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A preprint abstract from biorxiv.org discusses the dysfunction of epigenetic modulators, specifically the SWI/SNF complex, in various types of cancer. The focus of the study is on Epithelioid Sarcoma (EpS), a highly aggressive cancer characterized by a mutation in the SMARCB1 gene. The researchers generated a panel of EpS cell lines to study the function of the SMARCB1-deficient SWI/SNF complex and its role in tumorigenesis. They found that the loss of SMARCB1 leads to an overall loss of SWI/SNF chromatin affinity, resulting in uncontrolled proliferation and cell cycle progression. The study also suggests that EpS cell lines are more sensitive to pharmacological inhibition of the residual SWI/SNF complex, providing potential avenues for therapeutic intervention. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

A recent preprint abstract discusses the use of a computational tool called pyjacker to identify enhancer hijacking events in acute myeloid leukemia (AML). The study found that AML with complex karyotype (ckAML) often has high genomic complexity and frequent TP53 mutations and chromothripsis. The researchers hypothesized that these genomic rearrangements could lead to the aberrant expression of proto-oncogenes through the repositioning of active enhancers. Pyjacker identified the gene MNX1 as being aberrantly expressed in 1.4% of AML patients, often due to the hijacking of a CDK6 enhancer associated with a specific chromosomal deletion. The study also found that MNX1-activated cases showed co-occurrence with BCOR mutations and a gene signature shared with pediatric AML. The researchers demonstrated that MNX1 is a dependency gene, as its knockdown in a xenograft model reduced leukemia cell fitness. Overall, the study suggests that enhancer hijacking is a frequent mechanism for oncogene activation in AML. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

A recent preprint abstract discusses the development of a computational algorithm called HYENA, which aims to identify candidate oncogenes (both protein-coding and non-coding) activated by enhancer hijacking in cancer. Enhancer hijacking occurs when structural variations in cancer relocate distal enhancers to activate proto-oncogenes. The algorithm analyzes tumor whole-genome and transcriptome sequencing data to detect genes whose elevated expression is associated with somatic structural variations. The study identifies a total of 192 candidate oncogenes, including many non-coding genes, and highlights the contribution of genetic alterations in non-coding regions to tumorigenesis and tumor progression. However, it is important to note that this preprint has not been peer-reviewed. [Extracted from the article]

Anticancer Agents, Cancer, Cancer Therapy, Drug Resistance, Drugs and Therapies, Health and Medicine, Oncology, Protective Agents Keywords: Anticancer Agents; Cancer; Cancer Therapy; Drug Resistance; Drugs and Therapies; Health and Medicine; Oncology; Protective Agents EN Anticancer Agents Cancer Cancer Therapy Drug Resistance Drugs and Therapies Health and Medicine Oncology Protective Agents 790 790 1 05/08/23 20230509 NES 230509 2023 MAY 9 (NewsRx) -- By a News Reporter-Staff News Editor at Clinical Oncology Week -- Research findings on cancer are discussed in a new report. [Extracted from the article]

Keywords: Adefovir Dipivoxil Therapy; Adefovir Therapy; Antiinfectives; Antiretrovirals; Antivirals; Cancer; Carcinomas; Drug Candidates; Drug Development; Drugs and Therapies; Endocrinology; Genetics; Health and Medicine; Medullary Thyroid Cancer; Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Oncology; Pharmaceuticals; Thyroid Cancer EN Adefovir Dipivoxil Therapy Adefovir Therapy Antiinfectives Antiretrovirals Antivirals Cancer Carcinomas Drug Candidates Drug Development Drugs and Therapies Endocrinology Genetics Health and Medicine Medullary Thyroid Cancer Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Oncology Pharmaceuticals Thyroid Cancer 388 388 1 04/24/23 20230428 NES 230428 2023 APR 25 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Researchers detail new data in medullary thyroid cancer. Adefovir Dipivoxil Therapy, Adefovir Therapy, Antiinfectives, Antiretrovirals, Antivirals, Cancer, Carcinomas, Drug Candidates, Drug Development, Drugs and Therapies, Endocrinology, Genetics, Health and Medicine, Medullary Thyroid Cancer, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Oncology, Pharmaceuticals, Thyroid Cancer. [Extracted from the article]

Our news correspondents obtained a quote from the research from TaipeiMedical University and Academia Sinica: "Therefore, identifying novelbiomarkers for early diagnosis is crucial, as they will also influencestrategies for new targeted therapies. Oncology - Colon Cancer New research on colon cancer is the subject of a new report. [Extracted from the article]

The article discusses experiences and tips of early adopters of next-generation sequencing (NGS) blood tests. Topics include the move of Weill Cornell College of Medicine into NGS panels from single-gene tests of oncology specimens while proto-oncogene B-Raf (BRAF) NGS tests have been approved by the Food and Drug Administration (FDA). Also cited are the use of Thermo Fisher Ion AmpliSeq panel for 50 genes, the Illumina array-based solution and preimplantation genetic screening (PGS).

