Abstract Background: Primary tumor resection (PTR) in stage IV breast cancer (BC) patients currently lacks robust evidence supporting a prognostic benefit, and the guidelines do not actively endorse this practice. The circumstances under which patients may benefit from this procedure remain uncertain. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program in the United States offers treatment data for stage IV breast cancer patients. We conducted a screening of patients diagnosed with metastatic breast cancer between 2010 and 2015. The primary outcomes focused on were overall survival (OS) and cancer-specific survival (CSS). We employed Kaplan-Meier method, Cox proportional hazard regression models, propensity score matching (PSM) to balance key confounding variables, and sequential landmark analyses to mitigate the impact of time-related factors on the results. Results : This study included 11,359 patients with stage IV breast cancer (BC). Patients who received primary tumor resection (PTR) experienced improved overall survival (OS) and cancer-specific survival (CSS). For OS (median survival time), the comparisons were as follows: chemoradiotherapy plus PTR versus chemoradiotherapy, with survival times of 56 months versus 25 months (p < 0.001); radiotherapy plus PTR versus radiotherapy, with survival times of 51 months versus 27 months (p < 0.001); chemotherapy plus PTR versus chemotherapy, with survival times of 45 months versus 32 months (p < 0.001); and only PTR versus no treatment, with survival times of 35 months versus 22 months (p < 0.001). Multivariate adjustment analysis, propensity score matching (PSM), and sequential landmark analyses provided further validation of these results. When stratified by different metastasis patterns, PTR significantly improved OS and CSS in patients with metastases in other organs, excluding brain metastasis. Regarding OS, the adjust hazard ratios (aHR) for different metastasis sites were as follows: bone metastasis (aHR0.555, 95% CI 0.514-0.598, p < 0.001); liver metastasis (aHR0.703, 95% CI 0.593-0.835, p < 0.001); brain metastasis (aHR0.639, 95% CI 0.549-0.734, p < 0.001); bone-liver metastasis (aHR0.716, 95% CI 0.601-0.852, p < 0.001); bone-lung metastasis (aHR0.782, 95% CI 0.667-0.915, p = 0.002); bone, liver, and lung metastasis (aHR0.712, 95% CI 0.550-0.921, p = 0.010). Notably, many patients with brain metastasis did not derive significant benefits from chemotherapy, and patients with liver metastasis saw improvements with radiotherapy alone. Similar conclusions were observed for cancer-specific survival (CSS). Conclusion: In patients with stage IV breast cancer, PTR in combination with chemotherapy or chemoradiotherapy can improve survival time. However, in cases of solitary brain metastasis and multiple metastases including brain metastasis, the decision to use PTR should be made with caution.
Molybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer.MoS2 nanosheets were prepared by a hydrothermal reaction and modified. Afterward, the nanocarrier was characterised. In vitro cytotoxicity of the drug delivery systems on human breast adenocarcinoma cell lines was assessed.The nanocarrier was a flake-like structure with a uniform hydrodynamic diameter and possessing good colloidal stability. The nanocarrier showed the capacity to be deployed for co-delivery of Doxorubicin (DOX) and siRNA. The release of DOX could be triggered and enhanced by pH and application of near-infrared (NIR) laser. The nanocarrier had a good photothermic response and stability. The nanocarrier had little effect on the cells and exhibited good biocompatibility. Measurement of the therapeutic efficacy showed that synergistic therapy combining chemo-, gene- and photothermal therapy deploying this drug delivery system will achieve a better anticancer effect on drug-resistant cancer cells than DOX alone.Our results suggest that this drug delivery system has potential application in the therapeutic strategy for drug-resistant cancer.
Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis.Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort.uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort.uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.
Although numerous electrochemical DNA (E-DNA) sensors have been developed, a zero-background E-DNA sensor is badly desired for highly accurate real-sample assay. Herein, by means of a methylene blue (MB)-attached DNA probe and an inverted hybridization mode, we built a lambda exonuclease (λ-Exo)-assisted ligase chain reaction-based electrochemical biosensor, named λ-eLCR, for highly sensitive CYP2C19*2 allele genotyping with zero-background. Specifically, only in the presence of the mutant target (MT), a ligated MB-labelled single-stranded DNA (ssDNA) was exponentially generated by coupling LCR with λ-Exo digestion, then it was readily hybridized with the distal sequence of capture probe even in high-density DNA self-assembly monolayer, bringing the electroactive MB close to the surface of electrode. In this regard, the signal of the proposed λ-eLCR was only derived from a ligated MB-labelled ssDNA, ensuring the realization of zero-background and quantitatively related with the MT concentration. The λ-eLCR exhibited excellent performance in terms of good linear range (100 fM~10 pM) and a low detection limit (100 fM). Finally, this zero-background λ-eLCR successfully distinguished the CYP2C19*2 allele genotypes in the human whole blood samples, which provides a promising approach for reliable genotyping of substance-metabolizing enzyme and individualized medicine.
The prevalence of brain metastases (BM) in lung cancer patients is notably high and is associated with poor prognoses. The efficacy of standard treatment regimens in improving intracranial progression-free survival (IPFS) for lung cancer BM is markedly limited. While traditional Chinese medicine (TCM) has been effective in enhancing the quality of life and prognosis of lung cancer patients, its efficacy in treating BM remains unreported. Here, we present a case of a middle-aged female with lung cancer BM, whose condition was assessed as progressive post-standard treatment including two local surgeries (both involving resection of cerebellar space-occupying lesions), stereotactic radiotherapy, chemotherapy and EGFR-TKIs. Subsequently, she underwent treatment with the traditional Chinese herbal formula gubenxiaoyi (GBXY). The patient was treated with GBXY for a total duration of 55 months. After treatment, a significant reduction of about 50% in intracranial lesions was observed, accompanied by an extension of both Intracranial Progression-Free Survival (IPFS) and Cognitive Deterioration-Free Survival (CDFS) exceeding 50 months. These results demonstrate that in patients with lung cancer brain metastases (BM) unresponsive to standard treatments, GBXY not only has the potential to effectively prolong IPFS and decelerate cognitive decline, but may also contribute to a reduction in intracranial tumor burden. This suggests that GBXY could be a promising therapeutic option that warrants further investigation.
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