The "Heater" of "Cold" Tumors-Blocking IL-6.

The resolution of inflammation is not simply the end of the inflammatory response but rather a complex process that involves various cells, inflammatory factors, and specialized proresolving mediators following the occurrence of inflammation. Once inflammation cannot be cleared by the body, malignant tumors may be induced. Among them, IL-6, as an immunosuppressive factor, activates a variety of signal transduction pathways and induces tumorigenesis. Monitoring IL-6 can be used for the diagnosis, efficacy evaluation and prognosis of tumor patients. In terms of treatment, improving the efficacy of targeted and immunotherapy remains a major challenge. Blocking IL-6 and its mediated signaling pathways can regulate the tumor immune microenvironment and enhance immunotherapy responses by activating immune cells. Even transform "cold" tumors that are difficult to respond to immunotherapy into immunogenic "hot" tumors, acting as a "heater" for "cold" tumors, restarting the tumor immune cycle, and reducing immunotherapy-related toxic reactions and drug resistance. In clinical practice, the combined application of IL-6 inhibition with targeted therapy and immunotherapy may produce synergistic results. Nevertheless, additional clinical trials are imperative to further validate the safety and efficacy of this therapeutic approach.

Complete remission in a pretreated, microsatellite-stable, KRAS-mutated colon cancer patient after treatment with sintilimab and bevacizumab and platinum-based chemotherapy: a case report and literature review.

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.

Photodynamic therapy may salvage chemotherapy failure in gastric cancer: A case report and a literature review.

Given the highly heterogeneous characteristics of advanced gastric cancer (GC), most patients must receive neoadjuvant therapy or conversion therapy consisting of chemotherapy to decrease tumor grade and improve the likelihood of complete resection. Drug resistance, however, always leads to an aborted conversion therapy and inevitable death. When meet drug resistance, alternative drug regimens will be applied with immunotherapy or targeted therapy, whose clinical efficacy remains limited when new drug resistance or severer liver and kidney toxicity emerge. Photodynamic therapy (PDT), a novel treatment, has demonstrated remarkable therapeutic efficacy in different stages of GC. However, no report has been reported so far on the clinical application of photodynamic therapy in conversion therapy after drug resistance. Here we report a case of middle-aged patient with advanced GC, who experienced failure of conversion therapy consisted of multi-line chemotherapy along with immunotherapy. Ultimate success was achieved through a comprehensive conversion therapy of PDT, chemotherapy, immunotherapy, and targeted therapy. Subsequently, the patient underwent robotic-assisted radical gastrectomy while the surgical specimen showed no tumor cell exists. The patient underwent 3 cycles of systemic adjuvant therapy following surgical intervention. Presently, the patient remains 17 months in a satisfactory state of health.

Electrohydraulic lithotripsy through endoscopic retrograde cholangiopancreatography combined with SpyGlass in the treatment of complex pancreatic duct stones: A case report and literature review.

The incidence of pancreatic duct stones (PDS) is less than 1%. After the formation of stones, the lumen of the pancreatic duct is blocked, and the pancreatic juice cannot be discharged smoothly, resulting in the impairment of the internal and external secretions of the pancreas. Several national guidelines now recommend endoscopic retrograde cholangiopancreatography (ERCP) as the treatment for PDS. The emergence of SpyGlass makes it possible to visualize the ERCP blind area of the pancreatic system directly. Electrohydraulic lithotripsy (EHL) under SpyGlass can crush large and pressure-resistant stones into smaller fragments, significantly improving the success of the endoscopic treatment of large stones. Here, we report a patient presented with acute alcohol-associated pancreatitis, found to have PDS on imaging, who underwent ERCP combined with SpyGlass (EHL), avoiding surgery, reducing trauma, and being discharged from the hospital with a rapid recovery. Therefore, endoscopic therapy is effective and safe for PDS patients. The combination therapy of this patient is the first use of SpyGlass for PDS in our centre, which marks a new stage in the application of endoscopic therapy for pancreatic diseases.

PDT for Gastric Cancer - the view from China.

