Reprogrammed transsulfuration promotes basal-like breast tumor progression via realigning cellular cysteine persulfidation.

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast tumors with poor prognosis and limited molecular-targeted therapy options. We show that BLBC cells have a high Cys demand and reprogrammed Cys metabolism. Patient-derived BLBC tumors from four different cohorts exhibited elevated expression of the transsulfuration enzyme cystathione β-synthetase (CBS).

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes.

A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution.

Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary.

Introduction: Lynch syndrome is an autosomal dominant disorder, most frequent leading to colon cancer. Identification of patients with Lynch syndrome and screening of their family members are available prevention approach that can significantly decrease mortality. Unfortunately, routine screening still does not belong to standard of care in Hungary.

Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer.

Background/objectives: Malignant pancreatobiliary strictures are in many cases clinically indistinguishable and present a major problem to endoscopy specialists. Intraductal sampling procedures such as brush cytology are commonly used for diagnosis with a sensitivity that is low for a diagnostic test used in daily clinical practice. MicroRNA (miR) alterations detected in many cancers are disease-specific, which can be utilized in clinical applications.

Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.

Aim Of The Study: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells.

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

[Genetic information from tumor-infiltrating B lymphocytes as a driver tool ("GPS") for anti-tumor T cell CARs].

The rapidly growing field of gene therapy techniques to modify T cells with chimeric antigen receptors (CARs) for cancer care solutions, reached considerable achievements. However, there is an urgent need of reliable, well tolerable tumor-associated antigen specific antibodies. Tumor-infiltrating B (TIL-B) cell originated single chain Fv (scFv) gene regions could be selected with tumor specificity.

[PI3K/AKT pathway activation and therapeutic consequences in breast cancer].

The phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathway is commonly deregulated in breast cancer through several mechanisms, including PI3K catalytic subunit alpha (PIK3CA) mutations and loss of phosphatase and tensin homolog (PTEN). The hiperactivated PI3K/AKT signaling can be associated with endocrine or trastuzumab therapy resistance and underscore the impact of targeting the pathway. Our aim was to identify PIK3CA mutations and the mechanisms of PTEN loss and assess their therapeutic consequences in breast cancer patients.

The novel panel assay to define tumor-associated antigen-binding antibodies in patients with metastatic melanomas may have diagnostic value.

We aim to harness the natural humoral immune response by various technologies to get novel biomarkers. A complex antibody analysis in sera and in the tumor microenvironment leads to reveal tumor-specific antibodies. More strategies were introduced to select the most effective one to identify potential tumor antigen-binding capacity of the host.

MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.

Introduction: Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease.

Methods: In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis.

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families.

Lynch syndrome (Hereditary nonpolyposis colorectal cancer, HNPCC) is an inherited disease with variable phenotype causing the development of colon cancer and other malignancies. The basis of the disease is believed to be the mismatch repair gene mutations. Genetic screening has been performed among the patients who have undergone surgery for colon cancer at the University of Debrecen, Department of Surgery.

Continuous administration of the somatostatin structural derivative /TT-232/ by subcutaneously implanted osmotic pump improves the efficacy and potency of antitumor therapy in different mouse and human tumor models.

Background: The somatostatin structural derivative, TT-232, has a special 5-residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) and very different characteristics from the known growth hormone (GH) active somatostatin analogs. This somatostatin structural derivative has no GH release inhibitory or antisecretory activity and does not bind to rat pituitary or the cortex, where all the known somatostatin receptor subtypes are expressed. TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in vivo.

Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer.

Radiation is known to induce DNA damage resulting in the onset of apoptosis. The apoptosis is modulated by p53, Bcl2 and Bax proteins. High level of wild type p53 is required for radiation induced apoptosis.

Somatic APC inactivation mechanisms in sporadic colorectal cancer cases in Hungary.

The role of germline inactivation of the adenomatosis polyposis coli (APC) gene in hereditary colorectal cancer is well known, being the most important cause of familial adenomatosus polyposis (FAP) syndrome. Hereditary cases with germline mutations, however, account only for 5-10% of colorectal cancers. The somatic inactivation of this gene has also been observed in sporadic cases.

Difficulties in recognizing families with Hereditary Non-polyposis Colorectal Carcinoma. Presentation of 4 families with proven mutation.

