Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.

Thyroid cancer can be classified into three different types based on the degree of differentiation: well-differentiated, poorly differentiated, and anaplastic thyroid carcinoma. Well-differentiated thyroid cancer refers to cancer cells that closely resemble normal thyroid cells, while poorly differentiated and anaplastic thyroid carcinoma are characterized by cells that have lost their resemblance to normal thyroid cells. Advanced thyroid carcinoma, regardless of its degree of differentiation, is known to have a higher likelihood of disease progression and is generally associated with a poor prognosis. However, the process through which well-differentiated thyroid carcinoma transforms into anaplastic thyroid carcinoma, also known as "dedifferentiation", has been a subject of intensive research. In recent years, there have been significant breakthroughs in the treatment of refractory advanced thyroid cancer. Clinical studies have been conducted to evaluate the efficacy and safety of molecular targeted drugs and immune checkpoint inhibitors in the treatment of dedifferentiated thyroid cancer. These drugs work by targeting specific molecules or proteins in cancer cells to inhibit their growth or by enhancing the body's immune response against the cancer cells. This article aims to explore some of the possible mechanisms behind the dedifferentiation process in well-differentiated thyroid carcinoma. It also discusses the clinical effects of molecular targeted drugs and immune checkpoint inhibitors in thyroid cancer patients with different degrees of differentiation. Furthermore, it offers insights into the future trends in the treatment of advanced thyroid cancer, highlighting the potential for improved outcomes and better patient care.

Immunogenic Cell Death-Relevant Damage-Associated Molecular Patterns and Sensing Receptors in Triple-Negative Breast Cancer Molecular Subtypes and Implications for Immunotherapy.

Objectives: Triple-negative breast cancer (TNBC) is defined as a highly aggressive type of breast cancer which lacks specific biomarkers and drug targets. Damage-associated molecular pattern (DAMP)-induced immunogenic cell death (ICD) may influence the outcome of immunotherapy for TNBC patients. This study aims to develop a DAMPs gene signature to classify TNBC patients and to further predict their prognosis and immunotherapy outcome. Methods: We identified the DAMPs-associated subtypes of 330 TNBCs using K-means analysis. Differences in immune status, genomic alterations, and predicted immunotherapy outcome were compared among each subtype. Results: A total of 330 TNBCs were divided into three subtypes according to DAMPs gene expression: the nuclear DAMPs subtype, featuring the upregulation of nuclear DAMPs; the inflammatory DAMPs subtype, characterized by the gene set enrichment of the adaptive immune system and cytokine signaling in the immune system; and the DAMPs-suppressed subtype, having the lowest level of ICD-associated DAMPs. Among them, the inflammatory subtype patients had the most favorable survival, while the DAMPs-suppressed subtype was associated with the worst prognosis. The DAMPs subtyping system was successfully validated in the TCGA cohort. Furthermore, we systemically revealed the genomic alterations among the three DAMPs subtypes. The inflammatory DAMPs subtype was predicted to have the highest response rate to immunotherapy, suggesting that the constructed DAMPs clustering had potential for immunotherapy efficacy prediction. Conclusion: We established a novel ICD-associated DAMPs subtyping system in TNBC, and DAMPs expression might be a valuable biomarker for immunotherapy strategies. Our work could be helpful to the development of new immunomodulators and may contribute to the development of precision immunotherapy for TNBC.

Guilu Erxian Glue () Inhibits Chemotherapy-Induced Bone Marrow Hematopoietic Stem Cell Senescence in Mice May via p16INK4a-Rb Signaling Pathway.

OBJECTIVE: To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism. METHODS: The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX (100 mg/kg i.p.) was administrated to mice from day 1 to day 3 (d1-d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α (2.2 mg/(kg·d) i.p.) for 6 consecutive days (d4-d9), GEG (9.5 g/(kg·d) i.p.) for 9 consecutive days (d1-d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and ß -galactosidase (ß -gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2 (CDK2), CDK4, inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16 (p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma (pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively. RESULTS: Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced ß -gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group (P<0.05 or P<0.01). CONCLUSION: GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.

[Adjuvant function of guilu erxian glue cataplasm in treating carcinoma of the large intestine patients with myelosuppression after chemotherapy: a clinical observation].

OBJECTIVE: To observe the clinical effect of Guilu Erxian Glue Cataplasm (GEGC) on carcinoma of the large intestine patients with myelosuppression after chemotherapy, and further to confirm its efficiency and safety. METHODS: Totally 60 patients with carcinoma of the large intestine were randomly assigned to two groups. Meanwhile, they all accepted FOLFIRI chemotherapy. Patients in the treatment group were additionally applied at Shenque (RN8), exchanging once per every other day, for 14 successive days. Patients in the control group took placebos with the same dose and dosage as the treatment group. The blood cell counts (WBC, NE, and PLT) were detected before chemotherapy, at day 7, 10, and 14. The TCM symptoms integrals, Karnofsky performance score (KPS), liver and kidney functions were observed before chemotherapy, at day 7 and day 14. Adverse skin reactions were observed each day. And the usage of hematopoietic growth factors was recorded. RESULTS: (1) The KPS score at day 7 was more stable in the treatment group than in the control group; the WBC and NE counts in the peripheral blood at day 14 were higher in the treatment group than in the control group; and TCM symptoms integrals at day 14 was lower in the treatment group than in the control group, all with statistical difference (P < 0.05). (2) Compared with the control group, the PLT count was higher in the treatment group than in the control group, the usage of rhG-CSF and antibiotics was less in the treatment group than in the control group, all with no statistical difference (P > 0.05). (3) No obvious adverse reactions such as liver injury, renal injury, or skin allergy were observed. CONCLUSIONS: Adjuvant treatment of GEGC could improve carcinoma of the large intestine patients with myelosuppression to some extent. No relevant adverse reactions were found.

