METHODS: A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56).
RESULTS: Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death.
CONCLUSIONS: The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.
METHODS: This paper presents two hybrid methodologies that combines optimal control theory with multi-objective swarm and evolutionary algorithms and compares the performance of these methodologies with multi-objective swarm intelligence algorithms such as MOEAD, MODE, MOPSO and M-MOPSO. The hybrid and conventional methodologies are compared by addressing CMOOP.
RESULTS: The minimized tumor and drug concentration results obtained by the hybrid methodologies demonstrate that they are not only superior to pure swarm intelligence or evolutionary algorithm methodologies but also consumes far less computational time. Further, Second Order Sufficient Condition (SSC) is also used to verify and validate the optimality condition of the constrained multi-objective problem.
CONCLUSION: The proposed methodologies reduce chemo-medicine administration while maintaining effective tumor killing. This will be helpful for oncologist to discover and find the optimum dose schedule of the chemotherapy that reduces the tumor cells while maintaining the patients' health at a safe level.
METHODS: We recruited 10 patients with advanced breast cancer with ECOG (Eastern Cooperative Oncology Group) performance status score of zero to two, who needed chemotherapy in the first or second-line setting to receive two-weekly docetaxel for 8 cycles. The primary endpoint was safety and secondary endpoints were response rate and progression free survival.
RESULTS: The most reported adverse events were haematological (anaemia 100% and neutropenia 90%). The febrile neutropenia rate was 10%. The overall response rate was 20%. The median progression free survival was 5.0 months.
CONCLUSION: Two-weekly docetaxel may be a reasonable alternative treatment regimen for patients with advanced breast cancer in the first or second-line setting. This regimen is yet to be compared with standard 3-weekly schedule in a phase 3 randomised clinical trial.
OBJECTIVES: To systematically review the existing cost-effectiveness evaluations of breast-cancer medication in developing-countries.
METHODOLOGY: A systematic literature search was performed in PubMed, EMBASE, SCOPUS, and EconLit. Two researchers determined the final articles, extracted data, and evaluated their quality using the Quality of Health-Economic Studies (QHES) tool. The interclass-correlation-coefficient (ICC) was calculated to assess interrater-reliability. Data were summarized descriptively.
RESULTS: Fourteen pharmacoeconomic studies published from 2009 to 2019 were included. Thirteen used patient-life-years as their effectiveness unit, of which 10 used quality-adjusted life-years. Most of the evaluations focused on trastuzumab as a single agent or on regimens containing trastuzumab (n = 10). The conclusion of cost-effectiveness analysis varied among the studies. All the studies were of high quality (QHES score >75). Interrater reliability between the two reviewers was high (ICC = 0.76).
CONCLUSION: In many studies included in the review, the use of breast-cancer drugs in developing countries was not cost-effective. Yet, more pharmacoeconomic evaluations for the use of recently approved agents in different disease stages are needed in developing countries.
AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.
MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.
RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.
CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.
METHODS: fDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29.
RESULTS: fDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and -1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC50) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such.
CONCLUSION: In short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.