adrenomedullin and Carcinoma--Squamous-Cell

There is increasing evidence that antimicrobial peptides (AMPs) are differentially regulated in cancers such as oral squamous cell carcinomas (OSCC). Data showing that AMPs influence the growth of tumor cells, exhibit direct cytotoxic activity towards cancer cells, function as a tumor suppressor gene or activate the adaptive immunity suggest that a dysregulation of AMPs may be associated with the development of cancer. There is no question that, with increasing resistance against conventional chemotherapy, novel anticancer agents are needed. It is interesting to speculate that natural AMP or synthetic derivatives can be used to develop novel strategies to fight cancer diseases and may represent a novel family of anticancer agents. However, future research is needed to employ the role of AMPs in cancer and to investigate their role as potential anticancer drugs.

Topics: Adrenomedullin; Antimicrobial Cationic Peptides; Antineoplastic Agents; Carcinoma, Squamous Cell; Cathelicidins; Defensins; Histatins; Humans; Mouth Mucosa; Mouth Neoplasms; Structure-Activity Relationship

Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types.. We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk.. JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.

Topics: Adrenomedullin; Biomarkers, Tumor; Carcinoma, Squamous Cell; Epigenesis, Genetic; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Histones; Humans; Jumonji Domain-Containing Histone Demethylases; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Prognosis; Survival Rate

To observe the expression of adrenomedullin (AM) in the patients with laryngeal carcinoma.. Two-step immunohistochemistry method was used to examine the expression of AM in the patients with laryngeal carcinoma. Radioimmunoassay was applied to determine the concentration of AM in the laryngeal carcinoma tissues, adjacent laryngeal mucosa of carcinoma tissues and in the plasma of patients and controls.. Positive stainings for AM were found in all 21 specimen examined,distributed mainly in the cytoplasm of the laryngeal carcinoma cells. Positive stainings were more stronger in the circumference than in the center of tumor tissue for the highly and moderately differentiated tumors. While the stainings were distributed homogeneously for poorly and moderately differentiated tumors. The concentration of AM in the laryngeal carcinoma tissues (n = 44) and the adjacent mucosa (n = 44) were (49.67 +/- 28.33) pg/ml and (14.71 +/- 7.17) pg/ml (x +/- s) respectively and laryngeal tumor showed much higher concentration of AM than the adjacent mucosa (u = 135.00, P < 0.01). The concentration of AM in patients with laryngeal carcinoma of T2, T3 and T4 stage were (31.52 +/- 15.22), (56.63 +/- 18.51) and (96.12 +/- 18.22) pg/ml (x + s) respectively,and there were statistically significant difference among them. In the N stage, patients with higher stages were found to express significantly higher AM concentration, but there was not statistically significant difference between NO stage and N1 stage. In the M stage,patients with M1 stage were found to express significantly higher AM concentration (u = 31.00, P < 0.01). But there was not statistically significant difference between AM plasma concentration of laryngeal carcinoma patients and that of healthy controls.. The results suggested that high expression of AM in tissues of laryngeal carcinoma was related with the TNM stage of laryngeal carcinoma, AM may play an important role in the development of the laryngeal neoplasma.

Topics: Adrenomedullin; Aged; Carcinoma, Squamous Cell; Female; Humans; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging

The purpose of this study was to identify the role of Bcl-2 protein and adrenomedullin (AM) expression in relation to apoptosis in the neoplastic changes of squamous epithelium of the uterine cervix.. Apoptosis in sections of normal cervical epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinoma was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay. Bcl-2 protein and AM expression were analyzed using the avidin-biotin immunoperoxidase method.. On the basis of the TUNEL assay, the apoptosis positive rate of the nuclei in early invasive squamous carcinoma and in bulky invasive squamous carcinoma was significantly higher than that in normal cervical epithelium, but no such increase in the apoptosis-positive rate was noted in the nuclei in CIN. Immunohistochemical staining revealed that Bcl-2 protein and AM were immunolocalized in the cytoplasm of invasive squamous carcinoma cells, but not in either CIN lesions or normal cervical epithelium. Bcl-2 protein expression was more prominent in bulky invasive squamous carcinoma cells than in early invasive squamous carcinoma cells. AM expression was also more abundant in bulky invasive squamous carcinoma compared with that in early invasive squamous carcinoma.. The present results suggest that the expression of Bcl-2 protein and AM in invasive squamous carcinoma may play crucial roles in selecting carcinoma cells resistant to apoptosis and in promoting malignant progression.

Topics: Adrenomedullin; Adult; Aged; Apoptosis; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Squamous Cell; Cohort Studies; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Middle Aged; Neoplasm Invasiveness; Peptides; Probability; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; Uterine Cervical Neoplasms

Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including vasodilatation, growth regulation, and carcinogenesis. To elucidate the possible role of AM in the growth and invasion of uterine cervical carcinoma, the presence and distribution of AM and AM mRNA was examined in the neoplastic changes of squamous epithelium of the uterine cervix.. The expression of AM mRNA by CaSki, a uterine squamous cell carcinoma cell line, was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The presence and distribution of AM and AM mRNA in sections of normal cervical tissues, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinomas were evaluated by immunohistochemical staining with a specific antibody against AM and by in situ RT-PCR, respectively.. AM mRNA expression in CaSki cells was demonstrated by RT-PCR. Immunohistochemical staining for AM and in situ RT-PCR revealed that AM and AM mRNA were expressed in invasive squamous carcinoma cells, but not in normal cervical epithelium or in CIN lesions. Abundant expression of AM and AM mRNA was localized in the cytoplasm of carcinoma cells of bulky invasive carcinomas, while in early invasive carcinoma, the expression of AM and AM mRNA was more prominent in stromal cells adjacent to the early invasive carcinoma cells than in the carcinoma cells themselves.. Because AM expression was evident only in invasive cervical squamous carcinoma cells and the stromal cells adjacent to early invasive carcinomas, it is likely that AM may play an important role in the growth and invasion of squamous cell carcinoma of the uterine cervix.

Topics: Adrenomedullin; Carcinoma, Squamous Cell; DNA Primers; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Neoplasm Invasiveness; Peptides; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured; Uterine Cervical Neoplasms