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[A case of hepatocellular carcinoma with portal invasion and right adrenal gland metastasis showing marked contraction of primary tumor and metastasis with treated by UFT alone].

A 79-year-old female with hepatocellular carcinoma with portal invasion and right adrenal gland metastasis was treated by low dose UFT (200 mg/day). Two months after the initiation of UFT administration, CT scan revealed marked contraction of the primary liver tumor and right adrenal metastasis. Serum AFP and PIVKA-II were also reduced, and right flank pain disappeared. Six months later, CT scan and MRI study were performed. The findings of liver and metastatic lesion were the same as in the earlier study, and the liver function and the patient condition were well controlled. This case is probably rare, but suggestive in the choice of treatment for advanced hepatocellular carcinoma.

Adrenal Gland Neoplasms↗

Criteria for predicting the recurrence and metastasis of stage I and II gastric cancer without lymph node metastasis.

This study examined whether detection of occult neoplastic cells (ONCs) in lymph nodes or the high-risk criteria for recurrence/metastasis of colorectal cancer were useful for predicting the recurrence of primary gastric cancer. The subjects were 122 patients with node-negative stage I or stage II primary gastric cancer. Prediction of recurrence using ONCs showed a sensitivity of 25.0% (2/8), specificity of 97.1% (100/103), and accuracy of 61.1% in stage I patients, while the respective values were 75.0% (3/4), 100.0% (7/7), and 87.5% in stage II patients. Prediction of recurrence in patients who fulfilled 2 or more of the high-risk criteria showed a sensitivity of 37.5% (3/8), specificity of 94.2% (97/103), and accuracy of 65.9% for stage I patients, while the respective values were 100.0% (4/4), 85.7% (6/7), and 92.9% for stage II patients. These results suggest that the prediction of recurrence based on the high-risk criteria shows a high sensitivity, specificity, and accuracy in patients of stage II gastric cancer without lymph node metastasis.

Humans↗

Predicting recurrence and metastasis of primary esophageal cancer with or without lymph node metastasis.

We studied 42 patients, consisting of 11 stage I/II patients who were node-negative (LN-) and 31 stage II/III patients who were node-positive (LN+). In the LN- patients, detection of occult neoplastic cells (ONCs) in lymph nodes had a sensitivity of 0.0% (0/5), a false-positive (FP) rate of 33.3% (2/6), a specificity of 66.7% (4/6), a false-negative (FN) rate of 100% (5/5), a positive predictive value (PPV) of 0.0% (0/2), and a negative predictive value (NPV) of 44.4% (4/9). In the LN+ patients, the sensitivity of ONCs was 25.0% (5/20), FP rate was 36.4% (4/11), specificity was 63.6% (7/11), FN rate was 75.0% (15/20), PPV was 55.6% (5/9), and NPV was 31.8% (7/22). In LN- patients, positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 20.0% (1/5), FP rate of 16.7% (1/6), specificity of 83.3% (5/6), FN rate of 80.0% (4/5), PPV of 50.0% (1/2), and NPV of 55.6% (5/9). In LN+ patients, these criteria had a sensitivity of 75.0% (15/20), FP rate of 9.1% (1/11), specificity of 90.9% (10/11), FN rate of 25.0% (5/20), PPV of 93.8% (15/16), and NPV of 66.7% (10/15). These results suggest that the high-risk criteria may be useful for predicting recurrence or metastasis in stage II/III lymph node-positive patients with esophageal cancer.

Esophageal Neoplasms↗

The primary tumor is the primary source of metastasis in a human melanoma/SCID model. Implications for the direct autocrine and paracrine epigenetic regulation of the metastasis process.

