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Triple Negative Breast Cancer With Choroidal Metastasis Responsive to Sacituzumab Govitecan and Radiation Therapy 伴有脉络膜转移的三阴性乳腺癌对Sacituzumab、Govitecan和放疗有反应。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-06 DOI: 10.1002/cnr2.70462
Nellie Nafissi, Aditya Mahadevan, Elaine Chiao, Nejina Rijal, Ritesh Parajuli

Background

Orbital metastases are rare in patients with breast cancer. However, medical management of orbital metastases is limited by the inability of treatment options to penetrate the blood-brain barrier. In patients with triple negative breast cancer (TNBC), these treatment options are further limited. Sacituzumab govitecan, an antibody-drug conjugate, has emerged as a promising agent for metastatic TNBC. However, to date, patients with central nervous system (CNS) disease have been excluded from corresponding clinical trials, making the efficacy of sacituzumab govitecan in patients with orbital metastases unclear.

Case

A 61-year-old female was initially diagnosed with a left breast hormone receptor positive invasive ductal carcinoma, receiving neoadjuvant chemotherapy with doxorubicin, cyclophosphamide, and docetaxel and a partial mastectomy. Several years later, the patient presented with a cough and was subsequently diagnosed with metastatic triple negative breast cancer with hepatic, osseous, and right supraclavicular and thoracic nodal metastases. Concurrently, the patient noted floaters in her vision, later found to be consistent with orbital metastases. The patient received radiation therapy to both eyes and was started on Sacituzumab govitecan. Following cycle 1, the ophthalmic exam showed a dramatic decrease in the size of choroidal metastases.

Conclusion

This case report documents the first case of orbital metastases successfully treated with radiation therapy and sacituzumab govitecan. As such, this case highlights the importance of sacituzumab govitecan as a potentially effective option for TNBC patients with CNS disease. Further studies and real-world data are needed to investigate the efficacy of combined radiotherapy and sacituzumab govitecan toward ocular metastases.

背景:眼眶转移在乳腺癌患者中是罕见的。然而,眼眶转移的医疗管理受到治疗方案无法穿透血脑屏障的限制。在三阴性乳腺癌(TNBC)患者中,这些治疗选择进一步受到限制。Sacituzumab govitecan是一种抗体-药物缀合物,已成为治疗转移性TNBC的有希望的药物。然而,到目前为止,中枢神经系统(CNS)疾病患者被排除在相应的临床试验之外,这使得sacituzumab govitecan在眼眶转移患者中的疗效尚不清楚。病例:一名61岁女性,最初被诊断为左乳激素受体阳性浸润性导管癌,接受阿霉素、环磷酰胺和多西他赛新辅助化疗和乳房部分切除术。几年后,患者出现咳嗽,随后被诊断为转移性三阴性乳腺癌,伴肝、骨、右锁骨上和胸淋巴结转移。同时,患者发现她的视力中有漂浮物,后来发现与眼眶转移一致。患者接受双眼放射治疗,并开始使用Sacituzumab govitecan。第1周期后,眼科检查显示脉络膜转移灶明显缩小。结论:本病例报告记录了第一例放疗和舒妥珠单抗治疗成功的眼眶转移病例。因此,该病例强调了sacituzumab govitecan作为TNBC合并中枢神经系统疾病患者潜在有效选择的重要性。需要进一步的研究和实际数据来调查联合放疗和sacituzumab govitecan对眼部转移的疗效。
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引用次数: 0
Safety and Efficacy of Concomitant Administration of Nanoliposomal Irinotecan + 5-Fluorouracil/Levo-Leucovorin for Pancreatic Cancer 纳米脂质体伊立替康+ 5-氟尿嘧啶/左-亚叶酸钙联合治疗胰腺癌的安全性和有效性。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-05 DOI: 10.1002/cnr2.70485
Akane Wakabayashi, Rei Tanaka, Yurie Fukumuro, Keita Mori, Junya Sato, Hiroshi Ishikawa, Michihiro Shino, Takeshi Kawakami

Background

Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) therapy is recommended as the standard of care for unresectable locally advanced (UR-LA) and metastatic pancreatic cancer after failure of gemcitabine-containing regimens. Although the concomitant administration of nal-IRI and Levo-LV benefits from a reduced hospital stay, nal-IRI is usually administered after Levo-LV owing to insufficient data on compatibility reactions. This study aimed to compare the safety and efficacy of the sequential and concomitant administration of nal-IRI and Levo-LV.

Methods

Data of patients with UR-LA or metastatic pancreatic cancer who received nal-IRI plus 5-FU/Levo-LV between 2020 and 2023 at Shizuoka Cancer Center were retrospectively collected. Patients were classified into the sequential administration group (Group S) and concomitant administration group (Group C) to compare adverse events, infusion time, and survival. Univariate and multivariate analyses were performed to identify independent prognostic factors in each group.

