Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemotherapeutic activity of thymidine (dThd) was tested against four human tumor xenografts growing in nude mice, including a melanoma, an oat cell carcinoma of the lung, a colon carcinoma, and a breast carcinoma. Tumor-bearing mice were given an infusion of dThd (1 g/kg/day) s.c. for 72 hr each week for three weeks. Tumor growth in the treated mice was compared to that in randomized concurrent control mice infused with media alone. A significant effect was found only for the melanoma, and it was cytostatic rather than cytotoxic. Even when melanomas of very small initial volume were treated, there were no complete regressions, and tumor growth resumed when dThd treatment was stopped. In culture, sustained dThd concentrations of greater than 3.2 mM were required to cause death of the melanoma cells; in the mice the dThd level during infusion ranged from 1 to 5 mM. This exposure to dThd, although failing to produce a tumor response, did produce significant toxicity in the nude mice in the form of myelosuppression and leukopenia. Flow cytometric analysis of marrow cells during the dThd infusion showed an accumulation of cells in S phase, but proliferation was not completely halted since cells with G2-M content of DNA were present in the marrow even after 72 hr of dThd exposure. This study failed to demonstrate a therapeutically useful effect of dThd on these tumors.
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PMID:Activity of thymidine as a chemotherapeutic agent against human tumor xenografts in nude mice. 47 23

A human squamous cell carcinoma (SCC) of oral origin was transplanted into athymic mice that were then divided into six groups. The mice were killed at 1 to 6 weeks after tumor transplantation; the sixth group was killed 1 week after excision of SCC grafts. Plasma samples were obtained from each mouse at the time of death for the determination of SCC-associated antigen (SCCAA), a cytoskeletal protein fraction of about 48,000 daltons originally derived from SCC of the uterine cervix. The plasma SCCAA level rose gradually and proportionately to the growth of SCC xenografts from a baseline of 0.66 ng/ml [standard error (SE) + 0.12] to the preoperative peak of 8.44 ng/ml (SE + 1.86) at 5 weeks, to fall precipitously to the postoperative level of 1.05 ng/ml (SE + 0.27) at 6 weeks. No rise in plasma SCCAA level was observed in mice bearing a human malignant melanoma, and only modest rises were observed in mice bearing human adenocarcinomas and oat cell carcinoma. In this experimental model rising plasma SCCAA levels were found to be dependable indicators of SCC tumor growth. These observations and preliminary data on SCCAA levels in patients with or without SCC of the head and neck lend support to the clinical usefulness of serial plasma SCCAA determinations in monitoring patients with SCC of the oral cavity.
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PMID:Plasma levels of a squamous cell carcinoma-associated antigen in athymic nude mice bearing human squamous cell carcinoma xenografts of oral origin. With preliminary clinical data. 317 44

This study was undertaken to analyse the relationship between radiosensitivity and cell kinetics of human solid cancer in experimental nude mouse system. Four strains of tumors used for the experiment were poorly differentiated squamous cell carcinoma of the lung (Lu-9), oat cell carcinoma of the lung (Lu-24), well differentiated squamous cell carcinoma of the tongue (To-1) and moderately differentiated squamous cell carcinoma of the esophagus (Es-4) which were serially transplantable to BALB/c nude mice. Radiosensitivity was evaluated by tumor growth in terms of inhibition rate, histological change and host reaction after irradiation. Cell kinetics were studied by autoradiography with pulse administration of 3H-thymidine to mice. Although Lu-24 was most radiosensitive, followed by To-1, Es-4 and Lu-9 in the order of sensitivity, it was suggested that they might be more radioresistant in nude mice without T-cell function than in human. Regarding squamous cell carcinomas, well differentiated type was more radiosensitive than poorly differentiated one. All of these tumors in nude mouse revealed distinct percent labeled mitosis curves with two clear peaks which were quite different from those in human body. Lu-24 showed a characteristic pattern with a long time lag before visible growth, short G1, and low growth fraction, compared to other three tumors. Three strains of squamous cell carcinoma demonstrated similar cell kinetic factors which were almost the same as those in human body reported previously. The differences in volume doubling time of tumor, growth fraction and cell loss factor were partially related to those of radiosensitivities among tumors except for Lu-24. The theoretical volume doubling time was proved to be most reliable for estimation of effectiveness of irradiation, but the labeling index was not a valuable indicator for it.
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PMID:[Radiosensitivity and cell kinetics of the human solid cancer transplanted to nude mouse]. 632 44

