Human ovarian carcinomas (HOC) were established s.c. and i.p. in nude mice and the biological characteristics were investigated for 4 xenografts. HOC8 and HOC18, derived respectively from a primary tumor of the ovary and a pleural effusion (from 2 different patients) were established s.c. in nude mice. HOC10 and HOC22, derived from the ascites of 2 patients, were directly established as ascites after i.p. injection in nude mice. The s.c. and i.p. growth behavior of the 4 HOC lines was investigated. HOC18, HOC8 and HOC22 cells produced progressively growing tumor after s.c. injection but HOC10 ascites would not grow s.c. The cell suspension derived from HOC18 only produced carcinomatosis upon i.p. injection, while HOC8 cells produced both ascites and carcinomatosis. The 2 ascites HOC10 and HOC22 produced ascites in nude mice, but only HOC22 formed i.p. carcinomatosis. Histopathological characteristics of the patients' primary tumors persisted in nude mice, regardless of the site of tumor implantation. DNA histograms of the xenografts closely matched the patients' tumors and remained stable at different passages. Cisplatin, adriamycin and cyclophosphamide given i.v. were tested against HOC8 and HOC18 growing s.c. and HOC22 and HOC10 growing i.p. HOC8 showed a significant response to DDP and almost no sensitivity to ADR and CTX. HOC18 showed only moderate growth delay with all 3 drugs. Mice bearing HOC10 and HOC22 ascites had a prolonged survival time after DDP and ADR treatment.
The therapeutic activity against ovarian carcinoma xenografts supports the potential of taxol in the treatment of this neoplasia and forms the basis for future investigations aimed at optimizing the therapeutic activity of taxol given alone or in combination with other drugs.
AimsAmeloblastoma is a rare odontogenic tumour with an aggressive local behaviour. Mutations in the mitogen-activated protein kinase pathway, namely BRAF V600E mutations, are a common finding. To date, there is no clear correlation between BRAF V600 mutation and clinical outcome.MethodsWe retrospectively reviewed the medical records of patients who underwent surgery for ameloblastoma between May 1998 and June 2018, at 11 participating Italian centres. BRAF mutational status was evaluated by quantitative PCR/pyrosequencing. The primary end points were to determine BRAF mutational status in primitive and recurrent ameloblastoma, and to assess the relapse-free interval (RFI); the secondary end point was to investigate the correlation of BRAF mutational status with the clinical features of the tumour and survival outcomes.ResultsOverall, 74 patients were included: 33 (44.5%) were BRAF wild type and 41 (55.4%) BRAF V600 mutated. BRAF V600 mutated ameloblastomas occurred more frequently in younger patients (p=0.0031), were located at the mandible (p=0.0009) and presented with unicystic variant. After a median follow-up of 60 months, 21 (28.3%) patients relapsed (30.3% and 26.8% in the BRAF wild type and BRAF mutated group, respectively). At univariable Cox models, none of the investigated variables, including microscopic margin involvement, was associated with RFI.ConclusionsLocal recurrence occurs in 30% of patients with ameloblastoma. BRAFV600 mutation is associated with younger age, mandibular localisation and with unicystic ameloblastoma. Neither BRAF mutation nor microscopically positive surgical margins were associated with RFI. Further studies are needed to elucidate outcomes of this rare disease according to clinical, histopathological and comprehensive molecular features.
The MOC-25 tumour arose spontaneously in a female nude mouse and was established as a continuous line intraperitoneally in nude mice, where it reproduces the topological features of its origin, growing preferentially in the uterus, ovaries and liver. Karyotype analysis showed that MOC-25 cells are hyperdiploid. Tumorigenicity and malignant behaviour were studied by transplanting tumour cells into different sites in nude mice. The comparison of tumour take after i.p. and s.c. injections of scaled concentrations of MOC-25 cell suspension showed preferential growth in the peritoneum. Regardless of the route of implantation (s.c., i.v., i.p.), this tumour rapidly and preferentially disseminated to the liver, uterus, ovaries, spleen and bone marrow. No significant differences in tumour growth and metastatic behaviour were observed when MOC-25 was injected in ovariectomized nude mice or in male nude mice. Morphology studies using light and electron microscopy, immunophenotyping and molecular analysis indicated a B-lymphoid origin of the MOC-25 tumour.
Accurate testing for epidermal growth factor receptor (EGFR) variants is essential for informing treatment decisions in non-small cell lung cancer (NSCLC). Automated diagnostic workflows may allow more streamlined initiation of targeted treatments, where appropriate, while comprehensive variant analysis is ongoing. FACILITATE, a real-world, prospective, multicenter, European study, evaluated performance and analytical turnaround time of the Idylla™ EGFR Mutation Test compared with local reference methods. Sixteen sites obtained formalin-fixed paraffin-embedded biopsy samples with ≥ 10% neoplastic cells from patients with NSCLC. Consecutive 5 μm sections from patient samples were tested for clinically relevant NSCLC-associated EGFR variants using the Idylla™ EGFR Mutation Test and local reference methods; performance (concordance) and analytical turnaround time were compared. Between January 2019 and November 2020, 1,474 parallel analyses were conducted. Overall percentage agreement was 97.7% [n = 1,418; 95% confidence interval (CI): 96.8–98.3], positive agreement, 87.4% (n = 182; 95% CI: 81.8–91.4) and negative agreement, 99.2% (n = 1,236; 95% CI: 98.5–99.6). There were 38 (2.6%) discordant cases. Ninety percent of results were returned with an analytical turnaround time of within 1 week using the Idylla™ EGFR Mutation Test versus ∼22 days using reference methods. The Idylla™ EGFR Mutation Test performed well versus local methods and had shorter analytical turnaround time. The Idylla™ EGFR Mutation Test can thus support application of personalized medicine in NSCLC.
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