Search

Future projections of sea-level rise under strong warming scenarios are dominated by mass loss in the marine-grounded sectors of West Antarctica, where thinning shelves as a result of warming oceans can lead to reduced buttressing. This consequently leads to accelerated flow from the upstream grounded ice. However, the relation between warming oceans and increased melt rates under the shelves is very uncertain, especially when interactions with the changing shelf geometry are considered. Here, we compare six widely used, highly parameterised formulations relating sub-shelf melt to thermal forcing. We implemented them in an ice-sheet model, and applied the resulting set-up to an idealised-geometry setting, as well as to the Antarctic ice sheet. In our simulations, the differences in modelled ice-sheet evolution resulting from the choice of parameterisation, as well as the choice of numerical scheme used to apply sub-shelf melt near the grounding line, generally are larger than differences from ice-dynamical processes such as basal sliding, as well as uncertainties from the forcing scenario of the model providing the ocean forcing. This holds for the idealised-geometry experiments as well as for the experiments using a realistic Antarctic topography.

Aims A pattern of reduced basal longitudinal strain (BLS) is often observed with left ventricular (LV) hypertrophy (LVH). Whether this pattern is associated with poor outcome is unclear. We aimed to evaluate the prognostic value of regional longitudinal strain according to LV geometry. Methods and results We investigated participants in the 4th Copenhagen City Heart Study who had an echocardiogram with speckle tracking performed. Participants were stratified according to the presence of LVH (LV mass index >= 116 g/m(2) for men and >= 96 g/m(2) for women). The outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, and/or cardiovascular death. The study population consisted of 1090 participants. Mean LVEF was 60% and 160 (15%) had LVH. During a median follow-up of 14.7 years, there were 137 events. Both BLS and midventricular strain, but not apical strain, became incrementally impaired in the spectrum from normal to hypertensives subjects without LVH, and to participants with hypertension and LVH. After multivariable adjustment, BLS and midventricular strain were independently associated with MACE in participants with LVH (BLS: HR 1.08, 95% CI 1.00-1.17, P = 0.041; midventricular strain: HR 1.10, 95% CI 1.00-1.21, P = 0.041) but not in participants without LVH (BLS: HR 0.96, 95% CI 0.90-1.01, P = 0.13; midventricular strain: HR 0.97, 95% CI 0.91-1.03, P = 0.36). Conclusion BLS and midventricular strain, but not apical strain, become incrementally impaired in the spectrum from normal geometry to LVH, and are independently associated with MACE in participants with LVH.

Muscle-invasive urothelial carcinoma represents 20% of newly diagnosed cases of bladder cancer, and most cases show aggressive biological behavior with a poor prognosis. It is necessary to identify biomarkers that can be used as prognostic and predictive factors in daily clinical practice. In our study, we analyzed different antibodies in selected cases of muscle-invasive urinary bladder carcinoma and lymph node metastasis to identify immunohistochemical types and their value as possible prognostic factors. A total of 38 patients were included, 87% men and 13% women, with a mean age of 67.8 years. The most frequent histopathological type was urothelial carcinoma. In the primary lesion, the mixed type was the most common. In unilateral metastasis, the mixed type was the most frequently found. In cases of primary lesions and bilateral metastasis, the luminal and mixed types were observed. The luminal subtype was the most stable in immunohistochemical expression across primary tumors and metastases. The basal type showed a better prognosis in terms of disease-free survival. In conclusion, immunohistochemical studies are useful in assessing primary and metastatic lesions in patients with urothelial carcinoma. Immunohistochemical classification can typify muscle-invasive urothelial carcinoma, and the immunophenotype seems to have prognostic implications.

Basal cell carcinoma (BCC) can be a component of a collision tumor in which the skin cancer is present at the same cutaneous site as either a benign tumor or a malignant neoplasm. However, BCC can also concurrently occur at the same skin location as a non-neoplastic cutaneous condition. These include autoimmune diseases (vitiligo), cutaneous disorders (Darier disease), dermal conditions (granuloma faciale), dermal depositions (amyloid, calcinosis cutis, cutaneous focal mucinosis, osteoma cutis, and tattoo), dermatitis, miscellaneous conditions (rhinophyma, sarcoidal reaction, and varicose veins), scars, surgical sites, systemic diseases (sarcoidosis), systemic infections (leischmaniasis, leprosy and lupus vulgaris), and ulcers. The relationship between the BCC and the coexisting non-neoplastic condition may be coincidental or possibly related to the development of the BCC; alternatively, the development of the BCC may be unrelated to the coexisting non-neoplastic conditions and secondary to either a Koebner isomorphic response or a Wolf isotopic response in an immunocompromised district of skin. This paper reviews several of the case reports and studies that describe the association of BCC with these non-neoplastic cutaneous conditions.

[ES] Ante una amenaza de parto prematuro (APP) en la que los riesgos materno-fetales son mayores que en una gestación de más de 37 semanas, la discriminación de si éste realmente se dará de forma inminente (¿7 días) o más lejano (>7 días) es de gran relevancia para la mejor gestión de cada caso y de los recursos hospitalarios. Como valoración adicional del estado electrofisiológico del útero para distinguir entre ambas situaciones se propone la electrohisterografía. Partiendo de una base de datos de la UPV en colaboración con el Hospital La Fe de registros electrohisterográficos en mujeres con APP en condiciones clínicas habituales (bajo tratamientos tocolíticos), en este trabajo se analizan los cambios ante el parto inminente en parámetros de amplitud, espectrales y de complejidad valorados en tramos de actividad basal y contráctil de forma independiente y contrastados con el estudio `global¿ (promediado) usado en la bibliografía. Adicionalmente se valoran los ratios entre contracción y basal de los parámetros computados. Todo ello con énfasis en valorar su capacidad discriminatoria. Los resultados apuntan a que el número de parámetros obtenidos para discriminar entre grupos de pacientes es mayor con la valoración independiente en basal y contracción que en la global. Los parámetros de complejidad muestran que la señal se ordena a medida que se acerca el parto y los parámetros espectrales muestran un desplazamiento hacia bajas frecuencias. En todo caso, todas las familias de parámetros ofrecen capacidad discriminatoria entre parto inminente y no inminente. Por otro lado, el ratio entre tramos contráctiles y basales por parámetros muestra que los mayores cambios los sufren las pacientes de parto cercano. En futuros estudios se deberá valorar la complementariedad o redundancia de la información proporcionada por los distintos parámetros en los distintos tipos de tramos evaluados para el diagnóstico del parto inminente en APP., [EN] Faced with a threat of preterm labor (TPL) in which the maternal-fetal risks are greater than in a gestation of more than 37 weeks, the discrimination of whether it really will occur imminently (¿ 7 days) or more distant (>7 days) is relevant for the better management of each case and hospital resources. As an additional assessment of the electrophysiological state of the uterus to distinguish among both situations, it is proposed the use of electrohysterography. Based on a UPV database in collaboration with Hospital La Fe of electrohysterographic records in women with TPL in usual clinical conditions (under tocolytic treatments), this study analyses the changes in the face of imminent delivery in amplitude, spectral and complexity assessed in basal and contractile activity ranges independently and contrasted with the global study (averaged) used in the literature. Additionally, the ratios between contraction and baseline of the computed parameters are evaluated. All this with an emphasis on assessing their discriminatory capacity. The results suggest that the number of parameters obtained to discriminate between groups of patients is greater with the independent evaluation at baseline and contraction than in the global one. The complexity parameters show that the signal is ordered as parturition approaches and the spectral parameters shifts towards low frequences. In any case, all the families of parameters offer discriminatory capacity among imminent and non-imminent delivery. On the other hand, the ratio between contractile and basal sections by parameters shows that the greatest changes are suffered by patients with close labor. Future studies should assess the complementarity or redundancy of the information provided by the different parameters in the different types of sections evaluated for the diagnosis of imminent delivery in TPL.

