Watch-and-wait strategy in rectal cancer: Is there a tumour size limit? Results from two pooled prospective studies.

Background: Frequency and predictive factors for a clinical complete response (cCR) in unselected patients are unclear.

Material And Methods: Two prospective observational studies were designed and pooled to explore predictive factors for cCR. Both studies evaluated the watch-and-wait strategy in consecutive patients; the first single-institutional study in elderly with a small tumour, the second multi-institutional study in all the patients receiving standard of care preoperative radiotherapy.

Guidelines of the Association of Polish Surgeons and the Polish Society of Surgical Oncology on the accreditation of healthcare centers providing cytoreductive surgery and HIPEC for primary and secondary peritoneal cancers.

Surgical interventions in patients with peritoneal metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic treatment are becoming more common and, when applied to selected patient groups, they reach 5-year survival rates of 32-52%. Good clinical outcomes require experienced and well-equipped healthcare centers, experienced surgical team and adequate patient qualification process. As a result of the discussion on the need for evaluation of quality of care and treatment outcomes and at the request of the Peritoneal Cancer Section of the Polish Society of Surgical Oncology, accreditation standards have been developed and the Accreditation Committee has been established for healthcare centers providing cytoreductive surgery and HIPEC for the management of primary and secondary peritoneal cancers.

Evaluation of MDA-MB-468 Cell Culture Media Analysis in Predicting Triple-Negative Breast Cancer Patient Sera Metabolic Profiles.

Triple-negative breast cancer (TNBC) is characterized by limited survival, poor prognosis, and high recurrence. Understanding the metabolic adaptations of TNBC could help reveal improved treatment regiments. Here we performed a comprehensive H NMR metabolic characterization of the MDA-MB-468 cell line, a commonly used model of TNBC, followed by an analysis of serum samples obtained from TNBC patients and healthy controls.

The Influence of Tumor Microenvironment on ATG4D Gene Expression in Colorectal Cancer Patients.

Despite great progress in research on the subject, the involvement of autophagy in colorectal cancer (CRC) pathogenesis (initiation, progression, metastasis) remains obscure and controversial. Autophagy is a catabolic process, fundamental to cell viability and connected with degradation/recycling of proteins and organelles. In this study, we aimed at investigating the relative expression level of mRNA via Real-Time PCR of 16 chosen genes belonging to Atg8 mammalian orthologs and their conjugation system, comprising GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, MAP1LC3C, ATG3, ATG7, ATG10, ATG4A, ATG4B, ATG4C, ATG4D, and three genes encoding proteins building the multimeric ATG16L1 complex, namely ATG5, ATG12, and ATG16L1, in 73 colorectal tumors and paired adjacent normal colon mucosa.

Peritoneal metastases of colorectal origin - cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The financial aspect.

The incidence of peritoneal carcinomatosis of colorectal cancer amounts to 5%-15% for synchronous metastases and as much as 40% in cases of local recurrence. Best results are obtained for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment offers much better outcomes, leading to 5-year survival rates of as much as 30%-50%.

The BAX gene as a candidate for negative autophagy-related genes regulator on mRNA levels in colorectal cancer.

Autophagy is a catabolic process, which is involved in the maintenance of intracellular homeostasis by degrading redundant molecules and organelles. Autophagy begins with the formation of a double-membrane phagophore, followed by its enclosure, thus leading to the appearance of an autophagosome which fuses with lysosome. This process is highly conserved, precisely orchestrated and regulated by autophagy-related genes.

Customized Array Comparative Genomic Hybridization Analysis of 25 Phosphatase-encoding Genes in Colorectal Cancer Tissues.

Background/aim: Molecular mechanisms of alterations in protein tyrosine phosphatases (PTPs) genes in cancer have been previously described and include chromosomal aberrations, gene mutations, and epigenetic silencing. However, little is known about small intragenic gains and losses that may lead to either changes in expression or enzyme activity and even loss of protein function.

Materials And Methods: The aim of this study was to investigate 25 phosphatase genes using customized array comparative genomic hybridization in 16 sporadic colorectal cancer tissues.

