Intra‐tumor heterogeneity is a vivid problem of molecular oncology that could be addressed by imaging mass spectrometry. Here we aimed to assess molecular heterogeneity of oral squamous cell carcinoma and to detect signatures discriminating normal and cancerous epithelium. Tryptic peptides were analyzed by MALDI‐IMS in tissue specimens from five patients with oral cancer. Novel algorithm of IMS data analysis was developed and implemented, which included Gaussian mixture modeling for detection of spectral components and iterative k‐means algorithm for unsupervised spectra clustering performed in domain reduced to a subset of the most dispersed components. About 4% of the detected peptides showed significantly different abundances between normal epithelium and tumor, and could be considered as a molecular signature of oral cancer. Moreover, unsupervised clustering revealed two major sub‐regions within expert‐defined tumor areas. One of them showed molecular similarity with histologically normal epithelium. The other one showed similarity with connective tissue, yet was markedly different from normal epithelium. Pathologist's re‐inspection of tissue specimens confirmed distinct features in both tumor sub‐regions: foci of actual cancer cells or cancer microenvironment‐related cells prevailed in corresponding areas. Hence, molecular differences detected during automated segmentation of IMS data had an apparent reflection in real structures present in tumor.
Advances in genomics, molecular pathology and metabolism have generated many candidate biomarkers of colorectal cancer with potential clinical value. Epidemiological and biological studies suggest a role for adiposity, dyslipidaemia, hyperinsulinemia, altered glucose homeostasis, and elevated expression of insulin-like growth factor (IGF) axis members in the risk and prognosis of cancer. This review discusses some recent past and current approaches being taken by researches in obesity and metabolic disorders. The authors describe three main systems as the most studied metabolic candidates of carcinogenesis: dyslipidemias, adipokines and insulin/IGF axis. However, each of these components is unsuccessful in defining the diseases risk and progression, while their co-occurrence increases cancer incidence and mortality in both men and women.
Adamalisynes (ADAMs) play an important role in inter-membrane interactions, cell adhesion and fusion processes and protein shedding from the cell surface. Many reports indicate that members of the ADAMs family are overexpressed in human cancer. The aim of the present study was to evaluate ADAM28 and Insulin Like Growth Factor Binding Protein-3 (IGFBP-3)) gene expression in colorectal carcinoma tissues with regard to the overweight or obese status of the patients using an oligonucleotide micro array technique. Fresh tissue specimens were obtained from colorectal cancer patients during surgical treatment. Eighteen specimens from tumour and 18 normal tissue specimens from colorectal cancer patients at clinical stages III and IV were analysed. The examined patients were divided into two groups; those with BMI;::25 and those with normal BMI. The control group consisted of 18 specimens of non-neoplastic colon tissues, which were divided between overweight/obese and normal body weight patients. The gene transcriptional activity from the specimens was analysed using an oligonucleotide microarray technique. Microarrays and rinsing and marking solutions were prepared according to the procedure in the Gene Expression Analysis Technical Manual. The following conclusions were made: i) change of ADAM28 and IGFBP-3 genes expression are present in the normal tissue in overweight/obese patients with colorectal cancer only; ii) the observed molecular variability of ADAM28 and IGFBP-3 expression may be an initial process of cancer proliferation; iii) the histopathologically normal surgical margin in this group of patients was not equal to the molecular margin.Adamalisynes (ADAM -a disintegrin and metalloproteinase domain), also known as MCDs (metalloprotease/disintegrin/cysteine rich protein), belong to a large family of zinc-dependent proteins referred to as methizines. Admalisynes is a group consisting of more than 30 type I transmembrane
Vitamin D3 (1,25(OH)2D3 (1,25-dihydroxyvitamin D3)) is a hormone playing a crucial role in numerous biological processes in the human body, including induction and control of cell proliferation and differentiation. Numerous data relate the vitamin D3 level with various types of cancer. It has been suggested that SNPs in the vitamin D3 receptor (VDR) gene might influence both the risk of cancer occurrence and cancer progression. The aim of this study was to search for genetic correlations between individual SNPs in the VDR gene and the risk of oral cavity carcinoma. Two SNPs were selected based on the literature and our previous results. Seventy-three patients with squamous cell carcinoma of the head and neck and one hundred control subjects were investigated. Two SNPs in the VDR gene were genotyped in minisequencing reactions followed by capillary electrophoresis. Hardy-Weinberg equilibrium (HWE), the χ(2) test and logistic regression were used for statistical analysis. The SNP rs2238135 in the VDR gene displayed statistical differences in frequency between the tested groups (p=0,0007). Furthermore, the G/C genotype of the rs2238135 in the VDR gene was characterized by a 3.16 fold increased risk of oral cavity carcinoma. The obtained results provide evidence for a genetic association between rs2238135 in the VDR gene and the occurrence and risk of oral cavity cancer.
This preliminary report has demonstrated the feasibility of IORT-PRS for patients with early oral cancer with the indications for postoperative radiotherapy. This method may be considered an alternative boost technique, although additional studies are needed to establish long-term results in a larger group of patients.
Resections of malignant tumors involving the mandible and anterior tongue result in complex defects that are still real challenges for reconstructive surgeons. Whereas there are preferred methods for mandible reconstruction involving isolated or limited loss of soft tissues, there are no standards for extended bone-soft tissue intraoral defects. This article documents the modification of the fibula free flap where triple skin islands are used for reconstruction of anterior tongue and floor of the mouth. The technique also includes filing the submandibular space with an isolated part of the flexor hallucis longus muscle, based on individual perforator. The details of flap designing, harvesting, and insetting are also presented. Eight such reconstructions have been performed on patients who underwent complex resection of the anterior mandible together with the mobile part of the tongue. Flap survival rate was 100%. In all eight cases, understandable speech and return to unrestricted diet mastication and swallowing were achieved. Analysis of aesthetic effects showed generally very good results. The presented modification of fibula free flap can be an alternative to double flaps in complex reconstruction of the mandible and mobile tongue.
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