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Mercado Baird posted an update 10 months, 3 weeks ago
The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis.
The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis.1,25-Dihydroxyvitamin D3 (1,25D3) induces growth arrest and apoptosis in breast cancer cells in vivo and in vitro, however the exact mechanisms are unclear. Although the vitamin D receptor (VDR), a ligand dependent transcription factor, is required for growth regulation by vitamin D, the specific target genes that trigger these effects are unknown. Genomic profiling of murine mammary tumor cells with differential VDR expression identified 35 transcripts that were altered by the 1,25D3-VDR complex including Hyaluronan Synthase-2 (Has2). Here we confirmed that 1,25D3 reduces both HAS2 gene expression and hyaluronic acid (HA) synthesis in multiple models of breast cancer. Furthermore, we show that the growth inhibitory effects of 1,25D3 are partially reversed in the presence of high molecular weight HA. HAS2 expression and HA production are elevated in immortalized human mammary epithelial cells induced to undergo epithelial-mesenchymal transition (EMT) through stable expression of TGFβ, SNAIL or TWIST and in those expressing oncogenic H-RASV12, indicating that deregulation of HA production may be an early and frequent event in breast tumorigenesis. 1,25D3 also reduces HA secretion and acts additively with an HA synthesis inhibitor to slow growth of cells expressing TGFβ, SNAIL and TWIST. Analysis of mammary gland and tumors from Vdr knockout mice suggest that loss of VDR is associated with enhanced HAS2 expression and HA production in vivo. These data define a novel role for 1,25D3 and the VDR in control of HA synthesis in epithelial tissues that likely contributes to its anti-cancer actions.Targeted drug approaches have been a major focus for developing new anticancer therapies. Although many such agents approved in the last 20 years have improved outcomes, almost all have underperformed expectations. The full potential of such agents may yet be obtained through novel combinations. Previously, we showed that anti-estrogen drugs combined with a dendritic cell-based anti-HER-2 vaccine known to induce strong Th1-polarized immunity dramatically improved clinical response rates in patients with HER-2pos/ERpos early breast cancer. find more Here, we show that the small molecule Akt antagonist MK-2206, when combined with the Th1 cytokines IFN-gamma and TNF-alpha, maximize indicators of apoptotic cell death in a panel of phenotypically-diverse human breast cancer lines. These findings were mirrored by other, structurally-unrelated Akt-targeting drugs that work through different mechanisms. Interestingly, we found that MK-2206, as well as the other Akt antagonist drugs, also had a tendency to suppress Th1 cytokine expression in stimulated human and murine lymphocytes, potentially complicating their use in conjunction with active immunotherapy. After verifying that MK-2206 plus IFN-gamma could show similar combined effects against breast cancer lines, even in the absence of TNF-alpha, we tested in a rodent HER-2pos breast cancer model either a HER-2-based DC vaccine, or recombinant IFN-gamma with or without MK-2206 administration. We found that for MK-2206, co-administration of recombinant IFN-gamma outperformed co-administration of DC vaccination for slowing tumor growth kinetics. These findings suggest a combined therapy approach for Akt-targeting drugs that incorporates recombinant Interferon-gamma and is potentially translatable to humans.
A collecting duct carcinoma is a very rare, malignant renal epithelial tumor. Distant metastases are present in one third of cases at the time of diagnosis. It is known to have a poor prognosis.
A 42-year-old male was sent to our surgery clinic for removal of a 119.2 mm × 108.3 mm encapsulated cystic mass, which was localized in the 8
segment of the right liver lobe. The lesion was first identified on ultrasonography. A computed tomography scan confirmed the presence of a Bosniak type III cystic lesion, which affected the liver and convexity of the right kidney. Surgical intervention involved a right nephrectomy, with removal of the cystic mass. The patient was mobilized on the first postoperative day and was discharged after 7 d. The histological and immunohistochemical examination revealed a low-grade collecting duct renal carcinoma, which is a rare variant of papillary carcinoma, with low malignant potential. The patient did not receive chemotherapy and after 21 mo of follow-up, a radiological examination and laboratory analyses showed normal aspects. No relapse or other complications were reported.
To manage renal tumors properly, a correct histopathological diagnosis is crucial, as is early diagnosis and correct surgical treatment.
To manage renal tumors properly, a correct histopathological diagnosis is crucial, as is early diagnosis and correct surgical treatment.
Several studies have shown the safety, feasibility and oncologic adequacy of robotic right hemicolectomy (RRH). Laparoscopic right hemicolectomy (LRH) is considered technically challenging. Robotic surgery has been introduced to overcome this technical limitation, but it is related to high costs. To maximize the benefits of such surgery, only selected patients are candidates for this technique. In addition, due to progressive aging of the population, an increasing number of minimally invasive procedures are performed on elderly patients with severe comorbidities, who are usually more prone to post-operative complications.
To investigate the outcomes of RRH
LRH with regard to age and comorbidities.
We retrospectively analyzed 123 minimally invasive procedures (68 LRHs
55 RRHs) for right colon cancer or endoscopically unresectable adenoma performed in our Center from January 2014 until September 2019. The surgical procedures were performed according to standardized techniques. The primary clinical outcome of the study was the length of hospital stay (LOS) measured in days.