Results

A total of 94 patients were included (44 in Group S and 50 in Group C). There was no significant difference in the incidence of Grade 3 or higher adverse events between the two groups. The median total infusion times for nal-IRI plus 5-FU/Levo-LV in Groups S and C were 271 and 149 min, respectively (p < 0.001). Overall survival estimates were 5.6 months (95% confidence interval [CI] 3.78–8.57) in Group S and 8.4 months (95% CI 6.77–10.3) in Group C (unstratified HR 0.65, 95% CI 0.42–1.02; p = 0.058). In the multivariate analysis for PFS and OS, the method of administration was not identified as an independent prognostic factor. Concomitant administration of Levo-LV with nal-IRI may not increase adverse events or impact efficacy while reducing infusion time.

Conclusion

Concomitant administration of Levo-LV with nal-IRI may not increase adverse events or impact efficacy compared to sequential administration.

背景:纳米脂体伊立替康(nal-IRI)加5-氟尿嘧啶(5-FU)/左旋亚叶酸钙(lev - lv)治疗被推荐为吉西他滨治疗失败后不可切除的局部晚期(UR-LA)和转移性胰腺癌的标准治疗。虽然同时使用nal-IRI和左左- lv可减少住院时间,但由于相容性反应数据不足,通常在左左- lv之后使用nal-IRI。本研究旨在比较nal-IRI和lev - lv序贯和同时给药的安全性和有效性。方法:回顾性收集2020年至2023年在静冈癌症中心接受nal-IRI + 5-FU/ lev - lv治疗的UR-LA或转移性胰腺癌患者的资料。将患者分为序贯给药组(S组)和伴随给药组(C组),比较不良事件、输注时间和生存期。进行单因素和多因素分析,以确定每组的独立预后因素。结果:共纳入94例患者(S组44例,C组50例)。两组患者3级及以上不良事件的发生率无显著差异。S组和C组nal-IRI加5-FU/左旋- lv的中位总输注时间分别为271 min和149 min (p)。结论:与序贯给药相比,左旋- lv与nal-IRI同时给药可能不会增加不良事件或影响疗效。
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引用次数: 0
Primary Mediastinal Malignant Melanoma Presenting With Pleural Effusion: A Case Report 以胸腔积液为表现的原发性纵隔恶性黑色素瘤1例报告。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-02 DOI: 10.1002/cnr2.70484
Minlian Nong, Weifeng Wei, Naijian Li, Yunxiang Zeng, Jinlin Wang

Background

Primary mediastinal malignant melanoma (PMMM) presenting with pleural effusion as the initial manifestation is exceedingly rare, presenting significant diagnostic and therapeutic challenges. This article reports a case of PMMM that initially manifested as pleural effusion and includes a review of the relevant literature.

Case

The patient was admitted with pleural effusion and an anterior mediastinal mass. A pleural biopsy and fine-needle aspiration of the mediastinal mass led to a pathological diagnosis of malignant melanoma. Ultimately, based on clinical findings, a final diagnosis of PMMM was established. The patient subsequently developed pleural hemorrhage; although hemostasis was achieved through thoracoscopy, his condition stabilized only temporarily. He ultimately succumbed to lung infection and multiple organ failure.

Conclusion

PMMM presenting with pleural effusion lacks distinct clinical features, highlighting the importance of pathological diagnosis. Pleural hemorrhage associated with pleural metastasis may be a characteristic feature, and the prognosis for such cases is poor. Enhanced recognition and early intervention are essential to improve outcomes.

背景:以胸腔积液为首发表现的原发性纵隔恶性黑色素瘤(PMMM)极为罕见,给诊断和治疗带来了重大挑战。本文报告一例最初表现为胸腔积液的PMMM,并回顾了相关文献。病例:患者因胸腔积液和前纵隔肿块入院。胸膜活检和纵隔肿块的细针穿刺导致恶性黑色素瘤的病理诊断。最终,根据临床表现,确定了PMMM的最终诊断。患者随后出现胸膜出血;虽然通过胸腔镜进行了止血,但他的病情只是暂时稳定。他最终死于肺部感染和多器官衰竭。结论:以胸腔积液为临床表现的PMMM缺乏明显的临床特征,强调病理诊断的重要性。胸膜出血合并胸膜转移可能是一个特征性特征,这类病例的预后较差。加强认识和早期干预对改善结果至关重要。
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引用次数: 0
Hypofractionated Radiation Therapy for Pain Relief of Patients With Spinal Metastasis: A Real-World Analysis. 低分割放射治疗缓解脊柱转移患者疼痛:真实世界分析。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-01 DOI: 10.1002/cnr2.70451
Lu Sun, Fan Luo, Yajuan Zhou, Xiyou Liu, Pingping Zhang, Dan Li, Yi Peng

Purpose: Spinal metastases may cause pain, neurological compromise, paraplegia, and limb movement disorders; their management requires a comprehensive approach. Alongside systemic anti-tumor therapies, focal interventions such as radiotherapy, bone-modifying agents, and surgery are crucial for slowing disease progression and managing pain in spinal metastases. However, substantial variations exist in radiotherapy regimens for spinal metastases. In this study, we aimed to investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) regimens at our hospital, specifically to evaluate pain relief and incidence of re-irradiation after HFRT.

