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Cell Jun 2019Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of...
Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc, il2rga zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.
Topics: Animals; Animals, Genetically Modified; Antineoplastic Combined Chemotherapy Protocols; Female; Heterografts; Humans; K562 Cells; Male; Muscle Neoplasms; Neoplasm Transplantation; Phthalazines; Piperazines; Rhabdomyosarcoma; Temozolomide; Xenograft Model Antitumor Assays; Zebrafish
PubMed: 31031007
DOI: 10.1016/j.cell.2019.04.004 -
Cancer Nov 2008Neoadjuvant cisplatin-based chemotherapy improves survival in muscle-invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin)...
BACKGROUND
Neoadjuvant cisplatin-based chemotherapy improves survival in muscle-invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment.
METHODS
The authors retrospectively evaluated patients with muscle-invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan-Kettering Cancer Center. Post-therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle-invasion (
RESULTS
Four cycles of neoadjuvant GC were given over 12 weeks (n=42). Thirty-nine (93%) of 42 patients received 4 cycles, with a median 91% drug delivery for cisplatin and 90% for gemcitabine. The pT0 proportion was 26% (95% confidence interval [CI], 14-42), and no residual muscle-invasive disease proportion (
CONCLUSIONS
Neoadjuvant GC is feasible and allows for timely drug delivery. The proportion of GC-treated patients whose primary tumors were downstaged, with prolonged disease-free survival and minimal or no residual disease, was similar to MVAC-treated patients.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Cisplatin; Cystectomy; Deoxycytidine; Disease-Free Survival; Feasibility Studies; Female; Humans; Male; Middle Aged; Muscle Neoplasms; Neoadjuvant Therapy; Neoplasm Invasiveness; Retrospective Studies; Survival Rate; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 18823036
DOI: 10.1002/cncr.23848 -
Acta Ortopedica Mexicana 2021Mazabraud syndrome was first described in 1926 by Henschen, consisting of the association between bone fibrodysplasia and one or more intramuscular myxomas. The study...
Mazabraud syndrome was first described in 1926 by Henschen, consisting of the association between bone fibrodysplasia and one or more intramuscular myxomas. The study paper conducted by Mazabraud et al. in 1967, described an association between the two pathologies. Later literature referred to this relationship with the eponym described above. In this report, we present the case of a 43-year-old female patient with a known diagnosis of bone fibrodysplasia and subsequent development of a right antecubital fossa mass, which was histologically confirmed as intramuscular myxoma. After the removal of the tumor, the literature was reviewed to find a possible relationship between myxomas and fibrous bone dysplasia, finding positive the association, referred to in the documents reviewed as Mazabraud syndrome.
Topics: Adult; Female; Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic; Humans; Magnetic Resonance Imaging; Muscle Neoplasms; Myxoma; Syndrome
PubMed: 34731928
DOI: No ID Found -
TheScientificWorldJournal Feb 2011Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non-muscle-invasive disease and 25% of patients have... (Review)
Review
Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non-muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10-30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non-muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinoma in situ are the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.
Topics: Humans; Muscle Neoplasms; Neoplasm Staging; Prognosis; Urinary Bladder Neoplasms
PubMed: 21336453
DOI: 10.1100/tsw.2011.28 -
Cell Cycle (Georgetown, Tex.) 2016Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification... (Review)
Review
Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes 5 different histotypes, with 2 most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies 2 major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signaling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the "state of art" of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies.
Topics: Adolescent; Child; Forkhead Box Protein O1; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Humans; Muscle Neoplasms; Oncogene Proteins, Fusion; Oxidative Stress; PAX3 Transcription Factor; Paired Box Transcription Factors; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rhabdomyosarcoma; Signal Transduction; ras Proteins
PubMed: 26209235
DOI: 10.1080/15384101.2015.1071746 -
Clinical Orthopaedics and Related... Apr 2019
Topics: Bone Neoplasms; Congresses as Topic; Humans; Muscle Neoplasms; Treatment Outcome
PubMed: 30811356
DOI: 10.1097/CORR.0000000000000653 -
PloS One 2022To evaluate whether reduced field-of-view (rFOV) DWI sequence improves the differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder...
Comparison of reduced field-of-view DWI and full field-of view DWI for the differentiation between non-muscle invasive bladder cancer and muscle invasive bladder cancer using VI-RADS.
PURPOSE
To evaluate whether reduced field-of-view (rFOV) DWI sequence improves the differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) using VI-RADS.