The article informs that the annual meeting of the American Society of Clinical Oncology has featured a presentation on genomic tumor alterations by Foundation Medicine Inc. It mentions that next-generation sequencing is being used for altering the tumor genome in cancer patients. It further informs that tumor lacking oncogenic driver alterations develop a gene fusion, KIF5B-RET-RET which enables the inhibition of the proto-oncogene, RET.

Background: Neuroblastomas show different histopathologic phenotypes, and the tumor cells can carry normal or multiple copies of the N-myc proto-oncogene (MYCN). Studies of the N-myc gene and histopathology of untreated primary neuroblastomas have demonstrated that both these factors are important in risk assessment. Purpose: Our purpose was to determine if there are any associations between N-myc gene copy number, histopathologic features, clinical stage, and progression-free survival (PFS) and if joint analyses of histopathology and N-myc gene copy number improve risk assessment. Methods: The histopathologic phenotype and N-myc gene copy number were determined for 232 biopsy/surgery specimens obtained from untreated primary neuroblastoma patients. Tumors were classified as having favorable or unfavorable histology on the basis of Schwannian stroma (rich versus poor), neuroblastic differentiation (differentiating versus undifferentiated), and mitosis-karyorrhexis (fragmenting nucleus) index (MKI; high, intermediate, or low) in the context of age at diagnosis (Shimada classification). N-myc gene amplification was considered significant when the gene copy number was at least 10-fold higher than normal as determined by Southern blot analysis. Otherwise, tumors were classified as nonamplified for N-myc. Results: Among 19 stroma-rich tumors, 11 had grossly visible neuroblastic nodules, and two of these had N-myc amplification. Of 213 stroma-poor tumors, 51 had N-myc amplification, all of which were undifferentiated, and 45 (88% of 51) had high MKI. This histologic phenotype was present in less than 10% of tumors with nonamplified N-myc. Of 162 stroma-poor tumors that showed nonamplified N-myc, 45 (28%) were differentiating and 121 (75%) had low MKI. Neuroblastomas of clinical stages I, II, and IV-S nearly always had favorable histology and no amplification of N-myc. Stage III (regional) and particularly stage IV (metastatic) tumors, however, frequently had unfavorable histologic features with or without N-myc amplification. The estimated PFS at the end of 4 years after diagnosis was 83% for patients whose tumors had favorable histology and no N-myc amplification. The estimated PFS for the patients whose neuroblastomas had unfavorable histology, however, was 29% without and 13% with N-myc amplification, respectively. Subsets of patients with stage II, III, or IV disease were identified by both histologic evaluation and N-myc analysis. Multivariate Cox regression analysis indicated that both the histologic and N-myc-based stratifications provided prognostic information that was independent of staging. Conclusions: Neuroblastomas with N-myc amplification have a characteristic histopathologic phenotype and an aggressive clinical course. In contrast, neuroblastomas without N-myc amplification exhibit a wide range of histologic features that can define prognostic subsets.

Background. The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. Purpose: We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([[H.sup.3]]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. Methods: The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [[H.sup.3]]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [[H.sup.3]]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. Results: A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [[H.sup.3]]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [[H.sup.3]]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [[H.sup.3]]thymidine-labeling index was still statistically significant as a predictor for both events. Conclusion: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.

Background. The ret proto-oncogene activation (PTC/[ret.sup.TPC] oncogene) in thyroid papillary carcinoma has been reported in different populations with different frequencies. Thyroid papillary carcinoma appears to behave more aggressively in the Persian Gulf region than elsewhere. In the current study, the frequency of PTC/ret[sup.TPC] oncogene in thyroid tumors from Saudi Arabia was investigated. Methods. PTC/[ret.sup.TPC] oncogene transcripts were analyzed by the polymerase chain reaction amplification of cDNA synthesized by treatment of total RNA with reverse transcriptase. Seven multinodular goiters, 1 follicular adenoma, 4 follicular carcinomas, 40 papillary carcinomas, and 5 anaplastic carcinomas were studied. Results. Only one papillary carcinoma specimen was found to have PTC/[ret.sup.TPC] oncogene transcripts. The breakpoint of the rearranged PTC/[ret.sup.TPC] oncogene is identical to that previously described. The PTC/[ret.sup.TPC]-positive sample was also examined for p53 tumor suppressor gene mutations in exons 5-8. One transitional point mutation was detected at codon 161 (GCC to ACC), changing Ala to Thr. Conclusions. This study questions the relevance of [PTC/[ret.sup.TPC] oncogene in the carcinogenesis of thyroid papillary carcinomas in the Saudi population. Genetic background among races may contribute to the different frequencies of PTC/[ret.sup.TPC] oncogene in thyroid papillary carcinoma.

