Undifferentiated spindle‐cell sarcoma (USCS) is a recalcitrant cancer, resistant to conventional chemotherapy. A patient with high‐grade USCS from a striated muscle was implanted orthotopically in ...the right biceps femoris muscle of mice to establish a patient‐derived orthotopic xenograft (PDOX) model. The PDOX models were randomized into the following groups when tumor volume reached 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal i.p. injection, weekly, for 2 weeks); G3, temozolomide (TEM) (25 mg/kg, p.o., daily, for 14 days). Tumor size and body weight were measured with calipers and a digital balance twice a week. TEM significantly inhibited tumor volume growth compared to the untreated control and the DOX‐treated group on day 14 after treatment initiation: control (G1): 343 ± 78 mm3; DOX (G2): 308 ± 31 mm3, P = 0.272; TEM (G3): 85 ± 21 mm3, P < 0.0001. TEM significantly regressed the tumor volume compared to day 0 (P = 0.019). There were no animal deaths in any group. The body weight of treated mice was not significantly different in any group. Tumors treated with DOX were comprised of spindle‐shaped viable cells without apparent necrosis or inflammatory changes. In contrast, tumors treated with TEM showed extensive tumor necrosis. The present study demonstrates the potential power of matching the patient with an effective drug and saving the patient needless toxicity from ineffective drugs.
USCS PDOX histology in treated and untreated tumor. A, Hematoxylin and eosin (H&E)‐stained section of the original patient's tumor. B, Untreated PDOX tumor. C, PDOX tumor treated with DOX. D, PDOX tumor treated with TEM. Scale bars: 80 µm.
This evidence-based guideline intends to support patients, clinicians, and others regarding interventions and processes to support patient adherence to oral anticancer medications (OAMs).
A panel of ...healthcare professionals and patient representatives developed a clinical practice guideline to support patients taking OAMs. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and criteria for trustworthy guidelines were followed. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. A quantitative or narrative synthesis of the evidence was completed. Certainty of the evidence was assessed using GRADE.
The panel agreed on recommendations and suggested an adherence risk assessment, education addressing adherence, ongoing assessment, proactive follow-up, coaching, and motivational interviewing in addition to usual care. The panel suggested the implementation of a structured OAM program.
As cancer treatment shifts from clinic to home settings, interventions and programs to support patients on OAMs are needed.
Purpose This study examined the association between gender role orientation (GRO) and health-related quality of life (HRQOL) in youth, and how this relationship may differ between males and females ...as well as among African-American, White, and Hispanic individuals. GRO has been reported to influence serious health outcomes including cancer, heart disease, mental illness, and mortality rates. However, few studies have examined the link between GRO and health outcomes for children, even though gender identity is formed in childhood. Methods Data were examined from 4824 participants in the Healthy PassagesTM project, a population-based survey of fifth-grade children in three US metropolitan areas. Children reported their own HRQOL using the PedsQL and degree of female, male, and androgynous GRO using the Children's Sex Role Inventory. Results Based on structural equations analysis, male GRO was positively associated with HRQOL for all racial/ ethnic groups, regardless of sex, whereas female GRO was associated with better HRQOL for Hispanic and White females and poorer HRQOL for Hispanic males. Androgynous GRO was associated with better HRQOL among Hispanic and White females, but not males nor African-Americans of either sex. Conclusions Racial/ethnic differences emerged for female and androgynous, but not male, GROs. Hispanic males are the only group for which GRO (female) was associated with poorer HRQOL. Future research should find ways to help youth overcome negative effects on health from gender beliefs and behavior patterns with sensitivity to racial/ethnic membership.
Malignant peripheral nerve sheath tumors (MPNSTs) comprise a rare, aggressive subtype of soft tissue sarcoma. While surgery is the mainstay of therapy for this disease, the role of neoadjuvant ...therapy remains undefined.
This study reviewed patients 16 years of age and older who underwent surgical treatment for MPNST between 1974 and 2012 at the authors' institution. Univariate and multivariate analyses were performed of clinicopathologic and treatment variables predictive of disease-specific survival (DSS) and disease-free survival.
