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MORE STROMA: Inhibiting Fibroblast Growth Factor Disrupts Pancreatic Cancer Cell Invasion

As mentioned, stromal tissue can account for as much as 90% of the bulk in pancreatic cancer tumors (ductal adenocarcinoma of the pancreas). Thought in the past to have been relatively inert, it is increasingly clear that this dense tissue arising from a desmoplastic process is surprisingly dynamic. Thus, it is heartening to encounter a number of recent serious research efforts aimed in a practical way to begin to try to counteract the effects of the pancreatic cancer stromal tissue in ameliorating the effects of standard treatment modalities.  We have commented on two of these previous studies HERE and HERE.

Grose and colleagues from the Centre for Tumour Biology Barts Cancer Institute at Queen Mary University of London E-published the results of their pre-clinical work on February 6, 2014 in the open journal EMBO – Molecular Medicine.  They studied the fibroblast system that is active in the desmoplasic process resulting in the creation of pancreatic cancer tumor stromal tissue, with particular attention to the fibroblast growth factor (FGF) signalling cascade which appears to be active in pancreatic cancer cell survival and invasion.

FGFs and their receptors are frequently overexpressed in pancreatic cancer, as well as in a number of other tumor types. The researchers particularly looked at FGF1 and FGF2 and their receptors. The respective receptors are notated as FGFR1 and FGFR2. FGF2 over-expresion appears to be correlated with poor patient outcome in pancreatic cancer.

The authors demonstrate that blocking nuclear aspects of FGFR1 and FGFR2 appears to interrupt fibroblast proliferation, thus disrupting the pancreatic cancer “microenvironment.” The practical effect of this mechanism is that pancreatic cancer cell invasion is thwarted. The authors postulate that inhibiting the fibrogen growth factor cascade by therapeutic agents may target the pancreatic cancer stroma in a manner that interferes with the natural history of pancreatic cancer and thus could enhance patient outcomes.

This is another interesting and promising piece of the puzzle.


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Dale O’Brien, MD

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Gemzar for Post-Whipple Procedure Chemotherapy in Pancreatic Cancer?

The standard chemotherapy agent for adjuvant treatment of pancreatic cancer (ductal adenocarcinoma of the pancreas) has typically been Fluorouracil (5-FU) based. But there have been other adjuvant agents and modalities for pancreatic cancer under study including gemcitabine, combined chemotherapy (multiple drug agents), and chemoradiation.

On behalf of the German Study Group for Pancreatic Cancer (a branch of the German Cancer Society), Riess and colleagues from a widely based consortium of community oncologists and oncology centers in Germany and Austria studied pancreatic cancer patients enrolled from 1998 until 2004 in 88 hospitals. The result of this work was published in the October 9, 2013 issue of the Journal of the American Medical Association.

The authors followed 368 patients who received substantive surgery for pancreatic cancer according to the extent of the disease and the dictates of the local hospitals’ protocols. These patients were randomized 1:1 to the no adjuvant therapy arm of the trial OR to the adjuvant therapy with gemcitabine arm of the trial (six months of chemotherapy with a weekly dosage at 700 mg/m2).  There were 186 patients in the gemcitabine arm; 111 of the patients were able to receive all six cycles; 90% of patients in this arm received at least one single dose; 87% received at least one full gemcitabine cycle.

The pancreatic cancer patients in both arms of this Phase III trial were followed until September 2012. The data collection and coordination was undertaken by the Charité–Universitätsmedizin Berlin. The researchers found that the median overall survival of the patients in the gemcitabine arm was 22.8 months, compared with 20.2 months in the observation alone arm. This was found to be significant on a statistical basis.

Additionally, the five-year survival in the gemcitabine arm was 20.7%, compared with 10.4% in the observation alone arm.  And the ten-year survival in the gemcitabine arm was 12.2%, compared with 7.7% in the observation alone arm.

The researchers suggest that gemcitabine has acceptable toxicity levels and confers survival advantage as adjuvant chemotherapy post-pancreatic cancer surgery.   


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Dale O’Brien, MD

CT Measurements Predict Need for Venous Resection in Pancreatic Cancer

The evaluation and diagnosis of pancreatic cancer (ductal adenocarcinoma of the pancreas) is now largely initially accomplished through radiographic means, including CT scanning. This has produced changes in related areas such as the staging of pancreatic cancer, and the evaluation for potential resection.  Depending on tumor extension, as a part of the Whipple, the surgeon may need to surgically resect the superior mesenteric vein – portal vein complex (“SMV-PV”).

Researcher Katz and colleagues at the University of Texas / M.D. Anderson Cancer Center in Houston wondered if the necessity of the likelihood of this vascular aspect of the surgical procedure could be anticipated among resectable and borderline resectable cases using CT scan criteria. Their results were published in the February 2014 issue of the Journal of Gastrointestinal Surgery, the official publication of the Society for Surgery of the Alimentary Tract.

The researchers reviewed all patients who received the pancreaticoduodenectomy (Whipple procedure) at the M.D. Anderson Cancer Center for a seven year period (2004-2011).  This process eventually yielded 254 pancreatic cancer patients who met inclusion standards (39.6% of these patients eventually required SMV-PV resection at surgery).  The authors reexamined the CT images of these patients taken prior to surgery in regard to the extent of the tumor / SMV-PV interface in terms of four categories:  no interface, less than or equal to 180° of interface, more than 180° of interface, or full occlusion.

The authors found that 89.5% of patients with either full occlusion of the vein complex or those with more than 180° of interface had received the SMV-PV resection.  Also, they found that those with less than or equal to 180° of interface tended to have longer pancreatic cancer survival.

They conclude that this method of classification can be of help in pancreatic cancer surgical planning, and in prognosis. This is an interesting study suggesting fairly easy measurements that may that may prove to be very useful.  


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Dale O’Brien, MD

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