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IntroductionWe aim to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) in breast cancer patients by constructing a Nomogram based on radiomics models, clinicopathological features, and ultrasound features.MethodsUltrasound images of 464 breast cancer patients undergoing NAC were retrospectively analyzed. The patients were further divided into the training cohort and the validation cohort. The radiomics signatures (RS) before NAC treatment (RS1), after 2 cycles of NAC (RS2), and the different signatures between RS2 and RS1 (Delta-RS/RS1) were obtained. LASSO regression and random forest analysis were used for feature screening and model development, respectively. The independent predictors of pCR were screened from clinicopathological features, ultrasound features, and radiomics models by using univariate and multivariate analysis. The Nomogram model was constructed based on the optimal radiomics model and clinicopathological and ultrasound features. The predictive performance was evaluated with the receiver operating characteristic (ROC) curve.ResultsWe found that RS2 had better predictive performance for pCR. In the validation cohort, the area under the ROC curve was 0.817 (95%CI: 0.734-0.900), which was higher than RS1 and Delta-RS/RS1. The Nomogram based on clinicopathological features, ultrasound features, and RS2 could accurately predict the pCR value, and had the area under the ROC curve of 0.897 (95%CI: 0.866-0.929) in the validation cohort. The decision curve analysis showed that the Nomogram model had certain clinical practical value.DiscussionThe Nomogram based on radiomics signatures after two cycles of NAC, and clinicopathological and ultrasound features have good performance in predicting the NAC efficacy of breast cancer.

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.

PurposeTo explore the difference in the effectiveness of gallium-68 fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT and fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT for the initial staging of patients with nasopharyngeal carcinoma (NPC).MethodsThe Affiliated Hospital of Southwest Medical University hosted this single-center prospective investigation (Clinical Trials registration No.ChiCTR2100044131) between March 2020 and September 2021. Within a week, all subjects underwent MR scans, 68Ga-FAPI-04 PET/CT, and 18F-FDG PET/CT in order. The effectiveness of medical staging employing 68Ga-FAPI-04 and 18F-FDG PET/CT was compared.ResultsTwenty-eight patients with primary NPC were evaluated (mean age53 ± 11 years). 68Ga-FAPI-04 PET/CT indicated an elevated recognition rate for diagnosing primary tumors (28/28 [100%] vs. 27/28 [96%]) and lymph node metastases (263/285 [92%] vs. 228/285 [80%]), but a lower detection rate for distant metastases (5/7 [71%] vs. 7/7 [100%]) compared with 18F-FDG PET/CT. A significant association between the maximum standard uptake value (SUVmax) of 18F-FDG PET and 68Ga-FAPI-04 PET was found in the primary cancers (r = 0.691, p < 0.001). In comparison to 18F-FDG PET/CT, 68Ga-FAPI-04 PET/CT upstaged the T stage in five patients while downstaging the N stage in seven patients. 68Ga-FAPI-04 PET/CT corrected the overall staging of five patients on18F-FDG PET/CT.Conclusion68Ga-FAPI-04 PET/CT is preferable to 18F-FDG PET/CT for NPC staging in terms of the detection efficiency for primary tumors and lymph node metastasis. This is especially true when evaluating the primary cancer and any spread to contiguous tissues. It is possible to improve the staging assessment of NPC by using 68Ga-FAPI-04 PET/CT in conjunction with 18F-FDG PET/CT.

Distant metastasis is the main cause of death in nasopharyngeal carcinoma (NPC) patients. There is an urgent need to reveal the underlying mechanism of NPC metastasis and identify novel therapeutic targets. The ferroptosis resistance and survival ability of extracellular matrix (ECM)-detached tumor cells are important factors in determining the success of distant metastasis. In this study, we found that CAPRIN2 contributes to the ferroptosis resistance and survival of ECM-detached NPC cells. Moreover, CAPRIN2 serves as a positive regulator of NPC cell migration and invasion. HMGCR, the key metabolic enzyme of the mevalonate pathway, was identified as the key downstream molecule of CAPRIN2, which mediates its regulation of ferroptosis, survival, migration and invasion of NPC cells. Lung colonization experiments showed that downregulation of the CAPRIN2/HMGCR axis resulted in reduced lung metastasis of NPC cells. Erastin treatment inhibited the ability of NPC cells to colonize the lungs, which was further enhanced by CAPRIN2/HMGCR axis downregulation. Regulated by upstream LINC00941, CAPRIN2 is abnormally activated in NPC, and its high expression is associated with a poor prognosis. In conclusion, CAPRIN2 is a molecular marker of a poor prognosis in NPC, and the LINC00941/CAPRIN2/HMGCR axis provides a new target for the treatment of NPC metastasis and ferroptosis resistance.

