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A new rat model of bone cancer pain produced by rat breast cancer cells implantation of the shaft of femur at the third trochanter level.

ABSTRACT: Bone cancer pain remains one of the most challenging cancer pains to fully control. In order to clarify bone cancer pain mechanisms and examine treatments, animal models mimicking the human condition are required. In our model of Walker 256 tumor cells implantation of the shaft of femur at the third trochanter level, the anatomical structure is relatively simple and the drilled hole is vertical and in the cortical bone only 1-2 mm in depth without injury of the distal femur. Pain behaviors and tumor growth were observed for 21 days. And neurochemical changes were further investigated in this model. The results showed that cancer-bearing rats demonstrated a decreased limb use score from day 14, an increased spontaneous flinching and guarding times from day 7 and a decreased withdrawal threshold from day 6. The tumor infiltration of bone was monitored by MRI and further verified by histological examination. C-fos and the capsaicin receptor (TRPV1) positive neurons were more expressed in cancer-bearing rats and the substance P expression has no difference, suggesting that neurons were activated in the model. Our animal model demonstrated time-dependent tumor growth and pain behaviors and will be a novel animal model of bone cancer pain in the future.

SUBMITTER: Gui Q

PROVIDER: S-EPMC3572001 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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A new rat model of bone cancer pain produced by rat breast cancer cells implantation of the shaft of femur at the third trochanter level.

Gui Qi Q Xu Chengcheng C Zhuang Liang L Xia Shu S Chen Yu Y Peng Ping P Yu Shiying S

Cancer biology & therapy 20121219 2

Bone cancer pain remains one of the most challenging cancer pains to fully control. In order to clarify bone cancer pain mechanisms and examine treatments, animal models mimicking the human condition are required. In our model of Walker 256 tumor cells implantation of the shaft of femur at the third trochanter level, the anatomical structure is relatively simple and the drilled hole is vertical and in the cortical bone only 1-2 mm in depth without injury of the distal femur. Pain behaviors and t ...[more]

PMID: 23254954

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Project description:BackgroundThe purpose of this population-based registry study was to analyze both birth-related femur and humerus shaft fractures and diagnosed later in infancy, as regards incidence, perinatal characteristics, other diagnoses, and reported accidents.MethodsChildren born in 1997-2014, diagnosed with a femur or humerus shaft fracture before age 1 year, were identified in the Swedish Health Registries. Rate of birth fractures were estimated by combining femur and humerus shaft fractures coded as birth-related with femur and humerus shaft fractures diagnosed during day 1-7 without registered trauma or abuse. Incidence was computed by comparing infants with femur or humerus shaft fractures to the total at-risk population.ResultsThe incidence for birth-related femur shaft fractures was 0.024 per 1000 children (n = 45) and that for birth-related humerus shaft fractures was 0.101 per 1000 children (n = 188). The incidence was 0.154 per 1000 children for later femur shaft fractures (n = 287) and 0.073 per 1000 children for later humerus shaft fractures (n = 142). Birth-related femur shaft fracture was associated with shoulder dystocia, cesarean, multiple birth, breech, preterm, and small-for-gestational age, while humerus shaft fracture was associated with maternal obesity, dystocic labor, shoulder dystocia, vacuum-assisted delivery, male sex, multiple birth, breech, preterm, large-for-gestational age, birth weight > 4000 g, and injury of brachial plexus. A bone fragility diagnosis was recorded in 5% of those with birth-related or later femur shaft fractures. Among infants with birth-related humerus shaft fractures, 1% had a bone fragility diagnosis; the figure for later fractures was 6%. Maltreatment diagnosis was associated with later fractures of both types, especially among those aged < 6 months, where approximately 20% (femur) and 14% (humerus) of cases, respectively, were associated with abuse. Fall accidents were reported in 73 and 56% among those with later femur and humerus shaft fractures, respectively.ConclusionThis study provides data on epidemiology, birth, parental characteristics, and reported accidents in relation to femur and humerus shaft fractures during infancy. Few children had a bone fragility diagnosis. Fall accidents were the main contributor to femur or humerus shaft fracture during infancy; however, the proportion of fractures attributed to maltreatment was high in children under 6 months.

Project description:The pathophysiology of the osteomalacia in X-linked hypophosphatemia is uncertain. In this project, genomic DNA microarrays were used to identify novel genes with abnormal mRNA expression levels in mice with the dominant Hyp mutation of the Phex gene. Femoral shafts from five-week-old C57BL/6J mice, male and female, normal and Hyp (hemizygous male and heterozygous female), were flushed with saline to remove the marrow. RNA was extracted from each bone, pooled between two mice for each array, processed to cRNA, and hybridized to Affymetrix Mouse 430 2.0 GeneChip microarrays with probe sets for 45,101 genes. Twenty microarrays (40 mice) were done with 5 arrays for each treatment group (normal male, Hyp male, normal female and Hyp female). For each gene, factorial analysis of variance was performed for the main effects of genotype (normal vs. Hyp), sex (male vs. female), and genotype-by-sex interaction. The mRNA levels for 54 % of the genes on each array were scored as present. At P < 0.01, 2,635 genes were significant for genotype, 1,488 for sex, and 509 for genotype-by-sex interaction. There were two probes sets for the Phex gene. Probe 1450445, at the 3’ end of the coding sequence, was low in normal samples (246 ± 37 (10), mean ± SEM (n)) and absent in Hyp samples. Probe 1421979, at the far 3’ end of the untranslated region of the cDNA, 3,000 base pairs from the coding sequence, was high in normal mice (3,915 ± 315 (10); 8x brighter than the average gene), undetectable in Hyp males, and 725 ± 93 (5) in Hyp females. Both probe sets were scored as absent in kidney tissue. In Hyp bone, male and female, there was significant down-regulation of markers of osteoblasts and bone matrix synthesis with significant up-regulation of markers of blood vessel formation and cytoskeleton. No prominent skeletal gene was up-regulated in Hyp to attempt to compensate for the low skeletal mineralization. The genes with significant genotype-by-sex interaction did not show a marked fold difference between male and female Hyp mice. In conclusion, male and female Hyp mice showed similar depression of mRNA levels of genes related to bone synthesis in the femoral shaft. There was a high signal level from probes for a sequence in the 3’ untranslated region of the Phex gene of normal, but not Hyp, mice, suggesting the need for further study of the molecular organization of this gene. Keywords: 2x2 factorial design with complete blocks

