Malignant Tumors Of Epithelial Origin Research Articles

Tumor-associated macrophage-derived itaconic acid contributes to nasopharyngeal carcinoma progression by promoting immune escape via TET2

Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in South China, Southeast Asia and North Africa. The intervention of tumor-associated macrophages (Mφs) (TAMs)-mediated immunosuppression is a potential therapeutic strategy against tumor metastasis, but the exact mechanisms of TAM-mediated immunosuppression in nasopharyngeal carcinoma are unclear. Furthermore, how TAM affects the occurrence and development of nasopharyngeal carcinoma through metabolism is rarely involved. In this work, we revealed that NPC cells promoted M2-type Mφ polarization and elevated itaconic acid (ITA) release. Also, TAMs facilitated NPC cell proliferation, migration, and invasion through immune response gene 1 (IRG1)-catalyzed ITA production. Then, IRG1-mediated ITA production in TAMs repressed the killing of CD8+ T cells, induced M2-type polarization of TAMs, and reduced the phagocytosis of TAMs. Moreover, we demonstrated ITA played a tumor immunosuppressive role by binding and dampening ten-eleven translocation-2 (TET2) expression. Finally, we proved that ITA promotes NPC growth by facilitating immune escape in CD34+ hematopoietic stem cell humanized mice. In Conclusion, TAM-derived ITA facilitated NPC progression by enhancing immune escape through targeting TET2, highlighting that interfering with the metabolic pathway of ITA may be a potential strategy for NPC treatment.

Abstract LB127: A first-in-class bispecific ADC targeting FORL1 and MUC1 exhibits promising anti-tumor activity in a FOLR1low xenograft model

Abstract Folate receptor alpha (FOLR1) is specifically overexpressed in malignant tumors of epithelial origin, including ovarian, lung and breast cancers. While antibody-drug conjugate (ADC) therapies targeting FOLR1 have shown promise in clinical trials, there is still a large proportion of patients, particularly those with low FOLR1 expression, who do not respond, indicating new therapeutic strategies are needed. MUC1 is another tumor-associated antigen that is likewise overexpressed in epithelial ovarian cancer, breast cancer, and NSCLC, among other cancers; analysis of ovarian PDX tumors by immunohistochemistry (IHC) suggests that FOLR1 and MUC1 are both highly expressed in this cancer type. We therefore hypothesized that dual targeting of FOLR1 and MUC1 could provide therapeutic benefit in ovarian cancer as well as a broad range of tumors. We generated a FOLR1 x MUC1 bispecific antibody (bsAb) from anti-FOLR1 and anti-MUC1 monoclonal antibodies that were produced using RenLite® fully human common light chain mice. These parental monoclonal antibodies recognize both human and cynomolgus monkey antigens. Anti-FOLR1 antibodies were highly specific for FOLR1, as they did not recognize other FOLR family members. The anti-MUC1 antibody was previously confirmed to target MUC1-C, the juxtamembrane domain of MUC1, ensuring tumor cell recognition regardless of MUC1 cleavage. Assessment of the novel FORL1 x MUC1 bsAb indicates binding to several ovarian, breast and NSCLC cell lines, and shows enhanced internalization in MDA-MB-468 and T47D cell lines when compared to parental antibodies. Subsequently, the FORL1 x MUC1 bsAb was conjugated to vcMMAE with a DAR of 4, to generate a bispecific ADC, BCG023. BCG023 exhibited superior tumor growth inhibition compared to benchmark ADCs conjugated with the same payload and DAR in a low FOLR1-expressing NSCLC PDX model. These data suggest that targeting FOLR1 and MUC1 with a bispecific ADC is a promising therapeutic strategy for the treatment of ovarian and other tumors. Citation Format: Yifu Zhang, Chengzhang Shang, Chaoshe Guo, Yi Yang. A first-in-class bispecific ADC targeting FORL1 and MUC1 exhibits promising anti-tumor activity in a FOLR1low xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB127.

Clear Cell Odontogenic Carcinoma of the Mandible, Case Report

Caucasian patient, ECOG-PS 0, 38 years old, presented at the hospital with symptoms of pain in the lower left region of the mandible, objectively without swelling, on radiographic examination, she presented an extensive lesion with radiolucency in the region of element 37, with image filling, displacement of element 38 and apical involvement of element 36. In the tomographic exam, he presented a lesion with great destruction of the lingual wall and accentuated bone sequestration. It was opted for the differential diagnosis of the same by biopsy of the region with partial removal of healthy and diseased tissue associated with aspiration puncture, the histopathological examination was diagnosed as odontogenic clear cell carcinoma, a rare malignant tumor of epithelial origin, common in aged over 50 years and without behavioral pattern at its emergence.

