Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer remains a public-health issue on a global scale. We report new information about the disease from the past 5 years. Early age at first birth, increasing parity, and tamoxifen use are related to long-term lifetime reduction in breast-cancer risk. Ductal carcinomas in situ has been suggested to be renamed ductal intraepithelial neoplasia to emphasise its non-life-threatening nature. An alternative approach, the progenitor/stem cell theory, predicts that only some tumour cells cause cancer progression and that these should be targeted by treatment. Mammography and ultrasonography are still the most effective for women with non-dense and dense breast tissues, respectively. Additionally, MRI, lymphatic mapping, the nipple-sparing mastectomy, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant treatments are promising for subgroups of breast-cancer patients. Although tamoxifen can be offered for endocrine-responsive disease, aromatase inhibitors are increasingly used. Assessment of potential molecular targets is now important in primary diagnosis. Tyrosine-kinase inhibitors and other drugs with anti-angiogenesis properties are currently undergoing preclinical investigations.
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PMID:Breast cancer. 1627 38

Inactivation of the Transforming Growth Factor Beta (TGFbeta) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1gamma) has recently been proposed to be involved in TGFbeta signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1gamma in pancreatic carcinogenesis. Using conditional Tif1gamma knockout mice (Tif1gamma(lox/lox)), we selectively abrogated Tif1gamma expression in the pancreas of Pdx1-Cre;Tif1gamma(lox/lox) mice. We also generated Pdx1-Cre;LSL-Kras(G12D);Tif1gamma(lox/lox) mice to address the effect of Tif1gamma loss-of-function in precancerous lesions induced by oncogenic Kras(G12D). Finally, we analyzed TIF1gamma expression in human pancreatic tumors. In our mouse model, we showed that Tif1gamma was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-Kras(G12D);Smad4(lox/lox) mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1gamma don't have strictly redundant functions. Finally, we report that TIF1gamma expression is markedly down-regulated in human pancreatic tumors by quantitative RT-PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1gamma is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1gamma in the multifaceted functions of TGFbeta in carcinogenesis and development.
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PMID:Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. 1962 68

Ductal adenocarcinoma of the pancreas is a lethal disease. Surgical extirpation only offers the slim chance for long-term survival in localized disease. We report on a 73 year old female patient who initially underwent successful resection of pancreatic adenocarcinoma in May 2005. She was treated with adjuvant chemotherapy with gemcitabine. In October 2010 the patient noticed increasing dyspnea with haemoptysis. She was soon referred to our center. After the diagnosis of pulmonary adenocarcinoma with widespread metastasis, she was treated with systemic chemotherapy. For a period of next three years, she was treated with different chemotherapy regimens due to repeated episodes of tumor progression. To the best of our knowledge after reviewing the literature, this case represents an unusually clinical course with metachronous pulmonary adenocarcinoma arising after treatment of a primary pancreatic cancer after a long latency period.
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PMID:Pulmonary adenocarcinoma occurring 5 years after resection of a primary pancreatic adenocarcinoma: a relevant differential diagnosis. 2471 48

Epithelial tissues are essential for barrier function, secretion, and regulation of fluid transport. Their function requires cell polarity and cell-cell adhesion, mediated through intercellular junctions. Conversely, disruption of adhesion and polarity is thought to drive cancer progression. The mammary gland is an important model for cell adhesion due to its postnatal hormonally regulated development; ducts undergo branching morphogenesis in response to steroid hormones during puberty. These hormonal signals induce a transition from simple to stratified architecture, initiated by asymmetric luminal cell divisions. Ductal elongation is accomplished by this multilayered, low-polarity epithelium, and polarity is reestablished as elongation ceases. The requirement for cell adhesion has been tested in 3D culture and in vivo, using gene deletion, knockdown, and misexpression in both developmental and homeostatic contexts. Attention has focused on E-cadherin, the major classical cadherin in luminal epithelial cells. Classic studies revealed a requirement for E-cadherin during lactation, and E-cadherin loss is widely posited to promote metastasis. However, recent findings demonstrated a broader requirement for E-cadherin during branching morphogenesis and homeostasis and also, surprisingly, in epithelial dissemination. These studies suggest that long-standing models of the role of adhesion in epithelial biology need to be revisited. Advances in inducible gene expression and knockdown, CRISPR/Cas9 technology, and fluorescent labeling of genetically modified cells offer the opportunity to test the roles of diverse adhesion systems and to develop a mechanistic understanding of how cell adhesion regulates development and cancer.
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PMID:Adhesion in mammary development: novel roles for E-cadherin in individual and collective cell migration. 2573 46

