Benefits and challenges of Mohs micrographic surgery for human papilloma virus-associated cutaneous malignancies: a systematic review.

Mohs micrographic surgery is the gold standard for treating many types of skin cancer, particularly skin cancers of high-risk areas such as the face, genitalia, and digits, due to its tissue-sparing technique and low recurrence rates. The use of Mohs micrographic surgery for human papilloma virus-associated cutaneous malignancies has yet to be explored in a systematic review. The authors sought to assess outcomes including recurrence rates of Mohs micrographic surgery for human papilloma virus-associated cutaneous malignancies. PubMed was searched for the use of Mohs micrographic surgery in types of human papilloma virus-associated cutaneous malignancies. After application of exclusion and inclusion criteria, 33 articles were included. 700 cases from 33 studies were included. Overall recurrence rate following Mohs micrographic surgery was 39/478 (8.2%) at a mean follow-up time of 51.5 months. Recurrence rate for nail unit/digit squamous cell carcinoma was 10/103 (9.7%) at mean follow-up of 47.6 months. Recurrence rate for penile squamous cell carcinoma was 15/181 (8.3%) at mean follow-up of 45.9 months. Recurrence rate for Bowen's disease in extragenital areas was 11/189 (5.9%) at mean follow-up of 59.7 months. Patients overall reported satisfactory functional and cosmetic results. Mohs micrographic surgery demonstrates low recurrence rates and excellent functional and cosmetic outcomes in the treatment of human papilloma virus-associated cutaneous malignancies.

Squamous cell carcinoma of the urinary bladder in patients with chronic spinal cord injury: A case series.

INTRODUCTION: Patients with spinal cord injury/disorder (SCI/D) and neurogenic lower urinary tract dysfunction (NLUTD) are on a 16-28 folder higher risk for bladder cancer [1]. Whereas in the general population 90% of bladder tumors are transitional cell carcinoma (TCC) patients with NLUTD have a shift to squamous cell carcinoma with 36,8% and only 46.3% TCC [2]. In addition, there is a significant increase in the bladder cancer-specific death rate in SCI patients (3rd most common) compared to the general population (10th most common) [2]. Chronic inflammation and mechanical irritation by permanent indwelling catheters are discussed as risk factors for developing bladder cancer. Typical symptoms of bladder cancer are often absent in patients with NLUTD and a reliable screening has not been established. CASE PRESENTATION: We present a case series of six patients with SCI and with squamous cell carcinoma diagnosed in the last 5 years in our institution. In five patients, bladder management was performed by indwelling suprapubic catheters, one patient used reflex voiding. Three patients were diagnosed during the regular, annual neuro-urological check-up, the remaining due to increasing spasticity and autonomic dysregulation. Subsequently, five patients underwent cystectomy with ileal conduit or uretercutaneostomy, one patient refused further surgical treatment. Four patients died within one year after diagnosis. DISCUSSION: Squamous cell carcinoma of the bladder is more common in patients with NLUTD. Chronic inflammation and mechanical irritation may be the reasons for carcinoma genesis. A regular check including cystoscopy is strongly recommended to detect tumor development early.

Exploring the Association Between Atopic Dermatitis and Malignancy: A Comprehensive Review with Therapeutic Strategies.

Atopic dermatitis (AD) is a prevalent dermatologic condition affecting both children and adults, and the debate surrounding its association as either a risk or protective factor for malignancies has garnered significant attention. Proposed mechanisms suggest that AD may act protectively against cancer formation through chronic immune system activation or create an inflammatory state conducive to cancer development. This review discusses the relationship between AD and various skin cancers, solid tumors, and hematologic malignancies. Additionally, the authors explore the impact of AD treatments, particularly novel biologic drugs targeting molecular pathways such as JAK-STAT, IL-4, and IL-13 in association with malignancies.

Outcomes of Prophylactic Inguinal Lymph Node Dissection in Malignancies of Lower Limb.

