thymosin and Carcinoma--Squamous-Cell

Despite the ever growing collection of data concerning the function of the immune system in patients with epidermoid carcinoma of the head and neck, the precise mechanism by which these tumors effect the body's surveillance against foreign antigen is as yet unidentified. If these specific immunological characteristics of the cancer cell can be identified, laboratory analysis of these "markers" could lead to detection and treatment of cancer in its earliest stages. Included in this chapter is a review of the embryological development of the immune system, a description of the components of the immune system and their responses to invasion by tumor antigen. Measurements of immuno responsiveness of the individual are important in determining the pretreatment state of immuno-competence and in predicting prognosis following treatment. Measurements of T-lymphocyte functions and their response to immuno-manipulations can also aid in predicting which patients will benefit from immunotherapy. Finally, categorization of the multiple forms of immunotherapy including active, specific and non-specific, and adoptive mechanisms are discussed. More recent methods of related immunotherapy trials will also be mentioned. As of this writing, the trials of immunochemotherapy have not produced any conclusive results due to the lack of multi-institutional trials and limited quantities of immunotherapeutic agents for these clinical trials.

Topics: Adjuvants, Immunologic; Antigens, Neoplasm; B-Lymphocytes; Blood Proteins; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunocompetence; Immunoglobulins; Immunosuppression Therapy; Immunotherapy; Interferons; Macrophages; Prognosis; Retinoids; Steroids; T-Lymphocytes; Thymosin

One hundred five patients with advanced non-small cell lung cancer were randomized to receive thymosin fraction V immunotherapy during remission induction chemotherapy with vindesine, doxorubicin, and cisplatin (VAP). Fifty-four patients received VAP alone. Fifty-one patients received VAP + thymosin. Both groups were comparable; most patients were male, with a good performance status and with the diagnosis of adenocarcinoma. Among 99 evaluable patients, response was seen in 24 (2 CRs, 22 PRs) of 53 (45%) patients treated with VAP and 10 (all PRs) of 46 (22%) patients treated with VAP + thymosin (p = 0.03). VAP-treated patients responded better than those treated with VAP + thymosin in each tumor category: adenocarcinoma, 50% of 36 patients versus 22% of 27 patients; squamous cell carcinoma, 29% of 14 patients versus 21% of 13 patients; undifferentiated carcinoma, 67% of three patients versus 17% of six patients. Median survival duration was 34 weeks versus 25 weeks in favor of the VAP-treated group (p = 0.14). Thymosin treatment resulted in decreased graft-vs.-host reaction (p = 0.01) and increased suppressor effect on normal mitogen response to Con-A (p = 0.17). The activity of VAP chemotherapy is comparable with the most effective multidrug regimens of the present time in patients with advanced non-small cell tumors. The addition of thymosin immunotherapy appeared to have a negative effect on the activity of VAP.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Clinical Trials as Topic; Doxorubicin; Evaluation Studies as Topic; Female; Humans; Immunity, Cellular; Immunotherapy; Leukopenia; Lung Neoplasms; Male; Middle Aged; Prednisolone; Prospective Studies; Thrombocytopenia; Thymosin; Vincristine

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Head and Neck Neoplasms; Humans; Immunity, Cellular; Immunosuppression Therapy; Lymphocytes; Radiation Injuries; Thymosin; Thymus Hormones

The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression.. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels.. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells.. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC.

Topics: Aged; Carcinoma, Squamous Cell; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Keratin-13; Lymphatic Metastasis; Male; Mouth Mucosa; Mouth Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Profilins; RNA, Messenger; Thymosin

The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin β4 (Tβ4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tβ4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tβ4-overexpressing OSCCs, SCC-15_Tβ4 and SCC-25_Tβ4, enhanced cell proliferation and colony formation. In addition, we observed that Tβ4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tβ4 and SCC-25_Tβ4 cells. Tβ4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tβ4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tβ4 molecule would encourage the development of specific targets for cancer treatment.

Topics: Cadherins; Carcinoma, Squamous Cell; Cell Movement; Cell Proliferation; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Mouth Neoplasms; Neoplasm Invasiveness; Nuclear Proteins; Thymosin; Twist-Related Protein 1; Vimentin

Recent studies have shown that thymosin β4 (TB-4) is highly related with tumor metastasis and angiogenesis. In addition, TB-4 induced the expression of VEGF in melanoma cells. We investigated the expression patterns of TB-4 and related angiogenic proteins, VEGF, and HIF-1α, at various stages of cervical cancers and also identified the expression pattern of these proteins in metastatic cervical cancers. Expression patterns of TB-4, VEGF, and HIF-1α were studied with tissue microarray containing 42 samples of cervical cancers. In addition, 15 cervical cancers and metastatic tumors in lymph nodes from patients who have metastatic tumors were also analyzed to confirm the role of TB-4, VEGF, and HIF -1α in cervical cancer metastasis. The expression levels of TB-4, VEGF, and HIF-1α were very weak at early cancer stages (stages 0 to 1A) but significantly increased at stage 1B. The numbers of blood vessels in tumors were also increased at stage 1B. The expression patterns of TB-4, VEGF, and HIF-1α were compared in tumors without lymph node metastasis, primary tumors with lymph node metastasis, and metastatic tumors in lymph nodes. The expression levels of TB-4, VEGF, and HIF-1α in primary tumors with lymph node metastasis and their metastatic tumors in lymph node were less than in tumors without lymph node metastasis. These data suggest that TB-4, VEGF, and HIF-1α triggered angiogensis and tumor invasiveness to surrounding tissues at early stage of cervical carcinoma but have a negative or no effect on the metastatic potential.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Cervix Uteri; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Lymphatic Metastasis; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Thymosin; Tissue Array Analysis; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A

