Sidney Chalub | Universidade Federal do Amazonas (original) (raw)

Papers by Sidney Chalub

Journal of proteomics, Feb 14, 2016

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival ... more Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked...

Journal of Proteome Research, 2012

A strategy for treating cancer is to surgically remove the tumor together with a portion of appar... more A strategy for treating cancer is to surgically remove the tumor together with a portion of apparently healthy tissue surrounding it, the so-called "resection margin", to minimize recurrence. Here, we investigate whether the proteomic profiles from biopsies of gastric cancer resection margins are indeed more similar to those from healthy tissue than from cancer biopsies. To this end, we analyzed biopsies using an offline MudPIT shotgun proteomic approach and performed label-free quantitation through a distributed normalized spectral abundance factor approach adapted for extracted ion chromatograms (XICs). A multidimensional scaling analysis revealed that each of those tissue-types is very distinct from each other. The resection margin presented several proteins previously correlated with cancer, but also other overexpressed proteins that may be related to tumor nourishment and metastasis, such as collagen alpha-1, ceruloplasmin, calpastatin, and E-cadherin. We argue that the resection margin plays a key role in Paget's "soil to seed" hypothesis, that is, that cancer cells require a special microenvironment to nourish and that understanding it could ultimately lead to more effective treatments.

ANAIS DO PROGRAMA DE APOIO À INICIAÇÃO CIENTÍFICA PAIC – FHAJ – FAPEAM

Gastric cancer is one of most frequent causes of death in Brazil. The city of Manaus has one of t... more Gastric cancer is one of most frequent causes of death in Brazil. The city of Manaus has one of the highest incidences of this disease in Brazil. The Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that is classified as a group 1 carcinogen by the International Agency for Research on Cancer. We obtained biopsies from 6 control subjects and 10 patients with gastric carcinomas living in Manaus. In the patients, the samples were taken from tumors and from adjacent non-cancerous mucosa. These samples were screened for EBV DNA by PCR to amplify the 288-bp fragments from the Bam M region. The

Genetics and molecular research : GMR, 2013

Hepatocellular carcinoma is an infection of variable incidence that can be caused by hepatitis B ... more Hepatocellular carcinoma is an infection of variable incidence that can be caused by hepatitis B virus (HBV), which is endemic in the Amazon region. The diagnosis of HBV can be performed through the use of serum markers such as the hepatitis B surface antigen. The chronic HBV can cause mutagenesis and carcinogenesis, being the susceptibility of infection due to allele human leukocyte antigen (HLA). Thus, we evaluated the clinical, molecular and laboratory profile (histocompatibility complex) of HBV in 22 patients with hepatocellular carcinoma in Amazonia, including 18 males and 4 females, using a blood sample for generic HLA class II. The results showed increased frequency of disease evolution in adults between 25 and 64 years old, who comprised 19 of the 22 patients studied. Most patients (16/22) presented high levels of alpha-fetoprotein and transaminases (14/22). The most common HLA alleles were DRB1 04 (8/44), DRB1 08 (9/44), DRB 03 (16/44), and DQB1 04 (9/44). When we compared ...

BACKGROUND: According to the precepts of reduced surgical trauma and better cosmesis, an intermed... more BACKGROUND: According to the precepts of reduced surgical trauma and better cosmesis, an intermediate laparoscopic appendectomy technique between the conventional three-trocar procedure and Laparoendoscopic Single Site Surgery (LESS) was performed, based on literature review and experience of the surgical team. PATIENTS AND METHODS: Patients with early stage acute appendicitis and a favourable anatomical presentation were selected. The procedure was performed with two ports: A 10 mm trocar at the umbilicus site for laparoscope and a 5 mm one just above the pubic bone for grasper. The appendix was secured by external wire traction through a right iliac fossa puncture with 14-gauge intravenous catheter. RESULTS: From August 2009 to December 2012, we performed 42 cases; two required conversion to a conventional laparoscopic technique. There were no complications in the remaining, no wound infections and a mean operation time of 64.5 minutes. CONCLUSION: The use of two-port laparoscopic...