Introduction: Hereditary Non-polyposis Colorectal Carcinoma is the most frequent genetic disease leading to colon and other malignancies. Recognizing the condition requires extensive family history going back several generations focusing particularly on the types of tumors occurring in the family at different age groups.

Methods: In families who met the Amsterdam and Bethesda Criteria, the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis.

RAR beta2 suppression in head and neck squamous cell carcinoma correlates with site, histology and age.

Retinoids as important growth and differentiation regulating agents have a potential role in the chemoprevention of head and neck squamous cell carcinoma (HNSCC). Despite the promising preclinical and early clinical findings, limitations of application are raised by intrinsic resistance acquired during carcinogenesis. Retinoic acid receptor beta2 (RAR beta2) is one of the proximate mediators of retinoid signalling and its expression is often diminished in early stages of head and neck carcinogenesis.

[Fenotypical diversity of hereditary non-polyposis colorectal carcinoma. Pedigree and genetical analysis of two mutation carrier patients].

Introduction: The phenotype of HNPCC shows great diversity. Investigation of the disease needs the application of both the Amsterdam and Bethesda Guidelines. The clinical diagnosis of HNPCC can be established by means of thorough family history containing more generations.

Structure, enzymatic stability and antitumor activity of sea lamprey GnRH-III and its dimer derivatives.

Direct antitumor activity of sea lamprey (Petromyzon marinus) gonadotropin-releasing hormone III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH(2); lGnRH-III) was described on several tumor cells. To improve the selectivity of antitumor effects without increasing the hormone releasing activity and to enhance the enzymatic stability, lGnRH-III dimers were prepared via disulfide bond formation. Our results demonstrate that the lGnRH-III dimer derivatives exhibited higher antiproliferative effect and enzymatic stability in comparison with the native lGnRH-III, while lower LH-releasing potency was determined.

Two germline alterations in mismatch repair genes found in a HNPCC patient with poor family history.

The Bethesda guidelines may offer more useful criteria in patients' selection for germline mismatch repair gene mutation analysis than guidelines merely based on family background. An early onset double primary colorectal cancer patient with poor family history with MSI-H status was investigated for MLH1 promoter methylation, expression of the MLH1 and MSH2 gene by immunohistochemistry and mutations in the MLH1 and MSH2 genes. The index patient carried two germline alterations, the p.

A comparison of the tumor growth inhibitory effect of intermittent and continuous administration of the somatostatin structural derivative TT-232 in various human tumor models.

The tumor growth inhibitory efficacy of the somatostatin structural derivative TT-232 was studied using different routes of administration and treatment schedules in various human tumor models. TT-232, containing a five-residue ring structure, has a strong antitumor activity both in vitro and in vivo. The antineoplastic activity of TT-232 has been found to be associated with the induction of programmed cell death in tumor cells, resulting in highly-selective elimination of the neoplastic tissue.

Pedigree and genetic analysis of a novel mutation carrier patient suffering from hereditary nonpolyposis colorectal cancer.

Aim: To screen a suspected Hungarian HNPCC family to find specific mutations and to evaluate their effect on the presentation of the disease.

Methods: The family was identified by applying the Amsterdam and Bethesda Criteria. Immunohistochemistry was performed, and DNA samples isolated from tumor tissue were evaluated for microsatellite instability.

Relationship between sentinel lymph node status and regression of primary malignant melanoma.

The prognostic significance of spontaneous regression of primary melanoma is a controversial issue. Studies on sentinel lymph node status and circulating tumour cells may represent a step towards a better understanding. The clinical details of 269 melanoma patients who underwent sentinel lymph node biopsy were analysed.

Influence of hMLH1 methylation, mismatch repair deficiency and microsatellite instability on chemoresistance of testicular germ-cell tumors.

Background: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ-cell testicular tumors (GCTs). The response to cisplatin-based chemotherapy has been related to Microsatellite Instability (MSI), which is caused by genetic or epigenetic changes in genes of the DNA Mismatch Repair (MMR) pathway.

Patients And Methods: We investigated 15 refractory and 36 chemosensitive GCTs for immunohistochemical loss of hMLH1, hMSH2 and hMSH6 protein expressions, in conjunction with hMLH1 gene methylation and MSI of GCTs, with a complete follow-up.