Prothymosin-alpha, the precursor of thymosin-alpha1, may play a role in cell proliferation, and the plasma level of thymosin-alpha1 may reflect the degree of proliferation of the tumor cells.. Recently, a new sandwich immunoradiometric assay for thymosin-alpha1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-alpha1 in 131 lung cancer patients.. We found that the mean plasma thymosin-alpha1 levels in lung cancer patients were higher than in normal individuals (P < 0.001). However, half of the patients showed normal levels. Thymosin-alpha1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-alpha1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P = 0.03). Survival of patients with normal levels of plasma thymosin-alpha1 was significantly better than that with higher levels (P = 0.04).. The plasma level of thymosin-alpha1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Division; Female; Humans; Immunoradiometric Assay; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Thymalfasin; Thymosin

Altered cellular immunity in patients with advanced head and neck cancer includes impairments in lymphokine production, blastogenesis, in vitro cytotoxicity, and T-cell levels. Recent evidence for the potential importance of in lymphokine interleukin 2 (IL-2) in patients with cancer prompted a study of the kinetics of IL-2 receptor expression on lymphocytes from patients with untreated advanced head and neck cancer and normal subjects and an evaluation of the in vitro effects of the T-cell immune-reconstituting peptide, thymosin alpha 1. Concanavalin A-stimulated IL-2 receptor expression was maximal after 72 hours and was higher in normal subjects than in patients. This was due to lower levels of helper/inducer (CD4) cells expressing IL-2 receptors in the patients compared with the normal subjects. Thymosin alpha 1 further decreased levels of IL-2 receptor-positive (both CD4 and CD8) cells at 48 and at 72 hours. At 96 hours, levels of IL-2 receptor-positive cells and proportions of cells in G2 and M phases of the cell cycle were similar among both groups of subjects. Simultaneous cell kinetic studies indicated that thymosin alpha 1 down regulation of IL-2 receptors was not due to an effect on proliferation and that differences in IL-2 receptor expression at 72 hours among normal subjects and the patients with cancer were more likely related to differences in cell proliferation kinetics.

Topics: Carcinoma, Squamous Cell; CD4 Antigens; Concanavalin A; Down-Regulation; Flow Cytometry; Head and Neck Neoplasms; Humans; Kinetics; Receptors, Interleukin-2; Thymosin

In a preliminary study of the effects of SK-SD and thymosin on leukocyte migration inhibition in patients with squamous carcinoma of the head and neck, the cancer patients had significantly lower leukocyte migration inhibition of SK-SD than normal subjects. Thymosin increased the inhibition to SK-SD in the cancer patients to levels similar to those in normal subjects, and decreased the inhibition in normal subjects. These results confirm and extend the results of previous studies of the effects of thymosin in vitro, which show restoration of immune reactivity in patients with impaired cellular immunity and either no effect or a decrease in immune reactivity in subjects with normal cellular immunity. These combined observations provide a rationale for determining the clinical effects of thymosin in immunoincompetent patients with head and neck cancer and suggest that immunorestorative agents such as thymosin be used with caution in patients with normal cellular immunity.

Topics: Carcinoma, Squamous Cell; Cell Migration Inhibition; Head and Neck Neoplasms; Humans; Immunity, Cellular; Leukocyte Migration-Inhibitory Factors; Leukocytes; Streptodornase and Streptokinase; Thymosin; Thymus Hormones

Fifty-five patients with squamous cell carcinoma of the head and neck and esophagus were evaluated prior to irradiation and thymosin fraction 5 therapy. Immunity prior to treatment, as measured by total lymphocyte count, E and EAC rosettes, lymphocyte stimulation with phytohemagglutinin (PHA) and in mixed leukocyte culture (MLC) with allogeneic cells, delayed hypersensitivity skin tests, and quantitative serum immunoglobulins, was comparable and normal in the 40 control patients and in the 15 thymosin-treated patients. After irradiation, significant depression (P less than 0.01) was demonstrated in cellular immunity in both groups of patients with decreased T- and B-cell numbers and depressed phytohemagglutinin and MLC stimulation. Six months after irradiation, our preliminary results suggest that the thymosin-treated patients may be reversing their immunosuppression by a return of MLC function and positivity of delayed hypersensitivity skin tests. The ultimate effect of thymosin on disease control and survival remains uncertain.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Immunity; Immunosuppression Therapy; Lymphocytes; Male; Thymosin; Thymus Hormones