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At least 19 recordsLinked to original sources
PubMed2025

Single-cell RNA-seq of small-intestinal neuroendocrine tumors reveals the cell of origin and gene expression of early tumor development.

Patients with a hereditary form of small-intestinal neuroendocrine tumors (SI-NETs) present with multiple synchronous tumors and precursors at various stages. Using this germline trait, single-cell RNA sequencing is performed to define the cell-of-origin and gene-expression trajectory in early tumor development. A subset of CES1(+), LCN15(-) enterochromaffin (EC) cells, residing at +4 position and below in the crypts, distinct from EC cells migrating up the villi, emerges as the putative SI-NET origin. PRODH2 is identified as a key biomarker for precursor cells, revealing stage-specific gene expression linked to early tumor development. From precursor to fully developed tumors, notable changes include the up-regulation of UCHL1 and MBD3L2, as well as the significant down-regulation of cell-cycle inhibitory genes, CDKN1A, CDKN1C, and CDKN2B, which play roles in cell survival and tumorigenesis. The current study provides insight into SI-NET initiation and progression, offering potential advancements in diagnosis, prevention, and treatment.

Neuroendocrine Tumors↗
PubMed1979

Effect of thymectomy on tumor development and on T and B lymphocytes in tumor-bearing rats.

Tumor growth and changes in T and B lymphocyte ratio in spleen, draining lymph node and peripheral blood of thymectomized, irradiated rats, reconstituted with syngeneic bone marrow transplanted at various time intervals with MC-1 fibrosarcoma cells were followed. Control nonthymectomized or "sham" operated rats were transplanted an equal dose of tumor cells. Thymectomy and irradiation reduced the numbers of T lymphocytes in all lymphoid organs, while the enhanced numbers of B cells are probably related to reconstitution with cells of syngeneic bone marrow. The time interval between thymectomy, irradiation and transplantation of tumor cells proved to be a limiting factor for tumor growth and changes in T and B cell ratio. Early transplantation of tumor cells (7 days after irradiation) resulted in an enhanced resistance to tumor development, a reduced tumor growth rate and a progressing decline in the number of T cells. If the interval between thymectomy and tumor cell transplantation lasted 4 weeks, the T cell population became partially regenerated, and tumors grew progressively in correlation with a continuing T lymphocyte depletion. The results are discussed in terms of the role of various T cell subpopulations and the significance of residual, thymectomy- and irradiation-resistant T lymphocyte population, vital for a preservation of T cell immunological functions.

Animals↗
PubMed1975

Tumor development after polyoma infection in athymic nude mice.

Nude (nu/nu) mice in a CBA/H background show an age-dependent ssuceptibility to tumor development after polyoma virus infection (strain LID-1) when compared with nu/ + or CBA/H mice, which is apparent when 15- or 30-day-old mice are used: tumor incidence was 83 to 90% in nudes and 0 to 10% in controls. Latent perids for tumor development were also shortened in nudes. However, with increasing age nude mice become partially resistant and only 25% develop tumors when infected at 120 days of age. This partial resistance could be transferred with spleen cells to newborn mice. The cells in spleen responsible for this transfer can be eliminated by lysis with anti-Ig and complement or by pre-treatment of the donor with 100 mg/kg of cyclophosphamide and were not affected by treatment in vitro with anti-Thy.1.2 or procedures that remove adherent cells and/or macrophages. When the cells in 15-day-old nu/ + spleen were studied, both anti-Ig or anti-Thy.1.2 treatment eliminated tranfer of resistance to newborn. Virus replication in tissues of nude mice was increased 5 days after infection when compared with nu/ + but became comparable by day 15 after infection. Hemagglutination-inhibition antibodies in serum of nude and nu/ + had comparable titers when measured early after infection but higher titers were observed in nu/ + later after infection.

Age Factors↗
PubMed1979

Prevalent types of tumors developing in neonatally thymectomized mice.

