A Molecular Typing Method for Invasive Breast Cancer by Serum Raman Spectroscopy.

BACKGROUND: The incidence of breast cancer ranks highest among cancers and is exceedingly heterogeneous. Immunohistochemical staining is commonly used clinically to identify the molecular subtype for subsequent treatment and prognosis. PURPOSE: Raman spectroscopy and support vector machine (SVM) learning algorithm were utilized to identify blood samples from breast cancer patients in order to investigate a novel molecular typing approach. METHOD: Tumor tissue coarse needle aspiration biopsy samples, and peripheral venous blood samples were gathered from 459 invasive breast cancer patients admitted to the breast department of Sichuan Cancer Hospital between June 2021 and September 2022. Immunohistochemical staining and in situ hybridization were performed on the coarse needle aspiration biopsy tissues to obtain their molecular typing pathological labels, including: 70 cases of Luminal A, 167 cases of Luminal B (HER2-positive), 57 cases of Luminal B (HER2-negative), 84 cases of HER2-positive, and 81 cases of triple-negative. Blood samples were processed to obtained Raman spectra taken for SVM classification models establishment with machine algorithms (using 80% of the sample data as the training set), and then the performance of the SVM classification models was evaluated by the independent validation set (20% of the sample data). RESULTS: The AUC values of SVM classification models remained above 0.85, demonstrating outstanding model performance and excellent subtype discrimination of breast cancer molecular subtypes. CONCLUSION: Raman spectroscopy of serum samples can promptly and precisely detect the molecular subtype of invasive breast cancer, which has the potential for clinical value.

The Role of Meteorin-Like Peptide and Asprosin in Colon Carcinoma.

INTRODUCTION:  Colon cancer is one of the most frequent gastrointestinal system cancers on a global scale. Common colonoscopy tests have reduced the incidence of colorectal cancer (CRC). Although nutrition, microorganisms, and their metabolites are related to colon cancer, the exact mechanism of CRC is still not clear. For this reason, it is of great importance to elucidate the molecular mechanisms of colon oncogenesis. METHODS: This study was conducted retrospectively with samples obtained from the laboratory of Firat University Faculty of Medicine, Department of Pathology. A total of 30 patient samples were used. The control group consisted of healthy colon tissues from the same patients, and the other group consisted of colon carcinoma tissues from the same patients. Tissue samples of both groups were evaluated immunohistochemically with meteorin-like (METRNL) peptide and Asprosin. RESULTS: The immunoreactivity of METRNL was found to be lower in colon carcinoma tissues than in healthy colon tissues (0.2 ± 0.06 and 0.08 ± 0.03, respectively). Asprosin immunoreactivity was found to be higher in colon carcinoma tissues than in healthy colon tissues (0.4 ± 0.07 and 1.08 ± 0.15, respectively). CONCLUSION: As a result of this study, it was observed that there was a significant difference between healthy colon tissue and colon carcinoma tissue in terms of METRNL and Asprosin expression. Both proteins might be involved in the molecular mechanism of colon carcinoma. This situation is important in terms of diagnosis.

ATRA sensitized the response of hepatocellular carcinoma to Sorafenib by downregulation of p21-activated kinase 1.

BACKGROUND: Sorafenib resistance greatly reduces the efficacy of treatments in advanced hepatocellular carcinoma (HCC) patients, but the underlying mechanisms are not thoroughly understood. All-trans retinoic acid (ATRA), an anti-leukaemia agent, has attracted considerable attention due to its role in sensitizing cells to other anticancer treatments. We aimed to investigate the combined effect of ATRA and Sorafenib on HCC and the underlying mechanisms. METHODS: CCK-8, cell sphere formation, trans-well migration, and wound-healing assays were used to analyse the biological behaviours of HCC cells in vitro. Western blotting and qRT-PCR analysis were conducted to measure the expression of p21 activated kinase 1 (PAK1) and phospho-p21 activated kinase 1 (pPAK1). Xenograft models were established to confirm the synergistic effects of ATRA and Sorafenib in vivo. TUNEL assays and immunohistochemistry were utilized to determine apoptosis, proliferation, PAK1 and pPAK1 levels in tumour tissues. RESULTS: We observed that PAK1 was overexpressed in HCC, and its expression was negatively correlated with the survival of patients. PAK1 promoted the proliferation, self-renewal and epithelial-mesenchymal transition of HCC cells. Correlation analysis indicated that the IC50 of Sorafenib was positively correlated with the level of pPAK1 in HCC cell lines. ATRA inhibited the progression of HCC and sensitized HCC response to Sorafenib by downregulation of PAK1, as shown by the calculated coefficient of drug interaction and the data obtained from xenograft models. CONCLUSIONS: Our findings indicated that instead of treatment with Sorafenib alone, the combination of ATRA and Sorafenib provides a more effective treatment for HCC patients. Video Abstract.

Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and it usually occurs following chronic liver disease. Although some progress has been made in the treatment of HCC, the prognosis of patients with advanced HCC is not optimistic, mainly because of the inevitable development of drug resistance. Therefore, multi-target kinase inhibitors for the treatment of HCC, such as sorafenib, lenvatinib, cabozantinib, and regorafenib, produce small clinical benefits for patients with HCC. It is necessary to study the mechanism of kinase inhibitor resistance and explore possible solutions to overcome this resistance to improve clinical benefits. In this study, we reviewed the mechanisms of resistance to multi-target kinase inhibitors in HCC and discussed strategies that can be used to improve treatment outcomes.

Combining neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicted the prognosis of hepatocellular carcinoma patients after liver transplantation / 中华器官移植杂志

Objective:To explore the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio(PLR)and NLR-PLR score for carcinoma(HCC)patients undergoing liver transplantation(LT).Methods:From July 2015 to October 2021, clinical data are retrospectively reviewed for 110 HCC patients undergoing orthotopic LT at Third Hospital of Hebei Medical University.The values of NLR and PLR were calculated.And the cut-off values of NLR and PLR were obtained by receiver operating characteristic (ROC) curve and then grouped according to the cut-off values.Survival time is analyzed by Kaplan-Meier method and Log-rank test performed for inter-group comparison.Univariate and multivariate analyses are performed based on Cox proportional risk regression model.NLR <3.37 and PLR <105.96 are denoted as 0 point while NLR ≥3.37 and PLR ≥105.96 as 1 point.Two points are added up as NLR-PLR score.According to NLR-PLR score, they are divided into 3 groups of 0, 1 and 2.Results:Median overall survival(OS)is 27 months in patients with NLR-PLR score 0, 26.5 months in patients with NLR-PLR score 1 and 6 months in patients with NLR-PLR score 2.Median OS in patients with NLR-PLR score 2 is significantly shorter than that in those with NLR-PLR score 0/1.And the difference is statistically significant( P<0.001).Median disease-free survival(DFS)is 24.5 months in NLR-PLR 0 group, 24 months in NLR-PLR 1 group and 6 months in NLR-PLR 2 group.The difference is statistically significant( P=0.002).Univariate analysis show that Child-Pugh grade, MELD score, NLR/PLR level, NLR-PLR score, complying with University of California San Francisco Criteria(UCSF)criteria and absence/presence of microvascular invasion(MVI)have an impact on patient survival.Further multivariate analysis show that NLR-PLR score, complying with UCSF criteria and MELD score are independent risk factors affecting patients' prognosis and survival. Conclusions:NLR, PLR and NLR-PLR score may predict long-term survival of patients.And NLR-PLR score is an independent risk factor for patient survival.It has more predictive value than NLR/PLR.

TED: Two-stage expert-guided interpretable diagnosis framework for microvascular invasion in hepatocellular carcinoma.

