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Hepatoid adenocarcinoma of the lung: report of a case of an unusual alpha-fetoprotein-producing lung tumor.

We report on a rare tumor of the lung characterized by its morphologic hepatoid features and alpha-fetoprotein production. This unusual neoplasm arose in the left lung of a 36-year-old man in whom clinical and radiologic examinations did not reveal any other tumor. The serum level of alpha-fetoprotein was measured at 6,090 ng/mL and was parallel to the evolution of the tumor. Despite treatment, the patient died 7 months after the diagnosis. The microscopic appearance of the tumor was the same as observed in hepatocarcinoma and hepatoid adenocarcinoma of the ovary or the stomach, with a tubular, papillary, or trabecular pattern. Periodic acid-Schiff-positive hyaline globules were numerous, and tumor cells showed immunohistologic positivity for alpha-fetoprotein and carcinoembryonic antigen. This lung adenocarcinoma was first described by Ishikura et al. in 1990 and was named hepatoid lung adenocarcinoma. Like the rare hepatoid carcinoma of the gallbladder, the pancreas, the ampulla of Vater, the renal pelvis, and the bladder, the exact histogenesis and the prognosis of this type of lung tumor are not yet known.

Adenocarcinoma↗

Chemotherapy practices and perspectives in invasive bladder cancer.

Bladder cancer is the fifth most common cancer in adult patients. Two-thirds of patients have superficial tumors and their treatment is conservative. Nevertheless, 30% of superficial tumors become infiltrative and represent a third of tumors at initial diagnosis. Overall mortality from bladder cancer is 30%. Important molecular events may explain the carcinogenesis and evolution of these tumors. Infiltrating bladder cancers are currently treated by radical cystectomy. Neoadjuvant chemotherapy has demonstrated a positive impact on patients' outcomes before cystectomy. Adjuvant chemotherapy after cystectomy is currently being studied in an international randomized trial. Patients with advanced disease are treated by chemotherapy with palliative intentions. Two regimens are standard: the combination of methotrexate, vinblastine, adriamycin and cisplatin, and the combination of gemcitabine and cisplatin. The addition of paclitaxel to the latter regimen is the subject of ongoing study. Only a few patients have long-term nonevolutive disease. Research must be focused on the combination of chemotherapy and targeted drugs directed through gene methylation, cytokine-receptor activation and signaling pathways.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of two simultaneous carcinoma lesions of the colon and rectum with different differentiation and stage of neoplastic process].

It considers a patient with simuitant colorectal carcinoma. Both tumor lesions are from different stage and different histological type. The grade of invasion of tumor process does not correspond to the histological type of neoplasma and nider to the size of the primer tumor. The different evolution of those simuitants lesions does not correspond with criteria for histological type and with the stage of primer tumor as a prognostic factors.

Adenocarcinoma↗

All three polyoma early genes are involved in transformation of rat embryo fibroblast cells.

The tumor progression concept was first defined by Foulds at the end of the nineteen fifties. His work about the evolution of mammary tumors led to the conclusion that a tumor is initiated as soon as a cell interacts with an oncogenic agent and that the tumor progresses by acquiring in a permanent and irreversible way, new properties which are characteristic of neoplasms. Molecular biology made possible the identification in transformed cells of molecular events such as chromosomal rearrangements, mutations, the loss of certain genes or integration of viral genes. Experimental models have been introduced in order to try to identify in vitro the successive steps leading to transformation and the corresponding cellular phenotypes. One of these models is the cellular transformation phenomenon induced by polyoma virus. In this model, it now seems clear that several steps and several genes are involved in the cellular transformation phenomenon.

Animals↗

[Biological markers in cancer of the ovary].

The organism produces substances whose presence or amount indicate the existence of a neoplastic process, called biological tumor markers. They can be used in the clinical laboratory for diagnostic purposes, and also to orient about the evolution of the tumoral mass. There are about 90 tumor markers, 33 of them have studied in relation to cancer of the ovary, that are described in this work. Eight of them are the most important: CSAp, OCA, OCAA, IAP, Nagao's isoenzyme, hCG/hCG beta, hPL, and AFP.

Antigens, Neoplasm↗

[Life experience by children with brain tumors].