Tumor development was observed for 24 months in neonatally thymectomized (nTx) and normal (C3H/HeMs x 129/J)F1 mice. Thymectomy was performed at 3 days of age. Ovarian (29%, with significant difference from the control at P less than 0.001), pituitary (6%, P less than 0.08), and lymphoreticular tumors (16%, P less than 0.05) were observed in higher incidence in nTx females compared with normal controls, resulting in a significant increase in overall tumor incidence (99 tumors in 114 nTx females vs. 37 tumors in 71 normal females, P less than 0.01). No apparent difference in overall tumor incidence was observed between nTx and non-Tx males. Also, there was no higher risk for lung, liver, and mammary tumors in males and females after neonatal thymectomy. The finding that increased tumor incidence was limited to endocrine and lymphoreticular tissues does not support the concept of immune surveillance of carcinogenesis, but rather suggests the importance of tumor-prone conditioning of endocrine or immune systems as a result of neonatal thymectomy.

Animals↗
PubMed1978

Restraint-induced inhibition of 7,12-dimethylbenz[a]anthracene-induced mammary tumors: relation to stages of tumor development.

Experiments on the use of chronically applied restraint to reduce the number of mammary tumors developing in response to treatment of rats with 7,12-dimethylbenz[a]anthracene indicated that this inhibitory effect was largely due to restraint applied after the induction period; preinduction restraint and induction period restraint had no significant effect on tumor development. After termination of the restraint treatment, the rate at which new tumors appeared first increased and then decreased. Restraint did not affect the proportion of tumors regressing after ovariectomy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice.

The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 microgram MuMTV-S-derived vaccine significantly delayed the appearance of primary mammary tumors in GR and BALB/cfC3H mice (strains with high incidences of mammary cancer); in BALB/c and C3Hf mice, which have a moderate tumor incidence at an advanced age, this treatment resulted in a slight and substantial acceleration, respectively, of primary tumor development. The induced cellular immune reactivity for vaccination, as measured with the in vivo Winn test and the in vitro leukocyte adherence inhibition assay, was strongest in the GR strain as compared to the BALB/c strain. The titer of antibodies to tumor cells, as estimated by membrane immunofluorescence, was also higher in the GR strain. In BALB/cfC3H mice, the influence of different vaccination schemes with an MuMTV-O-derived protein vaccine on primary tumor development was studied. Before sc injection, the vaccine was precipitated on alum. A dose of 10 microgram vaccine resulted in a 61% decrease in tumor incidence. Two or five additional booster injections with 1 microgram protein vaccine had no beneficial effect, although the amount of antibody measured was increased after boosting.

Animals↗
PubMed1978

Immunization of mice against murine mammary tumor virus infection and mammary tumor development.

Formalin-inactivated whole murine mammary tumor virus (MuMTV), VuMTV membranes, the acid-soluble component of MuMTV, and purified MuMTV glycoprotein with a molecular weight of 55,000 (gp55; also designated as gp52) were used as vaccines in an attempt to identify the MuMTV antigen(s) that can protect mice from exogenous MuMTV infection and subsequent tumor development. Formalin-inactivated whole MuMTV, MuMTV membranes, and purified MuMTV gp55 were effective immunogens, whereas the acid-soluble component of MuMTV (which consists mainly of MuMTV gp55) failed to protect mice from challenge with live virus. These results suggest that (a) MuMTV gp55 is the major immunizing antigen and (b) its native conformation must be maintained for it to be an effective vaccine.

Acids↗
PubMed1977

Character of the tumors developing in young hamsters by the mixed cell transplantation of para-adeno-virus 12 and SV40 tumors-the similarity to the tumors induced by para-adenovirus 7.

