Preparation, evaluation and pharmacokinetic studies of spray dried PLGA polymeric submicron particles of simvastatin for the effective treatment of breast cancer

2018 ◽  
Vol 249 ◽  
pp. 609-616 ◽  
Author(s):  
Naqueeb Anzar ◽  
Mohd. Aamir Mirza ◽  
Khalid Anwer ◽  
Tahir Khuroo ◽  
Abdullah S. Alshetaili ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3557
Author(s):  
Charu Kothari ◽  
Alisson Clemenceau ◽  
Geneviève Ouellette ◽  
Kaoutar Ennour-Idrissi ◽  
Annick Michaud ◽  
...  

Triple-negative breast cancer (TNBC) is a major concern among the different subtypes of breast cancer (BC) due to the lack of effective treatment. In a previous study by our group aimed at understanding the difference between TNBC and non-TNBC tumors, we identified the gene TBC1 domain family member 9 (TBC1D9), the expression of which was lower in TNBC as compared to non-TNBC tumors. In the present study, analysis of TBC1D9 expression in TNBC (n = 58) and non-TNBC (n = 25) patient tumor samples validated that TBC1D9 expression can differentiate TNBC (low) from non-TNBC (high) samples and that expression of TBC1D9 was inversely correlated with grade and proliferative index. Moreover, we found that downregulation of the TBC1D9 gene decreases the proliferation marginally in non-TNBC and was associated with increased migratory and tumorigenic potential in both TNBC and luminal BC cell lines. This increase was mediated by the upregulation of ARL8A, ARL8B, PLK1, HIF1α, STAT3, and SPP1 expression in TBC1D9 knockdown cells. Our results suggest that TBC1D9 expression might limit tumor aggressiveness and that it has a differential expression in TNBC vs. non-TNBC tumors.


2021 ◽  
pp. 1-13
Author(s):  
Khushboo Katharotiya ◽  
Gajanan Shinde ◽  
Dhaval Katharotiya ◽  
Santosh Shelke ◽  
Rakesh Patel ◽  
...  

2019 ◽  
Vol 2 (2) ◽  
pp. 14-18
Author(s):  
Md. Niuz Morshed Khan ◽  
Maidul Islam

AbstractAmong all cancers, breast cancer is the most commonly occurring cancer in women and the second most common cancer overall, both in the developed and less developed country. It is a matter of concern worldwide, that there is no effective drug is available for cancer treatment. Although, Surgery, radiation, hormonal (anti-estrogen) therapy, and chemotherapy are being used for treatment of breast cancer in recent years, due to life threatening side effects, these treatment approaches becoming more vulnerable. However, researchers from across the world searching a safe and effective treatment approach that can be a breakthrough for this situation, as it is evident that natural compounds like shikonin from Lithospermum erythrorhizon can fight against aggressiveness of breast cancer by regulating apoptosis, necroptosis and estrogen receptor signaling pathway. In this review, we discussed about potential green chemical compounds with their mechanisms of actions, which can be very effective treatment regimen for breast cancer and can be more potent by their proper modifications and further molecular research. Hopefully in future, research focusing on the “shikonin” will open a new door for increasing the survival rate of breast cancer patients as well as cancer cure.


2018 ◽  
Vol 29 (12) ◽  
pp. 2920-2927 ◽  
Author(s):  
Ramona Strob ◽  
Adrian Dobrowolski ◽  
Damian Pieloth ◽  
Gerhard Schaldach ◽  
Helmut Wiggers ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13027-e13027
Author(s):  
Parva Purohit ◽  
Pathik Brahmkshatriya ◽  
Vishalgiri Goswami

e13027 Background: Fulvestrant, a potent, selective estrogen receptor degrader, is a primary drug of choice for treating advanced metastatic hormone receptor-positive breast cancer in postmenopausal women following anti-estrogen therapy. However, the existing therapy limits to inconvenient intramuscular injections due to low solubility, weak permeation, high metabolism, and poor pharmacokinetics profile. Additionally, it takes 30 days to reach maximal steady-state plasma concentration, limiting clinical efficacy. To overcome these issues, we modulated physicochemical properties of fulvestrant, enabling its oral delivery to improve bioavailability. Methods: Structurally diverse pro-moieties were appended on fulvestrant to improve solubility and ADME profile. Thermodynamic solubility, plasma/liver microsomal stability, and Caco-2 permeability studies were performed to identify lead molecules. Pharmacokinetic studies were performed for selected molecules in mice. Antitumor activity of once-daily oral dose of three molecules was evaluated in female nude mice using the MCF-7 xenograft model. The efficacy of lead molecules was compared with subcutaneously administered faslodex in terms of percentage tumor growth inhibition. Results: Several prodrugs of fulvestrant were synthesized and evaluated for their intrinsic properties suitable for increasing bioavailability of fulvestrant. Remarkable improvements (̃500 to 2000-fold increase) were achieved in solubility and permeability. The PoC established an increase in systemic plasma exposure of fulvestrant upon oral administration of prodrugs in mice with enhanced bioavailability (1.5-8.7-fold) as compared to fulvestrant given subcutaneously (Table). Herewith, we report the identification of KSHN001022, KSHN001075, and KSHN001126, the prodrugs of fulvestrant, which showed enhanced efficacy with better tumor volume reduction (̃48-88% regression in tumor volume) as compared to that of fulvestrant (78%) in the estrogen-dependent MCF-7 xenograft model. Conclusions: KSHN001 lead candidates demonstrated significantly higher bioavailability, hence, provides a novel strategy to deliver fulvestrant orally to pursue the potential benefits in patients with advanced metastatic disease.[Table: see text]


1998 ◽  
Vol 16 (10) ◽  
pp. 3353-3361 ◽  
Author(s):  
A D Seidman ◽  
C A Hudis ◽  
J Albanell ◽  
J Albanel ◽  
W Tong ◽  
...  

PURPOSE To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy. PATIENTS AND METHODS Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen patients had received prior anthracycline therapy, 12 of whom had demonstrated progression of disease within 12 months of it. All patients were assessable for efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of paclitaxel were also performed. RESULTS A total of 469 weekly paclitaxel infusions were administered to 30 patients (median, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CRs) and 43% partial responses (PRs). Median response duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18 (50%) patients with prior anthracycline therapy, including six of 12 (50%) with disease progression on anthracycline within 1 year (three of four within 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients; febrile neutropenia was not observed. Peripheral neuropathy prohibited dose escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21 patients at < or = 100 mg/m2. CONCLUSION Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.


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