Clinical relevance of glycosylation in triple negative breast cancer: a review.

Glycosylation alterations in TNBC have significant implications for tumor behavior, diagnosis, prognosis, and therapeutic strategies. Dysregulated glycosylation affects cell adhesion, signaling, immune recognition, and response to therapy in TNBC. Different types of glycosylation, including N-linked glycosylation, O-linked glycosylation, glycosphingolipid glycosylation, mucin-type glycosylation, and sialylation, play distinct roles in TNBC. The "barcoding" method based on glycosylation sites of the membrane type mannose receptor (MR) shows promise in accurately distinguishing breast cancer subtypes, including TNBC. Alpha-L-fucosidase 1 (FUCA1) and Monocarboxylate transporter 4 (MCT4) have been identified as potential diagnostic and prognostic markers for TNBC. The glycosylation status of PD-L1 impacts the response to immune checkpoint blockade therapy in TNBC. Inhibiting fucosylation of B7H3 enhances immune responses and improves anti-tumor effects. Targeting glycosylated B7H4 and modulating estrogen metabolism through glycosylation-related mechanisms are potential therapeutic strategies for TNBC. Understanding the role of glycosylation in TNBC provides insights into disease mechanisms, diagnosis, and potential therapeutic targets. Further research in this field may lead to personalized treatment approaches and improved outcomes for TNBC patients.

Sacituzumab Govitecan as a Second-Line Treatment in Relapsed/Refractory Metastatic Triple-Negative Breast Cancer Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Chemotherapy, the only treatment option for metastatic triple-negative breast cancer (mTNBC), showed decreased survival rates. Trophoblast cell surface antigen-2 (Trop-2) could be a possible target for antibody-drug conjugates (ADCs). OBJECTIVE: Sacituzumab govitecan (SG), an anti-Trop-2 ADC for pretreating relapsed/refractory mTNBC patients, was studied to know the efficacy and safety profile of the drug in mTNBC. METHODS: The present review searched MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until December 25, 2022. The studies searched comprised randomized trials and observational studies (retrospective [case-control, cross-sectional] and prospective [cohort designs]). Efficacy assessment was performed in terms of complete response (CR), partial response (PR), objective response rate (ORR), stable disease (SD), progressive disease (PD), and clinical benefit rate (CBR), and safety in terms of adverse events. RESULTS: The overall random-effects pooled prevalence of CR was 4.9 (95% CI: 3.2-7.1), PR was 35.6 (95% CI: 31.5-39.9), ORR was 6.8 (95% CI: 5.9-7.8), SD was 8.0 (95% CI: 6.7-9.4), PD was 5.1 (95% CI: 4.1-6.3), and CBR was 13.4 (95% CI: 11.8-15.1). Adverse events associated with the drug were neutropenia, fatigue, anemia, nausea, and others. CONCLUSION AND RELEVANCE: This is the first meta-analysis conducted in relapsed/refractory mTNBC patients and found that SG is efficacious but associated with some adverse effects that are related to exposure to the drug. The application of these results will allow clinicians to use SG in the management of patients with mTNBC.

Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis.

Background: Decompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood. Methods: A total of 164 decompensated cirrhotic-62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF-and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. Ex vivo co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR. Results: Frequencies of MDSCs and Tregs were significantly increased (p = 0.011 and p = 0.02) with decreased CD4 T cells (p = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) (p = 0.000, p = 0.07, and p = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (p = 0.016, p = 0.043, and p = 0.045). Ex vivo co-cultured MDSCs with T cells drove T-cell apoptosis (p = 0.03, p = 0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p = 0.044 and p = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+ Tregs but increased CD4 T-cell functionality and improved survival. Conclusion: MDSCs have an immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.

Immune Surveillance by Myeloid-Derived Suppressor Cells in Liver Diseases.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are immunosuppressive in nature, originate in the bone marrow, and are mainly found in the blood, spleen, and liver. In fact, liver acts as an important organ for induction and accumulation of MDSCs, especially during infection, inflammation, and cancer. In humans and rodents, models of liver diseases revealed that MDSCs promote regeneration and drive the inflammatory processes, leading to hepatitis, fibrogenesis, and cirrhosis, ultimately resulting in hepatocellular carcinoma. SUMMARY: This brief review is focused on the in-depth understanding of the key molecules involved in the expansion and regulation of MDSCs and their underlying immunosuppressive mechanisms in liver diseases. KEY MESSAGE: Modulated MDSCs can be used for therapeutic purposes in inflammation, cancer, and sepsis.

Normal and reconstituted high-density lipoprotein protects differentiated monocytes from oxidized low-density lipoprotein-induced apoptosis.

BACKGROUND: The progression of atherosclerosis is an ongoing struggle between cell division and cell death. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a novel receptor for oxidized low-density lipoprotein (ox-LDL), mediates ox-LDL-induced apoptosis of monocytes. The anti-atherogenic function of plasma high-density lipoprotein (HDL) includes the ability to inhibit apoptosis of macrophage, although the exact mechanism and consequences of apoptosis in the development and progression of this disease are still controversial. Thus, in the present study, the effect of normal HDL (nHDL) and reconstituted HDL (rHDL) on ox-LDL-induced cellular responses in differentiated monocytes in view of apoptosis and LOX-1 receptor expression was investigated. METHODS: The expression of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), caspase-3, and cytochrome c (cyt c) was assessed and substantiated in 30 hyper-LDL and control subjects. To assess the expression of LOX-1 on differentiated THP-1 cells, western blotting was carried out, followed by statistical analysis in 30 patients and control subjects. RESULTS: nHDL/rHDL inhibited the ox-LDL-induced apoptosis in the differentiated human monocytic cells, THP-1 cells, and differentiated monocytes of patient and control subjects. Enhanced expression of scavenger receptor, LOX-1, in the differentiated monocytes was also downregulated in presence of nHDL/rHDL. nHDL/rHDL could inhibit the ox-LDL-induced mitochondrial apoptotic pathway and aberrant expression of LOX-1 in patients. Double immunostaining using fluorescein isothiocyanate (FITC)-conjugated ox-LDL and LOX-1 in apoptotic cells indicates its significant role in the differentiated monocytes. CONCLUSION: It was observed that nHDL/rHDL could promote macrophage survival by preserving mitochondrial integrity from ox-LDL-induced apoptosis.

Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours.

INTRODUCTION: IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. AIM: To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. MATERIALS AND METHODS: A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. RESULTS: Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. CONCLUSION: IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use.

Pleural and Mediastinal Lipomatosis with Subpleural Fat as a Mimicker of Pleural Effusion- A Rare Case Report.

Subpleural and mediastinal lipomatosis are benign intrathoracic conditions discovered incidentally on plain chest radiographs. However, diagnosis is usually made by Computed Tomography (CT). A case of both mediastinal and pleural lipomatosis associated with use of steroids in a 58-year-old male patient presented with complaints of breathlessness and dry cough is discussed in this case report. Intially, pleural effusion and bilateral upper lobe patchy opacities were suspected as a cause of breathlessness on the basis of chest x-ray findings. For which, CT scan of chest was advised.

Role of Computed Tomography (CT) in Localisation and Characterisation of Suprahyoid Neck Masses.

BACKGROUND: Suprahyoid neck lesions are difficult to assess only by means of clinical inspection and therefore imaging techniques are required to precisely evaluate suprahyoid neck spaces. The aim of this study was to evaluate the distinctive role of computed tomography in the assessment of anatomical source and pathological type of masses involving the suprahyoid neck spaces. MATERIAL/METHODS: Sixty patients presenting with suprahyoid neck masses underwent computed tomography of the neck. The CT findings were correlated with histopathological findings and a final diagnosis was made. RESULTS: Overall, male preponderance was seen except in the case of parotid space lesions where female predominance was seen. The most common aetiology was squamous cell carcinoma and the majority of cases (30%) were seen in patients aged 41-50 years. The majority of lesions were found in the pharyngeal mucosal space (n=16) with squamous cell carcinoma being the most common pathology. In the parotid space, pleomorphic adenoma and in the prestyloid parapharyngeal space, squamous cell carcinoma were the most common lesions, respectively. In the retropharyngeal space, an equal incidence of malignant and inflammatory aetiologies was seen. Abscesses were the most common lesions in the prevertebral space. The pleomorphic adenoma was the most common benign tumour and was also the second most common tumour in the suprahyoid neck spaces. CT had an excellent correlation with histopathological findings with sensitivity of 96.4%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 91.67%. CONCLUSIONS: Computed tomography definitely has a major role to play in the evaluation of suprahyoid neck masses as it has an excellent correlation with post-operative histopathological diagnosis.

Colour Doppler Evaluation of Extracranial Carotid Artery in Patients Presenting with Acute Ischemic Stroke and Correlation with Various Risk Factors.

INTRODUCTION: Stroke is defined as an abrupt onset of neurologic deficit due to vascular cause. It is one of the leading causes of mortality and morbidity all over the world making early diagnosis and treatment inevitable. Lesions of extra cranial carotid arteries are implicated in majority of cases of acute ischemic stroke. Carotid Doppler is a non-invasive imaging technique, with sensitivity approaching that of angiography. Computed Tomography (CT) plays a major role to assess the site and nature of the lesion in patients with acute ischemic stroke. AIM: To evaluate the role of carotid Doppler sonography in patients presenting with acute ischemic stroke and find association between carotid artery stenosis and risk factors such as diabetes mellitus, hypertension, hyperlipidemia, smoking and age. MATERIALS AND METHODS: The present study was conducted on 50 patients. CT scan was done to diagnose acute ischemic stroke in patients who presented to emergency medicine with symptoms of acute ischemic stroke. Retrospectively CIMT and plaque characterization were done by gray scale ultrasound. Site and severity of stenosis were assessed on colour Doppler. All these findings were correlated with clinical presentation and risk factors. The collected data was statistically analyzed and multivariant logistic regression (R-value) test of significance was applied by using SPSS 16.0 version software. RESULTS: On carotid Doppler, ICA/CCA PSV ratio was good predictor of stenosis and ratio above three indicates significant stenosis (>60%). Carotid bulb was most common location of plaque formation. Hypertension and diabetes were the most prevalent risk factors for cerebral ischemic stroke. Out of total 50 patients, 32 had hypertension (64%) and 22 had diabetes (44%). Hypertension and hyperlipidemia showed maximum mean R-values (0.275 and 0.048 respectively) and positive correlation with stenosis and increased CIMT in acute ischemic stroke patients. CONCLUSION: The present study highlights the importance of Doppler sonography in acute ischemic stroke patients through surveillance of atherosclerosis.

Disseminated hydatidosis with rare presentation as "cystovesical fistula".

Disseminated hydatidosis is a rare disease and may involve any organ of the human body. In this case, an elderly female got infected by Echinococcus and presented with disseminated disease. A fistulous communication developed between one of the hydatid cysts present in the retrovesical region and the bladder, because of which the patient presented with hydatiduria.