Methods: In this retrospective study, data from 58 patients diagnosed with spinal metastasis who received HFRT (4.5-10Gy * 3-7F) at our center between December 2017 and June 2022 were analyzed. All patients were followed up from the initiation of HFRT to either death or their last follow-up visit. Degree of pain was assessed using the numeric rating scale (NRS) before and after 1 month of HFRT. A multivariate Cox regression model was established to identify the independent risk factors for prognostic analysis of spinal metastasis.

Results: HFRT could effectively manage pain in patients with spinal metastasis. The pain scores were significantly decreased after HFRT (3.43 vs. 1.5, p < 0.001), with 84.5% patients experiencing improved pain relief 1 month after radiotherapy. No cases of radiation myelitis were observed during the follow-up period. Furthermore, the incidence of re-radiotherapy was significantly increased in patients with spinal metastases who received moderate HFRT (< 5 Gy/day) (p = 0.01, HR = 0.43).

Conclusion: HFRT significantly reduced pain scores and reirradiation rates without increasing radiation myelitis incidence for spinal metastases.

目的:脊柱转移可能导致疼痛、神经系统损害、截瘫和肢体运动障碍;他们的管理需要一个综合的方法。除了全身抗肿瘤治疗外,局部干预如放疗、骨修饰剂和手术对于减缓疾病进展和控制脊柱转移的疼痛至关重要。然而,脊髓转移的放疗方案存在实质性差异。在本研究中,我们旨在探讨我院低分割放射治疗(HFRT)方案的安全性和有效性,特别是评估HFRT后的疼痛缓解和再照射发生率。方法:回顾性分析2017年12月至2022年6月在本中心接受HFRT (4.5-10Gy * 3-7F)治疗的58例脊柱转移患者的数据。从HFRT开始到死亡或最后一次随访,对所有患者进行随访。采用数值评定量表(NRS)对HFRT前后1个月的疼痛程度进行评估。建立多变量Cox回归模型,以确定脊柱转移预后分析的独立危险因素。结果:HFRT能有效控制脊柱转移患者的疼痛。HFRT后疼痛评分显著降低(3.43 vs. 1.5, p)。结论:HFRT显著降低疼痛评分和再照射率,且未增加脊柱转移性放射性脊髓炎的发生率。
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引用次数: 0
Metastatic Renal Cell Carcinoma Detected by Postprandial Abdominal Pain: A Case Report. 通过餐后腹痛检测转移性肾癌1例。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-01 DOI: 10.1002/cnr2.70490
Xinguang Wang, Nian Zhang, Shaowen Zeng

Background: Renal cell carcinoma (RCC), a prevalent malignancy in China, manifests annually in excess of 70 000 instances. At initial diagnosis, approximately one-tenth of these patients present with metastatic disease. The predominant sites for distant dissemination encompass pulmonary, osseous, hepatic, and adrenal regions, whereas gastric involvement remains exceedingly rare. We clinically characterized a case by postprandially abdominal discomfort, which was endoscopic-biopsy confirmed as a gastric tumor, and further diagnosis revealed the primary malignancy was kidney-originated.

Case: A 68-year-old male was admitted to our hospital for the evaluation of persistent postprandial abdominal pain and diarrhea that had persisted for 1 month. Gastroscopy revealed a gastric body tumor, leading to the performance of an endoscopic submucosal dissection (ESD). The initial pathological examination identified the tumor as gastric malignancy of undetermined origin. Concurrently, a comprehensive abdominal CT scan detected an additional renal tumor. Subsequent radical nephrectomy of the right kidney was performed, and the pathology confirmed the renal cell carcinoma shared the same origin as the gastric lesion. Over a follow-up period of 38 months postoperatively, there has been no evidence of tumor recurrence or progression.

Conclusion: Renal cell carcinoma has the potential to metastasize to the stomach, albeit this occurrence is not readily detectable in clinical practice unless it manifests as gastric symptoms. In instances where solitary superficial gastric metastasis is identified, aggressive surgical intervention can yield satisfactory clinical outcomes.

