Early Stages Of Tumor Progression Research Articles

A Tetracycline-Responsive Promoter System Reveals the Role of a Secreted Binding Protein for FGFs during the Early Phase of Tumor Growth

We showed previously that a secreted binding protein for FGFs (BP) can induce tumor growth and angiogenesis of a non-tumorigenic human cell line (SW-13). To study the contribution of BP to different phases of tumor growth, we employed a regulated promoter system which is highly active in SW-13 cells and can be downregulated >20-fold by treatment with tetracycline. We demonstrate that expression of BP in SW-13 cells (SW-13/tetBP cells) induces colony formation in soft agar and tumor growth in athymic nude mice. Tetracycline downregulated BP expression in these cells and prevented their colony formation in soft agar. Continuous tetracycline treatment of animals suppressed BP expression in tumors grown from SW-13/tetBP cells and reduced growth of the xenografts. Initiation of tetracycline treatment after xenograft tumors had been established had no effect on further tumor expansion in spite of downregulated BP levels. These data suggest that BP expression plays a role mainly in the early stages of tumor progression.

Activation but Not Inactivation of theMTS1Gene Is Associated with Primary Colorectal Carcinomas

Several investigators have reported that alterations of the multiple tumor suppressor 1 (MTS1) gene frequently occurred in certain types of tumors. We examined the expression levels and somatic mutations of theMTS1gene in primary colorectal carcinomas. TheMTS1transcript was quantitatively detected in 14 of 17 tumors, but in only one case of adjacent normal mucosa. Direct sequencing of the amplifiedMTS1gene showed no somatic mutation in 17 primary colorectal carcinomas. These results indicate that inactivation of theMTS1gene is not involved in pathogenesis of primary colorectal carcinomas, and that its enhanced expression is, instead, associated with primary colorectal carcinomas, especially markedly in the early stage of tumor progression.

Relationship between cell proliferation activity and morphological characteristics of papillary microcarcinoma in the thyroid of Graves' disease

Three hundred and seven lesions of papillary microcarcinoma of the thyroid (PMT), found in 6830 cases of Graves' disease, were reviewed to evaluate the morphological characteristics. The prevalence rate and incidence of multiplicity of PMT in Graves' disease were higher (P < 0.05 and P < 0.005, respectively) in females (4.03% and 0.73%, respectively) than in males (2.68% and 0.12%, respectively). All lesions of PMT were classified histologically into three types: sclerosing non-encapsulated (SNE), non-sclerosing encapsulated (NSE) and non-sclerosing non-encapsulated (NSNE). Comparison of the three types of PMT revealed that the mean age and tumor size of NSNE were less than those of NSE and SNE (P < 0.001 and P < 0.005, respectively), and 13 of 19 lesions less than 1 mm belonged to NSNE. In addition, cell proliferation and expression of estrogen and progesterone receptors were examined immunohistochemically in 257 lesions of PMT. The Ki-67 labeling index of NSE was lower than that of NSNE and SNE (P < 0.005). None of the cases of PMT was positive for estrogen or progesterone receptors. The present study indicated that NSNE may be an early stage in tumor progression, and that fibrous encapsulation has the potential to modify neoplastic cell proliferation.

A Novel Strategy for the Investigation of Clonality in Precancerous Disease States and Early Stages of Tumor Progression

A novel strategy for clonality determination from only 100 cells using the polymerase chain reaction in amplifying a 511 bp region located within the first intron of the human hypoxanthine phosphoribosyl transferase (HPRT) gene has been devised. The strategy rests on several observations: that this region in females contains two HpaII/MspI sites whose methylation remains both obligate with X chromosome inactivation and independent of tumor progression; and that this region contains single base allelic polymorphisms in 5-10% of females which can be detected by denaturing gradient gel electrophoresis (DGGE) on the PCR product. In polymorphic individuals, multiple bands (homo- and heteroduplexes) indicate multiclonality, single bands indicate monoclonality, and their comparative migrations indicate clonal identity/non-identity.

