Oxidative versus Reductive Stress in Breast Cancer Development and Cellular Mechanism of Alleviation: A Current Perspective with Anti-breast Cancer Drug Resistance.

Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and - catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.

Disseminated tuberculosis in rare association with hemophagocytic lymphocytosis - A case report from central India.

Hemophagocytic Lymphohistiocytosis (HLH) is an uncommon, diverse and rare genetic hyper-inflammatory syndrome. HLH associated with tuberculosis (TB-HLH) has been described as a clinical and diagnostic quandary. The co-existence leads to significantly higher morbidity and mortality. Our case highlights the presence of disseminated tuberculosis and worsening of the case due to underlying hemophagocytic syndrome leading to rapid deterioration of patient prognosis. Prompt diagnosis and treatment remains help to improve patient management.

Preliminary Experience in Post-COVID-19 Mycoses: A Pathologist's Perspective.

Background Coronavirus disease is caused by the severe acute respiratory syndrome coronavirus-19. Because of co-morbidities and indiscriminate use of steroids and antibiotics, the incidence of opportunistic fungal infections has increased in COVID-affected individuals. Aims and objectives The aim of the study is to analyze the various tissue reaction patterns of COVID-19-associated mucormycosis in the surgical debridement specimens using routine hematoxylin and eosin (H&E) stain and special stains like periodic acid-Schiff (PAS), Grocott-Gomori's methenamine silver (GMS), Masson trichrome (MT) and Prussian blue (PB), and to understand the pathogenesis of COVID-19 sequelae. Materials and methods This retrospective observational study was conducted after the approval from the Institute Human Ethical Committee (IHEC) on 45 tissue samples of COVID-associated mucormycosis using routine H&E and histochemical stains such as PAS, GMS, MT, and PB. Detailed demographic profiles, clinical information, radiological findings, and relevant microbiological data in available cases, like reports on potassium hydroxide (KOH) mount preparation, and fungal culture reports on Saboraud's Dextrose Agar (SDA) medium were collected. The different histomorphological tissue reaction patterns were observed and analyzed. Results All the surgical debridement specimens from post-COVID cases had histomorphology of mucormycosis displaying broad, aseptate, ribbon-like fungal hyphae with right-angle branching (45/45). Six of the 45 cases also reveal thin, narrow septate, acute angle branching hyphae, indicating co-existing Aspergillosis (6/45). The histological tissue reaction patterns observed were categorized as extensive tissue necrosis (100%), vascular proliferation (82%), angioinvasion (58%), giant cell reaction (53%), fibrin thrombi (47%), septic thrombi and angiodestruction (40%), fungal osteomyelitis (33%), necrotizing granulomas (31%). Conclusion This study infers that post-COVID-19 associated mucormycosis, alterations in the local tissue microenvironment are found to have a favorable effect on colonizing fungi and result in destructive tissue reactions such as angioinvasion, angiodestruction, necrosis, necrotizing granulomas, suppurative inflammation, and iron pigment deposition. The spectrum of morphological changes reflects the host's immune status.

Significance of Combined Analysis of High-Risk Human Papillomaviruses Polymerized Chain Reaction Analysis and Immunohistochemical Expression of p16INK4A in Cervical Cancer in a Cohort of South-Indian Population.

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide, and it continues to be a big issue in developing countries. The current case-control study sought to determine the presence of high-risk human papillomaviruses (hr-HPV) in the development of cervical cancer, as well as their relationship with the cell cycle inhibitor gene p16INK4A in cervical cancer. Methods The association between p16INK4A protein and the presence of hr-HPV DNA in cervical lesions was explored in this study, which included 150 cervical cancer patients and 100 normal cervix samples. The immunohistochemistry approach was used to identify the expression of the p16INK4A protein, while the semi-quantitative polymerized chain reaction (PCR) method was used to identify the genomic identity of hr-HPV. Results About 90.67% (n=136) of the 150 case samples were found to be hr-HPV positive. Within the 136 HPV-positive samples, 45 (33.08%) show moderate expression of the p16INK4A protein, whereas 91 (66.91%) show overexpression, which is statistically significant (0.05). Among the 136 HPV-positive samples, 22.08% (N=30) were classified as having cervical intraepithelial neoplasia (CIN), with 56.66% (n=17) having CIN3, 36.66% (n=11) having CIN2, and 6.67% (n=2) having CIN1. Conclusion Based on the semi-quantitative immune staining scoring method of p16INK4A protein, genomic expression of HPV demonstrates that the expression of p16INK4A protein increases with the infectious load of the hr-HPV genome in the host cell. The result directly shows that immunostaining of the p16INK4A protein, in conjunction with the assessment of high-risk HPV in the host genome, will aid in the identification of cervical cancer in the cervix.

Isolated primary hydatid cyst of the pancreas: Management challenges of a cystic masquerade.

Abdominal hydatid cyst disease mostly involves the liver. Involvement of the pancreas as an isolated primary organ is rare accounting for < 2% of all systemic echinococcosis cases. It mostly involves the head of the pancreas. Symptoms depend on the location, size, and associated complications; therefore, it can have varied presentations including acute pancreatitis. On imaging, it can mimic other common pancreatic cystic lesions like pseudocyst or cystic neoplasm. Accurate preoperative diagnosis is usually difficult and requires a very high index of suspicion even in endemic areas. Herein, a case of primary isolated hydatid cyst of the pancreas that was initially diagnosed and managed as acute pancreatic pseudocyst is reported.

Multicentric Chordoma in a Child.

Chordomas are primary malignant bone tumors that arise in the axial skeleton, believed to originate from remnants of embryologic notochordal cell rests. Multicentric origin of chordoma is extremely rare. To our literature search, we found only three cases of multicentric chordoma in adults. We report a first case of multicentric chordoma in pediatric age group. A 14-month-old child presented with torticolis and left upper limb monoparesis, imaging showed expansile bony destructive lesion in clivus and dorsal spine simultaneously. The child underwent laminectomy, decompression of cord, excision of lesion, and histopathology was suggestive of chordoma. Pediatric chordomas are aggressive tumors, require multidisciplinary management with maximal safe resection followed by radiotherapy (conventional and/or proton). Even with multidisciplinary management, pediatric chordomas have high morbidity and mortality.

Recurrent extradural hemangiopericytoma of thoracic spine: a case report.

Hemangiopericytoma (HPC) is a rare tumor that arises from pericapillary cells or pericytes of Zimmerman. In the central nervous system, it accounts for less than 1% of tumors, and spinal involvement is very rare. Meningeal hemangiopericytomas show morphological similarities with meningiomas particularly with angiomatous meningioma, where one needs to take the help of immunohistochemistry (IHC) to delineate HPC from meningioma. Here, we report a case of recurrent extradural HPC in a 16 year-old girl, who 5 years back had a pathological diagnosis of angiomatous meningioma, for D5-D6 lesion. On evaluation, magnetic resonance imaging (MRI) showed a large extradural tumor with a significant cord compression involving D5-D6 body, pedicle and ribs. Excision of the lesion and spinal stabilization was performed. The histopathological examination and immunohistochemistry performed on tumor sections revealed features favoring HPC. To conclude, detailed IHC is helpful in avoiding misdiagnosis and in further management of the patient.