背景:肾细胞癌(RCC)是中国常见的恶性肿瘤,每年有超过7万例。在最初诊断时,大约十分之一的患者出现转移性疾病。远处播散的主要部位包括肺、骨、肝和肾上腺区,而胃的播散仍然非常罕见。我们临床描述了一例餐后腹部不适,经内镜活检证实为胃肿瘤,进一步诊断显示原发性恶性肿瘤为肾源性。病例:一名68岁男性因持续1个月的餐后腹痛和腹泻入院。胃镜检查发现胃体肿瘤,导致内镜下粘膜下剥离(ESD)的表现。初步病理检查确定肿瘤为来源不明的胃恶性肿瘤。同时,腹部全面CT扫描发现另一个肾脏肿瘤。随后行右肾根治性肾切除术,病理证实肾细胞癌与胃病变有相同的起源。术后随访38个月,未见肿瘤复发或进展。结论:肾细胞癌有可能转移到胃,尽管这种情况在临床实践中不易发现,除非它表现为胃部症状。在发现孤立的浅表胃转移的情况下,积极的手术干预可以产生令人满意的临床结果。
{"title":"Metastatic Renal Cell Carcinoma Detected by Postprandial Abdominal Pain: A Case Report.","authors":"Xinguang Wang, Nian Zhang, Shaowen Zeng","doi":"10.1002/cnr2.70490","DOIUrl":"https://doi.org/10.1002/cnr2.70490","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC), a prevalent malignancy in China, manifests annually in excess of 70 000 instances. At initial diagnosis, approximately one-tenth of these patients present with metastatic disease. The predominant sites for distant dissemination encompass pulmonary, osseous, hepatic, and adrenal regions, whereas gastric involvement remains exceedingly rare. We clinically characterized a case by postprandially abdominal discomfort, which was endoscopic-biopsy confirmed as a gastric tumor, and further diagnosis revealed the primary malignancy was kidney-originated.</p><p><strong>Case: </strong>A 68-year-old male was admitted to our hospital for the evaluation of persistent postprandial abdominal pain and diarrhea that had persisted for 1 month. Gastroscopy revealed a gastric body tumor, leading to the performance of an endoscopic submucosal dissection (ESD). The initial pathological examination identified the tumor as gastric malignancy of undetermined origin. Concurrently, a comprehensive abdominal CT scan detected an additional renal tumor. Subsequent radical nephrectomy of the right kidney was performed, and the pathology confirmed the renal cell carcinoma shared the same origin as the gastric lesion. Over a follow-up period of 38 months postoperatively, there has been no evidence of tumor recurrence or progression.</p><p><strong>Conclusion: </strong>Renal cell carcinoma has the potential to metastasize to the stomach, albeit this occurrence is not readily detectable in clinical practice unless it manifests as gastric symptoms. In instances where solitary superficial gastric metastasis is identified, aggressive surgical intervention can yield satisfactory clinical outcomes.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 2","pages":"e70490"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
WRAP53 is Downregulated in Acute Myeloid Leukemia Patients and Positively Correlates With HTERT Expression. WRAP53在急性髓系白血病患者中下调并与HTERT表达呈正相关。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-01 DOI: 10.1002/cnr2.70464
Renan Brito Gadelha, Beatriz Maria Dias Nogueira, Caio Bezerra Machado, Flávia Melo Cunha de Pinho Pessoa, Anna Karolyna da Costa Machado, Germison Silva Lopes, Paulo Henrique Silva Rodrigues, Henrique Girão Martins, Deivide de Sousa Oliveira, Rodrigo Monteiro Ribeiro, Ricardo Parente Garcia Vieira, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, André Salim Khayat, Caroline Aquino Moreira-Nunes

Background: Acute myeloid leukemia (AML) is a prevalent hematologic malignancy in adults, marked by clonal disorders in hematopoietic cells, rapid progression, and genetic heterogeneity. The WRAP53 gene, which is associated with genomic stability due to its involvement in activities, such as DNA repair, TP53 regulation, and association with telomerase (hTERT), was the focus of this study.

Aims: This study aimed to identify new potential molecular markers with prognostic value, based on specific targets, in order to contribute to a more accurate stratification of patients.

Methods and results: We assessed WRAP53 and hTERT expression in 110 AML patients classified according to World Health Organization (WHO) guidelines. Using real-time quantitative PCR, we investigated their expression and correlation with clinical outcome variables. WRAP53 expression was significantly decreased in AML patients compared to controls, whereas we did not detect differences in hTERT expression. Correlation analysis revealed a moderate positive relationship between WRAP53 and hTERT expression. Concerning the clinical parameters analyzed, significant differences were observed for WRAP53 in terms of sex and age, whereas for hTERT, no differences in the parameters analyzed were observed. Overall survival analysis did not reveal a significant difference for either WRAP53 or hTERT. The results presented demonstrate a downregulation of WRAP53 in the studied sample and that, furthermore, the expression of the WRAP53 and hTERT genes was correlated. In addition, the expression of hTERT, which is already indicated as a biomarker in AML, could not be correlated with the clinical characteristics analyzed in this study.

Conclusion: We also suggest that the low expression of WRAP53 may be associated with other mechanisms in AML, such as DNA repair, thus becoming a possible new promising molecular biomarker related to genomic stability in AML.