C2orf40 inhibits metastasis and regulates chemo-resistance and radio-resistance of nasopharyngeal carcinoma cells by influencing cell cycle and activating the PI3K/AKT/mTOR signaling pathway.

BackgroundNasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in Southern China. C2orf40 has been identified as a tumor suppressor gene in many cancers. However, the roles of C2orf40 in nasopharyngeal carcinoma has not been studied.MethodsIn this study, a bioinformatics analysis was performed to identify the differentially expressed genes in NPC. The quantitative methylation levels was detected using pyrosequencing. qRT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to detect the expression level of related RNA and proteins. Cell proliferation was detected using CCK-8 assay, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. The apoptosis level of cells was assessed using TUNEL staining. Endogenous DNA damage and repair were assessed by the comet assay. Cell cycle analyses carried out by flow cytometry. Finally, We used a xenograft nude mouse to verify the roles of C2orf40 in chemoresistance and radioresistance in vivo.ResultsWe found that the C2orf40 expression was significantly downregulated in NPC tissues and inversely associated with a poor prognosis. In vivo and in vitro functional experiments confirmed that overexpression of C2orf40 significantly inhibited the migration and invasion of NPC cells, and promoted their sensitivity to radiotherapy and chemotherapy of NPC cells. Mechanically, the expression level of C2orf40 was negatively correlated with the expression levels of CCNE1 and CDK1. Overexpression of C2orf40 induced cell cycle arrest of NPC cells at G/M phase. In addition, C2orf40 can down-regulated the expression levels of homologous recombination-related proteins (BRCA1, BRCA2, RAD51, and CDC25A) and inhibited the activity of the PI3K/AKT/mTOR signaling pathway.ConclusionThe results clarified the biological functions and mechanisms of C2orf40, as a tumor suppressor gene, in NPC, and provided a potential molecular target for improving the sensitivity of NPC to radiotherapy and chemotherapy.

Novel Anti-FOLR1 Antibody-Drug Conjugate MORAb-202 in Breast Cancer and Non-Small Cell Lung Cancer Cells.

Antibody–drug conjugates (ADCs), which are currently being developed, may become promising cancer therapeutics. Folate receptor α (FOLR1), a glycosylphosphatidylinositol-anchored membrane protein, is an attractive target of ADCs, as it is largely absent from normal tissues but is overexpressed in malignant tumors of epithelial origin, including ovarian, lung, and breast cancer. In this study, we tested the effects of novel anti-FOLR1 antibody–eribulin conjugate MORAb-202 in breast cancer and non-small cell lung cancer (NSCLC) cell lines. FOLR1 expression, cell proliferation, bystander killing effects, and apoptosis were evaluated in seven breast cancer and nine NSCLC cell lines treated with MORAb-202. Tumor growth and FOLR1 expression were assessed in T47D and MCF7 orthotopic xenograft mouse models after a single intravenous administration of MORAb-202 (5 mg/kg). MORAb-202 was associated with inhibited cell proliferation, with specific selectivity toward FOLR1-expressing breast cancer cell lines. Eribulin, the payload of MORAb-202, was unleashed in HCC1954 cells, diffused into intercellular spaces, and then killed the non-FOLR1-expressing MCF7 cells in co-culture systems. In orthotopic xenograft mouse models, FOLR1-expressing T47D tumors and non-FOLR1-expressing MCF7 tumors were suppressed upon MORAb-202 administration. The novel anti-FOLR1 antibody–eribulin conjugate MORAb-202 has potential antitumor effects in breast cancer.

Combined and selective miR-21 silencing and doxorubicin delivery in cancer cells using tailored DNA nanostructures

MicroRNAs play an important role in tumorigenesis and, among them, miR-21 is found to be aberrantly up-regulated in various tumors. The tumor-associated antigen, folate receptor alpha is a GPI-membrane protein overexpressed in many malignant tumors of epithelial origin, including ovarian and cervical cancers. Covalently bound octahedral DNA nanocages were functionalized with folate molecules and utilized as scaffolds to engineer four sequestering units with a miR-21 complementary sequence for obtaining biocompatible Fol-miR21-NC non-toxic nanostructures, to be able to selectively recognize folate receptor alpha-overexpressing cancer cells and sequester the oncogenic miR-21. qPCR assays showed that Fol-miR21-NCs reduce the miR-21 expression up to 80% in cancer cells in the first 2 days of treatment. Functional assays demonstrated that miR-21 sequestering leads to up-regulation of miR-21 tumor suppressor targets (i.e., PTEN and Pdcd4), reduction in cancer cell migration, reduction in proliferation, and increase in cell death. Fol-miR21-NCs can be efficiently loaded with the chemotherapeutic agent doxorubicin. Co-delivery of anti-miR-21 and doxorubicin showed additive cytotoxic effects on tumor cells, paving the way for their use as selective nucleic acid drugs.

