Obesity and colorectal cancer: Role of adipokines in tumor initiation and progression

Several lines of investigation have revealed the apparent interplay between the immune system of the host and many conventional, “standard-of-care” anticancer therapies, including chemotherapy and ...

Machine learning (ML) has been recently introduced to develop prognostic classification models that can be used to predict outcomes in individual cancer patients. Here, we report the significance of an ML-based decision support system (DSS), combined with random optimization (RO), to extract prognostic information from routinely collected demographic, clinical and biochemical data of breast cancer (BC) patients. A DSS model was developed in a training set (n = 318), whose performance analysis in the testing set (n = 136) resulted in a C-index for progression-free survival of 0.84, with an accuracy of 86%. Furthermore, the model was capable of stratifying the testing set into two groups of patients with low- or high-risk of progression with a hazard ratio (HR) of 10.9 (p < 0.0001). Validation in multicenter prospective studies and appropriate management of privacy issues in relation to digital electronic health records (EHR) data are presently needed. Nonetheless, we may conclude that the implementation of ML algorithms and RO models into EHR data might help to achieve prognostic information, and has the potential to revolutionize the practice of personalized medicine.

Primary cardiac sarcomas are malignant neoplasms deriving from mesenchymal cells and confined to the heart at the time of diagnosis. Most cardiac sarcomas have the same histologic appearance similar to their soft tissue counterpart. Consequently, an extremely rare metastasis from a preexisting noncardiac sarcoma should be excluded. Nevertheless, primary heart sarcomas are exceptionally rare. In a large study by the American Medical Association, prevalence of primary cardiac sarcomas at autopsy was 0.0017%,¹ x 1 Straus, R and Merliss, R. Primary tumor of the heart. Arch Pathol. 1945; 39: 74–78 Google Scholar See all References with an incidence from 0.001 to 0.030%² x 2 McAllister, H and Fenoglio, J. Tumors of the Cardiovascular System Fascicle 15, 2nd Series. Armed Forces Institute of Pathology, Washington, D.C.; 1978 Google Scholar See all References and a general incidence of 0.07%.³ x 3 Chomette, G, Auriol, M, Cabrol, C et al. [Primary malignant tumors of the heart. Anatomo-clinical study of 12 cases]. Ann Med Interne (Paris). 1985; 136: 301–305 PubMed | Google Scholar See all References Cardiac metastases at autopsy occur 20 to 40 times more frequently than primary neoplasms⁴ x 4 Lymbumer, R. Tumours of the heart: histopathological and clinical study. Can Med Assoc J. 1934; 30: 368–373 PubMed | Google Scholar See all References and originate mainly from cutaneous melanoma, lung, and breast carcinomas. Sarcomas represent approximately 10 to 20% of total primary cardiac tumors⁵ x 5 Burke, AP and Virmani, R. Tumors of Heart and Great Vessels, Vol. 16, 3rd series. AFIP, Washington, D.C.; 1996 Google Scholar See all References ^{, 6} x 6 Shapiro, LM. Cardiac tumours: diagnosis and management. Heart. 2001; 85: 218–222 Crossref | PubMed | Google Scholar See all References and occur without any gender predilection. Cardiac sarcomas may arise in any area of the heart, although angiosarcoma is typically found in the right atrium,⁷ x 7 Janigan, DT, Husain, A, and Robinson, NA. Cardiac angiosarcomas. A review and a case report. Cancer. 1986; 57: 852–859 Crossref | PubMed | Scopus (156) | Google Scholar See all References whereas fibrosarcoma and undifferentiated sarcoma in the left atrium.⁵ x 5 Burke, AP and Virmani, R. Tumors of Heart and Great Vessels, Vol. 16, 3rd series. AFIP, Washington, D.C.; 1996 Google Scholar See all References ^{, 8} x 8 Burke, AP, Cowan, D, and Virmani, R. Primary sarcomas of the heart. Cancer. 1992; 69: 387–395 Crossref | PubMed | Scopus (402) | Google Scholar See all References Transthoracic echocardiography is the most common method of instrumental investigation.⁹ x 9 Edwards, LC III and Louie, EK. Transthoracic and transesophageal echocardiography for the evaluation of cardiac tumors, thrombi, and valvular vegetations. Am J Card Imaging. 1994; 8: 45–58 PubMed | Google Scholar See all References Elective therapy includes complete surgical excision when possible, followed by radio- and chemotherapy. Despite these therapeutic strategies, prognosis of cardiac sarcomas is very poor, with median survival of less than 1 year.¹⁰ x 10 Grebenc, ML, Rosado de Christenson, ML, Burke, AP et al. Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation. Radiographics. 2000; 20: 1073–1103 Crossref | PubMed | Scopus (303) | Google Scholar See all References

Purpose: The epithelial–mesenchymal transition (EMT) is emerging as a critical factor for the progression and metastasis of carcinomas, as well as drug resistance. The T-box transcription factor Brachyury has been recently characterized as a driver of EMT in human carcinoma cells. The purpose of this study was to characterize Brachyury as a potential target for lung cancer therapy. Experimental Design: The expression of Brachyury was evaluated by PCR and by immunohistochemistry in human lung tumors and adult normal tissues. Brachyury gene copy number and promoter methylation status were analyzed in tumor tissues with various levels of Brachyury expression. Lung carcinoma cells' susceptibility to T-cell lysis and EGF receptor (EGFR) kinase inhibition were also evaluated relative to the levels of Brachyury. Results: Our results showed Brachyury protein expression in 41% of primary lung carcinomas, including 48% of adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal testis and some thyroid tissues, the majority of normal tissues evaluated in this study were negative for the expression of Brachyury protein. Brachyury-specific T cells could lyse Brachyury-positive tumors and the level of Brachyury corresponded to resistance of tumor cells to EGFR kinase inhibition. Conclusion: We hypothesize that the elimination of Brachyury-positive tumor cells may be able to prevent and/or diminish tumor dissemination and the establishment of metastases. The ability of Brachyury-specific T-cell lines to lyse Brachyury-positive tumor cells, in vitro, supports the development of Brachyury-based immunotherapeutic approaches for the treatment of lung cancer. Clin Cancer Res; 18(14); 3868–79. ©2012 AACR.