ABSTRACT
New chemotherapeutic agents are needed for pancreatic cancer (PC). We have previously shown that phospho-valproic acid (MDC-1112) is effective in cell-line xenografts of PC. Here, we explored whether MDC-1112 is effective in additional clinically relevant animal models of PC and whether MDC-1112 enhances the anticancer effect of clinically used chemotherapeutic agents. MDC-1112 alone strongly reduced patient-derived pancreatic tumor xenograft growth, and extended survival of LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mice. In both models, MDC-1112 inhibited STAT3 activation and its downstream signals, including Bcl-xL and cyclin D1. In human PC cell lines, P-V enhanced the growth inhibitory effect of gemcitabine (GEM), Abraxane and 5-FU, but not that of irinotecan. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of MDC-1112/GEM combination. Furthermore, MDC-1112 enhanced GEM's effect on colony formation, apoptosis, cell migration, and cell invasion. In vivo, MDC-1112 and GEM, given alone, reduced patient-derived pancreatic tumor xenograft growth by 58% and 87%, respectively; whereas MDC-1112/GEM combination reduced tumor growth by 94%, inducing tumor stasis. In conclusion, MDC-1112 should be further explored as a potential agent to be used in combination with GEM for treating PC.
Subject(s)
Abnormalities, Multiple/drug therapy , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Keratoconus/congenital , Organophosphates/pharmacology , Pancreatic Neoplasms/drug therapy , Valproic Acid/analogs & derivatives , Abnormalities, Multiple/pathology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Disease Models, Animal , Humans , Keratoconus/drug therapy , Keratoconus/pathology , Mice , Pancreatic Neoplasms/pathology , Signal Transduction/drug effects , Valproic Acid/pharmacology , Xenograft Model Antitumor Assays , GemcitabineABSTRACT
RESUMEN Se presenta un caso clínico de un varón de 27 años de edad, con una ectasia corneal y presencia de queratoglobo en ambos ojos. La manifestación clínica fue disminución lenta y progresiva de la agudeza visual en ambos ojos y dolor en el ojo izquierdo. Al examen oftalmológico se constató hidrops corneal agudo en ojo izquierdo y otras complicaciones corneales, propias de esta anomalía. Se realizó un estudio oftalmológico que permitió un diagnóstico certero. Se aplicó la terapéutica correspondiente y se sugirieron otras opciones terapéuticas (AU).
ABSTRACT We present the clinical case of a male patient, aged 27 years, with corneal ectasia and keratoglobus in both eyes. The clinical manifestation was progressive and slow decrease of the visual acuity in both eyes and pain in the left eye. At the ophthalmologic examination, acute corneal hydrops was found in the left eye, and also other complications that are proper of this anomaly. An ophthalmologic study was carried out that lead to an accurate diagnosis. The correspondent therapy was applied and several therapeutic options were suggested (AU).
Subject(s)
Humans , Male , Adult , Atropine/therapeutic use , Vision Disorders , Corneal Diseases/diagnosis , Visually Impaired Persons , Corneal Perforation/prevention & control , Keratoconus/diagnosis , Visual Acuity , Corneal Topography , Eyeglasses , Keratoconus/congenital , Keratoconus/etiology , Keratoconus/drug therapy , Keratoconus/epidemiologyABSTRACT
RESUMEN Se presenta un caso clínico de un varón de 27 años de edad, con una ectasia corneal y presencia de queratoglobo en ambos ojos. La manifestación clínica fue disminución lenta y progresiva de la agudeza visual en ambos ojos y dolor en el ojo izquierdo. Al examen oftalmológico se constató hidrops corneal agudo en ojo izquierdo y otras complicaciones corneales, propias de esta anomalía. Se realizó un estudio oftalmológico que permitió un diagnóstico certero. Se aplicó la terapéutica correspondiente y se sugirieron otras opciones terapéuticas (AU).
ABSTRACT We present the clinical case of a male patient, aged 27 years, with corneal ectasia and keratoglobus in both eyes. The clinical manifestation was progressive and slow decrease of the visual acuity in both eyes and pain in the left eye. At the ophthalmologic examination, acute corneal hydrops was found in the left eye, and also other complications that are proper of this anomaly. An ophthalmologic study was carried out that lead to an accurate diagnosis. The correspondent therapy was applied and several therapeutic options were suggested (AU).
Subject(s)
Humans , Male , Adult , Atropine/therapeutic use , Vision Disorders , Corneal Diseases/diagnosis , Visually Impaired Persons , Corneal Perforation/prevention & control , Keratoconus/diagnosis , Visual Acuity , Corneal Topography , Eyeglasses , Keratoconus/congenital , Keratoconus/etiology , Keratoconus/drug therapy , Keratoconus/epidemiologyABSTRACT
BACKGROUND: Posterior keratoconus is a rare cause of a corneal opacity in an infant. It is characterized by thinning of the posterior cornea without ectasia of the anterior cornea. Imaging of this condition with anterior segment optical coherence tomography (AS-OCT) has not been reported in the literature. CASE PRESENTATION: A six week old African-American male presented with a congenital corneal opacity of the right eye. He underwent an examination under anesthesia in which photography and AS-OCT were performed. AS-OCT confirmed the diagnosis of posterior keratoconus. The patient subsequently underwent an optical iridectomy for visual development. CONCLUSION: AS-OCT is a useful tool in cases when a child presents with a corneal opacity of unknown or unclear etiology. In our patient, AS-OCT showed the classic description of central corneal thinning seen in this condition. Additionally, it revealed an associated detached Descemet membrane, a feature which has not been previously described in posterior keratoconus.
Subject(s)
Anterior Eye Segment/pathology , Corneal Opacity/diagnosis , Keratoconus/diagnosis , Tomography, Optical Coherence/methods , Corneal Opacity/congenital , Corneal Pachymetry , Gestational Age , Humans , Infant , Iridectomy , Keratoconus/congenital , MaleABSTRACT
BACKGROUND: Posterior keratoconus is a rare corneal disorder characterized by a diffuse or localized protrusion of the posterior corneal surface into a thinning stroma. It is believed to be a congenital, nonprogressive condition. CASE REPORT: A case of bilateral circumscribed posterior keratoconus is presented. Diagnostic ocular signs include localized protrusion of the posterior corneal surface, normal anterior corneal surface, stromal thinning, and endothelial changes. However, anterior corneal contour reveals progressive steepening in this case. CONCLUSION: Posterior keratoconus is an unusual corneal anomaly with subtle clinical features. Recognition of these signs is essential in the diagnostic and management processes.
Subject(s)
Corneal Stroma/pathology , Endothelium, Corneal/pathology , Keratoconus/diagnosis , Contact Lenses , Corneal Topography , Diagnosis, Differential , Eyeglasses , Female , Humans , Keratoconus/congenital , Keratoconus/therapy , Middle Aged , Prescriptions , Visual AcuityABSTRACT
A 16-year-old girl with bilateral congenital posterior keratoconus of the localized type had corneal transplantation performed on one eye. Around the scarred central corneal cone there was a ring of Descemet's membrane with large knob-like excrescences. A small anterior subcapsular cataract was also present in this eye. The pattern of corneal scarring, as seen by electron microscopy, suggested an iridocorneal or iridocorneolenticular adhesion present at the 8- to 20-mm embryonic stage. Associated systemic defects, which could be dated to the same period, were median facial clefting and severe genitourinary abnormalities. Several external features, such as short stature, abnormal gait, broad nose, and upward displacement of the lateral canthi, were similar to those in the Haney-Falls syndrome of familial posterior keratoconus. No appreciable chromosomal abnormalities were found.