Microvascular invasion (MVI) has been clinically recognized as a prognostic factor for hepatocellular carcinoma (HCC) after surgical treatment. Detection of MVI before surgical operation greatly benefit patients' prognosis and survival. Most of the existing methods for automatic diagnosis of MVI directly use deep neural networks to make predictions, which do not take into account clinical knowledge and lack of interpretability. To simulate the radiologists' decision process, this paper proposes a Two-stage Expert-guided Diagnosis (TED) framework for MVI in HCC. Specifically, the first stage aims to predict key imaging attributes for MVI diagnosis, and the second stage leverages these predictions as a form of attention as well as soft supervision through a variant of triplet loss, to guide the fitting of the MVI diagnosis network. The attention and soft supervision are expected to jointly guide the network to learn more semantically correlated representations and thereafter increase the interpretability of the diagnosis network. Extensive experimental analysis on a private dataset of 466 cases has shown that the proposed method achieves 84.58% on AUC and 84.07% on recall, significantly exceeding the baseline methods.

The global, regional, and national burden of nasopharyngeal carcinoma and its attributable risk factors in 204 countries and territories, 1990-2019.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in most areas of the world but poses a significant public health burden in endemic regions. OBJECTIVES: We provide an overview of the most recent global epidemiology of nasopharyngeal cancer (NPC). METHODS: We estimated the burden of NPC in 204 countries and territories by age, sex, and Socio-Demographic Index (SDI) from 1990 to 2019. RESULTS: At the GBD regional level, the most severe age-standardized incidence in 2019 occurred in East Asia. From 1990 to 2019, the East Asia and High-income Asia Pacific had the greatest increase in percentage in age-standardized incidence. Central Asia and the Caribbean had the greatest increase in percentage in age-standardized disability-adjusted life-years (DALY) and death rates. At the national level, Cabo Verde, Romania, and the Cyprus reported the largest percentage increases in the age-standardized incidence. Cabo Verde, Romania, and Jamaica reported the largest increases in the age-standardized DALY and death rates. CONCLUSIONS: The global age-standardized incidence of NPC increased globally between 1990 and 2019, especially in the East Asia.

4sc-202 and Ink-128 cooperate to reverse the epithelial to mesenchymal transition in OSCC.

Treatment of oral squamous cell carcinoma remains a challenge due to a high incidence of treatment resistance, which is followed by tumor recrudescence and metastasis to the lymph nodes. Thus, it is important to explore novel inhibitors of OSCC. Here, we aimed to identify drugs that may cooperate with histone deacetylase inhibitors to reverse the EMT, inhibit EMT and cell migration and invasion, and contribute to therapeutic efficacy. We found that treatment with 4sc-202 potently reversed the EMT and thereby inhibited cell migration and invasion in vitro, in part by inducing expression of the FoxO1 tumor-suppressor gene. Furthermore, 4sc-202 also synergized with Ink-128 to inhibit tumor migration and invasion in vitro. Mechanistically, 4sc-202 induced FoxO1 expression, whereas Ink-128 promoted nuclear translocation of FoxO1. Our findings indicated that FoxO1 might reverse the EMT by interacting with Twist1 in OSCC. In conclusion, we identified an effective combination therapy involving class I histone deacetylase and mammalian target of rapamycin complex 1/2 inhibition that effectively blocked the EMT of tumor cells by upregulating FoxO1 expression to inhibit Twist1 transcription. These data have implications for developing new targets for early diagnosis and treatment of OSCC.

Histiocytoid variant of invasive lobular breast carcinoma. A case report and literature review.

