Zeng Q, Mao Z, Sun S
… +9 more, Gao Z, Mu J, Pan Z, Li Q, Mao X, Xu J, Bai D, Huang S, Chen L
MedComm Oncol
· 2026 Mar · PMID 42089079
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X-linked inhibitor of apoptosis protein (XIAP) is a multifunctional protein that regulates many cellular functions. Anoikis resistance is necessary for hepatocellular carcinoma (HCC) intrahepatic spread and extrahepatic...X-linked inhibitor of apoptosis protein (XIAP) is a multifunctional protein that regulates many cellular functions. Anoikis resistance is necessary for hepatocellular carcinoma (HCC) intrahepatic spread and extrahepatic metastasis. However, limited information is available regarding the mechanism of XIAP underlying the resistance of HCC cells to anoikis. Here we show an increased expression of XIAP in microvascular tumor thrombosis (MVTT) of HCC, which is positively correlated with the expression of extracellular signal-regulated kinases 1/2 (ERK1/2). HCC cells exhibit an increase in XIAP expression when detached, leading to their resistance to anoikis. Furthermore, enhanced phosphorylation of XIAP promotes resistance to anoikis in HCC cells. In addition, the zinc-binding baculovirus IAP repeat (BIR) domains of XIAP, instead of the highly intriguing novel gene (RING) domain, are responsible for conferring resistance to anoikis in HCC cells. Importantly, our findings indicate that ERK1/2 can control the expression of XIAP, leading to the resistance of HCC to anoikis in cell-based and mouse models. The significance of the interaction between XIAP and ERK1/2 in resisting anoikis is emphasized by our discoveries, presenting novel avenues for HCC treatment.
Chen Y, Jiang Z, Jin S
… +16 more, Liu M, Chen M, Kuo TC, Zhou K, Pu L, Chen M, Chen S, Li X, Chen AS, Xie J, Zhang H, Wang Q, Xu J, Sheng J, Huang Y, Chen G
Mol Ther Oncol
· 2026 Jun · PMID 42088619
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Glioblastoma(GBM), a highly aggressive primary brain tumor characterized by rapid progression, frequent recurrence, and limited clinical options, remains one of the most lethal central nervous system malignancies. Here,...Glioblastoma(GBM), a highly aggressive primary brain tumor characterized by rapid progression, frequent recurrence, and limited clinical options, remains one of the most lethal central nervous system malignancies. Here, we report a gene therapy strategy to treat glioma utilizing NeuroD1, a neurogenic transcription factor with demonstrated capacity to reprogram both glial cells and GBM cells into neuronal lineages. We developed a self-complementary adeno-associated virus (scAAV) vector, scAAV6-NeuroD1, and evaluated its therapeutic potential across and GBM models, including multiple GBM cell lines, patient-derived organoids, and orthotopic models in immunodeficient mice. Our findings reveal that scAAV6-NeuroD1 preferentially infects glioma cells and induces dual therapeutic effects by simultaneously inhibiting glioma cell proliferation and inducing neuronal reprogramming. Importantly, scAAV6-NeuroD1-treated mice with orthotopic GBM transplants exhibited reduced tumor burden, infiltration of T cells into the glioma, attenuated tumor-induced body weight loss, and dose-dependent survival extension. Analysis of published patient datasets further revealed that high NeuroD1 expression level correlates with improved overall survival and lower tumor malignancy grade. Together, these findings position scAAV6-NeuroD1 as a promising therapeutic candidate, potentially redefining the therapeutic landscape for GBM.