AIM: To evaluate the role of early prophylactic inguinal node dissection in patients with squamous cell cancer and melanoma of lower limb. MATERIALS AND METHODS: From 2008 to 2018, a Tertiary Care Hospital connected to a teaching institute served as the site of this retrospective observational study. Patient records were gathered with the purpose of gathering clinical, investigative, surgical, pathological and follow-up information. RESULTS: We included 33 patients in this analysis out of the 47 patients we treated ourselves between 2008 and 2018; among these 33 patients, 21 (63.63%) had palpable inguinal nodes at the time of primary presentation. All 21 patients' FNAC tests were positive for metastases, in 16 patients (76.19%). 5 patients on FNAC (23.80%) exhibited not metastases. The remaining 12 patients did not have enlarged lymph nodes at the time of their initial presentation. Patients who did not have palpable lymph node were given the option of having a modified inguinal block dissection. 8 patients with metastatic disease have nodes that are positive in histology. In addition, out of 5 patients with negative nodes 4 (80%) showed evidence of metastasis. CONCLUSION: The conclusion of this retrospective observational study is that although palpable lymph nodes in groin are unquestionably a sign that inguinal nodes should be dissected, prophylactic lymph node dissection should be still done even if nodes are not palpable or provide a negative FNAC result. Given that delayed lymphadenectomy has a significant effect on survival, delaying inguinal lymphadenectomy in non-palpable nodes could cause you to lose the battle against cancer in your lower limb. The related surgical morbidity is the only downside to prophylactic lymph node dissection. This can, however, be effectively decreased with a modified inguinal lymphadenectomy operation.

Résumé Objectif:Évaluer le rôle de la dissection prophylactique précoce du ganglion inguinal chez les patients atteints d'un cancer épidermoïde et d'un mélanome du membre inférieur.Matériels et méthodes:De 2008 à 2018, un hôpital de soins tertiaires relié à un institut d'enseignement a servi de site à cette étude observationnelle rétrospective. Les dossiers des patients ont été rassemblés dans le but de recueillir des informations cliniques, d'investigation, chirurgicales, pathologiques et de suivi.Résultats:Nous avons inclus 33 patients dans cette analyse sur les 47 patients que nous avons nous-mêmes traités entre 2008 et 2018; parmi ces 33 patients, 21 (63,63 %) avaient des ganglions inguinaux palpables au moment de la présentation primaire. Les tests FNAC des 21 patients étaient positifs pour les métastases, chez 16 patients (76,19 %). 5 patients sous FNAC (23,80%) ne présentaient pas de métastases. Les 12 patients restants ne présentaient pas d'hypertrophie des ganglions lymphatiques au moment de leur présentation initiale. Les patients qui n'avaient pas de ganglion lymphatique palpable ont eu la possibilité de subir une dissection par bloc inguinal modifié. 8 patients atteints d'une maladie métastatique ont des ganglions positifs en histologie. De plus, sur 5 patients présentant des ganglions négatifs, 4 (80 %) présentaient des signes de métastases.Conclusion:La conclusion de cette étude observationnelle rétrospective est que même si les ganglions lymphatiques palpables dans l'aine sont incontestablement un signe que les ganglions inguinaux doivent être disséqués, un curage prophylactique des ganglions lymphatiques doit toujours être effectué même si les ganglions ne sont pas palpables ou fournissent un résultat FNAC négatif. Étant donné que le retardement du curage lymphatique a un effet significatif sur la survie, retarder le curage inguinal des ganglions non palpables pourrait vous faire perdre la bataille contre le cancer du membre inférieur. La morbidité chirurgicale associée est le seul inconvénient du curage prophylactique des ganglions lymphatiques. Ceci peut cependant être efficacement réduit grâce à une opération de lymphadénectomie inguinale modifiée.

Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas.

CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti-CD44v10 mAb, C44Mab-18 (IgM, kappa), to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with the previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3-10-overexpressed CHO-K1 (CHO/CD44v3-10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody-dependent cellular cytotoxicity (ADCC) against CHO/CD44v3-10. In contrast, C44Mab-46-mG2a showed a superior complement-dependent cytotoxicity (CDC) against CHO/CD44v3-10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CHO/CD44v3-10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.

ZIF-8 as a pH-Responsive Nanoplatform for 5-Fluorouracil Delivery in the Chemotherapy of Oral Squamous Cell Carcinoma.

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 µg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 µg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.

Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer.

The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Nanocarrier-based drug delivery system with dual targeting and NIR/pH response for synergistic treatment of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy.

Regulator of calcineurin 3 as a novel predictor of diagnosis and prognosis in pan-cancer.

AIM: To assess diagnostic and prognostic value of regulator of calcineurin 3 (RCAN3) in various malignancies. METHODS: RCAN3 expression levels were assessed across pan-cancer data sets including various molecular and immune subtypes. Receiver operating characteristic (ROC) and Kaplan-Meier curves were employed to determine the diagnostic and prognostic value of RCAN3 in pan-cancer, respectively. Enrichment analyses were used to identify RCAN3-associated terms and pathways. A special focus was placed on cervical squamous cell carcinoma and endocervical adenocarcinoma cervical cancer (CESC); we assessed the prognostic value of RCAN expression within distinct clinical subgroups and its effect on m6A modifications and immune infiltration. RESULTS: RCAN3 expression varied not only in different cancer types but also in different molecular and immune subtypes of cancers. RCAN3 displayed high accuracy in diagnosing and predicting cancers, and RCAN3 expression level was associated with the prognosis of certain cancers. CESC patients with a high RCAN3 level had a worse overall survival, disease-specific survival, and progression-free interval. RCAN3 expression was related to multiple m6A modifier genes and immune cells. CONCLUSION: In general, RCAN3 can serve as a novel biomarker for the diagnosis and prognosis in pan-cancer, especially in CESC. It may represent a promising molecular target for developing new treatments. However, our analysis is limited to bioinformatic predictions, and further biological experiments are necessary to verify our results.

Tumor Bed Margins Versus Specimen Margins in Oral Cavity Cancer: Too Close to Call?

INTRODUCTION: The routine assessment of intraoperative margins has long been the standard of care for oral cavity cancers. However, there is a controversy surrounding the best method for sampling surgical margins. The aim of our study is to determine the precision of a new technique for sampling tumor bed margins (TBMs), to evaluate the impact on survival and the rate of free flap reconstructions. METHODS: This retrospective cohort study involved 156 patients with primary cancer of the tongue or floor of the mouth who underwent surgery as initial curative treatment. Patients were separated into 2 groups: one using an oriented TBM derived from Mohs' technique, where the margins are taken from the tumor bed and identified with Vicryl sutures on both the specimen and the tumor bed, and the other using a specimen margins (SMs) driven technique, where the margins are taken from the specimen after the initial resection. Clinicopathologic features, including margin status, were compared for both groups and correlated with locoregional control. Precision of per-operative TBM sampling method was obtained. RESULTS: A total of 156 patients were included in the study, of which 80 were in TBM group and 76 were in SM group. Precision analysis showed that the oriented TBM technique pertained a 50% sensitivity, 96.6% specificity, 80% positive predictive value, and an 87.5% negative predictive value. Survival analysis revealed nonstatistically significant differences in both local control (86.88% vs 83.50%; P = .81) as well as local-regional control (82.57% vs 72.32%; P = .21). There was a significant difference in the rate of free flap-surgeries between the 2 groups (30% vs 64.5%; P < .001). CONCLUSION: Our described oriented TBM technique has demonstrated reduced risk of free flap reconstructive surgery, increased precision, and similar prognostic in terms of local control, locoregional control, and disease-free survival when compared to the SM method.