The long-term evolution (intellectual, affective, social) of children cured of their cerebral tumor is far from being satisfactory, despite progress in neurosurgery, chemotherapy and radiotherapy. The feelings of these children and of their family have rarely been studied. The author, on the basis of 60 interviews with such children and their parents, pinpoints the great violence of feelings and situations: feelings of terror, of non-sense, disturbance of the feeling of identity, breaking of relationships, loss of time landmarks. The psychological consequences can be severe: such as being enclosed in a frozen time wrap, and experiencing a lack of social life. If we knew the feelings of these children better, then we could start preventive actions (psychotherapy and specialized rehabilitation) early enough to avoid sequels which cannot be attributed, for all of them, to cerebral damage.

Adolescent↗

Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes.

Mice bearing a tumor necrosis factor (TNF) alpha transgene controlled by an insulin promoter developed an increasingly severe lymphocytic insulitis, apparently resulting from the induction of endothelial changes with features similar to those observed in other places of intense lymphocytic traffic. This was accompanied by dissociation of the endocrine tissue (without marked decrease in its total mass), islet fibrosis, and the development of intraislet ductules containing, by places, beta cells in their walls, suggesting a regenerative capacity. Islet disorganization and fibrosis did not result from lymphocytic infiltration, since they were also observed in SCID mice bearing the transgene. Diabetes never developed, even though a number of potentially inducing conditions were used, including the prolonged perfusion of interferon gamma and the permanent expression of a nontolerogenic viral protein on beta cells (obtained by using mice bearing two transgenes). It is concluded that (a) a slow process of TNF release in pancreatic islets induces insulitis, and may be instrumental in the insulitis resulting from local cell-mediated immune reactions, but (b) that insulitis per se is not diabetogenic, lymphocyte stimulation by cells other than beta cells being necessary to trigger extensive beta cell damage. This provides an explanation for the discrepancy between the occurrence of insulitis and that of clinical disease in autoimmune diabetes.

Animals↗

Follicular dendritic cell tumor of the mediastinum: expression of fractalkine and SDF-1alpha as mast cell chemoattractants.

Follicular dendritic cell tumor (FDCT) is a rare tumor mainly located in laterocervical lymph nodes. We report one case of mediastinal FDCT associated with a history of bullous skin disease and clinically obvious immunosuppression. This tumor was characterized by heavy mast cell infiltration. Mast cells were in close relationship with tumor cells as demonstrated by ultrastructural examination and their presence are probably related with the strong expression of mast cell chemoattractants as fraktalkine and stromal cell-derived factor-1alpha by tumor cells. The long follow-up period of more than 17 years allowed to us assess the relatively indolent evolution of this tumor characterized by three slowly growing local recurrences without metastasis.

Antigens, CD↗

[Sarcomatoid spindle-cell epithelioma. Anatomicoclinical study of 15 cases].

Sarcomatoid spindle cell carcinoma, which is a rather rare cancer, is of epithelial origin, but histologically resembles a connective spindle cell sarcoma. It remains subject to controversy, especially concerning the reality of epitheliomesenchymatous transformation of the neoplastic cells which, indeed, take on not only the shape but also the behaviour of connective cells. The debate is of both a dogmatic and practical nature, dogmatic in that it has bearing on the question of cellular specificity, and practical in that histological transmutation has repercussions on the macroscopic aspect of the tumor, its clinical evolution and even its behaviour vis-a-vis radiation therapy. The preferred, but not the only, sites of such tumors are the upper respiratory and digestive tracts. In many cases, they occur in subjects who many years previously had undergone radiological treatment, with the tumor appearing in the irradiated area. The problems raised by these unusual cancers explain and seem to justify the publication over the last few years of isolated cases or series of reports made in various centers. The present work concerns 15 anatomoclinical cases observed at the Institut Curie.

Adult↗

[Carcinoid tumors of the common bile duct: report of a case].

The authors discuss an uncommon case in the literature of a carcinoid tumor of in the bifurcation of common hepatic duct. The tumor was surgically resected and the duct was reconstructed by Y of Roux's technic. The patient had a good evolution and no tumoral lesion was found in post operative exams during the last six months. The authors present a literature review and discuss diagnosis, treatment and prognosis.