[ES] Ante una amenaza de parto prematuro (APP) en la que los riesgos materno-fetales son mayores que en una gestación de más de 37 semanas, la discriminación de si éste realmente se dará de forma inminente (¿7 días) o más lejano (>7 días) es de gran relevancia para la mejor gestión de cada caso y de los recursos hospitalarios. Como valoración adicional del estado electrofisiológico del útero para distinguir entre ambas situaciones se propone la electrohisterografía. Partiendo de una base de datos de la UPV en colaboración con el Hospital La Fe de registros electrohisterográficos en mujeres con APP en condiciones clínicas habituales (bajo tratamientos tocolíticos), en este trabajo se analizan los cambios ante el parto inminente en parámetros de amplitud, espectrales y de complejidad valorados en tramos de actividad basal y contráctil de forma independiente y contrastados con el estudio `global¿ (promediado) usado en la bibliografía. Adicionalmente se valoran los ratios entre contracción y basal de los parámetros computados. Todo ello con énfasis en valorar su capacidad discriminatoria. Los resultados apuntan a que el número de parámetros obtenidos para discriminar entre grupos de pacientes es mayor con la valoración independiente en basal y contracción que en la global. Los parámetros de complejidad muestran que la señal se ordena a medida que se acerca el parto y los parámetros espectrales muestran un desplazamiento hacia bajas frecuencias. En todo caso, todas las familias de parámetros ofrecen capacidad discriminatoria entre parto inminente y no inminente. Por otro lado, el ratio entre tramos contráctiles y basales por parámetros muestra que los mayores cambios los sufren las pacientes de parto cercano. En futuros estudios se deberá valorar la complementariedad o redundancia de la información proporcionada por los distintos parámetros en los distintos tipos de tramos evaluados para el diagnóstico del parto inminente en APP., [EN] Faced with a threat of preterm labor (TPL) in which the maternal-fetal risks are greater than in a gestation of more than 37 weeks, the discrimination of whether it really will occur imminently (¿ 7 days) or more distant (>7 days) is relevant for the better management of each case and hospital resources. As an additional assessment of the electrophysiological state of the uterus to distinguish among both situations, it is proposed the use of electrohysterography. Based on a UPV database in collaboration with Hospital La Fe of electrohysterographic records in women with TPL in usual clinical conditions (under tocolytic treatments), this study analyses the changes in the face of imminent delivery in amplitude, spectral and complexity assessed in basal and contractile activity ranges independently and contrasted with the global study (averaged) used in the literature. Additionally, the ratios between contraction and baseline of the computed parameters are evaluated. All this with an emphasis on assessing their discriminatory capacity. The results suggest that the number of parameters obtained to discriminate between groups of patients is greater with the independent evaluation at baseline and contraction than in the global one. The complexity parameters show that the signal is ordered as parturition approaches and the spectral parameters shifts towards low frequences. In any case, all the families of parameters offer discriminatory capacity among imminent and non-imminent delivery. On the other hand, the ratio between contractile and basal sections by parameters shows that the greatest changes are suffered by patients with close labor. Future studies should assess the complementarity or redundancy of the information provided by the different parameters in the different types of sections evaluated for the diagnosis of imminent delivery in TPL.

[ES] Ante una amenaza de parto prematuro (APP) en la que los riesgos materno-fetales son mayores que en una gestación de más de 37 semanas, la discriminación de si éste realmente se dará de forma inminente (¿7 días) o más lejano (>7 días) es de gran relevancia para la mejor gestión de cada caso y de los recursos hospitalarios. Como valoración adicional del estado electrofisiológico del útero para distinguir entre ambas situaciones se propone la electrohisterografía. Partiendo de una base de datos de la UPV en colaboración con el Hospital La Fe de registros electrohisterográficos en mujeres con APP en condiciones clínicas habituales (bajo tratamientos tocolíticos), en este trabajo se analizan los cambios ante el parto inminente en parámetros de amplitud, espectrales y de complejidad valorados en tramos de actividad basal y contráctil de forma independiente y contrastados con el estudio `global¿ (promediado) usado en la bibliografía. Adicionalmente se valoran los ratios entre contracción y basal de los parámetros computados. Todo ello con énfasis en valorar su capacidad discriminatoria. Los resultados apuntan a que el número de parámetros obtenidos para discriminar entre grupos de pacientes es mayor con la valoración independiente en basal y contracción que en la global. Los parámetros de complejidad muestran que la señal se ordena a medida que se acerca el parto y los parámetros espectrales muestran un desplazamiento hacia bajas frecuencias. En todo caso, todas las familias de parámetros ofrecen capacidad discriminatoria entre parto inminente y no inminente. Por otro lado, el ratio entre tramos contráctiles y basales por parámetros muestra que los mayores cambios los sufren las pacientes de parto cercano. En futuros estudios se deberá valorar la complementariedad o redundancia de la información proporcionada por los distintos parámetros en los distintos tipos de tramos evaluados para el diagnóstico del parto inminente en APP., [EN] Faced with a threat of preterm labor (TPL) in which the maternal-fetal risks are greater than in a gestation of more than 37 weeks, the discrimination of whether it really will occur imminently (¿ 7 days) or more distant (>7 days) is relevant for the better management of each case and hospital resources. As an additional assessment of the electrophysiological state of the uterus to distinguish among both situations, it is proposed the use of electrohysterography. Based on a UPV database in collaboration with Hospital La Fe of electrohysterographic records in women with TPL in usual clinical conditions (under tocolytic treatments), this study analyses the changes in the face of imminent delivery in amplitude, spectral and complexity assessed in basal and contractile activity ranges independently and contrasted with the global study (averaged) used in the literature. Additionally, the ratios between contraction and baseline of the computed parameters are evaluated. All this with an emphasis on assessing their discriminatory capacity. The results suggest that the number of parameters obtained to discriminate between groups of patients is greater with the independent evaluation at baseline and contraction than in the global one. The complexity parameters show that the signal is ordered as parturition approaches and the spectral parameters shifts towards low frequences. In any case, all the families of parameters offer discriminatory capacity among imminent and non-imminent delivery. On the other hand, the ratio between contractile and basal sections by parameters shows that the greatest changes are suffered by patients with close labor. Future studies should assess the complementarity or redundancy of the information provided by the different parameters in the different types of sections evaluated for the diagnosis of imminent delivery in TPL.

