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Conservative Resolution of a Vesicovaginal Fistula Including Laser Therapy in a Patient Who Underwent Recurrent Surgery After Prior Radiotherapy for Endometrial Cancer. 通过激光疗法保守治疗子宫内膜癌放疗后复发手术患者的膀胱阴道瘘
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1002/cnr2.70056
Alessandro Buda, Jessica Mauro, Francesco Varvello, Jacopo Antolini, Giuseppe Di Guardia, Enrica Bar, Federica Filipello, Rodolfo Milani

Background: Isolated vaginal vault recurrence of endometrial cancer can be treated with rescue radiotherapy. However, in previously irradiated patients, surgical resection can be considered the treatment of choice. Vesicovaginal fistulas (VVFs) sometimes complicate the surgical intervention because of the presence of massive ischemia and fibrosis of pelvic tissue from previous irradiation. Traditional strategies for the treatment of VVFs include endoscopic treatment (when feasible) or a laparoscopic, robotic, or open abdominal approach in some experiences through a transvesical route. The last approach can be associated with long inpatient hospital stays, postoperative complications, and failure, especially in obese patients. Our report proposes a conservative approach with prolonged catheterization and placement of nephrostomy tubes to treat a VVF with laser therapy of the fistula.

Case: We present the case of a woman with a second relapse of endometrial cancer at the level of the vaginal vault, after a hysterectomy and then radiotherapy for a first relapse, who underwent robotic partial colpectomy, with an intraoperative bladder lesion, which was repaired with interrupted stitches. However, the patient developed a vesicovaginal fistula. A conservative approach was initially undertaken as an alternative to the surgical repair of the fistula. After the clinical and radiological confirmation of the fistula andconsidering the patient's clinical condition, the multidisciplinary team proposed a conservative management of the fistula as an alternative to fistula surgical repair. Bladder catheter Ch 20 and bilateral nephrostomy did not completely resolve the fistula, with a minor residual linkage between the bladder and the vaginal vault after 8 months from the robotic surgery. A single/month diode laser application for 3 months was added to the conservative treatment. Cystography was negative at the end of laser sessions, and both nephrostomies were removed 1 week later. After 6 months, clinical and radiological follow-up was negative, and no further vaginal urine loss was recorded.

Conclusion: We believe that conservative management of a complex vesicovaginal fistula after multiple treatments for endometrial cancer is possible. In this scenario, laser therapy can be a valuable clinical tool to improve the outcome, with reduced invasiveness for the patient.

背景:子宫内膜癌孤立的阴道穹隆复发可通过抢救性放疗来治疗。然而,对于曾接受过放射治疗的患者,手术切除可被视为首选治疗方法。膀胱阴道瘘(VVF)有时会使手术治疗变得复杂,因为盆腔组织会因之前的放射治疗而大量缺血和纤维化。治疗膀胱阴道瘘的传统策略包括内窥镜治疗(如可行)或腹腔镜、机器人或经膀胱途径开腹手术。最后一种方法可能会导致住院时间过长、术后并发症和手术失败,尤其是肥胖患者。我们的报告提出了一种保守的方法,即通过长时间的导尿和放置肾造瘘管来治疗 VVF,并对瘘管进行激光治疗:我们报告的病例是一名子宫内膜癌在阴道穹隆水平第二次复发的妇女,她在第一次复发后接受了子宫切除术和放疗,并接受了机器人部分结肠切除术,术中出现膀胱病变,经间断缝合修复。然而,患者出现了膀胱阴道瘘。作为手术修补瘘管的替代方案,起初采取了保守疗法。经临床和放射学检查确认为瘘管后,考虑到患者的临床状况,多学科团队建议对瘘管进行保守治疗,以替代瘘管手术修补。膀胱导尿管 Ch 20 和双侧肾造瘘术并未彻底解决瘘管问题,机器人手术 8 个月后,膀胱和阴道穹隆之间仍有轻微的残留连接。在保守治疗的基础上,患者又接受了为期 3 个月的单次/月二极管激光治疗。激光治疗结束后,膀胱造影结果为阴性,一周后,两个肾造口均被移除。6 个月后,临床和放射学随访结果均为阴性,且未再出现阴道遗尿:我们认为,保守治疗子宫内膜癌多次治疗后的复杂性膀胱阴道瘘是可行的。在这种情况下,激光疗法可以作为一种有价值的临床工具来改善治疗效果,同时减少对患者的创伤。
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引用次数: 0
Immunotherapy-Induced Type 1 Diabetes Mellitus Causing Diabetic Ketoacidosis: A Case Report and Review of Current Guidelines. 免疫疗法诱发 1 型糖尿病导致糖尿病酮症酸中毒:病例报告和现行指南回顾。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1002/cnr2.70058
Patrick Disterhaft, Caleb Kerr, Daniel Barnett, Moti Salloum