Eighty-eight patients with primary localized MPNST underwent surgical treatment between 1974 and 2012 at our institution. Of these, 38 (43%) underwent neoadjuvant chemotherapy and had tissue available for analysis. Neoadjuvant radiation was given to 25 patients (68%). The median follow-up time for survivors was 12.5 years (range, 4 to 27 y). Nine patients (23%) had underlying MPNST. With a cutoff of ≥90% pathologic necrosis and/or fibrosis defining response, we identified 14 responders (36%). On univariate analysis, patient age, tumor size, and pathologic response were significantly associated with DSS (P=0.015, 0.011, and 0.030, respectively).
Although the impact of neoadjuvant chemotherapy on the outcome of primary localized MPNST patients continues to be debated, this study shows that a pathologic response to therapy is associated with a significant improvement in DSS. The challenge moving forward is to determine upfront which patients will be "responders" to standard systemic therapy and which patients should be considered for newer investigational agents as part of a clinical trial.
Germ band retraction involves a dramatic rearrangement of the tissues on the surface of the Drosophila embryo. As germ band retraction commences, one tissue, the germ band, wraps around another, the ...amnioserosa. Through retraction the two tissues move cohesively as the highly elongated cells of the amnioserosa contract and the germ band moves so it is only on one side of the embryo. To understand the mechanical drivers of this process, we designed a series of laser ablations that suggest a mechanical role for the amnioserosa. First, we find that during mid retraction, segments in the curve of the germ band are under anisotropic tension. The largest tensions are in the direction in which the amnioserosa contracts. Second, ablating one lateral flank of the amnioserosa reduces the observed force anisotropy and leads to retraction failures. The other intact flank of amnioserosa is insufficient to drive retraction, but can support some germ band cell elongation and is thus not a full phenocopy of ush mutants. Another ablation-induced failure in retraction can phenocopy mys mutants, and does so by targeting amnioserosa cells in the same region where the mutant fails to adhere to the germ band. We conclude that the amnioserosa must play a key, but assistive, mechanical role that aids uncurling of the germ band.
Display omitted
•In mid-GBR, segments in the crook of the germband are under anisotropic tension.•Laser ablation of half the amnioserosa reduces this anisotropy.•Laser ablation of half the amnioserosa causes failures in GBR.•However, this failure is not identical to that of ush mutants.•More localized ablation of specific amnioserosal regions phenocopies mys mutants.
SARCOIDOSIS AND CVID: WHAT IS THE LINK? MACDOWELL, SARAH M; SINGHA, ARINDAM; CROUSER, ELLIOTT D
Chest,
October 2023, 2023-10-00, Letnik:
164, Številka:
4
Journal Article
Objective
Using previously established mastery learning standards, this study compares outcomes of training on standard FLS (FLS) equipment with training on an ergonomically different (ED-FLS), but ...more portable, lower cost platform.
Methods
Subjects completed a pre-training FLS skills test on the standard platform and were then randomized to train on the FLS training platform (
n
= 20) or the ED-FLS platform (
n
= 19). A post-training FLS skills test was administered to both groups on the standard FLS platform.
Results
Group performance on the pretest was similar. Fifty percent of FLS and 32 % of ED-FLS subjects completed the entire curriculum. 100 % of subjects completing the curriculum achieved passing scores on the post-training test. There was no statistically discernible difference in scores on the final FLS exam (FLS 93.4, ED-FLS 93.3,
p
= 0.98) or training sessions required to complete the curriculum (FLS 7.4, ED-FLS 9.8,
p
= 0.13).
Conclusions
These results show that when applying mastery learning theory to an ergonomically different platform, skill transfer occurs at a high level and prepares subjects to pass the standard FLS skills test.
We examined whether social resources from the family and the community moderate the risk associated with low socioeconomic status (SES) for reduced quality of life (QL) among youth across ...racial/ethnic groups. Data were from 4,824 fifth-grade youth (age
X
¯
= 11.1, SD = 0.6; 49% females) in the Healthy Passages™ study (2004-2006) located in Birmingham, Alabama; Los Angeles County, California; and Houston, Texas. Youth reported their QL using the Pediatric Quality of Life Inventory Version 4.0 and the Global Self-Worth subscale of the Self-Perception Profile and their status for hypothesized protective social mechanisms. Overall, family cohesion, parental nurturance, other adult, and peer support were positively associated with QL across racial/ethnic groups. There were few significant interactions, but all suggested that higher SES youth benefited more than lower SES youth. In fact, family cohesion among African American youth and other adult support among Hispanic youth differentiated QL at higher, but not lower SES. Further research should examine other risk contexts and seek to inform targeted prevention efforts.
Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with ...recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.
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