INTRODUCTION: Histiocytoid breast carcinoma (HBC) is a variant of invasive lobular carcinoma. The occurrence of HBC is rare and the natural history and clinical course of HBC is still not well known due to limited numbers of reported cases. In reality, many tumors have been misdiagnosed and reported as benign lesions. CASE PRESENTATION: A 66-year-old- postmenopausal women, who has previous personal history of right breast invasive ductal carcinoma, for which she underwent right breast wide local excision with negative sentinel lymph node biopsy and received adjuvant radiotherapy and hormonal therapy. Two years later, a new left breast suspicious lesion was detected by Imaging. Breast Ultrasound showed left breast hypo-echoic area at 12-1 o'clock with irregular spiculated lesion 3 cm away from the nipple with posterior acoustic shadowing measuring 1 × 0.7 × 0.7 cm and mild tissue distortion with thicken cortical left Axillary lymph node. Mammography of both breasts confirmed the left breast lesion at 12o'clock with necrosis and irregular margins measuring 1.1 × 1.0 cm. MRI breasts showed, left breast heterogeneously enhancing mass at 12 o'clock with no other suspicious mass in the left or right breast. Ultrasound guided left breast biopsy of the suspicious lesion seen at 12-1 o'clock which confirmed the diagnosis of invasive lobular carcinoma, histiocytoid variant She underwent wire guided left breast wide local excision with left sentinel lymph node and axillary clearance. Final histopathology showed invasive lobular carcinoma, histiocytoid variant. CLINICAL DISCUSSION: The recognition of histiocytoid breast carcinoma is often a challenge, particularly when histiocytoid tumor cells occur in a metastatic site before the primary diagnosis of breast cancer. An awareness of histological features are needed to make the accurate diagnosis. CONCLUSION: Findings that support the correct diagnosis include identifying tumor cells with more cytological atypia, the presence of cytoplasmic vacuoles and secretions. Moreover, coexistence with invasive lobular carcinoma and/or lobular neoplasia and the use of immunohistochemistry to confirm their epithelial nature. clinico-radiological correlation is essential, as any discordance should trigger further diagnostic determination.

Influence of treatment access on survival of metastatic renal cell carcinoma in brazilian cancer center

ABSTRACT Background: Tyrosine kinase inhibitors (TKI) and immunotherapy improved survival in metastatic renal cell carcinoma (mRCC). Disparities in treatment access are present in healthcare systems globally. The aim of this study was to analyze survival outcomes of mRCC patients treated with first-line TKIs in the public (PHS) and private (PrS) health system in a Brazilian Cancer Center. Materials and Methods: Records from all mRCC patients treated with first-line TKIs from 2007-2018 were reviewed retrospectively. Categorial variables were compared by Fisher's exact test. Survival was estimated by Kaplan-Maier method and survival curves were compared using the log-rank test. Prognostic factors were adjusted by Cox regression model. Results: Of the 171 eligible patients, 37 (21.6%) were PHS patients and 134 (78.4%) were PrS patients. There were no difference in age, gender, or sites of metastasis. PHS patients had worse performance status (ECOG ≥2, 35.1% vs. 13.5%, p=0.007), poorer risk score (IMDC poor risk, 32.4% vs. 16.4%, p=0.09), and less nephrectomies (73% vs. 92.5%, p=0.003) than PrS patients. Median lines of therapy was one for PHS versus two for PrS patients (p=0.03). Median overall survival (OS) was 16.5 versus 26.5 months (p=0.002) and progression-free survival (PFS), 8.4 versus 11 months (p=0.01) for PHS and PrS patients, respectively. After adjusting for known prognostic factors on multivariate analysis, PHS patients still had a higher risk of death (HR: 1.61, 95% CI: 1.01-2.56, p=0.047). Conclusion: Patients with mRCC treated via the PHS had worse overall survival, possibly due to poorer prognosis at presentation and less drug access.

[Local and systhemic immunotherapy for bladder cáncer: from bench to bedside.] / Inmunoterapia local y sistémica en cáncer de vejiga: bases moleculares y traslación clínica.

Therapeutic approaches for treatment of urothelial transitional cell carcinoma based on immune system modulation, as well as the contribution of intravesica Bacillus de Calmette-Guérin (BCG) and the recentin corporation of checkpoint inhibitors had found irrefutable proofs of concept for the indication of antitumoral immunontherapy in such tumors. Its extension and development at the present time covers all the locations of the wide spectrum of presentation and evolution of these tumors. Nowadays, apart for the low grade non muscle-invasive tumors, we are facingan unpredictable development of antitumoral immunotherapy in bladder cancer not only as an option in the primary treatment, but also in other scenarios such asnon-responders when it comes to BCG, or the situation of ineligibility for systemic chemotherapy indication. The main objective of this review article is trying to translate the current basic mechanisms involved in different phases of transitional cell carcinomas antitumoral response, regardless of whether they are muscle-invasive or not, and to establish the rationale for their therapeutic intravesical or systemic administration. The role of the interactions established between urothelial tumor cells and the cellular and molecular elements of the immune system of patients is described, incorporating the relevant and recent advances in immunobiology and the molecular characterization of these tumors thatwill undoubtedly introduce far-reaching modifications intherapeutic regimes that will contrast with the traditional options available. Investigational lines that are already active in the clinical research phase with BCG and, checkpoints inhibitors ofthe immune response are also analyzed, high lighting theneed to find predictive response markers as a real option for treatments personalization. The approach to the knowledge of the individual reactivity of the immune system of each patient as a determining factor to achieve it is proposed.