Ductal adenocarcinoma is a rare subtype of prostate cancer with a worse prognosis.Histologically, it is characterized by the presence of tall, pseudostratified columnar epithelium with abundant cytoplasm organized in a papillary or cribriform-papillary pattern. Several clinical differences distinguish this subtype of prostate cancer by the conventional acinar adenocarcinoma: exophytic growth into the prostatic urethra, different clinical presentation, different sites of metastasis and more aggressiveness. The rarity of this tumour forced to base our knowledge on small case series or on individual case reports, and does not help to establish appropriate guidelines. Therefore, the diagnosis of this tumour masks clinical implications that are still not well-understood.We report the case of a 69-year-old Caucasian man with a diagnosis of pure prostate ductal adenocarcinoma that early developed multiple metastases after radical prostatectomy. The patient started hormonal therapy with a fast biochemical and radiologic (positron emission tomography-computed tomography, PET-CT) hormonal escape. Therefore, we took the decision to perform chemotherapy with Taxotere along with prednisolone with a relative stability of prostate-specific antigen (PSA) level, but a new PET-CT scan showed a further progression of the disease. Finally, the patient underwent therapy with Abiraterone acetate that did not stop the cancer progression.No therapeutic options available showed a good control of disease progression. PSA proved to be a poor marker while, on the contrary, PET-CT scan has proved to be particularly useful in the management of the disease progression. More efforts are required to add new knowledge about this tumour and assess what is known until now.
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PMID:Management and therapeutic response of a prostate ductal adenocarcinoma: a still unknown tumour? 2717 34

Alteration and activation of recepteur d'origine nantais (RON) expression is known to be associated with cancer progression and decreased survival in various types of human cancer, including pancreatic cancer. Therefore, in the present study, RON expression levels were determined in resected left-sided pancreatic cancer to evaluate the potential oncological role of RON in the clinical setting of distal pancreatic cancer. From January 2005 to December 2011, a total of 57 patients underwent radical distal pancreatectomy for left-sided pancreatic cancer. Ductal adenocarcinoma was confirmed in all patients. Among these patients, 17 patients who received preoperative neoadjuvant treatment and 7 patients without available paraffin-embedded tissue blocks were excluded from the present study. RON expression in a the pancreatic cancer cell lines ASPC-1, BxPC-3, MiaPaCa-3 and Panc-1, as well as in resected left-sided pancreatic cancer specimens was determined by Western blot analysis. RON and vascular endothelial growth factor (VEGF) overexpression in resected left-sided pancreatic cancer was also evaluated by immunohistochemistry using pre-diluted anti-RON and anti-VEGF antibodies. An association was identified between the oncological outcome and RON overexpression. Increased levels of RON expression were observed in two pancreatic cancer cell lines, AsPC-1 and BxPC-3. RON overexpression was detected in specimens from 15/33 patients (45.5%) using immunohistochemistry. No significant association was identified between RON overexpression and VEGF overexpression (25.5 vs. 87.9%; P=0.667). No significant differences in disease-free survival or disease-specific survival associated with RON overexpression were identified. Although the results of previous studies have suggested that RON is a potential target for the treatment of pancreatic cancer, in the present study no association between RON overexpression and any adverse oncological effect was identified.
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PMID:A missing link between RON expression and oncological outcomes in resected left-sided pancreatic cancer. 2894 31

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago ("Warburg effect" or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. There is now accumulating evidence that most cancers also rely on mitochondria to satisfy their metabolic needs. Indeed, the current view of cancer metabolism places mitochondria as key actors in all facets of cancer progression. Importantly, mitochondrial metabolism has become a very promising target in cancer therapy, including for refractory cancers such as Pancreatic Ductal AdenoCarcinoma (PDAC). In particular, mitochondrial oxidative phosphorylation (OXPHOS) is an important target in cancer therapy. Other therapeutic strategies include the targeting of glutamine and fatty acids metabolism, as well as the inhibition of the TriCarboxylic Acid (TCA) cycle intermediates. A better knowledge of how pancreatic cancer cells regulate mitochondrial metabolism will allow the identification of metabolic vulnerabilities and thus novel and more efficient therapeutic options for the benefit of each patient.
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PMID:Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies. 3275 81