In the past twenty years much efforts have been devoted to the development of ontologies and term... more In the past twenty years much efforts have been devoted to the development of ontologies and term bases for different fields. All this work has been done separately or with slight integration. The GENOMA-KB is a project whose main aim is to integrate, at least, both resources. In this paper, most relevant aspects of the project are presented. Each module is individually described and the links among them are highlighted. Finally, a query system to interrogate the knowledge base is briefly introduced.
Background: Fungal mannanases contribute to enzymatic degradation of lignocellulose. Results: New... more Background: Fungal mannanases contribute to enzymatic degradation of lignocellulose. Results: New fungal mannanases reveal striking differences in substrate specificities. A rigid linker tightly connects the family 26 glycoside hydrolase to its binding module. Conclusion: Podospora anserina mannanases display differences in substrate binding modes, transglycosylation activity, and modular organization. Significance: Information on the structure-function relationships of fungal mannanases is essential to improve the comprehension of biomass deconstruction.
Background: The gene encoding an atypical multi-modular glycoside hydrolase family 45 endoglucana... more Background: The gene encoding an atypical multi-modular glycoside hydrolase family 45 endoglucanase bearing five different family 1 carbohydrate binding modules (CBM1), designated PpCel45A, was identified in the Pichia pastoris GS115 genome.
The ascomycete Podospora anserina is a coprophilous fungus that grows at late stages on droppings... more The ascomycete Podospora anserina is a coprophilous fungus that grows at late stages on droppings of herbivores. Its genome encodes a large diversity of carbohydrate-active enzymes. Among them, four genes encode glycoside hydrolases from family 6 (GH6), the members of which comprise putative endoglucanases and exoglucanases, some of them exerting important functions for biomass degradation in fungi. Therefore, this family was selected for functional analysis. Three of the enzymes, P. anserina Cel6A (PaCel6A), PaCel6B, and PaCel6C, were functionally expressed in the yeast Pichia pastoris. All three GH6 enzymes hydrolyzed crystalline and amorphous cellulose but were inactive on hydroxyethyl cellulose, mannan, galactomannan, xyloglucan, arabinoxylan, arabinan, xylan, and pectin. PaCel6A had a catalytic efficiency on cellotetraose comparable to that of Trichoderma reesei Cel6A (TrCel6A), but PaCel6B and PaCel6C were clearly less efficient. PaCel6A was the enzyme with the highest stability at 45°C, while PaCel6C was the least stable enzyme, losing more than 50% of its activity after incubation at temperatures above 30°C for 24 h. In contrast to TrCel6A, all three studied P. anserina GH6 cellulases were stable over a wide range of pHs and conserved high activity at pH values of up to 9. Each enzyme displayed a distinct substrate and product profile, highlighting different modes of action, with PaCel6A being the enzyme most similar to TrCel6A. PaCel6B was the only enzyme with higher specific activity on carboxymethylcellulose (CMC) than on Avicel and showed lower processivity than the others. Structural modeling predicts an open catalytic cleft, suggesting that PaCel6B is an endoglucanase.
The GENOMA-KB knowledge base includes four independent modules: a textual database, a factual dat... more The GENOMA-KB knowledge base includes four independent modules: a textual database, a factual database, a terminological database and an ontology. We will briefly introduce in this paper the main features concerning each one of the modules, and we will highlight the process of enlarging both the term base and the ontology.
... provide a sound theoretical basis for computer-aided unit detection, semi-automatic mapping o... more ... provide a sound theoretical basis for computer-aided unit detection, semi-automatic mapping of ... This situation may be overcome by using multiple inheritance (each node may inherit ... also include some organisation for other parts of speech (POS): adjectives, verbs and adverbs ...
To analyse the etiology, diagnostic methods and response to therapy in 30 episodes of pneumonia d... more To analyse the etiology, diagnostic methods and response to therapy in 30 episodes of pneumonia diagnosed in 17 patients with chronic lymphocytic leukemia (CLL) between 1995 and 2000. In each episode of pneumonia the following data were analysed: age, gender, treatment of CLL, antiinfectious prophylaxis, granulocytopenia, CD4/CD8 lymphocytes ratio, hipogammaglobulinemia, origin of pneumonia (nosocomial or community-acquired), localisation, respiratory insufficiency, need for mechanical ventilation, antimicrobial therapy and response. Diagnostic methods included blood and sputum cultures, fiberoptic bronchoscopy and search for antigens in urine (Legionella pneumophila serogroup 1, galactomannan, and Streptococcus pneumoniae). Median age of the series was 60 yr. (range 50-86) and 12 patients were male. Chlorambucil and prednisone were used in 13 cases and fludarabine in 8. Granulocytopenia was present in 14 episodes, hypogammaglobulinemia was seen in 22 and CD4/CD8 ratio was lower tha...