Two mixtures of either allogeneic PARA-adenovirus 12 tumor cells or adenovirus (Adeno) 12 tumor cells and SV40 tumor cells in an equal number of 1 multiplied by 10(7) cells were transplanted subcutaneously at two sites of 10 young hamsters. The former two tumor cells were transplantable in nearly half of the transplants and the latter tumor cells in all of the transplants. By the mixture of PARA-Adeno 12 and SV40 tumor cells, 10 tumors were grown, 7 of which were mixed with Adeno and SV40 types and 3 were solely SV40 type. The other 10 tumors produced by the mixture of Adeno 12 and SV40 tumor cells revealed SV40 type only. Morphologically, Adeno type resembled the tumor induced by Adeno, and SV40 type by SV40. The results suggest that the existence of SV40 genetic information in Adeno type tumor cells is indispensable to the formation of mixed tumor in allogeneic tumor cell system. The similarity between the tumors developed by the mixed cell transplantation and those induced by PARA-adeno 7 was discussed both viro-immunologically and morphologically.

Adenoviridae↗
PubMed2025

Surgery/anesthesia may cause monocytes to promote tumor development.

BACKGROUND: The immune system of patients undergoing major surgery usually has obvious immune responses during the perioperative period, and the patient's immune status would affect the patient's prognosis. In this study single-cell sequencing technology was used to investigate the effect of surgery/anesthesia on peripheral blood mononuclear cells (PBMCs) in depth during the perioperative period. METHODS: We performed an in-depth analysis of our previously published data, which included a total of 4 patients were recruited in this study. Their peripheral blood samples were collected pre operation, 0, 24, and 48 h post operation, and then PBMCs were extracted, followed by single cell sequencing. The results of sequencing were analyzed with R packages seurat and scSTAR. Finally, RT-PCR technology was used to verify the expression of key genes in monocyte. RESULTS: The ratio of CD4+ and CD8+ T cells and Tregs showed little change, and the function of CD4+ and CD8+ T cells recovered soon. The function of Treg had not been restored 48 h post operation. Non-classical monocyte was impressed after surgery and showed no recovery trend within 48 h. Similar to scRNA-seq, the expression levels of MDM2 and SESN1 in patients with tumor increased significantly after surgery. CONCLUSIONS: Surgery/anesthesia had little effect on CD4+ and CD8+ T cells, and continued to affect the functional changes of Treg. It had more impact on monocytes, which may cause them to promote tumor development to a certain extent.

Humans↗
PubMed1979

Tumor development in organ transplants obtained from carcinogen-exposed rats.

F344 rats were exposed intragastrically to two different dose levels of N-nitrosoheptamethyleneimine (NHMI) resulting in a cumulative dose of either 225 or 450 mg/kg body weight. Tumor development was followed either in situ in the NHMI-exposed animals or in tracheas and esophagi from NHMI-exposed donors after these organs were grafted to isogeneic recipients. Tumor responses in situ and in organ grafts were compared. The results showed that the process of carcinogenesis is not disrupted by the transplantation procedure. The carcinogen dose-response relationship observed in situ was also seen in the transplanted organs. At the high carcinogen dose, the tumor incidence was 100% in situ and transplanted esophagi and 20% in tracheas in situ compared to 25% in tracheal transplants. At the low dose, the tumor incidence was 36% in the esophagi in situ compared to 100% in transplanted esophagi, which suggests a greater sensitivity of the transplant system to detect the carcinogenicity of NHMI. The proportion of carcinomas to papillomas was markedly higher in transplanted esophagi. The tracheal tumor response at both NHMI dose levels showed the same trend but was too low to allow any firm conclusions.

Animals↗
PubMed1979

Mice with spontaneous mammary tumors develop type-specific neutralizing and cytotoxic antibodies against the mouse mammary tumor virus envelope protein gp52.