High PTPRQ Expression and Its Relationship to Expression of PTPRZ1 and the Presence of KRAS Mutations in Colorectal Cancer Tissues.

Background: The risk of sporadic colorectal cancer (CRC) is strongly influenced by Iifestyle, environmental and genetic factors. Protein tyrosine phosphatases belong to a group of enzymes whose role in CRC has not yet been intensively studied. They play an important role in activation/de-activation of many enzymes, influencing cell biology by catalyzing reactions opposing those catalyzed by kinases.

Selection of appropriate end-points (pCR vs 2yDFS) for tailoring treatments with prediction models in locally advanced rectal cancer.

Purpose: Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient's sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict.

Methods: Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy.

Vitamin D receptor gene polymorphisms in relation to the risk of colorectal cancer in the Polish population.

The protective effect of vitamin D against several cancers including colorectal cancer is modulated by the vitamin D receptor (VDR) and its ligand, the active form of vitamin D. VDR response has been found to play a role in various genes encoding proteins involved in crucial cellular pathways. Single nucleotide polymorphisms (SNPs) of the VDR gene that modulate its activity are located in the promoter region, exons 2-9, and their vicinity and also in the 3'UTR region.

Copy number alterations of chromosomal regions enclosing protein tyrosine phosphatase receptor-like genes in colorectal cancer.

Protein tyrosine phosphatases that act in different cellular pathways are described most commonly as tumor suppressors, but also as oncogenes. Their role has previously been described in colorectal cancer, as well as in gastric, breast, thyroid, prostate, ovarian, pancreatic, glioma, liver, leukemia and many other cancers. In a previous study, we have described protein tyrosine phosphatase receptor type T, M, Z1 and Q genes (PTPRT, PTPRM, PTPRZ1 and PTPRQ) hypermethylated in sporadic colorectal cancer.

Intraoperative blood loss during surgical treatment of low-rectal cancer by abdominosacral resection is higher than during extra-levator abdominosacral amputation of the rectum.

Introduction: Abdominosacral resection (ASR) usually required blood transfusions, which are virtually no longer in use in the modified abdominosacral amputation of the rectum (ASAR). The aim of this study was to compare the intra-operative bleeding in low-rectal patients subjected to ASR or ASAR.

Material And Methods: The study included low-rectal cancer patients subjected to ASR (n = 114) or ASAR (n = 46) who were retrospectively compared in terms of: 1) the frequency of blood transfusions during surgery and up to 24 h thereafter; 2) the volume of intraoperative blood loss (ml of blood transfused) during surgery and up to 24 h thereafter; 3) hemoglobin concentrations (Hb) 1, 3 and 5 days after surgery; 4) the duration of hospitalization.

Prognostic value of the Fas/Fas ligand system in breast cancer.

Fas and its ligand (FasL) are known to play a crucial role in the genetically controlled mechanism of cell death, and their deregulation in cancer cells is involved in the immune escape of the tumor. The aim of this review is to analyze the current knowledge on the prognostic value of Fas/FasL in breast cancer patients. Both the results of other authors and our own experiences indicate that the lack of Fas ligand, and particularly Fas, is related to a significantly worse prognosis.

Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance.

Alternate colorectal cancer (CRC) screening and surveillance strategies are needed to pre-select candidates for invasive methods. We compared systemic inflammatory profiles in CRC (n=99), health (n=98), high CRC-risk conditions (n=48) and overt inflammation (n=69) by multiplexed analysis of IL-1β, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-B and CEA. Cytokines corresponded with CRC advancement.

Neoadjuvant treatment for unresectable rectal cancer: an interim analysis of a multicentre randomized study.

Purpose: To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer.

Methods: Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II).

Therapeutic radiation induces different changes in expression profiles of metallothionein (MT) mRNA, MT protein, Ki 67 and minichromosome maintenance protein 3 in human rectal adenocarcinoma.

Aim: The study aimed at the evaluation of the effects of radiotherapy on expression of metallothionein (MT) isoforms, both in the form of quantitative alterations in mRNA, and differences in expression of MTI/II proteins in rectal tumours.

