OBJECTIVE:This study aimed to determine the more suitable method for constructing parathyroid organoids. METHODS:Parathyroid organoids were established using two different culture conditions, and organoid morphology and ATP activity were assessed to evaluate their performance. Organoid identity and function were confirmed by STR profiling, histology, immunofluorescence, and ELISA. Organoids were further treated with different calcium concentrations, and changes in morphology, ATP activity, intracellular calcium, CaSR expression, and PTH secretion were examined. RESULTS:Organoids cultured in VEGF-121- and angiotensin-negative medium showed no noticeable morphological change from Day 1 to Day 3, and ATP activity declined over the same period. In contrast, organoids in VEGF-121+ and angiotensin-positive medium exhibited increased number and ATP activity over the same period. These organoids shared the same mutation profile and structural features as the original tissues and expressed PTH, GCM2, CaSR, and CHGA. PTH secretion remained stable across passages. Low calcium had minimal impact on morphology, viability, and PTH release but reduced intracellular calcium levels and CaSR expression. High calcium promoted ATP activity and elevated intracellular calcium, while suppressing PTH secretion and upregulating CaSR expression. CONCLUSIONS:VEGF-121+ and angiotensin-positive medium better supported the generation and maintenance of functional parathyroid organoids. This provides an in vitro model for further investigation into parathyroid-related signaling and applications in regenerative medicine.

Survival analysis according to treatment line, hormone receptor status and metastatic sites.

Photodynamic therapy (PDT) is regarded as an alternative anti-tumor therapy which involves the administration of photosensitizers (PSs) and irradiation with specific light. However, conventional PDT therapy has been limited to the efficiency of PS delivery. A nanocarrier system could provide an effective platform for PS delivery and improve the efficiency of antitumor PDT. In this article, we prepared a complex consisting of aluminum phthalocyanine (AlPcS) and CdSe/CdZnS core-shell structure QDs and investigated the interaction between the complex and tumor cells. A more significant internalization of the conjugation was observed compared to free AlPcS via confocal fluorescence imaging. The tumor cells exhibited an obvious apoptotic trend after QD–AlPcS-mediated PDT.

Background: Pertuzumab plus trastuzumab combined with chemotherapy has become a standard neoadjuvant therapy option for patients with high-risk human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). There is still not enough evidence for the efficacy and safety of neoadjuvant pertuzumab and trastuzumab plus chemotherapy in HER2-positive BC patients in China, both in clinical trials and real-world settings. This study aimed to assess the efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy in Chinese patients with HER2-positive BC in real-world clinical application. Methods: We retrospectively collected the data from the electronic medical records of HER2-positive patients treated with neoadjuvant trastuzumab and pertuzumab plus chemotherapy from December 2018 to May 2021 at 21 hospitals located in Hunan Province, China, including age, American Joint Committee on Cancer (AJCC) stage, clinical tumor size, clinical lymph node status, pathological characteristics (before neoadjuvant systemic therapy), treatment approach, adverse events to neoadjuvant therapy, and achievement of pathological complete response (pCR). The primary endpoint was the total rate of pCR, and the secondary endpoints were the rate of pCR of each subgroup and the safety of dual anti-HER2 therapy. Results: A total of 188 patients met the inclusion criteria and were included in the analysis. Of the 188 patients, 119 (63.3%) were diagnosed at stage II and 64 (34.0%) at stage III; 163 (86.7%) were cT2-3; 149 patients (79.3%) were >= cN1; 84 patients (44.7%) were hormone receptor (HR)-positive. pCR was observed in 88 of 188 patients (46.8%). The pCR rate of HR-negative patients (54.8%) was higher (P=0.014) than that of HR-positive patients (36.9%). Patients with Ki-67 <15% achieved a higher (P=0.033) pCR rate (68.2%) than those with Ki-67 >= 15% (44.0%). Anemia was the most common adverse event (63.4%), and the most common grade 3-4 adverse event was nausea and vomiting (8.5%). Conclusions: Our study confirmed the benefit of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy on pCR with a tolerable safety profile in routine clinical practice in Chinese patients with HER2-positive BC. HR-negativity and Ki-67 <15% were associated with pCR in these patients.

[This corrects the article DOI: 10.3389/fonc.2020.00811.].

Adenomyoepithelioma (AME) of the breast is a rare tumor that is composed of proliferating epithelial and myoepithelial cells. The pathogenesis of AME remains unclear, and no breast cancer cells have been identified in such tumor tissues. In this study, we established patient-derived breast cancer organoids from the surgical tumor samples of an elderly Chinese woman with an AME of the breast. Our findings confirmed the successful establishment of organoids from an AME of the breast of this patient. A short tandem repeat analysis revealed that the DNA signature of the AME of the breast organoids matched the DNA signature of the original tumor specimen. Moreover, diameter assay confirmed that the organoids from the breast AME showed sensitivity to paclitaxel and doxorubicin treatments, which was similar to, but lesser than that of primary culture cells. In conclusion, we established an efficient 3-dimensional breast cancer organoid culture platform from an AME of the breast. This platform can be effectively used for exploring clinicopathological and genomic characteristics of AME of the breast to identify possible treatments and increase awareness about this disease entity.

Purpose: Patients with HER2-positive (HER2(+)) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce. Experimental Design: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2(+) MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR), and overall response rate (ORR) were analyzed. Results: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR). Conclusions: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

Background: Pyrotinib, an irreversible pan-ERBB inhibitor, has shown promising antitumour activity, and acceptable tolerability. This research was conducted to evaluate the actual use and effectiveness of pyrotinib in China, therefore, contributed to solve the problem of real-world data scarcity. Methods: In this retrospective study, 168 patients who received pyrotinib treatment for HER2-positive metastatic breast cancer (MBC) in Hunan Province from June 2018 to August 2019 were included. Progression-free survival (PFS), tumor mutation burden (TMB), and drug-related adverse events (AEs) after pyrotinib administration were analyzed. Results: The median PFS (mPFS) time in the 168 participants was 8.07 months. The mPFS times in patients with pyrotinib in second-line therapy ( n = 65) and third-or-higher-line therapy ( n = 94) were 8.10 months and 7.60 months, respectively. Patients with brain metastases achieved 8.80 months mPFS time. In patients with pyrotinib in third-or-higher-line therapy, patients who had previously used lapatinib still got efficacy but showed a shorter mPFS time (6.43 months) than patients who had not (8.37 months). TMB was measured in 28 patients, K-M curve ( P = 0.0024) and Multivariate Cox analysis ( P = 0.0176) showed a significant negative association between TMB and PFS. Diarrhea occurred in 98.2% of participants (in any grade) and 19.6% in grade 3–4 AEs. Conclusion: Pyrotinib is highly beneficial to second-or-higher-line patients or HER2-positive MBC patients with brain metastases. Pyrotinib seems to be a feasible strategy both in combination of chemotherapeutic drugs or as a replacement of lapatinib if diseases progressed. TMB could be a potential predictor for evaluating pyrotinib's effectiveness in HER2-positive MBC.