Preserving Nipple Sensitivity after Breast Cancer Surgery: A Systematic Review and Meta-Analysis.

Purpose: As breast-conserving procedures become increasingly safe and viable options for surgical management of breast cancer, efforts have focused on assessing and optimizing patient-reported outcome measures (PROMs), such as nipple sensation. This study aims to evaluate the current understanding of nipple-areolar complex (NAC) sensation outcomes in breast cancer patients undergoing breast cancer surgeries, namely, nipple-sparing mastectomies (NSM), skin-sparing mastectomies (SSM), and lumpectomies. Methods: Articles including terms related to "nipple," "mastectomy," "sensation," and "patient-reported outcome" were queried from three databases according to PRISMA guidelines. Study characteristics, patient demographics, and surgical details were recorded. Outcomes of interest included objective nipple sensitivity testing and PROMs. Results: Of 888 manuscripts identified, 28 articles met the inclusion criteria. Twelve studies (n = 578 patients) used objective measures to evaluate sensitivity, such as monofilament testing. Sixteen studies (n = 1785 patients) assessed PROMs through validated or investigator-generated surveys. Three of the included studies reported NAC sensitivity in patients who received NSM with neurotization (n = 203 patients) through a variety of techniques that used various grafts to coapt a lateral intercostal nerve to the NAC nerve stumps. Results of investigator surveys showed that of 1565 patients without neurotization, nipple sensation was maintained in 29.0% (n = 453) of patients. Of 138 NSM patients without NAC neurotization, SWM testing showed an average loss of protective sensation in the nipple (average SWM score: 4.7) compared to normal or diminished sensation to light touch in nonoperated controls (average SWM score: 2.9, n = 195). Of patients who underwent NSM with neurotization, one study (n = 78) reported maintenance of NAC sensation in 100% of patients, while another study (n = 7) reported average diminished protective sensation in the nipple (average SWM score: 3.9). Conclusion: Our study has shown that objective and patient-reported results of nipple sensitivity support nipple-sparing techniques as a viable option for preserving NAC sensation, although patients can expect a decrease in sensation overall. Neurotization of the NAC during NSM shows promising results of improved postoperative nipple sensitivity, though additional studies are warranted to confirm this finding. Variations between study methodologies highlight the lack of standardization in sensory testing techniques when evaluating NAC sensation.

Regulation of Chemosensitivity in Human Medulloblastoma Cells by p53 and the PI3 Kinase Signaling Pathway.

In medulloblastoma, p53 expression has been associated with chemoresistance and radiation resistance and with poor long-term outcomes in the p53-mutated sonic hedgehog, MYC-p53, and p53-positive medulloblastoma subgroups. We previously established a direct role for p53 in supporting drug resistance in medulloblastoma cells with high basal protein expression levels (D556 and DAOY). We now show that p53 genetic suppression in medulloblastoma cells with low basal p53 protein expression levels (D283 and UW228) significantly reduced drug responsiveness, suggesting opposing roles for low p53 protein expression levels. Mechanistically, the enhanced cell death by p53 knockdown in high-p53 cells was associated with an induction of mTOR/PI3K signaling. Both mTOR inhibition and p110α/PIK3CA induction confirmed these findings, which abrogated or accentuated the enhanced chemosensitivity response in D556 cells respectively while converse was seen in D283 cells. Co-treatment with G-actin-sequestering peptide, thymosin ß4 (Tß4), induced p-AKTS473 in both p53-high and p53-low cells, enhancing chemosensitivity in D556 cells while enhancing chemoresistance in D283 and UW228 cells. IMPLICATIONS: Collectively, we identified an unexpected role for the PI3K signaling in enhancing cell death in medulloblastoma cells with high basal p53 expression. These studies indicate that levels of p53 immunopositivity may serve as a diagnostic marker of chemotherapy resistance and for defining therapeutic targeting.

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.

Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment.

MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence.

Among a number of non-coding RNAs, role of microRNAs (miRNAs) in cancer cell proliferation, cancer initiation, development and metastasis have been extensively studied and miRNA based therapeutic approaches are being pursued. Prostate cancer (PCa) is a major health concern and several deregulated miRNAs have been described in PCa. miR-212 is differentially modulated in multiple cancers however its function remains elusive. In this study, we found that miR-212 is downregulated in PCa tissues when compared with benign adjacent regions (n = 40). Also, we observed reduced levels of circulatory miR-212 in serum from PCa patients (n = 40) when compared with healthy controls (n = 32). Elucidating the functional role of miR-212, we demonstrate that miR-212 negatively modulates starvation induced autophagy in PCa cells by targeting sirtuin 1 (SIRT1). Overexpression of miR-212 also leads to inhibition of angiogenesis and cellular senescence. In conclusion, our study indicates a functional role of miR-212 in PCa and suggests the development of miR-212 based therapies.