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Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta-analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA-MB-231) with sodium L-lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L-lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings., (© 2024 International Federation of Cell Biology.)

Background: Rhabdomyosarcoma of the bladder is an infrequent neoplastic condition characterized by a pronounced malignant situation with challenges in treatment due to the lack of standardized guidelines and large-scale of clinical studies. The patient in this case is tested TP53 mutation that may provide new diagnostic and therapeutic options., Case Presentation: Here, we reported a 34-year-old male who received bladder tumor resection, and diagnosed as bladder rhabdomyosarcoma with TP53 mutation after the pathology test. This patient underwent 6 rounds of chemotherapy. However, the pelvic tumor recurred 11 months after the first surgery. So, the patient accepted the pelvic tumor resection. Only 3 months after the surgical intervention, the patient underwent abdominal massive metastasis and ultimately succumbed to the illness six months following the second surgery. The course of the illness was 22 months., Conclusion: Bladder rhabdomyosarcoma is a disease with an extremely poor prognosis. Genetic testing holds significant value in the diagnosis and treatment. Perhaps targeted therapy against TP53 is potential valuable for such rare diseases., 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 Li, Yang, Zheng, Wang, Umar, Fan, He, Chang and Wang.)

Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC., 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 Zheng, Yang, Li, Qu, Shao, Wang, Chang, Umar, Wang, Ding and Wang.)

Despite many efforts, a comprehensive understanding and clarification of the intricate connections within cancer cell metabolism remain elusive. This might pertain to intracellular dynamics and the complex interplay between cancer cells, and cells with the tumor stroma. Almost a century ago, Otto Warburg found that cancer cells exhibit a glycolytic phenotype, which continues to be a subject of thorough investigation. Past and ongoing investigations have demonstrated intricate mechanisms by which tumors modulate their functionality by utilizing extracellular glucose as a substrate, thereby sustaining the essential proliferation of cancer cells. This concept of "aerobic glycolysis," where cancer cells (even in the presence of enough oxygen) metabolize glucose to produce lactate plays a critical role in cancer progression and is regulated by various signaling pathways. Recent research has revealed that the canonical wingless-related integrated site (WNT) pathway promotes aerobic glycolysis, directly and indirectly, thereby influencing cancer development and progression. The present review seeks to gather knowledge about how the WNT/β-catenin pathway influences aerobic glycolysis, referring to relevant studies in different types of cancer. Furthermore, we propose the concept of impeding the glycolytic phenotype of tumors by employing specific inhibitors that target WNT/β-catenin signaling., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction and Importance: PHACE syndrome is a rare neurocutaneous disorder characterized by large segmental hemangiomas on the face and is associated with multiple developmental defects. PHACE stands for posterior fossa malformations, hemangiomas, arterial abnormalities, cardiac defects, and eye anomalies, with the most common manifestation being hemangioma in the cervico-facial region in early childhood., Case Presentation: The authors report a case of a 15-year-female with complaints of facial hemangioma which on multisystemic imaging showed features of central nervous system (CNS) anomalies that led to the diagnosis of PHACE syndrome. The patient was started on propanolol which decreased the size of hemangioma in follow-up visits., Clinical Discussion: The hemangioma in the frontotemporal and frontonasal area of the face are associated more with CNS and cardiovascular anomalies needing a detailed multisystem approach. CNS anomalies include posterior cerebral fossa enlargement, cystic dilation of the fourth ventricle, arachnoid cyst, and cerebellar hypoplasia which were present in our case. Propanolol is considered the first-line drug for facial hemangioma with reported evidence of remarkable improvement and good tolerance. However, regular follow-up of the patient is needed to rule out any recurrence., Conclusion: PHACE syndrome, although being a rare occurrence, must be kept as a differential diagnosis in infants and children with facial hemangioma. Imaging modalities like MRI/magnetic resonance arteriography must be used to rule out possible associations related to PHACE syndrome and focus on early treatment to prevent possible complications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients., (© 2023 Wiley Periodicals LLC.)

