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Inhibitory checkpoint blockade therapy is an immunomodulatory strategy that results in the restoration of T cell functions, and its efficacy depends on the recognition of tumor cells for destruction. Considering the factors at play, one could propose that anti-tumor responses will not occur if tumor cells are immunologically invisible to T cells. In this study, we tested a strategy based on the modulation of cancer cell's immunovisibility through HDAC inhibition. In a model (heterotopic and orthotopic) of mouse urothelial bladder cancer, we demonstrated that the use of intratumoral or intravesical HDACi in combination with systemic anti-PD-1 was effective at inducing curative responses with durable anti-tumor immunity capable of preventing tumor growth at a distal site. Mechanistically, we determined that protective responses were dependent on CD8 cells, but not NK cells. Of significance, in an in vitro human model, we found that fully activated T cells fail at killing bladder cancer cells unless tumor cells were pretreated with HDACi. Complementary to this observation, we found that HDACi cause gene deregulation, that results in the upregulation of genes responsible for mediating immunorecognition, NKG2D ligands and HSP70. Taken together, these data indicate that HDAC inhibition results in the elimination of the tumor cell's "invisibility cloak" that prevents T cells from recognizing and killing them. AY-22989 datasheet Finally, as checkpoint blockade therapy moves into the adjuvant setting, its combined use with locally administrated HDACi represents a new approach to be included in our current therapeutic treatment toolbox.Background Inflammatory myofibroblast tumor (IMT) is a rare tumor with obscure etiopathogenesis in which different inflammatory cells and myofibroblastic spindle cells are seen histologically. Although the majority of these neoplasms have a benign clinical course, the malignant form has also been reported. The gold standard is surgical treatment for complete removal. Our report describes a 50-year-old woman who underwent surgery for IMT of the lung. The aim is to determine whether cancer stem cells may be present in IMT of the lung. Methods In April 2018, the patient underwent surgery for tumor mass asportation through lateral thoracotomy. The histology of the tumor was consistent with IMT of the lung. The ALDEFLUOR assay, after tissue digestion, was used to identify and sort human lung cancer cells expressing high and low aldehyde dehydrogenase (ALDH) activity. SOX2, NANOG, OCT-4, and c-MYC positivity were additionally determined by immunohistochemistry. Results The specimen contained 1.10% ALDHhigh cells among all viable lung cancer cells, which indicates the population of cancer stem cells is not negligible. Immunohistochemically assessed cell positivity for ALDH1A1, SOX2, NANOG, OCT-4, and c-MYC, which are considered as lung cancer stem-like cells markers. Conclusion For the first time, we demonstrated the presence of cancer stem cells in a case of IMT of the lung. This finding may provide a base for considering new pathological and molecular aspects of this tumor. This perspective suggests further studies to understand the possibility of developing recurrence depending on the presence of cancer stem cells.Background Lobectomy with mediastinal lymph node dissection has always been recognized as the standardized treatment for early-stage non-small-cell lung cancer. However, the feasibility of segmentectomy performed in stage IB non-small-cell lung cancer (NSCLC) patients remains controversial. The present study aims to investigate whether the outcome of stage IB NSCLC patients undergoing segmentectomy was comparable to those who underwent lobectomy. Method We retrospectively collected data of 11,010 patients with primary stage IB non-small-cell lung cancer from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were assessed among patients who were performed lobectomy or segmentectomy. To further assess the impact of the surgical procedures on patients with different tumor sizes, subgroups stratified by tumor size were analyzed. Results A total of 11,010 patients who were pathologically confirmed to be stage IB were included, of whom 10,453 received lobectomy and 557 received segmentectomy. Both univariate and multivariate Cox regression analyses showed that the patients receiving lobectomy had better OS [hazards ratio (HR) = 1.197, 95% confidence interval (CI) (1.066, 1.343), P 30 and ≤ 40 mm. Segmentectomy may be acceptable in patients with an older age and a smaller TS.Background Primary signet-ring cell carcinoma (SRCC) is a rare variation of adenocarcinoma. Although SRCC of the urinary bladder is highly malignant, it is often neglected due to its rarity. Materials and Methods We used the national Surveillance, Epidemiology, and End Results (SEER) database (2004-2016) to compare SRCC with urothelial carcinoma (UC) and investigated the prognostic values of the clinicopathological characteristics and survival outcomes in SRCC of the urinary bladder. Multivariable Cox proportional hazard model, subgroup analyses, and propensity score matching (PSM) were used. Results In all, 318 patients with SRCC and 57,444 patients with UC were enrolled. Compared with those with UC, patients with SRCC were younger at diagnosis (P less then 0.001) and had higher rates of muscle invasive disease (P less then 0.001), lymph node metastasis (P less then 0.001), and distal metastasis (P less then 0.001), as well as higher-grade tumors (P = 0.004). A Cox proportional hazard regression analysis showed that the SRCC group was associated with significantly higher risks of overall mortality (OM) compared with the UC group [hazard ratios (HR) = 1.44, 95% confidence intervals (95% CI) = 1.26-1.63, P less then 0.0001]. Patients with SRCC also had a higher