Carcinomas Of Epithelial Origin Research Articles

Preparation of chitosan nanoparticle containing recombinant CD44v antigen and evaluation of its immunization capacity against breast cancer in BALB/c mice

Objective(s)Breast tumors show heterogeneity containing cancer stem cells as a small subpopulation of a tumor mass. CD44 as a cancer stem cells antigen is abnormally expressed by carcinomas of epithelial origin. Also, overexpression of CD44 variable isoforms (CD44v) is associated with malignancy in breast cancer. In the present research, our objective was to evaluate the immunogenicity of prepared nanoparticles containing a novel recombinant CD44v (rCD44v) protein in the mouse model.Materials and methodsCD44 gene was expressed in E. coli BL21 DE3 using the pET28a-CD44 vector. The expressed rCD44v protein was purified, encapsulated into the chitosan nanoparticles, and administered to BALB/c mice. ELISA was used to evaluate the immunoglobulin levels of immunized animals. For challenge experiment, 2 × 106 4T1-CD44 tumor cells were injected subcutaneously in mice, and tumor size, necrosis, and metastases were measured. Finally, cell proliferation assay, cytokines assay, and neutralization assay of the mouse anti-rCD44v on the human breast cancer cell line were examined.ResultsThe measured size of chitosan-rCD44v nanoparticles was 146.5 nm. Recombinant CD44v encapsulated by chitosan nanoparticles increases immunological responses via the adjuvant nature of chitosan nanoparticles. In the immunized mice, IgG and IgA titers were significantly increased. Tumor growth in injection and nano-injection test groups compared with the mice control groups displayed a significant reduction (P < 0.05). A high amount of splenocytes secreting IFNγ and IL-17 was seen in immunized mice with rCD44v (P < 0.05). Furthermore, a smaller size of lung metastases compared to the control mice groups was detected.ConclusionThe encapsulated rCD44v within the chitosan nanoparticles induced a significant immune response in mice and can establish significant protection against breast cancer. Therefore, it can be considered a vaccine candidate for breast cancer therapeutic modalities.

Metastatic Disease of the Temporal Bone: A Contemporary Review

To identify the frequency and primary site of metastatic pathologies to the temporal bone and characterize the associated symptomatology. The MEDLINE, Embase, and Web of Science databases were systematically reviewed according to the PRISMA guidelines to identify all cases of pathologically confirmed distant temporal bone metastases published with English translation until October 2019. Descriptive statistics were performed. Out of 576 full-length articles included for review, 109 met final criteria for data extraction providing 255 individual cases of distant temporal bone metastases. There was a male predominance (54.9%) with median age of 59.0 years (range 2-90). The most common locations of primary malignancy included the breasts (19.6%), lungs (16.1%), and prostate (8.6%). Most tumors were carcinomas of epithelial origin (75.3%) and predominantly adenocarcinoma (49.4%). The commonest metastatic sites encountered within the temporal bone were the petrous (72.0%) and mastoid (49.0%) portions. Bilateral temporal bone metastases occurred in 39.8% of patients. Patients were asymptomatic in 32.0% of cases. Symptomatic patients primarily reported hearing loss (44.3%), facial palsy (31.2%), and otalgia (16.6%) for a median duration of 1 month. Petrous lesions were associated with asymptomatic cases (P = .001) while mastoid lesions more often exhibited facial palsy (P = .026), otalgia (P < .001), and otorrhea (P < .001). Non-carcinomatous tumors were associated with petrosal metastasis (P = .025) and asymptomatic cases (P = .109). Carcinomatous metastases more often presented with otalgia (P = .003). Temporal bone metastasis is uncommon but should be considered in patients with subacute otologic symptoms or facial palsy and history of distant malignancy. Laryngoscope, 131:1101-1109, 2021.

The Overexpression of Folate Receptors in Gynecologic Oncology - a Diagnostic and Therapeutic Approach

Since the discovery of the overexpression of alpha folate receptors (α-FR) in different types of epithelial origin cancers, the arising implications in diagnosis, prognosis and therapy have been thoroughly studied. The α-FR is a glycosylphosphatidylinositol-anchored protein with high affinity for 5-methyltetrahydrofolate, the predominant plasma folate. The expression of FRα in healthy cells is found to be only on the apical surface, but the expression in numerous carcinomas of epithelial origin is 100-300 times higher than on healthy cells and it is in the order of 1-10 million receptor copies per cell. Due to the increased expression of α-FR in epithelial tumor cells, it has been emphasized that this receptor could represent a useful target for the development of new and selective anticancer drugs. For targeted delivery to FR expressing cells, it is involved the covalent linkage of folate to a variety of molecules, including chemotherapy or imaging agents. Exploiting the overexpression of α-FR in cervical dysplasia and cervical cancer, a new, cost effective and high sensitivity screening test has been developed. Keywords: folate receptor, gynecologic oncology, folate receptor-mediated staining procedures, cervical cancer screening

Thyroid Gland as a Target of Secondary Malignancies - an Autopsy Study and Review Data

Secondary malignancies of the thyroid gland are rarely diagnosed but their incidence at autopsy is not uncommon. To investigate the clinicopathological features of patients with metastatic tumours of the thyroid gland, we reviewed autopsy records and pathological features of 36 cases with thyroidal secondary tumours from 266 cases of malignant neoplasias (excluding cases of primary thyroid cancer), over a 16-year period. There were 19 men and 17 women in the study, ranging in age from 37 to 95 years (mean 70.4 years). The incidence of metastasis in thyroid gland was 0.9% in all autopsy cases, and 13.53% of the malignant tumours. The majority were carcinomas of epithelial origin. The lung was the most common primary tumour site (33.3%), followed by the breast (8.33%) and the kidney (8.33%). The most common non-epithelial malignancy was lymphoma, followed by leukaemia (total of both 25%). As for the microscopic morphological observations, diffuse infiltration pattern of tumour cells was noted in 63.89% of the cases, the formation of nodules in 33.33% of the cases and contiguous invasion in 2.79% of the cases. There were 35.71% cases of metastases associated with multinodular goitre and 28.57% cases associated with papillary microcarcinoma. Our study indicates that thyroid secondary malignancies are not infrequent and may constitute a diagnostic problem. Lung cancer is the most common neoplasm that metastasizes to the thyroid gland in north-western Greek population.

