Increased financial burden asa result of cancer care costs is the strongest independent predictor of poor quality of life among cancer survivors.

BackgroundA key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value.Methodology/Principal FindingsWe isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15–30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive.Conclusions/SignificanceThe novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance.

Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co‐occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P < 0.0001] treatment, respectively). The change in number of metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%, 13.4%, and 13.4%, for an increase of 0, 1, 2, and ≥3 metastatic sites, from initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08–4.16; P < 0.0001). Tumors with mutated KRAS were associated with an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS vs. 6.0% in patients with wild‐type KRAS; P = 0.0011). Our findings suggest that the capabilities of lung cancer to metastasize and cause cachexia might be linked intrinsically and are independent of treatments administered. KRAS‐mutated tumors were more commonly associated with cachexia.

No abstract

Microbial biodiversity provides an increasingly important source of medically and industrially useful compounds. We have isolated 14 actinomycete species from a collection of approximately 300 plant stem samples from the upper Amazonian rainforest in Peru. All of the cultured isolates produce substances with inhibitory activity directed at a range of potential fungal and bacterial pathogens. For some organisms, this activity is very broad in spectrum while other organisms show specific activity against a limited number of organisms. Two of these organisms preferentially inhibit bacterial test organisms over eukaryotic organisms. rDNA sequence analysis indicates that these organisms are not equivalent to any other cultured deposits in GenBank. Our results provide evidence of the untapped biodiversity in the form of biologically active microbes present within the tissues of higher plants.

No abstract

Purpose: Epidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.Patients and Methods: Patients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3+3 design. Dose-limiting toxicities (DLT) were assessed during the first five weeks of therapy. The primary objective was to determine the maximum tolerated dose (MTD) of metformin with fixed dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression free survival (PFS).Results: Eight patients were enrolled. Median number of prior therapies for metastatic disease was 2.5 (range 1-6). No DLT events were reported during the DLT assessment period. A majority of adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 AEs were reported. The best observed response was stable disease in two patients (25%). Median PFS was 60 days (range 36-61).

Experts have expressed concerns that patients with chronic conditions are being excessively excluded from cancer randomized clinical trials (RCTs), limiting generalizability. Accordingly, we queried clinicaltrials.gov to determine the extent to which patients with chronic conditions were excluded from phase III cancer trials, using National Cancer Institute-sponsored breast cancer RCTs as a test case. Two physicians independently coded for the presence of 19 prevalent chronic conditions within eligibility criteria. They also coded for exclusions based on performance status and vague criteria that could have broadly excluded patients with chronic conditions. The search identified 58 RCTs, initiated from 1993 to 2012. Overall, 88% of trials had at least one exclusion for a chronic condition, performance status, or vague criterion. The three most commonly excluded conditions were chronic kidney disease, heart failure, and ischemic heart disease. Our study demonstrated that patients with prevalent chronic conditions were commonly excluded from National Cancer Institute-sponsored RCTs.