背景:急性髓系白血病(AML)是一种常见于成人的血液系统恶性肿瘤,其特点是造血细胞克隆性疾病、进展迅速和遗传异质性。WRAP53基因参与DNA修复、TP53调控和端粒酶(hTERT)等活动,与基因组稳定性相关,是本研究的重点。目的:本研究旨在基于特定靶点,识别具有预后价值的新的潜在分子标志物,从而有助于更准确地对患者进行分层。方法和结果:我们评估了110例按照世界卫生组织(WHO)指南分类的AML患者中WRAP53和hTERT的表达。利用实时定量PCR,我们研究了它们的表达及其与临床结果变量的相关性。与对照组相比,AML患者的WRAP53表达显著降低,而我们未检测到hTERT表达的差异。相关分析显示WRAP53与hTERT表达呈正相关。在分析的临床参数中,WRAP53在性别和年龄方面存在显著差异,而hTERT在分析的参数中没有差异。总体生存分析没有显示WRAP53或hTERT的显著差异。结果表明,WRAP53在研究样本中表达下调,并且WRAP53与hTERT基因表达相关。此外,hTERT作为AML的生物标志物,其表达与本研究分析的临床特征没有相关性。结论:WRAP53的低表达可能与AML的其他机制有关,如DNA修复,因此可能成为与AML基因组稳定性相关的新的有前景的分子生物标志物。
{"title":"WRAP53 is Downregulated in Acute Myeloid Leukemia Patients and Positively Correlates With HTERT Expression.","authors":"Renan Brito Gadelha, Beatriz Maria Dias Nogueira, Caio Bezerra Machado, Flávia Melo Cunha de Pinho Pessoa, Anna Karolyna da Costa Machado, Germison Silva Lopes, Paulo Henrique Silva Rodrigues, Henrique Girão Martins, Deivide de Sousa Oliveira, Rodrigo Monteiro Ribeiro, Ricardo Parente Garcia Vieira, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, André Salim Khayat, Caroline Aquino Moreira-Nunes","doi":"10.1002/cnr2.70464","DOIUrl":"https://doi.org/10.1002/cnr2.70464","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a prevalent hematologic malignancy in adults, marked by clonal disorders in hematopoietic cells, rapid progression, and genetic heterogeneity. The WRAP53 gene, which is associated with genomic stability due to its involvement in activities, such as DNA repair, TP53 regulation, and association with telomerase (hTERT), was the focus of this study.</p><p><strong>Aims: </strong>This study aimed to identify new potential molecular markers with prognostic value, based on specific targets, in order to contribute to a more accurate stratification of patients.</p><p><strong>Methods and results: </strong>We assessed WRAP53 and hTERT expression in 110 AML patients classified according to World Health Organization (WHO) guidelines. Using real-time quantitative PCR, we investigated their expression and correlation with clinical outcome variables. WRAP53 expression was significantly decreased in AML patients compared to controls, whereas we did not detect differences in hTERT expression. Correlation analysis revealed a moderate positive relationship between WRAP53 and hTERT expression. Concerning the clinical parameters analyzed, significant differences were observed for WRAP53 in terms of sex and age, whereas for hTERT, no differences in the parameters analyzed were observed. Overall survival analysis did not reveal a significant difference for either WRAP53 or hTERT. The results presented demonstrate a downregulation of WRAP53 in the studied sample and that, furthermore, the expression of the WRAP53 and hTERT genes was correlated. In addition, the expression of hTERT, which is already indicated as a biomarker in AML, could not be correlated with the clinical characteristics analyzed in this study.</p><p><strong>Conclusion: </strong>We also suggest that the low expression of WRAP53 may be associated with other mechanisms in AML, such as DNA repair, thus becoming a possible new promising molecular biomarker related to genomic stability in AML.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 2","pages":"e70464"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insufficient Expression of the Autophagic Protein ATG16L1 Results in Accelerated Carcinogenesis Related to an Aberrant B Cell Response. 自噬蛋白ATG16L1表达不足导致与异常B细胞反应相关的加速癌变。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-02-01 DOI: 10.1002/cnr2.70438
Daniela Mendiola, Betsaida Ortiz, Oscar Nieto, Marisol I González, Danielle Vannan, Bertus Eksteen, Alejandro Martínez, Diego Mateos, Mónica G Mendoza-Rodríguez, Miriam Rodríguez-Sosa, Luis I Terrazas, José L Reyes

Background: Autophagy-related proteins (ATGs) regulate a great variety of cellular responses beyond autophagy. In cancer, the role of ATG proteins is central, as evidenced in spontaneous cancer emerging in animals lacking ATG proteins.

Aim: To determine whether ATG16L1 may be participating in tumorigenesis in colonic and oral mucosa and its likely association with adaptive immune cell deregulation (e.g., B cells).

Methods: Wild-type (WT) and ATG16L1 hypomorphic mice (ATG16L1HM) were induced with colitis-associated colon cancer (CAC) by delivering azoxymethane (AOM) and dextran sodium sulfate (DSS), whereas oral cancer was generated by administering 4-nitroquinoline-1-oxide (4NQO) in tap water. Tissue samples were collected and the histopathological damage was assessed. Also, secondary lymphoid organs (i.e., spleen and draining lymph nodes) were assayed for cytokine output and lymphocyte distribution by means of flow cytometry, and IgG levels were assayed in plasma samples.