Journal of Proteome Research, 2012

A strategy for treating cancer is to surgically remove the tumor together with a portion of appar... more A strategy for treating cancer is to surgically remove the tumor together with a portion of apparently healthy tissue surrounding it, the so-called "resection margin", to minimize recurrence. Here, we investigate whether the proteomic profiles from biopsies of gastric cancer resection margins are indeed more similar to those from healthy tissue than from cancer biopsies. To this end, we analyzed biopsies using an offline MudPIT shotgun proteomic approach and performed label-free quantitation through a distributed normalized spectral abundance factor approach adapted for extracted ion chromatograms (XICs). A multidimensional scaling analysis revealed that each of those tissue-types is very distinct from each other. The resection margin presented several proteins previously correlated with cancer, but also other overexpressed proteins that may be related to tumor nourishment and metastasis, such as collagen alpha-1, ceruloplasmin, calpastatin, and E-cadherin. We argue that t...

Journal of proteomics, Feb 14, 2016

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival ... more Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked...

Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery

In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. T... more In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. The cause is multivariate and the risks are well known. It has prognosis and treatment defined by the location and staging of the tumor and number of lymph nodes resected and involved. The Brazilian Consensus on Gastric Cancer promoted by ABCG was designed with the intention to issue guidelines that can guide medical professionals to care for patients with this disease. Were summarized and answered 43 questions reflecting consensus or not on diagnosis and treatment that may be used as guidance for its multidisciplinary approach. The method involved three steps. Initially, 56 digestive surgeons and related medical specialties met to formulate the questions that were sent to participants for answers on scientific evidence and personal experience. Summaries were presented, discussed and voted in plenary in two other meetings. They covered 53 questions involving: diagnosis and staging (six qu...

Journal of Proteome Research

Accessing localized proteomic profiles has emerged as a fundamental strategy to understand the bi... more Accessing localized proteomic profiles has emerged as a fundamental strategy to understand the biology of diseases, as recently demonstrated, for example, in the context of determining cancer resection margins with improved precision. Here, we analyze a gastric cancer biopsy sectioned into 10 parts, each one subjected to MudPIT analysis. We introduce a software tool, named Shotgun Imaging Analyzer and inspired in MALDI imaging, to enable the overlaying of a protein's expression heat map on a tissue picture. The software is tightly integrated with the NeXtProt database, so it enables the browsing of identified proteins according to chromosomes, quickly listing human proteins never identified by mass spectrometry (i.e., the so-called missing proteins), and the automatic search for proteins that are more expressed over a specific region of interest on the biopsy, all of which constitute goals that are clearly well-aligned with those of the C-HPP. Our software has been able to highl...

Biological Research, 2015

Background: DNA methylation is commonly linked with the silencing of the gene expression for many... more Background: DNA methylation is commonly linked with the silencing of the gene expression for many tumor suppressor genes. As such, determining DNA methylation patterns should aid, in times to come, in the diagnosis and personal treatment for various types of cancers. Here, we analyzed the methylation pattern from five colorectal cancer patients from the Amazon state in Brazil for four tumor suppressor genes, viz.: DAPK, CDH1, CDKN2A, and TIMP2 by employing a polymerase chain reaction (PCR) specific to methylation. Efforts in the study of colorectal cancer are fundamental as it is the third most of highest incidence in the world. Results: Tumor biopsies were methylated in 1/5 (20 %), 2/5 (40 %), 4/5 (80 %), and 4/5 (80 %) for CDH1, CDKN2A, DAPK, and TIMP2 genes, respectively. The margin biopsies were methylated in 3/7 (43 %), 2/7 (28 %), 7/7 (100 %), and 6/7 (86 %) for CDH1, CDKN2A, DAPK, and TIMP2, respectively. Conclusions: Our findings showed DAPK and TIMP2 to be methylated in most samples from both tumor tissues and adjacent non-neoplastic margins; thus presenting distinct methylation patterns. This emphasizes the importance of better understanding of the relation of these patterns with cancer in the context of different populations.

Transactions of The Royal Society of Tropical Medicine and Hygiene, 2007

Echinococcus vogeli has been reported to cause human polycystic echinococcosis. A 43-year-old Bra... more Echinococcus vogeli has been reported to cause human polycystic echinococcosis. A 43-year-old Brazilian woman was admitted to hospital complaining of mild epigastric discomfort. Computed tomography (CT) revealed multiple cystic lesions with calcified edges in several hepatic segments. At exploratory laparotomy, polycystic lesions were excised from the liver, omentum and peritoneum. No remaining cysts were observed on a post-surgery CT scan. The patient was asymptomatic when discharged on Day 19 post-operatively. She was prescribed albendazole therapy for 6 months. Follow-up CT performed 11 months later revealed no evidence of recurrence. Surgery combined with chemotherapy may improve the quality of life of patients with polycystic echinococcosis.

