Drug repositioning explores the reuse of non-cancer drugs to treat tumors. In this work, we evaluated the effect of the combination of chloroquine and propranolol on colorectal and triple-negative breast cancers. Using as in vitro models the colorectal cancer cell lines HCT116, HT29, and CT26, and as triple-negative breast cancer models the 4T1, M-406, and MDA-MB-231 cell lines, we evaluated the effect of the drugs combination on the viability, apoptosis, clonogenicity, and cellular migratory capacity. To explore the in vivo effects of the combination on tumor growth and metastasis development we employed graft models in BALB/c, nude, and CBi mice. In vitro studies showed that combined treatment decreased cell viability in a dose-dependent manner and increased apoptosis. Also, we demonstrated that these drugs act synergically and that it affects clonogenicity and migration. In vivo studies indicated that this drug combination was effective on colorectal models but only partially on breast cancer. These results contributed to the search for new and safe treatments for colorectal and triple-negative carcinomas.
From the General Clinical Research Center, Department of Surgery and the Department of Clinical Pathology, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York Department of Clinical Pathology.
The search for suitable mixtures as boiling fluids leads to the development of ternary liquid mixtures that could handle even higher heat fluxes than binary mixtures through the formation of stable bubble-micelles departing from the heater’s surface. The amount of experimental work for testing the combinations is reduced using the interfacial tension prediction capabilities of simulation software, although it is not possible to predict singularities in the interfacial tension behavior of the mixtures. The ethanol aqueous mixture shows a singularity in its interfacial tension value at 16% ethanol by weight. In this work was combined with glycols for enhancing boiling heat transfer by decreasing the mixture interfacial tension. Also, the effect of the surfactants Dodecyl Benzene Sodium Sulfonate (DBSS) and Sodium Lauryl Sulfonate (SLS) in the mixture interfacial tension was studied. The measurements of sessile drop contact angles of mixtures with added surfactant allowed finding the singularities in the surface tension values that are related to critical micelle concentrations and the increment in boiling heat transfer. The propilenglycol-ethanol-water mixture produced the lowest values of contact angles, while for the etilenglycol-ethanol-water mixtures no such reduction was obtained with the same amount of the glycol. The use of DBSS and SLS at their critical micelle concentration decreased further the interfacial tension of the propilenglycol ternary mixture to generate a mixture that could improve the convective heat transfer coefficient.
Introduction: Colorectal cancer (CRC) is the most incident in Spain, according to Spanish Network of Cancer Registries (REDECAN) and is the second cause of death by cancer in Spain. Although the OS in metastatic setting has increased to 24-30 months, the 5-year OS continues to be less than 12%. The first and second line of treatment are well defined; however, there are few therapeutic options for those patients who have progressed to these standard therapies. After progression to the second line of treatment, the only therapeutic options with approved specific indication are Regorafenib and Trifluridine and Tipiracil. Trifluridine and Tipiracil has shown its efficacy in two randomized clinical trials comparing Trifluridine and Tipiracil versus placebo: a Phase II and a Phase III study (RECOURSE). In the previous Phase II study, the mOS was 9.0 months in the group treated with Trifluridine and Tipiracil, compared to 6.6 months in the placebo group. In the RECOURSE study, among patients treated with Trifluridine and Tipiracil mPFS was 2 months versus 1.7 months among those treated with placebo, and mOS was 10,5 with Trifluridine and Tipiracil vs 7,6 with placebo. We described the clinical characteristic of patients treated with Trifluridine and Tipiracil in seven hospitals from Madrid; identifying and analyzing clinical factors associated with long-term response. Methods: We collected retrospectively the clinical data of 98 patients who had received treatment with Trifluridine and Tipiracil until January 2018 in seven different hospitals in Madrid. Results: The mean age at first use of Trifluridine and Tipiracil was 66± 9.45 years, 57.5% were men and 42.3% were women, most of them in good performance status (ECOG 0-1: 71.2%), 27.8% had ECOG ≥2 when started Trifluridine and Tipiracil. All of the patients were diagnosed of metastatic colorectal cancer (73.2% had liver metastases, 58.2% lung metastases and 30.9% peritoneal metastases). Tumor localization was: 73.2% left colon, 24.8% right colon, and only 2% small intestine or 1% two synchronous colonic tumors. KRAS mutations were found in 62.9%, NRAS mutations in 17.4% and BRAF mutations were found in 5.4% patients. The median of prior lines of chemotherapy was three. The median progression free survival was 3 months (95% CI 2.65 – 3.36). The median overall survival was 5 months (95% CI 4.23-5.78). The median duration of treatment was 3 cycles. 23.7% patients had an adverse event that led to treatment withdrawal. The requirement of dose-reduction was associated with longer PFS (4 months vs 3 months, p = 0.002) and OS (14 months vs 5 months, p = 0.017). The existence of BRAF mutation was also associated with shorter PFS (1 month vs 3 months, p = 0.002) and OS (1 month vs 5 months, p = 0.000). There was no statistically significant difference of PFS and OS according to primary tumor location. Conclusion: Trifluridine and Tipiracil is effective in metastatic colorectal cancer (in patients with ≥2 lines of treatment). The OS (5 months) and PFS (3 months) reached in our study in real clinical practice are consistent with findings from previous studies. Mutational status of BRAF was statistically significant associated with shortened PFS and OS. Dose reduction during treatment is associated with Trifluridine and Tipiracil efficacy in terms of prolonged OS and PFS.
