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1.
Ann Vasc Surg ; 98: 164-172, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37516427

RESUMEN

BACKGROUND: Acute aortic occlusion (AAO) is a morbid diagnosis in which mortality correlates with severity of ischemia on presentation. Visceral ischemia (VI) is challenging to diagnose and its presentation as a consequence of AAO is not well-studied. We aim to identify characteristics associated with VI in AAO to facilitate diagnosis. METHODS: Patients diagnosed with AAO who underwent revascularization were identified retrospectively from institutional records (2006-2020). The primary outcome was the development of VI (intra-abdominal ischemia). Univariate analysis was used to compare demographic, exam, imaging, and intraoperative variables between patients with and without VI in the setting of AAO. RESULTS: Ninety-one patients were included. The prevalence of VI was 20.9%. Preoperative comorbidities, time to revascularization, and operative approach did not differ between patients with and without VI. Patients with VI more frequently were transferred from outside institutions (100% vs. 53%, P = 0.02), presented with advanced acute limb ischemia (Rutherford III 36.9% vs. 7.5%, P < 0.01), and had elevated preoperative serum lactate (4.31 vs. 2.41 mmol/L, P < 0.01). VI patients had an increased occurrence of bilateral internal iliac artery (IIA) occlusion (47.4% vs. 18.1%, P = 0.01). Unilateral IIA occlusion, level of aortic occlusion, and patency of inferior mesenteric arteries were not associated with VI. Patients with VI had worse postoperative outcomes. In particular, VI conferred significant risk of mortality (odds ratio 5.45, P < 0.01). CONCLUSIONS: Visceral ischemia is a common consequence of AAO. Elevated lactate, bilateral IIA occlusion, and advanced acute limb ischemia (ALI) should increase clinical suspicion for concomitant VI with AAO and may facilitate earlier diagnosis to improve outcomes.


Asunto(s)
Enfermedades de la Aorta , Arteriopatías Oclusivas , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/epidemiología , Arteriopatías Oclusivas/cirugía , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/epidemiología , Enfermedades de la Aorta/cirugía , Isquemia/diagnóstico por imagen , Isquemia/epidemiología , Isquemia/cirugía , Lactatos
2.
J Surg Oncol ; 125(3): 475-483, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34705273

RESUMEN

BACKGROUND: Current guidelines favor transabdominal radical resection (RR) over transanal local excision (TAX) followed by adjuvant therapy (TAXa) for pT1N0 rectal tumors with high-risk features. Comparison of oncologic outcomes between these approaches is limited, although the former is associated with increased postoperative morbidity. We hypothesize that such treatment strategies result in equivalent long-term survival. METHODS: A retrospective cohort study was conducted using the National Cancer Database (2010-2016) to identify patients with pT1N0 rectal adenocarcinoma with high-risk features who underwent TAX or RR for curative intent. The primary outcome was 5-year overall survival (OS), evaluated with log-rank and Cox-proportional hazards testing. RESULTS: A total of 1159 patients (age 67.4 ± 12.9 years; 56.6% male; 83.3% White) met study criteria, of which 1009 (87.1%) underwent RR and 150 (12.9%) underwent TAXa. Patients undergoing TAXa had shorter lengths of stay (RR = 6.5 days, TAXa = 2.7 days, p < 0.001). The 5-year OS was equivalent between groups. TAX without adjuvant therapy was associated with an increased risk of mortality (hazard ratio 1.81, 95% confidence interval 1.17-2.78, p = 0.01). CONCLUSIONS: This is the largest study to demonstrate equivalent 5-year OS between TAXa and RR for T1N0 rectal cancer with high-risk features. These findings may guide the development of prospective, randomized trials and influence changes in practice recommendations for early-stage rectal cancer.


Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/terapia , Proctectomía , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adenocarcinoma/mortalidad , Adulto , Anciano , Terapia Combinada , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
5.
J Clin Anesth ; 49: 46-52, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29890381

RESUMEN

STUDY OBJECTIVE: Investigate the use of a postoperative continuous adductor canal block (cACB) after epidural analgesia to decreases opioid consumption and improve visual analog scale (VAS) scores compared to a sham catheter. DESIGN: Double-blinded randomized placebo-controlled trial. SETTING: Inpatient setting in tertiary care teaching hospital with outpatient follow-up. PATIENTS: One-hundred and sixty-five subjects (cACB n = 82 and sham catheter n = 83) with end-stage degenerative joint disease undergoing elective unilateral total knee arthroplasty. INTERVENTIONS: Patients were block randomized to receive a cACB or sham catheter. An epidural catheter was placed preoperatively and discontinued on postoperative day 1. Patients then received a cACB with bupivacaine or sham catheter which remained for the duration of the hospitalization. MEASUREMENTS: Primary outcome was total opioid consumption. Secondary outcomes included VAS scores, knee range of motion (ROM), ambulation distance, and WOMAC scores. MAIN RESULTS: Seventy patients completed the study (cACB n = 38 and sham catheter n = 32). Compared to sham catheter, in the first 20 h after placement of a cACB, patients used 22.5 mg less opioid (95% CI: -43.1 to -1.94 mg, P = 0.03). VAS score area under the curve decreased 7.8 mm (95% CI: -15.5 - -0.058 mm, P = 0.04) with a cACB. At 3-week follow-up, WOMAC scores were significantly improved with the cACB with a mean difference of 8.72 (95% CI: -17.3 to -0.11, P = 0.04). There were no statistically significant differences in secondary outcomes on postoperative day 2. Paired outcomes at 6 weeks compared to baseline ROM, showed significant improvement in knee ROM with a cACB (mean difference 11.77°, 95% CI: 3.1-20.5°, P = 0.01). CONCLUSION: A postoperative cACB after total knee arthroplasty significantly reduces total opioid consumption and pain scores compared to sham catheter. Ambulatory ability was not affected and patients recovered function earlier. ClinicalTrials.govNCT02121392.


Asunto(s)
Anestésicos Locales/administración & dosificación , Artroplastia de Reemplazo de Rodilla/efectos adversos , Nervio Femoral/efectos de los fármacos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/terapia , Anciano , Analgésicos Opioides/administración & dosificación , Bupivacaína/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Articulación de la Rodilla/fisiología , Articulación de la Rodilla/cirugía , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Periodo Posoperatorio , Rango del Movimiento Articular , Resultado del Tratamiento
6.
Surgery ; 161(1): 62-69, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27866715

RESUMEN

BACKGROUND: Normohormonal primary hyperparathyroidism presents diagnostic and intraoperative challenges, and current literature is conflicting about management. We aim to better define normohormonal primary hyperparathyroidism in order to improve the care for these patients. METHODS: In the study, 516 consecutive patients undergoing parathyroidectomy for primary hyperparathyroidism were divided into 2 groups: classic primary hyperparathyroidism (classic primary hyperparathyroidism, increased serum levels of calcium, and parathyroid hormone) and normohormonal primary hyperparathyroidism (hypercalcemia, normal serum levels of parathyroid hormone). We evaluated inter-group differences in presentation, gland weight, pathology, and complications. RESULTS: The normohormonal primary hyperparathyroidism group was comprised of 116 (22.5%) patients. Mean serum levels of parathyroid hormone and calcium were 62.1 pg/mL ± 10.1 and 10.6 mg/dL ± 0.63 in normohormonal primary hyperparathyroidism, and 142 ± 89.0pg/mL and 11.0 ± 0.88 (both P < .01) for classic primary hyperparathyroidism. Nephrolithiasis was more common in normohormonal primary hyperparathyroidism. Multigland hyperplasia was more common in normohormonal primary hyperparathyroidism 23 (19.8%) vs 44 (11%; P = .04). Concordant imaging studies were less likely in normohormonal primary hyperparathyroidism (82 [73.2%] vs 337 [87.1%; P < .01]), had a lesser total gland weight (531.8 mg ± 680.0 vs 1,039.6 mg ± 1,237.3; P < .01), and lesser 2-week parathyroid hormone (32.5 pg/mL ± 18.95 vs 41.0 pg/mL ± 27.8; P = .01). There was no difference in hypoparathyroidism (parathyroid hormone <15 pg/mL; P = .93) at 2 weeks postoperatively. CONCLUSION: Normohormonal primary hyperparathyroidism represents 22.5% of our primary hyperparathyroidism population, which is greater than reported previously. It is a distinct disease process from classic primary hyperparathyroidism in presentation, imaging, and operative findings. More hyperplasia and a lesser gland weight make it challenging to resect the ideal amount of tissue. Studies with long-term follow-up are needed to determine optimal operative management.


