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Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC. Mutant KRAS (KM) is associated with poor prognosis in lung cancer and reported to promote lipid metabolism. Here, the authors show that fatty acid synthesis, which provides lipids to repair oxidized phospholipids through the FASN-Lands cycle axis, is a specific vulnerability for KM lung cancer.

Interobserver reproducibility in the diagnosis of benign intraductal proliferative lesions has been poor. The aims of the study were to investigate the inter- and intraobserver variability and the impact of the addition of an immunostain for high- and low-molecular weight keratins on the variability. Nine pathologists reviewed 81 cases of breast proliferative lesions in three stages and assigned each of the lesions to one of the following three diagnoses: usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ . Hematoxylin and eosin slides and corresponding slides stained with ADH-5 cocktail (cytokeratins (CK) 5, 14. 7, 18 and p63) by immunohistochemistry were evaluated. Concordance was evaluated at each stage of the study. The interobserver agreement among the nine pathologists for diagnosing the 81 proliferative breast lesions was fair ( κ- value=0.34). The intraobserver κ -value ranged from 0.56 to 0.88 (moderate to strong). Complete agreement among nine pathologists was achieved in only nine (11%) cases, at least eight agreed in 20 (25%) cases and seven or more agreed in 38 (47%) cases. Following immunohistochemical stain, a significant improvement in the interobserver concordance (overall κ -value=0.50) was observed ( P =0.015). There was a significant reduction in the total number of atypical ductal hyperplasia diagnosis made by nine pathologists after the use of ADH-5 immunostain. Atypical ductal hyperplasia still remains a diagnostic dilemma with wide variation in both inter- and intraobserver reproducibility among pathologists. The addition of an immunohistochemical stain led to a significant improvement in the concordance rate. More importantly, there was an 8% decrease in the number of lesions classified as atypical ductal hyperplasia in favor of usual hyperplasia; in clinical practice, this could lead to a decrease in the number of surgeries carried out for intraductal proliferative lesions.

Raccoons (Procyon lotor) are important furbearers and ecological generalists that exist in a variety of landscapes. Numerous studies have examined raccoon space and macrohabitat use, but information detailing these parameters within pine-dominated landscapes is lacking. Furthermore, no studies using radiotracking have examined raccoon habitat use at multiple spatial scales. We radiomonitored 131 adult raccoons (99 M, 32 F) during 1991-1997 in central Mississippi, USA. We subsequently assessed space use and habitat selection at 3 spatial scales. Males maintained larger home ranges and core areas than females. Size of home ranges differed by season, but raccoons maintained similar-size core areas across seasons. Habitat use differed by gender only at the coarsest spatial scale. Raccoons consistently used mature (>30 years old) pine and hardwood habitats over other available habitats at all spatial scales. Although hardwood-dominated habitats were important to raccoons, our findings suggest that in pine-dominated landscapes, raccoons select multiple seral stages of pine. Raccoons also readily used ≤8-year-old pine habitats, likely because of increased foraging opportunities within these habitats, particularly during spring and summer. Our findings illustrate the importance of juxtaposition of habitat types for raccoons in pine-dominated landscapes, specifically the availability of mature pine and hardwood habitats, as well as early-successional habitats capable of providing beneficial foraging resources. Additionally, our findings offer evidence that prescribed burning may alter landscape use by raccoons, providing the potential that manipulating burning frequencies may allow managers to manage raccoon habitat-use patterns.

Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in mammary glands. Here we show that mice with diet-induced obesity display mislocalization of Par3, a regulator of cellular junctional complexes defining mammary epithelial polarity. We found that epithelial polarity loss also occurs in a 3D coculture system that combines acini with human mammary adipose tissue, and establish that a paracrine effect of the tissue adipokine leptin causes loss of polarity by overactivation of the PI3K/Akt pathway. Leptin sensitizes non-neoplastic cells to proliferative stimuli, causes mitotic spindle misalignment, and expands the pool of cells with stem/progenitor characteristics, which are early steps for cancer initiation. We also found that normal breast tissue samples with high leptin/adiponectin transcript ratio characteristic of obesity have an altered distribution of apical polarity markers. This effect is associated with increased epithelial cell layers. Our results provide a molecular basis for early alterations in epithelial architecture during obesity-mediated cancer initiation.

