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Overexpression of mucin glycoproteins has been demonstrated in many epithelial-derived cancers. The significance of this overexpression remains uncertain. The aim of this paper was to define the association of mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers by performing a systematic review of all published data. A systematic review of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify all papers that evaluated the association between mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers. PRISMA guidelines were adhered to. Results of individual studies were extracted and pooled together based on the organ in which the cancer was derived from. The initial search revealed 2031 papers, of which 90 were deemed eligible for inclusion in the study. The studies included details on MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC13, and MUC16. The majority of studies evaluated MUC1. MUC1 overexpression was consistently associated with resistance to apoptosis and resistance to chemotherapy. There was also evidence that overexpression of MUC2, MUC4, MUC5AC, MUC5B, MUC13, and MUC16 conferred resistance to apoptosis in epithelial-derived cancers. The overexpression of mucin glycoproteins is associated with resistance to apoptosis in numerous epithelial cancers. They cause resistance through diverse signaling pathways. Targeting the expression of mucin glycoproteins represents a potential therapeutic target in the treatment of epithelial-derived cancers. [ABSTRACT FROM AUTHOR]

This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h catumaxomab infusion with/without prednisolone premedication to reduce catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (catumaxomab plus prednisolone, 4.1; catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the catumaxomab plus prednisolone arm than in the catumaxomab arm, but the differences were not statistically significant ( p = 0.402 and 0.599, respectively). Median OS was longer in the catumaxomab plus prednisolone arm than in the catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant ( p = 0.186). The superiority of catumaxomab plus prednisolone versus catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main catumaxomab-related adverse events. The study confirms the safety and efficacy of catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites. [ABSTRACT FROM AUTHOR]

The adolescent and young adult (AYA) is defined as a patient of 15 to 39 years of age at initial cancer diagnosis, and this group has particular medical needs and age-related issues. Excluding violent deaths, cancer is the leading cause of death among the AYA population. Lymphomas, melanoma, testicular cancer, female genital tract malignancies, thyroid cancer, bone and soft tissue sarcomas, leukemias, central nervous system tumors, breast cancer, and nongonadal germ cell tumors account for 95 % of the cancers in this group. Among those, the epithelial cancer of AYA comprehends the minimum amount and its incidence rates tend to increase with age. This review presents information about epidemiology, biologic peculiarities, as well as standard treatment strategies for epithelial cancers in AYA. [ABSTRACT FROM AUTHOR]

Management of oral tongue squamous cell cancer (OTSCC) remains a challenge. This nationwide study reports the used treatment approach and the outcome of OTSCC in Finland. Retrospective study of OTSCC patients in 1995–1999 with a 5-year follow-up. The corresponding data from 1980 to 1989 is also included. About 235 patients (125 M, 110 F; mean age 61.6 years; range 24–90 years) were included, 77% had SCC of lateral border of the tongue and 25% were N+. Treatment with curative intent was given to 224 (95%) patients. Surgery of the primary tumour was performed in 218 (97%) patients and with a reconstruction in 69 (31%) patients. A neck dissection was performed ipsilaterally in 114 (51%) and bilaterally in 9 (4%) cases. Irradiation was given to 131 (58%) patients. The rate for locoregional recurrence was 28%. The 3- and 5-year overall survival (OS) rates were 66 and 47%, respectively. The corresponding disease specific survival (DSS) rates were 74 and 64%, respectively. The mean DSS for patients younger than 40 years and older than 40 years was 111 and 88 months, respectively ( P < 0.02). The 3- and 5-year DSS rates were: Stage I, 88 and 74%; Stage II, 74 and 62%; Stage III, 79 and 71% and Stage IV, 36 and 33%, respectively. In the present study the surgical treatment approach seems effective in controlling early stage OTSCC but the modest survival, in spite of combination of radiotherapy and surgery, points out the need to consider new strategies in the management of advanced stage disease. [ABSTRACT FROM AUTHOR]