Journal of proteomics, Feb 14, 2016

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival ... more Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked...

Journal of Proteome Research, 2012

A strategy for treating cancer is to surgically remove the tumor together with a portion of appar... more A strategy for treating cancer is to surgically remove the tumor together with a portion of apparently healthy tissue surrounding it, the so-called "resection margin", to minimize recurrence. Here, we investigate whether the proteomic profiles from biopsies of gastric cancer resection margins are indeed more similar to those from healthy tissue than from cancer biopsies. To this end, we analyzed biopsies using an offline MudPIT shotgun proteomic approach and performed label-free quantitation through a distributed normalized spectral abundance factor approach adapted for extracted ion chromatograms (XICs). A multidimensional scaling analysis revealed that each of those tissue-types is very distinct from each other. The resection margin presented several proteins previously correlated with cancer, but also other overexpressed proteins that may be related to tumor nourishment and metastasis, such as collagen alpha-1, ceruloplasmin, calpastatin, and E-cadherin. We argue that the resection margin plays a key role in Paget's "soil to seed" hypothesis, that is, that cancer cells require a special microenvironment to nourish and that understanding it could ultimately lead to more effective treatments.

ANAIS DO PROGRAMA DE APOIO À INICIAÇÃO CIENTÍFICA PAIC – FHAJ – FAPEAM

Gastric cancer is one of most frequent causes of death in Brazil. The city of Manaus has one of t... more Gastric cancer is one of most frequent causes of death in Brazil. The city of Manaus has one of the highest incidences of this disease in Brazil. The Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that is classified as a group 1 carcinogen by the International Agency for Research on Cancer. We obtained biopsies from 6 control subjects and 10 patients with gastric carcinomas living in Manaus. In the patients, the samples were taken from tumors and from adjacent non-cancerous mucosa. These samples were screened for EBV DNA by PCR to amplify the 288-bp fragments from the Bam M region. The

Genetics and molecular research : GMR, 2013

Hepatocellular carcinoma is an infection of variable incidence that can be caused by hepatitis B ... more Hepatocellular carcinoma is an infection of variable incidence that can be caused by hepatitis B virus (HBV), which is endemic in the Amazon region. The diagnosis of HBV can be performed through the use of serum markers such as the hepatitis B surface antigen. The chronic HBV can cause mutagenesis and carcinogenesis, being the susceptibility of infection due to allele human leukocyte antigen (HLA). Thus, we evaluated the clinical, molecular and laboratory profile (histocompatibility complex) of HBV in 22 patients with hepatocellular carcinoma in Amazonia, including 18 males and 4 females, using a blood sample for generic HLA class II. The results showed increased frequency of disease evolution in adults between 25 and 64 years old, who comprised 19 of the 22 patients studied. Most patients (16/22) presented high levels of alpha-fetoprotein and transaminases (14/22). The most common HLA alleles were DRB1 04 (8/44), DRB1 08 (9/44), DRB 03 (16/44), and DQB1 04 (9/44). When we compared ...

BACKGROUND: According to the precepts of reduced surgical trauma and better cosmesis, an intermed... more BACKGROUND: According to the precepts of reduced surgical trauma and better cosmesis, an intermediate laparoscopic appendectomy technique between the conventional three-trocar procedure and Laparoendoscopic Single Site Surgery (LESS) was performed, based on literature review and experience of the surgical team. PATIENTS AND METHODS: Patients with early stage acute appendicitis and a favourable anatomical presentation were selected. The procedure was performed with two ports: A 10 mm trocar at the umbilicus site for laparoscope and a 5 mm one just above the pubic bone for grasper. The appendix was secured by external wire traction through a right iliac fossa puncture with 14-gauge intravenous catheter. RESULTS: From August 2009 to December 2012, we performed 42 cases; two required conversion to a conventional laparoscopic technique. There were no complications in the remaining, no wound infections and a mean operation time of 64.5 minutes. CONCLUSION: The use of two-port laparoscopic...