Invasive melanoma is the deadliest type of skin cancer, with 101,110 expected cases to be diagnosed in 2021. Recurrent BRAF and NRAS mutations are well documented in melanoma. Biologic implications of gene fusions and the efficacy of therapeutically targeting them remains unknown. Retrospective review of patient samples that underwent next-generation sequencing of the exons of 592 cancer-relevant genes and whole transcriptome sequencing for the detection of gene fusion events and gene expression profiling. Expression of PDL1 and ERK1/2 was assessed by immunohistochemistry (IHC). There were 33 (2.6%) cases with oncogenic fusions (14 novel), involving BRAF, RAF1, PRKCA, TERT, AXL, and FGFR3. MAPK pathway-associated genes were over-expressed in BRAF and RAF1 fusion-positive tumors in absence of other driver alterations. Increased expression in tumors with PRKCA and TERT fusions was concurrent with MAPK pathway alterations. For a subset of samples with available tissue, increased phosphorylation of ERK1/2 was observed in BRAF, RAF1, and PRKCA fusion-positive tumors. Oncogenic gene fusions are associated with transcriptional activation of the MAPK pathway, suggesting they could be therapeutic targets with available inhibitors. Additional analyses to fully characterize the oncogenic effects of these fusions may support biomarker driven clinical trials.

The raccoon (Procyon lotor) provides recreational, aesthetic, and economic benefits throughout its range. Knowledge of survival and cause-specific mortality is necessary to understand dynamics of raccoon populations and enable effective management. Additionally, sportsmen in many Southeastern states have expressed interest in a summer raccoon hunting season; however, information on effects of summer hunting on raccoon survival and cause-specific mortality are unavailable. Consequently, we radiotracked 176 adult raccoons in central Mississippi during 1991-97. Annual survival differed (P = 0.031) between males (0.63 ± 0.09; x̄ ± SE) and females (0.50 ± 0.10). Annual survival varied among years for males (P < 0.01), but not for females (P = 0.117). Cause of death was known for 55% of raccoon mortalities; legal harvest accounted for most (58%) known deaths. Annual survival did not differ (P = 0.356) between raccoons in the summer hunting (0.60 ± 0.06) and control (0.69 ± 0.06) areas. However, patterns of mortality varied between the summer hunting and control areas (P < 0.001), and seasonally (P = 0.003). Our data suggest implementing a summer raccoon hunting season with conservative bag limits will not reduce raccoon populations by reducing annual survival.

A case of a successfully treated inflammatory pseudotumor (IPT) of the pelvis in a 9-year-old male is presented. Review of the literature indicates that IPTs have been reported from a variety of anatomic locations. They form a spectrum of lesions ranging from benign, infection-related lesions to low-grade malignancies, capable of local recurrences and rare distant metastases. The site of involvement seems to have prognostic implication. Pulmonary IPTs are found in older patients and are almost always benign, whereas extrapulmonary IPTs tend to occur in younger patients and are, in general, more aggressive, with a recurrence rate of up to 24 per cent and mortality of up to 7 per cent. The treatment of choice is complete resection of the lesion.

Recent interest in a summer hunting season for raccoon (Procyon lotor) in many southeastern states has prompted concern over effects of summer hunting on their populations. Because the effects of summer hunting on raccoon movement and home range are unknown, we radiomonitored 75 raccoons (57 male, 18 female) from 1 July to 23 August 1996-97 on 2 adjacent areas with or without a summer hunting season. We detected no differences in mean movement rate (P = 0.726) between males (764 ± 52 m/hr; x̄ ± SE) and females (669 ± 89 m/hr), or in mean movement rate (P = 0.741) between the hunted (757 ± 62 m/hr) and control areas (724 ± 66 m/hr). Similarly, we observed no differences (P = 0.307) in home range size between hunted (219 ± 25 ha, n = 42) and control raccoons (198 ± 14 ha, n = 51) during the summer hunting season. Our study indicated that summer hunting of raccoons on this area had little impact on movement patterns and home range characteristics.

Recent interest in a summer hunting season for raccoon (Procyon lotor) in many southeastern states has prompted concern over effects of summer hunting on their populations. Because the effects of summer hunting on raccoon movement and home range are unknown, we radiomonitored 75 raccoons (57 male, 18 female) from 1 July to 23 August 1996-97 on 2 adjacent areas with or without a summer hunting season.