Multivariate models from RNA-Seq SNVs yield candidate molecular targets for biomarker discovery: SNV-DA

Breast: up and downstream SNVs model. (CSV 22.1 kb

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p

One size does not fit all

With broad strokes, major contributing oncogenic factors include the patient’s genetic composition, environmental exposures, and the host microbiome. Within specific cancer types, such as lung cancer, regional differences of genetics, environmental exposure, and the biome result in tumors with differential behaviors. Therefore, optimal lung cancer treatments in one part of the world may not be applicable elsewhere. For more than a decade, the Japanese have led the world’s pursuit of sublobar resections for early-stage lung cancers. Okada and colleagues showed in 2006 that the 5-year overall survival for patients with peripheral lung cancers ≤2 cm was nearly identical between patients treated with sublobar resections compared to lobectomy. Importantly, the survival in both groups was 89%, while the most patients had tumors at the at upper end of the ≤2 cm spectrum. This survival was notably better than what has been observed for similarly staged lung cancers in other regions of the world. Consistently, Japanese series have demonstrated better long-term survival for lung cancer patients in general and superior outcomes after sublobar resections compared with outcomes elsewhere. At the same time, Japanese lung cancer series typically are composed of greater proportions of women and nonsmokers than series in other regions of the world. These differences in demographics and outcomes suggest fundamental biological differences. As a result, treatments appropriate in Japan may or may not be applicable elsewhere. Recent results of a prospective, randomized, multiinstitutional North American study did support sublobar resections of small peripheral lung cancers.4 That study randomized 697 patients with ≤2 cm tumors over a 10-year period to lobectomy vs sublobar resection, resulting in similar outcomes with 5-year overall survival rates of 78.9% vs 80.3%, respectively. Most retrospective reviews and prospective clinical trials have used 2 cm as a cutoff for tumors acceptably treated with sublobar resection. In this issue of The Annals of Thoracic Surgery, Mimae and colleagues have pushed the envelope further by examining the outcomes of patients with tumors 2-4 cm among a patient cohort aged >70 years. They observed statistically similar outcomes in patients treated with sublobar resections compared to lobectomy and concluded that a sublobar resection should be considered the procedure of choice for octogenarians with tumors up to 4 cm. It may be important to consider that excellent outcomes can be achieved with sublobar resections among older patients if similar selection criteria are used. Its notable that in the entire cohort, a lobectomy was performed more than 3 times more frequently than sublobar resections, suggesting that a lobectomy was actually the preferred approach. Differences between the 2 surgical groups imply that surgeons may have selectively offered sublobar resections to patients with more indolent-appearing tumors. A greater proportion of patients in the sublobar group had tumors 2-3 cm rather than 3-4 cm. In addition, patients in the sublobar group had tumors with a greater ground glass component. The comparable long-term survival results support the authors’ intuition leading them to recommend sublobar resections for patients with more indolent features

Casual observation

Pulmonary carcinoid tumors are a rare form of lung cancer subdivided into typical and atypical variants. Long-term outcomes after surgical resection are excellent, with 5-year survival rates approaching 85% even among patients with N2 lymph node involvement. Surgical resection of carcinoids remains the standard of care. However, in patients with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), a condition characterized by the presence of innumerable small pulmonary carcinoids, observing small carcinoids may be acceptable