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At least 19 recordsLinked to original sources
PubMed2025

Uveal Melanoma and the Lynch Syndrome Tumor Spectrum.

IMPORTANCE: To date, no environmental factors and few therapeutic options are known for uveal melanoma (UM), the most common malignant intraocular primary tumor in adults. Identification of new predisposition factors could lead to better monitoring and possibly improved treatments of patients with UM. OBJECTIVE: To identify new genetic alterations predisposing for UM. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted at Institut Curie in Paris, France, among 381 consecutive patients diagnosed with UM between July 2021 and February 2023. UM was diagnosed clinically by ophthalmologists, and a senior pathologist confirmed the diagnosis when tumor or biopsy was available. All participants received genetic counseling and consented to extended genetic testing. A panel of 122 genes predisposing to cancer were analyzed by targeted sequencing on germline DNA from these patients. MAIN OUTCOMES AND MEASURES: Frequency of pathogenic variants (PVs) in genes from a targeted panel, with classification of germline PVs done according to the American College of Medical Genetics and Genomics guidelines and the French Unicancer Genetics Group. RESULTS: A total of 79 PVs were identified in 70 participants (41 female and 29 male; mean [SD] age, 60.6 [15.3] years). Among them, 21 were found in clinically relevant genes, with an enrichment in the mismatch repair (MMR) genes, involved in Lynch syndrome, a frequent predisposition to colon and endometrial cancers. This finding suggested MMR germline PVs could also predispose to UM. One tumor was available from a participant carrying a MLH1 germline PV. The tumor exhibited a monosomy 3 with loss of the wild-type allele of MLH1, located on chromosome 3. Loss of expression of MLH1 was observed by immunohistochemistry, and MMR variant signatures SBS6, ID1, and ID2 were identified from the whole-genome sequencing of this tumor, supporting the possibility that MLH1 contributes to the oncogenesis of this UM. CONCLUSIONS AND RELEVANCE: This prospective germline study on patients with UM provided evidence supporting the notion that MMR germline alterations are enriched among patients with UM and may contribute to oncogenesis of UM, and that UM may therefore be a rare tumor manifestation of Lynch syndrome.

Humans↗
PubMed1979

[Ectopic hormone formation and tumor markers in bronchial neoplasms].

Carcinoma of the bronchus can produce several polypeptide hormones and therefore has the capacity to cause most syndromes of endocrine hyperfunction. All pituitary hormones can be synthesized ectopically; furthermore, the production of hormones from the hypothalamus (CRF), the placenta (HCG, HPL) and the C-cells of the thyroid (calcitonin), as well as parathormone and prostaglandins has been described. The paraneoplastic syndrome may often be more dangerous for the patient than the tumor growth itself, and can lead to early death. On the other hand, it may allow the early detection of an unsuspected tumor. The ectopic hormones and other nonendocrine proteins and peptides can be used as tumor markers, and can demonstrate the effect of treatment and early recurrence or metastases. An ideal tumor marker should have the following characteristics: 1. production exclusively by neoplastic tissue, 2. direct correlation with tumor size, 3. substances common to all tumor types ("large spectrum tumor marker") although specific tumor markers for special tumors should be available, 4. the assays must be easy and automation should be possible. At present no tumor marker satisfies all these conditions. The measurement of several tumor markers and the use of discriminant analysis may extend their diagnostic value and open the way for biochemical detection of cancer in the future.

Adrenocorticotropic Hormone↗
PubMed1976

Multimodal surgical adjuvant therapy for a broad spectrum of tumors in humans.?

Co-operative investigation of clinical therapy for cancer is used to test hypotheses developed in single institutions and in animal research laboratories. The present studies in a large co-operative organization, the Central Oncology Group, are being conducted in seven major solid tumors in adults; in these studies patients with a poor surgical prognosis are being treated with preoperative or postoperative chemotherapy, preoperative radiotion therapy of these modalities. Results of studies currently underway or recently completed in 1,278 patients are summarized. In most instances, the research has demonstrated little or no apparent improvement in the disease free interval or the survival time from adjuvant therapy, although only on of the studies has been completed and fully evaluated thus far. In carcinoma of the colon and rectum and melanoma, mild toxicity from drug therapy has been associated with statistically significant improvement in survival times. These studies have produced base line information on disease free intervals, time to progression and survival time in patients with cancer who are seen in the participating institutions. These observations are expected to useful in the planning of future adjuvant studies.

Adult↗
PubMed1976

Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumors.

Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil against various tumors was examined. Therapeutic ratio (ILSmax/ILS30) in L-1210 system was 4.5 by oral administration, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 1.9 and 1.0, respectively. Therapeutic ratio of the compound in C-1498 system was 11, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 3.3 and 2.5, respectively. 1-Hexylcarbamoyl-5-fluurouracil was also active against solid and ascites tumors by oral administration. It was markedly active against Nakahara-Fukuoka sarcoma, adenocarcinoma=755, and ascites sarcoma-180, and moderately active against Ehrlich ascites carcinoma. This compound had a wider tumor spectrum than 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil by oral administration.

Adenocarcinoma↗
PubMed1978

Contrasting characteristics of Marek's disease herpesvirus isolated from chickens with and without avian leukosis virus infection.

Marek's disease herpesvirus (MDHV) isolated from chickens free of naturally occurring avian leukosis virus (ALV) infection produced characteristic foci in both chicken embryo fibroblast (CEF) and chicken kidney cell (CKC) cultures. MDHV-A, which was extracted from the feather follicle epithelium of chickens naturally infected with ALV, did not induce cytologic changes in CEF cultures, but did cause focus formation in CK cultures. ALV was detected in MDHV-A, but not in MDHV preparations. MDHV-A (reconstructed in vivo) and MDHV were further distinguished from one another by inoculation of ALV-free LSI-SPF chickens. MDHV-A elicited a high incidence of early mortality which was not accompanied by the gross tumor spectrum characteristic of Marek's disease, although extensive histologic lesions were present. The differences between MDHV and MDHV-A were not as striking in another line of ALV-free chickens (SPAFAS). By contrast, among conventional chickens with naturally occurring ALV infection, neither MDHV-A nor MDHV caused appreciable early mortality although both were highly oncogenic (gross tumor development). These observations demonstrate that the presence of an oncornavirus (ALV), detected by radioimmune but not complement fixation assays, can influence the in vitro and in vivo characteristics of an oncogenic herpesvirus (MDHV). The observations recorded here resolve some of the inconsistencies reported in the literature. Thus, the apparent failure by some to find interactions between MDHV and oncornaviruses can be ascribed to the comparatively limited sensitivity of the complement fixation assay used to detect oncornaviruses (ALV). We have shown that the presence of oncornavirus detectable by radioimmune assay, but not by complement fixation, can influence the in vitro and in vivo responses of an oncogenic herpesvirus (MDHV). Our observations relating to viral interaction do not imply that MDHV required the presence of ALV to produce disease.

Animals↗
PubMed1979

Tumor variation in the cancer family syndrome: ovarian cancer.

The Cancer Family Syndrome is a hereditary disorder (autosomal dominant), characterized by early onset cancer of the colon (particularly the proximal colon) and endometrium, with an excess of multiple primary cancers. Recent evidence reflects the possibility of an even broader tumor spectrum consisting of carcinoma of the stomach, the ovary, the kidney, and possibly other organs. A family with the cardinal features of the Cancer Family Syndrome is described, including two sisters and their mother who had ovarian carcinoma at early ages (38, 46, and 49 years). Two of these three women have shown unusual tolerance to cancer, despite invasion of the primary tumors. Implications for cancer surveillance and management are discussed.

Adenocarcinoma↗
PubMed2026

Germline ATM Testing in Hereditary Cancer Syndromes: Feedback from a Five-Year Center Cohort.

PURPOSE: Germline ATM pathogenic or likely pathogenic (P/LP) variants are increasingly recognized as clinically relevant in hereditary cancer predisposition, their integration into routine testing remains heterogeneous across countries. We describe the prevalence, tumor spectrum and relative risk associated with germline ATM P/LP variants in individuals with breast and pancreatic cancer. METHODS: We conducted a five-year retrospective (2019-2025) reanalysis of the ATM gene in 1,707 probands tested with hereditary breast and ovarian cancer (HBOC) or pancreatic cancer panels in our center. For all probands that underwent targeted ATM reanalysis, relative risks (RR) and odds ratios (OR) were calculated. Family-based segregation was performed when possible. RESULTS: Targeted ATM re-analysis identified 33 additional probands with P/LP variants, increasing diagnostic yield from 7.3% to 9.1% in HBOC and from 4.3% to 9.7% in pancreatic cancer. Among 22 breast-cancer probands, mean age at diagnosis was 47 years. Case-control comparison yielded OR 3.85 (95% CI 2.43-6.08; P=8.5×10-9) for breast cancer and OR 15.81 (95% CI 6.31-39.66; P=4.0×10-9) for pancreatic cancer. CONCLUSION: This work strengthens the role of ATM in cancer predisposition panels and supports its inclusion in French national hereditary cancer panel recommendations, together with implementation of appropriate surveillance and counseling for individuals harboring ATM P/LP variants.