Isolation of Circulating Tumor Cells from Peripheral Blood Samples of Cancer Patients Using Microfluidic Technology.

The aim of the investigation was to study the potential of an innovative microfluidic technology for the isolation of circulating tumor cells (CTCs) from the peripheral blood samples of cancer patients.Materials and Methods.Peripheral blood samples from 5 patients with disseminated malignant tumors of epithelial origin were processed with the use of the microfluidic technology (based on a specifically designed silicone chip). The cells were separated according to their density criterion based on the lateral migration of solid particles in a liquid due to inertial forces. With the help of the designed chip configuration, the cells over 13 μm in size which is larger than the standard size of blood cells were isolated. The resulting target cell fraction was stained by the Romanowsky–Giemsa method. Staining with the fluorescent Anti-Cytokeratin (CK3-6H5)-FITC antibody was carried out to confirm the epithelial nature of the cells, and the DAPI dye was used to contrast the nucleus. The blood of a healthy volunteer and tumor cells of the A549 line were used for the immunocytochemical studies.Results.The tumor cells in peripheral blood (in the number of 1 to 9) were detected in all 5 patients. CTC clusters of 2–5 cells were identified in blood samples from the patients with laryngeal cancer, non-small cell lung cancer, and floor of the mouth cancer. A bright saturated staining of the A549 tumor cells was obtained using the Anti-Cytokeratin (CK3-6H5)-FITC antibody, corresponding to the staining of the cytoskeleton of epithelial cells. Successful nuclear staining with DAPI confirmed that the isolated target cells are not damaged during microfluidic separation.Conclusion.The microfluidic technology that has been used enables effective intact CTCs isolating from the peripheral blood of cancer patients. The epithelial nature of the isolated cells can be confirmed by immunocytochemical studies.

Effect of family support on quality of postoperative life in patients with digestive cancer.

Digestive tumors are malignant tumors of epithelial origin with high rates of morbidity and mortality worldwide. At present, surgery is the main treatment for patients with digestive tumors. In this study, we conducted a survey of patients with digestive cancers to explore the influence of family support on postoperative quality of life, with the aim of providing a basis of reference for further improvement of the quality of life of such patients. A total of 82 patients with digestive cancer who underwent surgery in Hospital of Chengdu University of Traditional Chinese Medicine between October, 2018 and April, 2019 were selected to take part. The self-made questionnaire, the European Cancer Research and Treatment Organization's Core Quality of Life Questionnaire for Cancer Patients, and the Family Support Scale were used to investigate the patients, and the collected data were statistically analyzed. The family support scores of the 82 enrolled patients ranged from 5 to 15 points, with an average score of (8.86±2.47) points; 60 cases (73.17%) scored ≥10 points and 12 cases (26.83%) scored <10 points. Patients who were married, aged under 30 years old, or employed as civil servants had higher family support scores than other patients (P<0.05). The scores for physical function, emotional function, and overall health status/quality of life in patients who had a high family support score were higher than those in patients who had a low family support score (P<0.05). According to the logistic regression model, Patients with higher age, getting married, with education level of bachelor degree or above, occupation as farmer and with other digestive tract tumor got higher family support score. (P<0.05). Good family support can effectively improve quality of postoperative life for patients with digestive cancer. Education, age, occupation and marriage are all independent factors that affect family support.