The survival figures for advanced stage oropharyngeal carcinoma (OPC) have remained moderate in spite of radical combined modality treatments. The purpose of this study was to investigate the used treatment approach and the outcome of OPC in a nationwide study. Retrospective clinicopathological data of all patients diagnosed with OPC between 1995 and 1999 at the five university hospitals in Finland were reviewed. All patients had a minimum 4-year follow-up. A total of 168 patients (145 men and 23 women, mean age 59 years; range 28 – 89 years) were included. The T categories were as follows: T1, n =34; T2, n =55; T3, n =40; T4, n =39. One hundred and seventeen (69.6%) patients presented with neck node metastases and three (1.8%) patients with distant metastases. In the majority (61.3%) of the patients the tumor was located in the lateral wall of the oropharynx. In 144 (85.7%) patients the treatment was performed with curative intent. Of these, surgery of the primary tumor was performed in 123 (85.4%) patients, and the defect was reconstructed with a pedicled flap or free tissue transfer in 66 (53.7%) of these patients. A neck dissection (ND) was performed in 86 (69.9%) out of these 123 cases. Surgery was the only treatment modality in 10 (6.9%) patients. Radiation therapy (RT) only (with or without chemotherapy) was given to 21 (14.6%), combined treatment with surgery + radiation therapy (S + RT) to 110 (76.4%) and surgery + chemoradiotherapy (S + CRT) to 3 (2.1%) patients. Overall (OS) 3- and 5-year survival rates were 58 and 45%, respectively. Disease-specific (DSS) 5-year survival rates by T-class for the patients treated with curative intent were as follows: T1, 77%; T2, 70%; T3, 66%; T4, 53%. The variable treatment approach, the frequent locoregional recurrences and the moderate survival point out the need to consider new strategies in the management of OPC. [ABSTRACT FROM AUTHOR]

The ectopic production of free hCGβ is a common phenomenon in epithelial tumours, a phenomenon originally believed to have no biological significance. However, it is now apparent that hCGβ may significantly effect tumour development by increasing cell populations through inhibition of apoptosis. The recently identified hCGββ homodimer, with topological similarities to cystine knot growth factors, has been suggested to be the responsible mediator of these novel tumourigenic responses. In this study we isolated hCGβ monomer from hCGββ homodimer using size exclusion chromatography and confirmed the separation by Western blotting. Using a tetrazolium bromide incorporation cell number quantification assay (MTT), we measured the growth effects of separated hCGβ fractions corresponding to monomeric (hCGβ) and dimeric (hCGββ) forms on the hCGβ responding cell line T24. Maximal increases in cell number corresponded to the elution peak of dimeric and monomeric hCGβ. In conclusion, it would appear that the recently observed hCGββ homodimer is no more bioactive than its monomeric counterpart, in stimulating bladder cancer cell growth. This strengthens the proposition that hCGβ may exert its antiapoptotic effects by antagonistic inhibition of other cystine knot growth factor receptors and not by a specific receptor-mediated homodimeric interaction as seen for its topological counterparts TGF, PDGF-B and NGF. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Several reverse-transcriptase polymerase chain reaction (rtPCR) assays have been designed for the detection of disseminated cancer cells. The specificity of these discussed molecular approaches is controversial. Biological interference of the cytokeratin-20 and mammaglobin rtPCR assays has been investigated. Cell lines of different lineages and bone marrow and peripheral stem cells from patients without epithelial cancer have been examined for the transcription of the cytokeratin-20 (CK20) and mammaglobin messages prior to and after stimulation with different cytokines in a total of 370 liquid cultures. Amplification of both messages from clinical samples prior to stimulation does not support the high specificity for the detection of disseminated epithelial cancer cells as reported. Cytokeratin-20 was amplified from the chronic myeloic leukemia (CML)-derived line K562. Transcription was not influenced by cytokines, either in cell-line experiments or in clinical samples. The thesis of a low-level background transcription in granulocytes is supported. Mammaglobin was induced in cell lines significantly by GM-CSF and in clinical samples additionally by several more cytokines. These results indicate that under certain conditions involving cytokine production, the use of mammaglobin rtPCR for the detection of epithelial cancer cells could be limited. In conclusion, the mechanism of interference of both rtPCR assays are completely different and further research is necessary before the cytokeratin-20 or mammaglobin rtPCR could become standard methods for the detection of disseminated epithelial cancer cells. These factors leading to so-called false-positive results have to be considered in future applications of rtPCR for the detection of minimal residual disease. [ABSTRACT FROM AUTHOR]

There is emerging evidence that epithelial tumor cells are able to disseminate to secondary organs at an early stage of primary tumor development. One of the most prominent secondary organs screened for this type of dissemination is bone marrow. Even in cancer entities where overt skeletal metastases are rare (e.g., colorectal and ovarian cancer), bone marrow is a prognostically relevant indicator organ for the presence of hematogenous micrometastases. The currently available data suggest that bone marrow micrometastases represent a selected population of dormant cancer cells which still express a considerable degree of heterogeneity. The analysis of micrometastatic cells will open a new avenue to assess the molecular determinants of early tumor cell dissemination and subsequent outgrowth into overt metastases. Moreover, monitoring the elimination of bone marrow micrometastases and identification of treatment-resistant tumor cell clones may help to increase the efficacy of adjuvant therapy. This review summarizes the current knowledge on the biological characteristics of micrometastatic cancer cells in bone marrow of patients with solid epithelial malignancies. [ABSTRACT FROM AUTHOR]