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

Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the antitumor effects of Rituximab (RTX), Cyclophosphamide (CTX), Dexamethasone (DEX) [RCD]-Regimen in vivo WSU-WM SCID xenograft and in a patient with WM. For the pre-clinical efficacy study, WSU-WM-bearing SCID mice were randomly assigned to receive RTX (150 mg/kg/inj, i.v., QDX5), CTX (90 mg/kg/inj, s.c. QDX5) as single agents or diluent. The combination group received RTX at 150 mg/kg/inj, QDX5; CTX at 150 mg/kg/inj, QODX3 and DEX at 1.0 mg/kg/inj, i.v., QDX5. Tumor growth inhibition (T/C), tumor growth delay (T - C), and log10 kill (net) for RTX and CTX were 24.5%, 37 days, 5.52 and 88%, 0.0 days, 0.0log10 kill, respectively. No cures were observed with either agent; however, all mice (6/6, with bilateral tumors) were cured when treated with RCD-regimen. A 57-year-old patient with relapsed WM was treated with the RCD-regimen and showed an excellent partial remission for seven months. The patient tolerated the treatment very well, the hemoglobin improved dramatically, platelets remained stable, the IgM level normalized and there was only minimal involvement of bone marrow. Based on these results, the RCD regimen is effective against WM and its activity should be further evaluated in clinical trials.
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PMID:Rituximab, Cyclophosphamide, Dexamethasone (RCD) regimen induces cure in WSU-WM xenograft model and a partial remission in previously treated Waldenstrom's macroglobulinemia patient. 1244 11

There is growing evidence that vasculogenesis (progenitor cell-derived generation of new blood vessels) is required for the growth of some neoplastic diseases. Here we show that the administration of cyclophosphamide (CTX) at the maximum tolerable dose with 21-day breaks or at more frequent low-dose (metronomic) schedules have opposite effects on the mobilization and viability of circulating endothelial progenitors (CEPs) in immunodeficient mice bearing human lymphoma cells. Animals treated with the maximum tolerable dose CTX experienced a robust CEP mobilization a few days after the end of a cycle of drug administration, and tumors rapidly became drug resistant. Conversely, the administration of metronomic CTX was associated with a consistent decrease in CEP numbers and viability and with more durable inhibition of tumor growth. Our findings suggest that metronomic low-dose chemotherapy regimens are particularly promising for avoiding CEP mobilization and, hence, to potentially reduce vasculogenesis-dependent mechanisms of tumor growth.
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PMID:Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. 1290 2

Continuous low-dose (metronomic) therapy, based on cyclophosphamide (CTX) combined with thalidomide (Tha), was evaluated on Dunning prostate R3327-AT1 rat tumors. Significantly delayed tumor growth (P < .001) was observed with oral CTX alone at a low dose (metronomic cyclophosphamide or M-CTX; 30 mg/kg per day) or combined with Tha. To investigate dynamic changes in tumor physiology during early stages of treatment, magnetic resonance imaging (MRI) was applied before and during the M-CTX or M-CTX + Tha therapy. Dynamic contrast-enhanced MRI revealed significant changes in the tumor center by day 3 (P < .01); by day 7, only a thin peripheral tumor region showed high signal enhancement. There was a significant correlation between poorly enhancing fraction on day 7 and ultimate tumor growth delay (P < .02). The apparent transverse relaxation rate (R2*) showed similar baseline tumor heterogeneity, but no obvious changes with growth or therapy. Histology confirmed substantial necrosis in the tumor center, leaving a thin live peripheral rim. Immunohistochemistry showed a significant increase in vascular endothelial growth factor, and apoptotic tumor and vascular endothelial cells. These results show the efficacy of the metronomic CTX +/- Tha for delaying tumor growth and indicate that MRI provides insights into the mode of action and early indication of efficacy.
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PMID:Continuous low-dose (metronomic) chemotherapy on rat prostate tumors evaluated using MRI in vivo and comparison with histology. 1602 47

This report describes the preparation, characterization and potential biological activities of a chemically sulfated polysaccharide (S-GAP-P), which was derived from water-insoluble polysaccharide of Grifola frondosa mycelia. S-GAP-P was determined to be a glucan sulfate with the average molecular weight of 28 kDa and the sulfur content of 16.4%. The antitumor and immunomodulating activities of the sulfated derivative were estimated in vitro and in vivo. S-GAP-P inhibited the proliferation of SGC-7901 cells and induced apoptosis, in a dose-dependent manner. And the results from in vivo experiments demonstrated that S-GAP-P significantly inhibited the tumor growth and enhanced the peritoneal macrophages phagocytosis in S180-bearing mice. It is noteworthy that S-GAP-P could accelerate the antitumor activity of CTX and improve the immunocompetence damaged by CTX, suggesting the combination might increase cytotoxic efficacy and decrease toxicity of some chemotherapeutic agents in cancer treatment.
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PMID:Preparation of a chemically sulfated polysaccharide derived from Grifola frondosa and its potential biological activities. 1682 41

We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in vivo. Kunming mice implanted with S(180) sarcoma cells were given 75 mGy whole body gamma-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by Western-blot. We discovered that tumor growth was significantly reduced in the group exposed to CTX add to LDR. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G(1) phase in the groups treated with CTX and CTX + LDR, but cell cycle was more significantly arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR or CTX chemotherapy. Concentration of bone marrow cells and proliferation index in CTX + LDR mice were higher than those in the untreated mice. LDR or CTX + LDR could induce greater cytochrome c levels and caspase-3 activity in tumors. These results suggest that low dose radiation can enhance the anti-tumor effect of the chemotherapy agent CTX markedly. Furthermore, LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance on adjuvant chemotherapy.
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PMID:Low dose radiation increased the therapeutic efficacy of cyclophosphamide on S(180) sarcoma bearing mice. 1754 41