Evaluación de Nimotuzumab para el tratamiento de cáncer de cabeza y cuello: Meta-análisis de ensayos controlados

Nimotuzumab, humanized monoclonal antibody, directed against the epidermal growth factor receptor: highly expressed protein in malignant tumors of epithelial origin. It has been registered for head and neck tumors since 2002. To determine the effectiveness of Nimotuzumab in head and neck cancer through the combined meta-analysis technique. A search was conducted in PubMed, in an indexed magazine with the words “Nimotuzumab”, “head and neck,” 48 articles published by Cuban and foreign authors were detected between April 1, 2005, and July 31, 2019, in which the results of clinical studies conducted with the monoclonal antibody Nimotuzumab are described. Seven clinical trials conducted in Cuba from 2005-2019 with Nimotuzumab are described; three Phase I / II (with 14, 10 and 10 patients respectively), a Phase II / III with 106 patients, a Phase II with 37 patients, two Phase IV (with 386 and 225 patients each) and a study promoted by the Researcher with 17 patients. From these studies, the three controlled trials were selected by the PRISMA flow chart. The meta-analysis consisted of the construction of the Forest Plot graph, the sensitivity analysis and the cumulative analysis. The meta-analysis shows favorable results for Nimotuzumab, without heterogeneity (I2 = 0%). The sensitivity analysis reveals that the test that differs most from the others is Phase II / III. The cumulative analysis indicates that after the second trial, there is already sufficient evidence.

Abstract 4743: Using genome-wide CRISPR screen to understand resistance mechanisms to PCA062, a P-cadherin targeting antibody-drug conjugate

Abstract P-cadherin (PCAD) is a member of the cadherin family that mediates calcium dependent cell-cell contacts in adherens-type junctions of epithelium. Expression of P-cadherin is high in malignant tumors of epithelial origin, such as breast, esophagus, head and neck cancers, but low in normal tissues. This expression pattern makes P-cadherin a potential good target for antibody-drug conjugates (ADCs). PCA062 is a first-in-class antibody drug conjugate targeting P-cadherin. PCA062 consists of a fully human anti-P-cadherin antibody of the IgG1/κ subtype, a non-cleavable bi-functional linker (SMCC) and a maytansine-derived cytotoxic payload (DM1, with a target average drug to antibody ratio (DAR) of 3.8). PCA062 activity was examined in a collection of cell lines expressing high level of PCAD. A subset of these PCAD high cell lines are resistant to PCA062 treatment while they remain sensitive to DM1, suggesting defects in the process of PCA062 uptake or the processing and release of DM1 into the cytoplasmic compartment. PCA062 internalization rate was measured by the uptake of a fluorescent dye labeled anti-PCAD antibody (CQY684, the Ab portion of PCA062) in both PCA062 sensitive and resistant lines. PCA062 resistant lines show slower CQY684 internalization as compared to PCA062 sensitive lines, indicating a defect in ADC internalization may contribute to PCA062 resistance. To explore additional resistance mechanisms to PCA062 as well as to find critical components for PCA062 internalization, a genome wide CRISPR screen was performed in PCA062 sensitive HCC1954 and in PCA062 resistant KYSE510 cell line in the presence and absence of PCA062 and DM1 to look for genes that when knocked out may specifically modulate PCA062 sensitivity. The multi-drug resistant gene MRP1 is a strong hit for PCA062 sensitization in both PCA062 resistant KYSE510 and PCA062 sensitive HCC1954 cells. Lysosomal transporter SLC46A3 and Saga transcription complex components are strong rescue hits for PCA062 in HCC1954. These data suggest that in addition to target expression level and cell intrinsic sensitivity to payload, genes involved in ADC internalization and payload cytoplasmic accumulation will also impact tumor cell sensitivity to ADCs. Citation Format: Angela Tam, Mark Zambrowski, Katherine Seiss, Si-Qi Liu, Tinya Abrams, Giordano Caponigro, William Tschantz, Jennifer Campbell, Tony DAlessio, Qing Sheng. Using genome-wide CRISPR screen to understand resistance mechanisms to PCA062, a P-cadherin targeting antibody-drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4743.

Pituitary Adenoma Pathogenesis: The Presence Of E-Cadherin and Its Influence on Tumor Invasiveness

Cadherin of epithelial origin (ECAD) is a cell adhesion protein encoded by gene CDH1. Its loss on cell surface is related to invasiveness, metastases and bad prognosis in several malignant tumors of epithelial origin.

Benign and non-neoplastic tumours of the duodenum.

This review study describes the problem of duodenal tumours, which are rare but important in gastrological practice. The most common location of small intestinal tumours is the duodenum, and this observation is probably partly due to the greater diagnostic availability for most proximal segments of the small intestine. Among tumours the following should be mentioned – benign: adenomas, lipomas, haemangiomas, and leiomyomas; and malignant: malignant tumours of epithelial origin, primary gastrointestinal stromal tumours, neuroendocrine tumours and carcinoids, lymphomas, sarcomas, teratomas, and secondary metastases. Early duodenal tumour recognition, especially with histological assessment, plays a crucial diagnostic role with future therapeutic implications. In recent years the prevalence of benign duodenal tumours has been rising due to a higher level of clinicians’ doubts and the convenience of gastrointestinal endoscopy; hence, knowledge of this problem is important in routine clinical practice. The method of duodenal tumour treatment should be selected on an individual basis.

