 tumors (18%), 1+ in 164(75%), 2+ in 11(5%), and unavailable in 4(2%). Half of the samples had positive staining in >10% of tumor cells. A high pER-α score was more common in women (female:56% vs male:45%; p = 0.07), older patients (>65years:56% vs 120mg/dl:66% vs Conclusions ER-α is expressed in a high proportion of patients with CRC and is associated with a worse prognosis, particularly in women, young, non-diabetic and stage II patients. Disclosure All authors have declared no conflicts of interest.
Acta Histochemica, 2017
Gastric cancer (GC) is an aggressive disease that remains the fourth most common type of cancer a... more Gastric cancer (GC) is an aggressive disease that remains the fourth most common type of cancer and is the second leading cause of cancer-related death worldwide. Treatment of advanced or metastatic GC has seen little progress and median overall survival in this group remains <1 year. It is urgent to investigate new mechanisms to understand GC progression. It is known that substance P (SP), after binding to the neurokinin-1 (NK-1) receptor, elicits GC proliferation; that GC cells and samples express NK-1 receptors; that NK-1 receptor antagonists, in a concentration dependent manner, inhibit the proliferation of GC cells and that these cells die by apoptosis. However, the presence of SP in GC and normal gastric cells is unknown. In order to know more on the involvement of the SP/NK-1 receptor system in GC, we studied in thirty human GC and normal gastric samples the immunolocalization of SP after using an immunohistochemical technique. SP was observed in the cytoplasm and in the nucleus of GC and normal gastric cells. The nuclear expression of SP was higher in GC cells than in normal cells. No significant difference was observed when the cytoplasmatic expression of SP in normal and GC cells was compared. The findings suggest that SP plays an important role in both nuclear function and GC.
Revista Espanola De Cirugia Oral Y Maxilofacial Publicacion Oficial De La Sociedad Espanola De Cirugia Oral Y Maxilofacial, 2008
Medicina clínica, Jan 23, 2008
Medicina oral, patología oral y cirugía bucal, 2007
Central giant cell granuloma is an uncommon benign intraosseus lesion of jaws. Traditional treatm... more Central giant cell granuloma is an uncommon benign intraosseus lesion of jaws. Traditional treatment has been local curettage, although aggressive sub-types have a high tendency to recur. This patient report describes a recurrent central giant cell granuloma involving the body of the mandible in a 48-year-old-woman. Initial treatment of lesion consisted of curettage and peripheral ostectomy. When recurrence was detected one year later, an en bloc resection and defect regeneration with a composite bone graft of autogenous bone, xenograft, and autologous platelet-rich plasma was carried out. Adequate new bone formation was observed during follow-up of 24 months. Two dental implants were placed, and implant-supported prosthesis was constructed, providing a satisfactory dental restoration.
Revista Española de Cirugía Oral y Maxilofacial, 2008
La esclerosis tuberosa es una anomalía congénita del desarrollo embrionario que se transmite de f... more La esclerosis tuberosa es una anomalía congénita del desarrollo embrionario que se transmite de forma autosómica dominante caracterizada por la presencia por trastornos neurológicos, cutáneos o dermatológicos, y retraso mental. Se pueden afectar otros órganos y sistemas, y dar manifestaciones orofaciales. La lesión a nivel del esmalte dental constituye la lesión intraoral más frecuente. Rara vez se pueden encontrar lesiones óseas en los maxilares. El fibroma desmoplásico es un infrecuente tumor fibroso intraóseo localmente agresivo de lento crecimiento, que se asocia muy rara vez a la esclerosis tuberosa. Presentamos el caso clínico de un paciente de 33 años afecto de esclerosis tuberosa con una lesión en la mandíbula diagnosticada como fibroma desmoplásico. Se discuten los métodos diagnósticos, presentación clínica y tratamiento.
Cancer Research, 2013
MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological and pathol... more MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological and pathological processes including colorectal cancer (CRC). From a clinical perspective, several studies have identified groups of miRNAs with potential utility for early diagnosis or prognostic stratification of CRC patients. However, very few have evaluated the potential ability of miRNA to predict response to selected chemotherapy regimens. The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). We examined tumor expression levels of 667 miRNAs in the training cohort by TaqMan Low Density Arrays (TLDA). In training cohort (N=39), we identified a miRNA molecular signature with significant association in relevant clinical endpoints (objective response, progression-free and overall survival). In validation cohort (N=39), we validated significantly higher expression levels of miR-107, and...