Long non-coding RNA MAGEA4-AS1 binding to p53 enhances MK2 signaling pathway and promotes the proliferation and metastasis of oral squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) regulate the occurrence, development and progression of oral squamous cell carcinoma (OSCC). We elucidated the expression features of MAGEA4-AS1 in patients with OSCC and its activity as an OSCC biomarker. Furthermore, the impact of up-regulation of MAGEA4-AS1 on the cellular behaviors (proliferation, migration and invasion) of OSCC cells and intrinsic signal mechanisms were evaluated. Firstly, we analyzed MAGEA4-AS1 expression data in The Cancer Genome Atlas (TCGA) OSCC using a bioinformatics approach and in 45 pairs of OSCC tissues using qPCR. Then CCK-8, ethynyl deoxyuridine, colony formation, transwell and wound healing assays were conducted to assess changes in the cell proliferation, migration and invasion protential of shMAGEA4-AS1 HSC3 and CAL27 cells. The RNA sequence of MAGEA4-AS1 was identified using the rapid amplification of cDNA ends (RACE) assay. And whole-transcriptome sequencing was used to identify MAGEA4-AS1 affected genes. Additionally, dual-luciferase reporter system, RNA-binding protein immunoprecipitation (RIP), and rescue experiments were performed to clarify the role of the MAGEA4-AS1-p53-MK2 signaling pathway. As results, we found MAGEA4-AS1 was up-regulated in OSCC tissues. We identified a 418 nucleotides length of the MAGEA4-AS1 transcript and it primarily located in the cell nucleus. MAGEA4-AS1 stable knockdown weakened the proliferation, migration and invasion abilities of OSCC cells. Mechanistically, p53 protein was capable to activate MK2 gene transcription. RIP assay revealed an interaction between p53 and MAGEA4-AS1. MK2 up-regulation in MAGEA4-AS1 down-regulated OSCC cells restored MK2 and epithelial-to-mesenchymal transition related proteins' expression levels. In conclusion, MAGEA4-AS1-p53 complexes bind to MK2 promoter, enhancing the transcription of MK2 and activating the downstream signaling pathways, consequently promoting the proliferation and metastasis of OSCC cells. MAGEA4-AS1 may serve as a diagnostic marker and therapeutic target for OSCC patients.

Paraneoplastic pemphigus associated with nonhuman papillomavirus-related tonsillar squamous cell carcinoma: A case report.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare, life-threatening autoimmune bullous disease. Among the ≈500 reported cases of PNP, only 1 case has been associated with tonsillar cancer, specifically, human papillomavirus (HPV)-positive squamous carcinoma. However, the occurrence of PNP in non-HPV-related tonsillar cancer is exceptionally rare and has not been reported to date. METHODS: We present a 58-year-old male with a history of smoking, who experienced recurrent oral ulcers, right neck swelling, and hoarseness for 5 months. Diagnosis of right tonsillar squamous cell carcinoma (cT1N3bM0) was confirmed through computed tomography/magnetic resonance imaging and pathology, not associated with HPV. Histological and immunohistochemical findings indicated PNP. RESULTS: The patient underwent primary tumor resection and ipsilateral neck dissection. Topical steroids and antifungal agents were administered to manage oral lesions and prevent secondary infections. Adjuvant concurrent chemoradiotherapy with cisplatin proceeded smoothly. Postconcurrent chemoradiotherapy follow-up at 3, 6, and 9 months, utilizing computed tomography/magnetic resonance imaging and nasopharyngoscopy, revealed no signs of recurrent cancer or PNP. CONCLUSION: Early indicators, such as oral mucosal ulcers and skin blisters, prompt consideration of underlying oral cancer in PNP. Comprehensive examination is crucial for diagnosing PNP and identifying concurrent internal neoplasms. Effective management includes occult malignancy treatment, postoperative steroid therapy, and infection prevention.