The use of immunotherapy or chemotherapy alone is generally ineffective against well-established tumors. To overcome this intrinsic resistance against therapy for tumors, we have attempted to combine immunotherapy with chemotherapy. In this study, we tried to induce a rapid antitumor effect via chemoimmunotherapy using a vaccinia viral vaccine as an immunotherapeutic agent with anticancer agents including epigallocatechin-3-gallate (EGCG) and conventional anticancer drugs. Although a combination of vaccinia-mediated vaccination and chemotherapy led to a strong inhibition of tumor growth, monotherapy alone failed to completely cure tumors. In contrast, intravenous injection of cisplatin (CDDP) or cyclophosphamide (CTX) after vaccinia virus vaccination led to complete regression of the established tumors. Interestingly, anticancer drugs appear to augment the antitumor effect of the vaccinia virus-mediated immunotherapy. This effect is mainly associated with the enhanced tumor-specific CD8(+) T cell immune response induced by vaccinia virus, which was demonstrated by antibody depletion. However, anticancer drugs alone failed to induce a significant enhancement of the tumor-specific CD8(+) T cell immune response. Taken together, these results suggest that combining vaccinia virus-based immunotherapy with anticancer drugs is particularly effective against established tumors by increasing the tumor antigen-specific CD8(+) T cell immune response, which is primed by vaccinia virus-mediated vaccination.
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PMID:Chemotherapy enhances CD8(+) T cell-mediated antitumor immunity induced by vaccination with vaccinia virus. 1755 2

Cancer treatments consisting of a combination of chemotherapy and immunotherapy have been vigorously exploited to further improve the efficacy of cancer therapies. In this study, we utilized a chitosan hydrogel (CH) system loaded with GMCSF and a cancer drug as a chemo-immunotherapeutic agent in an effort to assess the effects on tumor growth in mice using TC-1 cervical tumor cells, which express the tumor-specific antigen, HPV-16 E7. The growth of TC-1 tumors was significantly reduced in mice treated with a CH harboring a cancer drug (doxorubicin (DOX), cisplatin (CDDP), or cyclophosphamide (CTX)) and GMCSF (CH-a cancer drug + GMCSF), as compared to other groups that were treated with CH containing only a cancer drug(CH-a cancer drug) or GMCSF(CH-GMCSF). Among the cancer drugs, CTX exerted the most potent anti-tumor effects. Interestingly, the intra-tumoral injection of CH-a cancer drug + GMCSF induced a significant E7-specific CD8(+) T cell immune response as compared to CH-GMCSF or CH-a cancer drug. This enhancement of tumor antigen-specific CD8(+) T cell immunity was associated principally with the anti-tumor effects induced by CH-CTX + GMCSF, as demonstrated by antibody depletion. Collectively, the aforementioned results indicate that co-treatment of tumors with a combination of GMCSF and a cancer drug incorporated into a CH system results in synergistic anti-tumor effects, which occur via the induction of a tumor antigen-specific CD8(+) T cell-mediated anti-tumor immunity. This study demonstrates the use of a biodegradable hydrogel system for the co-delivery of an immunoadjuvant and an anti-cancer drug for successful chemo-immunotherapy.
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PMID:Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8+ T cell-mediated anti-tumor immunity. 1908 18

The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX) on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally) 24 hours before human ovarian carcinoma (SKOV3), small cell lung carcinoma (LX-1 SCLC), and glioma (UW28, U87MG, and U251) tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0%) of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive) infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.
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PMID:Cyclophosphamide enhances human tumor growth in nude rat xenografted tumor models. 1917 3

Granulocyte colony-stimulating factor (GCSF) is frequently used as an adjunctive agent in tumor chemotherapy. Bifidobacterium longums (B. longum) attracted researchers' interests due to its enhancement of immunity and selective location in solid tumors. B. longum-pBV22210-endostatin (Endo) was proved to have a definite inhibitive effect on tumor growth in our previous study. In the present study, we evaluated the effects of B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with cyclophosphamide (CTX) on H22 and S180 tumor-bearing mice. Based on our previous work, the plasmid pBV22210-GCSF was constructed and transformed by electroporation into B. longum. The B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with CTX were applied to treat H22 and S180 tumor-bearing mice. A leukocyte count was carried out and the tumor inhibition rate was calculated after treatment. In our study, CTX combined with B. longum-pBV22210-GCSF significantly raised the leukocyte level of tumor-bearing mice, while combined with B. longum-pBV22210-GCSF alone or B. longum-pBV22210-Endo alone combinations with CTX inhibited tumor growth by over 65%. The results showed that B. longum-pBV22210-GCSF had an effective antagonistic effect on bone marrow inhibited by CTX and could inhibit tumor growth when it was combined with B. longum-pBV22210-Endo and CTX. Our results provide an enhanced understanding of B. longum and GCSF as well as their potential as an adjunctive approach in cancer gene therapy.
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PMID:Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors. 1967 23

Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable beta-subunit human choriogonadotropin (beta-hCG), which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID) mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX), UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment.
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PMID:Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma. 2023 20


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