Background: Immune checkpoint inhibitors (ICIs) are becoming more frequently used in the treatment of many types of malignant cancers by disinhibiting T-cell activation, which promotes the destruction of cancer cells. This disinhibition can also result in autoimmune conditions, like endocrinopathies.

Case: We report a case of a 78-year-old male patient with malignant mesothelioma treated with combination ICI therapy who presented with diabetic ketoacidosis (DKA) with no history of diabetes mellitus or hyperglycemia. The patient was admitted to the intensive care unit and treated with intravenous (IV) fluid repletion and IV insulin for DKA. The patient was diagnosed with new-onset type 1 diabetes mellitus (T1DM) induced by ICI therapy.

Discussion: Approximately 75% of patients diagnosed with ICI-induced T1DM initially present with DKA. This, along with the rapid onset of hyperglycemia in this patient, suggests current guidelines for monitoring blood glucose are inadequate. Current guidelines recommend monitoring blood glucose at the following times: baseline, at the initiation of each cycle for 12 weeks, and then every 3-6 weeks thereafter. We propose the following schedule for monitoring blood glucose in patients receiving ICI therapy: baseline, twice weekly for the first six cycles, and then once weekly thereafter. This proposed update is supported by our patient's rapid onset of hyperglycemia and other case reports and reviews showing that most patients with this diagnosis have an initial presentation of DKA. Detecting hyperglycemia and starting treatment early is important in the prevention of acute complications from uncontrolled T1DM, like DKA.

Conclusion: This case adds to the existing body of literature and provides support for more frequent monitoring of blood glucose in patients receiving ICI therapy. Blood glucose monitoring is a simple, reliable, low risk, and inexpensive laboratory test that should be used in patients receiving ICI therapy to ensure prompt diagnosis and treatment of T1DM.

背景:免疫检查点抑制剂(ICIs)通过抑制T细胞活化来促进癌细胞的破坏,因此越来越多地被用于多种恶性癌症的治疗。这种抑制也可能导致自身免疫疾病,如内分泌病:我们报告了一例接受 ICI 综合疗法治疗的 78 岁男性恶性间皮瘤患者,患者出现糖尿病酮症酸中毒(DKA),但无糖尿病或高血糖病史。患者被送入重症监护室,接受了静脉补液和静脉注射胰岛素治疗 DKA。患者被诊断为 ICI 治疗诱发的新发 1 型糖尿病(T1DM):讨论:约 75% 被诊断为 ICI 诱导的 T1DM 患者最初会出现 DKA。这一点以及该患者迅速出现的高血糖表明,目前的血糖监测指南并不完善。目前的指南建议在以下时间监测血糖:基线、每个周期开始时,持续 12 周,之后每 3-6 周监测一次。我们建议在以下时间监测接受 ICI 治疗患者的血糖:基线,前六个周期每周两次,此后每周一次。我们的患者迅速出现高血糖,而其他病例报告和综述显示,大多数确诊患者最初表现为 DKA,这些都为我们的更新建议提供了支持。发现高血糖并及早开始治疗,对于预防未得到控制的 T1DM 引起的急性并发症(如 DKA)非常重要:本病例补充了现有文献,为更频繁地监测接受 ICI 治疗患者的血糖提供了支持。血糖监测是一种简单、可靠、低风险和廉价的实验室检测方法,应在接受 ICI 治疗的患者中使用,以确保及时诊断和治疗 T1DM。
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引用次数: 0
Outcomes of Cancer Patients Affected by COVID-19 in Different Settings: A Retrospective Study in Lebanon. 不同环境下受 COVID-19 影响的癌症患者的预后:黎巴嫩的一项回顾性研究
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1002/cnr2.70045
Ahmad El Mahmoud, Elie Jean Karam, Reine Abou Zeidane, Wafaa Khaled, Youssef Zougheib, Joe David Azzo, Hussein El Jebbawi, Ali Atoui, Razan Mohty, Tasnim Diab, Iman Abou Dalle, Maya Charafeddine, Hazem I Assi