[Retrospective study on the dynamic development of Chinese medical syndrome types of gastric cancer].

OBJECTIVE: To observe the effects of surgery and chemotherapy on the development of Chinese medical syndrome types on patients with gastric cancer (GC), thus providing the evidence for treating GC by Chinese medical syndrome differentiation and treatment by stages. METHODS: A retrospective study was carried out in 500 GC patients according to before and after surgery, the surgical ways, before and after chemotherapy to observe the dynamic development of Chinese medical syndrome types of GC. RESULTS: Pi deficiency syndrome dominated in GC patients of single syndrome or two syndromes before and after surgery. After surgery (after radical resection or palliative resection) Pi deficiency syndrome and blood deficiency syndrome significantly increased. There was statistical difference in syndrome type changes before and after chemotherapy (P < 0.05). CONCLUSIONS: Deficiency syndrome mainly dominated in GC patients. They should be treated by stages when Chinese medicine and pharmacy took part in its treatment.

[Treatment of acute radiation pneumonia with Qingfei Huatan Quyu method].

OBJECTIVE: To observe the therapeutic effect of Qingfei Huatan Quyu method (QHQ, a Chinese medicinal therapy for clearing Fei-heat and dissolving phlegm-stasis) combined with hormone-antibiotic therapy (HAT) on radiation pneumonia (RP). METHODS: Eighty-one patients with RP were randomized into two groups, 41 patients in the control group and 40 in the treatment group were treated with HAT alone and HAT combined with QHQ respectively for 21 days. The severity of RP was evaluated before and after treatment according to the criteria of the radiation therapy oncology group. The effect on TCM symptoms and chest roentgenogram, as well as on plasma levels of interleukin-6 ( IL-6) and transform growth factor-beta (TGF-beta) were detected. RESULTS: After treatment, number of patients with RP graded as 0, 1, 2, 3, and 4 in the treatment group was 23, 10, 4, 2, and 1, respectively, while in the control group, 14, 9, 11, 4, and 3, respectively. The combined therapy showed effects in improving RP grading (P <0.01) and TCM syndromes were superior to those of HAT respectively (P < 0.05). Besides, levels of IL-6 and TGF-beta were lowered after treatment in the treatment group, showing a significant difference to those in the control group (P <0.05). CONCLUSION: QHQ combined with HAT has a definite therapeutic effect on RP. It could efficiently decrease the plasma levels of IL-6 and TGF-beta in patients with RP.

[Effect of guilu erxianjiao in suppressing splenic T-lymphocyte apoptosis in mice undergoing chemotherpy].

OBJECTIVE: To investigate the effect of Guilu Erxianjiao (GLEXJ) in suppressing chemotherapy induced cell apoptosis in mice and to discuss its possible acting mechanism. METHODS: Seventy-two tumor-bearing Kunming mice were randomly divided into 6 groups, Group A, treated with normal saline; Group B treated with cyclophosphamide (CTX), Group C treated with Chinese herbal medicine, and Group D-F, the three combined treated group received CTX plus high, moderate and low dose GLEXJ. All mice were sacrificed after 9-day medication, their splenic tissues were taken for determining T-lymphocyte apoptosis with flow cytometer, the expression of bcl-2 mRNA and Caspase-3mRNA detected by RT-PCR. RESULTS: As compared with Group A, FITC+/PI- cell proportion of spleen T-lymphocyte cells and Caspase-3mRNA expression were higher, while bcl-2 mRNA expression was lower in Group B; as compared with Group B, the former two indexes were lower and the latter was higher in the three combined treated groups (all P <0.05). CONCLUSION: GLEXJ could efficiently suppress the splenic T-lymphocyte apoptosis in tumor bearing mice undergoing chemotherapy, one of its mechanisms may be through up-regulating of bcl-2 mRNA expression and down-regulating of Caspase-3mRNA expression.

[Effects of ethanol extracts of Panax notoginseng on liver metastasis of B16 melanoma grafted in mice].

OBJECTIVE: To observe the effects of ethanol extracts of Panax notoginseng on the tumor and the liver metastasis in experimental mice grafted with B16 melanoma. METHODS: B16 melanoma was transplanted in the spleen of C57BL/6 mice. The effects of different doses of ethanol extracts of Panax notoginseng on the inhibition rate of spleen tumors and the liver metastasis were observed respectively. RESULTS: The high-, medium-, and low-doses of the extracts and the interferon-alpha (IFN-alpha) can improve the quality of life of the experimental mice. The weights of spleen tumor were lower in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the normal saline (NS)-treated group (P<0.05 or P<0.01). The liver metastasis was less in the low- and medium-dose extracts-treated groups and the IFN-alpha-treated group than that in the NS-treated group (P<0.01). CONCLUSION: The ethanol extracts of Panax notoginseng can improve the quality of life of the experimental mice and inhibit the growth of tumor and the liver metastasis.