Canniesburn Hospital

Breast cancer remains the most prevalent malignancy among women globally, with its complexity linked to genetic variations and metabolic alterations within tumor cells. This study investigates the role of fumarate hydratase (FH), a key enzyme in the tricarboxylic acid (TCA) cycle, in breast cancer progression. Our findings reveal that FH mRNA and protein levels are significantly upregulated in breast cancer tissues and correlate with poor patient prognosis and aggressive tumor characteristics. Using in vitro and in vivo models, we demonstrate that FH overexpression enhances breast cancer cell proliferation, migration, and invasion through metabolic reprogramming and by increasing reactive oxygen species (ROS) production. Furthermore, we identify matrix metalloproteinase 1 (MMP1) as a downstream effector of FH, linked to p21 downregulation, elucidating a novel regulatory pathway influencing tumor behavior. Interestingly, unlike its tumor-suppressing role in other cancer types, this study highlights FH's oncogenic potential in breast cancer. Our results suggest that FH enhances cancer cell viability and aggressiveness via both catalytic and non-catalytic mechanisms. This work not only underscores the metabolic adaptations of breast cancer cells but also proposes FH as a potential biomarker and therapeutic target for breast cancer management.

Abstract Aim To evaluate the impact of COVID-19 on operative timing for hand trauma in a plastic surgery tertiary referral centre. Method Data was collected retrospectively on 80 patients who underwent surgical management for closed hand fractures, digital nerve injuries, and tendon injuries. Forty patients were in the pre-covid group (Jan-Mar 2019) and 40 in the post-covid group (Jan-Mar 2022). Outcome measures:Mean number of days between decision to operate and operation (operative delay time)Adherence to the operative timing requirements, as set by the British Society for Surgery of the Hand (BSSH) Results There was a statistically significant difference in operative delay time between the pre-covid group and the post-covid pre-vaccine group for hand fractures (2.5 vs 3.9, P = 0.0503), tendon injuries (1.4 vs 2.2, p = 0.016), and overall (1.9 vs 3.3, p = 0.0024). There was no significant difference between the 2 groups for nerve injuries (3.8 vs 1.8, p = 0.3062). In the post-covid group, BSSH operative timing requirements were met for a lower proportion of patients than the pre-covid group for hand fracture fixations (85% vs 100%), nerve repairs (87% vs 100%) tendon repairs (85% vs 100%). Overall, there was a statistically significant difference between the 2 groups (85% vs 100%, p = 0.0214). Operative delays were documented as being related to COVID-19 in 100% of patients who did not meet BSSH operative timing requirements. Conclusions COVID-19 has had a significant impact on operative timing for plastic surgery hand trauma. Further studies are needed to evaluate the usefulness of various interventions in the recovery of services following the COVID-19 global pandemic.

BackgroundInterleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated.MethodsTumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan–Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry.ResultsClinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin—a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes—reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin.ConclusionsThe current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.

The incidence of contact burns from heated hair straighteners is increasing. The aim of this paper is to assess the safety features of hair straighteners, the mechanism of contact burns and the resultant morbidity in children. This study involves retrospective analyses of patients' case notes and examination of hair straighteners during heating and cooling. Grabbing and stepping onto heated devices were the common mechanisms of injury involving mainly hands and feet. Healing time ranged from 2 to 79 days. Nineteen percent required extensive therapy to maintain good function. Most devices had locking mechanisms to keep the internal surfaces closed; however the external surfaces reached 72.8°C and took 8.6 min to cool below 50°C. Contact with heated hair straighteners causes significant morbidity. The devices, including the external surfaces remain dangerously hot for a prolonged period after being switched off. These findings call for appropriate safety measures to be redressed by manufacturers and awareness amongst users to avoid these preventable injuries.

The management of the clinically N0 (cN0) neck in patients with oral and oropharyngeal squamous cell carcinomas (SCC) remains controversial. Factors such as patient comorbidity, different personal opinions, pathological factors and other factors modify the treatment decisions. Our primary aim was to determine the management of the cN0 neck in oral and oropharyngeal SCC patients in different institutions in Scotland. The secondary aim was to evaluate the outcome of the patients who had not undergone any treatment of the neck in comparison with those who had undergone elective neck treatment, and also examine factors relating to overall survival in this population. Based on a prospective head and neck cancer audit carried out in Scotland between September 1999 and October 2001, we focused on the management of N0 neck in patients with oral or oropharyngeal SCC. Out of a total of 1,910 patients in the audit, 364 patients with oral or oropharyngeal SCC and cN0 neck were treated with curative intent. The overall survival data was available up to a minimum of 5 years, and a detailed clinical follow-up to a minimum of 18 months. One hundred patients had no treatment to the neck (observation group). A total of 112 patients received prophylactic neck (chemo)-irradiation without elective neck dissection (END). END was performed for 152 patients (of which 23 were bilateral), and 63 of them received postoperative radiotherapy. Histopathological examination revealed metastases in only 16% of the dissection specimens. In the observation group, six patients (6%) had a recurrence in the neck without any recurrence at the primary site. For the rest of the patients who had any sort of elective neck treatment, the respective figure was also 6% (15/264). Neck imaging was recorded in 186 patients only. There is a wide variation in the management of the cN0 within Scotland. The use of imaging for diagnosis is also variable. A surprisingly low percentage of patients proved to have had metastasis on pathological examination. Despite variations in treatment, neck recurrence was relatively uncommon. This audit demonstrates the need for more defined protocols for the management of the cN0.

Canniesburn Plastic Surgery Unit; Glasgow Royal Infirmary; Glasgow, UK Note from the editors: We welcome submissions reviewing relevant courses via a presubmission enquiry to both: [email protected] and [email protected]