[ES] Ante una amenaza de parto prematuro (APP) en la que los riesgos materno-fetales son mayores que en una gestación de más de 37 semanas, la discriminación de si éste realmente se dará de forma inminente (¿7 días) o más lejano (>7 días) es de gran relevancia para la mejor gestión de cada caso y de los recursos hospitalarios. Como valoración adicional del estado electrofisiológico del útero para distinguir entre ambas situaciones se propone la electrohisterografía. Partiendo de una base de datos de la UPV en colaboración con el Hospital La Fe de registros electrohisterográficos en mujeres con APP en condiciones clínicas habituales (bajo tratamientos tocolíticos), en este trabajo se analizan los cambios ante el parto inminente en parámetros de amplitud, espectrales y de complejidad valorados en tramos de actividad basal y contráctil de forma independiente y contrastados con el estudio `global¿ (promediado) usado en la bibliografía. Adicionalmente se valoran los ratios entre contracción y basal de los parámetros computados. Todo ello con énfasis en valorar su capacidad discriminatoria. Los resultados apuntan a que el número de parámetros obtenidos para discriminar entre grupos de pacientes es mayor con la valoración independiente en basal y contracción que en la global. Los parámetros de complejidad muestran que la señal se ordena a medida que se acerca el parto y los parámetros espectrales muestran un desplazamiento hacia bajas frecuencias. En todo caso, todas las familias de parámetros ofrecen capacidad discriminatoria entre parto inminente y no inminente. Por otro lado, el ratio entre tramos contráctiles y basales por parámetros muestra que los mayores cambios los sufren las pacientes de parto cercano. En futuros estudios se deberá valorar la complementariedad o redundancia de la información proporcionada por los distintos parámetros en los distintos tipos de tramos evaluados para el diagnóstico del parto inminente en APP., [EN] Faced with a threat of preterm labor (TPL) in which the maternal-fetal risks are greater than in a gestation of more than 37 weeks, the discrimination of whether it really will occur imminently (¿ 7 days) or more distant (>7 days) is relevant for the better management of each case and hospital resources. As an additional assessment of the electrophysiological state of the uterus to distinguish among both situations, it is proposed the use of electrohysterography. Based on a UPV database in collaboration with Hospital La Fe of electrohysterographic records in women with TPL in usual clinical conditions (under tocolytic treatments), this study analyses the changes in the face of imminent delivery in amplitude, spectral and complexity assessed in basal and contractile activity ranges independently and contrasted with the global study (averaged) used in the literature. Additionally, the ratios between contraction and baseline of the computed parameters are evaluated. All this with an emphasis on assessing their discriminatory capacity. The results suggest that the number of parameters obtained to discriminate between groups of patients is greater with the independent evaluation at baseline and contraction than in the global one. The complexity parameters show that the signal is ordered as parturition approaches and the spectral parameters shifts towards low frequences. In any case, all the families of parameters offer discriminatory capacity among imminent and non-imminent delivery. On the other hand, the ratio between contractile and basal sections by parameters shows that the greatest changes are suffered by patients with close labor. Future studies should assess the complementarity or redundancy of the information provided by the different parameters in the different types of sections evaluated for the diagnosis of imminent delivery in TPL.

Cytokeratin 5 is a marker of basal molecular subtypes of muscle-invasive bladder cancer (MIBC), which correlates with worse overall survival compared to luminal subtypes. Our observations have not confirmed CK5 as a marker of high-grade (HG) disease in Ta non-muscle-invasive bladder cancer (NMIBC). Therefore, to understand the basal-luminal immunohistochemistry profile in Ta NMIBC, we performed immunohistochemistry for CK5, P40, P63 (basal), GATA3 and CK20 (luminal) and studied the correlation with HG and clinical outcome in 109 patients with Ta NMIBC. HG and low-grade (LG) diseases were scored in each patient. Four different CK5 patterns were evaluated: absent (median 41.3%), normal (72.5%), rising (84.4%) and full thickness (23.9%). The median percentage of GATA3 was 100%. HG disease and CK5 expression and rising CK5 pattern had a significant inverse correlation, whereas HG disease and CK20 expression had a significant positive correlation. We also found a significant inverse correlation between CK5 expression and CK20 expression. Quantitative PCR confirmed that the presence of CK5 correlated with up-regulation of CK5 RNA. None of the markers could differentiate patients with regard to clinical outcome. Our results suggest a role for CK5 and CK20 in differentiating between LG and HG disease in Ta NMIBC.

Basal cell carcinoma (BCC) can be a component of a collision tumor in which the skin cancer is present at the same cutaneous site as either a benign tumor or a malignant neoplasm. However, BCC can also concurrently occur at the same skin location as a non-neoplastic cutaneous condition. These include autoimmune diseases (vitiligo), cutaneous disorders (Darier disease), dermal conditions (granuloma faciale), dermal depositions (amyloid, calcinosis cutis, cutaneous focal mucinosis, osteoma cutis, and tattoo), dermatitis, miscellaneous conditions (rhinophyma, sarcoidal reaction, and varicose veins), scars, surgical sites, systemic diseases (sarcoidosis), systemic infections (leischmaniasis, leprosy and lupus vulgaris), and ulcers. The relationship between the BCC and the coexisting non-neoplastic condition may be coincidental or possibly related to the development of the BCC; alternatively, the development of the BCC may be unrelated to the coexisting non-neoplastic conditions and secondary to either a Koebner isomorphic response or a Wolf isotopic response in an immunocompromised district of skin. This paper reviews several of the case reports and studies that describe the association of BCC with these non-neoplastic cutaneous conditions.

Pancreatic stellate cells (PSCs) are important pancreatic fibrogenic cells that interact with pancreatic cancer cells to promote the progression of pancreatic ductal adenocarcinoma (PDAC). In the tumor microenvironment (TME), several factors such as cytokines and nucleotides contribute to this interplay. Our aim was to investigate whether there is an interaction between IL-6 and nucleotide signaling, in particular, that mediated by the ATP-sensing P2X7 receptor (P2X7R). Using human cell lines of PSCs and cancer cells, as well as primary PSCs from mice, we show that ATP is released from both PSCs and cancer cells in response to mechanical and metabolic cues that may occur in the TME, and thus activate the P2X7R. Functional studies using P2X7R agonists and inhibitors show that the receptor is involved in PSC proliferation, collagen secretion and IL-6 secretion and it promotes cancer cell migration in a human PSC-cancer cell co-culture. Moreover, conditioned media from P2X7R-stimulated PSCs activated the JAK/STAT3 signaling pathway in cancer cells. The monoclonal antibody inhibiting the IL-6 receptor, Tocilizumab, inhibited this signaling. In conclusion, we show an important mechanism between PSC-cancer cell interaction involving ATP and IL-6, activating P2X7 and IL-6 receptors, respectively, both potential therapeutic targets in PDAC.

Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four‐gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString‐based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/‐/KRT20low/‐) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14‐/KRT5‐/GATA3‐/KRT20‐), null/double negative (non‐luminal/non‐basal). These three categories were meaningful in terms of overall cancer‐specific survival (p < 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (p < 0.0001), NMIBC vs. MIBC (p < 0.001), or by AJCC stage category Ta (p = 0.0012) and T1 (p < 0.0001) but did not reach significance in T2‐T4 (p = 0.563). PD‐ L1 expression (low vs. high) was also different according to molecular subtype, with high PD‐L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (p = 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer‐specific survival (p < 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer‐specific survival (p < 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and aff

Pancreatic stellate cells (PSCs) are important pancreatic fibrogenic cells that interact with pancreatic cancer cells to promote the progression of pancreatic ductal adenocarcinoma (PDAC). In the tumor microenvironment (TME), several factors such as cytokines and nucleotides contribute to this interplay. Our aim was to investigate whether there is an interaction between IL-6 and nucleotide signaling, in particular, that mediated by the ATP-sensing P2X7 receptor (P2X7R). Using human cell lines of PSCs and cancer cells, as well as primary PSCs from mice, we show that ATP is released from both PSCs and cancer cells in response to mechanical and metabolic cues that may occur in the TME, and thus activate the P2X7R. Functional studies using P2X7R agonists and inhibitors show that the receptor is involved in PSC proliferation, collagen secretion and IL-6 secretion and it promotes cancer cell migration in a human PSC-cancer cell co-culture. Moreover, conditioned media from P2X7R-stimulated PSCs activated the JAK/STAT3 signaling pathway in cancer cells. The monoclonal antibody inhibiting the IL-6 receptor, Tocilizumab, inhibited this signaling. In conclusion, we show an important mechanism between PSC-cancer cell interaction involving ATP and IL-6, activating P2X7 and IL-6 receptors, respectively, both potential therapeutic targets in PDAC.

Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four‐gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString‐based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/‐/KRT20low/‐) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14‐/KRT5‐/GATA3‐/KRT20‐), null/double negative (non‐luminal/non‐basal). These three categories were meaningful in terms of overall cancer‐specific survival (p < 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (p < 0.0001), NMIBC vs. MIBC (p < 0.001), or by AJCC stage category Ta (p = 0.0012) and T1 (p < 0.0001) but did not reach significance in T2‐T4 (p = 0.563). PD‐ L1 expression (low vs. high) was also different according to molecular subtype, with high PD‐L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (p = 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer‐specific survival (p < 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer‐specific survival (p < 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and aff

Organoids offer self-organizing, three-dimensional tissue structures that recapitulate physiological processes in the convenience of a dish. The murine mammary gland is composed of two distinct epithelial cell compartments, serving different functions: the outer, contractile myoepithelial compartment and the inner, secretory luminal compartment. Here, we describe a method by which the cells comprising these compartments are isolated and then combined to investigate their individual lineage contributions to mammary gland morphogenesis and differentiation. The method is simple and efficient and does not require sophisticated separation technologies such as fluorescence activated cell sorting. Instead, we harvest and enzymatically digest the tissue, seed the epithelium on adherent tissue culture dishes, and then use differential trypsinization to separate myoepithelial from luminal cells with ~90% purity. The cells are then plated in an extracellular matrix where they organize into bilayered, three-dimensional (3D) organoids that can be differentiated to produce milk after 10 days in culture. To test the effects of genetic mutations, cells can be harvested from wild type or genetically engineered mouse models, or they can be genetically manipulated prior to 3D culture. This technique can be used to generate mosaic organoids that allow investigation of gene function specifically in the luminal or myoepithelial compartment.

Organoids offer self-organizing, three-dimensional tissue structures that recapitulate physiological processes in the convenience of a dish. The murine mammary gland is composed of two distinct epithelial cell compartments, serving different functions: the outer, contractile myoepithelial compartment and the inner, secretory luminal compartment. Here, we describe a method by which the cells comprising these compartments are isolated and then combined to investigate their individual lineage contributions to mammary gland morphogenesis and differentiation. The method is simple and efficient and does not require sophisticated separation technologies such as fluorescence activated cell sorting. Instead, we harvest and enzymatically digest the tissue, seed the epithelium on adherent tissue culture dishes, and then use differential trypsinization to separate myoepithelial from luminal cells with ~90% purity. The cells are then plated in an extracellular matrix where they organize into bilayered, three-dimensional (3D) organoids that can be differentiated to produce milk after 10 days in culture. To test the effects of genetic mutations, cells can be harvested from wild type or genetically engineered mouse models, or they can be genetically manipulated prior to 3D culture. This technique can be used to generate mosaic organoids that allow investigation of gene function specifically in the luminal or myoepithelial compartment.

Prostate epithelial basal cells are highly plastic in their luminal differentiation capability. Basal stem cells actively produce luminal cells during organogenesis, but become restricted in the adult prostate unless receiving oncogenic or inflammatory stimuli. Given that the number of luminal cells increases relative to basal cells through development and that equilibrium is reached in the adulthood, we hypothesize that a negative-feedback mechanism exists to inhibit basal-to-luminal differentiation. We provide evidence supporting this hypothesis by comparing murine prostatic growth in a tissue reconstitution assay with cell recombinants of different basal-to-luminal ratios. Additionally, in organoid culture, hybrid organoids derived from adjacent basal and luminal cells showed reduced basal stem cell activities, suggesting contact inhibition. Importantly, removal of adult luminal cells in vivo via either an inducible Cre/loxP-Dre/rox dual-lineage-tracing system or orthotopic trypsin injection led to robust reactivation of basal stem cell activities, which acts independent of androgen. These data illustrate the prostate organ as a distinctive paradigm where cell contact from differentiated daughter cells restricts adult stem cell multipotency to maintain the steady-state epithelial architecture.

Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium.

Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium.

Prostate epithelial basal cells are highly plastic in their luminal differentiation capability. Basal stem cells actively produce luminal cells during organogenesis, but become restricted in the adult prostate unless receiving oncogenic or inflammatory stimuli. Given that the number of luminal cells increases relative to basal cells through development and that equilibrium is reached in the adulthood, we hypothesize that a negative-feedback mechanism exists to inhibit basal-to-luminal differentiation. We provide evidence supporting this hypothesis by comparing murine prostatic growth in a tissue reconstitution assay with cell recombinants of different basal-to-luminal ratios. Additionally, in organoid culture, hybrid organoids derived from adjacent basal and luminal cells showed reduced basal stem cell activities, suggesting contact inhibition. Importantly, removal of adult luminal cells in vivo via either an inducible Cre/loxP-Dre/rox dual-lineage-tracing system or orthotopic trypsin injection led to robust reactivation of basal stem cell activities, which acts independent of androgen. These data illustrate the prostate organ as a distinctive paradigm where cell contact from differentiated daughter cells restricts adult stem cell multipotency to maintain the steady-state epithelial architecture.

