Search Results (7)

Protein kinase C-iota (PKC-ι) is an oncogene overexpressed in many cancer cells including prostate, breast, ovarian, melanoma, and glioma cells. Previous in vitro studies have shown that 5-amino-1-((1R,2S,3R,4R)-2-3-dihydroxy-4-(hydroxymethyl)cyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S), a PKC-ι-specific inhibitor, has low toxicity in both acute and sub-acute mouse model toxicological testing and is an effective therapeutic against several cancer cell lines showing significant reductions in tumor growth when treating athymic nude mice with xenografted carcinoma cell lines. To further assess ICA-1S as a possible therapeutic agent, chronic mouse model toxicological testing was performed in vivo to provide inferences concerning the long-term effects and possible health hazards from repeated exposure over a substantial part of the animal’s lifespan. Subjects survived well after 30, 60, and 90 days of doses ranging from 50 mg/kg to 100 mg/kg. Heart, liver, kidney, and brain tissues were then analyzed for accumulations of ICA-1S including the measured assessment of aspartate transaminase (AST), alkaline phosphatase (ALK-P), gamma-glutamyl transferase (GGT), troponin, and C-reactive protein (CRP) serum levels to assess organ function. Predictive in vitro/in silico methods were used to predict compound-induced direct hepatocyte toxicity or renal proximal tubular cell (PTC) toxicity in humans based on the high-content imaging (HCI) of compound-treated cells in combination with phenotypic profiling. In conclusion, ICA-1S shows low toxicity in both acute and chronic toxicology studies, and shows promise as a potential therapeutic. Full article

Purpose: Breast cancer is the most common solid tumor and the second highest cause of death in the United States. Detection and diagnosis of breast tumors includes various imaging modalities, such as mammography (MMG), ultrasound (US), and contrast-enhancement MRI. Breast-specific gamma imaging (BSGI) is an emerging tool, whereas morphological imaging has the disadvantage of a higher absorbed dose. Our aim was to assess if this imaging method is a more valuable choice in detecting breast malignant lesions compared to morphological counterparts. Methods: research on Medline from 1995 to June 2022 was conducted. Studies that compared at least one anatomical imaging modality with BSGI were screened and assessed through QUADAS2 for risk of bias and applicability concerns assessment. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were reported. Results: A total of 15 studies compared BSGI with MMG, US, and MRI. BSGI sensitivity was similar to MRI, but specificity was higher. Specificity was always higher than MMG and US. BSGI had higher PPV and NPV. When used for the evaluation of a suspected breast lesion, the overall sensitivity was better than the examined overall sensitivity when BSGI was excluded. Risk of bias and applicability concerns domain showed mainly low risk of bias. Conclusion: BSGI is a valuable imaging modality with similar sensitivity to MRI but higher specificity, although at the cost of higher radiation burden. Full article

This study aimed to investigate which of the two frequently adopted perfusion models better describes the contrast enhanced ultrasound (CEUS) perfusion signal in order to produce meaningful imaging markers with the goal of developing a machine-learning model that can classify perfusion curves as benign or malignant in breast cancer data. Twenty-five patients with high suspicion of breast cancer were analyzed with exponentially modified Gaussian (EMG) and gamma variate functions (GVF). The adjusted R² metric was the criterion for assessing model performance. Various classifiers were trained on the quantified perfusion curves in order to classify the curves as benign or malignant on a voxel basis. Sensitivity, specificity, geometric mean, and AUROC were the validation metrics. The best quantification model was EMG with an adjusted R² of 0.60 ± 0.26 compared to 0.56 ± 0.25 for GVF. Logistic regression was the classifier with the highest performance (sensitivity, specificity, G_mean, and AUROC = 89.2 ± 10.7, 70.0 ± 18.5, 77.1 ± 8.6, and 91.0 ± 6.6, respectively). This classification method obtained similar results that are consistent with the current literature. Breast cancer patients can benefit from early detection and characterization prior to biopsy. Full article