Although previous autopsy and experimental studies had indicated that metastases can metastasize, the question of whether metastases from metastases increasingly contribute to the overall metastatic burden is crucial to the basic question of whether the metastatic process is more directly regulated by genetic or by epigenetic mechanisms. The highly metastatic human C8161 melanoma was transfected with either pSV2neo or pSV2hygro and clones of neo-C8161 and hyg-C8161 were injected intravenously and subcutaneously in SCID mice. In combination experiments, both the timing and size of inoculum of tumor cells were titrated to ensure that the hematogenously injected cells disseminated almost exclusively to the lungs and that the overall pulmonary burden was equal to the primary tumor. In s.c. injection experiments, no spontaneous metastases ever developed when the primary tumor was extirpated before it had grown to more then 0.5 cm in diameter. When the primary tumor approached 1 cm in diameter, widely-disseminated metastases developed within lungs, liver subcutaneous sites and other internal viscera. In the combination-injection experiments, while large numbers of both hematogenously and spontaneously metastatic clones were recovered from the lungs, a vast excess of only the latter clones was recovered from extrapulmonary sites. Both hematogenously and spontaneously metastatic pulmonary clones recovered showed similar levels of Matrigel invasion and collagenases by substrate gel electrophoresis, but significantly decreased levels when compared to the cell line. Primary tumor clones, in contrast, demonstrated increased invasion and increased collagenases. Our findings argue for the importance of paracrine (orthotopic) and autocrine (size) epigenetic mechanisms in the regulation of metastasis.

Animals↗

Identification of metastasis-associated proteins in a human tumor metastasis model using the mass-mapping technique.

For most cancer cell types, the acquisition of metastatic ability leads to clinically incurable disease. The identification of molecules whose expression is specifically correlated with the metastatic spread of cancer would facilitate the design of therapeutic interventions to inhibit this lethal process. In order to facilitate metastasis gene discovery we have previously characterized a pair of monoclonal cell lines from the human breast carcinoma cell line MDA-MB-435 that have different metastatic phenotypes in immune-compromised mice. In this study, serum-free conditioned media was collected from the cultured monoclonal cell lines and a mass mapping technique was applied in order to profile a component of each cell line proteome. We utilized chromatofocusing in the first dimension to obtain a high resolution separation based on protein pI, and nonporous silica reverse-phase high performance liquid chromatography was used for the second dimension. Selected proteins were identified on the basis of electrospray ionization time of flight mass spectrometry (ESI-TOF MS) intact protein mapping and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting. Using this approach we were able to map over 400 proteins and plot them as a 2-D map of pI versus accurate M(r). This was performed over a pI range of 4.0-6.2, and a mass range of 6-80 kDa. ESI-TOF MS data and further analysis using MALDI-TOF MS confirmed and identified 27 differentially expressed proteins. Proteins associated with the metastatic phenotype included osteopontin and extracellular matrix protein 1, whereas the matrix metalloproteinase-1 and annexin 1 proteins were associated with the non-metastatic phenotype. These findings demonstrate that the mass mapping technique is a powerful tool for the detection and identification of proteins in complex biological samples and which are specifically associated with a cellular phenotype.

Animals↗

Proteome analysis of gastric cancer metastasis by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of metastasis-related proteins.

A well-described animal model was used to understand the molecular mechanisms of carcinogenesis and metastasis of gastric cancer at the protein level. Gastric cancer was induced in 12 Wistar rats by oral administration of N-methyl-N'-Nitro-N-Nitrosoguanidine (MNNG). The protein expression patterns of normal gastric tissue, gastric cancer, and corresponding metastases were analyzed by proteomics in matched tissues of 3 rats. Proteins in the region of molecular masses of 15-75 kDa and an isoelectric point of 3-7 were separated by two-dimensional electrophoresis (2-DE) and identified by peptide fingerprinting with matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Twenty-seven spots corresponding to 25 different proteins served as landmarks for comparison between tissues. The identified proteins included cytoskeletal proteins, stress associated proteins, proteins involved in signal transduction, cell proliferation and differentiation, and metabolism. Eleven proteins were up-regulated and 2 proteins were down-regulated in tumor tissue when compared with normal tissue. Twelve proteins were up-regulated and 8 proteins were down-regulated in the metastases when compared with the primary tumor. The overexpression of HSP27 in gastric cancer was confirmed by immunohistochemical analysis of human gastric cancer specimens. Combining well-defined animal models with proteome analysis will improve our understanding of the fundamental changes that contribute to the process of carcinogenesis and the formation of metastases in gastric cancer.