Results: ATG16L1HM animals turned out to be more susceptible to colon and oral carcinogenesis than WT mice. In CAC, WT mice preserved colon length and presented individual colonic tumors, whereas ATG16L1HM mice presented shortened colons and tumor masses. Likewise, WT mice exhibited oral leukoplakia (pre-neoplastic lesions), whereas ATG16L1HM mice showed tumors. The greater susceptibility observed in ATG16L1HM animals was associated with imbalanced cytokine production (increased IL-4 levels and lower IL-15 output) and higher numbers of B cells in secondary lymphoid organs. This latter was also found under steady conditions, and despite having more B cells, cancer-induced ATG16L1HM mice presented lower levels of total circulating IgG.

Conclusion: Suboptimal expression of the autophagic protein ATG16L1 results in accelerated carcinogenesis, and an altered B cell response may be one of the aggravating factors.

背景:自噬相关蛋白(autophagy -related protein, ATGs)在自噬之外调节多种细胞反应。在癌症中,ATG蛋白的作用是中心的,这在缺乏ATG蛋白的动物中出现的自发性癌症中得到了证明。目的:确定ATG16L1是否可能参与结肠和口腔粘膜的肿瘤发生及其与适应性免疫细胞(如B细胞)失调的可能关联。方法:用偶氮氧甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导野生型(WT)和ATG16L1半形成型(ATG16L1)小鼠结肠炎相关结肠癌(CAC),用自来水中4-硝基喹啉-1-氧化物(4NQO)诱导口腔癌。收集组织样本,评估组织病理学损伤。此外,通过流式细胞术检测次级淋巴器官(即脾脏和引流淋巴结)的细胞因子输出和淋巴细胞分布,并检测血浆样品中的IgG水平。结果:ATG16L1HM小鼠比WT小鼠更容易发生结肠癌和口腔癌。在CAC中,WT小鼠保留了结肠长度并呈现单个结肠肿瘤,而ATG16L1HM小鼠呈现缩短的结肠和肿瘤团块。同样,WT小鼠表现为口腔白斑(肿瘤前病变),而ATG16L1HM小鼠表现为肿瘤。在ATG16L1HM动物中观察到的更大的易感性与细胞因子产生不平衡(IL-4水平升高和IL-15输出降低)和次级淋巴器官中B细胞数量增加有关。后者在稳定的条件下也被发现,尽管有更多的B细胞,癌症诱导的ATG16L1HM小鼠的总循环IgG水平较低。结论:自噬蛋白ATG16L1的次优表达导致癌变加速,B细胞反应的改变可能是加重因素之一。
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引用次数: 0
Perceived Benefits and Barriers of Breast Self-Examination and Mammography for Breast Cancer Screening in the PERSIAN Guilan Cohort Study (PGCS) Population 在波斯桂兰队列研究(PGCS)人群中,乳房自我检查和乳房x光检查用于乳腺癌筛查的益处和障碍
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-01-29 DOI: 10.1002/cnr2.70459
Farahnaz Joukar, Sara Zakaryapour, Fateme Sheida, Faezeh Fashkhami, Zahra Atrkar-Roshan, Farideh Hasavari, Fariborz Mansour-Ghanaei
<div> <section> <h3> Background</h3> <p>Breast examination and mammography help in the detection of breast cancer and are valid in improving survival by reducing mortality.</p> </section> <section> <h3> Aims</h3> <p>In this study, we aimed to investigate women's knowledge of breast cancer screening in the Prospective Epidemiological Research Studies (PERSIAN) Guilan Cohort Study (PGCS) population.</p> </section> <section> <h3> Methods and Results</h3> <p>This cross-sectional study was conducted on 476 women aged 35–70 among the PGCS population. The demographic and clinical data of participants were collected through a questionnaire. Also, the Champion Health Belief Model Scale, including the perceived benefits of breast self-examination (six phrases), perceived barriers to breast self-examination (nine phrases), perceived benefits of mammography (six phrases), and perceived barriers to mammography (nine phrases), was used to collect the knowledge data. The variables of the questionnaire were assessed using the Likert scale. Data were analyzed using SPSS version 20 by significant level < 0.05.</p> </section> <section> <h3> Results</h3> <p>Most of the research subjects were within the age of 45–55 years (35.9%) and most of them (64.9%) did not mention any history of prior mammography, but among those with positive history of mammography, most of them (55.1%) had done it without any problem and only based on recommendation. The average scores of benefits and barriers for breast self-examination among the participants were 9.9 ± 3.7 and 15.2 ± 4.6, respectively. Similarly, for mammography, the average scores were 9.9 ± 3.6 and 14.2 ± 4.7. In overall, factors including age 35–45 years, having insurance, higher education levels, having former visit of a doctor due to breast problem, family history of breast cancer in first degree relatives, and positive history of performing mammography were associated with better scores of perceived benefits and barriers in both breast self-examination and mammography (<i>p</i> ≤ 0.05).</p> </section> <section> <h3> Conclusion</h3> <p>According to the barriers and benefits identified in this study, it is possible and also necessary to plan for breast cancer screening with organized regional educational plans. It is recommended to focus more on attracting older women to perform screening programs. It is also necessary to encourage doctors to refer women for mammography and support insurance organizations to provide sc
背景:乳房检查和乳房x光检查有助于发现乳腺癌,并有效地通过降低死亡率来提高生存率。目的:在本研究中,我们旨在调查前瞻性流行病学研究(波斯)桂兰队列研究(PGCS)人群中女性乳腺癌筛查知识的情况。方法和结果:这项横断面研究对476名年龄在35-70岁的PGCS人群进行了研究。通过问卷调查收集参与者的人口学和临床数据。采用冠军健康信念模型量表,包括乳房自我检查的感知益处(6个短语)、乳房自我检查的感知障碍(9个短语)、乳房x光检查的感知益处(6个短语)和乳房x光检查的感知障碍(9个短语)来收集知识数据。问卷变量采用李克特量表进行评估。结果:大多数研究对象年龄在45-55岁之间(35.9%),其中大多数(64.9%)没有提及任何既往乳房x光检查史,但在有乳房x光检查阳性史的人中,大多数(55.1%)没有任何问题,只是根据推荐进行了检查。参与者对乳房自我检查的益处和障碍的平均得分分别为9.9±3.7分和15.2±4.6分。乳房x光检查的平均评分分别为9.9±3.6分和14.2±4.7分。总体而言,年龄35-45岁、有保险、受教育程度较高、曾因乳房问题就诊、一级亲属有乳腺癌家族史、积极的乳房x光检查史等因素与乳房自我检查和乳房x光检查的获益和障碍得分较高相关(p≤0.05)。结论:根据本研究发现的障碍和益处,通过有组织的区域教育计划来规划乳腺癌筛查是可能的,也是必要的。建议更多地关注吸引老年妇女进行筛查项目。鼓励医生推荐妇女进行乳房x光检查,并支持保险机构以较低的成本提供筛查服务也是必要的。
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引用次数: 0
A Case Report of Promising Response to Combination Therapy With an Immune Checkpoint Inhibitor (Pembrolizumab) and Multi-Targeted Tyrosine Kinase Inhibitor (Pazopanib) in Metastatic De-Differentiated Chondrosarcoma 免疫检查点抑制剂(Pembrolizumab)和多靶向酪氨酸激酶抑制剂(Pazopanib)联合治疗转移性去分化软骨肉瘤的病例报告
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-01-29 DOI: 10.1002/cnr2.70426
Matthew Youssef, Peter Grimison