Asunto(s)
Calcio/sangre , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/cirugía , Hormona Paratiroidea/sangre , Paratiroidectomía/métodos , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hiperparatiroidismo Primario/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Paratiroidectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
7.
Genes Dis ; 3(1): 56-71, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27239485

RESUMEN

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects. This strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials, osteoblastic stem cells, as well as osteoinductive growth factors and small molecules. One of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone regeneration. These properties include osteoconduction, osetoinduction, biocompatibility, biodegradability, vascularization, and progenitor cell retention. This review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

8.
Genes Dis ; 3(1): 11-40, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27077077

RESUMEN

Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities, including cell proliferation, calcium homeostasis, and cell polarity. The role of Wnt signaling in control of cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway, which is the best characterized among the multiple Wnt signaling branches. The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway, as many new components of Wnt signaling have been identified and linked to signaling regulation, stem cell functions, and adult tissue homeostasis. Additionally, a substantial body of evidence links Wnt signaling to tumorigenesis of many cancer types and implicates it in the development of cancer drug resistance. Thus, a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy. This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease. We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness, tumorigenesis, and cancer drug resistance. Ultimately, we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.

9.
Biomed Mater ; 11(2): 025021, 2016 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-27097687

RESUMEN

Successful bone tissue engineering requires at the minimum sufficient osteoblast progenitors, efficient osteoinductive factors, and biocompatible scaffolding materials. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we investigated the potential use of a biodegradable citrate-based thermosensitive macromolecule, poly(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin (PPCNG) as a scaffold for the delivery of BMP9-stimulated MSCs to promote localized bone formation. The addition of gelatin to PPCN effectively enhanced the cell adhesion and survival properties of MSCs entrapped within the gel in 3D culture. Using the BMP9-transduced MSC line immortalized mouse embryonic fibroblasts (iMEFs), we found that PPCNG facilitated BMP9-induced osteogenic differentiation of iMEFs in vivo and promoted the formation of well-ossified and vascularized trabecular bone-like structures in a mouse model of ectopic bone formation. Histologic evaluation revealed that vascularization of the bony masses retrieved from the iMEFs + PPCNG group was significantly more pronounced than that of the direct cell injection group. Accordingly, vascular endothelial growth factor (VEGF) expression was shown to be significantly higher in the bony masses recovered from the iMEFs + PPCNG group. Taken together, our results suggest that PPCNG may serve as a novel biodegradable and injectable scaffold and carrier for gene and cell-based bone tissue engineering.


Asunto(s)
Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Osteogénesis/fisiología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Resinas Acrílicas/química , Animales , Materiales Biocompatibles/química , Adhesión Celular , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular , Citratos/química , Femenino , Gelatina/química , Factor 2 de Diferenciación de Crecimiento , Factores de Diferenciación de Crecimiento/genética , Factores de Diferenciación de Crecimiento/fisiología , Células HEK293 , Humanos , Ensayo de Materiales , Melanoma Experimental , Ratones , Ratones Desnudos , Polietilenglicoles/química , Temperatura , Andamios del Tejido/química , Transducción Genética
10.
Tissue Eng Part C Methods ; 22(3): 280-9, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26959762

RESUMEN

Investigating the cellular processes underlying tendon healing can allow researchers to improve long-term outcomes after injury. However, conducting meaningful studies to uncover the injury healing mechanism at cellular and molecular levels remains challenging. This is due to the inherent difficulty in isolating, culturing, and expanding sufficient primary tenocytes, due to their limited proliferative capacity and short lifespan. In this study, we sought to establish a novel line of immortalized mouse Achilles tenocytes (iMATs) with primary tenocyte properties, but increased proliferative capacity suitable for extensive in vitro experimentation. We show that isolated primary mouse Achilles tenocytes (pMATs) can be effectively immortalized using a piggyBac transposon expressing SV40 large T antigen flanked by FLP recombination target site (FRT). The resulting iMATs exhibit markedly greater proliferation and survival, which can be reversed with FLP recombinase. Furthermore, iMATs express the same set of tendon-specific markers as that of primary cells, although in lower levels, and respond similarly to exogenous stimulation with bone morphogenetic protein 13 (BMP13) as has been previously reported with pMATs. Taken together, our results suggest that iMATs acquire long-term proliferative capacity while maintaining tenogenic properties. We believe that iMATs are a suitable model for studying not only the native cellular processes involved in injury and healing, but also potential therapeutic agents that may augment the stability of tendon repair.