MATERIAL AND METHODS
Eighty-nine patients underwent bladder MRI with full field-of-view (fFOV) DWI and rFOV DWI sequence. Images were independently evaluated by 2 radiologists. The sensitivities, specificities, accuracies, and areas under the curve (AUCs) for the differentiation between NMIBC and MIBC with fFOV DWI and with rFOV DWI sequence were calculated using VI-RADS. Apparent diffusion coefficients (ADC) values were measured for each patient and averaged.
RESULTS
The sensitivity, specificity, accuracy, and AUC by reader 1 were 92%, 78%, 82% and 0.905 with fFOV DWI, and 92%, 86%, 88% and 0.916 with rFOV DWI sequence, respectively. The sensitivity, specificity, accuracy and AUC by reader 2 were 96%, 76%, 82% and 0.900 with conventional DWI, and 96%, 81%, 85% and 0.907 with rFOV DWI sequence, respectively. The specificity and accuracy of reader 1 were significantly better with rFOV DWI sequence than with fFOV DWI, in contrast there was no significant difference for the others. The average of ADC values of fFOV DWI and rFOV DWI sequence were 1.004×10-6 mm2/s and 1.003×10-6 mm2/s, respectively.
CONCLUSION
The diagnostic ability of rFOV DWI sequence may be better than that of fFOV DWI using VI-RADS for the differentiation between NMIBC and MIBC regardless of image-reading experience, it is controversial.
Topics: Area Under Curve; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Humans; Muscle Neoplasms; Neoplasm Invasiveness; Sensitivity and Specificity; Urinary Bladder Neoplasms
PubMed: 35857788
DOI: 10.1371/journal.pone.0271470 -
Nature Reviews. Clinical Oncology Apr 2017Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop distant metastatic disease. Over the past three decades, perioperative cisplatin-based... (Review)
Review
Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop distant metastatic disease. Over the past three decades, perioperative cisplatin-based chemotherapy has been investigated for its ability to reduce the number of deaths from bladder cancer. Insufficient evidence is available to fully support the use of such chemotherapy in the adjuvant setting; however, neoadjuvant cisplatin-based combination chemotherapy has become a standard of care for eligible patients based on the improved disease-specific and overall survival demonstrated in two randomized phase III trials, compared with surgery alone. For patients with disease downstaging to non-MIBC at the time of radical cystectomy as a result of neoadjuvant chemotherapy, outcomes are outstanding, with 5-year overall survival of 80-90%. Nevertheless, the inability to define before treatment the patients who will and those who will not achieve such a response has impeded the achievement of better outcomes for patients with MIBC. High-throughput DNA and RNA profiling technologies might help to overcome this barrier and enable a more-personalized approach to the use of cytotoxic neoadjuvant chemotherapy. In the past 2 years, trial results have demonstrated the unprecedented ability of immune- checkpoint blockade to induce durable remissions in patients with metastatic disease that has progressed after chemotherapy; studies are now urgently needed to determine how best to incorporate this powerful therapeutic modality into the care of patients with MIBC. Herein, we review the evolution of chemotherapy and immunotherapy for muscle-invasive bladder cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cisplatin; Cystectomy; DNA Repair; Deoxycytidine; Evidence-Based Medicine; Humans; Immunotherapy; Lymphatic Metastasis; Muscle Neoplasms; Mutation; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Preoperative Care; Randomized Controlled Trials as Topic; Time Factors; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 27874062
DOI: 10.1038/nrclinonc.2016.188 -
Orthopaedics & Traumatology, Surgery &... Oct 2010Elastofibromas are rare benign soft tissue tumours that are usually located between the scapula and the rib cage deep in the serratus anterior muscle. Their anatomical...
Elastofibromas are rare benign soft tissue tumours that are usually located between the scapula and the rib cage deep in the serratus anterior muscle. Their anatomical location, distinctive clinical symptoms and radiological characteristics set them apart from malignant soft tissue tumours. Although they are rare, it is necessary to be aware of this benign tumour to avoid unnecessary biopsies; surgical resection may, however, be recommended to obtain a differential diagnosis from malignant sarcomas. We report three cases of elastofibroma dorsi in a 48-year-old man, a 33-year-old woman and a 42-year-old man.
Topics: Adult; Diagnosis, Differential; Female; Fibroma; Humans; Male; Middle Aged; Muscle Neoplasms; Scapula; Soft Tissue Neoplasms; Thoracic Neoplasms; Thoracic Wall; Tomography, X-Ray Computed
PubMed: 20708994
DOI: 10.1016/j.otsr.2010.03.019 -
Journal of the American Veterinary... Oct 2018
Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Hemangiosarcoma; Hindlimb; Lameness, Animal; Male; Muscle Neoplasms; Necrosis
PubMed: 30211648
DOI: 10.2460/javma.253.7.861