Background

We present the case of 72–year-old male with metastatic de-differentiated chondrosarcoma (“DDCS”). DDCS is a rare soft tissue cancer that carries a dismal prognosis in the metastatic stage, and is resistant to both traditional chemotherapy and radiotherapy. There is a distinct lack of proven systemic therapies.

Case

This case report is distinguished in that our patient had a significant clinical response to combination therapy with an immune checkpoint inhibitor (Pembrolizumab) and a multi-targeted tyrosine kinase inhibitor (Pazopanib). Our patient presented with bony pain after suffering a pathological fracture of the left humerus after grabbing a fence. He did not report prior constitutional symptoms or bony pain. On examination he was clinically in atrial fibrillation and reported reduced exercise tolerance with a New York Heart association grading of 2. There were no other pertinent clinical findings. FDG PET-CT scan revealed a 10cmx5cm destructive intra-osseous lesion of the proximal humerus, markedly FDG-avid, without evidence of metastatic disease. He underwent immediate surgical resection, followed by adjuvant radiotherapy to the left humerus. Tumour histology revealed a high-grade DDCS. Genetic sequencing revealed alterations in IDH2, PTCH1 and TERT promoter. Restaging FDG PET scan 3 months after diagnosis revealed lung metastases. The patient was commenced on Vismodegib with best disease response of progressive disease. Eight months after diagnosis he was commenced on combination therapy of Pazopanib and Pembrolizumab, with significant reduction in size of lung metastases. He sustained a progression free period of 6 months on this regime. Treatment course was complicated primarily by hepatotoxicity, which resolved with dose reduction of Pazopanib. Eleven months after diagnosis, FDG PET-CT revealed relapse and significant progression of metastatic disease and systemic therapy was ceased. The patient passed away 14 months after diagnosis.

Conclusion

This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.