Anastomosis, Roux-en-Y↗

[Natural history of tumors in carcinogenesis after ureterosigmoidostomy. I--Clinical approach].

It is admitted that the risk of developing an uro-colonic tumor in patients operated by an ureterosigmoidostomy (USS) is several hundred times higher more than in the normal population. However, the evolution of these tumors and the mechanisms of this particular type of carcinogenesis are not yet totally cleared. The analysis of the observations described in the literature and the recent datas on experimental models contribute to a better understanding of the natural history of these tumors. In this review, we have on one hand defined the clinical profile and the biological behaviour of these tumors with their practical approach and on the other hand discussed the different elements and hypothesis involved in this carcinogenesis after USS.

Animals↗

Mathematical tree models for cytogenetic development in solid tumors.

We present a new approach for modeling the occurrence of genetic changes in human tumors over time. In solid tumors, data on genetic alterations are usually only available at a single point in time, allowing no direct insight into the sequential order of genetic events. In our approach, genetic tumor development and progression is assumed to follow a probabilistic tree model. We use maximum likelihood estimation to reconstruct a tree model for the genetic evolution of a given tumor type. The use of the proposed method is illustrated by an application to cytogenetic data from 173 cases of clear cell renal cell carcinoma, which results in a model for the karyotypic evolution of this tumor.

Carcinoma, Renal Cell↗

Strain-dependent differences in malignant conversion of mouse skin tumors is an inherent property of the epidermal keratinocyte.

The multistage evolution of squamous skin tumors induced by chemical or viral carcinogens on mice from different genetic backgrounds has been a valuable model to define low penetrance loci that determine cancer susceptibility or resistance. Susceptibility determinants are multigenic, stage-specific, dependent on the carcinogenesis protocol, and in the case of initiating events, intrinsic properties of keratinocytes. In this study we examined the malignant conversion frequency of keratinocytes derived from FVB/N, inbred SENCARA/Pt, BALB/c or C57BL/6 mouse strains that differ substantially in the frequency of progression from papilloma to carcinoma. Keratinocytes were cultured from newborn mice and tested in an in vitro malignant conversion assay induced by a chemical carcinogen or immortalized by infection with replication defective human papillomavirus type 16 (HPV-16) E6/E7 retroviruses and tested for malignancy by grafting immortalized cell lines to nude mice. In vitro, FVB/N keratinocytes were 10-fold more sensitive to chemically induced malignant conversion than keratinocytes from other strains, consistent with the known sensitivity of this strain to pre-malignant progression in vivo. The E6/E7 genes induced immortalization of keratinocytes from FVB/N, SENCARA/Pt or C57BL/6 mice more efficiently than BALB/c, and HPV-16-immortalized FVB/N keratinocytes formed tumors more frequently (64%) than SENCARA/Pt (31%) BALB/c (1.9%) or C57BL/6 (2.5%). Furthermore, 78% of the tumors formed by FVB/N keratinocytes progressed to squamous carcinomas compared with 46% for SENCARA/Pt-derived cells and <3% for the others. In F(1) offspring of crosses from SENCARA/Pt and FVB/N mice, both the papilloma incidence and frequency of malignant conversion reflected the SENCARA/Pt parent indicating that predisposition to pre-malignant progression is not a dominant characteristic. This predisposition is an intrinsic property of the target keratinocytes and as such should be amenable to further study in isolated cells.

9,10-Dimethyl-1,2-benzanthracene↗

Systemic temozolomide combined with loco-regional mitoxantrone in treating recurrent glioblastoma.

Twenty-two recurrent GBM patients were enrolled for second tumor debulking with local positioning of a Rickam reservoir, in order to locally deliver chemotherapy with the aim of controlling local tumor recurrence. We designed a protocol using systemic temozolomide (150 mg/sqm days 1-5 every 28) in association with mitoxantrone, delivered through the reservoir (4 mg/day 1-5 every 28) positioned into the area of tumor exeresis. After re-operation a residual tumor mass no larger than 2 cm was identified in 18/22 patients. The patients were treated with monthly cycles of chemotherapy until evolution of the tumor, but in no case for more than 10 cycles. Responses were evaluated by MRI scans performed every 2 months and images assessed according to MacDonald's criteria. Response rate: no complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive disease (PD) occurred. The median progression-free survival (PFS) and survival time (ST) of the whole group of treated patients was 7 and 11 months, respectively and more than a quarter of the patients survived over 18 months. During the study, the patients' compliance was complete and no dropouts occurred. Hematological toxicity was mild and after repeated local injections only minor neurological side-effects occurred. Despite some bias in patients' selection not excluded in this pilot study, results are interesting: the PFS was as long as the survival of recurrent GBM reported in the literature.