Sera from C3H mammary tumor-bearing mice contain cytotoxic antibodies for mouse mammary tumor virus (MMTV)-producing cells, based on (51)Cr release in a complement-dependent serum cytotoxicity assay. The cytotoxic antibodies could be absorbed by purified C3H MMTV gp52 and C3H MMTV-infected cat cells (C3H [MMTV] CrFK) containing cell surface MMTV gp52. However, purified MMTV p27 and uninfected CrFK cat cells were negative. Absorption of the sera with GR (MMTV) CrFK cells also removed all of the cytotoxicity, whereas absorption with RIII (MMTV) CrFK cells was negative, even though all three infected cat cells contained equivalent amounts of gp52. The same C3H cytotoxic sera also neutralized the focus-forming capacity of a C3H MMTV pseudotype of Kirsten sarcoma virus containing MMTV gp52. In contrast, sera from mammary tumor-bearing GR and RIII mice did not neutralize the pseudotype. Furthermore, neutralization could be achieved only by anti-gp52 but not by anti-gp36, -p27, -p14, or -p10 C3H MMTV sera. The gp52's of C3H, GR, and RIII MMTV could also be distinguished by using a type-specific competition radioimmunoassay employing (125)I-gp52 of C3H MMTV and a hyperimmune rabbit anti-C3H MMTV serum. To demonstrate these differences directly, we studied the primary structure of gp52 on the surface of the C3H, GR, and RIII (MMTV) CrFK cells. Two-dimensional tryptic peptide maps of the cell surface lactoper-oxidase-catalyzed iodinated gp52's revealed a greater number of peptides common to the gp52's of C3H and GR MMTVs than to RIII MMTV gp52. These results demonstrate that gp52 is a major target antigen for both cytotoxic and neutralizing antibodies, that the cell surface and virion-associated gp52's of C3H, GR, and RIII MMTV contain both group- and type-specific determinants, and that C3H and GR MMTV gp52's are antigenically more related to each other than to RIII MMTV gp52. Furthermore, C3H mammary tumor-bearing mice develop type-specific antibodies capable of recognizing unique gp52 determinants and, therefore, are able to distinguish the gp52 of C3H MMTV from the gp52's of GR and RIII MMTV.

Animals↗
PubMed1979

Tumor development in lung of ddY mice following transplacental exposure to 1-ethyl-1-nitrosourea.

Transplacental induction of lung tumor by 1-ethyl-1-nitrosourea (ENU) was studied in pregnant ddY mice which were given a single intraperitoneal injection of 58.5 mg/kg of ENU in water between day 13 and 19 of gestation. Within 4 approximately 6 weeks after birth, pulmonary tumor nodules were found in all offsprings exposed to ENU, and they were histopathologically adenoma. Number of tumor nodules could be counted under the stereomicroscope from approximately day 40 after birth. The size of tumor increased with the lapse of time but the number of tumor nodules did not increase markedly. Weekly injections of urethan or ENU into mice pretreated with ENU in their fetal age enhanced the number of pulmonary adenoma. The development of other tumor was not seen except a few cases of lymphoma. Tumor development in the lung by injection of ENU in ddY mice during gestation is reproducible, relatively simple, and rapid. Therefore, it is considered that this may be a useful method for screening of antitumor agent.

Adenoma↗
PubMed1979

Ultrastructural study of somatotroph cells from mice bearing a fast growing transplanted hepatoma, in different periods of the tumor development.

The presence of a transplanted, fast-growing hepatoma (SS1-K) produces conspicuous ultrastructural changes in pituitary STH cells of C3H-S male mice. These changes are suggestive of an increased secretion of growth hormone only during the first stages of the tumor development. The hepatoma influence does not seem to be clearly related to the illumination regimen or time of killing.

Animals↗
PubMed1977

Pathology of tumors developed in guinea pigs given intraperitoneal injections of N-methyl-N-nitrosourea.

The carcinogenic effects of N-methyl-N-nitrosourea after repeated intraperitoneal administration in inbred strain NIH 13 guinea pigs were studied. 50% of the animals that survived beyond 22 weeks, after intraperitoneal injection of MNU at a dose of 10 mg/kg body weight/week for 18 weeks, developed a broad spectrum of tumors: these included adenocarcinoma of pancreas in 2 animals, fibrosarcoma of the mesentery in 2 animals, angiosarcoma of mesentery in 2 animals, mesothelioma of the peritoneum in 1 animal and tumors of small intestine in 3 animals. These studies indicate the susceptibility of different types of tissue to the local effects of MNU after intraperitoneal administration.

Adenocarcinoma↗