背景:我们报告一例72岁男性转移性去分化软骨肉瘤(“DDCS”)。DDCS是一种罕见的软组织癌,在转移期预后不佳,对传统的化疗和放疗都有耐药性。明显缺乏经证实的系统性治疗方法。病例:该病例报告的独特之处在于,我们的患者对免疫检查点抑制剂(Pembrolizumab)和多靶点酪氨酸激酶抑制剂(Pazopanib)联合治疗有显著的临床反应。我们的病人在抓住栅栏后出现左肱骨病理性骨折后出现骨痛。他没有报告先前的体质症状或骨痛。经检查,他临床表现为房颤,运动耐量降低,纽约心脏协会分级为2级。没有其他相关的临床发现。FDG PET-CT扫描显示肱骨近端10cmx5cm破坏性骨内病变,明显FDG-avid,无转移性疾病证据。他立即接受手术切除,随后对左肱骨进行辅助放疗。肿瘤组织学显示高级别DDCS。基因测序显示IDH2、PTCH1和TERT启动子发生改变。诊断后3个月的FDG PET扫描显示肺转移。患者开始服用维莫德吉,病情进展时疾病反应最佳。确诊后8个月,他开始接受Pazopanib和Pembrolizumab的联合治疗,肺转移灶的大小显著减少。在这种疗法下,他维持了6个月的无进展期。治疗过程主要以肝毒性为主,随着帕唑帕尼剂量的减少而缓解。诊断后11个月,FDG PET-CT显示复发和转移性疾病的显著进展,并停止全身治疗。患者在确诊后14个月去世。结论:该病例报告是一个有希望的新兴系统性治疗晚期DDCS的有价值的例子,目前的治疗标准缺乏有效的治疗方案。
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引用次数: 0
Breast Cancer–Specific Survival and Prognostic Factors in a Statewide Oncology Network in Brazil: A Registry-Linked Retrospective Cohort Study 巴西全州肿瘤网络中的乳腺癌特异性生存和预后因素:一项登记相关的回顾性队列研究。
IF 1.9 Q4 ONCOLOGY Pub Date : 2026-01-29 DOI: 10.1002/cnr2.70467
Raphael Manhães Pessanha, Wesley Rocha Grippa, Luiz Cláudio Barreto Silva Neto, Naira Santos D'Agostini, Luís Carlos Lopes-Júnior

Background

Breast cancer survival varies widely across middle-income settings and may be influenced by clinical stage at diagnosis and access pathways within oncology care networks. In Brazil, evidence from statewide cohorts using linked registry and mortality data remains limited.

Aim

To investigate the association between clinical factors and breast cancer–specific survival among women treated in all hospitals comprising the Oncology Care Network of a state in Southeastern Brazil.

Methods and Results

A retrospective cohort study was conducted using data from the Hospital Cancer Registry linked to the state Mortality Information System. Women aged ≥ 18 years diagnosed with primary breast cancer (ICD-10: C50.x) between 2000 and 2016 were included and followed until December 31, 2021. Five-year breast cancer–specific survival was estimated using the Kaplan–Meier method, and factors associated with mortality were assessed using cause-specific Cox proportional hazards models with complete-case analysis. A total of 12,096 women were included, of whom 7,191 had complete data for multivariable analysis. The mean age at diagnosis was 54.7 years. Five-year breast cancer–specific survival ranged from 97% (95% CI: 96−97%) in stage I to 32% (95% CI: 31−37%) in stage IV. Women referred from the private healthcare system had a significantly lower risk of breast cancer mortality than those referred from the public system (HR: 0.83; 95% CI: 0.75−0.93; p = 0.001). Advanced clinical stage remained the strongest predictor of mortality, and the presence of distant metastasis at diagnosis increased the risk of breast cancer death by 49% (HR: 1.49; 95% CI: 1.14−1.94; p = 0.003).

Conclusion

Breast cancer–specific survival in Espírito Santo is strongly determined by stage at diagnosis and by differential access pathways within the oncology care network. Strengthening early diagnostic strategies, improving referral coordination, and ensuring equitable access to timely treatment are essential to reduce survival disparities in this setting.

背景:乳腺癌生存率在中等收入环境中差异很大,可能受到诊断时的临床阶段和肿瘤护理网络中的获取途径的影响。在巴西,使用关联登记和死亡率数据的全州队列的证据仍然有限。目的:研究巴西东南部某州肿瘤护理网络所有医院中接受治疗的妇女的临床因素与乳腺癌特异性生存率之间的关系。方法和结果:采用与州死亡率信息系统相关的医院癌症登记处的数据进行回顾性队列研究。年龄≥18岁诊断为原发性乳腺癌的女性(ICD-10: C50)。包括2000年至2016年期间的x),并一直跟踪到2021年12月31日。使用Kaplan-Meier法估计5年乳腺癌特异性生存率,使用病因特异性Cox比例风险模型评估与死亡率相关的因素,并进行全病例分析。共纳入12096名妇女,其中7191名具有完整的多变量分析数据。平均诊断年龄为54.7岁。5年乳腺癌特异性生存率从I期的97% (95% CI: 96-97%)到IV期的32% (95% CI: 31-37%)不等。从私人医疗保健系统转介的妇女乳腺癌死亡风险明显低于从公共系统转介的妇女(HR: 0.83; 95% CI: 0.75-0.93; p = 0.001)。晚期临床阶段仍然是死亡率的最强预测因子,诊断时远处转移的存在使乳腺癌死亡风险增加49% (HR: 1.49; 95% CI: 1.14-1.94; p = 0.003)。结论:Espírito Santo的乳腺癌特异性生存率在很大程度上取决于诊断阶段和肿瘤护理网络内的不同通路。加强早期诊断战略,改善转诊协调,确保公平获得及时治疗,对于减少这种情况下的生存差异至关重要。
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