Cancer-bearing Tissue Research Articles

Distinct prognostic value of dynactin subunit 4 (DCTN4) and diagnostic value of DCTN1, DCTN2, and DCTN4 in colon adenocarcinoma.

BackgroundColon adenocarcinoma (COAD) is ranked as the third most commonly diagnosed cancer in both women and men, and it is the most frequently occurring malignant tumor. Dynactin is a protein compound based on multiple subunits, including dynactin 1–6 (DCTN1–6), in most categories of cytoplasmic dynein performance in eukaryotes. Nevertheless, correlations between the DCTN family and the prognosis and diagnosis of COAD remain unidentified.MethodsStatistics for DCTN mRNA expression in patients with COAD were acquired from The Cancer Genome Atlas. Kaplan–Meier analyses and a Cox regression model were applied to determine overall survival, with computation of HRs and 95% CIs. Several online data portals were used to assess the biological process, and pathway examination was performed using the Kyoto Encyclopedia of Genes and Genomes to predict the biological functionality of DCTN genes.ResultsWe found that high expression of DCTN4 was linked with satisfactory results for overall survival (P=0.042, HR=0.650, 95% CI 0.429–0.985). The expression of DCTN1, DATN2, and DCTN4 was closely correlated with the frequency of colon tumors (P<0.001, area under the curve [AUC]=0.8811, 95% CI 0.8311–0.9312; P<0.001, AUC=0.870, 96% CI 0.833–0.9071; and P=0.0051, AUC=0.6317, 95% CI 0.5725–0.6908, respectively). In the enrichment examination, the level of gene expression was related to the cell cycle, cell apoptosis, and the cell metastasis pathway.ConclusionThe expression levels of DCTN1, DCTN2, and DCTN4 could allow differentiation between cancer-bearing tissues and paracancerous tissue. These genes can be applied as biomarkers to predict the prognosis and diagnosis of COAD.

Infiltrating S100A8+ myeloid cells promote metastatic spread of human breast cancer and predict poor clinical outcome.

The mechanisms by which breast cancer (BrC) can successfully metastasize are complex and not yet fully understood. Our goal was to identify tumor-induced stromal changes that influence metastatic cell behavior, and may serve as better targets for therapy. To identify stromal changes in cancer-bearing tissue, dual-species gene expression analysis was performed for three different metastatic BrC xenograft models. Results were confirmed by immunohistochemistry, flow cytometry, and protein knockdown. These results were validated in human clinical samples at the mRNA and protein level by retrospective analysis of cohorts of human BrC specimens. In pre-clinical models of BrC, systemic recruitment of S100A8+ myeloid cells-including myeloid-derived suppressor cells (MDSCs)-was promoted by tumor-derived factors. Recruitment of S100A8+ myeloid cells was diminished by inhibition of tumor-derived factors or depletion of MDSCs, resulting in fewer metastases and smaller primary tumors. Importantly, these MDSCs retain their ability to suppress T cell proliferation upon co-culture. Secretion of macrophage inhibitory factor (MIF) activated the recruitment of S100A8+ myeloid cells systemically. Inhibition of MIF, or depletion of MDSCs resulted in delayed tumor growth and lower metastatic burden. In human BrC specimens, increased mRNA and protein levels of S100A8+ infiltrating cells are highly associated with poor overall survival and shorter metastasis free survival of BrC patients, respectively. Furthermore, analysis of nine different human gene expression datasets confirms the association of increased levels of S100A8 transcripts with an increased risk of death. Recruitment of S100A8+ myeloid cells to primary tumors and secondary sites in xenograft models of BrC enhances cancer progression independent of their suppressive activity on T cells. In clinical samples, infiltrating S100A8+ cells are associated with poor overall survival. Targeting these molecules or associated pathways in cells of the tumor microenvironment may translate into novel therapeutic interventions and benefit patient outcome.