Benign giant-cell tumor of the common bile duct: A case report

Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor's possible confusion with other malignant tumors.

Interaction of adriamycin with a promoter region of hmga1 and its inhibitory effect on HMGA1 expression in A431 human squamous carcinoma cell line

The high mobility group A1 (HMGA1) are non-histone chromosomal proteins consisting of HMGA1a and HMGA1b which act as architectural transcription factors. Elevated levels of HMGA1 are reported in a number of human cancers and suggested as tumor markers. Due to their role in neoplastic transformation and tumor progression, we considered HMGA1 as a potential target for downregulation at the transcriptional level. The present paper deals with the binding of a widely used chemotherapeutic agent, adriamycin (ADM), to hmg a1 gene promoter (-304 to -284), 21RY, and its effect on the expression of hmga1 at the mRNA and protein levels and further its cytotoxic efficacy in A431 cells. A strong complex (21RY-ADM) formation caused hypochromic and bathochromic changes in UV-absorption, considerable spectral changes in circular dichroism of adriamycin and DNA and significant quenching of fluorescence emission of ADM. Thermodynamics of 21RY-ADM interaction was studied by isothermal titration and differential scanning calorimetric techniques that revealed the binding to be exothermic and favored by both negative enthalpy and positive entropy changes. Further, even low concentrations (10.3 nM) of ADM showed cytotoxicity on human squamous carcinoma cells (A431) and caused downregulation (by ∼ 70%) of hmga1 at mRNA and protein levels. Present findings clearly support the inhibitory effect of ADM on hmg a1 which quite probably is the consequence of its binding to the targeted region of hmg a1. Therefore, it appears that hmg a1 is a novel potential chemotherapeutic target in treating carcinomas of epithelial origin like prostate, breast, thyroid etc.

Detection of Circulating Anti-Mucin 1 (MUC1) Antibodies in Breast Tumor Patients by Indirect Enzyme-Linked Immunosorbent Assay Using a Recombinant MUC1 Protein Containing Six Tandem Repeats and Expressed in Escherichia coli

Mucin 1 (MUC1), a tumor-associated antigen, is a transmembrane glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas of epithelial origin. Autoantibodies against MUC1 are often found in circulation, either free or bound to immune complexes, which might contribute to limit tumor outgrowth and dissemination by antibody-dependent cell-mediated cytotoxicity, and were found favorably predictive of survival in early breast cancer patients. There is no commercial enzyme-linked immunosorbent assay (ELISA) kit for detecting the anti-MUC1 antibodies in human serum thus far. To detect circulating anti-MUC1 antibodies, we established an indirect ELISA (I-ELISA) using a recombinant MUC1 protein containing six tandem repeat sequences of MUC1 after the antigenicity and specificity of the protein were confirmed. The I-ELISA had a sensitivity of 91.3% and a specificity of 94.1% when a competitive I-ELISA was used as a reference test. The results showed that more patients with benign breast tumors (P = 0.001) and breast cancer patients before primary treatment (P = 0.010) were found to have anti-MUC1 IgG than healthy women; anti-MUC1 IgG before primary treatment was found more than after primary treatment (P = 0.016) in breast cancer patients. Interestingly, the anti-MUC1 IgG serum level was reversely correlated to that of CA15-3 antigen in advanced-stage patients (r = -0.4294, P = 0.046). Our study has demonstrated the suitability of the established I-ELISA for detecting circulating anti-MUC1 antibodies in human serum. Furthermore, we found that circulating anti-MUC1 antibodies may still bind MUC1 shed into blood in stage IV breast cancer, which can support the use of MUC1-target immune therapy strategies.

Study of the retroperitoneal lymphatic spread of müllerian ovarian carcinoma, using lymphography

From January 1973 to May 1974, 117 patients with ovarian carcinomas were evaluated with lymphography. The tumors were staged and classified histopathologically according to FIGO (1971). Considering all cases, lymphography showed nodal metastases in 44 patients (38%). Lymphography was positive in 36% of serous cystoadenocarcinomas, in 26% of mucinous cystoadenocarcinomas, in 15% of endometrioid carcinomas and in 36% of unclassified carcinomas. Of the 10 cases not identified by cell type, lymphography was positive in 40% of cases. In 68% of cases bilateral involvement was found. The site of metastatic nodes was in 32% of cases only in the iliac chains were both involved. Considering the single node chains we found 36% of para-aortic, 27% of common iliac, 35% of external iliac and 2% of inguinal involvement. Metastases were observed, regardless of histological type, in 25% of cases in stage III, 62% iin stage IV, 54% in recurrences and only in 5% of cases in stage I. Therefore the lymphatic spread seems to occur in more advanced stages and in recurrences. In 28 of 117 patients node biopsy was performed. Histological-lymphographic correlation was correct in 7/7 positive cases and in 19/21 negative cases (93%). These results show that lymphography is a reliable tool in the evaluation of ovarian cancer.