Background: The diverse presentation of COVID-19 symptoms and outcomes has revealed a significant gap in understanding the specific risk factors and characteristics of the virus among immunocompromised cancer patients, particularly in the Middle East.

Aims: We our study aimed to address this gap by investigating the characteristics and outcomes of COVID-19 in cancer patients compared to non-cancer patients.

Methods and results: We carried out a retrospective analysis, collecting demographic, oncologic, and COVID-19-related data from electronic medical records of 248 patients admitted to our tertiary care center in Lebanon. Statistical analysis was conducted using SPSS to identify patterns. Patients with solid tumors were 3.433 times more likely to die than those who were cancer-free (p = 0.012). Moreover, patients with advancing disease were 2.805 times more likely to be admitted to the ICU (p = 0.03) and 14.7 times more likely to die (p < 0.001) compared with those in remission.

Conclusion: Our findings emphasize the critical need for tailored preventive measures and specialized care for immunocompromised cancer patients, given their heightened vulnerability to severe COVID-19 outcomes. These insights contribute to the development of specific strategies aimed at enhancing the protection and clinical management of this high-risk group.

背景:COVID-19的症状和预后表现多种多样,这表明在了解免疫力低下的癌症患者(尤其是中东地区的癌症患者)的特定风险因素和病毒特征方面存在巨大差距。研究目的:我们的研究旨在通过调查癌症患者与非癌症患者相比的COVID-19特征和预后来弥补这一差距:我们进行了一项回顾性分析,从黎巴嫩三级医疗中心收治的 248 名患者的电子病历中收集了人口统计学、肿瘤学和 COVID-19 相关数据。我们使用 SPSS 进行了统计分析,以找出其中的规律。实体瘤患者的死亡几率是无癌症患者的 3.433 倍(P = 0.012)。此外,病情恶化的患者住进重症监护室的几率是普通患者的 2.805 倍(p = 0.03),死亡几率是普通患者的 14.7 倍(p 结论:我们的研究结果表明,治疗肿瘤的关键在于对患者的健康状况进行评估:我们的研究结果表明,由于免疫力低下的癌症患者更容易出现严重的 COVID-19 结果,因此亟需为他们提供量身定制的预防措施和专门护理。这些见解有助于制定具体策略,以加强对这一高风险人群的保护和临床管理。
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引用次数: 0
Secondary Osteosarcoma After Carbon-Ion Radiotherapy for Desmoid-Type Fibromatosis: A Case Report. 蜕膜型纤维瘤症碳离子放疗后的继发性骨肉瘤:病例报告。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1002/cnr2.70062
Mizuki Aketo, Makoto Emori, Kohichi Takada, Kazuyuki Murase, Yohei Arihara, Junya Shimizu, Yasutaka Murahashi, Masahiko Okamoto, Shintaro Sugita, Atsushi Teramoto

Background: Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid-type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern.

Case: We present a case of secondary osteosarcoma after carbon-ion radiation therapy (CIRT). A 31-year-old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid-type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery.