The prostate epithelium is comprised predominantly of basal and luminal cells. In vivo lineage tracing has been utilized to define the differentiation capacity of mouse prostate basal and luminal cells during development, tissue-regeneration and transformation. However, evaluating cell-intrinsic and extrinsic regulators of prostate epithelial differentiation capacity using a lineage tracing approach often requires extensive breeding and can be cost-prohibitive. In the prostate organoid assay, basal and luminal cells generate prostatic epithelium ex vivo. Importantly, primary epithelial cells can be isolated from mice of any genetic background or mice treated with any number of small molecules prior to, or after, plating into three-dimensional (3D) culture. Sufficient material for evaluation of differentiation capacity is generated after 7-10 days. Collection of basal-derived and luminal-derived organoids for (1) protein analysis by Western blot and (2) immunohistochemical analysis of intact organoids by whole-mount confocal microscopy enables researchers to evaluate the ex vivo differentiation capacity of prostate epithelial cells. When used in combination, these two approaches provide complementary information about the differentiation capacity of prostate basal and luminal cells in response to genetic or pharmacological manipulation.

Metastatic basal cell carcinoma may be treated with hedgehog pathway inhibitors, including vismodegib and sonidegib. However, patients can demonstrate resistance to these agents. We describe a man with metastatic basal cell carcinoma who did not respond well to vismodegib and sonidegib. Next generation sequencing of his metastatic liver tumor demonstrated a high tumor mutational burden (103 mutations per megabase) and the genomic amplification of PD-L1, both of which are features that predict response to anti-PD1/PD-L1 immunotherapy. Treatment with nivolumab, an anti-PD1 checkpoint inhibitor, resulted in near complete remission. Yet, he developed new primary cutaneous basal cell carcinomas while receiving immunotherapy and while his metastatic disease showed an ongoing response. His new superficial skin cancer had a lower tumor mutational burden (45 mutations per megabase) than the metastatic disease. Since immunotherapy response rates are higher in patients with more genomically complex tumors, our observations suggest that, in contrast with the premise of earlier treatment is better, which holds true for targeted and cytotoxic therapies, immunotherapy may be better suited to more advanced disease.

Leonardite is a humifiedplant substance, very rich in organic matter, mainly composed of carbon (55% by weight), and humic materials (complex organic molecules such as Carboxyls, Hydroxyls and Carbonyl). This type of material is used for the extraction of humic and fulvic acids,the main components of humic substances. The objective of the present study was to determine the effect of humic substances (Humiplex Plus) on the cultivation of roses. The experiment was carried out on a farm belonging to the Otón parish of the Cayambe canton located in the province of Pichincha; which took place under greenhouse in beds 30 meters long by one-meter-wide at a height of 10 to 15 cm. above ground level; in the statistical design six treatments with four repetitions were applied. From the results obtained, it is concluded that with the application of 160 grams (T5) of humic substances (Humiplex Plus) / m2 in beds of cultivation of roses, a higher number of basal was obtained in 1.63, a number of upper legs in 1.08 and a plant height higher by 9.9 cm, compared to the control, figures that indicate that as the dose of humic substances increases (Humiplex Plus / m2 of soil) enriched with micro elements (Fe, Zn, Mg, Mn, Cu, Bo and S), the growth and development of various organs of the treated plant are stimulated., La Leonardita es una sustancia vegetal humificada, muy rica en materia orgánica, está constituida principalmente de carbono (55% en peso), y materiales húmicos (moléculas orgánicas complejas como Carboxilos, Hidroxilos y Carbonilos). Este tipo de materiales se utilizan para la extracción de ácidos húmicos y fúlvicos, componentes principales de las sustancias húmicas. El objetivo del presente estudio fue determinar el efecto de las sustancias húmicas (Humiplex Plus) sobre el cultivo de rosas. El experimento se desarrolló en una finca perteneciente a la parroquia Otón del cantón Cayambe ubicada en la provincia de Pichincha; el cual tuvo lugar bajo invernadero en camas de 30 metros de largo por un metro de ancho a una altura de 10 a 15 cm. sobre el nivel del suelo; en el diseño estadístico se aplicaron seis tratamientos con cuatro repeticiones. De los resultados obtenidos, se concluye que con la aplicación de 160 gramos (T5) de sustancias húmicas (Humiplex Plus)/m2 en camas de cultivo de rosas, se obtuvo un número de basales superior en 1.63, un número de medias piernas superior en 1.08 y una altura de plantas superior en 9.9 cm, frente al testigo, cifras que indican que a medida que se incrementa la dosis de sustancias húmicas (Humiplex Plus/m2 de suelo) enriquecida con micro elementos (Fe, Zn, Mg, Mn, Cu, Bo y S), se estimulan el crecimiento y desarrollo de varios órganos de la planta tratada.

Metastatic basal cell carcinoma may be treated with hedgehog pathway inhibitors, including vismodegib and sonidegib. However, patients can demonstrate resistance to these agents. We describe a man with metastatic basal cell carcinoma who did not respond well to vismodegib and sonidegib. Next generation sequencing of his metastatic liver tumor demonstrated a high tumor mutational burden (103 mutations per megabase) and the genomic amplification of PD-L1, both of which are features that predict response to anti-PD1/PD-L1 immunotherapy. Treatment with nivolumab, an anti-PD1 checkpoint inhibitor, resulted in near complete remission. Yet, he developed new primary cutaneous basal cell carcinomas while receiving immunotherapy and while his metastatic disease showed an ongoing response. His new superficial skin cancer had a lower tumor mutational burden (45 mutations per megabase) than the metastatic disease. Since immunotherapy response rates are higher in patients with more genomically complex tumors, our observations suggest that, in contrast with the premise of earlier treatment is better, which holds true for targeted and cytotoxic therapies, immunotherapy may be better suited to more advanced disease.

We report the final achievements of our project. These achievements include the successful building of a super-resolution microscope that is capable of performing 2D and 3D Stochastic Optical Reconstruction Microscopy (STORM) and Photoactivated Localization Microscopy (PALM), and a quantitative-phase imaging (QPI) system that enables the label-free imaging of cells over a period of days. With STORM imaging, we imaged the spatial organization or clustering of the CCR7 receptor on the surface of MCF-7 breast cancer cells that had been cultured on gelatin substrates. This imaging was the first of its kind for breast cancer. We also small controllable microenvironments, in which we can simultaneously culture small groups of cells and monitor their response to external perturbation. We subsequently examined the effects of microenvironments on breast cancer by creating arrays of polydimethlysiloxane (PDMS) microposts of different stiffness and sizes and seeded them with MCF-7 cells. We manipulated our micropost microenvironments to study the effects of microenvironment on cell lineage, namely the basal-luminal differentiation of MCF-7s. Finally, with QPI, we investigated the real-time response of breastcancer cells to different microenvironmental cues. We thus have begun to learn how protein density, growth rate, morphology, motility, and phenotype of these cells change and evolve in response to their microenvironment., The original document contains color images.