Surgery-based radiation-free multimodality treatment for locally advanced cervical cancer.

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.

SQLE-a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration.

BACKGROUND: Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. METHODS: RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. RESULTS: SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. CONCLUSION: SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Management of cervical cancer in pregnancy in a low resource setting: a rare case report.

BACKGROUND: Cervical cancer in pregnancy is a rare event. Diagnosis and management of cervical cancer in pregnancy is complicated and challenging in a low resource setting. CASE PRESENTATION: Herein, we present a case of cervical cancer (FIGO stage IB3) diagnosed at 28+ 5 weeks and successfully managed at 37+ 2 weeks of gestation in a 27-year-old woman. CONCLUSION: This is the first case report on cervical cancer in pregnancy from Bhutan. It highlights the diagnostic and management challenges in a low resource country.

The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.

Squamous Cell Carcinoma (SCC) is a subtype of Non-Melanoma Skin Cancer, the most common group of malignancies worldwide. Photodynamic therapy (PDT) is a non-invasive treatment approved for specific subtypes of SCC. Some malignancies resist PDT, forming more aggressive tumors and multiple relapses. Thus, new approaches aimed at optimizing the response to PDT are needed. The mTORC1 inhibitor rapamycin, also known as Sirolimus (SRL), interferes with protein synthesis and cell metabolism. The use of SRL as an immunosuppressant is associated to lower rates of SCC in kidney-transplanted patients, which are frequently affected by this pathology. We have evaluated SRL pre-treatment efficacy to enhance the damage induced by PDT with Methyl 5-aminolevulinate in two different cutaneous SCC established cell lines (SCC13 and A431) in vitro and therapy sensitization in PDT-resistant cell lines. We tested for the first time the SRL + PDT combination in a SKH-1 mouse model of photocarcinogenesis, diminishing the frequency of lesions and restraining tumor growth. Molecular studies revealed that protoporphyrin IX and reactive oxygen species production induced by PDT were promoted by SRL pre-treatment. Lastly, SRL modifies the expression and intracellular location of NRF2, interfering with the downstream antioxidant response modulated by NQO1 and HO-1. In conclusion, we propose SRL as a potential adjuvant to enhance PDT efficacy for SCC treatment.

Preoperative thromboelastography parameters in predicting the tumour stage of oral squamous cell carcinoma.

BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR.

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

Assessment of the quality of oral squamous cell carcinoma clinical records in oral surgery with Surgical Tool for Auditing Records (STAR) scoring.

BACKGROUND: The Surgical Tool for Auditing Records scoring system [STAR] focuses on surgical record auditing with promising outcomes. It offers a structured approach to evaluating the quality of surgical notes. AIMS AND OBJECTIVES: This study aimed to assess the effectiveness of the STAR in evaluating oral surgical records and identifying areas for improvement in documentation practices. MATERIALS AND METHODS: The data was obtained from the Dental Information Archival Software (DIAS) of our institution. The sample size was determined using G*Power 3.1.9.4 software. Fifty consecutive oral surgery clinical records of oral squamous cell carcinoma patients were evaluated using STAR. Each record was reviewed for adherence to documentation standards including Initial Assessment (10 points), Follow-up Entries (8 points), Consent Documentation (7 points), Anesthesia Report (7 points), Surgical Log (9 points), and Discharge Synopsis (9 points). compiling a total STAR score (50 points). The data was tabulated in Google Sheets. The descriptive statistics with inter-observer agreement and the mean score were recorded. RESULTS: We observed that each of the 50 records received a score of 49/50 points on the STAR. Deductions were necessary in the Operative record section due to the lack of information regarding the sutures used. CONCLUSION: To summarize, this study emphasizes the effectiveness of the STAR scoring system in evaluating the quality of oral surgical records. Identifying deficiencies, particularly in documenting operative details, can improve the completeness and accuracy of patient records. It can ultimately enhance patient care and facilitate better communication among healthcare professionals.