The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy.

Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies.Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas. In lung cancer, several transcriptional, epigenetic and genetic aberrations have been described to partly arise from environmental risk factors, but ethnic genetic predisposition factors may also play a role.The classification of the molecular hallmarks of cancer has been essential to study and achieve a comprehensive view of the interaction networks between cell signaling pathways and functional roles of the transcriptional and epigenetic regulatory mechanisms. This has in turn increased understanding on how these molecular networks are involved in embryo-layers and malignant diseases development. Ultimately, a major biomedicine goal is to achieve a thorough understanding of their roles as diagnostic, prognostic and treatment response indicators in lung oncological patients.Recently, several notable cell-signaling pathways have been studied based on their contribution to promoting and/or regulating the engagement of different cancer hallmarks, among them genome instability, exacerbated proliferative signaling, replicative immortality, tumor invasion-metastasis, inflammation, and immune-surveillance evasion mechanisms. Of these, the Hedgehog-GLI (Hh) cell-signaling pathway has been identified as a main molecular contribution into several of the abovementioned functional embryo-malignancy processes. Nonetheless, the systematic study of the regulatory epigenetic and transcriptional mechanisms has remained mostly unexplored, which could identify the interaction networks between specific biomarkers and/or new therapeutic targets in malignant tumor progression and resistance to lung oncologic therapy.In the present work, we aimed to revise the most important up-to-date experimental and clinical findings in biology, embryology and cancer research regarding the Hh pathway. We explore the potential control of the transcriptional-epigenetic programming versus reprogramming mechanisms associated with its Hh-GLI cell signaling pathway members. Last, we present a summary of this information to systematically integrate the Hh signaling pathway to identify and propose novel compound strategies or better oncological therapeutic schemes for lung cancer patients.

Rapid onset of squamous cell carcinoma in a thin skin graft donor site

Squamous cell carcinomas are malignant tumours of epithelial origin that can appear on sites subjected to chronic inflammation after a period of several years. The rapid development of squamous cell carcinoma at the donor site for a thin skin graft is a rare and poorly understood situation. We report the case of a patient undergoing thin skin grafting to cover the area of removal of a vertex squamous cell carcinoma and in whom squamous cell carcinoma appeared at the donor site within 9 weeks. In our case, we ruled out intraoperative contamination because two sets of surgical instruments were used. Given the number of cases reported in the literature, a chance event seems unlikely. The hypothesis of an acute inflammatory process caused by scarring of the thin skin graft site appears to us the most convincing. Development of cancer at the graft donor site may thus be added to the list of complications of thin skin grafting.

Epidemiological survey of oral and maxillofacial complex biopsies: 13 year retrospective study

Objective: To conduct a retrospective study through epidemiological survey of the biopsies of oral cavity performed at the Center of Pathology, Cytology, and Cytopathology– CEPACC in Parnaíba-PI, from 1998 to 2011. Material and Methods: One hundred and thirty-nine referrals and reports were analyzed by evaluating the group and prevalence of oral lesions, anatomical location, and distribution in relation to type, gender, and age. Results: Females (52%) showed the greatest prevalence, observing more cases in the age range of 41 to 60 years. The lip was the preferable location of the analyzed lesions. The groups of the lesions in salivary glands (17%), malignant tumors of epithelial origin, benign tumors of conjunctive origin, premalignant lesions of epithelial origin, and odontogenic cysts were the most common lesions. Considering the isolated lesions, squamous cell carcinoma was the most frequent. We observed a greater preference for salivary gland lesions, although great diversity of clinical cases was found. Conclusion: The reported lesions occurred mostly in adult females and in groups with salivary gland diseases. KeywordsEpidemiology; Oral lesions; Biopsy; Oral Pathology; Diagnosis.

Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.

