Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaemia is frequent in cancer and may increase tumour hypoxia that stimulates angiogenesis. However, erythropoietin is a hypoxia-inducible stimulator of erythropoiesis which seems to improve quality of life in cancer patients. Two recent phase III randomized studies showed negative results using erythropoietin in head and neck cancer patients and in metastatic breast cancer patients with impaired specific survival. In vitro and in vivo experiments have provided erythropoietin-receptor expression in endothelial cancer cells including malignant tumours of the breast, prostate, cervix, lung, head and neck, ovary, melanoma, stomach, gut, kidney etc. Biologic effect of erythropoietin and its receptor linkage induces proliferation of human breast cancer and angiogenesis and may limit anti-tumour effect of cancer treatment, in part, by tumour vascularization improvement. In addition, the use of exogenous erythropoietin could be able to favour tumour progression by improving tumour oxygenation and nutriment supply. If erythropoietin receptor were functional in human cancer, the assessment of erythropoietin receptor expression on tumour cell may help to select patients benefiting from exogenous erythropoietin. However, the relationship between erythropoietin receptor expression, tumour growth and exogenous erythropoietin, requires more studies. The results of recent clinical trials suggest that using erythropoietin should be avoided in non-anemic patients and discussed in patients receiving curative therapy.
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PMID:[Anaemia and radiation therapy]. 1567 42

Doxorubicin (DOX) has excellent antitumor activity when combined with paclitaxel (PTX) and this combination is used as first-line treatment for metastatic breast cancer. Results from clinical studies on pharmacokinetic interaction of these agents are not conclusive and pre-clinical studies are still needed. Pharmacokinetic studies were carried out in female Balb/c mice with combined DOX (6 mg/kg) and PTX (10 mg/kg) treatment. Combined treatment with PTX and DOX leads to alterations in the pharmacokinetics of both agents, with the predominant effect being elevated drug levels in liver and gut tissues. DOX levels in kidney and heart tissues were unaffected by concurrent PTX treatment. Further, plasma levels of DOX are not changed by concurrent PTX treatment suggesting that monitoring of plasma levels of DOX, when used in combination with another drug that is a P-glycoprotein (PGP) substrate, will not reflect actual pharmacokinetic changes occurring in other tissues.
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PMID:Pharmacokinetics of combined doxorubicin and paclitaxel in mice. 1576 91

African American (AA) women have a lower overall incidence of breast cancer than do Caucasian (CAU) women, but a higher overall mortality. Little is known as to why the incidence of breast cancer is lower yet mortality is higher in AA women. Many studies speculate that this is only a socio-economical problem. This investigation suggests the possibility that molecular mechanisms contribute to the increased mortality of AA women with breast cancer. This study investigates the expression of 14 genes which have been shown to play a role in cancer metastasis. Cell lines derived from AA and CAU patients were analyzed to demonstrate alterations in the transcription of genes known to be involved in cancer and the metastatic process. Total RNA was isolated from cell lines and analyzed by RT-PCR analysis. Differential expression of the 14 targeted genes between a spectrum model (6 breast cancer cell lines and 2 non-cancer breast cell lines) and a metastasis model (12 metastatic breast cancer cell lines) were demonstrated. Additionally, an in vitro comparison of the expression established differences in 5 of the 14 biomarker genes between African American and Caucasian breast cell lines. Results from this study indicates that altered expression of the genes Atp1b1, CARD 10, KLF4, Spint2, and Acly may play a role in the aggressive phenotype seen in breast cancer in African American women.
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PMID:Metastatic progression and gene expression between breast cancer cell lines from African American and Caucasian women. 1747 51

We report a case of a female with stage I infiltrating ductal carcinoma who received adjuvant therapy including trastuzumab. One year later she developed lytic lesions and was retreated with trastuzumab that was held after she developed symptomatic heart failure. Lytic lesions were attributed to relapse of breast cancer, and cardiac failure attributed to prior trastuzumab therapy. After complications necessitated multiple hospitalizations, a further workup revealed that the lytic lesions were not metastatic breast cancer but multiple myeloma. Her advanced multiple myeloma was associated with systemic amyloidosis involving gut and heart, which ultimately led to her demise. This report addresses the pitfalls of overlapping symptoms and the question of which patients with suspected metastatic disease should undergo a biopsy.
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PMID:Metastatic breast cancer or multiple myeloma? Camouflage by lytic lesions. 2022 44