Dynamic schema for near infrared detection of pressure-induced changes in solid tumors

Differentiation among malignant tumors, benign tumors, and normal tissue is highly important in the diagnosis and treatment of many malignancies. We have proposed a dynamic schema for noninvasive characterization of pressure-induced changes in solid tumors. Our hypothesis has been that the altered neovascularization processes within cancer-bearing tissues may significantly increase vascular resistance and cause a much slower response of hemoglobin concentration during a dynamic compression stimulus. This hypothesis was tested by the evaluation of data generated from human tumor clinical testing and from animal tumor model testing. In the human tumor clinical testing, a unified diagnostic criterion was derived that integrated the relative characteristics of tumor oxygen, hemoglobin, and hemoglobin dynamics. By applying such a unified criterion, we were able to differentiate benign breast lesions and malignant breast tumors with high sensitivity and specificity within a subset of 14 suspicious breast lesions with similar size and depth characteristics. In the animal testing, a stepped compression load was applied to the subcutaneous tumor deposit on an athymic NU/NU nude mouse model with subcutaneous xenograft BxPC-3 cancer. Characteristic differences were observed between the premortem tumor and the postmortem tumor in terms of pressure-induced tumor structural and functional changes.

Chemotherapeutic choice of ranimustine or nimustine on the basis of regional polyamine levels in rat brain

The aim of the present study was to improve the chemotherapeutic efficacy of anticancer drugs by choosing on the basis of the polyamine level induced by the drug in each host cancer-bearing tissue. We propose an "organ-specific therapy" in the article. The polyamines, putrescine, spermidine and spermine are strongly associated with tumor cell growth. The effects of ranimustine (MCNU) and nimustine (ACNU) on body weight, regional brain weights and concentrations of putrescine, spermidine and spermine in the cerebellum, hippocampus, corpus striatum, cortex, combined thalamus and hypothalamus and diencephalon of the brain were examined in rats. MCNU and ACNU reduced spermidine and spermine in the corpus striatum, and spermine in the diencephalon, but increased putrescine in the corpus striatum and combined thalamus and hypothalamus. These results indicate that both MCNU and ACNU are suitable for the treatment of cancers of the corpus striatum, but ACNU is not suitable for cancers of the corpus striatum, thalamus and hypothalamus.

Characterization of EBV-infected epithelial cell lines from gastric cancer-bearing tissues.

The long-term goal of our study is to explore how Epstein-Barr virus (EBV) associates with the pathogenesis of gastric carcinoma. The first goal is to establish EBV-positive epithelial cell lines from EBV-infected gastric carcinoma tissues and to characterize the cell lines and EBV infection in the cells. EBV, a ubiquitous human herpesvirus with oncogenic potential, is predominantly associated with the infection of two target tissues in vivo: (1) B lymphocytes, where the infection is largely nonproductive, and (2) the epithelium, in which virus replication occurs (Rickinson and Kieff 1996). Both target tissues are susceptible to EBV-associated malignant change, leading to tumors of B-cell origin, such as Burkitt’s lym-phoma, or of epithelial-cell origin, such as nasopharyngeal carcinoma (NPC) (Pathmanathan et al. 1995). Recently, EBV has also emerged as an etiologic agent implicated in gastric carcinoma (Min et al. 1991; Shibata et al. 1991; Shibata and Weiss 1992; Tokunaga et al. 1993a,b; Fukayama et al. 1994; Imai et al. 1994; Ohfuji et al. 1996; Iwasaki et al. 1998). EBV has been found in most cases of rare gastric lymphoepithelioma-like carcinomas (Min et al. 1991; Shibata et al. 1991; Ohfuji et al. 1996) and a small but significant proportion of common gastric adenocarcinomas (Shibata and Weiss 1992; Tokunaga et al. 1993a,b). EBV infection was found in approximately 7% of Japanese gastric carcinomas (Tokunaga et al. 1993a,b; Fukayama et al. 1994; Imai et al. 1994). The world distribution of gastric carcinomas with EBV infection is shown from 4% to 18% of total gastric carcinoma in different countries (Tashiro et al. 1998)KeywordsGastric CarcinomaEpithelial Cell LineSCID MouseLatent Membrane ProteinRaji CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Distribution of metastases in Stage I carcinoma of the cervix: A study of 66 autopsied cases