Primary Adenoid Cystic Carcinoma of the Orbital Apex

Adenoid cystic carcinoma is an uncommon malignant tumor of epithelial origin typically arising from salivary glands. Orbital involvement may occur via direct or perineural spread from a lacrimal gland or sinonasal source. Primary orbital adenoid cystic carcinoma without involvement of the lacrimal gland is rare. The authors report a 53-year-old woman who was examined for insidious monocular vision loss and was found to have a primary adenoid cystic carcinoma of the orbital apex and cavernous sinus. Systemic workup for a primary source, including ipsilateral lacrimal gland biopsy, was negative. One must maintain a high index of suspicion for adenoid cystic carcinoma when evaluating orbital tumors.

A novel multifunctional nanocomposite C225-conjugated Fe&amp;lt;sub&amp;gt;3&amp;lt;/sub&amp;gt;O&amp;lt;sub&amp;gt;4&amp;lt;/sub&amp;gt;/Ag enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy

Radiotherapy is the major treatment for nasopharyngeal carcinoma, a malignant tumor of epithelial origin. In this process, a tracer with high sensitivity is pivotal for diagnostic imaging in radiotherapy. Here, we designed a novel multifunctional magnetic silver nanocomposite, Fe(3)O(4)/Ag conjugated to an epidermal growth factor receptor-specific antibody (C225), which can be potentially used for synchronous cancer therapy and diagnosis via magnetic resonance imaging. Characteristics of Fe(3)O(4)/Ag/C225 were determined by transmission electron microscopy, energy dispersive X-ray spectroscopy, ultraviolet spectra, and dynamic light scattering. The results demonstrated that Fe(3)O(4)/Ag/C225 nanoparticles were spherical and dispersed well in water. The activity of C225 was preserved ∼80% in the Fe(3)O(4)/Ag/C225 nanoparticles. Futhermore, we tested the cytotoxicity and radiosensitivity of the nanocomposite for human nasopharyngeal carcinoma cell lines (CNEs) in vitro. MTT analysis revealed that Fe(3)O(4)/Ag/C225 could inhibit the proliferation of CNEs in a dose- and time-dependent manner. The clonogenic assay indicated that Fe(3)O(4)/Ag/C225 combined with X-ray treatment could increase the sensitivity of CNEs to irradiation. In a summary, the novel multifunctional nanocomposite Fe(3)O(4)/Ag/C225 might be a potential radiosensitizer for treating malign tumors in the clinic.

Adenocarcinoma y carcinoma tipo linfoepitelioma sincrónico en estómago: presentación de un caso y revisión de la literatura

Gastric cancer is one of the main causes of death in the world. In Venezuela, gastric tumors represent 37% of all malignant tumors of the digestive system, but only 1,6% to 3,1% of these cases are lymphoepithelioma-like carcinoma. Synchronous neoplastic lesions are also rare. The clinical case presented herein, a man with two synchronous tumor lesions, is the first of its kind in this country. Despite their incipient aspect, the histologic study reported two malignant tumors of epithelial origin: well-differentiated adenocarcinoma and lymphoepithelioma-like carcinoma.

Abstract 2591: Folate receptor alpha: A promoter of cancer cell proliferation that is independent of folate

Abstract Folate receptor alpha (FRα) is over-expressed in malignant tumors of epithelial origin, particularly in ovarian cancer, but largely absent in normal tissue. High levels of protein expression in tumor cells are associated with increased proliferative capacity and enhanced chemo-resistance to Cisplatinum (CP). However, the underlying mechanism remains unclear. We sought to evaluate the biological function of FRα in CP-resistant cancer and hypothesized that alterations of FRα expression levels in drug CP-resistant cancers would result in the re-sensitization of tumor cells to CP. We first developed a human ovarian cancer cell line, IGROV-1, with increased CP resistance and found that these cells also showed an increase in FRα expression over parental IGROV-1 cells. Then, we used FOLR1 specific siRNA to completely knock-down FRα expression. Surprisingly, ablation of FRα expression did not restore sensitivity to CP but had a substantial negative impact on proliferation in both parental and CP-resistant cells. Similar phenomena were also observed when FRα was knocked-down in 786-0 cells, a human renal carcinoma line that expresses robust levels of FRα. In contrast, when we applied FRα knock-down to the normal human kidney cells HK-2 (FRα+), we observed no impairment on proliferation. One explanation of these results is that removal of FRα in cancer cells impairs the ability of these cells to uptake reduced folates, a requirement for nucleic acid synthesis and other methylation reactions. However, even pharmacological concentrations of 5-methyltetrahydrofolate, provided only partial restoration of proliferation in these cells. Taken together, these results suggest that FRα plays an essential role in the proliferation of tumor cells, but not in normal cells via a yet undefined pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2591. doi:10.1158/1538-7445.AM2011-2591