Los abordajes terapéuticos para los carcinomas de células transicionales del urotelio desarrollados en torno a la modulación del sistema inmune encuentran, en la contribución del Bacillus de Calmettey Guérin (BCG) intravesical y más reciente la de los fármacos inhibidores de los puntos de control de la respuesta inmunitaria, indiscutibles pruebas de concepto de la indicación inmunoterapia antitumoral. Su extensión y desarrollo en el momento actual abarca todas las localizaciones del amplio espectro de presentación y evolución de estos tumores. A excepción, por el momento, de los tumores no-músculo infiltrantes debajo grado, acudimos a un desarrollo impredecible de la inmunoterapia antitumoral en el cáncer de vejiga no solo como opción en el tratamiento primario de alguno de ellos sino también en pacientes no-respondedores cuando se trata del BCG, de la quimioterapia sistémicao la situación de no-elegibilidad para su indicación. El objetivo de este artículo de revisión es intentar trasladar los mecanismos básicos actuales implicados en las distintas fases de la respuesta antitumoral de los carcinomas de células transicionales con independencia de que sean o no músculo infiltrantes y establecer los fundamentos para su traslación terapéutica por vía intravesical o sistémica. Se describe el papel de las interacciones que se establecen entre las células tumorales uroteliales y los elementos celulares y moleculares del sistema inmune de los pacientes incorporando los relevantes y recientes avances de la inmunobiológica y la caracterización molecular de estos tumores que sin duda introducirán modificaciones de alcance en su evolución y tratamiento que contrastaran con las opciones hasta hace poco tiempo disponibles. También se analizan las líneas de futuro ya activas en fase de investigación clínica con BCG y con inhibidores de los puntos de control de la respuesta inmunitaria destacando la necesidad de avanzar en la búsqueda de marcadores predictivos de respuesta como opción real para la personalización de los tratamientos planteando la aproximación al conocimiento de la reactividad individual del sistema inmune de cada paciente como factor determinante para poder alcanzarla.

Clinicopathological Features of Programmed Cell Death-ligand 1 Expression in Patients with Oral Squamous Cell Carcinoma.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) expression has been shown to play important roles in various types of cancer. However, the role of PD-L1 expression has not been conclusively reported in patients with oral squamous cell carcinoma (OSCC). Accordingly, in this meta-analysis, we investigated the clinicopathological value of PD-L1 expression in patients with OSCC. METHODS: Google Scholar, PubMed, EMBASE, and CNKI databases were searched to find relevant studies published through to September 16, 2019. The relationships between PD-L1 expression in patients with OSCC and clinicopathological features were assessed using risk ratio (RR) and 95% confidence intervals (CIs). RESULTS: Sixteen studies including 1989 participants were included. The results indicated that high PD-L1 expression was correlated with sex (RR = 1.28, 95% CI: 1.16-1.42, P < 0.001), N stage (RR = 1.19, 95% CI: 1.06-1.33, P = 0.003), M stage (RR = 1.64, 95% CI: 1.01-2.66, P = 0.044), low differentiation (RR = 1.16, 95% CI: 1.01-1.33, P = 0.034), and human papilloma virus infection (RR = 1.38, 95% CI: 1.14-1.68, P = 0.001), but unrelated to TNM stage or T stage. There was no significant publication bias in the studies included in this analysis. CONCLUSIONS: This meta-analysis revealed that high PD-L1 expression in patients with OSCC was correlated with clinicopathological features. Further large-scale studies are necessary to confirm our results.

Low Grade Ovarian Serous Carcinoma - A Clinical-Morphologic Study.

