Update on colorectal carcinomatosis - from molecular biology to diagnosis and management

After liver metastases, Peritoneal Carcinomatosis (PC) is the second most frequent cause of death in patients with Co-lorectal Cancer (CRC), although the precise incidence of Colorectal Cancer Peritoneal Carcinomatosis is not known, as the majority of the diagnostic studies cannot detect the disease in its initial stages, nowadays, the diagnosis of peritoneal carcinomatosis remains a challenge. The molecular biology of PC is only just beginning to be understood, future knowledge will permit not only identify novel strategies for PC prevention, but also contribute to therapeutic advances, through the development of molecular targeted therapies. The authors performed a literature revision about the Molecu-lar Biology, Diagnosis and Management of Colorectal Cancer Peritoneal carcinomatosis

Clinicopathological correlation and prognostic significance of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression in colorectal cancer

BACKGROUND: Colorectal cancer (CRC) is the third most common type of cancer and the fourth most frequent cause of cancer death. Literature indicates that vascular endothelial growth factor is a predominant angiogenic factor and that angiogenesis plays an important role in the progression of CRC. PATIENTS AND METHODS: The present series consisted of tissue samples obtained from 672 patients who had undergone large bowel resection between 2005 and 2010 at the Braga Hospital, Portugal. Archival paraffin-embedded CRC tissue and normal adjacent samples were used to build up tissue microarray blocks and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression was immunohistochemically assessed. RESULTS: We observed an overexpression of VEGF-C in CRC when tumour cells and normal-adjacent tissue were compared (p=0.004). In tumour samples, VEGF-C-positive cases were associated with VEGFR-3 expression (p=0.047). When assessing the correlation between VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expressions and the clinicopathological data, it was revealed that VEGF-A positive cases were associated with male gender (p=0.016) and well-differentiated tumours (p=0.001); VEGF-C with colon cancers (p=0.037), exophytic (p=0.048), moderately-differentiated (p=0.007) and T3/T4 (p=0.010) tumours; VEGFR-2 with invasive adenocarcinoma (p=0.007) and VEGFR-3 with the presence of hepatic metastasis (p=0.032). Overall survival curves for CRC were statistically significant for rectal cancer, VEGF-C expression and stage III (p=0.019) and VEGFR-3 expression and stage IV (p=0.047). CONCLUSION: Quantification of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression seems to provide valuable prognostic information in CRC and the correlation with clinicopathological data revealed an association with characteristics that contribute to progression, invasion and metastasis leading to poorer survival rates and prognosis

Predictive biomarkers in colorectal cancer: from the single therapeutic target to a plethora of options

Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy.info:eu-repo/semantics/publishedVersio

Papillomavirus from the bench to the clinics

[Excerpt] Human papillomavirus (HPV) represents an exciting subject of study because it is currently established as an essential etiological factor of uterine cervical cancer and strongly implicated in the development of other genital cancers as well, in addition to benign genital warts. Additionally, substantial amount of new data have been elaborated linking HPV with head and neck cancer and, more tentatively, also with esophageal, breast, prostate, and lung cancers. Despite the existing controversies, the possible link of HPV infection with these nongenital carcinomas opens a new fascinating era of HPV research. [...

Lymphangiogenesis: from the pig embryos to cancer

The discovery and the comprehension of lymphatic vessels suffered several historical delays and setbacks. The inherent anatomical problems slowed down the precise identification of the lymphatic system during the development of medical science. Gasparo Aselli, an Italian surgeon and anatomist, was the first to describe the lymphatic vessels in 1627 (De Lacteibus sive Lacteis Venis). However, most original descriptions that report the morphology of the lymphatic system in different organisms were done during the 19th and the 20th centuries. The recent identification of specific lymphatic vasculature molecular markers allows a more accurate identification and characterization of the lymphatic system evolution in different organs, as well as its role in different pathological conditions, including cancer. This study summarizes the current understanding of lymphangiogenesis in tumour progression, as well as it presents a review of the promising data regarding the prognostic value of lymphatic density and the use of therapeutic lymphangiogenic molecules.A descoberta dos vasos linfáticos e sua compreensão enfrentaram uma série de atrasos e dificuldades históricos. As inerentes dificuldades anatômicas retardaram a identificação precisa da rede vascular linfática durante o desenvolvimento da ciência médica. Gasparo Aselli, um anatomista e cirurgião italiano, foi o primeiro a descrever os vasos linfáticos, em 1627 (De Lacteibus sive Lacteis Venis). Entretanto, a maioria das descrições originais que relatam a morfologia do sistema linfático nos diferentes organismos foi realizada depois, entre os séculos XIX e XX. A recente identificação de marcadores moleculares específicos à vasculatura linfática permite agora identificação e caracterização mais acuradas da evolução da rede linfática nos vários órgãos e em diferentes situações, inclusive no câncer. Esta revisão resume o conhecimento sobre a linfangiogênese na progressão tumoral, bem como apresenta uma síntese dos dados mais promissores em relação ao valor prognóstico da densidade linfática e da utilização das moléculas linfangiogênicas como alvo terapêutico.(undefined