We evaluated the analytical reliability of the carcinoembryonic antigen (CEA) method of Hansen.Our experience is based on performing over 23,000 CEA assays in more than 10,000 clinical samples.The sensitivity of the assay is 0.5 nglml.The precision must be defined as a function of concentration.In the range 2.6 to 12 nglml the coefficient of variation is 4.96 to 7.39%.Long-range studies of the reproducibility of the standard curve, over a period of several years and including 435 standard curves, have shown an overall mean B/Bo of 31.45% which is close to the theoretical optimal of 33%.The long-term 90 and 50% intercepts are 0.55 ?0.15 and 7.11 2 1.0, respectively.Interlaboratory surveys show good agreement between the means of the survey group and the target values but rather large individual discrepancies.The CEA method studied here is sensitive and reproducible in intralaboratory studies but less so in interlaboratory comparisons.The reagents have performed uniformly and close to specifications over an extended period of time.
Journal Article Immunochemical Determination of LDH-1 Get access Frank Liu, Frank Liu Search for other works by this author on: Oxford Academic Google Scholar Robert Belding, Robert Belding Search for other works by this author on: Oxford Academic Google Scholar Magdalena Usategui-gomez, Magdalena Usategui-gomez Search for other works by this author on: Oxford Academic Google Scholar Gustavo Reynoso Gustavo Reynoso Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 75, Issue 5, 1 May 1981, Pages 701–707, https://doi.org/10.1093/ajcp/75.5.701 Published: 01 May 1981 Article history Received: 12 February 1979 Accepted: 04 December 1980 Published: 01 May 1981
Abstract Erythropoietin (ESF) levels were assayed in 19 female and male patients with intact kidneys with pituitary tumors or following open hypophysectomy or combined hypophysectomy and adrenalectomy for disseminated tumor states. Saline‐injected control mice had 0.38 ± 0.04% Fe 59 uptake (ESF). Hypophysectomized, adrenalectomized, castrated females had 2.96 ± 1.24% Fe 59 uptake (ESF) with an average peripheral hematocrit of 29.2 vol %. Hypophysectomized, castrated males had 1.59 ± 0.30% Fe 59 uptake (ESF) with an average peripheral hematocrit of 30.1 vol %. Thus, absence of the adrenals or functioning anterior pituitary gland does not prevent increased ESF activity. The presence of a pituitary tumor is also not consistently associated with increased ESF activity or release. The role of these endocrine organs in the regulation of ESF release in these states is therefore not essential but more likely represents a normal synergistic mechanism. Elevation of peripheral ESF levels is associated with improvement of anemia after hypophysectomy and may be an additional objective criterion and prognostic indicator of beneficial patient response to hypophysectomy in certain tumor states.
Carcinoembryonic antigen (CEA) is a cancer-specific antigen described by Gold in 1965. It is a glycoprotein present in malignant entodermal tissues, in fetal colonic mucosa, and in the plasma of patients with gastrointestinal tract cancers. We have measured plasma CEA levels in 346 patients using a new procedure which detects an ion-sensitive antigenic site in the carcinoembryonic molecule. Levels in 39 of 48 patients with gastrointestinal tract cancer and 90 of 281 with nonentodermally derived malignancies were abnormal. Following successful therapy CEA level returns to normal (colon, four of four; neuroblastoma, three of three). The identity between the antigen measured in the present study and the carcinoembryonic antigen of Gold has not been established. The assay appears to be useful in the follow-up of patients with cancer and may eventually be of diagnostic value in the asymptomatic patient.