Conclusions: In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy.

背景:放疗被认为是治疗无法切除或对药物有抗药性的类脂膜型纤维瘤病的一种替代疗法。虽然放疗能取得相对较好的局部控制效果,但继发恶性肿瘤的风险仍然令人担忧:我们介绍了一例碳离子放射治疗(CIRT)后继发骨肉瘤的病例。一名 31 岁的男性患者因左大腿疼痛就诊。肿瘤位于左侧臀大肌和臀中肌之间,并延伸至阔筋膜和股二头肌。针刺活检后,诊断为类脂样纤维瘤病。患者接受了多种药物治疗,包括环氧化酶 2 抑制剂和他莫昔芬,但左大腿疼痛并未改善。确诊 1 年后,他接受了 CIRT 治疗(67.2 Gy [相对生物有效性] 16fr/4wks)。8 年后,他患上了左股骨骨肉瘤。他接受了化疗和肿瘤切除术,并切除了左侧髋关节。明确手术后 6 个月和 17 个月发现肺转移瘤,并采用转移瘤切除术进行了切除。然而,他在明确手术后 29 个月因多发性肺转移复发而死亡:在这个病例中,我们认为股骨的低放射剂量可能导致了继发性恶性肿瘤。
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引用次数: 0
Development of a Serum Metabolome-Based Test for Early-Stage Detection of Multiple Cancers. 开发基于血清代谢组的多种癌症早期检测试剂盒。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1002/cnr2.70042
Rajnish Nagarkar, Mamillapalli Gopichand, Suparna Kanti Pal, Ankur Gupta, Najmuddin Md Saquib, Ahmad Ahmad, Ganga Sagar, Kanury V S Rao, Zaved Siddiqui, Imliwati Longkumer

Background: Detection of cancer at the early stage currently offers the only viable strategy for reducing disease-related morbidity and mortality. Various approaches for multi-cancer early detection are being explored, which largely rely on capturing signals from circulating analytes shed by tumors into the blood. The fact that biomarker concentrations are limiting in the early stages of cancer, however, compromises the accuracy of these tests. We, therefore, adopted an alternate approach that involved interrogation of the serum metabolome with machine learning-based data analytics. Here, we monitored for modulations in metabolite patterns that correlated with the presence or absence of cancer. Results obtained confirmed the efficacy of this approach by demonstrating that it could detect a total of 15 cancers in women with an average accuracy of about 99%.

Aims: To further increase the scope of our test, we conducted an investigator-initiated clinical trial involving a total of 6445 study participants, which included both cancer patients and non-cancer volunteers. Our goal here was to maximize the number of cancers that could be detected, while also covering cancers in both females and males.

Methods and results: Metabolites extracted from individual serum samples were profiled by ultra-performance liquid chromatography coupled to a high-resolution mass spectrometer using an untargeted protocol. After processing, the data were analyzed by our cancer detection machine-learning algorithm to differentiate cancer from non-cancer samples. Results revealed that our test platform could indeed detect a total of 30 cancers, covering both females and males, with an average accuracy of ~98%. Importantly, the high detection accuracy remained invariant across all four stages of the cancers.

Conclusion: Thus, our approach of integrating untargeted metabolomics with machine learning-powered data analytics offers a powerful strategy for early-stage multi-cancer detection with high accuracy.

Trial registration: Registration No: CTRI/2023/03/050316.