Journal of Proteome Research, 2012

A strategy for treating cancer is to surgically remove the tumor together with a portion of appar... more A strategy for treating cancer is to surgically remove the tumor together with a portion of apparently healthy tissue surrounding it, the so-called "resection margin", to minimize recurrence. Here, we investigate whether the proteomic profiles from biopsies of gastric cancer resection margins are indeed more similar to those from healthy tissue than from cancer biopsies. To this end, we analyzed biopsies using an offline MudPIT shotgun proteomic approach and performed label-free quantitation through a distributed normalized spectral abundance factor approach adapted for extracted ion chromatograms (XICs). A multidimensional scaling analysis revealed that each of those tissue-types is very distinct from each other. The resection margin presented several proteins previously correlated with cancer, but also other overexpressed proteins that may be related to tumor nourishment and metastasis, such as collagen alpha-1, ceruloplasmin, calpastatin, and E-cadherin. We argue that t...

Journal of proteomics, Feb 14, 2016

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival ... more Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked...

Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery

In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. T... more In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. The cause is multivariate and the risks are well known. It has prognosis and treatment defined by the location and staging of the tumor and number of lymph nodes resected and involved. The Brazilian Consensus on Gastric Cancer promoted by ABCG was designed with the intention to issue guidelines that can guide medical professionals to care for patients with this disease. Were summarized and answered 43 questions reflecting consensus or not on diagnosis and treatment that may be used as guidance for its multidisciplinary approach. The method involved three steps. Initially, 56 digestive surgeons and related medical specialties met to formulate the questions that were sent to participants for answers on scientific evidence and personal experience. Summaries were presented, discussed and voted in plenary in two other meetings. They covered 53 questions involving: diagnosis and staging (six qu...

Journal of Proteome Research

Accessing localized proteomic profiles has emerged as a fundamental strategy to understand the bi... more Accessing localized proteomic profiles has emerged as a fundamental strategy to understand the biology of diseases, as recently demonstrated, for example, in the context of determining cancer resection margins with improved precision. Here, we analyze a gastric cancer biopsy sectioned into 10 parts, each one subjected to MudPIT analysis. We introduce a software tool, named Shotgun Imaging Analyzer and inspired in MALDI imaging, to enable the overlaying of a protein's expression heat map on a tissue picture. The software is tightly integrated with the NeXtProt database, so it enables the browsing of identified proteins according to chromosomes, quickly listing human proteins never identified by mass spectrometry (i.e., the so-called missing proteins), and the automatic search for proteins that are more expressed over a specific region of interest on the biopsy, all of which constitute goals that are clearly well-aligned with those of the C-HPP. Our software has been able to highl...

Biological Research, 2015

Background: DNA methylation is commonly linked with the silencing of the gene expression for many... more Background: DNA methylation is commonly linked with the silencing of the gene expression for many tumor suppressor genes. As such, determining DNA methylation patterns should aid, in times to come, in the diagnosis and personal treatment for various types of cancers. Here, we analyzed the methylation pattern from five colorectal cancer patients from the Amazon state in Brazil for four tumor suppressor genes, viz.: DAPK, CDH1, CDKN2A, and TIMP2 by employing a polymerase chain reaction (PCR) specific to methylation. Efforts in the study of colorectal cancer are fundamental as it is the third most of highest incidence in the world. Results: Tumor biopsies were methylated in 1/5 (20 %), 2/5 (40 %), 4/5 (80 %), and 4/5 (80 %) for CDH1, CDKN2A, DAPK, and TIMP2 genes, respectively. The margin biopsies were methylated in 3/7 (43 %), 2/7 (28 %), 7/7 (100 %), and 6/7 (86 %) for CDH1, CDKN2A, DAPK, and TIMP2, respectively. Conclusions: Our findings showed DAPK and TIMP2 to be methylated in most samples from both tumor tissues and adjacent non-neoplastic margins; thus presenting distinct methylation patterns. This emphasizes the importance of better understanding of the relation of these patterns with cancer in the context of different populations.

Transactions of The Royal Society of Tropical Medicine and Hygiene, 2007

Echinococcus vogeli has been reported to cause human polycystic echinococcosis. A 43-year-old Bra... more Echinococcus vogeli has been reported to cause human polycystic echinococcosis. A 43-year-old Brazilian woman was admitted to hospital complaining of mild epigastric discomfort. Computed tomography (CT) revealed multiple cystic lesions with calcified edges in several hepatic segments. At exploratory laparotomy, polycystic lesions were excised from the liver, omentum and peritoneum. No remaining cysts were observed on a post-surgery CT scan. The patient was asymptomatic when discharged on Day 19 post-operatively. She was prescribed albendazole therapy for 6 months. Follow-up CT performed 11 months later revealed no evidence of recurrence. Surgery combined with chemotherapy may improve the quality of life of patients with polycystic echinococcosis.