Background. The need for preoperative chemoradiation or short-course radiation in all T3 rectal t... more Background. The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma. Methods. We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). Results. On an intent-to-treat analysis, the ORR was 78% (n 5 36; 95% confidence interval [CI]: 63%-89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9-33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75%
Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screenin... more Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screening process and this limits its detection to the late stages, with consequently high mortality rates. Volatile organic compounds (VOC) are chemical compounds (mainly the products of cell catabolism) found as gases in the human breath. Different methods have been developed to analyse VOCs and to compare them in healthy subjects and lung cancer patients. In this review, we summarise the different techniques used to analyse VOC. Many reports have been published with promising results similar to those achieved with accepted screening methods such as mammography. These methods show good perspectives on lung cancer screening.
Gene signatures can provide prognostic and predictive information to help in the treatment of ear... more Gene signatures can provide prognostic and predictive information to help in the treatment of early-stage breast cancer. Although many of these signatures have been described, only a few have been properly validated. MammaPrint and OncoType offer prognostic information and identify low-risk patients who do not benefit from adjuvant chemotherapy. With regard to prediction of response, molecular subtypes of breast cancer differ in their sensitivity to chemotherapy, although further studies are needed in this field. Cost, small sample size, and the need to use central laboratories are common limitations to the widespread use of these tools.
1989) A new prognostic system for multiple myeloma based on easily available parameters. British ... more 1989) A new prognostic system for multiple myeloma based on easily available parameters. British Journal of Haernatology. 72, Cox, D.R. (1 9 72) Regression models and lifetables. Journal ofthe Royal , T.A. (1985) Regression models for prognostic predictions: advantages, problems and suggested solutions. Cancer Treatment Reports, 69,1071-507-511.
Cancer patients search for information about prognosis and treatment. Internet has become a major... more Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient-physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient-physician relationship. Physicians should ensure that their patients receive reliable online information.
A phase II study with an alternating chemotherapeutic scheme, in advanced gastric cancer was cond... more A phase II study with an alternating chemotherapeutic scheme, in advanced gastric cancer was conducted. Twenty-two patients were treated with cisplatin and mitomycin C on day 1 and BCNU and doxorubicin on day 28. Tegafur p.o. was given daily from the start to the end of chemotherapy. This scheme was repeated every four weeks. Response rate was 25% (2 complete and 3 partial). However, remissions were short lived, and median survival for the entire group was 7 months. Haematological and gastrointestinal toxicities were severe. In conclusion, the low response rate and the high toxicity of this regimen preclude its use for the treatment of gastric cancer.
In the past twenty years much efforts have been devoted to the development of ontologies and term... more In the past twenty years much efforts have been devoted to the development of ontologies and term bases for different fields. All this work has been done separately or with slight integration. The GENOMA-KB is a project whose main aim is to integrate, at least, both resources. In this paper, most relevant aspects of the project are presented. Each module is individually described and the links among them are highlighted. Finally, a query system to interrogate the knowledge base is briefly introduced.
Background: Fungal mannanases contribute to enzymatic degradation of lignocellulose. Results: New... more Background: Fungal mannanases contribute to enzymatic degradation of lignocellulose. Results: New fungal mannanases reveal striking differences in substrate specificities. A rigid linker tightly connects the family 26 glycoside hydrolase to its binding module. Conclusion: Podospora anserina mannanases display differences in substrate binding modes, transglycosylation activity, and modular organization. Significance: Information on the structure-function relationships of fungal mannanases is essential to improve the comprehension of biomass deconstruction.
Background: The gene encoding an atypical multi-modular glycoside hydrolase family 45 endoglucana... more Background: The gene encoding an atypical multi-modular glycoside hydrolase family 45 endoglucanase bearing five different family 1 carbohydrate binding modules (CBM1), designated PpCel45A, was identified in the Pichia pastoris GS115 genome.
The ascomycete Podospora anserina is a coprophilous fungus that grows at late stages on droppings... more The ascomycete Podospora anserina is a coprophilous fungus that grows at late stages on droppings of herbivores. Its genome encodes a large diversity of carbohydrate-active enzymes. Among them, four genes encode glycoside hydrolases from family 6 (GH6), the members of which comprise putative endoglucanases and exoglucanases, some of them exerting important functions for biomass degradation in fungi. Therefore, this family was selected for functional analysis. Three of the enzymes, P. anserina Cel6A (PaCel6A), PaCel6B, and PaCel6C, were functionally expressed in the yeast Pichia pastoris. All three GH6 enzymes hydrolyzed crystalline and amorphous cellulose but were inactive on hydroxyethyl cellulose, mannan, galactomannan, xyloglucan, arabinoxylan, arabinan, xylan, and pectin. PaCel6A had a catalytic efficiency on cellotetraose comparable to that of Trichoderma reesei Cel6A (TrCel6A), but PaCel6B and PaCel6C were clearly less efficient. PaCel6A was the enzyme with the highest stability at 45°C, while PaCel6C was the least stable enzyme, losing more than 50% of its activity after incubation at temperatures above 30°C for 24 h. In contrast to TrCel6A, all three studied P. anserina GH6 cellulases were stable over a wide range of pHs and conserved high activity at pH values of up to 9. Each enzyme displayed a distinct substrate and product profile, highlighting different modes of action, with PaCel6A being the enzyme most similar to TrCel6A. PaCel6B was the only enzyme with higher specific activity on carboxymethylcellulose (CMC) than on Avicel and showed lower processivity than the others. Structural modeling predicts an open catalytic cleft, suggesting that PaCel6B is an endoglucanase.