Background: This is the case of a girl who sustained orbital injury while playing with a mobile phone charger., Case Report: The patient presented to the tertiary hospital 5 h after she sustained a penetrating injury with the power plug of a mobile phone charger to the right upper lid. There was associated headache, tearing, bleeding, discharge, and inability to open the right eye., On Examination: She was ill-looking and anxious, not febrile or pale. Systemic examination did not reveal any abnormality. Unaided visual acuity in the right eye (OD) could not be tested, left eye (OS)-6/9. The right eyelid was completely closed with a penetrating power plug of the phone charger in the supero-lateral aspect of the upper eyelid. A diagnosis of penetrating power plug of a charger in the right upper lid and orbit was made. Computed tomography scan showed the power plug of the charger in the right orbit with a little blood collection in the right maxillary sinus. She underwent examination under anaesthesia, foreign body removal, and repair of the lid penetration. The findings were right upper lid penetration with ptosis, corneal epithelial erosion, phone charger power plug in the medial orbital wall, and cataract. The foreign body was removed, and lid and conjunctival lacerations repaired. Eight weeks post-operatively, ptosis had resolved, leaving the anterior polar cataract (<3 mm) and a best corrected visual acuity of (OD) 6/6 and (OS) 6/5. About 6 months afterwards, the cataract matured with a visual acuity of 6/60 for which she had right phacoemulsification with posterior chamber intra-ocular lens implant insertion., Conclusion: Prompt presentation and management lead to good visual outcomes in this patient., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of the West African College of Surgeons.)

In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients ( p  = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., β-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-β-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.

Background: Salvia miltiorrhiza Bunge (Danshen), has been used for its therapeutic value in Traditional Chinese Medicine (TCM), for almost a thousand years. Dihydrotanshinone-I (DHTS) is a lipophilic compound isolated from the plant Salvia miltiorrhiza that has been shown to induce anti-proliferative and apoptotic effects on breast cancer cells. In the present study, we investigated the anti-migratory effect of DHTS on TNBC cell lines by studying the Epithelial Mesenchymal Transition (EMT) changes., Methods: IC50 values for DHTS in TNBC breast cancer cells were either discovered by literature search or by performing MTT assay. DHTS effect on EMT markers (viz. CD44, E-cadherin, Vimentin, N-cadherin, and active β-catenin) was studied using western blotting. Association between EMT and migration was further carried out in DHTS treated TNBC cells by wound healing assay. Cancer stemness and proliferation potential were further accessed using colony formation assay., Results: MTT assay revealed IC50 of MDA-MB-468 cells at 2 µM for 24 h. Subsequently, DHTS treatment in TNBC cell lines (MDA-MB-468 and MDA-MB-231) led to decrease in mesenchymal markers i.e. vimentin, N-cadherin and, active β-catenin. DHTS treated MDA-MB-468 cells showed a decrease in adhesion protein CD44 and an increase in epithelial protein E-cadherin. Additionally, a decrease in EMT potential was positively associated with the inhibition of migration and clonogenic potential in DHTS treated TNBC cells., Conclusion: In this study, we have demonstrated for the first time that DHTS has the potential to inhibit the migration and clonogenicity of highly aggressive TNBC cells by obstructing Epithelial to Mesenchymal Transition.