1.1. A study is presented of 66 cases of cervical cancer in which the patients died of causes unrelated to the cervical lesion, which was classified as Stage I in extent on the basis of microscopic examination of the cervix.2.2. Spread of the disease was demonstrated in: (a) 3 of 22 untreated cases with the primary lesion of 1 cm. or less in diameter; (b) 6 of 27 untreated cases with the primary lesion of more than 1 cm. in diameter; (c) 4 of 17 treated cases with the extent of the primary lesion estimated on the preirradiation records.3.3. Cancer cells, regardless of the site of the primary lesion, the histologic grade, and the age and parity of the patient, can spread in any direction. The direction and the degree of spread are not predictable.4.4. The anterior and posterior spread is almost as frequent as the lateral extension. Thus, any attempt to remove all possible cancer-bearing tissue must include these areas.5.5. A peristalsis-like action of the lymphatic vessels was noted and its importance in the dispersal pattern of cervical cancer emphasized.6.6. The response of lymph nodes to irradiation is discussed, but the equivocal observations continue to becloud the true effectiveness of this form of therapy.7.7. The importance of new observations on the relation of mitotic activity to cancer cell susceptibility as a possible new approach in therapy is discussed.8.8. The errors inherent in the present methods of comparing the effectiveness of surgery and irradiation are noted with the suggestion that new ground rules be provided.

Radium and X-ray Therapy as Palliative Measures in the Treatment of Rectal Cancer

EXCLUSIVE of the stomach and oral cavity, approximately 60 per cent of the remaining intestinal cancers are indigenous to the rectum. Rectal cancers are notoriously difficult to cure because 40 to 50 per cent are inoperable when first seen by the surgeon; the rectum is in daily use; the tumor mass is not easily accessible; the degree of dissemination cannot be estimated by physical examination; the complete removal of all cancer-bearing tissue is a difficult operative feat accompanied by a high immediate mortality. The Pathology of Rectal Carcinomas Epithelioma or squamous-cell carcinoma of the anus is uncommon, aggregating only 3 to 4 per cent of all rectal cancers. Its site of predilection is at the mucocutaneous junction in the mid-line, anteriorly. It forms a nodular, warty, flattened growth which tends to ulcerate and involve the rectum proper. Its radiosensitivity corresponds with that of the lip and the buccal mucosa; the most satisfactory plan of treatment is irradiation by the interstitial deposition of small metal-filtered radon implants, known as gold or platinum seeds. The remaining cancers of this region are adenocarcinomas, which are also the most frequent tumors. The symptomatology, growth tendencies, and pathology of these differ according to their location in the rectal canal. At the rectosigmoidal junction the tumor early encircles the bowel to form an annular stricture. The majority of carcinomas of the rectal ampulla begin on the posterior wall. The four common types of adenocarcinomas of this region are: (1) The papillary carcinoma. (2) The malignant adenoma, or adenoma destruens. (3) The colloid, or gelatinous carcinoma. (4) The scirrhus or fibrocarcinoma. The papilliferous, or papillomatous, carcinoma resembles the benign papilloma somewhat, except for the invasive nature of its base. This tumor may be frankly malignant from its onset, or it may be a malignant degeneracy of the benign papilloma. Its growth energy is expended largely by evertent or surface proliferation, producing a bulky exuberant tumor, before the bowel wall is infiltrated. This cancer is readily amenable to surgical extirpation; when radium therapy is to be employed, the papilliferous fronds are removed by surgical endothermy and gold or platinum filtered radon seeds are implanted into the base of the cancer. The scirrhus or fibrocarcinoma is a peculiar type of rectal carcinoma, exhibiting desmoplastic tendencies, in which the atypical cancer cells are growing diffusely and are nestled away among wide strands of new connective tissue. This cancer is markedly radioresistant. The colloid or gelatinous carcinoma is a degenerative type of adenocarcinoma. It usually forms a bulky, massive growth in which gelatinous or mucoid material replaces the tumor tissue. It likewise does not respond well to radiation therapy. Adenoma destruens is the most common type of cancer of the rectum.