Wang J, Sun Y, Starzyk J
… +7 more, Wang F, Dong X, Shan R, He X, Xie K, Xie G, Wu H
Mol Ther Oncol
· 2026 Jun · PMID 42088618
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Natural killer (NK) cells hold promise for adoptive cell therapy due to their innate cytotoxicity. Early clinical trials confirm their safety and efficacy in cancer and autoimmune disease treatment. Engineering NK cells...Natural killer (NK) cells hold promise for adoptive cell therapy due to their innate cytotoxicity. Early clinical trials confirm their safety and efficacy in cancer and autoimmune disease treatment. Engineering NK cells with chimeric antigen receptors (CARs) enhances target specificity and facilitates their development as off-the-shelf allogeneic therapies. However, both viral and non-viral engineering methods of NK cells present challenges. Here, we introduce locus integrated CAR killer (CLICK), a novel non-viral approach using a mini-circular single-stranded DNA genome editing system. CLICK enables efficient integration of CD19CAR sequences into the metabolic checkpoint locus, simultaneously disrupting and driving stable, progressively increasing CAR expression in peripheral blood-derived NK cells. CLICK-engineered CAR-NK cells exhibit potent cytotoxicity, enhanced anti-tumor activity and , extended persistence, and reduced exhaustion. Together, these findings highlight CLICK as a highly efficient and versatile platform for non-viral CAR-NK cell engineering, offering a scalable approach for next-generation allogeneic immune cell therapies.
The affordability of health care will be the top issue in the upcoming midterm elections. However, the discussion about health care affordability began more than 15 years ago with the passage of the Affordable Care Act (...The affordability of health care will be the top issue in the upcoming midterm elections. However, the discussion about health care affordability began more than 15 years ago with the passage of the Affordable Care Act (ACA), which was dubbed Obamacare. Under the ACA, every American was to have health insurance and access to care. Citing PolitiFact, Mark Memmott of National Public Radio in December 2013 reported that President Barack Obama told the "lie of the year," publicly claiming more than 35 times that "if you like your health care plan, you can keep it." The ACA was also supposed to allow patients to "keep their doctor" and save each family of 4 about $2500 per year, which never occurred.
The term synchronous refers to 2 or more primary independent malignancies, when the second (or subsequent) arises within 6 months after diagnosis of the first malignancy. Synchronous endometrial and ovarian cancers are f...The term synchronous refers to 2 or more primary independent malignancies, when the second (or subsequent) arises within 6 months after diagnosis of the first malignancy. Synchronous endometrial and ovarian cancers are found in 10% of patients with ovarian cancer and 5% of patients with endometrial cancer. Using a variety of criteria, pathologists can distinguish synchronous primary tumors from metastatic disease. Primary surgical staging remains the gold standard for treating patients with synchronous endometrial and ovarian cancers. Adjuvant therapy is still controversial in the early stages of the disease. Genetic evaluation of patients with a positive family history may be crucial for quicker diagnosis and to identify those with familial cancer syndrome. We present the case of a 47-year-old premenopausal woman with abdominal pain who qualified for surgery due to suspicion of an ovarian tumor during a physical examination and imaging studies. After the final histopathologic examination, the patient was diagnosed with synchronous endometrial cancer, FIGO IA, and ovarian cancer, FIGO IIIC stage .
BACKGROUND: Breast cancer is the most prevalent malignancy among women and frequently causes significant psychological distress, such as anxiety and depression. The perception and impact of social support in addressing t...BACKGROUND: Breast cancer is the most prevalent malignancy among women and frequently causes significant psychological distress, such as anxiety and depression. The perception and impact of social support in addressing these mental health challenges differ depending on cultural and societal factors, highlighting its crucial role. AIM: This study aimed to evaluate the association between anxiety and depression in Palestinian women with breast cancer and perceived social support (PSS). METHODS: A descriptive, cross-sectional design was employed. The study included 257 patients with breast cancer. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. PSS was measured using the Medical Outcomes Study Social Support Survey. RESULTS: Most participants (95%) were married. The mean age was 51 ± 9.8 years. The total PSS was relatively mild to moderate (M = 69.7 ± 9.5). The scores for anxiety and depression were in the borderline range(M = 7.8 ± 3.3 and M = 8.3 ± 3.6, respectively). All subclasses of PSS were negatively correlated with anxiety and depression ( P < .05). CONCLUSION: Every individual has a unique perception of social support. Depression and anxiety affect a sizable percentage of patients with breast cancer. Higher levels of social support may also assist in reducing depression and anxiety, as seen by the strong negative association found between these psychological states and PSS.