背景:目前,早期检测癌症是降低疾病相关发病率和死亡率的唯一可行策略。目前正在探索多种癌症早期检测方法,这些方法主要依靠捕捉肿瘤脱落到血液中的循环分析物信号。然而,在癌症的早期阶段,生物标记物的浓度是有限的,这就影响了这些检测方法的准确性。因此,我们采用了另一种方法,即通过基于机器学习的数据分析来检测血清代谢组。在这里,我们监测了与癌症存在与否相关的代谢物模式变化。目的:为了进一步扩大测试范围,我们开展了一项由研究人员发起的临床试验,共有 6445 名研究人员参与,其中包括癌症患者和非癌症志愿者。我们的目标是最大限度地增加可检测到的癌症数量,同时涵盖女性和男性癌症:从单个血清样本中提取的代谢物通过超高效液相色谱法和高分辨率质谱仪进行分析。处理后的数据由我们的癌症检测机器学习算法进行分析,以区分癌症和非癌症样本。结果显示,我们的测试平台确实能检测出 30 种癌症,涵盖女性和男性,平均准确率约为 98%。重要的是,高检测准确率在癌症的四个阶段都保持不变:因此,我们将非靶向代谢组学与机器学习驱动的数据分析相结合的方法为早期多发性癌症的高精度检测提供了一种强大的策略:注册号:CTRI/2023/03/050316。
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引用次数: 0
Hodgkin Lymphoma Presenting as Pel-Ebstein Fever: A Case Report. 表现为 Pel-Ebstein 热的霍奇金淋巴瘤:病例报告。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1002/cnr2.70039
Ujjawal Kumar Shriwastav, Deepak Sundriyal, Parmod Kumar, Amit Sehrawat

Background: Prolonged fever of more than a year duration can be a symptom of underlying malignancy. This article appreciates the need for diligent history taking and carefully performed clinical examination, which is fundamental to reaching an initial diagnosis.

Case: We report the case of a middle-aged male who presented to us with a fever of more than a year duration. The patient's residence was located in a remote area where the nearby tertiary care center was almost 250 km away. He was empirically treated with antibiotics without any success by local physicians. After more than a year, he reported to us and was diagnosed with Hodgkin lymphoma with a characteristic Pel-Ebstein pattern of fever missed earlier by the local physicians. His fever resolved within 5 days of chemotherapy, and he achieved complete remission.

Conclusion: Meticulous history-taking and clinical examination are essential for reaching a clinical diagnosis. Malignant causes should be considered in the differentials of prolonged fever.

背景:持续一年以上的长期发热可能是潜在恶性肿瘤的症状。这篇文章强调了认真采集病史和仔细进行临床检查的必要性,这是初步诊断的基础:我们报告了一例中年男性患者的病例。患者的住所位于偏远地区,附近的三级医疗中心距离此地将近 250 公里。当地医生对他进行了经验性抗生素治疗,但效果不佳。一年多后,他向我们报告,被诊断为霍奇金淋巴瘤,并伴有当地医生之前漏诊的特征性 Pel-Ebstein 发烧模式。他在接受化疗后 5 天内退烧,病情完全缓解:结论:缜密的病史采集和临床检查对临床诊断至关重要。结论:仔细询问病史和临床检查对临床诊断至关重要,在鉴别长期发热时应考虑恶性病因。
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引用次数: 0
Assessing the Concordance of Clinical and Pathological Diagnoses in Basal Cell Carcinoma Among the Iranian Population: A Cross-Sectional Analysis of 229 Cases 评估伊朗人基底细胞癌临床诊断与病理诊断的一致性:对 229 例病例的横断面分析。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1002/cnr2.70040
Fatemeh Farshad, Elham Behrangi, Alireza Jafarzadeh, Masoumeh Roohaninasab, Nasrin Shayanfar, Zeinab Aryanian, Parvaneh Hatami, Azadeh Goodarzi

Background

Nonmelanoma skin cancer (NMSC) is the most prevalent malignancy globally, with basal cell carcinoma (BCC) being the most common type.

Aims

This study aims to evaluate the concordance between clinical and pathological diagnoses of BCC, emphasizing the importance of early detection.

