A comprehensive review of healthy effects of vegetarian diets

Aims: A comprehensive review comparing the effect of vegetarian (V) and non-vegetarian (NV) diets on the major cardiometabolic diseases’ outcomes was performed. Data synthesis: We performed literature research (up to December 31, 2022) of the evidence separately for vascular disease (VD), obesity (OB), dyslipidemia (Dysl), hypertension (HPT), type 2 diabetes (T2D), metabolic syndrome (MetS), analyzing only cohort studies and randomized controlled studies (RCTs) and comparing the effect of V and NV diets. Cohort studies showed advantages of V diets compared to NV diets on incidence and/or mortality risk for ischemic heart disease, overweight and OB risk. Most cohort studies showed V had lower risk of HPT and lower blood pressure (BP) than NV and V diets had positive effects on T2D risk or plasma parameters. The few cohort studies on the risk of MetS reported mixed results. In RCTs, V diets, mainly low-fat-vegan ones, led to greater weight loss and improved glycemic control than NV diets and in the only one RCT a partial regression of coronary atherosclerosis. In most RCTs, V diets significantly reduced LDL-C levels (but also decreased HDL-C levels) and BP. Conclusions: In this comprehensive review of the association between V diets and cardiometabolic outcomes, we found that following this type of diet may help to prevent most of these diseases. However, the non-uniformity of the studies, due to ethnic, cultural, and methodological differences, does not allow for generalizing the present results and drawing definitive conclusions. Further, well-designed studies are warranted to confirm the consistency of our conclusions

Clinical significance of PTEN and p-Akt co-expression in HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies

Objective: The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3'-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies. Methods: Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry. Results: PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05). Conclusion: In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies

Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies with Lapatinib

The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted

DW-MRI as a Biomarker to Compare Therapeutic Outcomes in Radiotherapy Regimens Incorporating Temozolomide or Gemcitabine in Glioblastoma

The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf−/− PtenloxP/loxP/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/− ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials