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Urothelial carcinomas account for the majority of all primary bladder cancers, making bladder cancer the second most frequent genitourinary malignancy after prostate cancer. Bladder cancer risk rises with age and most of them return after resection due to their multifocal distribution, and they often develop in superficial locations. Like many other cancers, bladder carcinoma is associated with a few tumor markers that have been evaluated in the past. They include p53, p63, and HER2. This study was conducted on 88 patients suspected of urinary bladder carcinoma. This prospective study was done at the Department of Pathology, Osmania General Hospital, Hyderabad from August 2017 to July 2019. Of the 88 patients, 76 were diagnosed with bladder carcinoma and the remaining 12 were non-neoplastic. The primary neoplastic lesions of the urinary bladder were predominantly seen in patients older than 40 years and were found to be statistically significant (p<0.01). Of the 34 cases of high-grade papillary urothelial carcinoma (PUC), 26 (76.47%) were males, eight cases (23.53%) were females, while among the 25 cases of low-grade PUC, 20 cases (80%) were males, and five cases (20%) were females. In seven cases of squamous cell carcinoma, six cases (85.71%) were males and only one case (14.29%) was female. Of the two cases of adenocarcinoma, male and female gender accounted for one case each (50%). The two cases of papillary urothelial neoplasm of low malignant potential were males in the study. On the whole, the primary urinary bladder lesions are more predominant in the males (77.63%) than the females (22.37%). Overexpression of p53 is negatively connected to p63 expression, and HER2 and p53 were strongly associated with high tumor grade in urothelial carcinoma.
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Background Head and neck cancers are highly aggressive, frequently occurring cancers that are prevalent worldwide. The mainstay of their treatment is surgery, followed by adjuvant therapy. Various studies have documented the usefulness of molecular markers in carcinogenesis and have proven helpful in the diagnosis and treatment of head and neck cancers. Cyclin D1 is a protooncogene, overexpression of which leads to the accelerated entry of cells in the S phase of the cell cycle, causing uncontrolled proliferation of the cells. The dysregulation of human epidermal growth factor receptor 2 (HER2) neu is also related to multiple features of malignancy, including loss of cell cycle control, induction of angiogenesis, and resistance to apoptotic stimuli. This study seeks to identify a subset of patients with a bad prognosis who may require aggressive treatment strategies. Aim This study aims to determine the proportion of the expression of cyclin D1 and HER2 neu in head and neck squamous cell carcinoma (HNSCC) and analyze the association between the expression of cyclin D1 and HER2 neu using histological grading, tumor, node, and metastasis (TNM) staging, and nodal status of the tumor. Furthermore, this study also aims to document clinical outcomes, such as locoregional control, depth of invasion (DOI), and regional metastasis regarding the expression of cyclin D1 and HER2 neu in HNSCC. Setting and design This study is a laboratory-based observational study. Materials and methods Seventy histologically proven cases of HNSCC were studied for various histopathological parameters, and further immunohistochemistry (IHC) was performed for cyclin D1 and HER2 neu. The expression and intensity of cyclin D1 were multiplied, and the total score was derived. The College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guidelines for HER2 neu testing in breast cancer were used for scoring. Result Out of 70 cases, 52 (75%) demonstrated strong and moderate positivity for cyclin D1, and the p-values were 0.017, 0.001, and 0.032 for depth of invasion, TNM stage, and lymph node metastases, respectively, for cyclin D1, which was considered statistically significant. For HER2 neu, five out of 70 cases were positive, and the p-value was significant for depth of invasion (0.008). Conclusion The expression of the above marker cyclin D1 increases with stage, DOI, and positive lymph node status. Hence, cyclin D1 immunoexpression can be helpful in the early assessment of HNSCC behavior and can serve as an independent prognostic marker. Furthermore, it was observed that HER2 neu was significant with an increase in depth of invasion of tumor, which, in the American Joint Committee on Cancer (AJCC) eighth edition, is considered an important factor for determining the stage of the tumor. Further research is needed to examine whether HER2 neu can act as a prognostic factor for HNSCC and if it can be targeted for treatment options.
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Introduction The incidence of breast cancer in India is on the rise, and it is now the most common cancer affecting women in India. The main objective of our study was to estimate the prevalence of triple-negative breast cancer (TNBC) in our study population and compare the various clinicopathological characteristics of TNBC with those of non-TNBC in these patients. Methods A retrospective, cross-sectional study was conducted among 249 cases of female breast cancer who reported to a tertiary care hospital in Southern India from September 2017 to September 2021. Results The mean age at presentation was 52 years (range: 26-82 years). The prevalence of triple-negative breast cancer was 19.7%. Most of the subjects belonged to the age group of 40-60 years. The majority were with grade 2 and 3 diseases. Of the cases, 50.6% were estrogen receptor (ER) positive and 48.2% were progesterone receptor (PR) positive, and 40.1% were HER2/neu positive. Conclusion The prevalence of triple-negative breast cancer in our study population is 19.7%, which is in concordance with the literature. Large tumor size, high-grade tumors, and a higher rate of axillary lymph node metastasis are characteristic features of TNBC. TNBC are tumors with aggressive tumor biology and are associated with poor prognosis.
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In cancer diagnostics, specific analysis of blood-circulating proteins biomarkers of cancer is often complicated both by their inherently low concentrations and by strong interference from serum/blood proteins. Here, we report a simple and robust electrochemical cellulase-linked sandwich assay on magnetic beads (MBs) for fM-sensitive analysis of the Human Epidermal growth factor Receptor-2 HER-2/neu protein that is over-expressed in most aggressive breast cancers. In the assay, a sandwich is assembled by capturing HER-2/neu on either antibody (Ab) or aptamer-modified MBs accompanied by reaction with the second Ab or aptamer labelled with cellulase. On application of the sandwiches assembled on MBs onto a cost-effective graphite electrode modified with an insulating nitrocellulose film, the cellulase label digests the film. This results in the pronounced changes in the electrical properties of the modified electrodes. The chronocoulometrically-measured extent of the produced changes was proportional to the 10-15-10-10â¯M HER-2/neu in the analyzed samples, and down to 1â¯fM of HER-2/neu could be detected in human serum samples in an overall less than 3â¯h assay. The developed simple and electrochemically label-free methodology is general and can be easily adapted for testing of any other protein.
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Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Receptor ErbB-2/sangre , Aptámeros de Nucleótidos/química , Secuencia de Bases , Celulasa/química , ADN/química , Técnicas Electroquímicas/instrumentación , Electrodos , Grafito/química , Humanos , Fenómenos MagnéticosRESUMEN
The present study was aimed to develop an effective nanoliposomal vaccine delivery system with P435 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The nanoliposome formulation composed of DSPC/DSPG/Chol/DOPE and monophosphoryl lipid A was used as an adjuvant. Liposomal formulations were prepared and their physical properties were characterized. Anti-tumoral efficacy of formulations was evaluated by immunization of tumor-bearing BALB/c mice and the generated immune response was studied by using ELISpot and flow cytometry analysis. The results of the study demonstrated Lip + DOPE + P535 formulation caused the lowest tumor size and the longest survival time in TUBO mice model and could make it a promising candidate in developing effective vaccines against HER2-positive breast cancers.
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Vacunas contra el Cáncer , Neoplasias Mamarias Experimentales , Nanopartículas , Péptidos , Receptor ErbB-2 , Animales , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/farmacología , Línea Celular Tumoral , Femenino , Liposomas , Neoplasias Mamarias Experimentales/inmunología , Neoplasias Mamarias Experimentales/prevención & control , Ratones Endogámicos BALB C , Nanopartículas/química , Nanopartículas/uso terapéutico , Péptidos/química , Péptidos/inmunología , Péptidos/farmacología , Receptor ErbB-2/química , Receptor ErbB-2/inmunología , Receptor ErbB-2/uso terapéuticoRESUMEN
The study was aimed at evaluating antitumor and immunomodulatory effects of liposomal vaccine composed of P5 human epidermal growth factor receptor 2 (HER2)/neu-derived peptide coupled to the surface of high-temperature nanoliposomes containing distearoylphosphocholine:distearoylphosphoglycerol:Chol:dioleoylphosphatidylethanolamine (DOPE) comprising monophosphoryl lipid A (MPL) adjuvant in HER2/neu overexpressing the breast cancer model. BALB/c mice bearing TUBO carcinoma were subcutaneously immunized with formulations containing 10 µg P5 peptide and 25 µg MPL three times with 2-week intervals. To determine immuno responses in immunized mice, the amount of released interferon-γ and IL-4 were measured by the enzyme-linked immunospot method and the flow cytometric analysis on the isolated splenocytes. The results demonstrated that tumor-bearing mice immunized with Lip/DOPE/MPL/P5 formulation had the most released interferon-γ and the highest cytotoxic T lymphocyte responses that led to the lowest tumor size and the longest survival time than those of other formulations. The results achieved by Lip/DOPE/MPL/P5 formulation could make it a suitable candidate to induce effective antigen-specific tumor immunity against breast cancer.
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We have investigated the in vitro immunogenicity and in vivo prophylactic and therapeutic potential of lambda (λ) phage particles displaying the E75 peptide (derived from HER2 protein) in an implantable TUBO breast tumor model of BALB/c mice. The mice were immunized with the E75-displaying phage (λF7-gpD::E75) every 2-week intervals over a 6-week period, and the generated immune responses were studied. Results showed in vitro induction of immune responses by the λF7 (gpD::E75) construct compared to the control λF7 and buffer groups. In the in vivo prophylactic study, all the control and vaccinated mice groups developed tumors. However, in the therapeutic experiments, we observed a significant difference in tumor size at days 14-36 for mice immunized with λF7 (gpD::E75) compared to control groups (P < 0.05). Moreover, the survival time prolonged in mice immunized with λF7 (gpD::E75). The discrepancy between the results obtained from the in vitro and in vivo studies may have been a result of the induction of Foxp3 CD4+CD25+ which has been previously reported to hamper effective T cell functionality. In conclusion, we observed a significant immune stimulatory response in the in vitro study, while in vivo, the vaccine was not able to exert significant tumor inhibitory effects. We suggest that the presence of Foxp3+ CD4+CD25+ cells may have impaired the anti-tumor response in mice challenged in vivo with the TUBO xenograft tumor.
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Bacteriófago lambda/fisiología , Neoplasias de la Mama/terapia , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Glucosafosfato Deshidrogenasa/inmunología , Fragmentos de Péptidos/inmunología , Receptor ErbB-2/inmunología , Linfocitos T Reguladores/inmunología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Glucosafosfato Deshidrogenasa/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Nanopartículas , Fragmentos de Péptidos/genética , Receptor ErbB-2/genética , Carga Tumoral , VacunaciónRESUMEN
The purpose of this study was to optimize a method for the encapsulation of P5 peptide, a new designed peptide containing MHC class I epitopes from rat HER2/neu protein, into liposomes as an approach for breast cancer vaccine formulation. The efficiency of liposomal encapsulation of peptides is generally low and development of an optimized method to increase encapsulation efficiency is a big challenge. In this study, P5 peptide was encapsulated into liposomes using the following three different methods based on film-hydration procedure. In method A, the lipid film containing P5 was hydrated using buffer and then extruded to 100 nm using polycarbonate filter. In method B all the steps were the same as method A, except that the lipid film was hydrated in buffer containing 10% (v/v) of DMSO and P5 peptide. In method C, P5 peptide was added to preformed liposomes (40 mM) in the presence of ethanol (30% v/v) and incubated at 25 ºC for 1h. The highest peptide encapsulation efficiency was achieved using method C (44%). The presence of P5 peptide in purified liposomes was also confirmed using SDS- PAGE analysis. Investigation on the effects of procedure parameters of method C on encapsulation efficiency demonstrated that method is an optimized procedure for encapsulating P5 peptide. Maximal recovery from liposomes for the accurate quantification of peptide was discovered using acidified isopropanol at 1:2 of sample to solvent ratio (v/v). In conclusion, the optimal methods of encapsulation and peptide content determination in liposomes can accelerate the development of liposomal vaccine formulations.
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The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.