Adenocarcinoma↗

A model of human cancer metastasis: extensive spontaneous and artificial metastasis of a human pigmented melanoma and derived variant sublines in nude mice.

The extensive metastatic capacities in nude mice of variants of a human melanoma line, MeWo, were studied. BALB/c nude mice received subcutaneous implants of lung cubes impregnated in vitro with small numbers (less than 1,000) of MeWo cells as a result of previous in vitro coincubation. Such implants always resulted in lethal tumors, despite the fact that injection of dispersed 3 X 10(5) MeWo cells was normally required to obtain a tumor take. A BALB/c nude mouse that had received a MeWo lung cube implant was found to have numerous, large lung nodules 6 months after implantation. Transfer of the metastatic lung nodules to new recipients also led to the appearance of lung metastases. Cell lines established from such metastases, or from primary tumors that arose in nude mice implanted with MeWo-infiltrated cubes, showed a remarkable ability to colonize the lungs after iv injection, in contrast to the parent MeWo cells: Lungs were found to be engorged with hundreds of nodules, many, but not all, being melanotic. Widespread extrapulmonary metastases were also observed, but only after iv injection of MeWo sublines established from metastases. Karyotype analysis revealed that lung colonies established by iv cell injection had a near diploid (i.e., wild type) number of human chromosomes (mode: 44), whereas cell lines from spontaneous metastases possessed a near tetraploid number, a possible consequence of either selection or tumor progression in vivo. The results indicate that human tumor variants with unusually aggressive metastatic capabilities can be obtained in adult nude mice, similar in nature to some highly metastatic variants derived from mouse tumors (e.g., the B16 melanoma). The availability of such variants should be a valuable aid to study aspects of tumor cell heterogeneity, progression, and metastasis from a human cancer cell perspective.

Animals↗

Malignant seminoma with metastasis, Sertoli cell tumor, and pheochromocytoma in a spotted dolphin (Stenella frontalis) and malignant seminoma with metastasis in a bottlenose dolphin (Tursiops truncatus).

Seminoma with metastasis was diagnosed in a spotted dolphin (Stenella frontalis) and an Atlantic bottlenose dolphin (Tursiops truncatus). Sertoli cell tumor and pheochromocytoma were also diagnosed in the spotted dolphin. The spotted and bottlenose dolphins were adult males that stranded and died on the coasts of northwest Florida and southeast North Carolina, respectively. Neoplasia is infrequently reported in cetaceans. This is the first report of seminoma, Sertoli cell tumor, and pheochromocytoma in a dolphin, the first report of three distinct neoplasms in a dolphin, and one of the few reports of malignant neoplasia in dolphins.

Adrenal Gland Neoplasms↗

Tumour metastasis in mice with reduced immune reactivity. IV. Restoration of relative resistance to metastasis formation in thymectomized sub-lethally irradiated mice by spleen cells.

Adult thymectomy and/or sub-lethal irradiation increased spontaneous metastasis formation in several syngeneic murine systems (MCA-induced sarcomas MCG101 in C57BL/6J mice, MCG12 in CBA mice and MCA-induced epidermoid carcinoma EpCa1 in CBA mice). In order to differentiate between immunological and non-immunological effects of these treatments on tumour spread the effects of presumed selective restoration of immune competence by transfer of syngeneic spleen cells from normal donors shortly after irradiation (1.5 months before tumour transplantation) was perfomed. This procedure brought the resistance of thymectomized irradiated mice to tumour spread back to the level seen in untreated mice, providing further evidence for the conclusion that the indrease of tumour spread in this experimental model to a major part was immune-mediated. In thymectomized irradiated mice adoptive transfer of concomitant immunity by spleen cells from tumour-bearing mice soon after tumour transplantation completely inhibited the spread of the highly antigenic MCG101 and reduced that of the weakly antigenic MCG12 to control level. In contrast, adoptive transfer after tumour resection had no significant effect of the spread from either to the tumours.

Animals↗

Accuracy of criteria for predicting recurrence and metastasis in stage II and III gastric cancer patients with lymph node metastasis.

