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1.
Front Oncol ; 12: 851807, 2022.
Article in English | MEDLINE | ID: mdl-35875090

ABSTRACT

Early detection of metastatic breast cancer (MBC) is a serious issue for the healthcare system. It is essential to develop potential non-invasive, low-cost molecular biomarkers. The present study explored specific serum proteins of inflammatory, MAPK, and cytoskeletal signaling pathways involved in the progression of MBC to establish a panel of blood-based diagnostic and prognostic biomarkers. Healthy-control (HC), non-metastatic (NM), and metastatic (M) (pre- and post-therapy) breast cancer (BC) patients were recruited. LOX5, Rac1, Rac1b, p38α, phospho-p38α (Y182), LIMK1, phospho-LIMK1 (T508), cofilin1, and phospho-cofilin1 (S3) were quantified in the serum of the study group by real-time label-free surface plasmon resonance technology and verified by Western blot. Proteins were found to be significantly elevated in the serum of BC patients compared to HC and also higher in M compared to NM, which further downregulated in post-therapy M patients. Elevation of phospho-LIMK1 and phospho-cofilin1, which are critical for M, was also indicated in the serum level and can differentiate from NM. Receiver operating characteristics (ROC) derived area under the curve (AUC) (0.9) is very strong to differentiate between HC and BC. Moreover, the combined ROC of 3 molecules phospho-LIMK, p38α, and phospho-p38α were found to be a potent predictive panel of biomarkers between M and NM with AUC0.95. The panel of inflammatory cytoskeleton signaling regime proteins specified in this study can have significant clinical utility for diagnosis as well as prognosis of MBC at an early stage. The study may have a high translational value in a simple and cost-effective way by avoiding frequent CT/PET scans.

2.
Asian Pac J Cancer Prev ; 20(9): 2653-2657, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31554360

ABSTRACT

Introduction: Cancer of the cervix is the second most common cancer in women in India. Chemoradiotherapy is the standard treatment for locally advanced carcinoma cervix. Chemotherapy is not given on days of brachytherapy due to the fear of increased toxicity though studies supporting or refuting it are limited. We intended to study feasibility of adding chemotherapy to brachytherapy with assessment of acute toxicity and response rates. Methods: 29 patients of locally advanced carcinoma cervix (FIGO IIB to IIIB) were assigned to receive either three sessions of high dose rate (HDR) brachytherapy alone or HDR brachytherapy with concurrent chemotherapy of Paclitaxel and Carboplatin after completion of external beam radiation with concurrent Cisplatin. Patients were assessed for compliance of treatment, toxicity and response rates at three and six months. The p-value less than 0.05 was considered statistically significant. Fischer's exact test was used for statistical analysis. Results: 15 patients were assigned to the standard of care arm and 14 patients to the experimental chemo-brachytherapy arm. The median number of cycles of chemotherapy possible with brachytherapy was two (Range: 1 -3). At three months after treatment all patients except one patient in each arm had a complete response. There was two acute grade 3 hematological toxicity and two acute grade 3 or higher gastrointestinal toxicity in the experimental arm but none in the standard arm. The experimental arm had a statistically higher incidence of acute grade 3 and 4 toxicity than the standard arm (p=0.042). Conclusions: Chemo-brachytherapy is associated with higher acute toxicity with comparable response rates. Small patient numbers and short follow up impedes us from providing conclusive evidence.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brachytherapy/methods , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Uterine Cervical Neoplasms/therapy , Adult , Aged , Carboplatin/administration & dosage , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Uterine Cervical Neoplasms/pathology , Young Adult
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