Relationship of c-myc Amplification to Progression of Breast Cancer From In Situ to Invasive Tumor and Lymph Node Metastasis

Amplification of the c-myc gene (also known as MYC) occurs in up to 20%-30% of breast cancers and has been associated with poor prognosis. The purpose of this study was to define the relationship between c-myc amplification and breast cancer progression in order to better understand the biological significance of c-myc amplification. We identified invasive tumors with grossly detectable c-myc amplification by using Southern blot analysis to examine frozen tissue from 135 breast carcinomas and polymerase chain reaction (PCR) analysis to examine archival paraffin-embedded tissue from an additional 19 invasive tumors. These 19 tumors were selected on the basis of histologically identifiable in situ and invasive components within the primary tumor and associated lymph node metastases. Amplification of c-myc in these areas was then assessed by quantitative PCR assay. We detected gross c-myc amplification in 10 of the tumors examined--eight of the 135 frozen tissue specimens and two of the 19 archival specimens. We selected five of these 10 invasive tumors for further regional analysis. In all four cases where an in situ component was present, amplification of c-myc was present in both the in situ and the invasive components. However, c-myc amplification was present in the corresponding nodal metastases in only two of the four cases where this could be examined. These results suggest that c-myc amplification can occur at an early stage in tumor progression and that amplification does not always persist in the nodal metastasis.

Pathways and Dynamics in Metastatic Spread of Lung Cancer

Pathways and Dynamics in Metastatic Spread of Lung Cancer

Induction of oncofetal antigen-specific suppressor pathways, involving Thy-1 + cells, during the early stages of tumor progression

The early stages of tumor progression were modelled by intraperitoneally injecting BALB/c mice daily with exponentially increasing numbers of mitomycin C-treated, syngeneic MPC-11 tumor cells. At various stages of this regime, mesenteric lymph node (MLN) and spleen cells were assessed for regulatory activity on the induction of cytotoxic T lymphocytes (CTL) in vitro. Cells present in both MLN and spleens of mice whose daily tumor dose had reached 102,400 MPC-11 cells impaired the generation of CTL specific for MPC-11 and specific for oncofetal antigen(s) shared between MPC-11 and Day 14–15 syngeneic fetal liver cells. Depletion of Thy-1 + cells from the regulatory cell populations removed the suppressive activity. The regulatory cells did not affect the induction of CTL specific for H-2 b antigens in the context of H-2 d (i.e., BALB/c) class I MHC.

Do adrenal metastases from lung cancer develop by lymphogenous or hematogenous route?

In order to analyse the possible mode and pathways of adrenal metastases from lung cancer, the frequency of adrenal metastases ipsilateral and contralateral to the site of the primary cancer was investigated based on autopsied lung cancer cases. In 405 of 1,607 such cases, adrenal metastases could be found: on both sides, 234; ipsilateral only, 105; contralateral only, 66 cases. In the early stages of tumor progression, a striking difference can be seen between the two sides. Ipsilateral metastases were of significantly higher incidence in early metastatic tumor stages, but later, in cases having six or more involved organs, the ipsilateral/contralateral quotient reaches 1. It is postulated that in the early stages adrenal metastases from lung cancer probably develop mainly by lymphogenous, but later mainly by hematogenous routes.

DNA content in atypical glio-mesenchymal cells during chemical carcinogenesis in the albino rat cerebellum

The DNA content was determined by comparative microspectrophotometry in atypical glio-mesenchymal cells around the villous capsule surrounding the DMBA pellet, and in cells of microastrocytomas and microglioblastomas induced by DMBA. A characteristic feature of the late stages of this type of chemical carcinogenesis in the albino rat cerebellum was found to be the preservation of a well-marked diploid modal class, except in cases when the pathological process developed along malignant lines in the early stages of tumor progression (microglioblastoma).