Pathology & Oncology Research最新文献

Background: Extraocular sebaceous carcinoma (SC) arising in the vulva is extremely rare that no treatment consensus has been well-defined. Case presentation: We here presented two cases of vulval SC in a 31-year-old and a 62-year-old woman, respectively. Radical wide local excision was performed with free margin and they received no postoperative adjuvant therapy. No evidence of disease was detected after follow-ups for 12 months and 49 months, respectively. A comprehensive literature review of vulval SC was further conducted and other ten cases were included. The mean age was 55.9 years, nine patients were diagnosed with FIGO stage I diseases while the remaining three patients had metastatic lesions at initial diagnosis. Surgery was the mainstay treatment option that 11 (91.7%) underwent surgical resection, of which 5 patients received inguinal lymphadenectomy and 2 patients showed lymph nodes involved. Radiotherapy and chemotherapy were given in 2 and 1 patient, respectively. Two patients experienced recurrence within 1 year after initial therapy. At the final follow-up, ten patients had no evidence of disease, one patient was alive with the disease, and only one died of the disease. Conclusion: Radical wide local excision may be preferred in early-stage vulval SC and utilization of sentinel lymph node sampling should be recommended. Postoperative adjuvant therapy may be spared in patients with negative surgical margin and absence of lymph node involvement. Treatment of vulval SC referring to the guidelines of vulvar cancer should be administered in case of positive margins or metastatic disease.

Endocrine therapy has played an essential role in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. With the continuous development of endocrine targeting drugs, especially the emergence of selective cyclin-dependent kinase (CDK4/6) inhibitors, the overall survival time in patients with HR+HER2- advanced breast cancer has been greatly improved. Their adverse reactions also need more attention in response to the climbing number of CDK4/6 inhibitors. The common side effects of CDK4/6 inhibitors were hematological toxicity, diarrhea, and liver function damage. Skin toxicity related to CDK4/6 inhibitors was rare. We describe herein our preliminary observation of one HR+HER2- advanced metastatic breast cancer patient diagnosed with vitiligo-like lesions after 10 months of taking Palbociclib. Hoping to share our experience to increase the clinician awareness of this unusual adverse and contribute to the information in the literature.

Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher's precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ² = 6.632, p = 0.010; OS: χ² = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram's predictive clinical utility for clinical decision was better than IOSS. Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.

CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G₂/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.

Multiple myeloma (MM) is a hematologic disorder characterized by the accumulation of malignant plasma cells in the bone marrow. Genetic and environmental factors are contributed to the etiology of MM. Notably, studies have shown that obesity increases the risk of MM and worsens outcomes for MM patients. Adipokines play an important role in mediating the close association between MM and metabolic derangements. In this review, we summarize the epidemiologic studies to show that the risk of MM is increased in obese. Accumulating clinical evidence suggests that adipokines could display a correlation with MM. In vitro and in vivo studies have shown that adipokines are linked to MM, including roles in the biological behavior of MM cells, cancer-associated bone loss, the progression of MM, and drug resistance. Current and potential therapeutic strategies targeted to adipokines are discussed, proposing that adipokines can guide early patient diagnosis and treatment.

Background: Immune checkpoint blockade (ICB) can prompt durable and robust responses in multiple cancers, involving muscle-invasive bladder cancer (MIBC). However, only a limited fraction of patients received clinical benefit. Clarifying the determinants of response and exploring corresponding predictive biomarkers is key to improving outcomes. Methods: Four independent formerly published cohorts consisting of 641 MIBC patients were enrolled in this study. We first analyzed the associations between various cancer hallmarks and ICB therapy response in two immunotherapeutic cohorts to identify the leading prognostic hallmark in MIBC. Furthermore, advanced machine learning methods were performed to select robust and promising predictors from genes functioning in the above leading pathway. The predictive ability of selected genes was also validated in multiple MIBC cohorts. Results: We identified and verified IFNα response as the leading cancer hallmark indicating better treatment responses, favorable overall survival, and an inflamed tumor microenvironment with higher infiltration of immune effector cells in MIBC patients treated with ICB therapy. Subsequently, two commonly selected genes, CXCL10 and LAMP3, implied better therapy response and the CXCL10^highLAMP3^high patients would benefit more from ICB therapy, which was comprehensively validated from the perspective of gene expression, clinical response, patient survival and immune features. Conclusion: Higher IFNα response primarily predicted better ICB therapeutic responses and reflected an inflamed microenvironment in MIBC. A composite of CXCL10 and LAMP3 expression could serve as promising predictive biomarkers for ICB therapeutic responses and be beneficial for clinical decision-making in MIBC.

Lung cancer is one of the leading causes of cancer-related deaths worldwide, with small cell lung cancer (SCLC) having the worst prognosis. SCLC is diagnosed late in the disease's progression, limiting treatment options. The most common treatment for SCLC is chemotherapy. As the disease progresses, immunotherapy, most commonly checkpoint inhibitor medication, becomes more important. Efforts should be made in the development of immunotherapy to map specific biomarkers, which play a role in properly assigning a type of immunotherapy to the right cohort of patients, where the benefits outweigh any risks or adverse effects. The objective of this review was to provide a thorough assessment of current knowledge about the nature of the tumor process and treatment options for small cell lung cancer, with a focus on predictive biomarkers. According to the information obtained, the greatest potential, which has already been directly demonstrated in some studies, has characteristics such as tumor microenvironment composition, tumor mutation burden, and molecular subtyping of SCLC. Several other aspects appear to be promising, but more research, particularly prospective studies on a larger number of probands, is required. However, it is clear that this field of study will continue to expand, as developing a reliable method to predict immunotherapy response is a very appealing goal of current medicine and research in the field of targeted cancer therapy.

Despite significant advances in the diagnosis and treatment of esophageal squamous cell carcinoma (ESCC), esophageal cancer is still a heavy social and medical burden due to its high incidence. Uncontrolled division and proliferation is one of the characteristics of tumor cells, which will promote rapid tumor growth and metastasis. Early mitotic inhibitor 1 (Emi1), ubiquitin-conjugating enzyme 10 (UBCH10) and CyclinB1 are important proteins involved in the regulation of cell cycle. In this study, the expression of Emi1, UBCH10 and CyclinB1 in ESCC tissues and adjacent normal tissues will be analyzed by immunohistochemistry and in-situ hybridization techniques, and their relationship with tumor proliferation and apoptosis will be analyzed. The results showed that Emi1, UBCH10 and CyclinB1 genes and proteins were highly expressed in tumor tissues, which were correlated with tumor grade, lymph node metastasis and pathological stage, and positively correlated with tumor proliferation. Emi1, UBCH10 and CyclinB1 are also positively correlated. It is speculated that Emi1, UBCH10 and CyclinB1 genes synergically promote tumor proliferation and inhibit apoptosis, which may be potential diagnostic and therapeutic targets for ESCC.

Leiomyosarcoma with heterologous differentiation is relatively rare. To date, only 19 cases have been reported in the English literature. Heterologous components frequently show histological pleomorphism, while those exhibiting well-differentiated morphology are seldom reported. Here, we report a 34-year-old female diagnosed with leiomyosarcoma and developed abdominal wall recurrence 8 years after primary surgery. The recurrent tumor mainly comprised well-differentiated chondrosarcoma except a single focus of leiomyosarcoma. Due to the rarity and prolonged onset of such a transition, our case provides insight into the understanding of this phenomenon.

Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.