The GENOMA-KB knowledge base includes four independent modules: a textual database, a factual dat... more The GENOMA-KB knowledge base includes four independent modules: a textual database, a factual database, a terminological database and an ontology. We will briefly introduce in this paper the main features concerning each one of the modules, and we will highlight the process of enlarging both the term base and the ontology.
... provide a sound theoretical basis for computer-aided unit detection, semi-automatic mapping o... more ... provide a sound theoretical basis for computer-aided unit detection, semi-automatic mapping of ... This situation may be overcome by using multiple inheritance (each node may inherit ... also include some organisation for other parts of speech (POS): adjectives, verbs and adverbs ...
To analyse the etiology, diagnostic methods and response to therapy in 30 episodes of pneumonia d... more To analyse the etiology, diagnostic methods and response to therapy in 30 episodes of pneumonia diagnosed in 17 patients with chronic lymphocytic leukemia (CLL) between 1995 and 2000. In each episode of pneumonia the following data were analysed: age, gender, treatment of CLL, antiinfectious prophylaxis, granulocytopenia, CD4/CD8 lymphocytes ratio, hipogammaglobulinemia, origin of pneumonia (nosocomial or community-acquired), localisation, respiratory insufficiency, need for mechanical ventilation, antimicrobial therapy and response. Diagnostic methods included blood and sputum cultures, fiberoptic bronchoscopy and search for antigens in urine (Legionella pneumophila serogroup 1, galactomannan, and Streptococcus pneumoniae). Median age of the series was 60 yr. (range 50-86) and 12 patients were male. Chlorambucil and prednisone were used in 13 cases and fludarabine in 8. Granulocytopenia was present in 14 episodes, hypogammaglobulinemia was seen in 22 and CD4/CD8 ratio was lower tha...
Background. The need for preoperative chemoradiation or short-course radiation in all T3 rectal t... more Background. The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma. Methods. We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). Results. On an intent-to-treat analysis, the ORR was 78% (n 5 36; 95% confidence interval [CI]: 63%-89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9-33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75%
Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screenin... more Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screening process and this limits its detection to the late stages, with consequently high mortality rates. Volatile organic compounds (VOC) are chemical compounds (mainly the products of cell catabolism) found as gases in the human breath. Different methods have been developed to analyse VOCs and to compare them in healthy subjects and lung cancer patients. In this review, we summarise the different techniques used to analyse VOC. Many reports have been published with promising results similar to those achieved with accepted screening methods such as mammography. These methods show good perspectives on lung cancer screening.
Gene signatures can provide prognostic and predictive information to help in the treatment of ear... more Gene signatures can provide prognostic and predictive information to help in the treatment of early-stage breast cancer. Although many of these signatures have been described, only a few have been properly validated. MammaPrint and OncoType offer prognostic information and identify low-risk patients who do not benefit from adjuvant chemotherapy. With regard to prediction of response, molecular subtypes of breast cancer differ in their sensitivity to chemotherapy, although further studies are needed in this field. Cost, small sample size, and the need to use central laboratories are common limitations to the widespread use of these tools.
1989) A new prognostic system for multiple myeloma based on easily available parameters. British ... more 1989) A new prognostic system for multiple myeloma based on easily available parameters. British Journal of Haernatology. 72, Cox, D.R. (1 9 72) Regression models and lifetables. Journal ofthe Royal , T.A. (1985) Regression models for prognostic predictions: advantages, problems and suggested solutions. Cancer Treatment Reports, 69,1071-507-511.
Cancer patients search for information about prognosis and treatment. Internet has become a major... more Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient-physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient-physician relationship. Physicians should ensure that their patients receive reliable online information.
A phase II study with an alternating chemotherapeutic scheme, in advanced gastric cancer was cond... more A phase II study with an alternating chemotherapeutic scheme, in advanced gastric cancer was conducted. Twenty-two patients were treated with cisplatin and mitomycin C on day 1 and BCNU and doxorubicin on day 28. Tegafur p.o. was given daily from the start to the end of chemotherapy. This scheme was repeated every four weeks. Response rate was 25% (2 complete and 3 partial). However, remissions were short lived, and median survival for the entire group was 7 months. Haematological and gastrointestinal toxicities were severe. In conclusion, the low response rate and the high toxicity of this regimen preclude its use for the treatment of gastric cancer.
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