Journal of Chemotherapy最新文献

Lung transplantation is a well-established treatment for end-stage lung disease. Viral infections represent major infective complications after lung transplantation. Respiratory viruses can increase immune responses and the development of acute rejection. We describe the case of a 60-year-old man, who underwent bilateral lung transplantation in July 2023. He was admitted to our Unit in December 2024 for worsening shortness of breath associated to dry cough. Arterial blood gas analysis on room air showed respiratory failure. RT-PCR panel for respiratory viruses on a specimen obtained from bronchoalveolar lavage fluid came out positive for Coronavirus OC43, while chest CT-scan showed bilateral patchy infiltrates. Based on in vitro activity data, authorized off-label therapy with remdesivir was administered for 5 days Clinical conditions, together with laboratory data and arterial blood gas analysis, improved quickly. In conclusion, viral infections are a major clinical issue after lung transplant, however targeted therapy is not always possible. New treatment options are needed even to prevent complications, such as acute rejection. This clinical case suggests remdesivir could have a role in non-SARS-CoV-2 coronavirus infections.

Breast cancer is the most common malignancy, with approximately ∼20% of cases involving HER2 overexpression. Trastuzumab deruxtecan (T-DXd), an HER2-targeted antibody-drug conjugate, is approved for HER2-high and HER2-low disease. This meta-analysis assessed four randomized controlled trials (DESTINY-Breast02, -03, -04, and -06; 2555 patients) from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. A random-effects model revealed that T-DXd significantly improved progression-free survival (hazard ratio [HR] = 0.433; 95% confidence interval [CI]: 0.305-0.616; P < 0.001; I² = 90.7%) and overall survival (HR = 0.720; 95% CI: 0.636-0.816; P < 0.001; I² = 0%) versus control regimens, with consistent benefits across HER2 subgroups. However, T-DXd increased the risks of interstitial lung disease (relative risk [RR] = 13.832; P < 0.001), decreased left ventricular ejection fraction (RR = 2.247; P < 0.001), anemia, nausea, vomiting, decreased appetite, and alopecia; neutropenia and diarrhea risks were comparable between groups. These findings highlight T-DXd's survival benefits and toxicity profile warranting monitoring.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer represents the most prevalent subtype of breast cancer. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, in combination with endocrine therapy (ET), have shown substantial benefits in improving progression-free survival and, for ribociclib, an overall survival advantage. Despite clinical benefits, ribociclib is associated with elevated liver enzymes and severe liver dysfunction. We present a 44-year-old Caucasian woman with HR-positive, HER2-negative metastatic breast cancer who developed drug-induced autoimmune-like hepatitis (DI-ALH) after ribociclib therapy. Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Treatment was complicated by grade 3 hepatotoxicity, confirmed as DI-ALH by liver biopsy. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.

Immunotherapy has been advanced through multiple approaches, including immunogenic cytokines, monoclonal antibodies, therapeutic vaccinations, adoptive cell transfer, stem cell transplantation, and oncolytic viruses. This review analyses various strategies in genomics, transcriptomics, single-cell techniques, computational analysis, big data, and imaging technologies for the identification of tumour microbiota and microenvironments. Immunotherapy is becoming acknowledged as a feasible cancer treatment method, facilitating innovative cancer medicines and personalized medicine techniques.

This study aimed to evaluate the compatibility of generic ceftriaxone sodium preparations with various rubber closures used in pharmaceutical packaging, focusing on the release of butylated hydroxytoluene (BHT), an antioxidant present in rubber closures that may migrate into drug products. BHT levels were quantified using gas chromatography-mass spectrometry (GC-MS) to assess stability and safety. Results showed that all samples contained BHT, with concentrations ranging from below the quantification limit to a maximum of 5.65 ppm. Notably, 47.62% of the samples exceeded the threshold of toxicological concern (TTC) of 1.5 µg/day, raising significant safety concerns. Older samples exhibited higher BHT levels, and products from pharmacies generally had greater concentrations than those obtained from manufacturers. These findings underscore the critical importance of assessing interactions between drug formulations and packaging materials, emphasizing the need for rigorous quality control in injectable pharmaceuticals. Future research should explore strategies to mitigate BHT accumulation in these preparations.

