Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.
Topical timolol is not effective in the treatment of some superficial infantile hemangiomas (IHs). This is a prospective study aiming to investigate the predictors of treatment response of superficial IHs to topical timolol. Patients with superficial IHs were prescribed timolol 0.5% cream four times daily and followed up every 2-3 months until 1 year of age. IH thickness was objectively measured by ultrasound, and the proportional change was calculated as a regression rate. In total, 193 patients (211 lesions) were enrolled. Topical timolol was initiated at an average age of 3.1 (0-6) months for 7.4 (2-11) months. The average regression rate of all lesions was 41.8% (-137.5%-100%). Lesion thickness (p = 0.000) and patient age at initial treatment (p = 0.001) were major variables that predicted the treatment response. On average, an increase in lesion thickness of 1 mm decreased the regression rate by 22.1%, and lesions thicker than 1.9 mm were unlikely to respond (average regression rate = -0.27%). Available results did not show a significant effect of sex (p = 0.659), lesion size (p = 0.311), or location (p > 0.05) on regression. Treatment for superficial IHs should be individualized according to lesion thickness and patient age.
Objective
To investigate whether the combination of oral propranolol and topical 0.5% timolol maleate cream is more effective than oral propranolol alone for treating infantile hemangioma (IH).
Methods
From September 2015 to July 2016, 14 patients with proliferative IH, visited the infantile hemangioma outpatient clinic of the Department of Plastic and Reconstructive Surgery of Shanghai 9th People′s Hospital, were enrolled in this study. All patients took oral propranolol. Half of each IH lesion was treated with 0.5% timolol maleate cream. There were 5 male patients and 9 female patients, aged from 1.5 to 5.0 months. After 4 months of treatment, the color, size, extent, volume and the overall clinical outcomes of each lesion were measured, and the side effects were recorded. The therapeutic outcomes of oral propranolol alone and the combination of propranolol and timolol were analyzed and compared using Wilcoxon matched-pair signed-rank nonparametric tests.
Results
Both oral propranolol alone and oral propranolol combined with topical 0.5% timolol maleate cream were proved to effectively improve the regression of IH with minor side effects. The color VAS score of oral propranolol alone group was 6.92±2.63, while the combination group was 6.88±2.33 (Z=0.043, P=0.966). The volume VAS score of oral propranolol alone group was 6.94±2.00, while the combination group was 6.98±2.11(Z=-0.051, P=0.959).
Conclusions
Oral propranolol combined with topical application of 0.5% timolol maleate could not increase the efficacy in the treatment of IH, compared with oral propranolol alone in the short-term observation.
Key words:
Infantile hemangioma; Propranolol; Timolol
Growing evidence suggests that nutritional status and inflammation are associated with survival in various cancers. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and systemic inflammatory indexes (neutrophil/lymphocyte ratio [NLR], monocyte/lymphocyte ratio [MLR], and platelet/lymphocyte ratio [PLR]) in patients with stage IIB-III cervical cancer receiving radiotherapy.The ideal cutoff values for the PNI, GNRI, NLR, MLR, and PLR were 48.3, 97.04, 2.8, 0.41, and 186.67, respectively. Low PNI and GNRI scores were associated with poor OS and PFS. High NLR, MLR, and PLR also predicted inferior 5-year OS and PFS rates in patients with stage IIB-III cervical cancer. Multivariate Cox regression analysis identified tumor size, histological type, stage, number of metastatic lymph nodes, PNI, GNRI, NLR, PLR, and MLR as significant prognostic factors for OS and PFS.The current findings suggest that the PNI, GNRI, NLR, PLR, and MLR are essential parameters for predicting prognosis in patients with stage IIB-III cervical cancer receiving radiotherapy.
To recognize the indication of surgical reconstruction via the "direct entrance" surgical approach (superoanterior surgical approach) for congenital atresia of the external acoustic canal and malformations of the middle ear.A series of 53 ears operated on via the superoanterior surgical approach during 10 years from January 1988 to December 1997 was analyzed.The tympanic cavity was encountered without difficulty in 52 ears. Facial paralysis occurred postoperatively in one ear, which recovered after two months. The hearing improvement was observed in 45 ears (84.9%), of which 24 ears had hearing improvement greater than 30 dB and the air-bone conduction gap was within 15 dB (45.3%). A long-term (1-9 years) follow-up of 25 ears demonstrated that the hearing levels in 18 ears were kept unchanged. Postoperative stenosis of the canal occurred in one ear of a 2 years-old child.Based on the scanning images of the temporal bone by high-resolution computed tomography before the operation, the authors classified the bony structures of the paths of external acoustic canals into four types. Our results indicated that the selerotic and the diploetic paths of external acoustic cmeati could be indications for the "direct entrance" surgical approach, whereas the mixed type, either containing a little small cells or diploetic bone in sclerotic bone, might be suitable for this surgical approach also.
Local excision is an alternative to radical surgery that is indicated in patients with locally advanced rectal cancer (LARC) who have a good response to chemoradiotherapy (CRT). Regional lymph node status is a major uncertainty during local excision of LARC following CRT. We retrospectively reviewed clinicopathologic variables for 244 patients with LARC who were treated at our institute between December 2000 and December 2013 in order to identify independent predictors of regional lymph node metastasis. Multivariate analysis of the training sample demonstrated that histopathologic type, tumor size, and the presence of lymphovascular invasion were significant predictors of regional nodal metastasis. These variables were then incorporated into a scoring system in which the total scores were calculated based on the points assigned for each parameter. The area under the curve in the receiver operating characteristic analysis was 0.750, and the cutoff value for the total score to predict regional nodal metastasis was 7.5. The sensitivity of our system was 73.2% and the specificity was 69.4%. The sensitivity was 77.8% and the specificity was 51.2% when the scoring system was applied to the testing sample. Using this system, we could accurately predict regional nodal metastases in LARC patients following CRT, which may be useful for stratifying patients in clinical trials and selecting potential candidates for organ-sparing surgery following CRT for LARC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)