PurposeThis study aimed to compare the potential diagnostic efficacy of gallium68-fibroblast-activation protein inhibitor ([68Ga]Ga-FAPI-04) and fluorine18-fluorodeoxyglucose ([18F]-FDG) positron emission tomography-computed tomography (PET/CT) for primary tumors, lymph nodes, and distant metastatic lesions of gastric cancer (GC), and to explore the effects of [68Ga]Ga-FAPI-04 and [18F]-FDG on tumor staging and restaging in GC.MethodsThis single-center retrospective study (NCT2100044131) was conducted at the Affiliated Hospital of the Southwest Medical University between June 2020 and December 2021. Images of patients with GC who were pathologically confirmed and underwent contemporaneous [18F]-FDG and [68Ga]Ga-FAPI-04 PET/CT within 1 week were analyzed. The diagnostic efficacy of [68Ga]Ga-FAPI-04 PET/CT and [18F]-FDG PET/CT for TNM staging of GC was compared using McNemar test. The maximum standard uptake value (SUVmax) of each lesion in the two imaging types was compared using the Mann-Whitney U test.ResultsIn total, 25 patients with GC (mean age, 56 ± 12 years) were evaluated. [68Ga]Ga-FAPI-04 PET/CT exhibited higher sensitivity compared to [18F]-FDG PET/CT for detecting primary tumors (18/19 [94.74%] vs. 13/19 [68.42%], χ2 = 6.866, P < 0.01), lymph node metastasis (75/77 [97.40%] vs. 32/77 [41.56%], χ2 = 2.888, P =0.089), and distant metastases (275/283 [97.17%] vs. 122/283 [43.11%], χ2 = 11.858, P < 0.01). [68Ga]Ga-FAPI-04 accumulation was significantly higher than that of [18F]FDG in tumors (median SUVmax, 10.28 vs 3.20; U=59.00, P < 0.01), lymph node metastasis metastases (median SUVmax, 9.20 vs 3.15; U=53.50, P < 0.01), and distant metastases (median SUVmax, 8.00 vs 4.20; U=200.00, P < 0.01). Compared to [18F]-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT resulted in new oncological findings in 14/25 patients and corrected tumor staging or restaging in 7/25 patients.ConclusionOur preliminary results regarding the impact of [68Ga]Ga-FAPI-04 PET/CT on tumor staging highlight the potential of this approach for increasing the accuracy of GC diagnosis, which may facilitate treatment decision-making.

Neuroblastoma (NB) is a devastating malignancy threatening children’s health, and amplification of MYCN is associated with treatment failure and a poor outcome. Here, we aimed to demonstrate the role of cell division cycle 27 (CDC27), an important core subunit of the anaphase-promoting complex, and its clinical significance in NB patients. In functional assays, we illustrated that CDC27 promoted the cell growth, metastasis and sphere-formation ability of NB cells both in vitro and in vivo. To further understand the potential mechanism, SK-N-SH cells were transfected with CDC27 siRNA, and RNA-sequencing was performed. The results revealed that downregulation of CDC27 led to markedly reduced expression of ODC1, which is a well-established direct target of MYCN. Subsequently, we further illustrated that suppression of ODC1 significantly attenuated the promotion effect of CDC27 on the proliferation, metastasis, and sphere-formation ability of NB cells, hinting that CDC27 exerted its biological behavior in NB at least partly in an ODC1-dependent manner. In addition, CDC27 rendered cells more vulnerable to ferroptosis, while knockdown of ODC1 markedly reversed the pro-ferroptotic effect of CDC27. Collectively, our data is the first to report that the CDC27/ODC1 axis promotes tumorigenesis and acts as a positive regulator of ferroptosis in NB, highlighting that CDC27 may represent a novel therapeutic strategy and prognostic biomarker in neuroblastoma.