Project description:IntroductionPain management in patients with hip fractures can be challenging. Poor pain control is associated with reduced mobility and increased morbidity. Inadequate analgesia in patients with dementia is a concern. After using several different alternatives, transdermal buprenorphine was chosen as a standardised approach for analgesia in patients with fragility fracture in our hospital. There is limited evidence on the use of buprenorphine in this population. Our aim was to investigate the safety and effectiveness of transdermal buprenorphine in patients with hip fractures.MethodsA review of consecutive patients presenting with a hip fracture from June 2018 to December 2018 was conducted using medical records. Our primary outcome was the incidence of complications as a consequence of transdermal buprenorphine. Our secondary outcome was adequate analgesia measured by reviewing the requirement for analgesia during the first week following the patient's admission. Analgesia demands were considered adequate if patients required less than 20 mg of oral morphine in total during the first week following injury.ResultsIn total, 148 patients presented with a hip fracture during the study period. 128 patients had documented evidence of buprenorphine patch application. Complete data was available for the primary outcome of complications in all cases. Data was available for the secondary outcome in 124 patients. Buprenorphine was discontinued in 24 patients (19%), most commonly due to due to concerns about contribution to hypoactive delirium (9%), and when strong analgesia was no longer required (4%). There were no severe complications. Adequate analgesia was achieved using this regime in 68% patients. 38 patients (32%) required more than 20 mg of oral morphine sulphate solution in the first week post-admission.ConclusionThis series suggests that transdermal buprenorphine is safe and effective in the management of pain following a neck of femur fragility fracture.

Project description:BackgroundComplex proximal femoral deformities, including an elevated greater trochanter, short femoral neck, and aspherical head-neck junction, often result in pain and impaired hip function resulting from intra-/extraarticular impingement. Relative femoral neck lengthening may address these deformities, but mid-term results of this approach have not been widely reported.Questions/purposesDo patients who have undergone relative femoral neck lengthening show (1) less hip pain and greater function; (2) improved radiographic parameters; (3) significant complications requiring subsequent surgery; and (4) progression of osteoarthrosis (OA) or conversion to total hip arthroplasty (THA) at mid-term followup?MethodsWe retrospectively reviewed 40 patients (41 hips) with isolated relative femoral neck lengthening between 1998 and 2006 with sequelae of Legg-Calvé-Perthes disease (38 hips [93%]), slipped capital femoral epiphysis (two hips [5%]), and postseptic arthritis (one hip [2%]). During this time, the general indications for this procedure included a high-riding greater trochanter with a short femoral neck with abductor weakness and symptomatic intra-/extraarticular impingement. Mean patient followup was 8 years (range, 5-13 years), and complete followup was available in 38 patients (39 hips [95%]). We evaluated pain and function with the impingement test, limp, abductor force, Merle d'Aubigné-Postel score, and range of motion. Radiographic parameters included trochanteric height, alpha angle, and progression of OA. Subsequent surgeries, complications, and conversion to THA were summarized.ResultsThe proportion of positive anterior impingement tests decreased from 93% (38 of 41 hips) preoperatively to 49% (17 of 35 hips) at latest followup (p = 0.002); the proportion of limp decreased from 76% (31 of 41 hips) to 9% (three of 35 hips; p < 0.001); the proportion of normal abductor strength increased from 17% (seven of 41 hips) to 91% (32 of 35 hips; p < 0.001); mean Merle d'Aubigné-Postel score increased from 14 ± 1.7 (range, 9-17) to 17 ± 1.5 (range, 13-18; p < 0.001); mean internal rotation increased to 25° ± 15° (range, 0°-60°; p = 0.045), external rotation to 32° ± 14° (range, 5°-70°; p = 0.013), and abduction to 37° ± 13° (range, 10°-50°; p = 0.004). Eighty percent of hips (33 of 41 hips) showed normal trochanteric height; alpha angle improved to 42° ± 10° (range, 27°-90°). Two hips (5%) had subsequent surgeries as a result of lack of containment; four of 41 hips (10%) had complications resulting in reoperation. Fourteen of 35 hips (40%) showed progression of OA; four of 40 hips (10%) converted to THA.ConclusionsRelative femoral neck lengthening in hips with combined intra- and extraarticular impingement results in reduced pain, improved function, and improved radiographic parameters of the proximal femur. Although lack of long-term complications is gratifying, progression of OA was not prevented and remains an area for future research.

Dataset Information

A new rat model of bone cancer pain produced by rat breast cancer cells implantation of the shaft of femur at the third trochanter level.

Publications

A new rat model of bone cancer pain produced by rat breast cancer cells implantation of the shaft of femur at the third trochanter level.

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