Asunto(s)
Tendón Calcáneo/citología , Tenocitos/citología , Animales , Antígenos Transformadores de Poliomavirus/metabolismo , Biomarcadores/metabolismo , Proteínas Morfogenéticas Óseas/farmacología , Línea Celular Transformada , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN Nucleotidiltransferasas/metabolismo , Células HEK293 , Humanos , Ratones , Células 3T3 NIH , Reacción en Cadena en Tiempo Real de la Polimerasa , Tenocitos/efectos de los fármacos
11.
Lab Invest ; 96(2): 116-36, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26618721

RESUMEN

The canonical WNT/ß-catenin signaling pathway governs a myriad of biological processes underlying the development and maintenance of adult tissue homeostasis, including regulation of stem cell self-renewal, cell proliferation, differentiation, and apoptosis. WNTs are secreted lipid-modified glycoproteins that act as short-range ligands to activate receptor-mediated signaling pathways. The hallmark of the canonical pathway is the activation of ß-catenin-mediated transcriptional activity. Canonical WNTs control the ß-catenin dynamics as the cytoplasmic level of ß-catenin is tightly regulated via phosphorylation by the 'destruction complex', consisting of glycogen synthase kinase 3ß (GSK3ß), casein kinase 1α (CK1α), the scaffold protein AXIN, and the tumor suppressor adenomatous polyposis coli (APC). Aberrant regulation of this signaling cascade is associated with varieties of human diseases, especially cancers. Over the past decade, significant progress has been made in understanding the mechanisms of canonical WNT signaling. In this review, we focus on the current understanding of WNT signaling at the extracellular, cytoplasmic membrane, and intracellular/nuclear levels, including the emerging knowledge of cross-talk with other pathways. Recent progresses in developing novel WNT pathway-targeted therapies will also be reviewed. Thus, this review is intended to serve as a refresher of the current understanding about the physiologic and pathogenic roles of WNT/ß-catenin signaling pathway, and to outline potential therapeutic opportunities by targeting the canonical WNT pathway.


Asunto(s)
Carcinogénesis , Neoplasias/tratamiento farmacológico , Células Madre , Proteínas Wnt , Vía de Señalización Wnt , Animales , Descubrimiento de Drogas , Humanos , Ratones
12.
Genes Dis ; 3(1): 3-6, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28491932

RESUMEN

Two recent studies provide intriguing evidence that challenges the role of the epithelial-mesenchymal transition (EMT) as a critical mediator of cancer metastasis, while revealing an unexpected role in cancer drug resistance.1,2 While these findings may not settle the EMT's role in metastasis, these studies suggest that targeting the EMT may inhibit both cancer metastasis and chemoresistance.

13.
Sci Rep ; 5: 17523, 2015 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-26639992

RESUMEN

Ovarian cancer is the most lethal gynecologic malignancy with an overall cure rate of merely 30%. Most patients experience recurrence within 12-24 months of cure and die of progressively chemotherapy-resistant disease. Thus, more effective anti-ovarian cancer therapies are needed. Here, we investigate the possibility of repurposing antibiotic monensin as an anti-ovarian cancer agent. We demonstrate that monensin effectively inhibits cell proliferation, migration and cell cycle progression, and induces apoptosis of human ovarian cancer cells. Monensin suppresses multiple cancer-related pathways including Elk1/SRF, AP1, NFκB and STAT, and reduces EGFR expression in ovarian cancer cells. Monensin acts synergistically with EGFR inhibitors and oxaliplatin to inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Xenograft studies confirm that monensin effectively inhibits tumor growth by suppressing cell proliferation through targeting EGFR signaling. Our results suggest monensin may be repurposed as an anti-ovarian cancer agent although further preclinical and clinical studies are needed.