BackgroundNormal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture.ResultsAll of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells.ConclusionsThe cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools.

Background: Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas.Purpose: To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome.Methods: Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated.Results: Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision.Conclusions: Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

BackgroundNormal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture.ResultsAll of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells.ConclusionsThe cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools.

The infrared greenhouse gas heat trap at the top of the atmosphere controls anthropogenic global warming (AGW) heat balance. Processes at the top of the ocean similarly control the 93% of AGW in the oceans. The tropics are a global year-round ocean heat source. Heat is transported in the ocean by sinking brine from tropical evaporation and polar freezing. Buoyant freshwater and ice barriers limit heat loss from the surface layer. The almost completely unstudied ocean surface skin is critically important to understanding global warming and climate change processes. Studies to date have concentrated on atmospheric warming mainly from land-air data. In this paper we present the first hourly meridional 3m and surface observations in the equatorial Pacific from Tahiti to Hawaii for direct measurement of evaporation and ocean boundary layer heat trapping. We relate this to poleward heat and freshwater transport and ocean warming moderation by basal icemelt of floating ice explored in a second paper [1]. We show heat sequestration below 3m in the hypersaline (>35.5°) southern hemisphere (SH) is limited to ~6M Jm -2 day-1 but evaporation is 7.3mmm-2day--1, at salinity ~36.4° and temperature >28ºC. In the northern hemisphere (NH) tropics the corresponding figures are ~12 MJm-2day-1 and ~4.5mmm -2day--1. Equatorial upwelling and the 50m deep Bering Strait limit buoyant surface outflow from the North Pacific. We found pairs of counter-rotating vertical meridional tropical cells (MTCs), ~300-1200km wide, ~100m deep form separate SH and NH systems with little cross-equatorial flux. Counter-rotating Lagrangian wind-driven gyres transport heat and freshwater polewards in seasonally and tidally moderated stratified surface waters. The zonal geostrophic balance is maintained by the Equatorial Undercurrent (EUC) with an eastbound core ~140cms-1 and density ~25.0 at 50-150m. Global warming and polar icemelt has been underestimated from wrong assumptions of the processes in the t

The infrared greenhouse gas heat trap at the top of the atmosphere controls anthropogenic global warming (AGW) heat balance. Processes at the top of the ocean similarly control the 93% of AGW in the oceans. The tropics are a global year-round ocean heat source. Heat is transported in the ocean by sinking brine from tropical evaporation and polar freezing. Buoyant freshwater and ice barriers limit heat loss from the surface layer. The almost completely unstudied ocean surface skin is critically important to understanding global warming and climate change processes. Studies to date have concentrated on atmospheric warming mainly from land-air data. In this paper we present the first hourly meridional 3m and surface observations in the equatorial Pacific from Tahiti to Hawaii for direct measurement of evaporation and ocean boundary layer heat trapping. We relate this to poleward heat and freshwater transport and ocean warming moderation by basal icemelt of floating ice explored in a second paper [1]. We show heat sequestration below 3m in the hypersaline (>35.5°) southern hemisphere (SH) is limited to ~6M Jm -2 day-1 but evaporation is 7.3mmm-2day--1, at salinity ~36.4° and temperature >28ºC. In the northern hemisphere (NH) tropics the corresponding figures are ~12 MJm-2day-1 and ~4.5mmm -2day--1. Equatorial upwelling and the 50m deep Bering Strait limit buoyant surface outflow from the North Pacific. We found pairs of counter-rotating vertical meridional tropical cells (MTCs), ~300-1200km wide, ~100m deep form separate SH and NH systems with little cross-equatorial flux. Counter-rotating Lagrangian wind-driven gyres transport heat and freshwater polewards in seasonally and tidally moderated stratified surface waters. The zonal geostrophic balance is maintained by the Equatorial Undercurrent (EUC) with an eastbound core ~140cms-1 and density ~25.0 at 50-150m. Global warming and polar icemelt has been underestimated from wrong assumptions of the processes in the t

Background: Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas.Purpose: To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome.Methods: Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated.Results: Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision.Conclusions: Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

BackgroundNormal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture.ResultsAll of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells.ConclusionsThe cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools.

La presente investigación muestra cinco métodos para la inducción de brotación en las plántulas de la variedad de rosa Blush de los Andes (Rosa spp). Los tratamientos empleados fueron: primero, agobio de la plántula con semiquiebre, previa formación de escobilla; segundo, agobio de la plántula por arqueo, previa formación de escobilla; tercero, cosecha de la primera flor en punto de corte ruso; cuarto, agobio de la plántula por arqueo, previo descabece del primer botón floral en punto garbanzo; y por último, descabece del primer botón floral en punto de corte ruso más desyeme de brotes axilares. Se evaluó semana a semana el número de basales brotados por planta de cada tratamiento, la longitud en centímetros alcanzada por cada basal, el calibre en milímetros alcanzado por cada uno de los tallos, y se determinó el número de días a corte (ciclo del cultivo), desde la siembra de la plántula hasta la cosecha en punto ruso; y desde la implementación del tratamiento hasta la cosecha en el mismo punto de cada tallo basal evaluado. En cuanto al número de basales por planta, no se encontró diferencia significativa; en cuanto la longitud de basales en centímetros, el mejor tratamiento fue el segundo con una longitud promedio de 97,21 cm por tallo, al igual que en el calibre (diámetro) con un promedio de 6,39 mm por tallo, en la variable ciclo de cultivo desde la ‘siembra’, los mejores resultados se encontraron en los dos primeros tratamientos, en la misma variable pero desde la ejecución de los tratamientos, los mejores resultados se presentaron en el quinto caso.

La presente investigación muestra cinco métodos para la inducción de brotación en las plántulas de la variedad de rosa Blush de los Andes (Rosa spp). Los tratamientos empleados fueron: primero, agobio de la plántula con semiquiebre, previa formación de escobilla; segundo, agobio de la plántula por arqueo, previa formación de escobilla; tercero, cosecha de la primera flor en punto de corte ruso; cuarto, agobio de la plántula por arqueo, previo descabece del primer botón floral en punto garbanzo; y por último, descabece del primer botón floral en punto de corte ruso más desyeme de brotes axilares. Se evaluó semana a semana el número de basales brotados por planta de cada tratamiento, la longitud en centímetros alcanzada por cada basal, el calibre en milímetros alcanzado por cada uno de los tallos, y se determinó el número de días a corte (ciclo del cultivo), desde la siembra de la plántula hasta la cosecha en punto ruso; y desde la implementación del tratamiento hasta la cosecha en el mismo punto de cada tallo basal evaluado. En cuanto al número de basales por planta, no se encontró diferencia significativa; en cuanto la longitud de basales en centímetros, el mejor tratamiento fue el segundo con una longitud promedio de 97,21 cm por tallo, al igual que en el calibre (diámetro) con un promedio de 6,39 mm por tallo, en la variable ciclo de cultivo desde la ‘siembra’, los mejores resultados se encontraron en los dos primeros tratamientos, en la misma variable pero desde la ejecución de los tratamientos, los mejores resultados se presentaron en el quinto caso.