Angiogenesis and Breast Cancer

Angiogenesis is an essential step for breast cancer progression and dissemination. The development of new blood vessels in cancer setting (angiogenesis) is conducted by numerous physiological and pathological stimuli, where the main stimulus is hypoxia. The knowledge of different molecular pathways regulating angiogenesis is constantly growing. An increased and complex scenario of angiogenesis is nowadays available in breast cancer, specifically, and permits not only to understand most of the important phases of neoplastic growth but also offer an exciting perspective for new therapeutic proposals based on blocking new blood vessels sprouting. This review focused on historical and recent understanding of angiogenesis occurrence in breast cancer

Methodology for single nucleotide polymorphism selection in promoter regions for clinical use. An example of its applicability

Genetic variability in humans can explain many differences in disease risk factors. Polymorphism-related studies focus mainly on the single nucleotide polymorphisms (SNPs) of coding regions of the genes. SNPs on DNA binding motifs of the promoter region have been less explored. On a recent study of SNPs in patients with non-Hodgkin lymphomas we faced the problem of SNP selection from promoter regions and developed a practical methodology for clinical studies. The process consists in identifying SNPs in the coding and promoter regions of the antigen-processing system using the 'dbSNP' database. With the 'HapMap' program, we select SNPs with frequencies >20% in Caucasian populations. For coding regions, we sought biologically and clinically relevant SNPs described in the literature. For the promoter regions, we determined their chromosomal location on 'QiagenSABioscience' site database. The nucleotide sequence of ancestral and variant alleles is available in the 'dbSNP'. These sequences were used in ` Promoter TESS' to determine binding differences of transcription factors. Each sequence may have affinity to different TFs. Thus, SNP selection on the promoter regions was based in the differences on TF binding pattern between the old and the new allele. The potential clinical relevance of the new TFs was also evaluated before the final selection. With this approach, we found that almost half of the relevant SNP fall within the promoter region. In conclusion, we were able to develop a methodology of oriented selection of promoter regions of human genes, comparing the TF with affinity to the ancestral allele with the TF to a variant allele. We selected those SNPs that change the TF's affinity to a pattern with functional significance.(undefined)info:eu-repo/semantics/publishedVersio

A hospital based cohort study of colorectal cancer cases treated at Braga Hospital, Northern Portugal

Background: Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nonetheless, despite being a frequent cancer on which many epidemiological international studies have already been written, Portuguese epidemiological data are scarce and in particular there are very few specific data for Minho Region, which is traditionally recognized as a high incidence area. Aim: Characterize CRC patients treated at Braga Hospital. Methods: Data regarding clinical and preoperative diagnostic examinations, operative reports and histopathological and follow-up data was collected prospectively and stored in two Excel PC databases (colon and rectal cancer) and statistically analysed using the Statistical Package for the Social Sciences, version 19.0 (SPSS Inc., Chicago, Illinois, USA). All comparisons were examined for statistical significance using Pearson’s chi-square (?2) test and Fisher’s exact test (when n<5), with the threshold for significance P values <0.05. Overall survival and Survival free disease were both assessed using the Kaplan-Meier method. Results: The study comprises 672 patients with histological diagnosis of CRC treated in Braga Hospital between 2005 and 2009. It included 62.3% males and 37.7% females and most patients (60.5%) were between 61-80 years old. 65.3% of the cases arose from colon cancer and 34.7% from rectal cancer. We observed that 94.8% of the patients had no previous history of colorectal polyps. 4.1% had a previous personal history of CRC and 7.7% of a different cancer. 9.7% had a positive CRC family history. Most patients (81.3%) were symptomatic at diagnosis, while 18.8% were detected by routine colonoscopies. Colon and rectal cancer from most patients was at IIA stage and IV stage respectively. Follow-up time ranged between 1 and 5 years and, during this period, 26.7% of colon cancer patients and 25.3% of rectal cancer patients died from a colorectal cancer-related cause; also, 14.6% and 19.3% respectively had recurrence, mainly in the liver. Conclusion: This is the first study of a large cohort of CRC patients from the Minho Region in Northern Portugal. The large majority of the 672 cases were diagnosed because symptomatic and at an advanced stage, with a relatively poor prognosis. These findings emphasize the need to start a screening program and diagnose CRC at an early stage, thus increasing cure rates and improving resource management

Immunoscore and Microbiome in Colorectal Cancer: What’s New?

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer death in the world, accounting for about 1.4 million new cases and almost 700,000 deaths in 2012. The clinical outcome and the tumor progression are now considered the result of a balance between the invasiveness of the tumor and the immune response of the patient against the tumor. The immune system has the ability to control and shape cancer through a mechanism called immunoediting, which include elimination, equilibrium, and escape. The consensus Immunoscore is a scoring system that outlines the density of CD3+ and CD8+ T-cell effectors existent in the tumor and its invasive margin. The pre-existing intra-tumoral immunity could be enhanced and activated by immunotherapy. Immunoscore could be a good prognostic marker, by identifying patients at high risk of tumor recurrence and stratifying patients who could benefit from adjuvant therapies. Human surfaces and cavities are populated by numerous microbial communities, and they play an indispensable role in human health, as they interact with the immune system. The authors made a literature revision concerning the role of Immunoscore and microbiome in colorectal cancer