Background. Amplification and/or overexpression of the C-erbB-2 gene has been demonstrated in breast and gastric cancer and is thought to be involved in the process of gastric cancer metastasis. Methods. The expression of C-erbB-2 protein in human gastric cancer was examined by immunohistochemistry and amplification of the C-erbB-2 gene by Southern blot hybridization. Results. C-erbB-2 protein was located on the cell membrane of cancer cells in formalin-fixed, paraffin-embedded sections. Fourteen percent of specimens were positive for C-erbB-2, and no positive reaction was evident in noncancerous tissue. The presence of C-erbB-2 in gastric cancer was correlated with the depth of invasion, histologic type, growth pattern, and presence of liver metastasis. C-erbB-2 was found more often in advanced cancers (P < 0.05), papillary adenocarcinoma (P < 0.01), nonscirrhous cancer (P < 0.05), and cancers with liver metastasis (P < 0.01). The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01). Patients with C-erbB-2-positive tumors had poorer survival rates those with C-erbB-2-negative tumors in the early stages (P < 0.001), but not in the advanced stages. Amplification of the C-erbB-2 gene was detected at the primary site and in metastatic nodes in the same case, and expression of the protein was also evident. Conclusions. The expression and/or gene amplification of C-erbB-2 is related to invasion and nodal involvement in differentiated adenocarcinoma of the human stomach.

Background. It is unclear whether HER-2/neu proto-oncogene expression in ovarian epithelial neoplasms is related to prognosis. Methods. The authors performed immunohistochemical stains on 20 serous tumors of low malignant potential (STLMP) in Stages I and II and 19 serious carcinomas in the same stages. They used three different commercial antibodies to make comparisons. Results. Two of four Stage I STLMP in patients who experienced disease progression showed positive staining for the gene product, whereas none of seven Stage I nonprogressive STLMP showed positive staining. Five of the six Stage III nonprogressive STLMP showed positive staining, whereas none of three Stage III STLMP that progressed showed positive staining. Three carcinomas (one Stage I and two Stage III) also showed positive staining. Conclusions. Expression of HER-2/neu may be associated with high stage in serous ovarian neoplasms, but it is not likely to identify the small fraction of patients with STLMP who will experience disease progression. Cancer 1992; 70:2857-60.

Reports that proto-oncogenes encode proteins with a neural role. Mediation of the transcription of proteins from genetic instructions; Search for proto-oncogene activity in neurons; Proto-oncogene expression.

Examines the relationship between proto-concogenes and lung cancer in the Netherlands. Code for proteins that are vital to normal cellular processes; Mechanism in the activation of proto-oncogenes; Function of the ras genes codes for proteins.

The article describes the case of an unusual (B-Raf proto-oncogene) BRAF mutation in a 57-year-old white female with a history of metastatic melanoma presented with several weeks of pleural congestion and worsening shortness of breath. Topics covered include metastases to the liver and brain, pyrosequencing BRAF test, identification of alterations after the next-generation sequencing, V600E mutation, and S602T alteration.

The article reports on the use of positron emission tomography (PET) to evaluate the treatment for thyroid cancer. It mentions that PET can image metabolic changes in thyroid cancer treatment following the use of the drug vandetanib. It notes that the drug vandetanib is being tested in clinical trials in which it inhibits the role of rearranged-during-transfection (RET) protein proto-oncogene and other protein kinases.

Breast cancer is the most common cause of malignancy-related death among women. Poor prognosis among such patients is associated with pathological features such as tumour size, histological grade and node involvement. In the US, approximately 192 000 new cases of breast cancer are diagnosed each year, resulting in about 40 800 deaths annually. It has been determined that nearly 25-30% of breast tumours feature an overexpression of the proto-oncogene HER2/neu or its protein receptor HER2; over-expression of the HER2 receptor is associated with poor prognosis and outcome. The cost effectiveness of adjuvant trastuzumab for the treatment of patients with HER2+ early-stage breast cancer was evaluated in several studies presented at the 10th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) [ABSTRACT FROM AUTHOR]

The article discusses research being done on the cancer vaccine HER2/neu (E75). It references a study by G. E. Peoples et al published in the October 20, 2005 issue of the "Journal of Clinical Oncology." The results indicate that there was a significant rise in CD8+ E75-specific cells both during and after vaccination compared with pre-vaccination. Patients also developed a significant delayed-type hypersensitivity reaction to E75, compared with normal saline as a control. Despite the vaccination group having worse prognostic indicators, only two deaths occurred in the control group.

Investigates the gene responsible for the Rous sarcoma virus. Proto-oncogenes mediating cell division and growth; Transformation of oncogenes into tumor cells; Lessons learned about tumor development and normal cell function.

Examines the use of computers to reconstruct three-dimensional models of proto-oncogene int-1 distribution in embryonic neural tissues. Expression of int-1 in the brain and spinal cord; Role of int-1 in the early development of the central nervous system; Control of cell differentiation.

An article in 30 June issue (";Dangerous' liaisons in cell biology," p. 1539), which discussed the commentary in the 2 June issue of the journal Cell by Max L. Birnstiel and Meinrad Busslinger regarding the transgenic mice experiments of Corrado Spadafora and co-workers, stated that Vienna's Institute of Molecular Pathology (IMP), for which Birnstiel and Busslinger work, was seeking patents on extensions of the Spadafora experiments. On further investigation, we have learned that this is not correct. At present no applications have been applied for or granted to IMP or its parent companies Genentech and Boehringer Ingelheim. We wish to correct the record, apologize to Dr. Birnstiel and Dr. Busslinger for this misstatement, and alert our readers to their letter, which is printed in our Letters section on page 243.