Methods and Results

In this cross-sectional study, we conducted a retrospective review of clinical and pathological records for 229 patients diagnosed with BCC between 2020 and 2024. The analysis focused on gender, age, lesion location, and diagnostic accuracy. Among the 229 patients, 193 were men (84.3%), and 131 (57.2%) had recorded clinical diagnoses. The mean age of diagnosed patients was 67.72 years. Lesions were primarily located on the scalp (29.5%), face (26.4%), and nose (13.9%). Of the pathological evaluations, 184 cases (80.3%) confirmed BCC, while 45 cases had alternative diagnoses. Notably, 94.6% of clinically diagnosed patients were suspected to have BCC by their physicians. A significant portion of cases (42%) lacked prior clinical diagnoses, reflecting a potential gap in education among nondermatologists regarding BCC recognition.

Conclusion

The study found high concordance between clinical and pathological diagnoses of BCC, underscoring the need for improved clinical assessment skills among healthcare providers. Collaboration with dermatologists is essential for accurate diagnosis and improved patient outcomes. Enhanced training in recognizing BCC symptoms is recommended to address the identified gaps in clinical suspicion.

背景:非黑色素瘤皮肤癌(NMSC)是全球发病率最高的恶性肿瘤,其中基底细胞癌(BCC)是最常见的类型。目的:本研究旨在评估BCC临床诊断和病理诊断之间的一致性,强调早期检测的重要性:在这项横断面研究中,我们对2020年至2024年间确诊为BCC的229名患者的临床和病理记录进行了回顾性审查。分析的重点是性别、年龄、病变位置和诊断准确性。在这 229 名患者中,193 人为男性(84.3%),131 人(57.2%)有临床诊断记录。确诊患者的平均年龄为 67.72 岁。病变主要位于头皮(29.5%)、面部(26.4%)和鼻部(13.9%)。在病理评估中,184 例(80.3%)确诊为 BCC,45 例为其他诊断。值得注意的是,94.6%的临床诊断患者被其医生怀疑患有 BCC。相当一部分病例(42%)之前没有临床诊断,这反映出非皮肤科医生在BCC识别教育方面可能存在差距:研究发现,BCC 的临床诊断和病理诊断之间的一致性很高,这说明医疗服务提供者需要提高临床评估技能。与皮肤科医生合作对于准确诊断和改善患者预后至关重要。建议加强识别 BCC 症状的培训,以弥补临床怀疑方面的不足。
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引用次数: 0
JAK Inhibitor Upadacitinib Induces Remission in Refractory Immune-Related Colitis Triggered by CTLA-4 and PD-1 Inhibitor Combination Therapy in Malignant Pleural Mesothelioma: A Case Report JAK抑制剂乌达替尼诱导恶性胸膜间皮瘤CTLA-4和PD-1抑制剂联合疗法引发的难治性免疫相关性结肠炎缓解:病例报告。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1002/cnr2.70032
Masashi Kono, Yoriaki Komeda, Hisato Kawakami, Satoru Hagiwara, George Tribonias, Kohei Handa, Shunsuke Omoto, Mamoru Takenaka, Hiroshi Kashida, Naoko Tsuji, Masatoshi Kudo

Background

Immune checkpoint inhibitors have demonstrated efficacy against various cancers; however, there is a rising incidence of immune-related colitis. Some cases of immune-related colitis prove resistant to treatment, even with the administration of glucocorticoids or infliximab, and there is currently no established standard treatment for such cases.

Case

The patient, a 73-year-old male, had undergone combination therapy for malignant pleural mesothelioma for 2 years, utilizing both ipilimumab (a CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor). Unfortunately, the treatment led to side effects, specifically immune-related adverse event (irAE) enterocolitis. Steroid and infliximab treatment failed to improve the patient's condition. Treatment with tacrolimus was attempted, but the patient remained unresponsive. Subsequently, 45 mg of upadacitinib, a Janus kinase (JAK) inhibitor, was administered. Symptoms improved rapidly following upadacitinib administration, and endoscopy also revealed positive results. With the increasing incidence of immune-related colitis, some patients have become resistant to treatment with glucocorticoids and infliximab. In this case, the irAE enterocolitis was improved by upadacitinib administration.