La presente investigación muestra cinco métodos para la inducción de brotación en las plántulas de la variedad de rosa Blush de los Andes (Rosa spp). Los tratamientos empleados fueron: primero, agobio de la plántula con semiquiebre, previa formación de escobilla; segundo, agobio de la plántula por arqueo, previa formación de escobilla; tercero, cosecha de la primera flor en punto de corte ruso; cuarto, agobio de la plántula por arqueo, previo descabece del primer botón floral en punto garbanzo; y por último, descabece del primer botón floral en punto de corte ruso más desyeme de brotes axilares. Se evaluó semana a semana el número de basales brotados por planta de cada tratamiento, la longitud en centímetros alcanzada por cada basal, el calibre en milímetros alcanzado por cada uno de los tallos, y se determinó el número de días a corte (ciclo del cultivo), desde la siembra de la plántula hasta la cosecha en punto ruso; y desde la implementación del tratamiento hasta la cosecha en el mismo punto de cada tallo basal evaluado. En cuanto al número de basales por planta, no se encontró diferencia significativa; en cuanto la longitud de basales en centímetros, el mejor tratamiento fue el segundo con una longitud promedio de 97,21 cm por tallo, al igual que en el calibre (diámetro) con un promedio de 6,39 mm por tallo, en la variable ciclo de cultivo desde la ‘siembra’, los mejores resultados se encontraron en los dos primeros tratamientos, en la misma variable pero desde la ejecución de los tratamientos, los mejores resultados se presentaron en el quinto caso.

La presente investigación muestra cinco métodos para la inducción de brotación en las plántulas de la variedad de rosa Blush de los Andes (Rosa spp). Los tratamientos empleados fueron: primero, agobio de la plántula con semiquiebre, previa formación de escobilla; segundo, agobio de la plántula por arqueo, previa formación de escobilla; tercero, cosecha de la primera flor en punto de corte ruso; cuarto, agobio de la plántula por arqueo, previo descabece del primer botón floral en punto garbanzo; y por último, descabece del primer botón floral en punto de corte ruso más desyeme de brotes axilares. Se evaluó semana a semana el número de basales brotados por planta de cada tratamiento, la longitud en centímetros alcanzada por cada basal, el calibre en milímetros alcanzado por cada uno de los tallos, y se determinó el número de días a corte (ciclo del cultivo), desde la siembra de la plántula hasta la cosecha en punto ruso; y desde la implementación del tratamiento hasta la cosecha en el mismo punto de cada tallo basal evaluado. En cuanto al número de basales por planta, no se encontró diferencia significativa; en cuanto la longitud de basales en centímetros, el mejor tratamiento fue el segundo con una longitud promedio de 97,21 cm por tallo, al igual que en el calibre (diámetro) con un promedio de 6,39 mm por tallo, en la variable ciclo de cultivo desde la ‘siembra’, los mejores resultados se encontraron en los dos primeros tratamientos, en la misma variable pero desde la ejecución de los tratamientos, los mejores resultados se presentaron en el quinto caso.

We evaluated whether men with shorter telomere length in prostate cancer tissue and in normal appearing prostate tissue adjacent to adenocarcinoma have a higher risk of aggressive prostate cancer than men with longer telomere length. We included 663 men in the Health Professionals Follow-up Study who underwent radical prostatectomy and for whom tissue was obtained and arrayed on six tissue microarrays. We used FISH to conduct relative quantitation of telomere length in ~4000 digitally-imaged spots equating to ~40,000 records. For each man, we determined telomere length in normal stroma, normal epithelium (basal and luminal cells), cancer (luminal cells), high-grade prostatic intraepithelial neoplasia (basal and luminal cells), normal stroma associated with cancer, and normal stroma associated with PIN. The data were entered into software developed at Hopkins called Telometer. We are in the data cleaning phase, will perform the statistical analysis over the next few months, and will submit an abstract to a national cancer meeting next year while concurrently preparing the manuscript.

Epithelial mesenchymal transition (EMT) has long been associated with breast cancer cell invasiveness and evidence of EMT processes in clinical samples is growing rapidly. Genome-wide transcriptional profiling of increasingly larger numbers of human breast cancer (HBC) cell lines have confirmed the existence of a subgroup of cell lines (termed Basal B/Mesenchymal) with enhanced invasive properties and a predominantly mesenchymal gene expression signature, distinct from subgroups with predominantly luminal (termed Luminal) or mixed basal/luminal (termed Basal A) features (Neve et al Cancer Cell 2006). Studies providing molecular and cellular analyses of EMT features in these cell lines are summarised, and the expression levels of EMT-associated factors in these cell lines are analysed. Recent clinical studies supporting the presence of EMT-like changes in vivo are summarised. Human breast cancer cell lines with mesenchymal properties continue to hold out the promise of directing us towards key mechanisms at play in the metastatic dissemination of breast cancer.

We examined the effects of cage size and testosterone (T) levels on basal and peak metabolic rates (BMR and PMR, respectively) and on pectoral and leg muscle masses of male house sparrows (Passer domesticus). Birds were housed either in small birdcages or in flight aviaries for at least 2 weeks prior to the initial metabolic evaluations. They were then implanted with either empty or T-filled silastic capsules and remeasured 5-6 weeks later. Birds treated with single T implants achieved breeding levels (4-6 ng/mL) and one group given double implants reached 10 ng/mL. There was no effect of T on BMR or PMR in any group studied, but there was an effect of caging. Caged birds showed significant reductions in PMR over the course of captivity, whereas PMR in aviary-housed birds were indistinguishable from their free-living counterparts. Testosterone treatment significantly increased leg muscle mass in caged birds, but had no effect on muscle mass in aviary-housed sparrows. We conclude that testosterone has no direct effect on sparrow metabolic rate or muscle mass, but may interact with cage conditions to produce indirect changes to these variables.

We examined the effects of cage size and testosterone (T) levels on basal and peak metabolic rates (BMR and PMR, respectively) and on pectoral and leg muscle masses of male house sparrows (Passer domesticus). Birds were housed either in small birdcages or in flight aviaries for at least 2 weeks prior to the initial metabolic evaluations. They were then implanted with either empty or T-filled silastic capsules and remeasured 5-6 weeks later. Birds treated with single T implants achieved breeding levels (4-6 ng/mL) and one group given double implants reached 10 ng/mL. There was no effect of T on BMR or PMR in any group studied, but there was an effect of caging. Caged birds showed significant reductions in PMR over the course of captivity, whereas PMR in aviary-housed birds were indistinguishable from their free-living counterparts. Testosterone treatment significantly increased leg muscle mass in caged birds, but had no effect on muscle mass in aviary-housed sparrows. We conclude that testosterone has no direct effect on sparrow metabolic rate or muscle mass, but may interact with cage conditions to produce indirect changes to these variables.

