The mammalian ureter contains a water-tight epithelium surrounded by smooth muscle. Key molecules have been defined which regulate ureteric bud initiation and drive the differentiation of ureteric ...mesenchyme into peristaltic smooth muscle. Less is known about mechanisms underlying the developmental patterning of the multilayered epithelium characterising the mature ureter. In skin, which also contains a multilayered epithelium, cytokeratin 15 (CK15), an acidic intermediate filament protein, marks cells whose progeny contribute to epidermal regeneration following wounding. Moreover, CK15+ precursor cells in skin can give rise to basal cell carcinomas. In the current study, using transcriptome microarrays of embryonic wild type mouse ureters, Krt15, coding for CK15, was detected. Quantitative polymerase chain reaction analyses confirmed the initial finding and demonstrated that Krt15 levels increased during the fetal period when the ureteric epithelium becomes multilayered. CK15 protein was undetectable in the ureteric bud, the rudiment from which the ureter grows. Nevertheless, later in fetal development, CK15 was immunodetected in a subset of basal urothelial cells in the ureteric stalk. Superficial epithelial cells, including those positive for the differentiation marker uroplakin III, were CK15-. Transformation-related protein 63 (P63) has been implicated in epithelial differentiation in murine fetal urinary bladders. In wild type fetal ureters, CK15+ cells were positive for P63, and p63 homozygous null mutant ureters lacked CK15+ cells. In these mutant ureters, sections of the urothelium were monolayered versus the uniform multilayering found in wild type littermates. Human urothelial cell carcinomas account for considerable morbidity and mortality. CK15 was upregulated in a subset of invasive ureteric and urinary bladder cancers. Thus, in ureter development, the absence of CK15 is associated with a structurally simplified urothelium whereas, postnatally, increased CK15 levels feature in malignant urothelial overgrowth. CK15 may be a novel marker for urinary tract epithelial precursor cells.
Development of malignancy after solid-organ trans?lant is a well-known long-term complication of immunosuppressive therapy. Thus far, there are no specific oncologic recommendations regarding ...management of de novo tumors in transplanted kidneys. Here, we present the case of a 63-year-old male patient who developed a de novo renal cell carcinoma 6 years after the transplant procedure. The patient underwent nephron-sparing surgery with transperitoneal enucleation of the tumor. We discuss the decision-making process and the operative challenges that we faced. We conclude that this technique should be considered as a therapeutic strategy for selected patients so that transplant nephrectomy can be avoided.
Breast core biopsy is one of the major nonoperative methods of diagnosis. Increasingly, there is also a need to provide prognostic data to facilitate timely patient management. We present the results ...from 500 patients with invasive breast carcinoma, who underwent core biopsy followed by a therapeutic surgical procedure. Grade and type of the invasive and in situ carcinoma, together with the presence or absence of vascular invasion, were determined in both biopsy and definitive surgical excision and the results compared. There was 67% agreement with overall grade (kappa value 0.48), with scores for tubule formation, pleomorphism, and mitotic scoring achieving values of 82%, 73%, and 58%, respectively. Only 60% of grade 1 and 2 carcinomas showed concordance, but 84% of grade 3 tumors showed agreement between core and excision results. Tumor typing, vascular invasion, and grading of ductal carcinoma in situ had agreement values of 74%, 69%, and 65%, respectively. The major problem with assessing prognostic factors on needle biopsy specimens is undersampling of the most informative areas. However, in those patients in whom preoperative assessment of prognostic factors is most likely to be beneficial, i.e., those with grade 3 carcinomas, a high level of agreement was achieved in this large study.
Hypoxia modification improves overall survival in muscle-invasive bladder cancer patients who undergo radiotherapy. There is evidence that hypoxic tumors benefit most from hypoxia modification. The ...study aimed to identify or derive a hypoxia gene signature that predicts benefit from hypoxia-modifying treatment in bladder cancer.
Published hypoxia signatures were tested and a new one derived by analyzing bladder cancer transcriptomic data from public databases. Tumor samples were available from the BCON phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). Gene expression data were generated for 151 tumors using Affymetrix Human 1.0 Exon ST arrays and used for independent validation.
A 24-gene signature was derived, which was prognostic in four of six independent surgical cohorts (
= 679; meta HR, 2.32; 95% CI, 1.73-3.12;
< 0.0001). The signature was also prognostic in BCON patients receiving radiotherapy alone (
= 75; HR for local relapse-free survival, 2.37; 95% CI, 1.26-4.47;
= 0.0076). The signature predicted benefit from CON (
= 76; HR, 0.47; 95% CI, 0.26-0.86;
= 0.015). Prognostic significance (
= 0.017) and predictive significance (
= 0.058) remained after adjusting for clinicopathologic variables. A test for interaction between hypoxia status and treatment arms was significant (
= 0.0094).
A 24-gene hypoxia signature has strong and independent prognostic and predictive value for muscle-invasive bladder cancer patients. The signature can aid identification of patients likely to benefit from the addition of carbogen and nicotinamide to radiotherapy.
.
Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. ...The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types.
Samples were available from 157 T2-T4 laryngeal cancer and 185 T1-T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide (ARCON) and bladder carbogen nicotinamide (BCON) phase III randomized trials of radiotherapy alone or with carbogen and nicotinamide (CON) respectively. Customized TaqMan low density arrays (TLDA) were used to assess expression of the 26-gene signature using quantitative real-time PCR. The median expression of the 26 genes was used to derive a hypoxia score (HS). Patients were categorized as TLDA-HS low (≤median) or TLDA-HS high (>median). The primary outcome measures were regional control (RC; ARCON) and overall survival (BCON).
Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors. Five-year RC was 81% (radiotherapy alone) versus 100% (CON) for TLDA-HS high (P=0.009). For TLDA-HS low, 5-year RC was 91% (radiotherapy alone) versus 90% (CON; P=0.90). TLDA-HS did not predict benefit from CON in bladder cancer.
The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer. These findings will be evaluated in a prospective clinical trial.
A man who brought the war home with him Ballardie, Francis W, Dr; Cowley, Richard, PhD; Cox, Alan, MPhil ...
The Lancet (British edition),
2008-Nov-29, Letnik:
372, Številka:
9653
Journal Article
Recenzirano
Further blood tests showed a normal concentration of angiotensin-converting enzyme, and absence of antibodies to nuclear factor, neutrophil cytoplasm, DNA, endomysium, and neurones; results of ...electrophoresis were normal.
Sertoliform cystadenoma of the rete testis Sinclair, Andrew M.; Gunendran, Thiru; Napier-Hemy, Richard D. ...
Pathology international,
09/2006, Letnik:
56, Številka:
9
Journal Article
PDF