A young father faces a potential lymphoma diagnosis, revealing how medical language, restraint, and rapid coordination reshape care and ease uncertainty.A young father faces a potential lymphoma diagnosis, revealing how medical language, restraint, and rapid coordination reshape care and ease uncertainty.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoma with a poor prognosis. The human T-lymphotropic virus 1 (HTLV-1) is associated with immunodeficiency and increased extranodal involvement in patients with d...Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoma with a poor prognosis. The human T-lymphotropic virus 1 (HTLV-1) is associated with immunodeficiency and increased extranodal involvement in patients with diffuse large B-cell lymphoma (DLBCL). We report on a 47-year-old woman with spastic paraparesis and hepatitis B who was diagnosed with the acute form of ATLL. The clinical picture reveals peripheral generalized lymphadenopathy and splenomegaly. Findings on a hematologic exam indicated leukocytosis with lymphocytosis. A bone marrow biopsy/aspiration confirmed 50% T-cell lymphoid infiltration. Biochemistry results revealed hypercalcemia and a high lactate dehydrogenase value. Results of a CT scan indicated abdominal and thoracic adenopathy as well as moderate splenomegaly. A supraclavicular lymph node biopsy established a DLBCL diagnosis. The final diagnosis was composite lymphoma, DLBCL, and ATLL. The CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], and prednisone) regimen was chosen due to the patient's ECOG performance status. Multiple infectious complications were diagnosed during chemotherapy-induced secondary aplasia. A complete remission, confirmed via PET-CT imaging, was obtained. After 1 month, a skin tumor on the upper right thigh was discovered and biopsied, and the histopathological exam and immunochemistry findings indicated Epstein-Barr virus-DLBCL lymphoma. The association of 2 aggressive lymphomas in a single HTLV-1 carrier is a rare report, and the evolution was severe, complicated by opportunistic infections, and unfavorable.
Clin Med Insights Oncol
· 2026 · PMID 42064232
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BACKGROUND: Compared with chemotherapy, tarlatamab significantly prolonged overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed during or after platinum-based chemot...BACKGROUND: Compared with chemotherapy, tarlatamab significantly prolonged overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed during or after platinum-based chemotherapy. The aim of this study was to evaluate the cost-effectiveness of tarlatamab versus chemotherapy as a second-line treatment for ES-SCLC from the perspective of the US health care system. METHODS: A partitioned survival model was constructed to simulate disease progression on the basis of the DeLLphi-304 trial results. A 28-day cycle length and a 10-year time horizon were adopted for the model. Direct medical costs and health utility estimates were extracted from previously published studies and publicly available databases. The model outputs included the total and incremental costs and quality-adjusted life years (QALYs). The primary outcome was the incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) thresholds were set at $150 000/QALY and $200 000/QALY for the United States. One-way sensitivity analysis and probabilistic sensitivity analyses were performed to evaluate the robustness of the model outcomes. RESULTS: At an incremental cost of $203 332.28, tarlatamab yielded an additional 0.29 QALYs compared with chemotherapy. This resulted in an ICER of $701 145.79/QALY, which substantially exceeded the WTP thresholds. The cost of tarlatamab emerged as a major influential parameter in the sensitivity analyses, demonstrating its substantial impact on cost-effectiveness outcomes. Sensitivity and scenario analyses confirmed the robustness of the cost-effectiveness results. CONCLUSION: At WTP thresholds of $150 000/QALY and $200 000/QALY, tarlatamab was not considered a cost-effective option at the current price compared with chemotherapy for the treatment of recurrent ESCLC from the US payer perspective.