Purpose: This study aimed to compare the potential diagnostic efficacy of gallium68- fibroblast-activation protein inhibitor ([68Ga]Ga-FAPI-04) and fluorine18- fluorodeoxyglucose ([18F]-FDG) positron emission tomography-computed tomography (PET/CT) for primary tumors, lymph nodes, and distant metastatic lesions of gastric cancer (GC), and to explore the effects of [68Ga]Ga-FAPI-04 and [18F]-FDG on tumor staging and restaging in GC. Methods: This single-center retrospective study (NCT2100044131) was conducted at the Affiliated Hospital of the Southwest Medical University between June 2020 and December 2021. Images of patients with GC who were pathologically confirmed and underwent contemporaneous [18F]-FDG and [68Ga]Ga-FAPI-04 PET/CT within 1 week were analyzed. The diagnostic efficacy of [68Ga]Ga-FAPI-04 PET/CT and [18F]-FDG PET/CT for TNM staging of GC was compared using McNemar test. The maximum standard uptake value (SUVmax) of each lesion in the two imaging types was compared using the Mann-Whitney U test. Results: In total, 25 patients with GC (mean age, 56 ± 12 years) were evaluated. [68Ga] Ga-FAPI-04 PET/CT exhibited higher sensitivity compared to [18F]-FDG PET/CT for detecting primary tumors (18/19 [94.74%] vs. 13/19 [68.42%], c2 = 6.866, P < 0.01), lymph node metastasis (75/77 [97.40%] vs. 32/77 [41.56%], c2 = 2.888, P =0.089), and distant metastases (275/283 [97.17%] vs. 122/283 [43.11%], c2 = 11.858, P < 0.01). [68Ga]Ga-FAPI-04 accumulation was significantly higher than that of [18F]FDG in tumors (median SUVmax, 10.28 vs 3.20; U=59.00, P < 0.01), lymph node metastasis metastases (median SUVmax, 9.20 vs 3.15; U=53.50, P < 0.01), and distant metastases (median SUVmax, 8.00 vs 4.20; U=200.00, P < 0.01). Compared to [18F]-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT resulted in new oncological findings in 14/25 patients and corrected tumor staging or restaging in 7/25 patients. Conclusion: Our preliminary results regarding the impact of [68Ga]Ga-FAPI-04 PET/CT on tumor staging highlight the potential of this approach for increasing the accuracy of GC diagnosis, which may facilitate treatment decision-making. [ABSTRACT FROM AUTHOR]

Primary endometrial squamous cell carcinoma (PESCC) is a rare malignant tumor. To investigate the clinical and pathological features of PESCC, two cases of PESCC in Fujian Maternal and Child Health Hospital were retrospectively studied and the literatures were reviewed. Both of the two cases were menopausal women aged 57-62 years, clinically presenting with "vaginal discharge". Case 1 was a non-keratinising squamous cell carcinoma with high-risk HPV infection. Tumor infiltrated in deep myometrium with multifocal intravascular thrombus and macro metastases to one pelvic lymph node (1/15) and abdominal aortic lymph node (1/1). Lung metastasis occurred 36 months after the surgery. After surgical resection and without postoperative supplemental therapy, the patient remained tumor-free for 110 months to date. Case 2 had a history of breast cancer for 5 years and long-term intake of aromatase inhibitor drugs without HPV infection. It was a keratinized squamous cell carcinoma. Tumor also infiltrated in deep myometrium with multifocal intravascular thrombus and one pelvic lymph node metastasis (1/18), However, no metastasis was seen elsewhere. To date, the patient survived for 16 months without tumor after surgery. Both of the two cases expressed squamous epithelial markers P40, P63, and CK5/6, but neither expressed PAX8 or PR. Case 1 had diffuse expression of P16, wild-type P53, and ER-negative. Case 2 had negative P16, mutant P53, and focal positive ER. PESCC is often associated with HPV infection and low estrogen levels. However, studies in the literatures have found that P16 expression is not always consistent with HPV infection, indicating that PESCC cannot be easily classified as HPV-associated or non-dependent like cervical cancer. There are two main patterns of P16 and P53 expression, P16-positive/P53 wild-type and P16-negative/P53-mutant, but no positive expression of both has been seen so far. It is worth noting that we reported the second case of PESCC with a history of breast cancer, where the patient had been taking the oral aromatase inhibitor drug (exemestane) for a long period of time to reduce the estrogen level, indicating the low estrogen level may be also a key factor in the pathogenesis of PESCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Lin, Lin, Lin, Luo and Xu.)