This study assessed the prediction of gastric cancer recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes, and by using criteria that were developed to identify patients with a high risk of recurrence/metastasis. The subjects were 60 patients of stage II or III gastric cancer with lymph node metastasis. Prediction of recurrence based on the detection of ONCs showed a sensitivity of 33.3% (2/6), specificity of 70.0% (7/10), and accuracy of 51.7% in stage II patients, while the sensitivity was 73.5% (25/34), specificity was 100.0% (10/10), and accuracy was 86.8% in stage III patients. Prediction of recurrence based on the presence of at least 2 high-risk criteria had a sensitivity of 33.3% (2/6), specificity of 100.0% (10/10), and accuracy of 66.7% in stage II patients, while the sensitivity was 82.4% (28/34), specificity was 80.0% (8/10), and accuracy was 81.2% in stage III patients. These results suggest that prediction of recurrence/metastasis soon after surgery using ONCs plus the high-risk criteria can increase the specificity in stage II cancer, and can achieve a sensitivity of 80% or more with a high specificity and accuracy in stage III cancer.

Humans↗

Relationship between primary tumor volume and lung metastasis in Lewis lung carcinoma (1). Assay for time course of development of metastasis.

Relationship between primary tumor volume and development of lung metastases was investigated in Lewis lung carcinoma in male C57BL/6 mice. Tumor cells (1-3 X 10(5] were injected into the muscle of the right hind legs and growth curves of primary tumors were obtained. The time course of development of metastases was determined from the size of lung colonies at autopsy by using growth rate of lung colonies. The first development of metastasis was 4 to 7 days after injection. The incidence of metastases increased as a function of time and was presented by Gompertz function as in primary tumor volume. Therefore, a linear relationship was found to exist between the incidence of metastases and the primary tumor volume. This assay is considered to be useful to understand the time course of development of metastases without resection of the primary tumors.

Animals↗

[Statistical studies on metastasis of breast cancer and cancer metastasis to the breast].

Metastasis of breast cancer is examined by the database of the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1983. Breast cancer metastases to the lungs (70.3%), liver (58.4%), bone marrow (53.1%), pleura (29.0%), adrenals (27.9%), skin-subcutaneous tissue (19.7%), brain (14.3%) are frequent in decreasing order. Bone marrow, adrenals, ovaries (11.5%) and thyroid gland (11.1%) are more likely invaded by breast cancer than others. After menopause, the metastases become less frequent than before, especially after 65 years. Breast cancer is one of the highly widespread metastatic cancers, such as malignant melanoma, neuroblastoma, leukemia and malignant lymphoma. On the contrary, cancers metastatic to the breasts are rare (less than 1%). There is no special cancer metastatic to the breast.

Adult↗

Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors: a possible approach to metastasis prevention.

Abnormal platelet aggregation on circulating and lodged cancer cells may play an important role in the early stages of metastasis formation. The immediate drop in the number of circulating platelets following intravenous injection of Walker-256 carcinosarcoma cells in rats represents the experimental counterpart of the morphologic finding of tumor cells associated with tumor clusters in the pulmonary arterioles and capillaries.

Animals↗

Intravital videomicroscopic evidence for regulation of metastasis by the hepatic microvasculature: effects of interleukin-1alpha on metastasis and the location of B16F1 melanoma cell arrest.