Conclusion

In cases where immune-related colitis proves resistant to treatment with glucocorticoids, infliximab, or tacrolimus, upadacitinib represents a potential option as a JAK inhibitor.

背景:免疫检查点抑制剂对多种癌症具有疗效,但免疫相关性结肠炎的发病率却在不断上升。病例:患者是一名 73 岁的男性,接受了 2 年的恶性胸膜间皮瘤联合治疗,同时使用了伊匹单抗(CTLA-4 抑制剂)和尼维单抗(PD-1 抑制剂)。不幸的是,治疗导致了副作用,特别是免疫相关不良事件(irAE)肠炎。类固醇和英夫利昔单抗治疗未能改善患者的病情。医生尝试使用他克莫司治疗,但患者仍无反应。随后,患者接受了 45 毫克的达帕西替尼(一种 Janus 激酶 (JAK) 抑制剂)治疗。服用达帕替尼后,症状迅速得到改善,内镜检查也显示出阳性结果。随着免疫相关性结肠炎发病率的增加,一些患者对糖皮质激素和英夫利昔单抗的治疗产生了耐药性。在本病例中,服用达帕替尼后irAE肠炎得到了改善:结论:在免疫相关性结肠炎对糖皮质激素、英夫利昔单抗或他克莫司治疗耐药的病例中,达帕替尼是一种潜在的 JAK 抑制剂。
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引用次数: 0
Plant-Based Anticancer Compounds With a Focus on Breast Cancer 以植物为基础的抗癌化合物,重点关注乳腺癌。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-10-25 DOI: 10.1002/cnr2.70012
Amin Moradi Hasan-Abad, Amir Atapour, Ali Sobhani-Nasab, Hossein Motedayyen, Reza ArefNezhad

Breast cancer is a common form of cancer among women characterized by the growth of malignant cells in the breast tissue. The most common treatments for this condition include chemotherapy, surgical intervention, radiation therapy, hormone therapy, and biological therapy. The primary issues associated with chemotherapy and radiation therapy are their adverse events and significant financial burden among patients in underdeveloped countries. This highlights the need to explore and develop superior therapeutic options that are less detrimental and more economically efficient. Plants provide an abundant supply of innovative compounds and present a promising new avenue for investigating cancer. Plants and their derivations are undergoing a revolution due to their reduced toxicity, expediency, cost-effectiveness, safety, and simplicity in comparison to conventional treatment methods. Natural products are considered promising candidates for the development of anticancer drugs, due perhaps to the diverse pleiotropic effects on target events. The effects of plant-derived products are limited to cancer cells while leaving healthy cells unaffected. Identification of compounds with strong anticancer properties and development of plant-based medications for cancer treatment might be crucial steps in breast cancer therapy. Although bioactive compounds have potent anticancer properties, they also have drawbacks that need to be resolved before their application in clinical trials and improved for the approved drugs. This study aims to give comprehensive information on known anticancer compounds, including their sources and molecular mechanisms of actions, along with opportunities and challenges in plant-based anticancer therapies.

乳腺癌是女性中常见的一种癌症,其特征是乳腺组织中恶性细胞的生长。最常见的治疗方法包括化疗、手术治疗、放射治疗、激素治疗和生物治疗。与化疗和放疗相关的主要问题是其不良反应和对不发达国家患者造成的巨大经济负担。这凸显了探索和开发危害更小、更经济有效的优质治疗方案的必要性。植物提供了丰富的创新化合物,为研究癌症提供了一条前景广阔的新途径。与传统治疗方法相比,植物及其衍生物具有毒性低、方便快捷、成本效益高、安全简单等优点,因此正在经历一场革命。天然产品被认为是开发抗癌药物的理想候选物,这可能是因为它们对目标事件具有多种多样的多效应。植物提取物的作用仅限于癌细胞,而健康细胞则不受影响。鉴定具有强大抗癌特性的化合物和开发治疗癌症的植物药物可能是乳腺癌治疗的关键步骤。虽然生物活性化合物具有很强的抗癌特性,但它们也有一些缺点,需要在应用于临床试验之前加以解决,并改进为已批准的药物。本研究旨在全面介绍已知的抗癌化合物,包括其来源和分子作用机制,以及植物抗癌疗法的机遇和挑战。
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引用次数: 0
Inhibiting lncRNA NEAT1 Increases Glioblastoma Response to TMZ by Reducing Connexin 43 Expression 抑制lncRNA NEAT1可通过减少Connexin 43的表达增加胶质母细胞瘤对TMZ的反应
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-10-25 DOI: 10.1002/cnr2.70031
Jinxing Liang, Jia-xiu Xie, Junhui He, Yi Li, Dongmei Wei, Rongfei Zhou, Guining Wei, Xuehua Liu, Qiudan Chen, Dongmei Li