Small cell carcinoma (SCC) of the pancreas is a rare disease, with an extremely poor prognosis; only 24 cases have been reported in the literature. However, as some patients have been successfully treated with combination chemotherapy, it is important to obtain both a definite diagnosis and a precise evaluation of the effect of the treatment. A 69-year-old woman presented with an abdominal tumor and pain. She had been observed for sensory neuropathy and swelling of the pancreatic head by the referring doctor over the previous 9 months. The patient was diagnosed with SCC of the pancreas after surgery and had two courses of combination chemotherapy (cisplatin and etoposide). Initially, the tumor disappeared completely on computed tomography (CT) scans, but she died of disease recurrence 3 months after completing the chemotherapy. Changes in serum neuron-specific enolase (NSE) levels were monitored constantly during the progress of the disease. NSE levels had already increased above the upper limit of normal 8 months before the patient's admission to our hospital, and levels changed concurrently not only with tumor growth but also subsequently with remission and then relapse of the disease after treatment. These results indicate that NSE is a good marker, both as a diagnostic indicator for SCC of the pancreas and as a means of evaluating response to treatment.
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PMID:Changes to levels of serum neuron-specific enolase in a patient with small cell carcinoma of the pancreas. 1575 8

Small cell carcinoma of the gallbladder is very rare, but shows high malignant potential with frequent metastasis. Chemotherapeutic regimens for the treatment of gallbladder small cell carcinoma have not yet been established. In this study, we examined in vivo chemosensitivity tests for the GB-04-JCK human gallbladder small cell carcinoma, which were previously established as a serial-transplantable xenograft in nude mice. We used four anticancer drugs: docetaxel, irinotecan, nedaplatine and gemcitabine. Docetaxel maximally suppressed xenograft tumor growth in mice (P<0.01), and showed complete tumor regression after chemotherapy day 35. Irinotecan and nedaplatine suppressed tumor growth without complete regression (P<0.01). Gemcitabine did not affect tumor growth significantly. This in vivo experimental study proposed chemotherapeutic regimens for human gallbladder small cell carcinoma.
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PMID:In vivo chemotherapeutic profile of human gallbladder small cell carcinoma. 1899 40

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal malignancy that mainly impacts young women. SCCOHT is characterized by a diploid genome with loss of SMARCA4 and lack of SMARCA2 expression, two mutually exclusive ATPases of the SWI/SNF chromatin-remodeling complex. We and others have identified the histone methyltransferase EZH2 as a promising therapeutic target for SCCOHT, suggesting that SCCOHT cells depend on the alternation of epigenetic pathways for survival. In this study, we found that SCCOHT cells were more sensitive to pan-HDAC inhibitors compared with other ovarian cancer lines or immortalized cell lines tested. Pan-HDAC inhibitors, such as quisinostat, reversed the expression of a group of proteins that were deregulated in SCCOHT cells due to SMARCA4 loss, leading to growth arrest, apoptosis, and differentiation in vitro and suppressed tumor growth of xenografted tumors of SCCOHT cells. Moreover, combined treatment of HDAC inhibitors and EZH2 inhibitors at sublethal doses synergistically induced histone H3K27 acetylation and target gene expression, leading to rapid induction of apoptosis and growth suppression of SCCOHT cells and xenografted tumors. Therefore, our preclinical study highlighted the therapeutic potential of combined treatment of HDAC inhibitors with EZH2 catalytic inhibitors to treat SCCOHT.
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PMID:Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type. 3023 45