Chemical studies of gut bacteria of the carpenter ant Camponotus kiusiuensis led to the discovery of two new alkaloids, camporidines A and B (1 and 2), from Streptomyces sp. STA1. The structures of 1 and 2 were established as new polyketide alkaloids bearing a piperidine-cyclopentene-epoxide 6/5/3 tricyclic system based on NMR spectroscopic and mass spectrometric analysis. The relative configurations of the camporidines were determined by their 1H-1H NOESY/ROESY and 1D NOE NMR correlations. The experimental ECD spectra of 1 and 2 were compared with their calculated ECD spectra to assign their absolute configurations. Camporidine A (1) displayed antimetastatic activity by suppression of cell invasion against the metastatic breast cancer cell line MDA-MB-231 and showed an anti-inflammatory effect by suppressing nitric oxide production induced by lipopolysaccharide. In addition, the putative biosynthetic gene cluster of the camporidines was identified, and the biosynthetic pathway of the camporidines was proposed based on bioinformatic analysis of the full genome of Streptomyces sp. STA1. Camporidines A and B (1 and 2) could be biosynthesized by a modular type I PKS containing an acyl transferase domain that accepts an unusual extender unit, which becomes the (C1'-C6') hexyl side chain. The post-PKS modification enzymes were predicted to perform an amination and an oxidation along with spontaneous Schiff base formation and generate the unique piperidine-cyclopentene-epoxide 6/5/3 tricyclic framework.
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PMID:Camporidines A and B: Antimetastatic and Anti-inflammatory Polyketide Alkaloids from a Gut Bacterium of Camponotus kiusiuensis. 3091 43

It is unknown why some patients with hormone receptor-positive (HR+) breast cancer present with more aggressive and invasive disease. Metastatic dissemination occurs early in disease and is facilitated by cross-talk between the tumor and tissue environment, suggesting that undefined host-intrinsic factors enhance early dissemination and the probability of developing metastatic disease. Here, we have identified commensal dysbiosis as a host-intrinsic factor associated with metastatic dissemination. Using a mouse model of HR+ mammary cancer, we demonstrate that a preestablished disruption of commensal homeostasis results in enhanced circulating tumor cells and subsequent dissemination to the tumor-draining lymph nodes and lungs. Commensal dysbiosis promoted early inflammation within the mammary gland that was sustained during HR+ mammary tumor progression. Furthermore, dysbiosis enhanced fibrosis and collagen deposition both systemically and locally within the tumor microenvironment and induced significant myeloid infiltration into the mammary gland and breast tumor. These effects were recapitulated both by directly targeting gut microbes using nonabsorbable antibiotics and by fecal microbiota transplantation of dysbiotic cecal contents, demonstrating the direct impact of gut dysbiosis on mammary tumor dissemination. This study identifies dysbiosis as a preexisting, host-intrinsic regulator of tissue inflammation, myeloid recruitment, fibrosis, and dissemination of tumor cells in HR+ breast cancer. SIGNIFICANCE: Identification of commensal dysbiosis as a host-intrinsic factor mediating evolution of metastatic breast cancer allows for development of interventions or diagnostic tools for patients at highest risk for developing metastatic disease.See related commentary by Ingman, p. 3539.
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PMID:Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer. 3130 36

Purpose: Low-dose metronomic chemotherapy can achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose. Characterizing the gut microbiota of cancer patients under different dosage regimens may describe a new role of gut microbiota associated with drug efficacy. Therefore, we evaluated the composition and the function of gut microbiome associated with metronomic capecitabine compared to conventional dosage. Methods: The fecal samples of HER2-negative metastatic breast cancer patients treated with capecitabine as maintenance chemotherapy were collected and analyzed by 16S ribosome RNA gene sequencing. Results: A total of 15 patients treated with metronomic capecitabine were compared to 16 patients under a conventional dose. The unweighted-unifrac index of the metronomic group was statistically significantly lower than that of the routine group (P = 0.025). Besides that, the Bray-Curtis distance-based redundancy analysis illustrated that the microbial genera between the two groups can be separated partly. Nine Kyoto Encyclopedia of Genes and Genomes (KEGG) modules were enriched in the metronomic group, while no KEGG modules were significantly enriched in the routine group. Moreover, univariate and multivariate analyses suggested that the median progression-free survival (PFS) was significantly shorter in patients with the gut microbial composition of Slackia (9.2 vs. 32.7 months, P = 0.004), while the patients with Blautia obeum had a significantly prolonged PFS than those without (32.7 vs. 12.9 months, P = 0.013). Conclusions: The proof-of-principle study suggested that the gut microbiota of patients receiving metronomic chemotherapy was different in terms of diversity, composition, and function from those under conventional chemotherapy, and the presence of specific bacterial species may act as microbial markers associated with drug resistance monitoring and prognostic evaluation.
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PMID:Gut Microbiota Profiling in Patients With HER2-Negative Metastatic Breast Cancer Receiving Metronomic Chemotherapy of Capecitabine Compared to Those Under Conventional Dosage. 3273 88