Adult↗

Association of primary central nervous system lymphomas with the Epstein-Barr virus.

The incidence of primary central nervous system lymphoma (PCNSL), previously a rare tumor, has increased significantly over the past few decades, partly due to the AIDS epidemic but also in immunocompetent individuals. Studies from Western countries have shown a consistent association of tumors occurring in immunocompromised individuals with the Epstein-Barr virus (EBV) suggesting an important role for the virus in the pathogenesis of these tumors, but an infrequent association of the virus with PCNSL in the immunocompetent host has also been noted. We studied 11 patients with PCNSL who had no evidence of an immunocompromised state. All the tumors were aggressive B cell lymphomas. EBV association was studied using EBER in-situ hybridization. 10 out of the 11 tumors were negative for EBV, indicating that tumors in immunocompetent individuals in developing countries are also infrequently EBV associated and that a different pathogenetic mechanism is operative in the evolution of these tumors.

Adult↗

Advances and challenges in human 3D solid tumor models.

The field of cancer biology and therapeutics has soared in the past several decades with new therapeutic modalities and options for patients, such as chemoradiotherapy, immunotherapy, and combination therapy. This dramatic success in expanding patient options is primarily attributed to the development of various model systems to elucidate drivers of oncogenesis, tumor maturation and evolution, and response to therapeutics. While mouse models have been a workhorse of cancer research, technological progress in ex vivo patient-derived tumor models has afforded more tunable and scrutable systems for patient-predictive platforms and mechanistic study. This review explores the technological innovations in 3D solid tumor models and their applicability to various aspects of cancer biology and identification of therapeutics. Features of the tumor and tumor microenvironment like spatial heterogeneity, multicellular populations and genomic variations are addressed and elaborated through the establishment of new in vitro models. We further address the integration of perfusable vasculature with 3D tumor models and the potentially wide-ranging applications of these more complex platforms in precision medicine and cancer immunotherapy. Finally, we provide an outlook on the future of experimental cancer models for both biological investigation and bench-to-bedside pipeline development.

Journal Article↗

MHC class I antigens, immune surveillance, and tumor immune escape.

Oncogenic transformation in human and experimental animals is not necessarily followed by the appearance of a tumor mass. The immune system of the host can recognize tumor antigens by the presentation of small antigenic peptides to the receptor of cytotoxic T-lymphocytes (CTLs) and reject the nascent tumor. However, cancer cells can sometimes escape these specific T-cell immune responses in the course of somatic (genetic and phenotypic) clonal evolution. Among the tumor immune escape mechanisms described to date, the alterations in the expression of major histocompatibility complex (MHC) molecules play a crucial step in tumor development due to the role of MHC antigens in antigen presentation to T-lymphocytes and the regulation of natural killer cell (NK) cell function. In this work, we have (1) updated information on the mechanisms that allow CTLs to recognize tumor antigens after antigen processing by transformed cells, (2) described the altered MHC class I phenotypes that are commonly found in human tumors, (3) summarized the molecular mechanisms responsible for MHC class I alteration in human tumors, (4) provided evidence that these altered human leukocyte antigens (HLA) class I phenotypes are detectable as result of a T-cell immunoselection of HLA class I-deficient variants by an immunecompetent host, and (5) presented data indicating the MHC class I phenotype and the immunogenicity of experimental metastatic tumors change drastically when tumors develop in immunodeficient mice.

Animals↗

Perspectives on the origins of multiple myeloma and plasmacytomas in mice.

The natural history of multiple myeloma and related human plasma cell tumors is compared to the process of plasmacytomagenesis in mice. Intriguing new findings are beginning to give a more complete picture of the evolution of these tumors. Mouse plasmacytomas consistently develop chromosomal translocations that dysregulate c-myc, but consistent oncogenic mutations have not yet been defined in multiple myeloma.

Animals↗