Laimer G, Johnston EW, Overduin CG
… +70 more, Paolucci I, Ahmed M, Arellano RS, Beermann M, Beyer LP, Breen DJ, Burgmans MC, Calandri M, Chern MC, Crocetti L, van Dam RM, Denys A, Edwin B, Filippiadis D, Fong Y, Fotiadis N, Freedman J, Fretland ÅA, Gimenez M, Garcia RG, Grasso RF, Helmberger TK, Hendriks P, Iezzi R, Jenniskens SF, Kupferthaler A, Lachenmayer A, Lee FT, Lee JM, van der Lei S, van der Leij C, Liang P, Lin CC, Luerken L, Maglione M, Mahnken A, McWilliams JP, Menezes M, Narayanan G, Orsi F, Pereira PL, Pua U, Puijk RS, Rhim H, Rilling WS, Ruiter SJS, Ryan AG, Schullian P, Shyn PB, Siriwardena AK, Smits MLJ, Sofocleous CT, Solbiati L, Sotirchos V, Stättner S, van Strijen M, Syversveen T, Tinguely P, Tselikas L, Vauthey JN, Vogl TJ, Wah TM, White SB, Wiggermann P, Wood BJ, van der Meulen J, Goldberg SN, Meijerink MR, Odisio BC, Bale R
Thermal ablation offers a safer, less invasive, and more cost-effective curative-intent treatment for selected patients with primary and metastatic liver tumours than surgery; when done with appropriate technique, ablati...Thermal ablation offers a safer, less invasive, and more cost-effective curative-intent treatment for selected patients with primary and metastatic liver tumours than surgery; when done with appropriate technique, ablation can deliver similar oncological outcomes. However, effectiveness in routine practice varies because structured training, planning, and procedural governance remain scarce. These international multidisciplinary, multi-society guidelines-formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology-define key domains contributing to procedural difficulty and practice variation in liver tumour thermal ablation. A Delphi consensus initiative held in Innsbruck, Austria, engaged 72 experts across three iterative rounds of scoring across 135 statements grouped into five domains: credentialing, indications, approach, procedural factors, and safety measures. Consensus was achieved for 94 (70%) of 135 statements. The least invasive route-typically percutaneous-should be prioritised, and margin adequacy was reaffirmed as the principal technical goal. Procedural difficulty was considered context-dependent, shaped by tumour factors, institutional infrastructure, and operator experience. Organ displacement techniques were endorsed to maintain safety and expand treatable indications. Complex ablations should be done by experienced operators (more than 100 previous cases), with programmes underpinned by structured training, multidisciplinary team participation, and routine audit. Future efforts should develop and validate practical tools such as difficulty scoring systems, standardised procedural reporting templates, and comprehensive training curricula to improve consistency, standardisation, and clinical outcomes globally.
Paolucci I, Overduin CG, Johnston EW
… +70 more, Laimer G, Ahmed M, Arellano RS, Beerman M, Beyer LP, Breen DJ, Burgmans MC, Calandri M, Chern MC, Crocetti L, van Dam RM, Denys A, Edwin B, Filippiadis D, Fong Y, Fotiadis N, Freedman J, Fretland ÅA, Gimenez M, Garcia RG, Grasso RF, Helmberger TK, Hendriks P, Iezzi R, Jenniskens SF, Kupferthaler A, Lachenmayer A, Lee FT, Lee JM, van der Lei S, van der Leij C, Liang P, Lin CC, Luerken L, Maglione M, Mahnken A, McWilliams JP, Menezes M, Narayanan G, Orsi F, Pereira PL, Pua U, Puijk RS, Rhim H, Rilling WS, Ruiter SJS, Ryan AG, Schullian P, Shyn PB, Siriwardena AK, Smits MLJ, Sofocleous CT, Solbiati L, Sotirchos V, Stättner S, van Strijen M, Syversveen T, Tinguely P, Tselikas L, Vauthey JN, Vogl TJ, Wah TM, White SB, Wiggermann P, Wood BJ, van der Meulen J, Goldberg SN, Meijerink MR, Bale R, Odisio BC
This multisociety, multidisciplinary consensus-formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncol...This multisociety, multidisciplinary consensus-formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology-was developed to standardise the assessment of ablation margins in liver tumour thermal ablation. A modified Delphi process, consisting of two online surveys and a hybrid (online and in-person meeting in Innsbruk) consensus meeting of 72 experts from North America, South America, Europe, and Asia. Formal consensus was reached for 150 (75%) of 199 statements. Strong agreement was observed between interventional and surgical oncologists, with only 12 (6%) of 199 statements showing significantly different ratings. Participants agreed that ablation margins should be assessed and documented for every treated tumour. Margins should be assessed quantitatively in three dimensions, with contrast-enhanced CT or MRI, preferably intraprocedurally with ablation confirmation software. Ablation margins should be categorised as A0 (tumour completely covered with sufficient margin), A1 (tumour completely covered but insufficient margin), or A2 (portion of tumour remains unablated). This effort is, to our knowledge, the first international consensus initiative to define best-practice recommendations for margin assessment in liver tumour thermal ablation to standardise practices, aiming to improve and promote uniform outcomes.
Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life i...Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.