Low grade ovarian serous carcinomas (LGSC) are rare tumors, representing only a small part of all ovarian carcinomas. The study included six LGSC cases for which we followed the clinical-epidemiological and morphological parameters depending on the tumoral stages. The tumors corresponded to stage I in four cases, in one case to stage II and in another case to stage III. The majority of the analyzed histopathological parameters were present in all tumoral stages. The accuracy of the diagnostic and the correct staging of the LGSC affected patients is very important, because the grade and stage of the serous ovarian tumors impose the therapy and the prognosis.

Identification and analysis of genes associated with papillary thyroid carcinoma by bioinformatics methods.

The molecular mechanism of the occurrence and development of papillary thyroid carcinoma (PTC) has been widely explored, but has not been completely elucidated. The present study aimed to identify and analyze genes associated with PTC by bioinformatics methods. Two independent datasets were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PTC tissues and matched non-cancerous tissues were identified using GEO2R tool. The common DEGs in the two datasets were screened out by VennDiagram package, and analyzed by the following tools: KOBAS, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Search tool for the retrieval of interacting genes/proteins (STRING), UALCAN and Gene expression profiling interactive analysis (GEPIA). A total of 513 common DEGs, including 259 common up-regulated and 254 common down-regulated genes in PTC, were screened out. These common up-regulated and down-regulated DEGs were most significantly enriched in cytokine-cytokine receptor interaction and metabolic pathways, respectively. Protein-protein interactions (PPI) network analysis showed that the up-regulated genes: FN1, SDC4, NMU, LPAR5 and the down-regulated genes: BCL2 and CXCL12 were key genes. Survival analysis indicated that the high expression of FN1 and NMU genes significantly decreased disease-free survival of patients with thyroid carcinoma. In conclusion, the genes and pathways identified in the current study will not only contribute to elucidating the pathogenesis of PTC, but also provide prognostic markers and therapeutic targets for PTC.

Targeting autophagy in chemotherapy-resistant of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. Surgical resection is recommended for very early-stage and early-stage HCC, but HCC is still prone to recurrence and metastasis after surgery. Furthermore, treatment options for intermediate- and advanced-stage HCC are relatively limited. Systemic therapy is the preferred method to kill residual cancer cells after surgery and prolong survival time of inoperable patients, but most cases are insensitive to chemotherapeutic agents, restricting widespread clinical application of systemic therapy. Many studies have found that various chemotherapeutic drugs for HCC treatment can increase autophagic flux of HCC cells, and it may be related with enhancing drug resistance and promoting cell survival. However, enhancement of autophagic flux may also induce tumor cell death in some cases, leading to marked inconsistency across studies. Here we reviewed the mechanisms underlying the increase in autophagic flux in HCC cells induced by chemotherapeutic drugs and examined the contributions of autophagy and related pathways to chemotherapy drug resistance. Our aim was to identify potential autophagy-related targets for improving the sensitivity of HCC to chemotherapeutic drugs.

miR-124 inhibits progression of hepatocarcinoma by targeting KLF4 and promises a novel diagnostic marker.

Hepatocarcinoma is one of the most lethal malignancy haunting the Chinese population, which is partially due to the difficulties in diagnosis at an early stage. The search for a biomarker that could signify the presence and progress of hepatocarcinoma is never ended. MicroRNAs are 22-nt RNAs that could bind to 3' UTR of target mRNAs, mediating degradation of mRNAs or inhibiting the translation. Although much has been investigated, the role of miR-124 in hepatocarcinoma remained elusive. We first detected aberrant expression level of miR-124 in HCC tissues of 112 patients. By exploring the clinical parameters, we found a significantly inverse correlation between miR-124 level and TNM stages. Consistent with this, the survival analysis indicated the association of low miR-124 with longer survival time. Subsequent forced expression miR-124 resulted in reduced cell viability of Hep3B and SMMC-7221, which cell lines have high and low background expression of miR-124, respectively. TargetScan prediction rendered a subset of target candidates, which were selected for experimental validation, KLF4 was subject to luciferase assay. Ectopic expression of KLF4 increased the sphere formation ability and CD44/133-positive cell numbers, which can be reversed by abundant expression of miR-124, suggesting that KLF4 is a functional target of miR-124 in tumourigenesis and cancer progression of HCC.