Asunto(s)
Antibacterianos/farmacología , Receptores ErbB/antagonistas & inhibidores , Monensina/farmacología , Compuestos Organoplatinos/farmacología , Neoplasias Ováricas/patología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Femenino , Células HEK293 , Humanos , Oxaliplatino , Inhibidores de Proteínas Quinasas/farmacología , Receptor IGF Tipo 1/metabolismo , Transducción de Señal/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Cell Physiol Biochem ; 37(6): 2375-92, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26646427

RESUMEN

BACKGROUND/AIMS: Although osteosarcoma (OS) is the most common primary malignancy of bone, its molecular pathogenesis remains to be fully understood. We previously found the calcium-binding protein S100A6 was expressed in ∼80% of the analyzed OS primary and/or metastatic tumor samples. Here, we investigate the role of S100A6 in OS growth and progression. METHODS: S100A6 expression was assessed by qPCR and Western blotting. Overexpression or knockdown of S100A6 was carried out to determine S100A6's effect on proliferation, cell cycle, apoptosis, tumor growth, and osteogenic differentiation. RESULTS: S100A6 expression was readily detected in human OS cell lines. Exogenous S100A6 expression promoted cell proliferation in vitro and tumor growth in an orthotopic xenograft model of human OS. S100A6 overexpression reduced the numbers of OS cells in G1 phase and increased viable cells under serum starvation condition. Conversely, silencing S100A6 expression induced the production of cleaved caspase 3, and increased early stage apoptosis. S100A6 knockdown increased osteogenic differentiation activity of mesenchymal stem cells, while S100A6 overexpression inhibited osteogenic differentiation. BMP9-induced bone formation was augmented by S100A6 knockdown. CONCLUSION: Our findings strongly suggest that S100A6 may promote OS cell proliferation and OS tumor growth at least in part by facilitating cell cycle progression, preventing apoptosis, and inhibiting osteogenic differentiation. Thus, it is conceivable that targeting S100A6 may be exploited as a novel anti-OS therapy.


Asunto(s)
Proteínas de Ciclo Celular/fisiología , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Osteogénesis , Osteosarcoma/patología , Proteínas S100/fisiología , Animales , Línea Celular Tumoral , Xenoinjertos , Humanos , Ratones , Proteína A6 de Unión a Calcio de la Familia S100
15.
J Biomed Res ; 302015 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-26496981

RESUMEN

Osteosarcoma (OS) is a devastating illness with rapid rates of dissemination and a poor overall prognosis, despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens. Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets. Defects in mesenchymal stem cell differentiation, abnormal expression of oncogenes and tumor suppressors, and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes. As such, a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies. Born out of these and similar investigations, a variety of emerging therapies are now undergoing various phases of OS clinical testing. They broadly include angiogenesis inhibitors, drugs that act on the bone microenvironment, receptor tyrosine kinase inhibitors, immune system modulators, and other radio- or chemo-sensitizing agents. As new forms of drug delivery are being developed simultaneously, the possibility of targeting tumors locallywhile minimizing systemic toxicityis is seemingly more achievable now than ever. In this review, we not only summarize our current understanding of OS disease processes, but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

16.
Genes Dis ; 2(3): 219-221, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26491709

RESUMEN

Cancer death is usually caused by incurable drug-resistant and metastatic cancers. Although tremendous progress has been made in anticancer drug development during the past two decades, cancer medicine still faces unprecedented challenges associated with choosing effective treatments for individual patients. Three recent reports have offered encouraging approaches towards potentially personalized cancer drug selection.

17.
Genes Dis ; 2(1): 13-25, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25984556

RESUMEN

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies. There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy. By better understanding both the IGF-dependent and -independent mechanisms by which pathway members can influence drug sensitivity, we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy. This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance. We offer a brief overview of IGF signaling and its general role in neoplasia, and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy. Ultimately, our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

19.
Genes Dis ; 2(4): 307-327, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26835506

RESUMEN

Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature. Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue. Here, we review the current understanding of the most important biological regulators of chondrogenesis and their interactions, to provide insight into potential applications for cartilage tissue engineering. These include various signaling pathways, including: fibroblast growth factors (FGFs), transforming growth factor ß (TGF-ß)/bone morphogenic proteins (BMPs), Wnt/ß-catenin, Hedgehog, Notch, hypoxia, and angiogenic signaling pathways. Transcriptional and epigenetic regulation of chondrogenesis will also be discussed. Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering.

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