ATM↗
PubMed1979

Tumor-associated phenylalanyl transfer RNA found in a wide spectrum of rat and mouse tumors but absent in normal adult, fetal, and regenerating tissues.

RPC-5 chromatography was used to examine the phenylalanyl transfer RNA (Phe-tRNA) of 25 normal rat and mouse tissues including adult, fetal, and regenerating liver; whole embryos; and other adult organs. Only a single major isoaccepting Phe-tRNA was found in every case. Phe-tRNA's from 25 transplantable rat tumors and 33 transplantable mouse tumors were similarly examined. Seventeen rat tumors and 10 mouse tumors, of a wide spectrum of histological types, were found to have an additional, tumor-associated Phe-tRNA isoacceptor. This tumor-associated Phe-tRNA was not found in the livers of animals bearing tumors that contained this isoacceptor. Differences in chromatographic behavior between the rat and mouse tumor-associated Phe-tRNA's strongly suggest that they have different structures. Our data suggest that these differences result from different degrees of incompleteness of posttranscriptional modification, most likely at the normally very hypermodified Wye (formerly called Y) base.

Animals↗
PubMed1977

Lymphoma in cotton-top marmosets after inoculation with Epstein-Barr virus: tumor incidence, histologic spectrum antibody responses, demonstration of viral DNA, and characterization of viruses.

6 of 20 cotton-top tamarins (Saguinus oedipus) inoculated with Epstein-Barr virus (EBV) developed diffuse malignant lymphoma resembling reticulum cell or immunoblastic sarcoma of man. Hyperplastic lymphoreticular lesions were induced in three additional animals; in two instances the hyperplastic lesions regressed. Inapparent infection with development of antibody occured in eight animals. In two animals there was no evidence of EBV infection. One animal died in the first week after inoculation of parasitic infection. 10 animals uninoculated or mock-inoculated developed neither lymphoproliferative disease nor antibody. The malignant lymphoma appeared to arise from a cell with an uncleaved vesicular nucleus found in the center of the germinal follicle. The prominent cytologic features of this cell were extensive formation or rough endoplasmic reticulum and elaboration of the cytoplasmic membrane with microvilli. Cell lines derived from these tumors did not have receptors for complement. IgFc, or sheep erythrocytes, and the cell lines adhered to glass and plastic. EB nuclear antigen was found in imprints of two lymph nodes, one with lymphoma and one with hyperplasia. EB virus DNA was detected directly in the tumors of three animals and in cell lines from two lymphomas. Typical herpes virus particles were found in supernatant fluids from cell lines obtained from lymph nodes with tumors and hyperplasia, as well as in lines derived from blood leukocytes of marmosets with inapparent infection. These virus preparations had the biologic property characteristic of EBV, namely, stimulation of cellular DNA synthesis and immortalization of human lymphocytes. The virus derived from two cell lines was neutralized by reference human sera with EBV antibody and not by antibody-negative human sera. The virus derived from the experimental lesions is thus indistinghishable from human EBV. The marmoset has enhanced susceptibility to oncogenesis by EB virus. Among identified factors which may play a role in the heightened tumorigenicity of EB virus in this species are the increased production of virus by transformed cells and the absence of membrane receptors for complement or IgFc on transformed cells.

Animals↗
PubMedDate not supplied

[Comparative study of the tRNA-methylases of normal and tumor tissues. I. Spectrum of renal and carcinoma RA methylases].

A comparative study of rat kidney and carcinoma RA tRNA-methylase activity has been carried out using partially purified enzyme preparations and total E. coli tRNA. Also the nuclease activity of the methylase preparations from kidney and carcinoma was compared. It was established that the methylase activity in carcinoma preparations is higher, whereas the nuclease activity is lower in comparison to the enzyme preparations from liver. No formation of some specific methylated compounds could be established in the case of carcinoma. It was established that the relative contribution of individual methylases to the elevated level of total tRNA-methylase activity in carcinoma is different. Maximal enhancement of activity was established for the methylase forming m5U, whereas the activity of the enzymes, transfering the methyl group to the fifth position of C is practically equal in kidney and carcinoma tissues. Experimental results and theoretical evaluation of the hypotheses suggested to explain the higher methylase activity in tumor tissues allowed to reject some of them.

Animals↗
PubMed1976

The clinical spectrum of malignant nasal tumors.