Objectives

Glioblastoma multiforme (GBM) is considered the most assailant subtype of gliomas, presenting a formidable obstacle because of its inherent resistance to temozolomide (TMZ). This study aimed to characterize the function of lncRNA NEAT1 in facilitating the advancement of gliomas.

Methods

The expression level of NEAT1 in glioma tissues and cells was detected by qRT-PCR. RNA interference experiment, cell proliferation assay, FITC/PI detection assay, immunoblotting, bioinformatics prediction, a double luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, SLDT assay and correlation analysis of clinical samples were performed to explore the regulatory effects of NEAT1, miR-454-3p and Cx43 and their role in malignant progression of GBM. The role of NEAT1 in vivo was investigated by an intracranial tumor formation experiment in mice.

Results

The results showed that recurring gliomas displayed elevated levels of NEAT1 compared to primary gliomas. The suppression of NEAT1 led to a restoration of sensitivity in GBM cells to TMZ. NEAT1 functioned as a competitive endogenous RNA against miR-454-3p. Connexin 43 was identified as a miR-454-3p target. NEAT1 was found to regulate gap junctional intercellular communication by modulating Connexin 43, thereby impacting the response of GBM cells to TMZ chemotherapy. Downregulation of NEAT1 resulted in enhanced chemosensitivity to TMZ and extended the survival of mice.

Conclusions

Overall, these results indicated that the NEAT1/miR-454-3p/Connexin 43 pathway influences GBM cell response to TMZ and could offer a potential new strategy for treating GBM.

研究目的多形性胶质母细胞瘤(GBM)被认为是胶质瘤中最具攻击性的亚型,因其对替莫唑胺(TMZ)固有的抗药性而构成了巨大的障碍。本研究旨在阐明lncRNA NEAT1在促进胶质瘤发展中的功能:方法:通过 qRT-PCR 检测神经胶质瘤组织和细胞中 NEAT1 的表达水平。通过RNA干扰实验、细胞增殖实验、FITC/PI检测实验、免疫印迹、生物信息学预测、双荧光素酶报告基因实验、RNA免疫沉淀(RIP)实验、SLDT实验和临床样本的相关性分析,探讨NEAT1、miR-454-3p和Cx43的调控作用及其在GBM恶性进展中的作用。通过小鼠颅内肿瘤形成实验研究了 NEAT1 在体内的作用:结果表明,与原发性胶质瘤相比,复发性胶质瘤的 NEAT1 水平升高。抑制 NEAT1 可使 GBM 细胞恢复对 TMZ 的敏感性。NEAT1 对 miR-454-3p 起着竞争性内源性 RNA 的作用。发现Connexin 43是miR-454-3p的靶点。研究发现,NEAT1通过调节Connexin 43来调节细胞间隙连接通讯,从而影响GBM细胞对TMZ化疗的反应。下调 NEAT1 可增强小鼠对 TMZ 的化疗敏感性,延长小鼠的生存期:总之,这些结果表明,NEAT1/miR-454-3p/Connexin 43通路影响了GBM细胞对TMZ的反应,可为治疗GBM提供一种潜在的新策略。
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引用次数: 0
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Cancer reports
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