risk of cancer-specific mortality (CSM; HR = 1.40, 95% CI = 1.18-1.65, P less then 0.0001). After PSM, the SRCC group also experienced higher risks of OM (HR = 1.45, 95% CI = 1.24-1.68, P less then 0.0001) and CSM (HR = 1.47, 95% CI = 1.20-1.79, P = 0.0001) compared with the UC group. In the subgroup analyses, no significant interactions were observed in sex, age, N stage, M stage, and lymph nodes removed in terms of both OM and CSM. link2 Conclusion The prognosis of SRCC is poorer than that of UC, even after adjustment for baseline demographic and clinicopathological characteristic as well as cancer treatment. SRCC is an independent prognostic factor for patients with urinary bladder cancer.Background Lumican (LUM) is a member of the small leucine-rich proteoglycan family and plays dual roles as an oncogene and a tumor suppressor gene. The effect of LUM on tumors is still controversial. Methods Gene expression profiles and clinical data of gastric cancer (GC) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression difference of LUM in GC tissues and adjacent nontumor tissues was analyzed by R software and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and comprehensive meta-analysis. link3 The relationship between LUM expression and clinicopathological parameters was assessed by chi-square test and logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards regression model were chosen to assess the effect of LUM expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in GC between the low and the high LUM expression datasets. Results The expression of LUM in GC tissues was significvival (HR, 1.189; 95% CI, 1.011-1.400; P = 0.037). GSEA indicated that 14 signaling pathways were evidently enriched in samples with the high-LUM expression phenotype. Conclusions LUM might act as an oncogene in the progression of GC and could be regarded as a potential prognostic indicator and therapeutic target for GC.New tools are needed to match cancer patients with effective treatments. Patient-derived organoids offer a high-throughput platform to personalize treatments and discover novel therapies. Currently, methods to evaluate drug response in organoids are limited because they overlook cellular heterogeneity. In this study, non-invasive optical metabolic imaging (OMI) of cellular heterogeneity was characterized in breast cancer (BC) and pancreatic cancer (PC) patient-derived organoids. Baseline heterogeneity was analyzed for each patient, demonstrating that single-cell techniques, such as OMI, are required to capture the complete picture of heterogeneity present in a sample. Treatment-induced changes in heterogeneity were also analyzed, further demonstrating that these measurements greatly complement current techniques that only gauge average cellular response. Finally, OMI of cellular heterogeneity in organoids was evaluated as a predictor of clinical treatment response for the first time. Organoids were treated with the same drugs as the patient's prescribed regimen, and OMI measurements of heterogeneity were compared to patient outcome. OMI distinguished subpopulations of cells with divergent and dynamic responses to treatment in living organoids without the use of labels or dyes. OMI of organoids agreed with long-term therapeutic response in patients. With these capabilities, OMI could serve as a sensitive high-throughput tool to identify optimal therapies for individual patients, and to develop new effective therapies that address cellular heterogeneity in cancer.Background Fibroma or leiomyoma is the most common benign tumor of the female reproductive system, which is usually found in the uterus, but may also occur in other places, such as the ovary, the broad ligament, and in rare cases in the abdominal wall. The formation of the abdominal wall leiomyoma may result from the implantation of myometrium tissue following surgical removal of the uterine leiomyoma, but sometimes these masses occur in a person who has no history of myomectomy. Case presentation This case was a patient who became a candidate for laparoscopy due to abnormal uterine bleeding and pain in the right upper quadrant of the abdomen and ovarian mass. The patient underwent laparotomy due to the inability of surgeons to insert the veress needle because of the presence of mass in the abdominal wall. The pathologic report of the abdominal mass was leiomyoma. This article has been approved by the Ethics Committee of the University (6562276). Conclusion The formation of myoma on the abdominal wall is rare but given the fact that leiomyoma can be created at each part of the body with smooth muscles, including the anterior abdominal wall, this diagnosis should be considered for the differential diagnosis of abdominal masses.Background The objective of this case presentation was describing a live birth in an advanced-age woman with an extremely enlarged uterus, an ovary with blocked fallopian tubes, hypothyroidism and generalized anxiety disorder caused by child-birth following intracytoplasmic sperm injection/embryo transfer (ICSI-ET) with autologous oocytes. Case presentation A 47-year-old patient with an enlarged uterus due to recurrent multiple fibroids following myomectomy was referred to clinical laboratory with a high level of desire to follow the prescribed recommendations and approaches to retrieve her fertility. The patient underwent two cycles of oocyte retrieval and two rounds of frozen-thawed embryo transfer. To achieve a successful pregnancy after oocyte retrieval (birth weight of 3300 g at 38 weeks of gestation), a frozen/thawed embryo in the second cycle of ET was transferred. Conclusion Usage of efficient planning and management of ICSI treatments in patient with autologous oocytes and concurrent disorders, can be used as a new approach to cure the affected individuals.
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