Matrix-producing metaplastic breast carcinoma - a rare tumor with heterologous elements.

Metaplastic breast carcinomas are ductal carcinomas that undergo metaplasia into non-glandular growth patterns. They are very rare and account for less than 1% of all invasive breast carcinomas. Matrix-producing carcinoma is an extremely rare and aggressive subtype of metaplastic breast carcinoma that is characterized by a ductal carcinomatous component with direct transition to areas with cartilaginous/osseous differentiation without an intervening spindle cell element. It has a better prognosis than metaplastic carcinoma. Even though these tumors are composed of a mixture of infiltrating ductal carcinomas and areas of heterologous stroma, each of which behaves aggressively individually, these composite tumors have a better 5-year survival rate with rare nodal metastasis. Immunohistochemically, they are positive for keratin, epithelial membrane antigen and S100. The tumor, which is matrix-producing, is S100-reactive and nonreactive for cytokeratin. They are usually hormone receptor-negative. The average age of these patients is approximately 58 years. Since these tumors are usually triple-negative, chemotherapy after surgery is the mainstay of therapy, using either mastectomy or local excision. Our report highlights this rare entity in a 55-year-old female patient with matrix-producing metaplastic breast carcinoma. Its distinctive histological features and peculiar clinical behavior warrants clear knowledge about this unique entity.

Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma.

Circular RNAs (circRNAs) have been emerged as an indispensable part of endogenous RNA network. However, the expression significance of circRNAs in hepatocellular carcinoma (HCC) is rarely revealed. The aim of this study was to determine the circRNA expression profile in HCC, and to investigate their clinical significances and relevant mechanisms for cancer progression. The global circRNA expression profile in HCC was measured by circRNA microarray. Levels of one representative circRNAs, hsa_circ_0004018, were confirmed by real-time reverse transcription-polymerase chain reaction. The expression levels of hsa_circ_0004018 in HCC were significantly lower compared with para-tumorous tissue (P<0.001). Our data further showed that lower expression of hsa_circ_0004018 was correlated with serum alpha-fetoprotein (AFP) level, tumor diameters, differentiation, Barcelona Clinic Liver Cancer stage and Tumor-node-metastasis stage. More importantly, we detected liver tissues from chronic hepatitis, cirrhosis and HCC patients; and found that hsa_circ_0004018 harbored HCC-stage-specific expression features in diverse chronic liver diseases (P<0.001). The area under receiver operating characteristic curve was up to 0.848 (95% CI=0.803-0.894, P<0.001). The sensitivity and specificity were 0.716 and 0.815, respectively. Finally, hsa_circ_0004018 might be involved in cancer-related pathways via interactions with miRNAs.

Microsatellite Instability in Medullary Carcinoma of the Colon.

Medullary carcinoma (MC) of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI). We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX-4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin) for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.

Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors.

Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. We have previously identified the hydrazide-hydrazone scaffold as a promising hepatitis C virus (HCV) and hepatocelluler inhibitor. Herein we describe the design a number of 2',4'-difluoro-4-hydroxy-N'-(arylmethylidene) biphenyl-3-carbohydrazide (3a-t) as anti-HCV and anticancer agents. Results from evaluation of anti-HCV activity indicated that most of the synthesized hydrazone derivatives inhibited viral replication in the Huh7/Rep-Feo1b and Huh 7.5-FGR-JCI-Rluc2A reporter systems. Antiproliferative activities of increasing concentrations of 2',4'-difluoro-4-hydroxy-N'-(2-pyridyl methylidene)biphenyl-3-carbohydrazide 3b and diflunisal (2.5-40 µM) were assessed in liver cancer cell lines (Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475) with sulforhodamine B assay for 72 h. Compound 3b with 2-pyridinyl group in the hydrazone part exhibited promising cytotoxic activity against all cell lines with IC50 values of 10, 10.34 16.21 4.74, 9.29 and 8.33 µM for Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G0 phase as an indicator of apoptotic cell death induction.