Unlike other head and neck cancer, which is almost exclusively squamous cell carcinoma, nasal malignancies present a wide and varied spectrum of tumor types. Classification of these tumors is not standardized and treatment tends to be individualized. In a review of 35 patients with primary nasal malignancies, only 33% had squamous cell carcinoma. Glandular, neurogenic, and hemopoietic tumors accounted for the other major subgroups. Despite the diverse histopathological tumor types, the diagnosis, treatment, and clinical problems seem related more to the nasal location than to the actual type of tumor. Selected cases are presented to illustrate the clinical behavior and problems that occur with nasal tumors.

Adenocarcinoma↗
PubMed1976

A spectrum of malignant epithelial tumors of the prostate gland.

Conceptually, the prostatic territory encompasses neoplams whose origins are intraprostatic, paraprostatic or extraprostatic. Our objectives in this review are to 1) present a classification of the spectrum of malignant epithelial growth encountered in the prostatic territory, 2) show examples of these neoplasms and remark upon their histogenesis, enzyme production and endocrine sensitivity, and 3) suggest re-evaluation of some of our current routine therapeutic procedures.

Adenocarcinoma↗
PubMed1977

Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.

A therapeutic strategy for combined radiotherapy and chemotherapy of experimental solid tumors has been devised. More effective utilization of combined chemotherapy and radiotherapy may be realized clinically if comparable information is obtained in man. The overall treatment efficiency of successive courses of treatment has been determined by a method that defines tumor response quantitatively over an entire spectrum of tumor responses. The findings of this study have shown that an individual tumor that responds well to the first course of therapy will respond well to the second and third courses of combined modality therapy. Various solid tumors in different animal species have demonstrated variability of response to treatment, analogous to the many types of response found clinically.

Animals↗
PubMed1979

Vascular leiomyoblastoma of the stomach -- Observations supporting its origin from Zimmermann's pericyte.

Gastric leiomyoblastoma with small mesenteric metastasis in a 44-year-old man has been studied by light and electron microscopy. Histologically, the tumor, having "epithelioid" tumor cells mixed with spindle leiomyomatous cells, was rich in blood vessels and focally simulated hemangiopericytoma. Electron microscopy revealed the tumor cells in variable stages of differentiation from poorly differentiated polygonal cells to smooth muscular cells. The intermediate cells had numerous cytoplasmic processes which interlocked each other. In addition, an intimate association was noted between the tumor cell processes and the small vessels including capillaries. With the recent characterization of the pericyte as a pluripotent mesenchymal cell that may serve as a precursor to the vascular smooth muscle cell, the present observations support the view that some leiomyoblastomas originate from the pericyte of Zimmermann. Leiomyoblastoma may be placed between hemangiopericytoma and glomus tumor in the spectrum of pericytic tumors.

Adult↗
PubMed1979

Carcinogenicity of methylated derivatives of N-nitrosodiethylamine and related compounds in Sprague-Dawley rats.

Five nitrosamines, which can be considered alkyl derivatives of N-nitrosodiethylamine, were tested for carcinogenicity by administration to Sprague-Dawley rats in drinking water at approximately equimolar concentrations. N-Nitrosodi-n-propylamine was a potent carcinogen but less so than N-nitrosodiethylamine and gave the same spectrum of tumors. N-Nitrosodiisopropylamine was very much weaker than N-nitrosodiethylamine and induced only tumors of the nasal turbinates in significant incidence. At the doses given, neither N-nitrosodiisobutylamine nor N-nitrosodi-sec-butylamine was significantly carcinogenic. In contrast, the cyclic nitrosamine N-nitrosohexamethyleneimine was equally potent with N-nitrosodiethylamine and gave the same spectrum of tumors in liver, esophagus, and nasal turbinates. The results support the concept that oxidation at the alpha carbon atom of nitrosamines is a significant step in carcinogenesis.

Animals↗
PubMed1976

Spontaneous regression in choriocarcinoma and related gestational trophobalstic neoplasms.

Gestational trophoblastic neoplasia represents a biologic spectrum of tumors progressing from the hydatid mole, to invasive mole, and to choriocarcinoma. This progression is reflected in increasing degrees of aneuploidy in the respective lesions. Just as there is a natural tendency for the rejection of the trophoblast of a normal pregnancy culminating either in parturition or in spontaneous abortion, rejection of tumors of trophoblast occurs at any point in the progression of the disease spectrum. The unusual effectiveness of chemotherapy in trophoblastic disease may be related to this natural tendency to rejection. This tendency, in turn, is thought to derive from the genetic disparity between the maternal host and the tumor tissue of fetal origin, since the fetus possesses both maternal and fetal antigens.

Aneuploidy↗