Materials And Methods: Material for the study originated from 21 patients with rectal cancer at stage II or III. Material for immunohistochemical studies [MTI/II, Minichromosome Maintenance Protein 3 (MCM3), Ki-67] and real-time polymerase chain reaction (PCR) (mRNA of MT1F, MT1X and MT2A) was sampled twice: during rectoscopic examination before the start of the preoperative radiotherapy (samples A) and from the post operative specimen, following radiotherapy (samples B).

Intermediate- and low-methylation epigenotypes do not correspond to CpG island methylator phenotype (low and -zero) in colorectal cancer.

Background: Most recent genome-wide studies on the CpG island methylation in colorectal cancer (CRC) have led to the discovery of at least 3 distinct methylation clusters. However, there remains an uncertainty whether the CRC clusters identified in these studies represent compatible phenotypes.

Methods: We carried out comprehensive genome-scale DNA methylation profiling by Illumina Infinium HumanMethylation27 of 21 DNA pools that represent 84 CRC samples divided according to their high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively) and 70 normal-adjacent colonic tissues.

Protein tyrosine phosphatase receptor-like genes are frequently hypermethylated in sporadic colorectal cancer.

The activity of phosphatases could be influenced by genetic, as well as epigenetic alterations. In our study, we have investigated the methylation status of four PTPRs: PTPRM, PTPRT, PTPRR and PTPRZ1, which were pre-selected using microarray techniques as being alternatively methylated in sporadic colorectal cancer (CRC). The analyses were carried out on 131 surgical specimens obtained from sporadic CRC patients.

Preoperative treatment does not improve the therapeutic results of abdominosacral amputation of the rectum.

Background: This study reviewed the impact of preoperative chemoradiotherapy/short-term radiotherapy on abdominosacral amputations of the rectum (ASAR) for the treatment of low-rectum cancers in terms of postoperative morbidity, local recurrence rates, and survival.

Methods: A total of 198 patients with stage II and III tumors located within 6 cm of the anorectal junction underwent ASAR between 1998 and 2008 and were selected for further analysis. Patients were compared according to the following groups: those who had surgery only (Group A) and those who had preoperative chemoradiotherapy/short-term radiotherapy (Group B).

Assessment of chromosomal imbalances in CIMP-high and CIMP-low/CIMP-0 colorectal cancers.

Data presented in a number of recent studies have revealed a negative correlation between CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) measured by a loss of heterozygosity (LOH) of selected loci, suggesting that CIN and CIMP represent two independent mechanisms in sporadic colorectal cancer (CRC) carcinogenesis. However, CIN is a heterogeneous phenomenon, which may be studied not only by employing LOH analysis but also by observing chromosomal imbalances (gains and deletions). The current study aimed to investigate the relationship between CIMP and chromosomal gains and deletions (assessed by comparative genomic hybridization) in a group of 20 CIMP-high and 79 CIMP-low/CIMP-0 CRCs.

Assessment of three epigenotypes in colorectal cancer by combined bisulfite restriction analysis.

Recent investigations have demonstrated the clear heterogeneity of sporadic colorectal cancer (CRC) with regard to CpG island methylation. Two unsupervised cluster analyses revealed that CRCs form three distinct DNA methylation subsets, which are referred to as the high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively). A recent study by Yagi et al.

Age- and disease-related innate immunity of human leukocytes ex vivo.

Two mechanisms of innate immunity, i.e. resistance to viral infection and the production of cytokines by leukocytes, were compared in blood isolated from four groups of donors: healthy young (19-35 years old), healthy elderly (over 60), elderly Alzheimer's disease (AD) patients, and elderly patients with alimentary tract cancer (CA).

Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials.

Purpose: The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up.

Patients And Methods: All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set.

Serum vascular endothelial growth factors a, C and d in human breast tumors.

Available evidence suggests that vascular endothelial growth factor (VEGF) a potent regulator of vasculogenesis and tumor angiogenesis may be a predictor of recurrence in breast cancer patients. We sought to determine whether VEGF serum levels (VEGF-A, VEGF-C and VEGF-D) in 377 patients with malignant and benign breast tumors differ and whether there is association between vascular growth factors, clinicopathologic features and prognosis. There was no significant difference in investigated circulating angiogenic markers between patients with malignant and non malignant lesions.