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1.
J Theor Biol ; 585: 111781, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38432504

ABSTRACT

This paper aims to present a comprehensive framework for coupling tumor-bone remodeling processes in a 2-dimensional geometry. This is achieved by introducing a bio-inspired damage that represents the growing tumor, which subsequently affects the main populations involved in the remodeling process, namely, osteoclasts, osteoblasts, and bone tissue. The model is constructed using a set of differential equations based on the Komarova's and Ayati's models, modified to incorporate the bio-inspired damage that may result in tumor mass formation. Three distinct models were developed. The first two models are based on the Komarova's governing equations, with one demonstrating an osteolytic behavior and the second one an osteoblastic model. The third model is a variation of Ayati's model, where the bio-inspired damage is induced through the paracrine and autocrine parameters, exhibiting an osteolytic behavior. The obtained results are consistent with existing literature, leading us to believe that our in-silico experiments will serve as a cornerstone for paving the way towards targeted interventions and personalized treatment strategies, ultimately improving the quality of life for those affected by these conditions.


Subject(s)
Neoplasms , Quality of Life , Humans , Osteoclasts , Osteoblasts , Bone and Bones , Bone Remodeling
2.
Cancer Sci ; 107(11): 1667-1676, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27581340

ABSTRACT

Fibroblast growth factor receptor (FGFR) gene alterations are relatively frequent in lung squamous cell carcinoma (LSCC) and are a potential targets for therapy with FGFR inhibitors. However, little is known regarding the clinicopathologic features associated with FGFR alterations. The angiokinase inhibitor nintedanib has shown promising activity in clinical trials for non-small cell lung cancer. We have now applied next-generation sequencing (NGS) to characterize FGFR alterations in LSCC patients as well as examined the antitumor activity of nintedanib in LSCC cell lines positive for FGFR1 copy number gain (CNG). The effects of nintedanib on the proliferation of and FGFR signaling in LSCC cell lines were examined in vitro, and its effects on tumor formation were examined in vivo. A total of 75 clinical LSCC specimens were screened for FGFR alterations by NGS. Nintedanib inhibited the proliferation of FGFR1 CNG-positive LSCC cell lines in association with attenuation of the FGFR1-ERK signaling pathway in vitro and in vivo. FGFR1 CNG (10.7%), FGFR1 mutation (2.7%), FGFR2 mutation (2.7%), FGFR4 mutation (5.3%), and FGFR3 fusion (1.3%) were detected in LSCC specimens by NGS. Clinicopathologic features did not differ between LSCC patients positive or negative for FGFR alterations. However, among the 36 patients with disease recurrence after surgery, prognosis was significantly worse for those harboring FGFR alterations. Screening for FGFR alterations by NGS warrants further study as a means to identify patients with LSCC recurrence after surgery who might benefit from nintedanib therapy.


Subject(s)
Carcinoma, Squamous Cell/genetics , Indoles/pharmacology , Indoles/therapeutic use , Lung Neoplasms/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Receptor, Fibroblast Growth Factor, Type 4/genetics , Animals , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Cell Proliferation/drug effects , DNA Copy Number Variations/genetics , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice , Molecular Targeted Therapy , Mutant Proteins/genetics , Neoplasm Recurrence, Local , Survival Analysis , Xenograft Model Antitumor Assays
3.
Am J Case Rep ; 14: 354-8, 2013.
Article in English | MEDLINE | ID: mdl-24046802

ABSTRACT

PATIENT: Female, 54 FINAL DIAGNOSIS: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly MEDICATION: - Clinical Procedure: - Specialty: Transplantology • Critical Care Medicine. OBJECTIVE: Unusual clinical course. BACKGROUND: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the "piggyback" technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. CASE REPORT: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. CONCLUSIONS: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications.

4.
Int J Urol ; 17(12): 989-95, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20946473

ABSTRACT

OBJECTIVES: Renal ischemia-reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti-oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model. METHODS: Twenty-four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr. RESULTS: Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI-induced damage in kidneys from carvedilol-treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8-hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol. CONCLUSIONS: Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.


Subject(s)
Antihypertensive Agents/pharmacology , Carbazoles/pharmacology , Kidney Tubules/drug effects , Oxidative Stress/drug effects , Propanolamines/pharmacology , Renal Insufficiency/prevention & control , Reperfusion Injury/drug therapy , 8-Hydroxy-2'-Deoxyguanosine , Animals , Apoptosis/drug effects , Carvedilol , Creatinine/blood , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Disease Models, Animal , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Kidney Tubules/cytology , Kidney Tubules/metabolism , Male , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Superoxide Dismutase/metabolism
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