Cervical cancer is one of the most common gynecologic malignancies worldwide. 5-Fluorouracil (5-Fu) is a widely used anticancer drug for various cancers, but the development of 5-Fu resistance poses a challenge in treating cervical cancer patients. This study examined the roles and molecular mechanisms of LncRNA-FGD5-AS1 in 5-Fu resistant cervical cancer cells through in vitro and in vivo experiments. We discovered FGD5-AS1 and the RNA methylation reader protein, YTHDF2, were positively associated with 5-Fu resistance in cervical cancer. A positive correlation between FGD5-AS1 and YTHDF2 was found in cervical tumor tissues. Expressions of FGD5-AS1 and YTHDF2 were significantly upregulated in the established 5-Fu resistant cervical cancer cells. MiRNA-microArray analysis screened that FGD5-AS1 downregulated miR-130a-3p expression in cervical cancer cells. Subsequently, we demonstrated FGD5-AS1 acted as a ceRNA by sponging miR-130a-3p, which targeted the 3'UTR of YTHDF2 mRNA. Rescue experiments validated overexpression of FGD5-AS1 increased 5-Fu resistance in cervical cancer cells, which was reversed by miR-130a-3p overexpression. Finally, combining FGD5-AS1 silencing with 5-Fu treatments resulted in a synergistic inhibitory effect (CI < 1) on the viability of cervical cancer cells. This study reveals a FGD5-AS1-miR-130a-3p-YTHDF2 axis that could be a promising therapeutic target for overcoming 5-Fu resistance in cervical cancer.

This study aimed to evaluate the effectiveness and safety of Meropenem-Vaborbactam(M-V) for treating carbapenem-resistant Enterobacterales (CRE) infections based on real-world data. A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted, considering studies up to October 31, 2024. Real-world evidence from registries and nonselected case series involving 10 or more adult patients treated with Meropenem-Vaborbactam for CRE infections was included. Meta-analyses using a random-effects model were performed, with the primary outcomes being clinical efficacy and survival, including 30-day and 90-day survival rates. Out of 1862 potentially relevant publications, six studies were included in the meta-analysis. The pooled clinical success rate was 75% (95% CI, 66%-82%), and the pooled 30-day and 90-day survival rates were 75% (95% CI, 71%-78%) and 69% (95% CI, 61%-76%), respectively. Importantly, no serious adverse effects were reported. In conclusion, Meropenem-Vaborbactam demonstrated both efficacy and safety in treating CRE infections in real-world settings. This study was registered with PROSPERO (CRD42022370880).

Managing locally advanced, or metastatic radioactive iodine-refractory differentiated thyroid cancers (RAIR-DTC) poses substantial challenges, with few available treatment options. The aim of this study was to evaluate clinical outcomes of patients receiving sorafenib as first line treatment. In addition, prognostic markers affecting progression-free survival (PFS) were identified. This retrospective, 6 centers study included 62 patients with locally advanced or RAIR-DTC treated 2008-2023. The median PFS was 16.5 months. The presence of liver metastases was strongly associated with a lower PFS (3.1 months (p < 0.001)). The use of sorafenib as initial treatment resulted longer PFS compared to chemotherapy, with a median of 25.5 vs 4.7 months respectively (p = 0.01). Increased neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with worse outcomes (p = 0.01; p = 0.009, respectively). In conclusion, sorafenib has demonstrated significant PFS benefits when used as first-line treatment. It has been shown that the presence of liver metastases and higher levels of NLR and PLR are associated with a more unfavorable prognosis.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. LncRNA NORAD is frequently upregulated and positively associated with various cancer progressions. We discovered NORAD was significantly upregulated in CRC tissues and cells. NORAD sponged miR-106a-5p to form a ceRNA complex. MiR-106a-5p was remarkedly downregulated in CRC tumors and cells. Silencing NORAD or overexpression of miR-106a-5p effectively increased cisplatin sensitivity. In the established cisplatin resistant cell line, NORAD was upregulated and miR-106a-5p was downregulated. Furthermore, we disclosed miR-106a-5p directly targeted 3'UTR of CCND1, which is an important cell cycle regulator and is frequently overexpressed in human cancers. Rescue experiments showed restoration of CCND1 in miR-106a-5p-overexpressing CRC cells successfully recovered cisplatin resistance. Finally, restoration of miR-106a-5p in NORAD-overexpressing CRC cells re-sensitized cisplatin resistance by targeting CCND1. Summarily, this study uncovered a NORAD-promoted cisplatin resistance through modulating the miR-106a-5p-CCND1 axis, contributing to developing novel therapy for treating chemoresistant CRC.

The emergence of resistance to 5-Fluorouracil (5-FU) is a staple in breast cancer chemotherapy. This paper delves into the role of PTEN in breast cancer resistance to 5-FU and examines the underlying molecular pathways. PTEN expression was detected in bioinformatics databases and upstream transcription factors (TFs) were identified. PTEN mRNA and protein levels, aerobic glycolysis proteins, lactate production, glucose consumption, and cell viability were measured. Binding interactions were confirmed, and cell proliferation assessed. In breast cancer cells, PTEN expression was downregulated. PTEN overexpression counteracted 5-FU resistance through the suppression of aerobic glycolysis. KLF9, as a TF upstream of PTEN, enhanced the levels of PTEN. In conclusion, the TF KLF9 inhibits the aerobic glycolysis level of breast cancer cells by up-regulating PTEN expression, thereby reducing their resistance to 5-FU. The discovery of this mechanism provides a new theoretical basis for the treatment of breast cancer.