Hypoxia within solid tumors is a major determinant of outcome after anticancer therapy. Analysis of gene expression changes during hypoxia indicated that unfolded protein response genes were one of the most robustly induced groups of genes. In this study, we investigated the hypoxic regulation of X-box binding protein (XBP1), a major transcriptional regulator of the unfolded protein response. Hypoxia induced XBP1 at the transcriptional level and activated splicing of its mRNA, resulting in increased levels of activated XBP1 protein. After exposure to hypoxia, apoptosis increased and clonogenic survival decreased in XBP1-deficient cells. Loss of XBP1 severely inhibited tumor growth due to a reduced capacity for these transplanted tumor cells to survive in a hypoxic microenvironment. Taken together, these studies directly implicate XBP1 as an essential survival factor for hypoxic stress and tumor growth.
Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege.
Therapeutic study, level IV.
To compare the outcomes of a large cohort undergoing biliopancreatic diversion/duodenal switch (DS) vs gastric bypass (GB).
Introduction: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease. Therefore, monitoring how disease responds to therapy requires standardization in order to ultimately optimize patient outcomes. Unfortunately, how best to do this remains a topic of debate among oncologists, pathologists, and colorectal surgeons. There may not be one single best approach. The goal of the present article is to shed some light on current approaches and challenges to monitoring treatment response for colorectal cancer.Methods: A literature search was conducted utilizing PubMed and the OVID library. Key-word combinations included colorectal cancer metastases, neoadjuvant therapy, rectal cancer, imaging modalities, CEA, down-staging, tumor response, and biomarkers. Directed searches of the embedded references from the primary articles were also performed in selected circumstances.Results: Pathologic examination of the post-treatment surgical specimen is the gold standard for monitoring response to therapy. Endoscopy is useful for evaluating local recurrence, but not in assessing tumor response outside of the limited information gained by direct examination of intra-lumenal lesions. Imaging is used to monitor tumors throughout the body for response, with CT, PET, and MRI employed in different circumstances. Overall, each has been validated in the monitoring of patients with colorectal cancer and residual tumors.Conclusion: Although there is no imaging or serum test to precisely correlate with a tumor's response to chemo- or radiation therapy, these modalities, when used in combination, can aid in allowing clinicians to adjust medical therapy, pursue operative intervention, or (in select cases) identify complete responders. Improvements are needed, however, as advances across multiple modalities could allow appropriate selection of patients for a close surveillance regimen in the absence of operative intervention.
IMPORTANCE Venous thromboembolism (VTE) is an important complication of colorectal surgery, but its incidence is unclear in the era of VTE prophylaxis. OBJECTIVE To describe the incidence of and risk factors associated with thromboembolic complications and contemporary VTE prophylaxis patterns following colorectal surgery. DESIGN, SETTING, AND PARTICIPANTS Prospective data from the Washington State Surgical Care and Outcomes Assessment Program (SCOAP) linked to a statewide hospital discharge database. At 52 Washington State SCOAP hospitals, participants included consecutive patients undergoing colorectal surgery between January 1, 2006, and December 31, 2011. MAIN OUTCOMES AND MEASURES Venous thromboembolism complications in-hospital and up to 90 days after surgery. RESULTS Among 16 120 patients (mean age, 61.4 years; 54.5% female), the use of perioperative and in-hospital VTE chemoprophylaxis increased significantly from 31.6% to 86.4% and from 59.6% to 91.4%, respectively, by 2011 (P < .001 for trend for both). Overall, 10.6% (1399 of 13 230) were discharged on a chemoprophylaxis regimen. The incidence of VTE was 2.2% (360 of 16 120). Patients undergoing abdominal operations had higher rates of 90-day VTE compared with patients having pelvic operations (2.5% [246 of 9702] vs 1.8% [114 of 6413], P = .001). Those having an operation for cancer had a similar incidence of 90-day VTE compared with those having an operation for nonmalignant processes (2.1% [128 of 6213] vs 2.3% [232 of 9902], P = .24). On adjusted analysis, older age, nonelective surgery, history of VTE, and operations for inflammatory disease were associated with increased risk of 90-day VTE (P < .05 for all). There was no significant decrease in VTE over time. CONCLUSIONS AND RELEVANCE Venous thromboembolism rates are low and largely unchanged despite increases in perioperative and postoperative prophylaxis. These data should be considered in developing future guidelines.
Background and Objectives For patients with cutaneous melanoma, primary tumors located in the head and neck is associated with poor outcomes. The reason for this difference and whether it is applicable to all locations within the head and neck remains unclear. We hypothesized that scalp melanoma is uniquely distinguished from other anatomic sites and is independently responsible for the poor prognosis of head and neck melanoma. Methods Query and analysis of a prospectively maintained melanoma database of all patients treated for primary cutaneous melanoma from 1971 – 2010. Results Of 11,384 patients identified, 7% (n=799) of lesions originated on the scalp. Scalp primaries were more often found in males and were associated with increased Breslow thickness and were more frequently ulcerated compared to all other anatomic sites (p=0.0001). On multivariate analysis, scalp location was an independent predictor of worse melanoma-specific (HR 1.75; CI 1.50–2.04; p<0.0001) and overall survival (HR 1.62; CI 1.41–1.86: p<0.0001). Conclusions This, the largest series examining scalp melanoma, confirms that scalp location is independently responsible for the negative prognosis associated with head and neck melanoma. Although the pathophysiology of this difference remains to be determined, these data argue for more rigorous surveillance of this anatomic location.
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