The incidence rate and mortality of gastric cancer remain elevated. Traditionally, surgical treatment (including endoscopic surgery and traditional surgery), chemotherapy, targeted therapy, and immunotherapy were used for the treatment of gastric cancer. Although the emergence of targeted therapy and immunotherapy can effectively prolong the survival of some patients with gastric cancer and improve the quality of life of patients after chemotherapy or surgery, the overall survival rate of gastric cancer has not been significantly improved. Photodynamic therapy is a local photochemical therapy with the advantages of high safety, few adverse reactions, and repeatability, although it may cause some toxic reactions. There are some differences between East and West in the treatment of gastric cancer with PDT, and most earlier studies concentrated on using PDT alone. However, some studies have indicated that PDT may enhance the efficacy of chemotherapy and other medications. This paper summarizes the study on the use of PDT and its combination therapy in gastric cancer, which is anticipated to offer novel thoughts for the treatment of gastric cancer.

Research progress of potential factors influencing photodynamic therapy for gastrointestinal cancer.

Gastrointestinal cancer is a malignant tumor of the gastrointestinal tract and its associated digestive organs, including esophageal cancer, gastric cancer, carcinoma of the ampulla, pancreas, bile duct, intestines and rectal cancer. They account for about 30% of global cancer-related incidence and about 40% of mortality. Photodynamic therapy (PDT), as a treatment mode, has been applied to the treatment of gastrointestinal cancer due to potential advantages targeting and potentially lower toxic side effects. However, In the course of clinical treatment, we have found that different patients have various responsiveness to PDT, and even the same patients may have different clinical effects after receiving treatment in different time periods. For influencing factors, traditionally, we only focus on adjusting the dose of photosensitizer and the intensity and time of irradiation,while minimizing other potential factors.Therefore, this paper looks for factors that affect PDT from the patient's own conditions, tumor characteristics and tumor microenvironment(including:tumor acidic microenvironment,tumor hypoxic microenvironment, multi-drug resistance, different tumor characteristics and the immune status of patients) and summarizes how to potentially improve the curative effect of PDT.

Rh(III)-Catalyzed Dual C-H Functionalization and C-O/C-N Annulations of Monoamide Fumarates.

Pyrano[4,3-c]pyridine-diones, which are the key skeleton of bioactive compounds and functional materials, are usually prepared via a multistep synthesis using expensive substrates. This work demonstrates that Rh(III)-catalyzed dual C(sp2)-H functionalization and C-O/C-N annulation of monoamide fumarates can produce pyrano[4,3-c]pyridine-1,5(6H)-diones in high yield (up to 82%) in a single step. The substrates of monoamide fumarates and acetylenes are structurally simple, readily available, and inexpensive. The additive AgSbF6 effectively raised the yields. On account of easier dehydrogenation of OH in the COOH group than NH in the amide group in the reaction, the process first undergoes C-O annulation and then is succeeded by C-N annulation.

Case Report: Anlotinib combined with PD-1 inhibitor and sequential GA regimen or FOLFIRINOX Chemotherapy in treatment of KRAS G12V mutated pancreatic ductal adenocarcinoma with liver metastasis: A case and literature review.

There is a high mortality rate associated with pancreatic cancer, and the incidence has been rising globally in recent decades. When patients are diagnosed, there is little chance that surgery will be beneficial. Systemic chemotherapy is the currently accepted treatment option for patients with metastatic advanced pancreatic cancer. However, a very limited survival improvement is possible with chemotherapy for advanced pancreatic cancer, and chemotherapy resistance plays a significant role in poor prognosis. Despite the fact that targeting growth factor receptor inhibitors such as anti-vascular endothelial growth factor (VEGFR) antibodies significantly improves survival in pancreatic cancer, only a very small number of patients benefit from the treatment. As emerging drugs, immune checkpoint inhibitors (ICIs) have demonstrated significant therapeutic effects in several tumor types, but monotherapy is not effective in pancreatic cancer. In the first-line treatment of solid tumors, combination therapy may result in remarkable outcomes. Here in, we have reported a younger patient with pancreatic ductal adenocarcinoma with liver metastasis (PDACLM) who had a long-term partial response and good tolerance to the combination of anlotinib and programmed cell death protein 1 (PD-1) inhibitor and chemotherapy. Gene analysis suggested only one mutation in the Kirsten rat sarcoma viral oncogene (KRAS) G12V gene. Consequently, there is some hope for patients with pancreatic cancer, especially for KRAS G12V gene mutated patients. Upon reviewing the literature, this patient's combination therapy is the first to have been reported.

