Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer

The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ. Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R2 = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R2 = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.

Elevated SOX11 expression distinguishes basal-like human breast cancer.

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of SRY-box 11, SOX11, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. SOX11 mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that SOX11 primary tumor expression was correlated with overall survival, with higher SOX11 associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. Elevated SOX11 expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.

High VEGF-A expression distinguishes basal-like human breast cancer.

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of the vascular endothelial growth factor A, VEGFA, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. VEGF-A mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that VEGF-A primary tumor expression was correlated with recurrence-free survival, with higher VEGF-A associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. High VEGF-A expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.

Low GATA3 expression distinguishes basal-like human breast cancer.

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of the transcription factor GATA3 when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. GATA3 mRNA was present at significantly reduced quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that GATA3 primary tumor expression was correlated with distant metastasis-free survival, with low GATA3 expression correlated with inferior survival outcomes. Low GATA3 expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.

Prognostic Value of Intratumoral Collagen Quantification in Canine Oral Melanomas

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.