There have been few reported visual observations of metastatic cancer cell arrest in vivo. To seek evidence that inducible vascular adhesive properties can regulate hepatic metastasis, groups of 9-14 c57bl/6 mice were given 1.5 microg of interleukin-1alpha (IL-1alpha) 4 h before the injection of 3 x 10(5) B16F1 melanoma cells into a mesenteric vein. After 7 days, these mice had an 11-22-fold greater hepatic tumor burden than controls given i.p. saline. In both groups, small metastases were seen in the portal tract region. Twice as many 125I-labeled UdR-labeled B16F1 cells were detected in the livers of IL-1alpha-treated animals 5 min after injection, and 7 times as many were found after 24 h. Intravital videomicroscopy showed marked differences in the arrest pattern of the B16F1 cells between controls and IL-1alpha-treated mice. In controls, arrest occurred at a median distance of 32 microm beyond the sinusoidal inlet, where the median sinusoidal diameter was 16 microm. However, in IL-1alpha-treated mice, arrest occurred in the presinusoidal portal vein branches, which had a median diameter of 34 microm. Maximum observed tumor cell velocities were 2-fold less in the IL-1alpha-treated mice, although there was no significant difference in the flow rate of RBCs. To look for effects on the adhesive properties of the hepatic microvasculature, 5 x 10(4) B16F1 cells were incubated for 15 min on 5-microm sections of liver from control and IL-1alpha-treated mice. Three-fold more cells adhered to sections of liver from IL-1alpha-treated mice. This phenomenon was blocked by GRGDS peptides and by antibodies to E-selectin, ICAM-1, VCAM-1, and the alpha v integrin subunit. We postulate that pretreatment of mice with IL-1alpha alters a number of adhesive interactions between B16F1 cells and the hepatic microvasculature, contributing to the site of arrest and to the subsequent fate of the arrested cells.

Animals↗

Endocrine implications in experimental tumoral metastasis. III. The influence of the thyroid status on the metastasis of 256 Walker carcinosarcoma intratesticularly grafted and on the in vitro proliferation of the tumoral cells.

The influence of thyroid status modifications on the metastasis of 256 Walker carcinosarcoma intratesticularly grafted to rats was examined. Inhibition of metastasization and of the secondary tumoral growth was noticed in animals chronically treated with thyroxine, while hypothyroidization realized either by surgery or by administration of synthetical antithyroid drugs enhanced metastasization and growth of the secondary tumors. The primary tumoral development was not significantly influenced by the thyroid status modifications. The variations of the thyroid hormonal level influenced nonspecifically the proliferation of the in vitro cultivated tumoral cells.

Animals↗

Cardiac metastasis of cloacagenic carcinoma of the vagina: a case and review of gynecologic malignancies with cardiac metastasis.

We report of a case of a 44-year-old woman with a vaginal cloacagenic carcinoma who initially presented with a hymenal lesion that metastasized first to the perihilar lymph nodes and then consequently to the right ventricle. The embryological tumor is rare with only a few cases of vaginal or vulvar involvement. We present the first case of cloacagenic cancer of the vagina with metastasis to the heart. The lesion was surgically resected after completion of neoadjuvant therapy. Herein we present this unique case and the clinical manifestations of intracardiac and pericardial lesions from gynecologic malignancies.

Adult↗

[Surgery of lung metastasis: results of a hospital survey in the Autonomous Community of Madrid. Working Group on Surgery of Lung Metastasis (GT-CMP)].

The Task Force on Pulmonary Metastasis Surgery of the Oncology Department of the Madrid Pneumology and Chest Surgery Society designed a questionnaire to determine guidelines for surgery to resect lung metastases in the Autonomous Community of Madrid, an area with over four million inhabitants. The questionnaire was divided into five sections: indications, diagnostic procedures, extension studies, disciplinary foci and surgical techniques. Ten of the hospitals surveyed answered the questionnaire. We found that disagreement is high regarding patient screening, and that there are differences regarding some preoperative procedures and extension studies, as well as in therapeutic approach. Eighty percent of the respondents were not in favor of using video assisted thoracoscopy as a therapeutic technique, and disagreement was greater regarding approaches technique, and disagreement was greater, regarding approaches to bilateral metastases. We infer that between 100 and 120 cases are treated surgically every year. Procedures to join The International Lung Metastases Registry have started.

Hospitals↗

Metastasis of cutaneous malignant melanoma to angiolipoma: the tumor-to-tumor metastasis phenomenon.

BACKGROUND: Although the phenomenon of tumor-to tumor metastasis is not rare, it has been reported in only eight cases with malignant melanoma as the primary tumor. METHODS: This case describes a patient with cutaneous malignant melanoma that metastasized to an angiolipoma. To our knowledge this is the second case of a malignant melanoma metastasizing to another primary cutaneous tumor and the first to do so in a lipoma. CONCLUSION: In this report we present the clinical and histopathologic features of this special case and review the relevant literature.

Adult↗