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis.

Background: Although multiple gene promoter hypermethylation has been associated with gastric carcinogenesis, data on their specific relationship remains scant. We aimed to investigate the correlation between the status of multiple gene promoter methylation and gastric cancer (GC). Methods: We searched PubMed, EMBASE, CNKI, Wanfang, Cqvip and Cochrane Library up to May 2021. We systematically assessed the association between methylation status of the CpG islands and the risk of GC. We compared the incidence of DNA methylation between tumor and non-tumor tissues, and evaluated the clinicopathological significance of the DNA methylation in gastric carcinoma. The data was presented by an odds ratio (OR) with an accompanying 95% confidence interval (CI). We then generated forest plots calculated by fixed-effects or random-effects model. Results: This study enrolled a total of 201 studies (140 papers). Our analysis showed a higher frequency of methylation of the CpG islands in GC tissues compared to non-neoplastic tissues. Besides, the data demonstrated that polygene's aberrant promoter methylation might be linked to the initial development and progression of GC. Discussion: The genes with altered DNA methylation might serve as epigenetic biomarkers, providing a promising molecular diagnostic and prognostic tool for human GC. However, our findings need further evaluation in large randomized controlled trials.

The "Light Knife" for Gastric Cancer: Photodynamic Therapy.

Photodynamic therapy (PDT) has been used clinically to treat cancer for more than 40 years. Some solid tumors, including esophageal cancer, lung cancer, head and neck cancer, cholangiocarcinoma, and bladder cancer, have been approved for and managed with PDT in many countries globally. Notably, PDT for gastric cancer (GC) has been reported less and is not currently included in the clinical diagnosis and treatment guidelines. However, PDT is a potential new therapeutic modality used for the management of GC, and its outcomes and realization are more and more encouraging. PDT has a pernicious effect on tumors at the irradiation site and can play a role in rapid tumor shrinkage when GC is combined with cardiac and pyloric obstruction. Furthermore, because of its ability to activate the immune system, it still has a specific effect on systemic metastatic lesions, and the adverse reactions are mild. In this Review, we provide an overview of the current application progress of PDT for GC; systematically elaborate on its principle, mechanism, and the application of a new photosensitizer in GC; and focus on the efficacy of PDT in GC and the prospect of combined use with other therapeutic methods to provide a theoretical basis for clinical application.

Intestinal congestion and reperfusion injury: damage caused to the intestinal tract and distal organs.

In clinical practice, intestinal autologous diseases, ailments and organ transplants can cause severe congestive damage to the intestinal tract. However, after the etiological factor is gotten rid of and blood flow is free without any hinderance, further damage to the intestinal wall often occurs, causing other related organ dysfunctions. This ultimately results in intestinal congestion reperfusion injury (ICRI). When the structure and function of the intestine are destroyed, bacteria, metabolites and endotoxins in the intestinal tract perfuse and enter the portal vein through the already compromised intestinal mucosa, to the other organs via the liver. Nevertheless, this gives rise to further aggravation of the injury, and reperfusion injury syndrome occurs. ICRI is a very common complication encountered by clinicians, and its harm is more severe and serious as compared with that caused by ischemia-reperfusion. Quite a few number of studies on ICRI have been reported to date. The exact mechanism of the injury is still idiopathic, and effective treatment strategies are still limited. Based on recent studies, this article is aimed at reviewing the destruction, damage mechanisms resulting from ICRI to the intestinal anatomical sites and distant organs. It is geared towards providing new ideas for the prevention and therapeutic approaches of ICRI.