Microscopy research and technique, 2013
Substance P (SP) after binding to the neurokinin-1 (NK-1) receptor regulates many biological func... more Substance P (SP) after binding to the neurokinin-1 (NK-1) receptor regulates many biological functions. Both SP and the NK-1 receptor are expressed in human normal placenta cells, monocytes, and macrophages. However, to our knowledge, the presence of both SP and the NK-1 receptor in macrophages of the placenta, the Hofbauer cells, is unknown. We demonstrate by immunohistochemistry in human normal placenta samples the presence of both SP and NK-1 receptors in the cytoplasm and in the nucleus of Hofbauer cells. The findings suggest a functional role of the SP/NK-1 receptor system in the physiology and pathophysiology of Hofbauer cells in the human placenta.
International journal of oncology, 2014
Osteosarcoma is a highly malignant bone tumor in children and adolescents. Aprepitant is a select... more Osteosarcoma is a highly malignant bone tumor in children and adolescents. Aprepitant is a selective high‑affinity antagonist of the human neurokinin‑1 (NK‑1) receptor (NK1R) with robust antitumor activity. No data exist on the presence of NK1R in osteosarcoma and whether this tumor responds to NK1R antagonists. Here, we analyzed the expression of NK1R in the human osteosarcoma cell line MG-63 with western blot analysis and PCR and found significant expression both at the protein and mRNA levels. We further studied the growth inhibitory capacity of aprepitant and other NK1R antagonists on MG-63 in vitro using an MTS cytotoxicity assay and DAPI staining. All antagonists induced tumor growth inhibition and apoptosis. Synergism was observed for the combination of L-733,060 with common cytostatic drugs in MG-63, but not in non-malignant HEK293 cells. Pretreatment of HEK293 with L-733,060 prior to exposure to cytostatic drugs partially protected HEK293 cells from inhibition by these drug...
International journal of oncology, 2014
The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development... more The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development of cancer. No in-depth studies of the involvement of this system in breast cancer (BC) have been carried out, and the action exerted by the drug aprepitant on BC cells is currently unknown. We show the involvement of this system in human BC cell lines: i) these cells express mRNA for the NK-1 receptor; ii) they overexpress NK-1 receptors; iii) the NK-1 receptor is involved in their viability; iv) SP induces their proliferation; v) NK-1 receptor antagonists block SP-induced mitogen stimulation of these cells; vi) the specific antitumor action of such antagonists on these cells occurs through the NK-1 receptor; and vii) BC cell death is due to apoptosis. We also found NK-1 receptors and SP in all human BC samples studied. The NK-1 receptor may be a promising target in the treatment of BC and NK-1 receptor antagonists could be candidates as a new antitumor drug in the treatment of BC.
Gastroenterología y Hepatología, 2007
Revista Española de Patología, 2011
Schwannoma; Neurofibroma intraneural; Melanoma; Tumor maligno de vaina neural periférica; Sarcoma... more Schwannoma; Neurofibroma intraneural; Melanoma; Tumor maligno de vaina neural periférica; Sarcoma sinovial monofásico Resumen Los tumores del nervio periférico son lesiones relativamente comunes que con frecuencia plantean problemas diagnósticos de marcada trascendencia. En la presente revisión se estudian de modo comparativo lesiones con nombres o con características morfológicas parecidas para poner en relieve los hallazgos diferenciales más significativos. En esta primera parte se revisan los siguientes diagnósticos: schwannoma convencional de tejidos blandos vs. neurofibroma intraneural; neurofibroma plexiforme vs. schwannoma plexiforme; schwannoma celular vs. tumor maligno de la vaina neural periférica (TMVNP); TMVNP vs. Melanoma, y TMVNP vs. sarcoma sinovial monofásico.
BMC Cancer, 2014
Background: MicroRNAs (miRNAs) are involved in numerous biological and pathological processes inc... more Background: MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). Methods: We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was analysed by RT-qPCR in an independent cohort. For a set of selected miRNAs, bioinformatic target predictions and pathway analysis were also performed. Results: Eight miRNAs (let-7 g*, miR-107, miR-299-5p, miR-337-5p, miR-370, miR-505*, miR-889 and miR-99a-3p) were significant predictors of response to chemotherapy in the training cohort. In addition, overexpression of miR-107, miR-337-5p and miR-99a-3p, and underexpression of miR-889, were also significantly associated with improved progression-free and/or overall survival. MicroRNA-107 and miR-99a-3p were further validated in an independent cohort as predictive markers for chemotherapy response. In addition, an inverse correlation was confirmed in our study population between miR-107 levels and mRNA expression of several potential target genes (CCND1, DICER1, DROSHA and NFKB1). Conclusions: MiR-107 and miR-99a-3p were validated as predictors of response to standard fluoropyrimidine-based chemotherapy in patients with mCRC.
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Papers by andres carranza