In the present study, we have explored the prognostic value of the Phosphofructokinase Platelet-type (PFKP) expression and its therapeutic relevance in metastatic breast cancer. PFKP immunohistochemistry was performed on Invasive ductal carcinomas (IDCs; n = 87) of breast, and its association with clinicopathological parameters were evaluated. Using online meta-analysis tools, PFKP's prognostic value was investigated in overall breast cancer as well as in triple negative subtype (TNBCs). For in vitro analysis, MDA-MB-231 cells model was used in order to elucidate mechanisms behind PFKP regulated glycolysis and its impact on cancer cell physiology. Therapeutic relevance of PFKP was further evaluated using PFKP siRNA and Quercetin. PFKP protein expression was found to be positively associated with nodal invasion (p = 0.009), receptor (ER & PR) negative status (p = 0.005 & p = 0.028) and reduced overall survival in breast cancer patients (p = 0.014). In MDA-MB-231 cells, quercetin treatment impaired PFKP-LDHA signaling axis thereby inhibiting aerobic glycolysis mediated increased migration of cancer cells. Our present study demonstrates that elevated PFKP levels are associated with basal cells/TNBC subtypes and might serve as prognostic indicator for TNBC patients. Ability of quercetin to inhibit aerobic glycolysis, cell migration and clonogenic potential of malignant breast cancer cells advocates possibility of quercetin in aggressive breast cancer treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The prevalence of gastroesophageal reflux disease (GERD) in Africa is not known but is believed to be increasing because of demographic and epidemiologic transition. The main objectives of this study were to determine the prevalence and risk factors of GERD, and its degree of overlap with dyspepsia and irritable bowel syndrome (IBS) in Nigeria, a typical African population., Methods: This was an observational, cross-sectional and descriptive study of adult Nigerians. Diagnosis of GERD was by means of the gastroesophageal reflux disease questionnaire (GERDQ) while the diagnosis of dyspepsia and IBS was based on the Rome III criteria for the diagnosis of functional gastrointestinal disorders. The GERDQ and Rome III questionnaires for dyspepsia and IBS were merged into a composite questionnaire and administered to the study participants who were recruited with a multi-stage sampling technique., Results: Out of 3520 subjects who participated in the study across the country, 269 (7.6%) satisfied the diagnostic criteria for GERD, while 107 (3.0%) had GERD associated with significant impairment of quality of life. Risk factors of GERD (represented by odds ratios) were age 1.014(95% CI: 1.006-1.022), use of analgesics 1.461 (95% CI: 1.060-2.025), and use of herbs 1.318 (95% CI: 1.020-1.704). Overlap of GERD with dyspepsia and/or IBS was observed in over 50% of cases., Conclusions: The prevalence of GERD in this study is 7.6%. Age, use of analgesics and use of herbs increase the risk, albeit minimally. A high degree of overlap with dyspepsia and IBS exists in Nigerian patients with GERD.

Objectives: This study assesses the extent to which the strength of a recommendation in a World Health Organization (WHO) guideline affects uptake of the recommendation in national guidelines., Study Design and Setting: The uptake of recommendations included in HIV and TB guidelines issued by WHO from 2009 to 2013 was assessed across guidelines from 20 low- and middle-income countries in Africa and Southeast Asia. Associations between characteristics of recommendations (strength, quality of the evidence, type) and uptake were assessed using logistic regression., Results: Eight WHO guidelines consisting of 109 strong recommendations and 49 conditional recommendations were included, and uptake assessed across 44 national guidelines (1,255 recommendations) from 20 countries. Uptake of WHO recommendations in national guidelines was 82% for strong recommendations and 61% for conditional recommendations. The odds of uptake comparing strong recommendations and conditional recommendations was 1.9 (95% confidence interval: 1.4, 2.7), after adjustment for quality of evidence. Higher levels of evidence quality were associated with greater uptake, independent of recommendation strength., Conclusion: Guideline developers should be confident that conditional recommendations are frequently adopted. The fact that strong recommendations are more frequently adopted than conditional recommendations underscores the importance of ensuring that such recommendations are justified., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Oesophageal varices are common sequelae of cirrhosis, which when they bleed can be difficult to control. Oesophageal variceal band ligation, being the best modality for controlling variceal bleeding has not been common practice in West Africa, a region recognized to have a high prevalence of liver diseases. We present a case of band ligation of the varices of a patient that presented to our hospital with variceal haemorrhage, secondary to liver cirrhosis., Method: We started by presenting a summary of the presentation of a 31 year old man at the Jos University Teaching Hospital and how we established the diagnosis of grade IV bleeding oesophageal varices. The subject had four bands applied to the oesophageal varices using a saeed six shooter oesophageal Multi-band ligator (North Carolina, USA) using a forward-viewing GIF P30 gastroscope (Tokyo, Japan) with the bands mounted on an Opti-vu barrel-shaped piece. He had a total of three sessions after which he was maintained on propranolol., Result: The last recheck endoscopy demonstrated obliterated varices after which he was maintained on propranolol., Conclusion: We present a case of successful variceal band ligation of a cirrhotic with extensive oesophageal varices presenting in a resource-constraint medical setting.