We examined the effects of cage size and testosterone (T) levels on basal and peak metabolic rates (BMR and PMR, respectively) and on pectoral and leg muscle masses of male house sparrows (Passer domesticus). Birds were housed either in small birdcages or in flight aviaries for at least 2 weeks prior to the initial metabolic evaluations. They were then implanted with either empty or T-filled silastic capsules and remeasured 5-6 weeks later. Birds treated with single T implants achieved breeding levels (4-6 ng/mL) and one group given double implants reached 10 ng/mL. There was no effect of T on BMR or PMR in any group studied, but there was an effect of caging. Caged birds showed significant reductions in PMR over the course of captivity, whereas PMR in aviary-housed birds were indistinguishable from their free-living counterparts. Testosterone treatment significantly increased leg muscle mass in caged birds, but had no effect on muscle mass in aviary-housed sparrows. We conclude that testosterone has no direct effect on sparrow metabolic rate or muscle mass, but may interact with cage conditions to produce indirect changes to these variables.

Background The PTCH tumour suppressor gene is involved in the development of nearly all basal cell carcinomas (BCCs) of the skin and a fraction of squamous cell carcinomas (SCCs). A nonconservative Pro/Leu nucleotide polymorphism within PTCH exon 23 at codon 1315 was recently reported to be potentially important for the development of breast epithelial cell cancers. Objectives Accordingly, the status of PTCH codon 1315 was analysed for a possible association with the development of nonmelanoma skin cancers (NMSCs) in a pilot study. Because skin cancer risk is affected by specific population-dependent phenotypes such as skin and hair colour, codon 1315 was also analysed for normal allele frequency variation in human populations having differing extents of eumelanin vs. phaeomelanin. Methods The single nucleotide polymorphism in codon 1315 of the human PTCH gene was analysed in genomic DNA from six different populations comprising 472 blood samples and from 170 patients in four different categories with NMSC. Polymerase chain reaction and pyrosequencing were used to determine the allele frequencies. Allelic loss was furthermore determined in tumours following microdissection. Results The Pro/Pro genotype frequency ranged from 30% to 65% between populations, with a significant trend for a reduced frequency of the Pro/Pro genotype in populations having lighter pigmentation (P = 0.020). Pro/Pro frequency showed an increasing trend with increasing tumour case severity (P = 0.027). In 260 samples from 180 Swedish patients with NMSC and a control group of 96 healthy ethnically matched volunteers, no statistically significant pairwise differences between groups were detected in the PTCH codon 1315 allelic distribution, neither was a difference seen for multiple or early onset cases of BCC in the Swedish population. In Swedish patients with single tumours, allelic loss (loss of heterozygosity) was observed in 20 of 30 (67%) patients with BCC and four of 22 (18%) patients with, QC 20100525

Five to ten per cent of all breast carcinomas are of hereditary origin. Many of them have been associated to mutations in the BRCA1 and BRCA2 susceptibility genes. No "BRCA3" gene has been found to account for the non-BRCA1/BRCA2 breast cancer (BRCAx) families, and BRCAx tumors are increasingly believed to originate from multiple distinct genetic events. Phenotype studies have questioned the existence of specific "portraits" among hereditary breast carcinomas (HBC). They have shown that most BRCA1 tumors have a "basal (epithelial)-like" aspect, while BRCA2 and BRCAx HBC are more heterogeneous. HBC have also been submitted to genetic analyses, notably with the objective of resolving the heterogeneity of BRCAx lesions. The present review aims to summarize recent data on BRCA1, BRCA2, and BRCAx HBC, including hypotheses on the origin of BRCA1 tumors and their paradoxical relations to estrogen-sensitivity., SCOPUS: re.j, info:eu-repo/semantics/published

Biopsies were obtained from the quadriceps femoris muscle of two male patients deficient in phosphofructokinase (PFK) 1. In the basal state the patients had markedly higher contents of UDP-glucose (~5-fold), hexose monophosphates (~7- to 13-fold), inosine monophosphate (IMP) (~15-fold), and fructose 2,6-bisphosphate (F-2,6-P 2; ~6-fold) than controls. Fructose 1,6-bisphosphate was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry wt) than in controls [72 ?? 4 (SD)]. Patients had normal fasting plasma glucose and insulin levels and basal glucose turnover rates and responded normally to a 75-g oral glucose challenge. Patients were also studied during euglycemic hyperinsulinemia (~95 mg/dl; 40 and 400 mU ?? m -2 ?? min -1). Whole body glucose disposal rates were normal during both insulin infusion rates. Biopsies taken after the 400 mU insulin infusion showed decreases in acetylcarnitine and citrate and increases in the fractional activity of glycogen synthase. It is suggested that the high basal levels of F-2,6-P 2 are, at least partly, a consequence of the high levels of fructose 6-phosphate, which will stimulate flux through PFK- and inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP contents indicate that carbohydrate availability is important for control of high-energy phosphate metabolism, even in the basal state. The insulin-mediated decreases in acetylcarnitine and citrate suggest an activation of the tricarboxylic acid cycle in skeletal muscle but an absence of the normal response to replenish these intermediates.

Biopsies were obtained from the quadriceps femoris muscle of two male patients deficient in phosphofructokinase (PFK) 1. In the basal state the patients had markedly higher contents of UDP-glucose (~5-fold), hexose monophosphates (~7- to 13-fold), inosine monophosphate (IMP) (~15-fold), and fructose 2,6-bisphosphate (F-2,6-P 2; ~6-fold) than controls. Fructose 1,6-bisphosphate was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry wt) than in controls [72 ?? 4 (SD)]. Patients had normal fasting plasma glucose and insulin levels and basal glucose turnover rates and responded normally to a 75-g oral glucose challenge. Patients were also studied during euglycemic hyperinsulinemia (~95 mg/dl; 40 and 400 mU ?? m -2 ?? min -1). Whole body glucose disposal rates were normal during both insulin infusion rates. Biopsies taken after the 400 mU insulin infusion showed decreases in acetylcarnitine and citrate and increases in the fractional activity of glycogen synthase. It is suggested that the high basal levels of F-2,6-P 2 are, at least partly, a consequence of the high levels of fructose 6-phosphate, which will stimulate flux through PFK- and inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP contents indicate that carbohydrate availability is important for control of high-energy phosphate metabolism, even in the basal state. The insulin-mediated decreases in acetylcarnitine and citrate suggest an activation of the tricarboxylic acid cycle in skeletal muscle but an absence of the normal response to replenish these intermediates.