Background: The present retrospective study was designed to evaluate the relative diagnostic utility of breast-specific gamma imaging (BSGI) and breast magnetic resonance imaging (MRI) as means of evaluating female breast cancer patients in China. Methods: A total of 229 malignant breast cancer patients underwent ultrasound, mammography, BSGI, and MRI between January 2015 and December 2018 for initial tumor staging. Of these patients, 73 were subsequently treated via definitive breast surgery following neoadjuvant chemotherapy (NAC), of whom 17 exhibited a complete pathologic response (pCR) to NAC. Results: BSGI and MRI were associated with 76.8% (43/56) and 83.9% (47/56) sensitivity (BSGI vs. MRI, p = 0.341) values, respectively, as a means of detecting residual tumors following NAC, while both these approaches exhibited comparable specificity in this diagnostic context. The specificity of BSGI for detecting residual tumors following NAC was 70.6% (12/17), and that of MRI was 58.8% (10/17) (BSGI vs. MRI, p = 0.473). Conclusion: These results demonstrate that BSGI is a useful auxiliary approach to evaluating pCR to NAC treatment. Full article

Breast cancer is one of the leading causes of cancer-related morbidity and mortality in women worldwide. Early diagnosis and effective treatment of all types of cancers are crucial for a positive prognosis. Patients with small tumor sizes at the time of their diagnosis have a significantly higher survival rate and a significantly reduced probability of the cancer being fatal. Therefore, many novel technologies are being developed for early detection of primary tumors, as well as distant metastases and recurrent disease, for effective breast cancer management. Theranostics has emerged as a new paradigm for the simultaneous diagnosis, imaging, and treatment of cancers. It has the potential to provide timely and improved patient care via personalized therapy. In nanotheranostics, cell-specific targeting moieties, imaging agents, and therapeutic agents can be embedded within a single formulation for effective treatment. In this review, we will highlight the different diagnosis techniques and treatment strategies for breast cancer management and explore recent advances in breast cancer theranostics. Our main focus will be to summarize recent trends and technologies in breast cancer diagnosis and treatment as reported in recent research papers and patents and discuss future perspectives for effective breast cancer therapy. Full article

Bone metastases frequently occur in breast cancer patients and lack appropriate treatment options. Hence, understanding the molecular mechanisms involved in the multistep process of breast cancer bone metastasis and tumor-induced osteolysis is of paramount interest. The serine/threonine kinase AKT plays a crucial role in breast cancer bone metastasis but the effect of individual AKT isoforms remains unclear. Therefore, AKT isoform-specific knockdowns were generated on the bone-seeking MDA-MB-231 BO subline and the effect on proliferation, migration, invasion, and chemotaxis was analyzed by live-cell imaging. Kinome profiling and Western blot analysis of the TGFβ/CTGF axis were conducted and metastasis was evaluated by intracardiac inoculation of tumor cells into NOD scid gamma (NSG) mice. MDA-MB-231 BO cells exhibited an elevated AKT3 kinase activity in vitro and responded to combined treatment with AKT- and mTOR-inhibitors. Knockdown of AKT3 significantly increased migration, invasion, and chemotaxis in vitro and metastasis to bone but did not significantly enhance osteolysis. Furthermore, knockdown of AKT3 increased the activity and phosphorylation of pro-metastatic HER2 and DDR1/2 but lowered protein levels of CTGF after TGFβ-stimulation, an axis involved in tumor-induced osteolysis. We demonstrated that AKT3 plays a crucial role in bone-seeking breast cancer cells by promoting metastatic potential without facilitating tumor-induced osteolysis. Full article

The main purpose of this pilot investigation was to evaluate the possible relationship among [⁹⁹mTc]Tc-Sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of molecules involved in bone metabolism, such as estrogen receptor, bone morphogenetic proteins-2, and PTX3. To this end, forty consecutive breast cancer patients who underwent both breast-specific gamma imaging with [^99mTc]Tc-Sestamibi and breast bioptic procedure were retrospectively enrolled. From each diagnostic paraffin block collected in the study, histological diagnosis, immunohistochemical investigations, and energy dispersive X-ray microanalysis were performed. Our data highlight the possible use of breast-specific gamma imaging with [⁹⁹mTc]Tc-Sestamibi for the early detection of breast cancer lesions expressing bone biomarkers in the presence of breast osteoblast-like cells. Specifically, we show a linear association among sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of estrogen receptor, bone morphogenetics proteins-2, and PTX3. Notably, we also observed an increase of [⁹⁹mTc]Tc-Sestamibi in breast cancer lesions with magnesium-substituted hydroxyapatite. In conclusion, in this pilot study we evaluated data from the nuclear medicine unit and anatomic pathology department on breast cancer osteotropism, identifying a new possible interpretation of Breast Specific Gamma Imaging with [⁹⁹mTc]Tc-Sestamibi analysis. Full article