Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer.

Somatostatin receptor 2 (SSTR2) is overexpressed in a majority of neuroendocrine neoplasms, including small-cell lung carcinomas (SCLCs). SSTR2 was previously considered an inhibitory receptor on cell growth, but its agonists had poor clinical responses in multiple clinical trials. The role of this receptor as a potential therapeutic target in lung cancer merits further investigation. We evaluated the expression of SSTR2 in a cohort of 96 primary tumors from patients with SCLC and found 48% expressed SSTR2. Correlation analysis in both CCLE and an SCLC RNAseq cohort confirmed high-level expression and identified an association between NEUROD1 and SSTR2. There was a significant association with SSTR2 expression profile and poor clinical outcome. We tested whether SSTR2 expression might contribute to tumor progression through activation of downstream signaling pathways, using in vitro and in vivo systems and downregulated SSTR2 expression in lung cancer cells by shRNA. SSTR2 downregulation led to increased apoptosis and dramatically decreased tumor growth in vitro and in vivo in multiple cell lines with decreased AMPKα phosphorylation and increased oxidative metabolism. These results demonstrate a role for SSTR2 signaling in SCLC and suggest that SSTR2 is a poor prognostic biomarker in SCLC and potential future therapeutic signaling target.

The state of molecular biomarkers for the early detection of lung cancer.

Using biomarkers to select the most at-risk population, to detect the disease while measurable and yet not clinically apparent has been the goal of many investigations. Recent advances in molecular strategies and analytic platforms, including genomics, epigenomics, proteomics, and metabolomics, have identified increasing numbers of potential biomarkers in the blood, urine, exhaled breath condensate, bronchial specimens, saliva, and sputum, but none have yet moved to the clinical setting. Therefore, there is a recognized gap between the promise and the product delivery in the cancer biomarker field. In this review, we define clinical contexts where risk and diagnostic biomarkers may have use in the management of lung cancer, identify the most relevant candidate biomarkers of early detection, provide their state of development, and finally discuss critical aspects of study design in molecular biomarkers for early detection of lung cancer.

Somatostatin Receptors in Lung Cancer: From Function to Molecular Imaging and Therapeutics.

Lung cancer is a deadly disease that is difficult to diagnose and even more difficult to treat effectively. Many pathways are known to affect tumor growth, and targeting these pathways provides the cornerstone by which cancer is treated. Somatostatin receptors (SSTR) are a family of G protein coupled receptors that signal to alter hormonal secretion, increase apoptosis, and decrease cellular proliferation. These receptors are expressed in many normal and malignant cells, including both small cell and non-small cell lung cancer. Synthetic analogs of SSTRs are commercially available, but their effects in lung cancer are still largely uncertain. Signaling pathway studies have shown that SSTRs signal through phosphotyrosine phosphatases to induce apoptosis as well as to decrease cell proliferation. Radiolabeled SSTR2 analogs are utilized for radiographic imaging of tumors, which, when combined with positron emission tomography-computed tomography (PET-CT) may improve detection of lung cancer. These radiolabeled SSTR2 analogs also hold promise for targeted chemotherapy as well as radiotherapy. In this review, we summarize what is known about SSTRs and focus our discussion on the knowledge as it relates to lung cancer biology, as well as discuss current and future uses of these receptors for imaging and therapy of lung cancer.

Clinical outcome at a minimum of five years after reconstruction of the anterior cruciate ligament.

BACKGROUND: We are not aware of any previous studies in which independent measurements of function with validated outcome questionnaires such as the Knee Injury and Osteoarthritis Outcome Score and the International Knee Documentation Committee score were evaluated five years after reconstruction of the anterior cruciate ligament. We hypothesized that patient demographics, mechanism of injury, and intra-articular injuries and their treatment are factors associated with function five years after reconstruction of the anterior cruciate ligament. METHODS: A consecutive series of unilateral, arthroscopically assisted primary reconstructions of the anterior cruciate ligament performed by one surgeon using a patellar tendon graft was evaluated. Data on patient demographics, injury variables, and intra-articular lesions noted at the time of surgery were collected prospectively. Multivariable regression analysis was used to identify independent predictors of outcomes as measured with five questionnaires. RESULTS: Sixty-nine percent (217) of 314 knees with a reconstruction of the anterior cruciate ligament were followed for an average of 5.4 years. The average age at the time of the operation was twenty-seven years. Independent predictors of a worse outcome, which was measured with the overall Knee Injury and Osteoarthritis Outcome Score, the International Knee Documentation Committee score, the Lysholm score, and the Western Ontario and McMaster Universities Osteoarthritis Index score, included the patient's recollection of hearing or feeling a pop at the time of the injury, a weight gain of >15 lb (6.8 kg), and no change in educational level since the surgery. There was a lack of association between the outcome and either the occurrence or the form of treatment of a meniscal tear or chondromalacia of the articular cartilage. CONCLUSIONS: To our knowledge, we performed the first prospective cohort study to evaluate the prognosis following reconstruction of the anterior cruciate ligament by identifying significant associations between multiple variables and clinical outcomes as measured with validated questionnaires. The clinician can counsel patients about the intermediate-term functional outcomes of reconstructions of the anterior cruciate ligament on the basis of these findings. Suggestions regarding weight control and future education may improve intermediate-term outcomes.

An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory.

CD4+ CD45RO+ T cells are the major latent viral reservoir in HIV-infected individuals and hence a major obstacle in curing the disease. An anti-CD45RO immunotoxin (IT) can decrease the number of both productively and latently infected CD4+ T cells obtained from HIV-infected individuals with detectable viremia. In this study, we determined whether this IT could also kill latently infected replication-competent CD4+ T cells obtained from infected individuals without detectable plasma viremia. Our results demonstrate that ex vivo treatment with the anti-CD45RO IT significantly reduced the frequency of these cells. In contrast, the IT had only a modest effect on the cytomegalovirus-specific memory responses of CD8+ T cells. These results suggest that purging latent cells from infected individuals on highly active antiretroviral therapy with the anti-CD45RO IT might reduce the HIV latent reservoir without seriously compromising CD8+ T cell memory responses.

Pop bottle explosions.

To our knowledge, there are only two brief reports in the medical literature of injury sustained as a result of a carbonated soft-drink (pop) bottle explosion. We report three such cases and review pertinent data on this hazard.