| 1. |
- Armstrong, Andrew J, et al.
(author)
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Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC).
- 2014
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In: Urologic oncology. - : Elsevier BV. - 1873-2496. ; 32:8, s. 1308-1316
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Journal article (peer-reviewed)abstract
- Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC).
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| 2. |
- Grankvist, Anna, et al.
(author)
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Multi-locus sequence analysis (MLSA) of clinical "CandidatusNeoehrlichia mikurensis" strains from Europe.
- 2015
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In: Journal of Clinical Microbiology. - 1098-660X. ; 53:10, s. 3126-3132
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Journal article (peer-reviewed)abstract
- CandidatusNeoehrlichia mikurensis is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of Neoehrlichia has been studied only by comparing 16S rRNA gene and groEL operon sequences. We describe the development and use of a multi-locus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinicalNeoehrlichiastrains in Europe and their relatedness to other species within the Anaplasmataceae family.Six genes were selected:ftsZ, clpB, gatB,lipA,groEL and 16SrRNA. Each MLSA locus was amplified by real-time PCR, and the PCR-products sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed Neoehrlichia infection from Sweden (n = 9), the Czech Republic (n = 2) and Germany (n = 1) were analyzed with the MLSA protocol.Threeof the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other.One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16SrRNA,ftsZ, gatB, and groEL.According to the MLSA, Neoehrlichia is most closely related to E. ruminantium, less so to A. phagocytophilum and least to Wolbachiaendosymbiont, among the Anaplasmataceae.To conclude, three sequence types of infectious Neoehrlichia wereidentified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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| 3. |
- Hamdi, Yosr, et al.
(author)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Journal article (peer-reviewed)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 4. |
- Pili, Roberto, et al.
(author)
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Phase II Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
- 2011
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:30, s. 4022-4028
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Journal article (peer-reviewed)abstract
- Purpose: The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms. Patients and Methods: We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen. Results: Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P = .0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40% of patients receiving TASQ versus 10% receiving placebo; deep vein thrombosis (4% v 0%) was more common in the TASQ arm. Conclusion: TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.
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| 5. |
- Stadler, M, et al.
(author)
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Exclusion from spheroid formation identifies loss of essential cell-cell adhesion molecules in colon cancer cells
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 1151-
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Journal article (peer-reviewed)abstract
- Many cell lines derived from solid cancers can form spheroids, which recapitulate tumor cell clusters and are more representative of the in vivo situation than 2D cultures. During spheroid formation, a small proportion of a variety of different colon cancer cell lines did not integrate into the sphere and lost cell-cell adhesion properties. An enrichment protocol was developed to augment the proportion of these cells to 100% purity. The basis for the separation of spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation. This protocol gives rise to sub-populations of colon cancer cells with stable loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost α-catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these molecules in the corresponding spheroid-forming cells demonstrated that loss of the respective proteins were indeed responsible for the NSF phenotypes. Loss of the spheroid forming phenotype was associated with increased migration and invasion properties in all cell lines tested. Hence, we identified critical molecules involved in spheroid formation in different cancer cell lines. We present here a simple, powerful and broadly applicable method to generate new sublines of tumor cell lines to study loss of cell-cell adhesion in cancer progression.
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| 6. |
- Sternberg, Cora N., et al.
(author)
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Chemotherapy for bladder cancer : Treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer
- 2007
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In: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 69, s. 62-79
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Research review (peer-reviewed)abstract
- To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Societe Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of TO medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients with advanced urothelial cancer. A panel of international experts has formulated grade A through D recommendations for the management of patients with locally advanced and metastatic urothelial cancer on the basis of level I to 3 evidence and the findings of phase 2 trials, prospective randomized clinical trials, and meta-analyses.
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| 7. |
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| 8. |
- Zamora, Juan Carlos, et al.
(author)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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In: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Journal article (peer-reviewed)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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